ID   TMPS2_HUMAN             Reviewed;         492 AA.
AC   O15393; A8K6Z8; B2R8E5; B7Z459; D3DSJ2; F8WES1; Q6GTK7; Q9BXX1;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2006, sequence version 3.
DT   24-JAN-2024, entry version 207.
DE   RecName: Full=Transmembrane protease serine 2 {ECO:0000305};
DE            EC=3.4.21.122 {ECO:0000269|PubMed:32703818};
DE   AltName: Full=Serine protease 10 {ECO:0000305};
DE   Contains:
DE     RecName: Full=Transmembrane protease serine 2 non-catalytic chain;
DE   Contains:
DE     RecName: Full=Transmembrane protease serine 2 catalytic chain;
DE   Flags: Precursor;
GN   Name=TMPRSS2 {ECO:0000312|HGNC:HGNC:11876}; Synonyms=PRSS10;
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] (ISOFORM 1), AND VARIANTS MET-160 AND GLN-329.
RX   PubMed=9325052; DOI=10.1006/geno.1997.4845;
RA   Paoloni-Giacobino A., Chen H., Peitsch M.C., Rossier C., Antonarakis S.E.;
RT   "Cloning of the TMPRSS2 gene, which encodes a novel serine protease with
RT   transmembrane, LDLRA, and SRCR domains and maps to 21q22.3.";
RL   Genomics 44:309-320(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT MET-160.
RX   PubMed=11414763; DOI=10.1006/geno.2001.6551;
RA   Teng D.-H., Chen Y., Lian L., Ha P.C., Tavtigian S.V., Wong A.K.C.;
RT   "Mutation analyses of 268 candidate genes in human tumor cell lines.";
RL   Genomics 74:352-364(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF SER-441, FUNCTION,
RP   AND SUBCELLULAR LOCATION.
RX   PubMed=11245484;
RA   Afar D.E.H., Vivanco I., Hubert R.S., Kuo J., Chen E., Saffran D.C.,
RA   Raitano A.B., Jakobovits A.;
RT   "Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in
RT   its secretion by prostate and prostate cancer epithelia.";
RL   Cancer Res. 61:1686-1692(2001).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Prostate, Testis, and Tongue;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Liver;
RA   Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA   Tanaka A., Yokoyama S.;
RL   Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=10830953; DOI=10.1038/35012518;
RA   Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA   Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA   Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA   Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA   Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA   Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA   Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA   Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA   Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA   Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA   Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT   "The DNA sequence of human chromosome 21.";
RL   Nature 405:311-319(2000).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=PNS;
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   [9]
RP   TISSUE SPECIFICITY.
RX   PubMed=11169526;
RX   DOI=10.1002/1096-9896(2000)9999:9999<::aid-path743>3.0.co;2-t;
RA   Vaarala M.H., Porvari K.S., Kellokumpu S., Kyllonen A.P., Vihko P.T.;
RT   "Expression of transmembrane serine protease TMPRSS2 in mouse and human
RT   tissues.";
RL   J. Pathol. 193:134-140(2001).
RN   [10]
RP   FUNCTION.
RX   PubMed=15537383; DOI=10.1042/bj20041066;
RA   Wilson S., Greer B., Hooper J., Zijlstra A., Walker B., Quigley J.,
RA   Hawthorne S.;
RT   "The membrane-anchored serine protease, TMPRSS2, activates PAR-2 in
RT   prostate cancer cells.";
RL   Biochem. J. 388:967-972(2005).
RN   [11]
RP   IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, AND GLYCOSYLATION.
RX   PubMed=20382709; DOI=10.2353/ajpath.2010.090665;
RA   Chen Y.W., Lee M.S., Lucht A., Chou F.P., Huang W., Havighurst T.C.,
RA   Kim K., Wang J.K., Antalis T.M., Johnson M.D., Lin C.Y.;
RT   "TMPRSS2, a serine protease expressed in the prostate on the apical surface
RT   of luminal epithelial cells and released into semen in prostasomes, is
RT   misregulated in prostate cancer cells.";
RL   Am. J. Pathol. 176:2986-2996(2010).
RN   [12]
RP   FUNCTION (MICROBIAL INFECTION), SUBCELLULAR LOCATION, AUTOCATALYTIC
RP   CLEAVAGE, AND INTERACTION WITH ACE2.
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   [13]
RP   FUNCTION (MICROBIAL INFECTION), AND TISSUE SPECIFICITY.
RX   PubMed=21325420; DOI=10.1128/jvi.02232-10;
RA   Glowacka I., Bertram S., Muller M.A., Allen P., Soilleux E., Pfefferle S.,
RA   Steffen I., Tsegaye T.S., He Y., Gnirss K., Niemeyer D., Schneider H.,
RA   Drosten C., Pohlmann S.;
RT   "Evidence that TMPRSS2 activates the severe acute respiratory syndrome
RT   coronavirus spike protein for membrane fusion and reduces viral control by
RT   the humoral immune response.";
RL   J. Virol. 85:4122-4134(2011).
