ID ACE2_HUMAN Reviewed; 805 AA.
AC Q9BYF1; A0A7D6JAD5; C7ECU1; Q6UWP0; Q86WT0; Q9NRA7; Q9UFZ6;
DT 02-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 02-AUG-2005, sequence version 2.
DT 28-JUN-2023, entry version 195.
DE RecName: Full=Angiotensin-converting enzyme 2;
DE EC=3.4.17.23 {ECO:0000269|PubMed:10924499, ECO:0000269|PubMed:11815627, ECO:0000269|PubMed:19021774};
DE AltName: Full=Angiotensin-converting enzyme homolog {ECO:0000303|PubMed:10924499};
DE Short=ACEH {ECO:0000303|PubMed:10924499};
DE AltName: Full=Angiotensin-converting enzyme-related carboxypeptidase {ECO:0000303|PubMed:10969042};
DE Short=ACE-related carboxypeptidase;
DE EC=3.4.17.- {ECO:0000269|PubMed:10924499, ECO:0000269|PubMed:10969042, ECO:0000269|PubMed:11815627, ECO:0000269|PubMed:19021774, ECO:0000269|PubMed:27217402, ECO:0000269|PubMed:28293165, ECO:0000269|PubMed:33077916};
DE AltName: Full=Metalloprotease MPROT15 {ECO:0000303|Ref.6};
DE Contains:
DE RecName: Full=Processed angiotensin-converting enzyme 2 {ECO:0000303|PubMed:24227843};
DE Flags: Precursor;
GN Name=ACE2 {ECO:0000312|HGNC:HGNC:13557}; ORFNames=UNQ868/PRO1885;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, FUNCTION, ACTIVITY
RP REGULATION, CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
RC TISSUE=Heart;
RX PubMed=10969042; DOI=10.1161/01.res.87.5.e1;
RA Donoghue M., Hsieh F., Baronas E., Godbout K., Gosselin M., Stagliano N.,
RA Donovan M., Woolf B., Robison K., Jeyaseelan R., Breitbart R.E., Acton S.;
RT "A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2)
RT converts angiotensin I to angiotensin 1-9.";
RL Circ. Res. 87:E1-E9(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, GLYCOSYLATION, FUNCTION,
RP ACTIVITY REGULATION, AND CATALYTIC ACTIVITY.
RC TISSUE=Lymphoma;
RX PubMed=10924499; DOI=10.1074/jbc.m002615200;
RA Tipnis S.R., Hooper N.M., Hyde R., Karran E., Christie G., Turner A.J.;
RT "A human homolog of angiotensin-converting enzyme. Cloning and functional
RT expression as a captopril-insensitive carboxypeptidase.";
RL J. Biol. Chem. 275:33238-33243(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=15231706; DOI=10.1210/en.2004-0443;
RA Douglas G.C., O'Bryan M.K., Hedger M.P., Lee D.K.L., Yarski M.A.,
RA Smith A.I., Lew R.A.;
RT "The novel angiotensin-converting enzyme (ACE) homolog, ACE2, is
RT selectively expressed by adult Leydig cells of the testis.";
RL Endocrinology 145:4703-4711(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-638.
RC TISSUE=Lung, and Testis;
RX PubMed=15937940; DOI=10.1002/ajmg.a.30779;
RA Itoyama S., Keicho N., Hijikata M., Quy T., Phi N.C., Long H.T., Ha L.D.,
RA Ban V.V., Matsushita I., Yanai H., Kirikae F., Kirikae T., Kuratsuji T.,
RA Sasazuki T.;
RT "Identification of an alternative 5'-untranslated exon and new
RT polymorphisms of angiotensin-converting enzyme 2 gene: lack of association
RT with SARS in the Vietnamese population.";
RL Am. J. Med. Genet. A 136:52-57(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Suzuki Y., Watanabe M., Sugano S.;
RT "Cloning, expression analysis and chromosomal localization of a novel ACE
RT like enzyme.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Southan C., Burgess N.;
RT "MPROT15 polypeptide and MPROT15 polynucleotide.";
RL Patent number CA2248987, 13-NOV-1999.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Li K.K.B., Yip C.W., Hon C.C., Lam C.Y., Leung F.C.C.;
RT "Comparative susceptibility to SARS-CoV mediated by ACE2 protein of 15
RT different species.";
RL Submitted (JUN-2009) to the EMBL/GenBank/DDBJ databases.
RN [8] {ECO:0000312|EMBL:QLP88822.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION (ISOFORM 2), INDUCTION BY
RP IFN (ISOFORM 2), AND ALTERNATIVE SPLICING.
RX PubMed=33077916; DOI=10.1038/s41588-020-00731-9;
RA Onabajo O.O., Banday A.R., Stanifer M.L., Yan W., Obajemu A., Santer D.M.,
RA Florez-Vargas O., Piontkivska H., Vargas J.M., Ring T.J., Kee C.,
RA Doldan P., Tyrrell D.L., Mendoza J.L., Boulant S., Prokunina-Olsson L.;
RT "Interferons and viruses induce a novel truncated ACE2 isoform and not the
RT full-length SARS-CoV-2 receptor.";
RL Nat. Genet. 52:1283-1293(2020).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-26.
RG SeattleSNPs variation discovery resource;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-805.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [14]
RP PROTEIN SEQUENCE OF 679-689, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP INTERACTION WITH ITGB1.
RX PubMed=15276642; DOI=10.1016/j.bbadis.2004.05.005;
RA Lin Q., Keller R.S., Weaver B., Zisman L.S.;
RT "Interaction of ACE2 and integrin beta1 in failing human heart.";
RL Biochim. Biophys. Acta 1689:175-178(2004).
RN [15]
RP TISSUE SPECIFICITY.
RX PubMed=12459472; DOI=10.1016/s0014-5793(02)03640-2;
RA Harmer D., Gilbert M., Borman R., Clark K.L.;
RT "Quantitative mRNA expression profiling of ACE 2, a novel homologue of
RT angiotensin converting enzyme.";
RL FEBS Lett. 532:107-110(2002).
RN [16]
RP ACTIVITY REGULATION.
RX PubMed=12358520; DOI=10.1021/ja0277226;
RA Dales N.A., Gould A.E., Brown J.A., Calderwood E.F., Guan B., Minor C.A.,
RA Gavin J.M., Hales P., Kaushik V.K., Stewart M., Tummino P.J., Vickers C.S.,
RA Ocain T.D., Patane M.A.;
RT "Substrate-based design of the first class of angiotensin-converting
RT enzyme-related carboxypeptidase (ACE2) inhibitors.";
RL J. Am. Chem. Soc. 124:11852-11853(2002).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP SPECIFICITY, ACTIVITY REGULATION, AND COFACTOR.
RX PubMed=11815627; DOI=10.1074/jbc.m200581200;
RA Vickers C., Hales P., Kaushik V., Dick L., Gavin J., Tang J., Godbout K.,
RA Parsons T., Baronas E., Hsieh F., Acton S., Patane M.A., Nichols A.,
RA Tummino P.;
RT "Hydrolysis of biological peptides by human angiotensin-converting enzyme-
RT related carboxypeptidase.";
RL J. Biol. Chem. 277:14838-14843(2002).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, AND INDUCTION.
RX PubMed=14504186; DOI=10.1161/01.cir.0000094734.67990.99;
RA Zisman L.S., Keller R.S., Weaver B., Lin Q., Speth R., Bristow M.R.,
RA Canver C.C.;
RT "Increased angiotensin-(1-7)-forming activity in failing human heart
RT ventricles: evidence for upregulation of the angiotensin-converting enzyme
RT Homologue ACE2.";
RL Circulation 108:1707-1712(2003).
RN [19]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH SARS-COV SPIKE
RP GLYCOPROTEIN (MICROBIAL INFECTION), GLYCOSYLATION, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=14647384; DOI=10.1038/nature02145;
RA Li W., Moore M.J., Vasilieva N., Sui J., Wong S.-K., Berne M.A.,
RA Somasundaran M., Sullivan J.L., Luzuriaga K., Greenough T.C., Choe H.,
RA Farzan M.;
RT "Angiotensin-converting enzyme 2 is a functional receptor for the SARS
RT coronavirus.";
RL Nature 426:450-454(2003).
RN [20]
RP INDUCTION.
RX PubMed=15151696; DOI=10.1186/1741-7015-2-19;
RA Goulter A.B., Goddard M.J., Allen J.C., Clark K.L.;
RT "ACE2 gene expression is up-regulated in the human failing heart.";
RL BMC Med. 2:19-19(2004).
RN [21]
RP TISSUE SPECIFICITY.
RX PubMed=15141377; DOI=10.1002/path.1570;
RA Hamming I., Timens W., Bulthuis M.L.C., Lely A.T., Navis G.J., van Goor H.;
RT "Tissue distribution of ACE2 protein, the functional receptor for SARS
RT coronavirus. A first step in understanding SARS pathogenesis.";
RL J. Pathol. 203:631-637(2004).
RN [22]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH SARS-COV SPIKE
RP GLYCOPROTEIN (MICROBIAL INFECTION).
RX PubMed=15452268; DOI=10.1128/jvi.78.20.11429-11433.2004;
RA Li W., Greenough T.C., Moore M.J., Vasilieva N., Somasundaran M.,
RA Sullivan J.L., Farzan M., Choe H.;
RT "Efficient replication of severe acute respiratory syndrome coronavirus in
RT mouse cells is limited by murine angiotensin-converting enzyme 2.";
RL J. Virol. 78:11429-11433(2004).
RN [23]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-90.
RC TISSUE=Bile;
RX PubMed=15084671; DOI=10.1074/mcp.m400015-mcp200;
RA Kristiansen T.Z., Bunkenborg J., Gronborg M., Molina H., Thuluvath P.J.,
RA Argani P., Goggins M.G., Maitra A., Pandey A.;
RT "A proteomic analysis of human bile.";
RL Mol. Cell. Proteomics 3:715-728(2004).
RN [24]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=15671045; DOI=10.1093/eurheartj/ehi114;
RA Burrell L.M., Risvanis J., Kubota E., Dean R.G., MacDonald P.S., Lu S.,
RA Tikellis C., Grant S.L., Lew R.A., Smith A.I., Cooper M.E., Johnston C.I.;
RT "Myocardial infarction increases ACE2 expression in rat and humans.";
RL Eur. Heart J. 26:369-375(2005).
RN [25]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH SARS-COV SPIKE
RP GLYCOPROTEIN (MICROBIAL INFECTION), AND MUTAGENESIS.
RX PubMed=15791205; DOI=10.1038/sj.emboj.7600640;
RA Li W., Zhang C., Sui J., Kuhn J.H., Moore M.J., Luo S., Wong S.-K.,
RA Huang I.-C., Xu K., Vasilieva N., Murakami A., He Y., Marasco W.A.,
RA Guan Y., Choe H., Farzan M.;
RT "Receptor and viral determinants of SARS-coronavirus adaptation to human
RT ACE2.";
RL EMBO J. 24:1634-1643(2005).
RN [26]
RP PROTEOLYTIC CLEAVAGE, AND SUBCELLULAR LOCATION.
RX PubMed=15983030; DOI=10.1074/jbc.m505111200;
RA Lambert D.W., Yarski M., Warner F.J., Thornhill P., Parkin E.T.,
RA Smith A.I., Hooper N.M., Turner A.J.;
RT "Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated
RT ectodomain shedding of the severe-acute respiratory syndrome-coronavirus
RT (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2).";
RL J. Biol. Chem. 280:30113-30119(2005).
RN [27]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HCOV-NL63 SPIKE
RP GLYCOPROTEIN (MICROBIAL INFECTION).
RX PubMed=15897467; DOI=10.1073/pnas.0409465102;
RA Hofmann H., Pyrc K., van der Hoek L., Geier M., Berkhout B., Poehlmann S.;
RT "Human coronavirus NL63 employs the severe acute respiratory syndrome
RT coronavirus receptor for cellular entry.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:7988-7993(2005).
RN [28]
RP FUNCTION, ACTIVE SITE, AND MUTAGENESIS OF ARG-273; HIS-345 AND HIS-505.
RX PubMed=16008552; DOI=10.1111/j.1742-4658.2005.04756.x;
RA Guy J.L., Jackson R.M., Jensen H.A., Hooper N.M., Turner A.J.;
RT "Identification of critical active-site residues in angiotensin-converting
RT enzyme-2 (ACE2) by site-directed mutagenesis.";
RL FEBS J. 272:3512-3520(2005).
RN [29]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, AND MUTAGENESIS OF ARG-169; TRP-271; LYS-481 AND ARG-514.
RX PubMed=19021774; DOI=10.1111/j.1742-4658.2008.06733.x;
RA Rushworth C.A., Guy J.L., Turner A.J.;
RT "Residues affecting the chloride regulation and substrate selectivity of
RT the angiotensin-converting enzymes (ACE and ACE2) identified by site-
RT directed mutagenesis.";
RL FEBS J. 275:6033-6042(2008).
RN [30]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=18424768; DOI=10.1096/fj.08-107300;
RA Kowalczuk S., Broeer A., Tietze N., Vanslambrouck J.M., Rasko J.E.,
RA Broeer S.;
RT "A protein complex in the brush-border membrane explains a Hartnup disorder
RT allele.";
RL FASEB J. 22:2880-2887(2008).
RN [31]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-546.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [32]
RP FUNCTION, AND MUTAGENESIS OF ARG-273.
RX PubMed=19185582; DOI=10.1053/j.gastro.2008.10.055;
RA Camargo S.M., Singer D., Makrides V., Huggel K., Pos K.M., Wagner C.A.,
RA Kuba K., Danilczyk U., Skovby F., Kleta R., Penninger J.M., Verrey F.;
RT "Tissue-specific amino acid transporter partners ACE2 and collectrin
RT differentially interact with hartnup mutations.";
RL Gastroenterology 136:872-882(2009).
RN [33]
RP PROTEOLYTIC CLEAVAGE.
RX PubMed=21563828; DOI=10.1021/bi200525y;
RA Lai Z.W., Hanchapola I., Steer D.L., Smith A.I.;
RT "Angiotensin-converting enzyme 2 ectodomain shedding cleavage-site
RT identification: determinants and constraints.";
RL Biochemistry 50:5182-5194(2011).
RN [34]
RP SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, AND INTERACTION WITH TMPRSS2.
