ID ACE2_HUMAN Reviewed; 805 AA. AC Q9BYF1; C7ECU1; Q6UWP0; Q86WT0; Q9NRA7; Q9UFZ6; DT 02-AUG-2005, integrated into UniProtKB/Swiss-Prot. DT 02-AUG-2005, sequence version 2. DT 02-DEC-2020, entry version 183. 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}; 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] 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 [9] 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 [10] 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 [11] 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 [12] 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 [13] 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 [14] 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 [15] 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 [16] 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 [17] 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 [18] 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 [19] 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 [20] 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 [21] 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 [22] 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 [23] 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 [24] 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 [25] 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 [26] 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 [27] 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 [28] 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 [29] 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 [30] 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 [31] 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 [32] 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 [33] 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 [34] 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 [35] 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 [36] 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 [37] 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 [38] 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 [39] 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 [40] 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 [41] 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 [42] 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 [43] 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 [44] 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 [45] 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. 0:0-0(2020). RN [46] 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 0:0-0(2020). RN [47] 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 [48] {ECO:0000244|PDB:1R42, ECO:0000244|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 [49] {ECO:0000244|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 [50] {ECO:0000244|PDB:6ACG, ECO:0000244|PDB:6ACJ, ECO:0000244|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 [51] {ECO:0000244|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 [52] {ECO:0000244|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 0:0-0(2020). RN [53] {ECO:0000244|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 0:0-0(2020). RN [54] {ECO:0000244|PDB:6M17, ECO:0000244|PDB:6M18, ECO:0000244|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 0:0-0(2020). RN [55] 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:24227843, CC ECO:0000269|PubMed:32142651, ECO:0000269|PubMed:32155444, CC ECO:0000269|PubMed:32221306, ECO:0000269|PubMed:32225175}. 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=[des-Arg(9)]-bradykinin + H2O = [des-Phe(8), des-Arg(9)]- CC bradykinin + L-phenylalanine; Xref=Rhea:RHEA:63536, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:58095, ChEBI:CHEBI:133069, CC ChEBI:CHEBI:147352; Evidence={ECO:0000269|PubMed:10969042, CC 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 ITGB1 CC (PubMed:15276642). Interacts with the catalytically active form of CC TMPRSS2 (PubMed:21068237). Interacts with SLC6A19; this interaction is CC essential for expression and function of SLC6A19 in intestine (By CC similarity). {ECO:0000250|UniProtKB:Q8R0I0, CC ECO:0000269|PubMed:15276642, ECO:0000269|PubMed:21068237, CC ECO:0000269|PubMed:32132184}. 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. {ECO:0000269|PubMed:32075877, CC ECO:0000269|PubMed:32132184, ECO:0000269|PubMed:32155444, CC ECO:0000269|PubMed:32225175}. CC -!