RN   [14]
RP   FUNCTION (MICROBIAL INFECTION).
RX   PubMed=23536651; DOI=10.1128/jvi.03372-12;
RA   Bertram S., Dijkman R., Habjan M., Heurich A., Gierer S., Glowacka I.,
RA   Welsch K., Winkler M., Schneider H., Hofmann-Winkler H., Thiel V.,
RA   Pohlmann S.;
RT   "TMPRSS2 activates the human coronavirus 229E for cathepsin-independent
RT   host cell entry and is expressed in viral target cells in the respiratory
RT   epithelium.";
RL   J. Virol. 87:6150-6160(2013).
RN   [15]
RP   FUNCTION (MICROBIAL INFECTION).
RX   PubMed=23966399; DOI=10.1128/jvi.01490-13;
RA   Abe M., Tahara M., Sakai K., Yamaguchi H., Kanou K., Shirato K., Kawase M.,
RA   Noda M., Kimura H., Matsuyama S., Fukuhara H., Mizuta K., Maenaka K.,
RA   Ami Y., Esumi M., Kato A., Takeda M.;
RT   "TMPRSS2 is an activating protease for respiratory parainfluenza viruses.";
RL   J. Virol. 87:11930-11935(2013).
RN   [16]
RP   FUNCTION (MICROBIAL INFECTION).
RX   PubMed=24027332; DOI=10.1128/jvi.01890-13;
RA   Shirato K., Kawase M., Matsuyama S.;
RT   "Middle East respiratory syndrome coronavirus infection mediated by the
RT   transmembrane serine protease TMPRSS2.";
RL   J. Virol. 87:12552-12561(2013).
RN   [17]
RP   FUNCTION (MICROBIAL INFECTION).
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   [18]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=25122198; DOI=10.1158/2159-8290.cd-13-1010;
RA   Lucas J.M., Heinlein C., Kim T., Hernandez S.A., Malik M.S., True L.D.,
RA   Morrissey C., Corey E., Montgomery B., Mostaghel E., Clegg N., Coleman I.,
RA   Brown C.M., Schneider E.L., Craik C., Simon J.A., Bedalov A., Nelson P.S.;
RT   "The androgen-regulated protease TMPRSS2 activates a proteolytic cascade
RT   involving components of the tumor microenvironment and promotes prostate
RT   cancer metastasis.";
RL   Cancer Discov. 4:1310-1325(2014).
RN   [19]
RP   FUNCTION.
RX   PubMed=26018085; DOI=10.1158/0008-5472.can-14-3297;
RA   Ko C.J., Huang C.C., Lin H.Y., Juan C.P., Lan S.W., Shyu H.Y., Wu S.R.,
RA   Hsiao P.W., Huang H.P., Shun C.T., Lee M.S.;
RT   "Androgen-Induced TMPRSS2 activates matriptase and promotes extracellular
RT   matrix degradation, prostate cancer cell invasion, tumor growth, and
RT   metastasis.";
RL   Cancer Res. 75:2949-2960(2015).
RN   [20]
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   [21]
RP   TISSUE SPECIFICITY.
RX   DOI=10.1016/j.cell.2020.04.035;
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., 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 0:0-0(2020).
RN   [22]
RP   FUNCTION (MICROBIAL INFECTION).
RX   PubMed=33051876; DOI=10.15252/embj.2020106267;
RA   Buchrieser J., Dufloo J., Hubert M., Monel B., Planas D., Rajah M.M.,
RA   Planchais C., Porrot F., Guivel-Benhassine F., Van der Werf S.,
RA   Casartelli N., Mouquet H., Bruel T., Schwartz O.;
RT   "Syncytia formation by SARS-CoV-2-infected cells.";
RL   EMBO J. 39:e106267-e106267(2020).
RN   [23]
RP   ERRATUM OF PUBMED:33051876.
RX   PubMed=33522642; DOI=10.15252/embj.2020107405;
RA   Buchrieser J., Dufloo J., Hubert M., Monel B., Planas D., Rajah M.M.,
RA   Planchais C., Porrot F., Guivel-Benhassine F., Van der Werf S.,
RA   Casartelli N., Mouquet H., Bruel T., Schwartz O.;
RT   "Syncytia formation by SARS-CoV-2-infected cells.";
RL   EMBO J. 40:e107405-e107405(2021).
RN   [24]
RP   FUNCTION (MICROBIAL INFECTION), AND FUNCTION.
RX   PubMed=32703818; DOI=10.26508/lsa.202000786;
RA   Bestle D., Heindl M.R., Limburg H., Van Lam van T., Pilgram O., Moulton H.,
RA   Stein D.A., Hardes K., Eickmann M., Dolnik O., Rohde C., Klenk H.D.,
RA   Garten W., Steinmetzer T., Boettcher-Friebertshaeuser E.;
RT   "TMPRSS2 and furin are both essential for proteolytic activation of SARS-
RT   CoV-2 in human airway cells.";
RL   Life. Sci Alliance 3:1-14(2020).