RX PubMed=21068237; DOI=10.1128/jvi.02062-10;
RA Shulla A., Heald-Sargent T., Subramanya G., Zhao J., Perlman S.,
RA Gallagher T.;
RT "A transmembrane serine protease is linked to the severe acute respiratory
RT syndrome coronavirus receptor and activates virus entry.";
RL J. Virol. 85:873-882(2011).
RN [35]
RP FUNCTION (MICROBIAL INFECTION), SUBCELLULAR LOCATION, AND PROTEOLYTIC
RP CLEAVAGE.
RX PubMed=24227843; DOI=10.1128/jvi.02202-13;
RA Heurich A., Hofmann-Winkler H., Gierer S., Liepold T., Jahn O.,
RA Poehlmann S.;
RT "TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by
RT TMPRSS2 augments entry driven by the severe acute respiratory syndrome
RT coronavirus spike protein.";
RL J. Virol. 88:1293-1307(2014).
RN [36]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, 3D-STRUCTURE
RP MODELING, AND ACTIVE SITE.
RX PubMed=27217402; DOI=10.1161/hypertensionaha.115.06892;
RA Wang W., McKinnie S.M., Farhan M., Paul M., McDonald T., McLean B.,
RA Llorens-Cortes C., Hazra S., Murray A.G., Vederas J.C., Oudit G.Y.;
RT "Angiotensin-Converting Enzyme 2 Metabolizes and Partially Inactivates Pyr-
RT Apelin-13 and Apelin-17: Physiological Effects in the Cardiovascular
RT System.";
RL Hypertension 68:365-377(2016).
RN [37]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=28293165; DOI=10.3389/fnins.2017.00092;
RA Yang P., Kuc R.E., Brame A.L., Dyson A., Singer M., Glen R.C., Cheriyan J.,
RA Wilkinson I.B., Davenport A.P., Maguire J.J.;
RT "[Pyr1]Apelin-13(1-12) Is a Biologically Active ACE2 Metabolite of the
RT Endogenous Cardiovascular Peptide [Pyr1]Apelin-13.";
RL Front. Neurosci. 11:92-92(2017).
RN [38]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=32142651; DOI=10.1016/j.cell.2020.02.052;
RA Hoffmann M., Kleine-Weber H., Schroeder S., Krueger N., Herrler T.,
RA Erichsen S., Schiergens T.S., Herrler G., Wu N.H., Nitsche A.,
RA Mueller M.A., Drosten C., Poehlmann S.;
RT "SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a
RT clinically proven protease inhibitor.";
RL Cell 181:1-10(2020).
RN [39]
RP INTERACTION WITH SARS-COV-2 SPIKE GLYCOPROTEIN (MICROBIAL INFECTION).
RX PubMed=32075877; DOI=10.1126/science.abb2507;
RA Wrapp D., Wang N., Corbett K.S., Goldsmith J.A., Hsieh C.L., Abiona O.,
RA Graham B.S., McLellan J.S.;
RT "Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation.";
RL Science 367:1260-1263(2020).
RN [40]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH SARS-COV-2 SPIKE
RP GLYCOPROTEIN (MICROBIAL INFECTION).
RX PubMed=32155444; DOI=10.1016/j.cell.2020.02.058;
RA Walls A.C., Park Y.J., Tortorici M.A., Wall A., McGuire A.T., Veesler D.;
RT "Structure, function, and antigenicity of the SARS-CoV-2 spike
RT glycoprotein.";
RL Cell 180:1-12(2020).
RN [41]
RP TISSUE SPECIFICITY, AND INDUCTION BY ISR.
RX PubMed=32413319; DOI=10.1016/j.cell.2020.04.035;
RG HCA Lung Biological Network. Electronic address: lung-network@humancellatlas.org;
RG HCA Lung Biological Network;
RA Ziegler C.G.K., Allon S.J., Nyquist S.K., Mbano I.M., Miao V.N.,
RA Tzouanas C.N., Cao Y., Yousif A.S., Bals J., Hauser B.M., Feldman J.,
RA Muus C., Wadsworth M.H. II, Kazer S.W., Hughes T.K., Doran B., Gatter G.J.,
RA Vukovic M., Taliaferro F., Mead B.E., Guo Z., Wang J.P., Gras D.,
RA Plaisant M., Ansari M., Angelidis I., Adler H., Sucre J.M.S., Taylor C.J.,
RA Lin B., Waghray A., Mitsialis V., Dwyer D.F., Buchheit K.M., Boyce J.A.,
RA Barrett N.A., Laidlaw T.M., Carroll S.L., Colonna L., Tkachev V.,
RA Peterson C.W., Yu A., Zheng H.B., Gideon H.P., Winchell C.G., Lin P.L.,
RA Bingle C.D., Snapper S.B., Kropski J.A., Theis F.J., Schiller H.B.,
RA Zaragosi L.E., Barbry P., Leslie A., Kiem H.P., Flynn J.L., Fortune S.M.,
RA Berger B., Finberg R.W., Kean L.S., Garber M., Schmidt A.G., Lingwood D.,
RA Shalek A.K., Ordovas-Montanes J.;
RT "SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway
RT Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.";
RL Cell 181:1016-1035.e19(2020).
RN [42]
RP TISSUE SPECIFICITY, AND INDUCTION BY CIGARETTE SMOKE.
RX PubMed=32425701; DOI=10.1016/j.devcel.2020.05.012;
RA Smith J.C., Sausville E.L., Girish V., Yuan M.L., Vasudevan A., John K.M.,
RA Sheltzer J.M.;
RT "Cigarette smoke exposure and inflammatory signaling increase the
RT expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract.";
RL Dev. Cell 0:0-0(2020).
RN [43]
RP TISSUE SPECIFICITY.
RX PubMed=32170560; DOI=10.1007/s11684-020-0754-0;
RA Zou X., Chen K., Zou J., Han P., Hao J., Han Z.;
RT "Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals
RT the potential risk of different human organs vulnerable to 2019-nCoV
RT infection.";
RL Front. Med. 14:185-192(2020).
RN [44]
RP INTERACTION WITH ITGA5:ITGB1, AND INTERACTION WITH SARS-COV-2 SPIKE
RP GLYCOPROTEIN (MICROBIAL INFECTION).
RX PubMed=33102950; DOI=10.1016/j.jacbts.2020.10.003;
RA Beddingfield B.J., Iwanaga N., Chapagain P.P., Zheng W., Roy C.J., Hu T.Y.,
RA Kolls J.K., Bix G.J.;
RT "The Integrin Binding Peptide, ATN-161, as a Novel Therapy for SARS-CoV-2
RT Infection.";
RL JACC Basic Transl. Sci. 6:1-8(2021).
RN [45]
RP INDUCTION BY ALLERGEN AND IL13, TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP AND PROTEOLYTIC CLEAVAGE.
RX PubMed=32333915; DOI=10.1016/j.jaci.2020.04.009;
RA Jackson D.J., Busse W.W., Bacharier L.B., Kattan M., O'Connor G.T.,
RA Wood R.A., Visness C.M., Durham S.R., Larson D., Esnault S., Ober C.,
RA Gergen P.J., Becker P., Togias A., Gern J.E., Altman M.C.;
RT "Association of respiratory allergy, asthma, and expression of the SARS-
RT CoV-2 receptor ACE2.";
RL J. Allergy Clin. Immunol. 146:203.e3-206.e3(2020).
RN [46]
RP TISSUE SPECIFICITY.
RX PubMed=32715618; DOI=10.15252/msb.20209610;
RA Hikmet F., Mear L., Edvinsson A., Micke P., Uhlen M., Lindskog C.;
RT "The protein expression profile of ACE2 in human tissues.";
RL Mol. Syst. Biol. 16:e9610-e9610(2020).
RN [47]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=32221306; DOI=10.1038/s41467-020-15562-9;
RA Ou X., Liu Y., Lei X., Li P., Mi D., Ren L., Guo L., Guo R., Chen T.,
RA Hu J., Xiang Z., Mu Z., Chen X., Chen J., Hu K., Jin Q., Wang J., Qian Z.;
RT "Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and
RT its immune cross-reactivity with SARS-CoV.";
RL Nat. Commun. 11:1620-1620(2020).
RN [48]
RP TISSUE SPECIFICITY.
RX PubMed=32327758; DOI=10.1038/s41591-020-0868-6;
RG HCA Lung Biological Network;
RA Sungnak W., Huang N., Becavin C., Berg M., Queen R., Litvinukova M.,
RA Talavera-Lopez C., Maatz H., Reichart D., Sampaziotis F., Worlock K.B.,
RA Yoshida M., Barnes J.L.;
RT "SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells
RT together with innate immune genes.";
RL Nat. Med. 26:681-687(2020).
RN [49]
RP TISSUE SPECIFICITY.
RX PubMed=32358202; DOI=10.1126/science.abc1669;
RA Lamers M.M., Beumer J., van der Vaart J., Knoops K., Puschhof J.,
RA Breugem T.I., Ravelli R.B.G., Paul van Schayck J., Mykytyn A.Z.,
RA Duimel H.Q., van Donselaar E., Riesebosch S., Kuijpers H.J.H.,
RA Schippers D., van de Wetering W.J., de Graaf M., Koopmans M., Cuppen E.,
RA Peters P.J., Haagmans B.L., Clevers H.;
RT "SARS-CoV-2 productively infects human gut enterocytes.";
RL Science 369:50-54(2020).
RN [50]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=33000221; DOI=10.3892/mmr.2020.11510;
RA Davies J., Randeva H.S., Chatha K., Hall M., Spandidos D.A., Karteris E.,
RA Kyrou I.;
RT "Neuropilin-1 as a new potential SARS-CoV-2 infection mediator implicated
RT in the neurologic features and central nervous system involvement of COVID-
RT 19.";
RL Mol. Med. Report. 22:4221-4226(2020).
RN [51]
RP INTERACTION WITH SARS-COV-2 SPIKE GLYCOPROTEIN (MICROBIAL INFECTION),
RP MUTAGENESIS OF SER-19; GLN-24; ALA-25; THR-27; LEU-29; LYS-31; ASN-33;
RP HIS-34; LEU-39; PHE-40; TYR-41; GLN-42; TRP-69; PHE-72; GLU-75; GLN-76;
RP LEU-79; GLN-89; ASN-90; LEU-91; THR-92; THR-324; GLN-325; ASN-330; LEU-351;
RP ALA-386; PRO-389; ARG-393 AND ARG-518, AND BIOTECHNOLOGY.
RX PubMed=32753553; DOI=10.1126/science.abc0870;
RA Chan K.K., Dorosky D., Sharma P., Abbasi S.A., Dye J.M., Kranz D.M.,
RA Herbert A.S., Procko E.;
RT "Engineering human ACE2 to optimize binding to the spike protein of SARS
RT coronavirus 2.";
RL Science 369:1261-1265(2020).
RN [52]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=33082294; DOI=10.1126/science.abd3072;
RA Daly J.L., Simonetti B., Klein K., Chen K.E., Williamson M.K.,
RA Anton-Plagaro C., Shoemark D.K., Simon-Gracia L., Bauer M., Hollandi R.,
RA Greber U.F., Horvath P., Sessions R.B., Helenius A., Hiscox J.A.,
RA Teesalu T., Matthews D.A., Davidson A.D., Collins B.M., Cullen P.J.,
RA Yamauchi Y.;
RT "Neuropilin-1 is a host factor for SARS-CoV-2 infection.";
RL Science 370:861-865(2020).
RN [53]
RP TISSUE SPECIFICITY.
RX PubMed=32404436; DOI=10.1126/sciimmunol.abc3582;
RA Zang R., Gomez Castro M.F., McCune B.T., Zeng Q., Rothlauf P.W.,
RA Sonnek N.M., Liu Z., Brulois K.F., Wang X., Greenberg H.B., Diamond M.S.,
RA Ciorba M.A., Whelan S.P.J., Ding S.;
RT "TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal
RT enterocytes.";
RL Sci. Immunol. 5:0-0(2020).
RN [54]
RP FUNCTION (MICROBIAL FUNCTION), INTERACTION WITH SARS-COV-2 SPIKE
RP GLYCOPROTEIN (MICROBIAL FUNCTION), AND SUBCELLULAR LOCATION.
RX PubMed=33713620; DOI=10.1016/j.cell.2021.02.053;
RA Yeung M.L., Teng J.L.L., Jia L., Zhang C., Huang C., Cai J.P., Zhou R.,
RA Chan K.H., Zhao H., Zhu L., Siu K.L., Fung S.Y., Yung S., Chan T.M.,
RA To K.K., Chan J.F., Cai Z., Lau S.K.P., Chen Z., Jin D.Y., Woo P.C.Y.,
RA Yuen K.Y.;
RT "Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with
RT proteins related to the renin-angiotensin system.";
RL Cell 0:0-0(2021).
RN [55]
RP INTERACTION WITH NHERF1, AND MUTAGENESIS OF 802-GLN--PHE-805.
RX PubMed=34189428; DOI=10.1016/j.isci.2021.102770;
RA Zhang Q., Gefter J., Sneddon W.B., Mamonova T., Friedman P.A.;
RT "ACE2 interaction with cytoplasmic PDZ protein enhances SARS-CoV-2
RT invasion.";
RL IScience 24:102770-102770(2021).
RN [56]
RP FUNCTION (MICROBIAL FUNCTION), AND INTERACTION WITH SARS-COV-2 SPIKE
RP GLYCOPROTEIN (MICROBIAL FUNCTION).
RX PubMed=33432067; DOI=10.1038/s41598-020-80464-1;
RA Shilts J., Crozier T.W.M., Greenwood E.J.D., Lehner P.J., Wright G.J.;
RT "No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding
RT receptor.";
RL Sci. Rep. 11:413-413(2021).
RN [57]
RP FUNCTION (ISOFORM 2) (MICROBIAL FUNCTION), INDUCTION BY IFN (ISOFORM 2),
RP ALTERNATIVE SPLICING, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=33432184; DOI=10.1038/s41588-020-00759-x;
RA Blume C., Jackson C.L., Spalluto C.M., Legebeke J., Nazlamova L.,
RA Conforti F., Perotin J.M., Frank M., Butler J., Crispin M., Coles J.,
RA Thompson J., Ridley R.A., Dean L.S.N., Loxham M., Reikine S., Azim A.,
RA Tariq K., Johnston D.A., Skipp P.J., Djukanovic R., Baralle D.,
RA McCormick C.J., Davies D.E., Lucas J.S., Wheway G., Mennella V.;
RT "A novel ACE2 isoform is expressed in human respiratory epithelia and is
RT upregulated in response to interferons and RNA respiratory virus
RT infection.";
RL Nat. Genet. 53:205-214(2021).