- SUBUNIT: (Microbial infection) Interacts with human coronavirus CC NL63/HCoV-NL63 spike glycoprotein. {ECO:0000269|PubMed:15897467}. CC -!- INTERACTION: CC Q9BYF1; PRO_0000032457 [P01019]: AGT; NbExp=2; IntAct=EBI-7730807, EBI-25493366; CC Q9BYF1; PRO_0000417390 [Q01523]: DEFA5; NbExp=2; IntAct=EBI-7730807, EBI-25634589; CC Q9BYF1; P05556: ITGB1; NbExp=4; IntAct=EBI-7730807, EBI-703066; CC Q9BYF1; PRO_0000006688 [P01042]: KNG1; NbExp=2; IntAct=EBI-7730807, EBI-6623273; CC Q9BYF1; PRO_0000019524 [P30990]: NTS; NbExp=2; IntAct=EBI-7730807, EBI-6655817; CC Q9BYF1; Q695T7: SLC6A19; NbExp=3; IntAct=EBI-7730807, EBI-25475705; CC Q9BYF1; O15393: TMPRSS2; NbExp=3; IntAct=EBI-7730807, EBI-12549863; CC Q9BYF1; P0DTC2: S; Xeno; NbExp=35; IntAct=EBI-7730807, EBI-25474821; CC Q9BYF1; P59594: S; Xeno; NbExp=37; 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=3; IntAct=EBI-7730807, EBI-15814420; CC -!- SUBCELLULAR LOCATION: [Processed angiotensin-converting enzyme 2]: CC Secreted {ECO:0000269|PubMed:15983030}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18424768}; CC Single-pass type I membrane protein {ECO:0000255}. Cytoplasm CC {ECO:0000250|UniProtKB:Q8R0I0}. Note=Detected in both cell membrane and CC cytoplasm in neurons. {ECO:0000250|UniProtKB:Q8R0I0}. 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). Coexpressed with TMPRSS2 within some CC lung alveolar type 2 cells, ileal absorptive enterocytes, intestinal CC epithelial cells, cornea, gallbladder and nasal goblet secretory cells CC (PubMed:32413319, PubMed:32327758, PubMed:32358202). Coexpressed with CC TMPRSS4 within mature enterocytes (PubMed:32404436). CC {ECO:0000269|PubMed:10924499, ECO:0000269|PubMed:10969042, CC ECO:0000269|PubMed:12459472, ECO:0000269|PubMed:15141377, CC ECO:0000269|PubMed:15231706, ECO:0000269|PubMed:15671045, CC ECO:0000269|PubMed:18424768, ECO:0000269|PubMed:32170560, CC ECO:0000269|PubMed:32327758, ECO:0000269|PubMed:32358202, CC ECO:0000269|PubMed:32404436, ECO:0000269|PubMed:32413319, CC ECO:0000269|PubMed:32425701, ECO:0000269|PubMed:32715618}. 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). CC {ECO:0000269|PubMed:14504186, ECO:0000269|PubMed:15151696, CC ECO:0000269|PubMed:15671045, ECO:0000269|PubMed:32413319, CC ECO:0000269|PubMed:32425701}. 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 -!- 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 -!- 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). Also cleaved by serine proteases: TMPRSS2, TMPRSS11D CC 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 -!- 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 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 PIR; T14762; T14762. DR RefSeq; NP_068576.1; NM_021804.2. DR PDB; 1R42; X-ray; 2.20 A; A=1-615. DR PDB; 1R4L; X-ray; 3.00 A; A=1-615. DR PDB; 1XJP; Model; -; B=19-615. 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 PDBsum; 1R42; -. DR PDBsum; 1R4L; -. DR PDBsum; 1XJP; -. 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 SMR; Q9BYF1; -. DR BioGRID; 121864; 17. 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; 23. DR MINT; Q9BYF1; -. DR STRING; 9606.ENSP00000389326; -. DR BindingDB; Q9BYF1; -. DR ChEMBL; CHEMBL3736; -. 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-onverting enzyme 2 (ace2) family. DR GlyConnect; 1012; 4 N-Linked glycans (3 sites). DR GlyConnect; 2841; 103 N-Linked glycans (7 sites), 3 O-Linked glycans (3 sites). DR GlyGen; Q9BYF1; 7 sites. DR iPTMnet; Q9BYF1; -. DR PhosphoSitePlus; Q9BYF1; -. DR BioMuta; ACE2; -. DR DMDM; 71658783; -. DR jPOST; Q9BYF1; -. DR MassIVE; Q9BYF1; -. DR PaxDb; Q9BYF1; -. DR PeptideAtlas; Q9BYF1; -. DR PRIDE; Q9BYF1; -. DR Antibodypedia; 344; 916 antibodies. DR GeneID; 59272; -. DR KEGG; hsa:59272; -. DR UCSC; uc004cxa.2; human. DR CTD; 59272; -. DR DisGeNET; 59272; -. DR EuPathDB; HostDB:ENSG00000130234.10; -. DR GeneCards; ACE2; -. DR HGNC; HGNC:13557; ACE2. DR HPA; ENSG00000130234; Tissue enriched (intestine). DR MIM; 300335; gene. DR neXtProt; NX_Q9BYF1; -. DR OpenTargets; ENSG00000130234; -. DR PharmGKB; PA425; -. DR eggNOG; KOG3690; Eukaryota. DR GeneTree; ENSGT00940000158077; -. DR HOGENOM; CLU_014364_3_0_1; -. DR InParanoid; Q9BYF1; -. DR OMA; RWWEMKR; -. DR OrthoDB; 422699at2759; -. 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 SABIO-RK; Q9BYF1; -. DR SIGNOR; Q9BYF1; -. DR BioGRID-ORCS; 59272; 2 hits in 472 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 jejunal mucosa and 142 other tissues. 