RN   [25]
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   [26]
RP   FUNCTION (MICROBIAL INFECTION), AND 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   [27]
RP   FUNCTION (MICROBIAL INFECTION).
RX   PubMed=34159616; DOI=10.15252/embj.2021107821;
RA   Koch J., Uckeley Z.M., Doldan P., Stanifer M., Boulant S., Lozach P.Y.;
RT   "TMPRSS2 expression dictates the entry route used by SARS-CoV-2 to infect
RT   host cells.";
RL   EMBO J. 40:1-20(2021).
RN   [28]
RP   VARIANTS MET-160; CYS-254; GLN-329 AND ASN-491.
RX   PubMed=17918732; DOI=10.1002/humu.20617;
RA   Guipponi M., Toh M.-Y., Tan J., Park D., Hanson K., Ballana E., Kwong D.,
RA   Cannon P.Z.F., Wu Q., Gout A., Delorenzi M., Speed T.P., Smith R.J.H.,
RA   Dahl H.-H.M., Petersen M., Teasdale R.D., Estivill X., Park W.J.,
RA   Scott H.S.;
RT   "An integrated genetic and functional analysis of the role of type II
RT   transmembrane serine proteases (TMPRSSs) in hearing loss.";
RL   Hum. Mutat. 29:130-141(2008).
RN   [29]
RP   VARIANTS THR-28; ARG-74 AND MET-160.
RX   PubMed=32867305; DOI=10.3390/genes11091010;
RA   Latini A., Agolini E., Novelli A., Borgiani P., Giannini R., Gravina P.,
RA   Smarrazzo A., Dauri M., Andreoni M., Rogliani P., Bernardini S.,
RA   Helmer-Citterich M., Biancolella M., Novelli G.;
RT   "COVID-19 and Genetic Variants of Protein Involved in the SARS-CoV-2 Entry
RT   into the Host Cells.";
RL   Genes (Basel) 11:0-0(2020).
CC   -!- FUNCTION: Plasma membrane-anchored serine protease that cleaves at
CC       arginine residues (PubMed:32703818). Participates in proteolytic
CC       cascades of relevance for the normal physiologic function of the
CC       prostate (PubMed:25122198). Androgen-induced TMPRSS2 activates several
CC       substrates that include pro-hepatocyte growth factor/HGF, the protease
CC       activated receptor-2/F2RL1 or matriptase/ST14 leading to extracellular
CC       matrix disruption and metastasis of prostate cancer cells
CC       (PubMed:15537383, PubMed:26018085, PubMed:25122198). In addition,
CC       activates trigeminal neurons and contribute to both spontaneous pain
CC       and mechanical allodynia (By similarity).
CC       {ECO:0000250|UniProtKB:Q9JIQ8, ECO:0000269|PubMed:15537383,
CC       ECO:0000269|PubMed:25122198, ECO:0000269|PubMed:26018085,
CC       ECO:0000269|PubMed:32703818}.
CC   -!- FUNCTION: (Microbial infection) Facilitates human coronaviruses SARS-
CC       CoV and SARS-CoV-2 infections via two independent mechanisms,
CC       proteolytic cleavage of ACE2 receptor which promotes viral uptake, and
CC       cleavage of coronavirus spike glycoproteins which activates the
CC       glycoprotein for host cell entry (PubMed:24227843, PubMed:32142651,
CC       PubMed:32404436, PubMed:34159616, PubMed:33051876). The cleavage of
CC       SARS-COV2 spike glycoprotein occurs between the S2 and S2' site
CC       (PubMed:32703818). Upon SARS-CoV-2 infection, increases syncytia
CC       formation by accelerating the fusion process (PubMed:34159616,
CC       PubMed:33051876). Proteolytically cleaves and activates the spike
CC       glycoproteins of human coronavirus 229E (HCoV-229E) and human
CC       coronavirus EMC (HCoV-EMC) and the fusion glycoproteins F0 of Sendai
CC       virus (SeV), human metapneumovirus (HMPV), human parainfluenza 1, 2, 3,
CC       4a and 4b viruses (HPIV). Essential for spread and pathogenesis of
CC       influenza A virus (strains H1N1, H3N2 and H7N9); involved in
CC       proteolytic cleavage and activation of hemagglutinin (HA) protein which
CC       is essential for viral infectivity. {ECO:0000269|PubMed:21068237,
CC       ECO:0000269|PubMed:21325420, ECO:0000269|PubMed:23536651,
CC       ECO:0000269|PubMed:23966399, ECO:0000269|PubMed:24027332,
CC       ECO:0000269|PubMed:24227843, ECO:0000269|PubMed:32142651,
CC       ECO:0000269|PubMed:32404436, ECO:0000269|PubMed:32703818,
CC       ECO:0000269|PubMed:33051876, ECO:0000269|PubMed:34159616}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=The enzyme cleaves angiotensin-converting enzyme 2 (EC
CC         3.4.17.23) and cleaves influenzea A and B virus and coronavirus spike
CC         glycoproteins at arginine residues.; EC=3.4.21.122;
CC         Evidence={ECO:0000269|PubMed:32703818};
CC   -!- SUBUNIT: The catalytically active form interacts with ACE2.