RN [58]
RP DOMAIN, AND PHOSPHORYLATION AT TYR-781 AND SER-783.
RX PubMed=33436497; DOI=10.1126/scisignal.abd0334;
RA Meszaros B., Samano-Sanchez H., Alvarado-Valverde J., Calyseva J.,
RA Martinez-Perez E., Alves R., Shields D.C., Kumar M., Rippmann F.,
RA Chemes L.B., Gibson T.J.;
RT "Short linear motif candidates in the cell entry system used by SARS-CoV-2
RT and their potential therapeutic implications.";
RL Sci. Signal. 14:0-0(2021).
RN [59]
RP DOMAIN, PHOSPHORYLATION AT TYR-781 AND SER-783, AND INTERACTION WITH AP2M1.
RX PubMed=33436498; DOI=10.1126/scisignal.abf1117;
RA Kliche J., Kuss H., Ali M., Ivarsson Y.;
RT "Cytoplasmic short linear motifs in ACE2 and integrin beta3 link SARS-CoV-2
RT host cell receptors to mediators of endocytosis and autophagy.";
RL Sci. Signal. 14:0-0(2021).
RN [60]
RP INTERACTION WITH SARS-COV-2 SPIKE GLYCOPROTEIN (MICROBIAL INFECTION).
RX PubMed=36228039; DOI=10.1371/journal.pbio.3001805;
RA Song J., Chow R.D., Pena-Hernandez M.A., Zhang L., Loeb S.A., So E.Y.,
RA Liang O.D., Ren P., Chen S., Wilen C.B., Lee S.;
RT "LRRC15 inhibits SARS-CoV-2 cellular entry in trans.";
RL PLoS Biol. 20:e3001805-e3001805(2022).
RN [61]
RP INTERACTION WITH SARS-COV-2 SPIKE GLYCOPROTEIN (MICROBIAL INFECTION).
RX PubMed=36735681; DOI=10.1371/journal.pbio.3001959;
RA Shilts J., Crozier T.W.M., Teixeira-Silva A., Gabaev I., Gerber P.P.,
RA Greenwood E.J.D., Watson S.J., Ortmann B.M., Gawden-Bone C.M., Pauzaite T.,
RA Hoffmann M., Nathan J.A., Poehlmann S., Matheson N.J., Lehner P.J.,
RA Wright G.J.;
RT "LRRC15 mediates an accessory interaction with the SARS-CoV-2 spike
RT protein.";
RL PLoS Biol. 21:e3001959-e3001959(2023).
RN [62]
RP INTERACTION WITH SARS-COV-2 SPIKE GLYCOPROTEIN (MICROBIAL INFECTION).
RX PubMed=36757924; DOI=10.1371/journal.pbio.3001967;
RA Loo L., Waller M.A., Moreno C.L., Cole A.J., Stella A.O., Pop O.T.,
RA Jochum A.K., Ali O.H., Denes C.E., Hamoudi Z., Chung F., Aggarwal A.,
RA Low J.K.K., Patel K., Siddiquee R., Kang T., Mathivanan S., Mackay J.P.,
RA Jochum W., Flatz L., Hesselson D., Turville S., Neely G.G.;
RT "Fibroblast-expressed LRRC15 is a receptor for SARS-CoV-2 spike and
RT controls antiviral and antifibrotic transcriptional programs.";
RL PLoS Biol. 21:e3001967-e3001967(2023).
RN [63] {ECO:0007744|PDB:1R42, ECO:0007744|PDB:1R4L}
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-615 IN COMPLEXES WITH ZINC;
RP CHLORIDE AND MLN-4760 INHIBITOR, DOMAIN, REACTION MECHANISM, ACTIVE SITE,
RP DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-53; ASN-90; ASN-103; ASN-322;
RP ASN-432 AND ASN-546.
RX PubMed=14754895; DOI=10.1074/jbc.m311191200;
RA Towler P., Staker B., Prasad S.G., Menon S., Tang J., Parsons T., Ryan D.,
RA Fisher M., Williams D., Dales N.A., Patane M.A., Pantoliano M.W.;
RT "ACE2 X-ray structures reveal a large hinge-bending motion important for
RT inhibitor binding and catalysis.";
RL J. Biol. Chem. 279:17996-18007(2004).
RN [64] {ECO:0007744|PDB:2AJF}
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 19-615 IN COMPLEX WITH ZINC, AND
RP GLYCOSYLATION AT ASN-53; ASN-90; ASN-322 AND ASN-546.
RX PubMed=16166518; DOI=10.1126/science.1116480;
RA Li F., Li W., Farzan M., Harrison S.C.;
RT "Structure of SARS coronavirus spike receptor-binding domain complexed with
RT receptor.";
RL Science 309:1864-1868(2005).
RN [65] {ECO:0007744|PDB:3KBH}
RP X-RAY CRYSTALLOGRAPHY (3.31 ANGSTROMS) OF 19-615, GLYCOSYLATION AT ASN-90
RP AND ASN-546 IN COMPLEX WITH HUMAN CORONAVIRUS NL63 SPIKE PROTEIN,
RP INTERACTION WITH HUMAN CORONAVIRUS NL63 SPIKE PROTEIN (MICROBIAL
RP INFECTION), AND FUNCTION (MICROBIAL INFECTION).
RX PubMed=19901337; DOI=10.1073/pnas.0908837106;
RA Wu K., Li W., Peng G., Li F.;
RT "Crystal structure of NL63 respiratory coronavirus receptor-binding domain
RT complexed with its human receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:19970-19974(2009).
RN [66] {ECO:0007744|PDB:6ACG, ECO:0007744|PDB:6ACJ, ECO:0007744|PDB:6ACK}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.20 ANGSTROMS) OF 19-615.
RX PubMed=30102747; DOI=10.1371/journal.ppat.1007236;
RA Song W., Gui M., Wang X., Xiang Y.;
RT "Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex
RT with its host cell receptor ACE2.";
RL PLoS Pathog. 14:e1007236-e1007236(2018).
RN [67] {ECO:0007744|PDB:6CS2}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.40 ANGSTROMS) OF 19-615.
RX PubMed=30356097; DOI=10.1038/s41598-018-34171-7;
RA Kirchdoerfer R.N., Wang N., Pallesen J., Wrapp D., Turner H.L.,
RA Cottrell C.A., Corbett K.S., Graham B.S., McLellan J.S., Ward A.B.;
RT "Stabilized coronavirus spikes are resistant to conformational changes
RT induced by receptor recognition or proteolysis.";
RL Sci. Rep. 8:15701-15701(2018).
RN [68] {ECO:0007744|PDB:6M0J}
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 19-615 IN COMPLEX WITH SARS-COV-2
RP SPIKE GLYCOPROTEIN.
RX PubMed=32225176; DOI=10.1038/s41586-020-2180-5;
RA Lan J., Ge J., Yu J., Shan S., Zhou H., Fan S., Zhang Q., Shi X., Wang Q.,
RA Zhang L., Wang X.;
RT "Structure of the SARS-CoV-2 spike receptor-binding domain bound to the
RT ACE2 receptor.";
RL Nature 581:215-220(2020).
RN [69] {ECO:0007744|PDB:6VW1}
RP X-RAY CRYSTALLOGRAPHY (2.68 ANGSTROMS) OF 19-615 AND IN COMPLEX WITH
RP SARS-COV-2 SPIKE GLYCOPROTEIN, INTERACTION WITH SARS-COV-2 SPIKE
RP GLYCOPROTEIN (MICROBIAL INFECTION), INTERACTION WITH SARS-COV SPIKE
RP GLYCOPROTEIN (MICROBIAL INFECTION), AND FUNCTION (MICROBIAL INFECTION).
RX PubMed=32225175; DOI=10.1038/s41586-020-2179-y;
RA Shang J., Ye G., Shi K., Wan Y., Luo C., Aihara H., Geng Q., Auerbach A.,
RA Li F.;
RT "Structural basis of receptor recognition by SARS-CoV-2.";
RL Nature 581:221-224(2020).
RN [70] {ECO:0007744|PDB:6M17, ECO:0007744|PDB:6M18, ECO:0007744|PDB:6M1D}
RP STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) OF 18-805, INTERACTION
RP WITH SARS-COV-2 SPIKE GLYCOPROTEIN (MICROBIAL INFECTION), INTERACTION WITH
RP SLC6A19, SUBUNIT, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=32132184; DOI=10.1126/science.abb2762;
RA Yan R., Zhang Y., Li Y., Xia L., Guo Y., Zhou Q.;
RT "Structural basis for the recognition of the SARS-CoV-2 by full-length
RT human ACE2.";
RL Science 367:1444-1448(2020).
RN [71]
RP VARIANT ASP-720.
RX PubMed=33133145; DOI=10.3389/fgene.2020.551220;
RA Shikov A.E., Barbitoff Y.A., Glotov A.S., Danilova M.M., Tonyan Z.N.,
RA Nasykhova Y.A., Mikhailova A.A., Bespalova O.N., Kalinin R.S.,
RA Mirzorustamova A.M., Kogan I.Y., Baranov V.S., Chernov A.N.,
RA Pavlovich D.M., Azarenko S.V., Fedyakov M.A., Tsay V.V., Eismont Y.A.,
RA Romanova O.V., Hobotnikov D.N., Vologzhanin D.A., Mosenko S.V.,
RA Ponomareva T.A., Talts Y.A., Anisenkova A.U., Lisovets D.G., Sarana A.M.,
RA Urazov S.P., Scherbak S.G., Glotov O.S.;
RT "Analysis of the Spectrum of ACE2 Variation Suggests a Possible Influence
RT of Rare and Common Variants on Susceptibility to COVID-19 and Severity of
RT Outcome.";
RL Front. Genet. 11:551220-551220(2020).
RN [72]
RP VARIANTS ARG-26; VAL-468; SER-638 AND ASP-720.
RX PubMed=32558308; DOI=10.1002/mgg3.1344;
RA Li Q., Cao Z., Rahman P.;
RT "Genetic variability of human angiotensin-converting enzyme 2 (hACE2) among
RT various ethnic populations.";
RL Mol. Genet. Genomic Med. 0:0-0(2020).
CC -!- FUNCTION: Essential counter-regulatory carboxypeptidase of the renin-
CC angiotensin hormone system that is a critical regulator of blood
CC volume, systemic vascular resistance, and thus cardiovascular
CC homeostasis (PubMed:27217402). Converts angiotensin I to angiotensin 1-
CC 9, a nine-amino acid peptide with anti-hypertrophic effects in
CC cardiomyocytes, and angiotensin II to angiotensin 1-7, which then acts
CC as a beneficial vasodilator and anti-proliferation agent,
CC counterbalancing the actions of the vasoconstrictor angiotensin II
CC (PubMed:10969042, PubMed:10924499, PubMed:11815627, PubMed:19021774,
CC PubMed:14504186). Also removes the C-terminal residue from three other
CC vasoactive peptides, neurotensin, kinetensin, and des-Arg bradykinin,
CC but is not active on bradykinin (PubMed:10969042, PubMed:11815627).
CC Also cleaves other biological peptides, such as apelins (apelin-13,
CC [Pyr1]apelin-13, apelin-17, apelin-36), casomorphins (beta-casomorphin-
CC 7, neocasomorphin) and dynorphin A with high efficiency
CC (PubMed:11815627, PubMed:27217402, PubMed:28293165). In addition, ACE2
CC C-terminus is homologous to collectrin and is responsible for the
CC trafficking of the neutral amino acid transporter SL6A19 to the plasma
CC membrane of gut epithelial cells via direct interaction, regulating its
CC expression on the cell surface and its catalytic activity
CC (PubMed:18424768, PubMed:19185582). {ECO:0000269|PubMed:10924499,
CC ECO:0000269|PubMed:10969042, ECO:0000269|PubMed:11815627,
CC ECO:0000269|PubMed:14504186, ECO:0000269|PubMed:18424768,
CC ECO:0000269|PubMed:19021774, ECO:0000269|PubMed:19185582,
CC ECO:0000269|PubMed:27217402}.
CC -!- FUNCTION: (Microbial infection) Acts as a receptor for human
CC coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus
CC NL63/HCoV-NL63. {ECO:0000269|PubMed:14647384,
CC ECO:0000269|PubMed:15452268, ECO:0000269|PubMed:15791205,
CC ECO:0000269|PubMed:15897467, ECO:0000269|PubMed:19901337,
CC ECO:0000269|PubMed:24227843, ECO:0000269|PubMed:32142651,
CC ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32221306,
CC ECO:0000269|PubMed:32225175, ECO:0000269|PubMed:33000221,
CC ECO:0000269|PubMed:33082294, ECO:0000269|PubMed:33432067}.
CC -!- FUNCTION: [Isoform 2]: Non-functional as a carboxypeptidase.
CC {ECO:0000269|PubMed:33077916}.
CC -!- FUNCTION: [Isoform 2]: (Microbial infection) Non-functional as a
CC receptor for human coronavirus SARS-CoV-2.