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:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. 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:0016021; C:integral component of membrane; IEA:UniProtKB-KW. 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: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:BHF-UCL. 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: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:0032800; P:receptor biosynthetic process; IMP:BHF-UCL. DR GO; GO:0046813; P:receptor-mediated virion attachment to host cell; IDA:UniProtKB. DR GO; GO:0097746; P:regulation of blood vessel diameter; IC:BHF-UCL. 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 CDD; cd06461; M2_ACE; 1. DR DisProt; DP02854; -. DR InterPro; IPR031588; Collectrin_dom. DR InterPro; IPR001548; Peptidase_M2. DR PANTHER; PTHR10514; PTHR10514; 1. DR Pfam; PF16959; Collectrin; 1. DR Pfam; PF01401; Peptidase_M2; 1. DR PRINTS; PR00791; PEPDIPTASEA. DR PROSITE; PS00142; ZINC_PROTEASE; 1. PE 1: Evidence at protein level; KW 3D-structure; Carboxypeptidase; Cell membrane; Chloride; Cytoplasm; KW Direct protein sequencing; Disulfide bond; Glycoprotein; KW Host cell receptor for virus entry; Host-virus interaction; Hydrolase; KW Membrane; Metal-binding; Metalloprotease; Polymorphism; Protease; Receptor; KW Reference proteome; Secreted; Signal; Transmembrane; Transmembrane helix; KW 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" FT TOPO_DOM 762..805 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" 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 345..346 FT /note="Substrate binding" FT /evidence="ECO:0000305|PubMed:14754895" 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 ACT_SITE 375 FT /note="Proton acceptor" FT /evidence="ECO:0000305|PubMed:14754895, FT ECO:0000305|PubMed:27217402" FT ACT_SITE 505 FT /note="Proton donor" FT /evidence="ECO:0000305|PubMed:14754895" FT METAL 374 FT /note="Zinc; catalytic" FT /evidence="ECO:0000269|PubMed:14754895" FT METAL 378 FT /note="Zinc; catalytic" FT /evidence="ECO:0000269|PubMed:14754895" FT METAL 402 FT /note="Zinc; catalytic" FT /evidence="ECO:0000269|PubMed:14754895" FT BINDING 169 FT /note="Chloride" FT /evidence="ECO:0000269|PubMed:14754895, FT ECO:0000305|PubMed:19021774" FT BINDING 273 FT /note="Substrate" FT /evidence="ECO:0000305|PubMed:14754895" FT BINDING 477 FT /note="Chloride" FT /evidence="ECO:0000269|PubMed:14754895, FT ECO:0000305|PubMed:19021774" FT BINDING 481 FT /note="Chloride" FT /evidence="ECO:0000269|PubMed:14754895, FT ECO:0000305|PubMed:19021774" FT BINDING 515 FT /note="Substrate" FT /evidence="ECO:0000305|PubMed:14754895" 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" 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" FT CARBOHYD 690 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 133..141 FT /evidence="ECO:0000269|PubMed:14754895" FT DISULFID 344..361 FT /evidence="ECO:0000269|PubMed:14754895" FT DISULFID 530..542 FT /evidence="ECO:0000269|PubMed:14754895" FT VARIANT 26 FT /note="K -> R (polymorphism; dbSNP:rs4646116)" FT /evidence="ECO:0000269|PubMed:32558308, ECO:0000269|Ref.9" FT /id="VAR_023082" FT VARIANT 468 FT /note="I -> V (polymorphism)" FT /evidence="ECO:0000269|PubMed:32558308" FT /id="VAR_083726" FT VARIANT 638 FT /note="N -> S (polymorphism; dbSNP:rs183135788)" FT /evidence="ECO:0000269|PubMed:15937940, FT ECO:0000269|PubMed:32558308" FT /id="VAR_023083" FT VARIANT 720 FT /note="N -> D (polymorphism)" FT /evidence="ECO:0000269|PubMed:32558308" FT /id="VAR_083727" 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 31 FT /note="K->D: Abolishes interaction with SARS-CoV spike FT glycoprotein." FT /evidence="ECO:0000269|PubMed:15791205" 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 41 FT /note="Y->A: Strongly inhibits interaction with SARS-CoV FT spike glycoprotein." FT /evidence="ECO:0000269|PubMed:15791205" FT MUTAGEN 68 FT /note="K->D: Slightly inhibits interaction with SARS-CoV FT spike glycoprotein." FT /evidence="ECO:0000269|PubMed:15791205" FT MUTAGEN 82..84 FT /note="MYP->NFS: Inhibits interaction with SARS-CoV spike FT glycoprotein." FT /evidence="ECO:0000269|PubMed:15791205" 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 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 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 389 FT /note="P->A: Slightly inhibits interaction with SARS-CoV FT spike glycoprotein." FT /evidence="ECO:0000269|PubMed:15791205" FT