CC       {ECO:0000269|PubMed:21068237}.
CC   -!- INTERACTION:
CC       O15393; Q9BYF1: ACE2; NbExp=3; IntAct=EBI-12549863, EBI-7730807;
CC       O15393; P01009: SERPINA1; NbExp=2; IntAct=EBI-12549863, EBI-986224;
CC       O15393-2; Q15848: ADIPOQ; NbExp=3; IntAct=EBI-12345267, EBI-10827839;
CC       O15393-2; Q86W74-2: ANKRD46; NbExp=3; IntAct=EBI-12345267, EBI-12109402;
CC       O15393-2; P29972: AQP1; NbExp=3; IntAct=EBI-12345267, EBI-745213;
CC       O15393-2; O95393: BMP10; NbExp=3; IntAct=EBI-12345267, EBI-3922513;
CC       O15393-2; Q12982: BNIP2; NbExp=3; IntAct=EBI-12345267, EBI-752094;
CC       O15393-2; Q12983: BNIP3; NbExp=3; IntAct=EBI-12345267, EBI-749464;
CC       O15393-2; Q6PL45-2: BRICD5; NbExp=3; IntAct=EBI-12345267, EBI-12244618;
CC       O15393-2; Q86Z23: C1QL4; NbExp=3; IntAct=EBI-12345267, EBI-12062109;
CC       O15393-2; O14523: C2CD2L; NbExp=3; IntAct=EBI-12345267, EBI-12822627;
CC       O15393-2; Q9BXR6: CFHR5; NbExp=3; IntAct=EBI-12345267, EBI-11579371;
CC       O15393-2; Q9BXN2-6: CLEC7A; NbExp=3; IntAct=EBI-12345267, EBI-11989440;
CC       O15393-2; Q9NWW5: CLN6; NbExp=3; IntAct=EBI-12345267, EBI-6165897;
CC       O15393-2; Q96FZ5: CMTM7; NbExp=3; IntAct=EBI-12345267, EBI-2807956;
CC       O15393-2; Q6PI25: CNIH2; NbExp=3; IntAct=EBI-12345267, EBI-12815321;
CC       O15393-2; Q8TBE1: CNIH3; NbExp=3; IntAct=EBI-12345267, EBI-12208021;
CC       O15393-2; Q4LDR2: CTXN3; NbExp=3; IntAct=EBI-12345267, EBI-12019274;
CC       O15393-2; Q07325: CXCL9; NbExp=3; IntAct=EBI-12345267, EBI-3911467;
CC       O15393-2; Q9BQA9: CYBC1; NbExp=3; IntAct=EBI-12345267, EBI-2680384;
CC       O15393-2; P81534: DEFB103B; NbExp=3; IntAct=EBI-12345267, EBI-12074168;
CC       O15393-2; P56851: EDDM3B; NbExp=3; IntAct=EBI-12345267, EBI-10215665;
CC       O15393-2; Q9UKR5: ERG28; NbExp=3; IntAct=EBI-12345267, EBI-711490;
CC       O15393-2; Q92520: FAM3C; NbExp=3; IntAct=EBI-12345267, EBI-2876774;
CC       O15393-2; Q96IV6: FAXDC2; NbExp=3; IntAct=EBI-12345267, EBI-12142299;
CC       O15393-2; P24593: IGFBP5; NbExp=3; IntAct=EBI-12345267, EBI-720480;
CC       O15393-2; Q6ZSS7: MFSD6; NbExp=3; IntAct=EBI-12345267, EBI-2858252;
CC       O15393-2; O75425: MOSPD3; NbExp=3; IntAct=EBI-12345267, EBI-12179105;
CC       O15393-2; Q9NZG7: NINJ2; NbExp=3; IntAct=EBI-12345267, EBI-10317425;
CC       O15393-2; Q9UHJ9-5: PGAP2; NbExp=3; IntAct=EBI-12345267, EBI-12092917;
CC       O15393-2; Q9Y342: PLLP; NbExp=3; IntAct=EBI-12345267, EBI-3919291;
CC       O15393-2; P26678: PLN; NbExp=3; IntAct=EBI-12345267, EBI-692836;
CC       O15393-2; P60201-2: PLP1; NbExp=3; IntAct=EBI-12345267, EBI-12188331;
CC       O15393-2; Q04941: PLP2; NbExp=4; IntAct=EBI-12345267, EBI-608347;
CC       O15393-2; Q13635-3: PTCH1; NbExp=3; IntAct=EBI-12345267, EBI-14199621;
CC       O15393-2; P53801: PTTG1IP; NbExp=3; IntAct=EBI-12345267, EBI-3906138;
CC       O15393-2; O00767: SCD; NbExp=4; IntAct=EBI-12345267, EBI-2684237;
CC       O15393-2; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-12345267, EBI-8652744;
CC       O15393-2; Q9Y6D0: SELENOK; NbExp=3; IntAct=EBI-12345267, EBI-9679163;
CC       O15393-2; P11686: SFTPC; NbExp=3; IntAct=EBI-12345267, EBI-10197617;
CC       O15393-2; P78382: SLC35A1; NbExp=3; IntAct=EBI-12345267, EBI-12870360;
CC       O15393-2; Q9NVC3: SLC38A7; NbExp=3; IntAct=EBI-12345267, EBI-10314552;
CC       O15393-2; B2RUZ4: SMIM1; NbExp=3; IntAct=EBI-12345267, EBI-12188413;
CC       O15393-2; O15400: STX7; NbExp=4; IntAct=EBI-12345267, EBI-3221827;