CC {ECO:0000269|PubMed:33077916, ECO:0000269|PubMed:33432184}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=angiotensin II + H2O = angiotensin-(1-7) + L-phenylalanine;
CC Xref=Rhea:RHEA:26554, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095,
CC ChEBI:CHEBI:58506, ChEBI:CHEBI:58922; EC=3.4.17.23;
CC Evidence={ECO:0000269|PubMed:10924499, ECO:0000269|PubMed:11815627,
CC ECO:0000269|PubMed:19021774, ECO:0000305|PubMed:14504186};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26555;
CC Evidence={ECO:0000269|PubMed:14504186};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=angiotensin I + H2O = angiotensin-(1-9) + L-leucine;
CC Xref=Rhea:RHEA:63532, ChEBI:CHEBI:15377, ChEBI:CHEBI:57427,
CC ChEBI:CHEBI:147350, ChEBI:CHEBI:147351;
CC Evidence={ECO:0000269|PubMed:10924499, ECO:0000269|PubMed:10969042,
CC ECO:0000269|PubMed:11815627, ECO:0000269|PubMed:19021774};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63533;
CC Evidence={ECO:0000305|PubMed:10924499, ECO:0000305|PubMed:10969042,
CC ECO:0000305|PubMed:11815627, ECO:0000305|PubMed:19021774};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=bradykinin(1-8) + H2O = bradykinin(1-7) + L-phenylalanine;
CC Xref=Rhea:RHEA:63536, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095,
CC ChEBI:CHEBI:133069, ChEBI:CHEBI:147352;
CC Evidence={ECO:0000269|PubMed:10969042, ECO:0000269|PubMed:11815627};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63537;
CC Evidence={ECO:0000305|PubMed:10969042, ECO:0000305|PubMed:11815627};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + neurotensin = L-leucine + neurotensin-(1-12);
CC Xref=Rhea:RHEA:63540, ChEBI:CHEBI:15377, ChEBI:CHEBI:57427,
CC ChEBI:CHEBI:147362, ChEBI:CHEBI:147363;
CC Evidence={ECO:0000269|PubMed:10969042};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63541;
CC Evidence={ECO:0000305|PubMed:10969042};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + neurotensin-(1-8) = L-arginine + neurotensin-(1-7);
CC Xref=Rhea:RHEA:63572, ChEBI:CHEBI:15377, ChEBI:CHEBI:32682,
CC ChEBI:CHEBI:147393, ChEBI:CHEBI:147394;
CC Evidence={ECO:0000269|PubMed:11815627};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63573;
CC Evidence={ECO:0000305|PubMed:11815627};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + kinetensin = kinetensin-(1-8) + L-leucine;
CC Xref=Rhea:RHEA:63544, ChEBI:CHEBI:15377, ChEBI:CHEBI:57427,
CC ChEBI:CHEBI:147364, ChEBI:CHEBI:147365;
CC Evidence={ECO:0000269|PubMed:10969042};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63545;
CC Evidence={ECO:0000305|PubMed:10969042};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dynorphin A-(1-13) + H2O = dynorphin A-(1-12) + L-lysine;
CC Xref=Rhea:RHEA:63556, ChEBI:CHEBI:15377, ChEBI:CHEBI:32551,
CC ChEBI:CHEBI:147381, ChEBI:CHEBI:147383;
CC Evidence={ECO:0000269|PubMed:11815627};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63557;
CC Evidence={ECO:0000305|PubMed:11815627};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=apelin-13 + H2O = apelin-12 + L-phenylalanine;
CC Xref=Rhea:RHEA:63564, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095,
CC ChEBI:CHEBI:147395, ChEBI:CHEBI:147396;
CC Evidence={ECO:0000269|PubMed:11815627};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63565;
CC Evidence={ECO:0000305|PubMed:11815627};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[Pyr1]apelin-13 + H2O = [Pyr1]apelin-12 + L-phenylalanine;
CC Xref=Rhea:RHEA:63604, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095,
CC ChEBI:CHEBI:147415, ChEBI:CHEBI:147416;
CC Evidence={ECO:0000269|PubMed:27217402, ECO:0000269|PubMed:28293165};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63605;
CC Evidence={ECO:0000269|PubMed:27217402};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=apelin-17 + H2O = apelin-16 + L-phenylalanine;
CC Xref=Rhea:RHEA:63608, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095,
CC ChEBI:CHEBI:147421, ChEBI:CHEBI:147422;
CC Evidence={ECO:0000269|PubMed:27217402};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63609;
CC Evidence={ECO:0000269|PubMed:27217402};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-casomorphin-7 + H2O = beta-casomorphin-6 + L-isoleucine;
CC Xref=Rhea:RHEA:63568, ChEBI:CHEBI:15377, ChEBI:CHEBI:58045,
CC ChEBI:CHEBI:147390, ChEBI:CHEBI:147391;
CC Evidence={ECO:0000269|PubMed:11815627};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63569;
CC Evidence={ECO:0000305|PubMed:11815627};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + neocasomorphin = L-isoleucine + neocasomorphin-(1-5);
CC Xref=Rhea:RHEA:63600, ChEBI:CHEBI:15377, ChEBI:CHEBI:58045,
CC ChEBI:CHEBI:147417, ChEBI:CHEBI:147418;
CC Evidence={ECO:0000269|PubMed:11815627};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63601;
CC Evidence={ECO:0000305|PubMed:11815627};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:11815627};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:11815627};
CC -!- COFACTOR:
CC Name=chloride; Xref=ChEBI:CHEBI:17996;
CC Evidence={ECO:0000269|PubMed:11815627};
CC Note=Binds 1 Cl(-) ion per subunit. {ECO:0000269|PubMed:11815627};
CC -!- ACTIVITY REGULATION: Regulated by chloride and fluoride, but not
CC bromide (PubMed:11815627). Chloride increases angiotensin I and
CC decreases angiotensin II cleavage (PubMed:19021774). Inhibited by MLN-
CC 4760, cFP_Leu, and EDTA (PubMed:15231706, PubMed:10924499), but not by
CC the ACE inhibitors lisinopril, captopril and enalaprilat
CC (PubMed:10969042, PubMed:10924499). Highly potent and selective in
CC vitro ACE2 inhibitors were identified (PubMed:12358520).
CC {ECO:0000269|PubMed:10924499, ECO:0000269|PubMed:10969042,
CC ECO:0000269|PubMed:11815627, ECO:0000269|PubMed:12358520,
CC ECO:0000269|PubMed:15231706, ECO:0000269|PubMed:19021774}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.9 uM for angiotensin I {ECO:0000269|PubMed:11815627};
CC KM=2.0 uM for angiotensin II {ECO:0000269|PubMed:11815627};
CC KM=6.8 uM for apelin-13 {ECO:0000269|PubMed:11815627};
CC KM=290 uM for [des-Arg(9)]-bradykinin {ECO:0000269|PubMed:11815627};
CC KM=130 uM for Lys-[des-Arg(9)]-bradykinin
CC {ECO:0000269|PubMed:11815627};
CC KM=31 uM for beta-casomorphin {ECO:0000269|PubMed:11815627};
CC KM=5.5 uM for dynorphin A-(1-13) {ECO:0000269|PubMed:11815627};
CC KM=300 uM for neurotensin-(1-8) {ECO:0000269|PubMed:11815627};
CC KM=58.6 uM for angiotensin II {ECO:0000269|PubMed:19021774};
CC KM=12 uM for [Pyr1]apelin-13 {ECO:0000269|PubMed:27217402};
CC KM=19 uM for apelin-17 {ECO:0000269|PubMed:27217402};
CC Vmax=28.7 nmol/min/mg enzyme with angiotensin II as substrate
CC {ECO:0000269|PubMed:19021774};
CC Note=kcat is 0.034 sec(-1) with angiotensin I as substrate. kcat is
CC 3.5 sec(-1) with angiotensin II as substrate. kcat is 13 sec(-1) with
CC apelin-13 as substrate. kcat is 62 sec(-1) with [des-Arg(9)]-
CC bradykinin as substrate. kcat is 26 sec(-1) with Lys-[des-Arg(9)]-
CC bradykinin as substrate. kcat is 6.8 sec(-1) with beta-casomorphin as
CC substrate. kcat is 16 sec(-1) with dynorphin A-(1-13) as substrate.
CC kcat is 57 sec(-1) with neurotensin-(1-8) as substrate
CC (PubMed:11815627). kcat is 19.1 sec(-1) with [Pyr1]apelin-13 as
CC substrate. kcat is 7.7 sec(-1) with apelin-17 as substrate
CC (PubMed:27217402). {ECO:0000269|PubMed:11815627,
CC ECO:0000269|PubMed:27217402};
CC pH dependence:
CC Optimum pH is 6.5 in the presence of 1 M NaCl. Active from pH 6 to 9.
CC {ECO:0000269|PubMed:11815627};
CC -!- SUBUNIT: Homodimer (PubMed:32132184). Interacts with the catalytically
CC active form of TMPRSS2 (PubMed:21068237). Interacts with SLC6A19; this
CC interaction is essential for expression and function of SLC6A19 in
CC intestine (By similarity). Interacts with ITGA5:ITGB1 (PubMed:15276642,
CC PubMed:33102950). Probably interacts (via endocytic sorting signal
CC motif) with AP2M1; the interaction is inhibited by phosphorylation of
CC Tyr-781 (PubMed:33436498). Interacts (via PDZ-binding motif) with
CC NHERF1 (via PDZ domains); the interaction may enhance ACE2 membrane
CC residence (PubMed:34189428). {ECO:0000250|UniProtKB:Q8R0I0,
CC ECO:0000269|PubMed:15276642, ECO:0000269|PubMed:21068237,
CC ECO:0000269|PubMed:32132184, ECO:0000269|PubMed:33102950,
CC ECO:0000269|PubMed:33436498, ECO:0000269|PubMed:34189428}.
CC -!- SUBUNIT: (Microbial infection) Interacts with SARS coronavirus/SARS-CoV
CC spike protein. {ECO:0000269|PubMed:14647384,
CC ECO:0000269|PubMed:15452268, ECO:0000269|PubMed:15791205,
CC ECO:0000269|PubMed:32225175}.
CC -!- SUBUNIT: (Microbial infection) Interacts with SARS coronavirus-2/SARS-
CC CoV-2 spike protein (via RBD domain). {ECO:0000269|PubMed:32075877,
CC ECO:0000269|PubMed:32132184, ECO:0000269|PubMed:32155444,
CC ECO:0000269|PubMed:32225175, ECO:0000269|PubMed:32753553,
CC ECO:0000269|PubMed:33102950, ECO:0000269|PubMed:33432067,
CC ECO:0000269|PubMed:36228039, ECO:0000269|PubMed:36735681,
CC ECO:0000269|PubMed:36757924}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human coronavirus NL63
CC spike protein. {ECO:0000269|PubMed:19901337}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human coronavirus
CC NL63/HCoV-NL63 spike glycoprotein. {ECO:0000269|PubMed:15897467}.
CC -!- SUBUNIT: [Processed angiotensin-converting enzyme 2]: (Microbial
CC infection) Interacts with SARS coronavirus-2/SARS-CoV-2 spike protein;
CC the interaction is increased by AVP/Arg-vasopressin with which they may
CC form a complex. {ECO:0000269|PubMed:33713620}.
CC -!- INTERACTION:
CC Q9BYF1; Q9BYF1: ACE2; NbExp=8; IntAct=EBI-7730807, EBI-7730807;
CC Q9BYF1; PRO_0000032457 [P01019]: AGT; NbExp=2; IntAct=EBI-7730807, EBI-25493366;
CC Q9BYF1; PRO_0000032458 [P01019]: AGT; NbExp=5; IntAct=EBI-7730807, EBI-6622938;
CC Q9BYF1; Q96CW1: AP2M1; NbExp=2; IntAct=EBI-7730807, EBI-297683;
CC Q9BYF1; PRO_0000000092 [P05067]: APP; NbExp=3; IntAct=EBI-7730807, EBI-821758;
CC Q9BYF1; Q9H2X3: CLEC4M; NbExp=3; IntAct=EBI-7730807, EBI-1391211;
CC Q9BYF1; PRO_0000417390 [Q01523]: DEFA5; NbExp=4; IntAct=EBI-7730807, EBI-25634589;
CC Q9BYF1; Q14416: GRM2; NbExp=2; IntAct=EBI-7730807, EBI-10232876;
CC Q9BYF1; P11021: HSPA5; NbExp=6; IntAct=EBI-7730807, EBI-354921;
CC Q9BYF1; P05556: ITGB1; NbExp=4; IntAct=EBI-7730807, EBI-703066;
CC Q9BYF1; O60341: KDM1A; NbExp=19; IntAct=EBI-7730807, EBI-710124;
CC Q9BYF1; PRO_0000006688 [P01042]: KNG1; NbExp=5; IntAct=EBI-7730807, EBI-6623273;
CC Q9BYF1; PRO_0000019524 [P30990]: NTS; NbExp=2; IntAct=EBI-7730807, EBI-6655817;
CC Q9BYF1; Q5T2W1: PDZK1; NbExp=3; IntAct=EBI-7730807, EBI-349819;
CC Q9BYF1; P35247: SFTPD; NbExp=2; IntAct=EBI-7730807, EBI-11316157;
CC Q9BYF1; Q9Y566: SHANK1; NbExp=2; IntAct=EBI-7730807, EBI-3442234;
CC Q9BYF1; Q695T7: SLC6A19; NbExp=4; IntAct=EBI-7730807, EBI-25475705;
CC Q9BYF1; O14745: SLC9A3R1; NbExp=7; IntAct=EBI-7730807, EBI-349787;
CC Q9BYF1; Q96L92: SNX27; NbExp=2; IntAct=EBI-7730807, EBI-2514865;
CC Q9BYF1; O15393: TMPRSS2; NbExp=3; IntAct=EBI-7730807, EBI-12549863;
CC Q9BYF1; P08670: VIM; NbExp=4; IntAct=EBI-7730807, EBI-353844;
CC Q9BYF1; P52293: Kpna2; Xeno; NbExp=4; IntAct=EBI-7730807, EBI-3043908;
CC Q9BYF1; A0A6B9WHD3: S; Xeno; NbExp=2; IntAct=EBI-7730807, EBI-25496413;
CC Q9BYF1; A0A6G6A1M4: S; Xeno; NbExp=4; IntAct=EBI-7730807, EBI-26997256;
CC Q9BYF1; A0A6M3G9R1: S; Xeno; NbExp=4; IntAct=EBI-7730807, EBI-26997195;
CC Q9BYF1; P0DTC2: S; Xeno; NbExp=254; IntAct=EBI-7730807, EBI-25474821;
CC Q9BYF1; PRO_0000449647 [P0DTC2]: S; Xeno; NbExp=2; IntAct=EBI-7730807, EBI-25490323;
CC Q9BYF1; P59594: S; Xeno; NbExp=57; IntAct=EBI-7730807, EBI-15582614;
CC Q9BYF1; PRO_0000037209 [P59594]: S; Xeno; NbExp=3; IntAct=EBI-7730807, EBI-25475261;
CC Q9BYF1; Q5GDB5: S; Xeno; NbExp=2; IntAct=EBI-7730807, EBI-25566398;
CC Q9BYF1; Q6Q1S2: S; Xeno; NbExp=9; IntAct=EBI-7730807, EBI-15814420;
CC -!- SUBCELLULAR LOCATION: [Processed angiotensin-converting enzyme 2]:
CC Secreted {ECO:0000269|PubMed:15983030, ECO:0000269|PubMed:33713620}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18424768};
CC Single-pass type I membrane protein {ECO:0000255}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q8R0I0}. Cell projection, cilium
CC {ECO:0000269|PubMed:33432184}. Apical cell membrane
CC {ECO:0000269|PubMed:33432184}. Note=Detected in both cell membrane and
CC cytoplasm in neurons. {ECO:0000250|UniProtKB:Q8R0I0}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Apical cell membrane
CC {ECO:0000269|PubMed:33432184}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=long {ECO:0000303|PubMed:33432184};
CC IsoId=Q9BYF1-1; Sequence=Displayed;
CC Name=2; Synonyms=delta {ECO:0000303|PubMed:33077916}, dACE2
CC {ECO:0000303|PubMed:33077916}, short {ECO:0000303|PubMed:33432184};
CC IsoId=Q9BYF1-3; Sequence=VSP_060903;
CC -!- TISSUE SPECIFICITY: Expressed in endothelial cells from small and large
CC arteries, and in arterial smooth muscle cells (at protein level)
CC (PubMed:15141377). Expressed in enterocytes of the small intestine,
CC Leydig cells and Sertoli cells (at protein level) (PubMed:15141377).