MUTAGEN 393 FT /note="R->A: Slightly inhibits interaction with SARS-CoV FT spike glycoprotein." FT /evidence="ECO:0000269|PubMed:15791205" 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 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 CONFLICT 18 FT /note="Q -> H (in Ref. 12; CAB53682)" FT /evidence="ECO:0000305" FT CONFLICT 508 FT /note="N -> D (in Ref. 8; 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:0000244|PDB:1R42" FT HELIX 56..77 FT /evidence="ECO:0000244|PDB:1R42" FT TURN 78..82 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 85..87 FT /evidence="ECO:0000244|PDB:6M0J" FT HELIX 91..100 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 104..107 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 110..129 FT /evidence="ECO:0000244|PDB:1R42" FT STRAND 131..134 FT /evidence="ECO:0000244|PDB:1R42" FT STRAND 137..143 FT /evidence="ECO:0000244|PDB:1R42" FT TURN 144..146 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 148..154 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 158..171 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 173..193 FT /evidence="ECO:0000244|PDB:1R42" FT STRAND 196..198 FT /evidence="ECO:0000244|PDB:1R4L" FT HELIX 199..204 FT /evidence="ECO:0000244|PDB:1R42" FT TURN 205..207 FT /evidence="ECO:0000244|PDB:1R42" FT TURN 213..215 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 220..251 FT /evidence="ECO:0000244|PDB:1R42" FT TURN 253..255 FT /evidence="ECO:0000244|PDB:1R42" FT STRAND 258..260 FT /evidence="ECO:0000244|PDB:6LZG" FT HELIX 264..266 FT /evidence="ECO:0000244|PDB:1R42" FT STRAND 267..271 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 276..278 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 279..282 FT /evidence="ECO:0000244|PDB:1R42" FT TURN 284..287 FT /evidence="ECO:0000244|PDB:1R42" FT TURN 294..297 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 298..300 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 304..316 FT /evidence="ECO:0000244|PDB:1R42" FT TURN 317..319 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 327..330 FT /evidence="ECO:0000244|PDB:1R42" FT TURN 337..339 FT /evidence="ECO:0000244|PDB:6M0J" FT STRAND 347..352 FT /evidence="ECO:0000244|PDB:1R42" FT STRAND 355..359 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 366..384 FT /evidence="ECO:0000244|PDB:1R42" FT TURN 385..387 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 390..392 FT /evidence="ECO:0000244|PDB:1R42" FT STRAND 396..399 FT /evidence="ECO:0000244|PDB:6M17" FT HELIX 400..413 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 415..420 FT /evidence="ECO:0000244|PDB:1R42" FT TURN 422..426 FT /evidence="ECO:0000244|PDB:1R4L" FT HELIX 432..446 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 449..465 FT /evidence="ECO:0000244|PDB:1R42" FT STRAND 466..468 FT /evidence="ECO:0000244|PDB:1R4L" FT HELIX 470..472 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 473..483 FT /evidence="ECO:0000244|PDB:1R42" FT STRAND 486..488 FT /evidence="ECO:0000244|PDB:3D0G" FT HELIX 499..502 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 504..507 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 514..531 FT /evidence="ECO:0000244|PDB:1R42" FT TURN 532..534 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 539..541 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 548..558 FT /evidence="ECO:0000244|PDB:1R42" FT TURN 559..562 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 566..574 FT /evidence="ECO:0000244|PDB:1R42" FT STRAND 575..578 FT /evidence="ECO:0000244|PDB:1R42" FT HELIX 582..598 FT /evidence="ECO:0000244|PDB:1R42" FT STRAND 600..602 FT /evidence="ECO:0000244|PDB:1R42" FT STRAND 607..609 FT /evidence="ECO:0000244|PDB:1R42" FT TURN 612..615 FT /evidence="ECO:0000244|PDB:6M17" FT STRAND 618..622 FT /evidence="ECO:0000244|PDB:6M17" FT HELIX 624..627 FT /evidence="ECO:0000244|PDB:6M17" FT STRAND 629..631 FT /evidence="ECO:0000244|PDB:6M18" FT HELIX 637..657 FT /evidence="ECO:0000244|PDB:6M17" FT HELIX 667..669 FT /evidence="ECO:0000244|PDB:6M17" FT STRAND 670..673 FT /evidence="ECO:0000244|PDB:6M17" FT STRAND 677..686 FT /evidence="ECO:0000244|PDB:6M17" FT STRAND 690..694 FT /evidence="ECO:0000244|PDB:6M18" FT HELIX 697..706 FT /evidence="ECO:0000244|PDB:6M17" FT HELIX 708..715 FT /evidence="ECO:0000244|PDB:6M17" FT STRAND 719..724 FT /evidence="ECO:0000244|PDB:6M17" FT HELIX 741..766 FT /evidence="ECO:0000244|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 //