CC       O15393-2; Q9UNK0: STX8; NbExp=3; IntAct=EBI-12345267, EBI-727240;
CC       O15393-2; P17152: TMEM11; NbExp=3; IntAct=EBI-12345267, EBI-723946;
CC       O15393-2; A0PK00: TMEM120B; NbExp=3; IntAct=EBI-12345267, EBI-10171534;
CC       O15393-2; Q5BJH2-2: TMEM128; NbExp=3; IntAct=EBI-12345267, EBI-10694905;
CC       O15393-2; A2RU14: TMEM218; NbExp=3; IntAct=EBI-12345267, EBI-10173151;
CC       O15393-2; Q9H0R3: TMEM222; NbExp=3; IntAct=EBI-12345267, EBI-347385;
CC       O15393-2; Q8NBD8: TMEM229B; NbExp=3; IntAct=EBI-12345267, EBI-12195227;
CC       O15393-2; Q9BU79: TMEM243; NbExp=3; IntAct=EBI-12345267, EBI-12887458;
CC       O15393-2; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-12345267, EBI-2852148;
CC       O15393-2; Q9BSE2: TMEM79; NbExp=3; IntAct=EBI-12345267, EBI-8649725;
CC       O15393-2; Q8N2M4: TMEM86A; NbExp=3; IntAct=EBI-12345267, EBI-12015604;
CC       O15393-2; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-12345267, EBI-2548832;
CC       O15393-2; P01375: TNF; NbExp=3; IntAct=EBI-12345267, EBI-359977;
CC       O15393-2; Q5BVD1: TTMP; NbExp=5; IntAct=EBI-12345267, EBI-10243654;
CC       O15393-2; O00526: UPK2; NbExp=3; IntAct=EBI-12345267, EBI-10179682;
CC       O15393-2; O95183: VAMP5; NbExp=3; IntAct=EBI-12345267, EBI-10191195;
CC       O15393-2; Q9BQB6: VKORC1; NbExp=3; IntAct=EBI-12345267, EBI-6256462;
CC       O15393-2; O95159: ZFPL1; NbExp=3; IntAct=EBI-12345267, EBI-718439;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20382709,
CC       ECO:0000269|PubMed:21068237}; Single-pass type II membrane protein
CC       {ECO:0000269|PubMed:20382709, ECO:0000269|PubMed:21068237}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protease serine 2 catalytic
CC       chain]: Secreted {ECO:0000269|PubMed:20382709}. Note=Activated by
CC       cleavage and secreted. {ECO:0000269|PubMed:11245484,
CC       ECO:0000269|PubMed:20382709}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=O15393-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O15393-2; Sequence=VSP_045083;
CC   -!- TISSUE SPECIFICITY: Expressed in several tissues that comprise large
CC       populations of epithelial cells with the highest level of transcripts
CC       measured in the prostate gland. Expressed in type II pneumocytes in the
CC       lung (at protein level). Expressed strongly in small intestine. Also
CC       expressed in colon, stomach and salivary gland. Coexpressed with ACE2
CC       within lung type II pneumocytes, ileal absorptive enterocytes,
CC       intestinal epithelial cells, cornea, gallbladder and nasal goblet
CC       secretory cells (Ref.21). {ECO:0000269|PubMed:11169526,
CC       ECO:0000269|PubMed:20382709, ECO:0000269|PubMed:21325420,
CC       ECO:0000269|PubMed:32404436, ECO:0000269|Ref.21}.
CC   -!- INDUCTION: By androgenic hormones in vivo.
CC       {ECO:0000269|PubMed:25122198}.
CC   -!- PTM: Proteolytically processed; by an autocatalytic mechanism.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00274}.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="https://atlasgeneticsoncology.org/gene/42592/TMPRSS2";
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DR   EMBL; U75329; AAC51784.1; -; mRNA.
DR   EMBL; AF123453; AAD37117.1; -; mRNA.
DR   EMBL; AF270487; AAK29280.1; -; mRNA.
DR   EMBL; AK291813; BAF84502.1; -; mRNA.
DR   EMBL; AK296860; BAH12445.1; -; mRNA.
DR   EMBL; AK313338; BAG36142.1; -; mRNA.
DR   EMBL; AK222784; BAD96504.1; -; mRNA.