CC Expressed in the renal proximal tubule and the small intestine (at
CC protein level) (PubMed:18424768). Expressed in heart, kidney, testis,
CC and gastrointestinal system (at protein level) (PubMed:10969042,
CC PubMed:10924499, PubMed:15231706, PubMed:12459472, PubMed:15671045,
CC PubMed:32715618, PubMed:32170560). In lung, expressed at low levels in
CC some alveolar type 2 cells, the expression seems to be individual-
CC specific (at protein level) (PubMed:32425701, PubMed:15141377,
CC PubMed:32715618, PubMed:32170560, PubMed:33432184). Expressed in nasal
CC epithelial cells (at protein level) (PubMed:33432184, PubMed:32333915).
CC Coexpressed with TMPRSS2 within some lung alveolar type 2 cells, ileal
CC absorptive enterocytes, intestinal epithelial cells, cornea,
CC gallbladder and nasal goblet secretory cells (PubMed:32413319,
CC PubMed:32327758, PubMed:32358202). Coexpressed with TMPRSS4 within
CC mature enterocytes (PubMed:32404436). {ECO:0000269|PubMed:10924499,
CC ECO:0000269|PubMed:10969042, ECO:0000269|PubMed:12459472,
CC ECO:0000269|PubMed:15141377, ECO:0000269|PubMed:15231706,
CC ECO:0000269|PubMed:15671045, ECO:0000269|PubMed:18424768,
CC ECO:0000269|PubMed:32170560, ECO:0000269|PubMed:32327758,
CC ECO:0000269|PubMed:32333915, ECO:0000269|PubMed:32358202,
CC ECO:0000269|PubMed:32404436, ECO:0000269|PubMed:32413319,
CC ECO:0000269|PubMed:32425701, ECO:0000269|PubMed:32715618,
CC ECO:0000269|PubMed:33432184}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in nasal and bronchial
CC epithelial cells (at protein level). {ECO:0000269|PubMed:33432184}.
CC -!- INDUCTION: Up-regulated in failing heart (PubMed:14504186,
CC PubMed:15151696, PubMed:15671045). Expression is induced by IFNA and
CC IFNG (PubMed:32413319, PubMed:32425701). Exposure to cigarette smoke
CC increases expression in lungs (PubMed:32425701). Expression is
CC decreased in nasal and bronchial epithelium of individuals with allergy
CC after allergen challenge (PubMed:32333915). IL13 stimulation decreases
CC expression in nasal and bronchial epithelium (PubMed:32333915).
CC {ECO:0000269|PubMed:14504186, ECO:0000269|PubMed:15151696,
CC ECO:0000269|PubMed:15671045, ECO:0000269|PubMed:32333915,
CC ECO:0000269|PubMed:32413319, ECO:0000269|PubMed:32425701}.
CC -!- INDUCTION: [Isoform 1]: Not induced by interferons such as IFNA, IFNB
CC and IFNG. {ECO:0000269|PubMed:33077916}.
CC -!- INDUCTION: [Isoform 2]: Expression is induced by interferons such as
CC IFNA, IFNB and IFNG. It seems that isoform 2 is an interferon-
CC stimulated gene (ISG) but not isoform 1. {ECO:0000269|PubMed:33077916}.
CC -!- INDUCTION: (Microbial infection) In airway epithelial cells, expression
CC is increased upon influenza A virus infection (PubMed:32413319).
CC {ECO:0000269|PubMed:32413319}.
CC -!- INDUCTION: [Isoform 2]: (Microbial infection) In airway epithelial
CC cells, expression is induced by viruses such rhinoviruses and influenza
CC virus. {ECO:0000269|PubMed:33077916, ECO:0000269|PubMed:33432184}.
CC -!- INDUCTION: [Isoform 2]: (Microbial infection) Induced by human
CC coronavirus SARS-CoV-2. {ECO:0000269|PubMed:33077916}.
CC -!- DOMAIN: The extracellular region of the ACE2 enzyme is composed of two
CC domains. The first is a zinc metallopeptidase domain (residues 19-611).
CC The second domain is located at the C-terminus (residues 612-740) and
CC is 48% identical to human collectrin. {ECO:0000269|PubMed:14754895}.
CC -!- DOMAIN: The cytoplasmic tail contains several linear motifs such as
CC LIR, PDZ-binding, PTB and endocytic sorting signal motifs that would
CC allow interaction with proteins that mediate endocytic trafficking and
CC autophagy. {ECO:0000305|PubMed:33436497, ECO:0000305|PubMed:33436498}.
CC -!- PTM: N-glycosylation on Asn-90 may limit SARS infectivity.
CC {ECO:0000269|PubMed:10924499, ECO:0000269|PubMed:14647384,
CC ECO:0000269|PubMed:14754895, ECO:0000269|PubMed:15084671,
CC ECO:0000269|PubMed:19159218}.
CC -!- PTM: Proteolytic cleavage by ADAM17 generates a secreted form
CC (PubMed:15983030, PubMed:33713620). Also cleaved by serine proteases:
CC TMPRSS2, TMPRSS11D and HPN/TMPRSS1. {ECO:0000269|PubMed:15983030,
CC ECO:0000269|PubMed:21068237, ECO:0000269|PubMed:21563828,
CC ECO:0000269|PubMed:24227843, ECO:0000269|PubMed:32132184,
CC ECO:0000269|PubMed:33713620}.
CC -!- PTM: Phosphorylated. Phosphorylation at Tyr-781 probably inhibits
CC interaction with AP2M1 and enables interactions with proteins
CC containing SH2 domains. {ECO:0000305|PubMed:33436497,
CC ECO:0000305|PubMed:33436498}.
CC -!- BIOTECHNOLOGY: An engeneered stable, dimeric and secreted receptor with
CC combined mutations that increase the affinity for human coronavirus
CC SARS-CoV-2 spike protein shows potent SARS-CoV and SARS-CoV-2
CC neutralization in vitro. {ECO:0000269|PubMed:32753553}.
CC -!- SIMILARITY: Belongs to the peptidase M2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ89076.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/ace2/";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=A way in - Issue 223 of
CC March 2020;
CC URL="https://web.expasy.org/spotlight/back_issues/223/";
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DR EMBL; AF291820; AAF99721.1; -; mRNA.
DR EMBL; AF241254; AAF78220.1; -; mRNA.
DR EMBL; AY623811; AAT45083.1; -; mRNA.
DR EMBL; AB193259; BAD99266.1; -; mRNA.
DR EMBL; AB193260; BAD99267.1; -; mRNA.
DR EMBL; AB046569; BAB40370.1; -; mRNA.
DR EMBL; E39033; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; GQ262784; ACT66268.1; -; mRNA.
DR EMBL; MT505392; QLP88822.1; -; mRNA.
DR EMBL; AY358714; AAQ89076.1; ALT_SEQ; mRNA.
DR EMBL; AY217547; AAO25651.1; -; Genomic_DNA.
DR EMBL; CH471074; EAW98892.1; -; Genomic_DNA.
DR EMBL; BC039902; AAH39902.1; -; mRNA.
DR EMBL; BC048094; AAH48094.2; -; mRNA.
DR EMBL; AL110224; CAB53682.1; -; mRNA.
DR CCDS; CCDS14169.1; -. [Q9BYF1-1]
DR CCDS; CCDS94556.1; -. [Q9BYF1-3]
DR PIR; T14762; T14762.
DR RefSeq; NP_068576.1; NM_021804.2. [Q9BYF1-1]
DR PDB; 1R42; X-ray; 2.20 A; A=1-615.
DR PDB; 1R4L; X-ray; 3.00 A; A=1-615.
DR PDB; 2AJF; X-ray; 2.90 A; A/B=19-615.
DR PDB; 3D0G; X-ray; 2.80 A; A/B=56-615.
DR PDB; 3D0H; X-ray; 3.10 A; A/B=56-615.
DR PDB; 3D0I; X-ray; 2.90 A; A/B=56-615.
DR PDB; 3KBH; X-ray; 3.31 A; A/B/C/D=19-615.
DR PDB; 3SCI; X-ray; 2.90 A; A/B=19-615.
DR PDB; 3SCJ; X-ray; 3.00 A; A/B=19-615.
DR PDB; 3SCK; X-ray; 3.00 A; A/B=83-615.
DR PDB; 3SCL; X-ray; 3.00 A; A/B=83-615.
DR PDB; 6ACG; EM; 5.40 A; D=19-615.
DR PDB; 6ACJ; EM; 4.20 A; D=19-615.
DR PDB; 6ACK; EM; 4.50 A; D=19-615.
DR PDB; 6CS2; EM; 4.40 A; D=19-615.
DR PDB; 6LZG; X-ray; 2.50 A; A=19-614.
DR PDB; 6M0J; X-ray; 2.45 A; A=19-615.
DR PDB; 6M17; EM; 2.90 A; B/D=18-805.
DR PDB; 6M18; EM; 2.90 A; B/D=18-805.
DR PDB; 6M1D; EM; 4.50 A; B/D=18-805.
DR PDB; 6VW1; X-ray; 2.68 A; A/B=19-615.
DR PDB; 7A91; EM; 3.60 A; D=19-613.
DR PDB; 7A92; EM; 4.20 A; D=19-613.
DR PDB; 7A94; EM; 3.90 A; D=19-615.
DR PDB; 7A95; EM; 4.30 A; D=19-615.
DR PDB; 7A96; EM; 4.80 A; D=19-615.
DR PDB; 7A97; EM; 4.40 A; D/E=19-615.
DR PDB; 7A98; EM; 5.40 A; D/E/F=19-615.
DR PDB; 7BH9; EM; 2.90 A; A=19-615.
DR PDB; 7CT5; EM; 4.00 A; D/E/F=18-805.
DR PDB; 7DDO; EM; 3.40 A; A=19-615.
DR PDB; 7DDP; EM; 3.40 A; A=19-615.
DR PDB; 7DF4; EM; 3.80 A; A=17-615.
DR PDB; 7DMU; X-ray; 3.20 A; A/C=18-615.
DR PDB; 7DQA; EM; 2.80 A; A=1-805.
DR PDB; 7DRV; X-ray; 3.09 A; A/B=19-614.
DR PDB; 7DWX; EM; 8.30 A; B/D=2-805.
DR PDB; 7DX4; EM; 3.60 A; A=19-615.
DR PDB; 7DX5; EM; 3.30 A; D=2-805.
DR PDB; 7DX6; EM; 3.00 A; D=2-805.
DR PDB; 7DX7; EM; 3.40 A; D=2-805.
DR PDB; 7DX8; EM; 2.90 A; D/E=2-805.
DR PDB; 7DX9; EM; 3.60 A; D/E=2-805.
DR PDB; 7E7E; X-ray; 3.80 A; A/B=18-615.
DR PDB; 7EDJ; EM; 3.30 A; I/J/K=1-617.
DR PDB; 7EFP; X-ray; 2.70 A; A=19-615.
DR PDB; 7EFR; X-ray; 2.49 A; A=19-615.
DR PDB; 7EKC; X-ray; 2.80 A; A=19-615.
DR PDB; 7EKE; X-ray; 2.70 A; A=19-615.
DR PDB; 7EKF; X-ray; 2.85 A; A=19-615.
DR PDB; 7EKG; X-ray; 2.63 A; A=19-615.
DR PDB; 7EKH; X-ray; 2.40 A; A=19-615.
DR PDB; 7FDG; EM; 3.69 A; A=1-615.
DR PDB; 7FDH; EM; 3.72 A; A=1-615.
DR PDB; 7FDI; EM; 3.12 A; A=1-615.
DR PDB; 7FEM; EM; 4.10 A; D=18-740.
DR PDB; 7JVO; X-ray; 2.20 A; B=766-779.
DR PDB; 7KJ2; EM; 3.60 A; D=11-615.
DR PDB; 7KJ3; EM; 3.70 A; D/E=11-615.
DR PDB; 7KJ4; EM; 3.40 A; D/E/F=11-615.
DR PDB; 7KMB; EM; 3.39 A; F=19-615.
DR PDB; 7KMS; EM; 3.64 A; D/E/F=19-615.
DR PDB; 7KMZ; EM; 3.62 A; D/E=19-615.
DR PDB; 7KNB; EM; 3.93 A; D=19-615.
DR PDB; 7KNE; EM; 3.85 A; D=19-615.
DR PDB; 7KNH; EM; 3.74 A; D/E=19-615.
DR PDB; 7KNI; EM; 3.91 A; D/E/F=19-615.
DR PDB; 7L0N; X-ray; 2.78 A; E/F=19-615.
DR PDB; 7L7F; EM; 3.24 A; B/D=1-805.
DR PDB; 7LO4; X-ray; 2.46 A; A=19-614.
DR PDB; 7MJM; EM; 2.83 A; D/E=18-615.
DR PDB; 7MJN; EM; 3.29 A; E=18-615.
DR PDB; 7NXC; X-ray; 3.14 A; A=19-615.
DR PDB; 7P19; X-ray; 3.24 A; A/B=19-615.
DR PDB; 7P55; NMR; -; A=21-42.
DR PDB; 7P8I; X-ray; 4.50 A; A/C=19-615.
DR PDB; 7P8J; X-ray; 6.58 A; A/C=19-615.
DR PDB; 7PKI; X-ray; 2.94 A; A=19-614.
DR PDB; 7R0Z; EM; 3.50 A; D=19-613.
