ID TM11A_HUMAN Reviewed; 418 AA. AC Q6ZMR5; J3KNQ8; Q2NKI9; Q6JE90; Q7RTY4; Q86TK8; DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot. DT 24-JAN-2024, sequence version 3. DT 27-MAR-2024, entry version 149. DE RecName: Full=Transmembrane protease serine 11A; DE EC=3.4.21.-; DE AltName: Full=Airway trypsin-like protease 1; DE AltName: Full=Epidermal type-II transmembrane serine protease; DE AltName: Full=Esophageal cancer-susceptibility gene 1 protein; GN Name=TMPRSS11A; Synonyms=ECRG1, HATL1, HESP; 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 2), TISSUE SPECIFICITY, AND VARIANT RP ARG-290. RC TISSUE=Esophagus; RX PubMed=10920976; RA Su T., Liu H., Lu S.-H.; RT "Cloning and identification of cDNA fragments related to human esophageal RT cancer."; RL Zhonghua Zhong Liu Za Zhi 20:254-257(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Mariotti F., Mastrogiacomo A.; RT "Identification and characterization of a novel human type II transmembrane RT serine protease."; RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-290. RC TISSUE=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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT ARG-290. 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 [6] RP IDENTIFICATION. RX PubMed=12838346; DOI=10.1038/nrg1111; RA Puente X.S., Sanchez L.M., Overall C.M., Lopez-Otin C.; RT "Human and mouse proteases: a comparative genomic approach."; RL Nat. Rev. Genet. 4:544-558(2003). RN [7] RP INTERACTION WITH ZBTB17. RX PubMed=15095404; DOI=10.1002/jcb.20025; RA Zhao N., Wang J., Cui Y., Guo L., Lu S.-H.; RT "Induction of G1 cell cycle arrest and P15INK4b expression by ECRG1 through RT interaction with Miz-1."; RL J. Cell. Biochem. 92:65-76(2004). RN [8] RP VARIANT ARG-290. RX PubMed=16267096; DOI=10.1093/carcin/bgi258; RA Li Y., Zhang X., Huang G., Miao X., Guo L., Lin D., Lu S.-H.; RT "Identification of a novel polymorphism Arg290Gln of esophageal cancer RT related gene 1 (ECRG1) and its related risk to esophageal squamous cell RT carcinoma."; RL Carcinogenesis 27:798-802(2006). CC -!- FUNCTION: Probable serine protease which may play a role in cellular CC senescence. Overexpression inhibits cell growth and induce G1 cell CC cycle arrest. CC -!- SUBUNIT: May interact with ZBTB17. CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type II CC membrane protein {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=2; CC IsoId=Q6ZMR5-2; Sequence=Displayed; CC Name=1; CC IsoId=Q6ZMR5-1; Sequence=VSP_061449; CC -!- TISSUE SPECIFICITY: Expressed in esophagus, liver, colon and lung. CC Down-regulated in esophagus cancers. {ECO:0000269|PubMed:10920976}. CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE- CC ProRule:PRU00274}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD41463.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=CAD67985.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; 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; AF071882; AAD41463.1; ALT_FRAME; mRNA. DR EMBL; AY498712; AAS78642.1; -; mRNA. DR EMBL; AK131518; BAD18660.1; -; mRNA. DR EMBL; AC096653; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC096727; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC111796; AAI11797.1; -; mRNA. DR EMBL; BN000133; CAD67985.1; ALT_SEQ; mRNA. DR CCDS; CCDS3519.1; -. [Q6ZMR5-1] DR CCDS; CCDS47065.1; -. [Q6ZMR5-2] DR RefSeq; NP_001107859.1; NM_001114387.1. [Q6ZMR5-2] DR RefSeq; NP_872412.3; NM_182606.3. [Q6ZMR5-1] DR AlphaFoldDB; Q6ZMR5; -. DR SMR; Q6ZMR5; -. DR BioGRID; 130971; 14. DR IntAct; Q6ZMR5; 7. DR STRING; 9606.ENSP00000334611; -. DR MEROPS; S01.292; -. DR TCDB; 8.A.131.1.7; the transmembrane protease serine 3 (tmprss3) family. DR GlyCosmos; Q6ZMR5; 2 sites, No reported glycans. DR GlyGen; Q6ZMR5; 2 sites. DR iPTMnet; Q6ZMR5; -. DR PhosphoSitePlus; Q6ZMR5; -. DR BioMuta; TMPRSS11A; -. DR DMDM; 74758674; -. DR MassIVE; Q6ZMR5; -. DR PaxDb; 9606-ENSP00000334611; -. DR PeptideAtlas; Q6ZMR5; -. DR ProteomicsDB; 67906; -. [Q6ZMR5-1] DR ProteomicsDB; 67907; -. [Q6ZMR5-2] DR TopDownProteomics; Q6ZMR5-2; -. [Q6ZMR5-2] DR Antibodypedia; 57609; 109 antibodies from 21 providers. DR DNASU; 339967; -. DR