DR   EMBL; AP001610; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471079; EAX09597.1; -; Genomic_DNA.
DR   EMBL; CH471079; EAX09598.1; -; Genomic_DNA.
DR   EMBL; BC051839; AAH51839.1; -; mRNA.
DR   CCDS; CCDS33564.1; -. [O15393-1]
DR   CCDS; CCDS54486.1; -. [O15393-2]
DR   RefSeq; NP_001128571.1; NM_001135099.1. [O15393-2]
DR   RefSeq; NP_005647.3; NM_005656.3. [O15393-1]
DR   RefSeq; XP_011528033.1; XM_011529731.2.
DR   PDB; 7MEQ; X-ray; 1.95 A; A=109-492.
DR   PDBsum; 7MEQ; -.
DR   AlphaFoldDB; O15393; -.
DR   SMR; O15393; -.
DR   BioGRID; 112968; 339.
DR   IntAct; O15393; 63.
DR   STRING; 9606.ENSP00000381588; -.
DR   BindingDB; O15393; -.
DR   ChEMBL; CHEMBL1795140; -.
DR   DrugBank; DB09019; Bromhexine.
DR   DrugBank; DB13729; Camostat.
DR   DrugBank; DB16737; MM3122.
DR   GuidetoPHARMACOLOGY; 2421; -.
DR   MEROPS; S01.247; -.
DR   TCDB; 8.A.131.1.6; the transmembrane protease serine 3 (tmprss3) family.
DR   GlyConnect; 1848; 4 N-Linked glycans (2 sites).
DR   GlyCosmos; O15393; 2 sites, 4 glycans.
DR   GlyGen; O15393; 2 sites, 4 N-linked glycans (2 sites).
DR   iPTMnet; O15393; -.
DR   PhosphoSitePlus; O15393; -.
DR   SwissPalm; O15393; -.
DR   BioMuta; TMPRSS2; -.
DR   EPD; O15393; -.
DR   jPOST; O15393; -.
DR   MassIVE; O15393; -.
DR   MaxQB; O15393; -.
DR   PaxDb; 9606-ENSP00000381588; -.
DR   PeptideAtlas; O15393; -.
DR   ProteomicsDB; 31938; -.
DR   ProteomicsDB; 48634; -. [O15393-1]
DR   ABCD; O15393; 1 sequenced antibody.
DR   Antibodypedia; 2685; 355 antibodies from 35 providers.
DR   DNASU; 7113; -.
DR   Ensembl; ENST00000332149.10; ENSP00000330330.5; ENSG00000184012.14. [O15393-1]
DR   Ensembl; ENST00000398585.7; ENSP00000381588.3; ENSG00000184012.14. [O15393-2]
DR   Ensembl; ENST00000454499.6; ENSP00000389006.2; ENSG00000184012.14. [O15393-1]
DR   Ensembl; ENST00000458356.6; ENSP00000391216.1; ENSG00000184012.14. [O15393-1]
DR   Ensembl; ENST00000676973.1; ENSP00000504705.1; ENSG00000184012.14. [O15393-1]
DR   Ensembl; ENST00000678348.1; ENSP00000503556.1; ENSG00000184012.14. [O15393-1]
DR   Ensembl; ENST00000679054.1; ENSP00000502928.1; ENSG00000184012.14. [O15393-1]
DR   GeneID; 7113; -.
DR   KEGG; hsa:7113; -.
DR   MANE-Select; ENST00000332149.10; ENSP00000330330.5; NM_005656.4; NP_005647.3.
DR   UCSC; uc002yzj.4; human. [O15393-1]
DR   AGR; HGNC:11876; -.
DR   CTD; 7113; -.
DR   DisGeNET; 7113; -.
DR   GeneCards; TMPRSS2; -.
DR   HGNC; HGNC:11876; TMPRSS2.
DR   HPA; ENSG00000184012; Tissue enhanced (prostate, stomach).
DR   MIM; 602060; gene.
DR   neXtProt; NX_O15393; -.
DR   OpenTargets; ENSG00000184012; -.
DR   PharmGKB; PA36577; -.
DR   VEuPathDB; HostDB:ENSG00000184012; -.
DR   eggNOG; KOG3627; Eukaryota.
DR   GeneTree; ENSGT00940000155207; -.
DR   InParanoid; O15393; -.
DR   OMA; AQRKSWH; -.
DR   OrthoDB; 4629979at2759; -.
DR   PhylomeDB; O15393; -.
DR   TreeFam; TF351678; -.
DR   BRENDA; 3.4.21.B60; 2681.
DR   PathwayCommons; O15393; -.
DR   Reactome; R-HSA-9678110; Attachment and Entry.
DR   Reactome; R-HSA-9694614; Attachment and Entry.
DR   Reactome; R-HSA-9733458; Induction of Cell-Cell Fusion.
DR   SABIO-RK; O15393; -.
DR   SignaLink; O15393; -.
DR   SIGNOR; O15393; -.
DR   BioGRID-ORCS; 7113; 20 hits in 1166 CRISPR screens.