DR PDB; 7R10; EM; 4.00 A; D=19-613.
DR PDB; 7R11; EM; 3.50 A; D=19-613.
DR PDB; 7R12; EM; 3.30 A; D=19-613.
DR PDB; 7R1A; EM; 3.90 A; D/E/F=19-613.
DR PDB; 7RPV; X-ray; 3.54 A; A/B/C/D=19-615.
DR PDB; 7SN0; X-ray; 3.08 A; A/B=1-615.
DR PDB; 7SXX; EM; 2.66 A; E=18-615.
DR PDB; 7SXY; EM; 2.79 A; E=18-615.
DR PDB; 7SXZ; EM; 2.61 A; E=18-615.
DR PDB; 7SY0; EM; 3.00 A; E=18-615.
DR PDB; 7SY1; EM; 2.83 A; E=18-615.
DR PDB; 7SY2; EM; 3.11 A; E=18-615.
DR PDB; 7SY3; EM; 2.95 A; E=18-615.
DR PDB; 7SY4; EM; 3.35 A; E=18-615.
DR PDB; 7SY5; EM; 2.59 A; D/E/F=18-615.
DR PDB; 7SY6; EM; 2.81 A; E=18-615.
DR PDB; 7SY7; EM; 2.81 A; E=18-615.
DR PDB; 7SY8; EM; 3.14 A; E=18-615.
DR PDB; 7T9K; EM; 2.45 A; D/E=18-615.
DR PDB; 7T9L; EM; 2.66 A; D=18-615.
DR PDB; 7TEW; EM; 3.52 A; E=18-615.
DR PDB; 7TEX; EM; 3.27 A; E=18-615.
DR PDB; 7TEZ; EM; 3.27 A; E=18-615.
DR PDB; 7TF0; EM; 3.02 A; E=18-615.
DR PDB; 7TN0; X-ray; 2.85 A; E/F=19-615.
DR PDB; 7U0N; X-ray; 2.61 A; A/B=19-615.
DR PDB; 7UFK; X-ray; 2.38 A; A/B=19-615.
DR PDB; 7V61; EM; 3.20 A; B/D=2-805.
DR PDB; 7V7Z; EM; 3.10 A; D/E/F=1-617.
DR PDB; 7V80; EM; 3.90 A; F=1-617.
DR PDB; 7V81; EM; 3.20 A; D/E=1-617.
DR PDB; 7V82; EM; 2.80 A; D/E/F=1-617.
DR PDB; 7V83; EM; 2.80 A; D/E/F=1-617.
DR PDB; 7V84; EM; 3.00 A; F=1-617.
DR PDB; 7V85; EM; 3.30 A; F/H=1-617.
DR PDB; 7V86; EM; 2.80 A; F/G/H=1-617.
DR PDB; 7V87; EM; 3.30 A; F=1-617.
DR PDB; 7V88; EM; 3.30 A; F/G=1-617.
DR PDB; 7V89; EM; 2.80 A; F/G/H=1-617.
DR PDB; 7V8A; EM; 2.70 A; F/G/H=1-617.
DR PDB; 7V8B; EM; 3.20 A; F=1-617.
DR PDB; 7VIB; X-ray; 3.20 A; A/C=19-615.
DR PDB; 7VX4; EM; 3.90 A; A=17-615.
DR PDB; 7VX5; EM; 3.80 A; A=17-615.
DR PDB; 7VX9; EM; 4.00 A; C=19-615.
DR PDB; 7VXA; EM; 3.90 A; C=17-615.
DR PDB; 7VXB; EM; 3.90 A; C=17-615.
DR PDB; 7VXC; EM; 3.90 A; C=17-615.
DR PDB; 7VXD; EM; 4.00 A; C=17-615.
DR PDB; 7VXF; EM; 3.60 A; C=17-615.
DR PDB; 7VXK; EM; 3.70 A; C=17-615.
DR PDB; 7VXM; EM; 3.60 A; C=17-615.
DR PDB; 7W98; EM; 3.60 A; D=17-615.
DR PDB; 7W99; EM; 3.40 A; B=17-615.
DR PDB; 7W9B; EM; 3.40 A; A=17-615.
DR PDB; 7W9C; EM; 3.20 A; A=17-615.
DR PDB; 7W9I; EM; 3.40 A; A=17-615.
DR PDB; 7WBL; EM; 3.40 A; A=19-614.
DR PDB; 7WBP; X-ray; 3.00 A; A=19-614.
DR PDB; 7WBQ; X-ray; 3.34 A; A/C=19-614.
DR PDB; 7WGB; EM; 3.50 A; D/F=19-612.
DR PDB; 7WGC; EM; 3.60 A; A=19-612.
DR PDB; 7WHH; X-ray; 2.60 A; A=19-615.
DR PDB; 7WK4; EM; 3.69 A; A=17-615.
DR PDB; 7WK5; EM; 3.66 A; A=17-615.
DR PDB; 7WK6; EM; 3.67 A; A=17-615.
DR PDB; 7WNM; X-ray; 2.70 A; B=1-740.
DR PDB; 7WPA; EM; 2.77 A; D=1-805.
DR PDB; 7WPB; EM; 2.79 A; D=1-805.
DR PDB; 7WPC; EM; 2.57 A; D=1-805.
DR PDB; 7WS8; EM; 3.00 A; D/E=19-613.
DR PDB; 7WS9; EM; 2.90 A; D=19-613.
DR PDB; 7WSA; EM; 3.00 A; D=19-613.
DR PDB; 7WVP; EM; 3.70 A; A=17-615.
DR PDB; 7WVQ; EM; 4.04 A; A=17-615.
DR PDB; 7XAZ; X-ray; 3.00 A; A/C=19-614.
DR PDB; 7XB0; X-ray; 2.90 A; A=19-614.
DR PDB; 7XB1; X-ray; 2.70 A; A=19-614.
DR PDB; 7XBF; X-ray; 3.51 A; A/C=18-615.
DR PDB; 7XBG; X-ray; 3.37 A; A/C=18-615.
DR PDB; 7XBH; X-ray; 3.02 A; A=18-619.
DR PDB; 7XCH; EM; 3.40 A; D/E=19-614.
DR PDB; 7XCI; EM; 3.20 A; A=19-614.
DR PDB; 7XCP; EM; 3.05 A; A=19-614.
DR PDB; 7XID; EM; 3.30 A; D/E=2-805.
DR PDB; 7XO7; EM; 3.38 A; E/F=1-805.
DR PDB; 7XO8; EM; 3.48 A; D/E/F=1-805.
DR PDB; 7XO9; EM; 3.00 A; D=1-805.
DR PDB; 7XWA; X-ray; 3.36 A; A/C=19-617.
DR PDB; 7Y75; EM; 3.10 A; A/C=2-805.
DR PDB; 7Y76; EM; 3.20 A; A/C=2-805.
DR PDB; 7Y9Z; EM; 2.85 A; D=19-614.
DR PDB; 7YA0; EM; 3.10 A; D/E/F=19-614.
DR PDB; 7YA1; EM; 3.11 A; A=19-614.
DR PDB; 7YDI; EM; 3.98 A; A=19-615.
DR PDB; 7YEG; EM; 3.73 A; E/J/M=19-615.
DR PDB; 7YR2; EM; 3.30 A; A=19-615.
DR PDB; 7YR3; EM; 3.52 A; D/G=19-615.
DR PDB; 7ZDQ; EM; 3.20 A; A=19-615.
DR PDB; 7ZF7; X-ray; 3.46 A; A=19-615.
DR PDB; 8AQS; EM; 2.92 A; B=19-620.
DR PDB; 8ASY; X-ray; 2.85 A; A=19-615.
DR PDB; 8DF5; X-ray; 2.70 A; E/F=1-805.
DR PDB; 8DLJ; EM; 2.91 A; E=18-615.
DR PDB; 8DLK; EM; 3.04 A; E=18-615.
DR PDB; 8DLM; EM; 2.89 A; E=18-615.
DR PDB; 8DLN; EM; 3.04 A; E=18-615.
DR PDB; 8DLP; EM; 2.64 A; D/E/F=18-615.
DR PDB; 8DLQ; EM; 2.77 A; E=18-615.
DR PDB; 8DLU; EM; 3.14 A; D/E=18-615.
DR PDB; 8DLV; EM; 3.11 A; E=18-615.
DR PDB; 8DM5; EM; 2.51 A; D/E=18-615.
DR PDB; 8DM6; EM; 2.77 A; D=18-615.
DR PDB; 8DV1; EM; 3.40 A; D=18-740.
DR PDB; 8DV2; EM; 3.50 A; D=18-740.
DR PDB; 8E7M; EM; 3.30 A; A=1-615.
DR PDBsum; 1R42; -.
DR PDBsum; 1R4L; -.
DR PDBsum; 2AJF; -.
DR PDBsum; 3D0G; -.
DR PDBsum; 3D0H; -.
DR PDBsum; 3D0I; -.
DR PDBsum; 3KBH; -.
DR PDBsum; 3SCI; -.
DR PDBsum; 3SCJ; -.
DR PDBsum; 3SCK; -.
DR PDBsum; 3SCL; -.
DR PDBsum; 6ACG; -.
DR PDBsum; 6ACJ; -.
DR PDBsum; 6ACK; -.
DR PDBsum; 6CS2; -.
DR PDBsum; 6LZG; -.
DR PDBsum; 6M0J; -.
DR PDBsum; 6M17; -.
DR PDBsum; 6M18; -.
DR PDBsum; 6M1D; -.
DR PDBsum; 6VW1; -.
DR PDBsum; 7A91; -.
DR PDBsum; 7A92; -.
DR PDBsum; 7A94; -.
DR PDBsum; 7A95; -.
DR PDBsum; 7A96; -.
DR PDBsum; 7A97; -.
DR PDBsum; 7A98; -.
DR PDBsum; 7BH9; -.
DR PDBsum; 7CT5; -.
DR PDBsum; 7DDO; -.
DR PDBsum; 7DDP; -.
DR PDBsum; 7DF4; -.
DR PDBsum; 7DMU; -.
DR PDBsum; 7DQA; -.
DR PDBsum; 7DRV; -.
DR PDBsum; 7DWX; -.
DR PDBsum; 7DX4; -.
DR PDBsum; 7DX5; -.
DR PDBsum; 7DX6; -.
DR PDBsum; 7DX7; -.
DR PDBsum; 7DX8; -.
DR PDBsum; 7DX9; -.
DR PDBsum; 7E7E; -.
DR PDBsum; 7EDJ; -.
DR PDBsum; 7EFP; -.
DR PDBsum; 7EFR; -.
DR PDBsum; 7EKC; -.
DR PDBsum; 7EKE; -.
DR PDBsum; 7EKF; -.
DR PDBsum; 7EKG; -.
DR PDBsum; 7EKH; -.
DR PDBsum; 7FDG; -.
DR PDBsum; 7FDH; -.
DR PDBsum; 7FDI; -.
DR PDBsum; 7FEM; -.
DR PDBsum; 7JVO; -.
DR PDBsum; 7KJ2; -.
DR PDBsum; 7KJ3; -.
DR PDBsum; 7KJ4; -.
DR PDBsum; 7KMB; -.
DR PDBsum; 7KMS; -.
DR PDBsum; 7KMZ; -.
DR PDBsum; 7KNB; -.
DR PDBsum; 7KNE; -.
DR PDBsum; 7KNH; -.
DR PDBsum; 7KNI; -.
DR PDBsum; 7L0N; -.
DR PDBsum; 7L7F; -.
DR PDBsum; 7LO4; -.
DR PDBsum; 7MJM; -.
DR PDBsum; 7MJN; -.
DR PDBsum; 7NXC; -.
DR PDBsum; 7P19; -.
DR PDBsum; 7P55; -.
DR PDBsum; 7P8I; -.
DR PDBsum; 7P8J; -.
DR PDBsum; 7PKI; -.
DR PDBsum; 7R0Z; -.
DR PDBsum; 7R10; -.
DR PDBsum; 7R11; -.
DR PDBsum; 7R12; -.
DR PDBsum; 7R1A; -.
DR PDBsum; 7RPV; -.
DR PDBsum; 7SN0; -.
DR PDBsum; 7SXX; -.
DR PDBsum; 7SXY; -.
DR PDBsum; 7SXZ; -.
DR PDBsum; 7SY0; -.
DR PDBsum; 7SY1; -.
DR PDBsum; 7SY2; -.
DR PDBsum; 7SY3; -.
DR PDBsum; 7SY4; -.
DR PDBsum; 7SY5; -.
DR PDBsum; 7SY6; -.
DR PDBsum; 7SY7; -.
DR PDBsum; 7SY8; -.
DR PDBsum; 7T9K; -.
DR PDBsum; 7T9L; -.
DR PDBsum; 7TEW; -.
DR PDBsum; 7TEX; -.
DR PDBsum; 7TEZ; -.
DR PDBsum; 7TF0; -.
DR PDBsum; 7TN0; -.
DR PDBsum; 7U0N; -.
DR PDBsum; 7UFK; -.
DR PDBsum; 7V61; -.
DR PDBsum; 7V7Z; -.
DR PDBsum; 7V80; -.
DR PDBsum; 7V81; -.
DR PDBsum; 7V82; -.
DR PDBsum; 7V83; -.
DR PDBsum; 7V84; -.
DR PDBsum; 7V85; -.
DR PDBsum; 7V86; -.
DR PDBsum; 7V87; -.
DR PDBsum; 7V88; -.
DR PDBsum; 7V89; -.
DR PDBsum; 7V8A; -.
DR PDBsum; 7V8B; -.
DR PDBsum; 7VIB; -.
DR PDBsum; 7VX4; -.
DR PDBsum; 7VX5; -.
DR PDBsum; 7VX9; -.
DR PDBsum; 7VXA; -.
DR PDBsum; 7VXB; -.
DR PDBsum; 7VXC; -.
DR PDBsum; 7VXD; -.
DR PDBsum; 7VXF; -.
DR PDBsum; 7VXK; -.
DR PDBsum; 7VXM; -.
DR PDBsum; 7W98; -.
DR PDBsum; 7W99; -.
DR PDBsum; 7W9B; -.
DR PDBsum; 7W9C; -.
DR PDBsum; 7W9I; -.
DR PDBsum; 7WBL; -.
DR PDBsum; 7WBP; -.
DR PDBsum; 7WBQ; -.
DR PDBsum; 7WGB; -.
