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 27-MAR-2024, entry version 208. 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 CC (EC 3.4.17.23) and cleaves influenzea A and B virus and coronavirus CC spike 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"; 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; 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; 340. 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 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; PTHR24252; ACROSIN-RELATED; 1. DR PANTHER; PTHR24252:SF11; TRANSMEMBRANE SERINE PROTEASE 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. DR Genevisible; O15393; HS. 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 //