DR   ChiTaRS; TMPRSS2; human.
DR   GeneWiki; TMPRSS2; -.
DR   GenomeRNAi; 7113; -.
DR   Pharos; O15393; Tchem.
DR   PRO; PR:O15393; -.
DR   Proteomes; UP000005640; Chromosome 21.
DR   RNAct; O15393; Protein.
DR   Bgee; ENSG00000184012; Expressed in mucosa of transverse colon and 159 other cell types or tissues.
DR   ExpressionAtlas; O15393; baseline and differential.
DR   Genevisible; O15393; HS.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProt.
DR   GO; GO:0008236; F:serine-type peptidase activity; TAS:ProtInc.
DR   GO; GO:0046598; P:positive regulation of viral entry into host cell; IDA:UniProtKB.
DR   GO; GO:0016540; P:protein autoprocessing; IMP:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR   GO; GO:0019081; P:viral translation; TAS:UniProt.
DR   CDD; cd00112; LDLa; 1.
DR   CDD; cd00190; Tryp_SPc; 1.
DR   Gene3D; 4.10.400.10; Low-density Lipoprotein Receptor; 1.
DR   Gene3D; 3.10.250.10; SRCR-like domain; 1.
DR   Gene3D; 2.40.10.10; Trypsin-like serine proteases; 1.
DR   InterPro; IPR036055; LDL_receptor-like_sf.
DR   InterPro; IPR023415; LDLR_class-A_CS.
DR   InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR   InterPro; IPR001314; Peptidase_S1A.
DR   InterPro; IPR001190; SRCR.
DR   InterPro; IPR017448; SRCR-like_dom.
DR   InterPro; IPR036772; SRCR-like_dom_sf.
DR   InterPro; IPR001254; Trypsin_dom.
DR   InterPro; IPR018114; TRYPSIN_HIS.
DR   InterPro; IPR033116; TRYPSIN_SER.
DR   PANTHER; PTHR24253; TRANSMEMBRANE PROTEASE SERINE; 1.
DR   PANTHER; PTHR24253:SF89; TRANSMEMBRANE PROTEASE SERINE 2; 1.
DR   Pfam; PF15494; SRCR_2; 1.
DR   Pfam; PF00089; Trypsin; 1.
DR   PRINTS; PR00722; CHYMOTRYPSIN.
DR   SMART; SM00192; LDLa; 1.
DR   SMART; SM00202; SR; 1.
DR   SMART; SM00020; Tryp_SPc; 1.
DR   SUPFAM; SSF57424; LDL receptor-like module; 1.
DR   SUPFAM; SSF56487; SRCR-like; 1.
DR   SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR   PROSITE; PS01209; LDLRA_1; 1.
DR   PROSITE; PS50068; LDLRA_2; 1.
DR   PROSITE; PS50287; SRCR_2; 1.
DR   PROSITE; PS50240; TRYPSIN_DOM; 1.
DR   PROSITE; PS00134; TRYPSIN_HIS; 1.
DR   PROSITE; PS00135; TRYPSIN_SER; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Autocatalytic cleavage; Cell membrane;
KW   Disulfide bond; Glycoprotein; Host-virus interaction; Hydrolase; Membrane;
KW   Protease; Reference proteome; Secreted; Serine protease; Signal-anchor;
KW   Transmembrane; Transmembrane helix; Zymogen.
FT   CHAIN           1..255
FT                   /note="Transmembrane protease serine 2 non-catalytic chain"
FT                   /id="PRO_0000027855"
FT   CHAIN           256..492
FT                   /note="Transmembrane protease serine 2 catalytic chain"
FT                   /id="PRO_0000027856"
FT   TOPO_DOM        1..84
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        85..105
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        106..492
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          112..149
FT                   /note="LDL-receptor class A"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT   DOMAIN          150..242
FT                   /note="SRCR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT   DOMAIN          256..489
FT                   /note="Peptidase S1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   ACT_SITE        296
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        345
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        441
FT                   /note="Charge relay system"
FT   SITE            255..256
FT                   /note="Cleavage"
FT                   /evidence="ECO:0000269|PubMed:11245484"
FT   CARBOHYD        213
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        249
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        113..126
FT                   /evidence="ECO:0000250"
FT   DISULFID        120..139
FT                   /evidence="ECO:0000250"
FT   DISULFID        133..148
FT                   /evidence="ECO:0000250"
FT   DISULFID        172..231
FT                   /evidence="ECO:0000250"
FT   DISULFID        185..241
FT                   /evidence="ECO:0000250"
FT   DISULFID        244..365
FT                   /note="Interchain (between non-catalytic and catalytic
FT                   chains)"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00124,
FT                   ECO:0000255|PROSITE-ProRule:PRU00196, ECO:0000255|PROSITE-
FT                   ProRule:PRU00274"
FT   DISULFID        281..297
FT                   /evidence="ECO:0000250"
FT   DISULFID        410..426
FT                   /evidence="ECO:0000250"
FT   DISULFID        437..465
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         1
FT                   /note="M -> MPPAPPGGESGCEERGAAGHIEHSRYLSLLDAVDNSKM (in
FT                   isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_045083"
FT   VARIANT         28
FT                   /note="A -> T"
FT                   /evidence="ECO:0000269|PubMed:32867305"
FT                   /id="VAR_084538"
FT   VARIANT         74
FT                   /note="G -> R"
FT                   /evidence="ECO:0000269|PubMed:32867305"
FT                   /id="VAR_084539"
FT   VARIANT         160
FT                   /note="V -> M (in dbSNP:rs12329760)"
FT                   /evidence="ECO:0000269|PubMed:11414763,