DR PDBsum; 7WGC; -.
DR PDBsum; 7WHH; -.
DR PDBsum; 7WK4; -.
DR PDBsum; 7WK5; -.
DR PDBsum; 7WK6; -.
DR PDBsum; 7WNM; -.
DR PDBsum; 7WPA; -.
DR PDBsum; 7WPB; -.
DR PDBsum; 7WPC; -.
DR PDBsum; 7WS8; -.
DR PDBsum; 7WS9; -.
DR PDBsum; 7WSA; -.
DR PDBsum; 7WVP; -.
DR PDBsum; 7WVQ; -.
DR PDBsum; 7XAZ; -.
DR PDBsum; 7XB0; -.
DR PDBsum; 7XB1; -.
DR PDBsum; 7XBF; -.
DR PDBsum; 7XBG; -.
DR PDBsum; 7XBH; -.
DR PDBsum; 7XCH; -.
DR PDBsum; 7XCI; -.
DR PDBsum; 7XCP; -.
DR PDBsum; 7XID; -.
DR PDBsum; 7XO7; -.
DR PDBsum; 7XO8; -.
DR PDBsum; 7XO9; -.
DR PDBsum; 7XWA; -.
DR PDBsum; 7Y75; -.
DR PDBsum; 7Y76; -.
DR PDBsum; 7Y9Z; -.
DR PDBsum; 7YA0; -.
DR PDBsum; 7YA1; -.
DR PDBsum; 7YDI; -.
DR PDBsum; 7YEG; -.
DR PDBsum; 7YR2; -.
DR PDBsum; 7YR3; -.
DR PDBsum; 7ZDQ; -.
DR PDBsum; 7ZF7; -.
DR PDBsum; 8AQS; -.
DR PDBsum; 8ASY; -.
DR PDBsum; 8DF5; -.
DR PDBsum; 8DLJ; -.
DR PDBsum; 8DLK; -.
DR PDBsum; 8DLM; -.
DR PDBsum; 8DLN; -.
DR PDBsum; 8DLP; -.
DR PDBsum; 8DLQ; -.
DR PDBsum; 8DLU; -.
DR PDBsum; 8DLV; -.
DR PDBsum; 8DM5; -.
DR PDBsum; 8DM6; -.
DR PDBsum; 8DV1; -.
DR PDBsum; 8DV2; -.
DR PDBsum; 8E7M; -.
DR AlphaFoldDB; Q9BYF1; -.
DR SMR; Q9BYF1; -.
DR BioGRID; 121864; 847.
DR ComplexPortal; CPX-5683; SARS-CoV-2 Spike - human ACE2 receptor complex.
DR ComplexPortal; CPX-5684; SARS-CoV-2 Spike - human ACE2-SLC6A19 complex.
DR ComplexPortal; CPX-5695; SARS-CoV Spike - human ACE2 receptor complex.
DR DIP; DIP-44689N; -.
DR IntAct; Q9BYF1; 59.
DR MINT; Q9BYF1; -.
DR STRING; 9606.ENSP00000389326; -.
DR BindingDB; Q9BYF1; -.
DR ChEMBL; CHEMBL3736; -.
DR DrugBank; DB09019; Bromhexine.
DR DrugBank; DB00608; Chloroquine.
DR DrugBank; DB01611; Hydroxychloroquine.
DR DrugBank; DB15643; N-(2-Aminoethyl)-1-aziridineethanamine.
DR DrugBank; DB05203; SPP1148.
DR GuidetoPHARMACOLOGY; 1614; -.
DR MEROPS; M02.006; -.
DR TCDB; 2.A.22.6.3; the neurotransmitter:sodium symporter (nss) family.
DR TCDB; 8.A.139.1.1; the angiotensin-converting enzyme 2 (ace2) family.
DR GlyConnect; 1012; 115 N-Linked glycans (3 sites), 1 O-Fuc glycan, 14 O-Linked glycans (1 site).
DR GlyCosmos; Q9BYF1; 8 sites, 161 glycans.
DR GlyGen; Q9BYF1; 19 sites, 218 N-linked glycans (8 sites), 35 O-linked glycans (11 sites).
DR iPTMnet; Q9BYF1; -.
DR PhosphoSitePlus; Q9BYF1; -.
DR SwissPalm; Q9BYF1; -.
DR BioMuta; ACE2; -.
DR DMDM; 71658783; -.
DR jPOST; Q9BYF1; -.
DR MassIVE; Q9BYF1; -.
DR PaxDb; Q9BYF1; -.
DR PeptideAtlas; Q9BYF1; -.
DR ProteomicsDB; 79634; -. [Q9BYF1-1]
DR ABCD; Q9BYF1; 2 sequenced antibodies.
DR Antibodypedia; 344; 1302 antibodies from 46 providers.
DR DNASU; 59272; -.
DR Ensembl; ENST00000252519.8; ENSP00000252519.3; ENSG00000130234.13. [Q9BYF1-1]
DR Ensembl; ENST00000427411.2; ENSP00000389326.1; ENSG00000130234.13. [Q9BYF1-1]
DR Ensembl; ENST00000677282.1; ENSP00000504747.1; ENSG00000130234.13. [Q9BYF1-3]
DR Ensembl; ENST00000678073.1; ENSP00000504103.1; ENSG00000130234.13. [Q9BYF1-1]
DR Ensembl; ENST00000680121.1; ENSP00000505992.1; ENSG00000130234.13. [Q9BYF1-1]
DR GeneID; 59272; -.
DR KEGG; hsa:59272; -.
DR MANE-Select; ENST00000252519.8; ENSP00000252519.3; NM_001371415.1; NP_001358344.1.
DR UCSC; uc004cxa.2; human. [Q9BYF1-1]
DR AGR; HGNC:13557; -.
DR CTD; 59272; -.
DR DisGeNET; 59272; -.
DR GeneCards; ACE2; -.
DR HGNC; HGNC:13557; ACE2.
DR HPA; ENSG00000130234; Tissue enhanced (gallbladder, intestine, kidney).
DR MIM; 300335; gene.
DR neXtProt; NX_Q9BYF1; -.
DR OpenTargets; ENSG00000130234; -.
DR PharmGKB; PA425; -.
DR VEuPathDB; HostDB:ENSG00000130234; -.
DR eggNOG; KOG3690; Eukaryota.
DR GeneTree; ENSGT00940000158077; -.
DR HOGENOM; CLU_014364_3_0_1; -.
DR InParanoid; Q9BYF1; -.
DR OMA; MTEGFWK; -.
DR OrthoDB; 2898149at2759; -.
DR PhylomeDB; Q9BYF1; -.
DR TreeFam; TF312861; -.
DR BRENDA; 3.4.15.1; 2681.
DR BRENDA; 3.4.17.23; 2681.
DR PathwayCommons; Q9BYF1; -.
DR Reactome; R-HSA-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR Reactome; R-HSA-9678110; Attachment and Entry.
DR Reactome; R-HSA-9679191; Potential therapeutics for SARS.
DR Reactome; R-HSA-9694614; Attachment and Entry.
DR Reactome; R-HSA-9733458; Induction of Cell-Cell Fusion.
DR SABIO-RK; Q9BYF1; -.
DR SignaLink; Q9BYF1; -.
DR SIGNOR; Q9BYF1; -.
DR BioGRID-ORCS; 59272; 35 hits in 793 CRISPR screens.
DR ChiTaRS; ACE2; human.
DR EvolutionaryTrace; Q9BYF1; -.
DR GeneWiki; Angiotensin-converting_enzyme_2; -.
DR GenomeRNAi; 59272; -.
DR Pharos; Q9BYF1; Tchem.
DR PRO; PR:Q9BYF1; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q9BYF1; protein.
DR Bgee; ENSG00000130234; Expressed in ileal mucosa and 94 other tissues.
DR ExpressionAtlas; Q9BYF1; baseline and differential.
DR Genevisible; Q9BYF1; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0031526; C:brush border membrane; IDA:ARUK-UCL.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005929; C:cilium; IEA:UniProtKB-SubCell.
DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0045121; C:membrane raft; TAS:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004180; F:carboxypeptidase activity; IDA:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004181; F:metallocarboxypeptidase activity; EXP:Reactome.
DR GO; GO:0008237; F:metallopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008241; F:peptidyl-dipeptidase activity; IDA:UniProtKB.
DR GO; GO:0001618; F:virus receptor activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; TAS:BHF-UCL.
DR GO; GO:0002003; P:angiotensin maturation; TAS:Reactome.
DR GO; GO:0003051; P:angiotensin-mediated drinking behavior; IMP:BHF-UCL.
DR GO; GO:0097746; P:blood vessel diameter maintenance; IC:BHF-UCL.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEA:Ensembl.
DR GO; GO:0061025; P:membrane fusion; NAS:ComplexPortal.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:2000272; P:negative regulation of signaling receptor activity; IMP:ARUK-UCL.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0051957; P:positive regulation of amino acid transport; IMP:UniProtKB.
DR GO; GO:0060452; P:positive regulation of cardiac muscle contraction; IEA:Ensembl.
DR GO; GO:1903598; P:positive regulation of gap junction assembly; IMP:BHF-UCL.
DR GO; GO:1905737; P:positive regulation of L-proline import across plasma membrane; IGI:ARUK-UCL.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IC:BHF-UCL.
DR GO; GO:0019065; P:receptor-mediated endocytosis of virus by host cell; NAS:ComplexPortal.
DR GO; GO:0046813; P:receptor-mediated virion attachment to host cell; IDA:UniProtKB.
DR GO; GO:1903779; P:regulation of cardiac conduction; IMP:BHF-UCL.
DR GO; GO:0042127; P:regulation of cell population proliferation; TAS:BHF-UCL.
DR GO; GO:0001817; P:regulation of cytokine production; IC:BHF-UCL.
DR GO; GO:0050727; P:regulation of inflammatory response; IC:BHF-UCL.
DR GO; GO:0003081; P:regulation of systemic arterial blood pressure by renin-angiotensin; IMP:BHF-UCL.
DR GO; GO:0022898; P:regulation of transmembrane transporter activity; IGI:ARUK-UCL.
DR GO; GO:0019229; P:regulation of vasoconstriction; IC:BHF-UCL.
DR GO; GO:0015827; P:tryptophan transport; IEA:Ensembl.
DR GO; GO:0046718; P:viral entry into host cell; IDA:UniProtKB.
DR GO; GO:0019058; P:viral life cycle; NAS:ComplexPortal.
DR CDD; cd06461; M2_ACE; 1.
DR DisProt; DP02854; -.
DR Gene3D; 1.10.1370.30; -; 1.
DR InterPro; IPR031588; Collectrin_dom.
DR InterPro; IPR001548; Peptidase_M2.
DR PANTHER; PTHR10514; ANGIOTENSIN-CONVERTING ENZYME; 1.
DR PANTHER; PTHR10514:SF24; ANGIOTENSIN-CONVERTING ENZYME 2; 1.
DR Pfam; PF16959; Collectrin; 1.
DR Pfam; PF01401; Peptidase_M2; 1.
DR PRINTS; PR00791; PEPDIPTASEA.
DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR PROSITE; PS52010; COLLECTRIN_LIKE; 1.
DR PROSITE; PS52011; PEPTIDASE_M2; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Carboxypeptidase; Cell membrane;
KW Cell projection; Chloride; Cytoplasm; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Host cell receptor for virus entry;
KW Host-virus interaction; Hydrolase; Membrane; Metal-binding;
KW Metalloprotease; Phosphoprotein; Protease; Receptor; Reference proteome;
KW Secreted; Signal; Transmembrane; Transmembrane helix; Zinc.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..805
FT /note="Angiotensin-converting enzyme 2"
FT /id="PRO_0000028570"
FT CHAIN 18..708
FT /note="Processed angiotensin-converting enzyme 2"
FT /id="PRO_0000292268"
FT TOPO_DOM 18..740
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 741..761
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01354"
FT TOPO_DOM 762..805
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 19..607
FT /note="Peptidase M2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355"
FT DOMAIN 614..805
FT /note="Collectrin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01354"
FT REGION 30..41
FT /note="Interaction with SARS-CoV spike glycoprotein"
FT /evidence="ECO:0000269|PubMed:15791205"
FT REGION 82..84
FT /note="Interaction with SARS-CoV spike glycoprotein"
FT /evidence="ECO:0000269|PubMed:15791205"
FT REGION 353..357
FT /note="Interaction with SARS-CoV spike glycoprotein"
FT /evidence="ECO:0000269|PubMed:15791205"
FT REGION 652..659
FT /note="Essential for cleavage by ADAM17"
FT /evidence="ECO:0000269|PubMed:24227843"
FT REGION 697..716
FT /note="Essential for cleavage by TMPRSS11D and TMPRSS2"
FT /evidence="ECO:0000269|PubMed:24227843"
FT REGION 772..805
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 778..786
FT /note="LIR"
FT /evidence="ECO:0000305|PubMed:33436497,
FT ECO:0000305|PubMed:33436498"
FT MOTIF 781..785
FT /note="SH2-binding"
FT /evidence="ECO:0000305|PubMed:33436497,
FT ECO:0000305|PubMed:33436498"
FT MOTIF 781..784
FT /note="Endocytic sorting signal"
FT /evidence="ECO:0000305|PubMed:33436497,
FT ECO:0000305|PubMed:33436498"
FT MOTIF 792..795
FT /note="PTB"
FT /evidence="ECO:0000305|PubMed:33436497,
FT ECO:0000305|PubMed:33436498"
FT MOTIF 803..805
FT /note="PDZ-binding"
FT /evidence="ECO:0000305|PubMed:33436497,
FT ECO:0000305|PubMed:33436498"
FT COMPBIAS 785..805
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 375
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355,
FT ECO:0000305|PubMed:14754895, ECO:0000305|PubMed:27217402"
FT ACT_SITE 505
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355,
FT ECO:0000305|PubMed:14754895"
FT BINDING 169
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355,
FT ECO:0000269|PubMed:14754895, ECO:0000305|PubMed:19021774"
FT BINDING 273
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:14754895"
FT BINDING 345..346
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:14754895"
FT BINDING 374
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355,
FT ECO:0000269|PubMed:14754895"
FT BINDING 378
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355,
FT ECO:0000269|PubMed:14754895"
FT BINDING 402
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355,
FT ECO:0000269|PubMed:14754895"
FT BINDING 477
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355,
FT ECO:0000269|PubMed:14754895, ECO:0000305|PubMed:19021774"
FT BINDING 481
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355,
FT ECO:0000269|PubMed:14754895, ECO:0000305|PubMed:19021774"
FT BINDING 515
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:14754895"
FT MOD_RES 781
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305|PubMed:33436497,
FT ECO:0000305|PubMed:33436498"
FT MOD_RES 783
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:33436497,
FT ECO:0000305|PubMed:33436498"
FT CARBOHYD 53
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:14754895"
FT CARBOHYD 90
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14754895,
FT ECO:0000269|PubMed:15084671, ECO:0000269|PubMed:19901337"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14754895"
FT CARBOHYD 322
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:14754895"
FT CARBOHYD 432
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14754895"
FT CARBOHYD 546
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14754895,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19901337"
FT CARBOHYD 690
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 133..141
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355,
FT ECO:0000269|PubMed:14754895"
FT DISULFID 344..361
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355,
FT ECO:0000269|PubMed:14754895"
FT DISULFID 530..542
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355,
FT ECO:0000269|PubMed:14754895"
FT VAR_SEQ 1..356
FT /note="MSSSSWLLLSLVAVTAAQSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNT
FT NITEENVQNMNNAGDKWSAFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSED
FT KSKRLNTILNTMSTIYSTGKVCNPDNPQECLLLEPGLNEIMANSLDYNERLWAWESWRS
FT EVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHT
FT FEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYSLTVPFGQK
FT PNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPT
FT AWDLGKGDF -> MREAGWDKGG (in isoform 2)"
FT /id="VSP_060903"
FT VARIANT 26
FT /note="K -> R (in dbSNP:rs4646116)"
FT /evidence="ECO:0000269|PubMed:32558308, ECO:0000269|Ref.10"
FT /id="VAR_023082"
FT VARIANT 468
FT /note="I -> V"
FT /evidence="ECO:0000269|PubMed:32558308"
FT /id="VAR_083726"
FT VARIANT 638
FT /note="N -> S (in dbSNP:rs183135788)"
FT /evidence="ECO:0000269|PubMed:15937940,
FT ECO:0000269|PubMed:32558308"
FT /id="VAR_023083"
FT VARIANT 720
FT /note="N -> D"
FT /evidence="ECO:0000269|PubMed:32558308,
FT ECO:0000269|PubMed:33133145"
FT /id="VAR_083727"
FT MUTAGEN 19
FT /note="S->P: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 24..26
FT /note="QAK->KAE: Slightly inhibits interaction with SARS-
FT CoV spike glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 24
FT /note="Q->T: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 25
FT /note="A->V: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 27
FT /note="T->Y: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein. In sACE2.v2.2;
FT increases interaction with RBD domain of SARS-CoV-2 spike
FT protein; when associated with Y-330 and L-386."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 29
FT /note="L->F: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 31
FT /note="K->D: Abolishes interaction with SARS-CoV spike
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 31
FT /note="K->Y: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 33
FT /note="N->D: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 34
FT /note="H->A: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 37
FT /note="E->A: No effect on interaction with SARS-CoV spike
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 38
FT /note="D->A: No effect on interaction with SARS-CoV spike
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 39
FT /note="L->R: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 40
FT /note="F->D: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 41
FT /note="Y->A: Strongly inhibits interaction with SARS-CoV
FT spike glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 41
FT /note="Y->R: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 42
FT /note="Q->L: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 68
FT /note="K->D: Slightly inhibits interaction with SARS-CoV
FT spike glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 69
FT /note="W->V: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 72
FT /note="F->Y: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 75
FT /note="E->K: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 76
FT /note="Q->T: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 79
FT /note="L->T: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 82..84
FT /note="MYP->NFS: Inhibits interaction with SARS-CoV spike
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 89
FT /note="Q->P: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 90
FT /note="N->Q: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 91
FT /note="L->P: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 92
FT /note="T->Q: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 110
FT /note="E->P: No effect on interaction with SARS-CoV spike
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 135..136
FT /note="PD->SM: No effect on interaction with SARS-CoV spike
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 160
FT /note="E->R: No effect on interaction with SARS-CoV spike
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 169
FT /note="R->Q: About 95% loss of angiotensin I cleavage."
FT /evidence="ECO:0000269|PubMed:19021774"
FT MUTAGEN 192
FT /note="R->D: No effect on interaction with SARS-CoV spike
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 219
FT /note="R->D: No effect on interaction with SARS-CoV spike
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 239
FT /note="H->Q: No effect on interaction with SARS-CoV spike
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 271
FT /note="W->Q: About 95% loss of angiotensin I cleavage."
FT /evidence="ECO:0000269|PubMed:19021774"
FT MUTAGEN 273
FT /note="R->Q: Complete loss of enzyme activity. Does not
FT affect amino acid transport activity of SLC6A19."
FT /evidence="ECO:0000269|PubMed:16008552,
FT ECO:0000269|PubMed:19185582"
FT MUTAGEN 309
FT /note="K->D: No effect on interaction with SARS-CoV spike
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 312
FT /note="E->A: No effect on interaction with SARS-CoV spike
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 324
FT /note="T->A: No effect on interaction with SARS-CoV spike
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 324
FT /note="T->P: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 325
FT /note="Q->P: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 330
FT /note="N->Y: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein. In sACE2.v2.2;
FT increases interaction with RBD domain of SARS-CoV-2 spike
FT protein; when associated with Y-27 and L-386."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 338..340
FT /note="NVQ->DDR: No effect on interaction with SARS-CoV
FT spike glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 345
FT /note="H->A: Complete loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:16008552"
FT MUTAGEN 350
FT /note="D->A: No effect on interaction with SARS-CoV spike
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 351
FT /note="L->F: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 353
FT /note="K->H,A,D: Abolishes interaction with SARS-CoV spike
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 355
FT /note="D->A: Strongly inhibits interaction with SARS-CoV
FT spike glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 357
FT /note="R->A: Strongly inhibits interaction with SARS-CoV
FT spike glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 359
FT /note="L->K,A: No effect on interaction with SARS-CoV spike
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 383
FT /note="M->A: Slightly inhibits interaction with SARS-CoV
FT spike glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 386
FT /note="A->L: Increases slightly the interaction with RBD
FT domain of SARS-CoV-2 spike protein. In sACE2.v2.2;
FT increases interaction with RBD domain of SARS-CoV-2 spike
FT protein; when associated with Y-27 and Y-330."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 389
FT /note="P->A: Slightly inhibits interaction with SARS-CoV
FT spike glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 389
FT /note="P->D: Increases very slightly the interaction with
FT RBD domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 393
FT /note="R->A: Slightly inhibits interaction with SARS-CoV
FT spike glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 393
FT /note="R->K: Increases very slightly the interaction with
FT RBD domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 425..427
FT /note="SPD->PSN: Slightly inhibits interaction with SARS-
FT CoV spike glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 465..467
FT /note="KGE->QDK: No effect on interaction with SARS-CoV
FT spike glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 481
FT /note="K->Q: About 80% loss of angiotensin I cleavage."
FT /evidence="ECO:0000269|PubMed:19021774"
FT MUTAGEN 505
FT /note="H->A: Complete loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:16008552"
FT MUTAGEN 514
FT /note="R->Q: About 50% loss of angiotensin I cleavage but
FT two-fold greater activity with angiotensin II."
FT /evidence="ECO:0000269|PubMed:19021774"
FT MUTAGEN 518
FT /note="R->G: Increases very slightly the interaction with
FT RBD domain of SARS-CoV-2 spike protein."
FT /evidence="ECO:0000269|PubMed:32753553"
FT MUTAGEN 559
FT /note="R->S: Slightly inhibits interaction with SARS-CoV
FT spike glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 603
FT /note="F->T: No effect on interaction with SARS-CoV spike
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:15791205"
FT MUTAGEN 802..805
FT /note="QTSF->AAAA: Loss of interaction with NHERF1."
FT /evidence="ECO:0000269|PubMed:34189428"
FT CONFLICT 18
FT /note="Q -> H (in Ref. 13; CAB53682)"
FT /evidence="ECO:0000305"
FT CONFLICT 508
FT /note="N -> D (in Ref. 9; AAQ89076)"
FT /evidence="ECO:0000305"
FT CONFLICT 631
FT /note="K -> R (in Ref. 5; BAB40370)"
FT /evidence="ECO:0000305"
FT HELIX 23..52
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 56..77
FT /evidence="ECO:0007829|PDB:1R42"
FT TURN 78..82
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 85..87
FT /evidence="ECO:0007829|PDB:7UFK"
FT HELIX 91..100
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 104..107
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 110..129
FT /evidence="ECO:0007829|PDB:1R42"
FT STRAND 131..134
FT /evidence="ECO:0007829|PDB:1R42"
FT STRAND 137..143
FT /evidence="ECO:0007829|PDB:1R42"
FT TURN 144..146
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 148..154
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 158..171
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 173..193
FT /evidence="ECO:0007829|PDB:1R42"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:7WPB"
FT HELIX 199..204
FT /evidence="ECO:0007829|PDB:1R42"
FT TURN 205..207
FT /evidence="ECO:0007829|PDB:1R42"
FT TURN 213..215
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 220..251
FT /evidence="ECO:0007829|PDB:1R42"
FT TURN 253..255
FT /evidence="ECO:0007829|PDB:1R42"
FT STRAND 258..260
FT /evidence="ECO:0007829|PDB:7UFK"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:1R42"
FT STRAND 267..271
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 276..278
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 279..282
FT /evidence="ECO:0007829|PDB:1R42"
FT TURN 284..287
FT /evidence="ECO:0007829|PDB:1R42"
FT TURN 294..297
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 298..300
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 304..316
FT /evidence="ECO:0007829|PDB:1R42"
FT TURN 317..319
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 327..330
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 337..339
FT /evidence="ECO:0007829|PDB:7UFK"
FT STRAND 347..352
FT /evidence="ECO:0007829|PDB:1R42"
FT STRAND 355..359
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 366..384
FT /evidence="ECO:0007829|PDB:1R42"
FT TURN 385..387
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 390..392
FT /evidence="ECO:0007829|PDB:1R42"
FT STRAND 396..399
FT /evidence="ECO:0007829|PDB:7WPC"
FT HELIX 400..413
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 415..420
FT /evidence="ECO:0007829|PDB:1R42"
FT TURN 422..426
FT /evidence="ECO:0007829|PDB:1R4L"
FT HELIX 432..446
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 449..465
FT /evidence="ECO:0007829|PDB:1R42"
FT STRAND 466..468
FT /evidence="ECO:0007829|PDB:1R4L"
FT HELIX 470..472
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 473..483
FT /evidence="ECO:0007829|PDB:1R42"
FT STRAND 486..488
FT /evidence="ECO:0007829|PDB:3D0G"
FT STRAND 494..496
FT /evidence="ECO:0007829|PDB:7V8A"
FT HELIX 499..502
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 504..507
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 514..531
FT /evidence="ECO:0007829|PDB:1R42"
FT TURN 532..534
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 539..541
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 548..558
FT /evidence="ECO:0007829|PDB:1R42"
FT TURN 559..562
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 566..574
FT /evidence="ECO:0007829|PDB:1R42"
FT STRAND 575..578
FT /evidence="ECO:0007829|PDB:1R42"
FT HELIX 582..598
FT /evidence="ECO:0007829|PDB:1R42"
FT STRAND 600..602
FT /evidence="ECO:0007829|PDB:1R42"
FT STRAND 607..609
FT /evidence="ECO:0007829|PDB:1R42"
FT TURN 612..615
FT /evidence="ECO:0007829|PDB:6M17"
FT STRAND 618..622
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 624..627
FT /evidence="ECO:0007829|PDB:6M17"
FT STRAND 629..631
FT /evidence="ECO:0007829|PDB:6M18"
FT HELIX 637..657
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 667..669
FT /evidence="ECO:0007829|PDB:6M17"
FT STRAND 670..673
FT /evidence="ECO:0007829|PDB:6M17"
FT STRAND 677..686
FT /evidence="ECO:0007829|PDB:6M17"
FT STRAND 690..694
FT /evidence="ECO:0007829|PDB:6M18"
FT HELIX 697..706
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 708..715
FT /evidence="ECO:0007829|PDB:6M17"
FT STRAND 719..724
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 741..765
FT /evidence="ECO:0007829|PDB:6M17"
SQ SEQUENCE 805 AA; 92463 MW; 8EE6EB0A931550E8 CRC64;
MSSSSWLLLS LVAVTAAQST IEEQAKTFLD KFNHEAEDLF YQSSLASWNY NTNITEENVQ
NMNNAGDKWS AFLKEQSTLA QMYPLQEIQN LTVKLQLQAL QQNGSSVLSE DKSKRLNTIL
NTMSTIYSTG KVCNPDNPQE CLLLEPGLNE IMANSLDYNE RLWAWESWRS EVGKQLRPLY
EEYVVLKNEM ARANHYEDYG DYWRGDYEVN GVDGYDYSRG QLIEDVEHTF EEIKPLYEHL
HAYVRAKLMN AYPSYISPIG CLPAHLLGDM WGRFWTNLYS LTVPFGQKPN IDVTDAMVDQ
AWDAQRIFKE AEKFFVSVGL PNMTQGFWEN SMLTDPGNVQ KAVCHPTAWD LGKGDFRILM
CTKVTMDDFL TAHHEMGHIQ YDMAYAAQPF LLRNGANEGF HEAVGEIMSL SAATPKHLKS
IGLLSPDFQE DNETEINFLL KQALTIVGTL PFTYMLEKWR WMVFKGEIPK DQWMKKWWEM
KREIVGVVEP VPHDETYCDP ASLFHVSNDY SFIRYYTRTL YQFQFQEALC QAAKHEGPLH
KCDISNSTEA GQKLFNMLRL GKSEPWTLAL ENVVGAKNMN VRPLLNYFEP LFTWLKDQNK
NSFVGWSTDW SPYADQSIKV RISLKSALGD KAYEWNDNEM YLFRSSVAYA MRQYFLKVKN
QMILFGEEDV RVANLKPRIS FNFFVTAPKN VSDIIPRTEV EKAIRMSRSR INDAFRLNDN
SLEFLGIQPT LGPPNQPPVS IWLIVFGVVM GVIVVGIVIL IFTGIRDRKK KNKARSGENP
YASIDISKGE NNPGFQNTDD VQTSF
//