FT                   ECO:0000269|PubMed:17918732, ECO:0000269|PubMed:32867305,
FT                   ECO:0000269|PubMed:9325052"
FT                   /id="VAR_027674"
FT   VARIANT         254
FT                   /note="S -> C"
FT                   /evidence="ECO:0000269|PubMed:17918732"
FT                   /id="VAR_038002"
FT   VARIANT         329
FT                   /note="E -> Q (in dbSNP:rs775137340)"
FT                   /evidence="ECO:0000269|PubMed:17918732,
FT                   ECO:0000269|PubMed:9325052"
FT                   /id="VAR_038003"
FT   VARIANT         449
FT                   /note="K -> N (in dbSNP:rs1056602)"
FT                   /id="VAR_011692"
FT   VARIANT         491
FT                   /note="D -> N (in dbSNP:rs779875214)"
FT                   /evidence="ECO:0000269|PubMed:17918732"
FT                   /id="VAR_038004"
FT   MUTAGEN         255
FT                   /note="R->Q: Loss of cleavage."
FT                   /evidence="ECO:0000269|PubMed:11245484"
FT   MUTAGEN         441
FT                   /note="S->A: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:11245484"
FT   CONFLICT        26
FT                   /note="Y -> H (in Ref. 4; BAF84502)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        62
FT                   /note="N -> S (in Ref. 4; BAH12445)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        163
FT                   /note="S -> P (in Ref. 4; BAF84502)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        242
FT                   /note="I -> L (in Ref. 1; AAC51784)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        489..491
FT                   /note="RAD -> KAN (in Ref. 1; AAC51784)"
FT                   /evidence="ECO:0000305"
FT   STRAND          149..152
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   TURN            153..156
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   STRAND          157..161
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   STRAND          168..172
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   HELIX           178..187
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   STRAND          196..200
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   STRAND          209..212
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   STRAND          225..229
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   STRAND          236..242
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   TURN            264..266
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   STRAND          270..275
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   STRAND          278..293
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   HELIX           295..298
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   HELIX           305..307
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   STRAND          308..313
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   HELIX           317..319
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   STRAND          325..333
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   TURN            339..342
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   STRAND          347..353
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   STRAND          358..360
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   STRAND          378..384
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   STRAND          398..405
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   HELIX           407..410
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   TURN            413..418
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   STRAND          424..428
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   STRAND          433..435
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   STRAND          444..449
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   STRAND          452..461
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   STRAND          463..466
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   STRAND          472..476
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   HELIX           477..490
FT                   /evidence="ECO:0007829|PDB:7MEQ"
FT   VARIANT         O15393-2:8
FT                   /note="G -> R (in dbSNP:rs200291871)"
FT                   /evidence="ECO:0000269|PubMed:32867305"
FT                   /id="VAR_084541"
FT   VARIANT         O15393-2:8
FT                   /note="G -> V (in dbSNP:rs75603675)"
FT                   /evidence="ECO:0000269|PubMed:32867305"
FT                   /id="VAR_084540"
SQ   SEQUENCE   492 AA;  53859 MW;  C05B5531C8A311C7 CRC64;
     MALNSGSPPA IGPYYENHGY QPENPYPAQP TVVPTVYEVH PAQYYPSPVP QYAPRVLTQA
     SNPVVCTQPK SPSGTVCTSK TKKALCITLT LGTFLVGAAL AAGLLWKFMG SKCSNSGIEC
     DSSGTCINPS NWCDGVSHCP GGEDENRCVR LYGPNFILQV YSSQRKSWHP VCQDDWNENY
     GRAACRDMGY KNNFYSSQGI VDDSGSTSFM KLNTSAGNVD IYKKLYHSDA CSSKAVVSLR
     CIACGVNLNS SRQSRIVGGE SALPGAWPWQ VSLHVQNVHV CGGSIITPEW IVTAAHCVEK
     PLNNPWHWTA FAGILRQSFM FYGAGYQVEK VISHPNYDSK TKNNDIALMK LQKPLTFNDL
     VKPVCLPNPG MMLQPEQLCW ISGWGATEEK GKTSEVLNAA KVLLIETQRC NSRYVYDNLI
     TPAMICAGFL QGNVDSCQGD SGGPLVTSKN NIWWLIGDTS WGSGCAKAYR PGVYGNVMVF
     TDWIYRQMRA DG
//