Ensembl; ENST00000334830.11; ENSP00000334611.7; ENSG00000187054.16. [Q6ZMR5-1] DR Ensembl; ENST00000508048.6; ENSP00000426911.2; ENSG00000187054.16. [Q6ZMR5-2] DR GeneID; 339967; -. DR KEGG; hsa:339967; -. DR MANE-Select; ENST00000508048.6; ENSP00000426911.2; NM_001114387.2; NP_001107859.1. DR UCSC; uc003hds.2; human. [Q6ZMR5-2] DR AGR; HGNC:27954; -. DR CTD; 339967; -. DR DisGeNET; 339967; -. DR GeneCards; TMPRSS11A; -. DR HGNC; HGNC:27954; TMPRSS11A. DR HPA; ENSG00000187054; Tissue enhanced (esophagus, lymphoid tissue, vagina). DR MIM; 611704; gene. DR neXtProt; NX_Q6ZMR5; -. DR OpenTargets; ENSG00000187054; -. DR PharmGKB; PA142670726; -. DR VEuPathDB; HostDB:ENSG00000187054; -. DR eggNOG; KOG3627; Eukaryota. DR GeneTree; ENSGT00940000161698; -. DR InParanoid; Q6ZMR5; -. DR OrthoDB; 4629979at2759; -. DR PhylomeDB; Q6ZMR5; -. DR TreeFam; TF351684; -. DR BRENDA; 3.4.21.B61; 2681. DR PathwayCommons; Q6ZMR5; -. DR SignaLink; Q6ZMR5; -. DR BioGRID-ORCS; 339967; 9 hits in 1145 CRISPR screens. DR ChiTaRS; TMPRSS11A; human. DR GenomeRNAi; 339967; -. DR Pharos; Q6ZMR5; Tbio. DR PRO; PR:Q6ZMR5; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; Q6ZMR5; Protein. DR Bgee; ENSG00000187054; Expressed in esophagus mucosa and 33 other cell types or tissues. DR ExpressionAtlas; Q6ZMR5; baseline and differential. DR GO; GO:0005576; C:extracellular region; IEA:InterPro. DR GO; GO:0005886; C:plasma membrane; IEA:InterPro. DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR CDD; cd00190; Tryp_SPc; 1. DR Gene3D; 3.30.70.960; SEA domain; 1. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2. DR InterPro; IPR017329; Pept_S1A_HAT/DESC1. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR000082; SEA_dom. DR InterPro; IPR036364; SEA_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:SF7; HYALIN; 1. DR Pfam; PF01390; SEA; 1. DR Pfam; PF00089; Trypsin; 1. DR PIRSF; PIRSF037941; TMPRSS11ABCDE; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF82671; SEA domain; 1. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1. DR PROSITE; PS50024; SEA; 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 Alternative splicing; Cell cycle; Disulfide bond; Glycoprotein; Hydrolase; KW Membrane; Protease; Reference proteome; Serine protease; Signal-anchor; KW Transmembrane; Transmembrane helix. FT CHAIN 1..418 FT /note="Transmembrane protease serine 11A" FT /id="PRO_5000095974" FT TOPO_DOM 1..18 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 19..39 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 40..418 FT /note="Extracellular" FT /evidence="ECO:0000255" FT DOMAIN 47..164 FT /note="SEA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00188" FT DOMAIN 187..417 FT /note="Peptidase S1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT ACT_SITE 227 FT /note="Charge relay system" FT /evidence="ECO:0000250" FT ACT_SITE 272 FT /note="Charge relay system" FT /evidence="ECO:0000250" FT ACT_SITE 368 FT /note="Charge relay system" FT /evidence="ECO:0000250" FT CARBOHYD 153 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 303 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 212..228 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 337..353 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 364..393 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT VAR_SEQ 84 FT /note="L -> LVSQ (in isoform 1)" FT /evidence="ECO:0000303|PubMed:10920976, FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2" FT /id="VSP_061449" FT VARIANT 290 FT /note="Q -> R (in dbSNP:rs353163)" FT /evidence="ECO:0000269|PubMed:10920976, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:16267096" FT /id="VAR_034797" FT CONFLICT 50 FT /note="Y -> F (in Ref. 1; AAD41463)" FT /evidence="ECO:0000305" FT CONFLICT 52 FT /note="H -> P (in Ref. 1; AAD41463)" FT /evidence="ECO:0000305" FT CONFLICT 170 FT /note="T -> I (in Ref. 1; AAD41463)" FT /evidence="ECO:0000305" FT CONFLICT 264 FT /note="Y -> C (in Ref. 1; AAD41463)" FT /evidence="ECO:0000305" FT CONFLICT 268 FT /note="A -> P (in Ref. 1; AAD41463)" FT /evidence="ECO:0000305" FT CONFLICT 270 FT /note="E -> K (in Ref. 1; AAD41463)" FT /evidence="ECO:0000305" FT CONFLICT 285 FT /note="S -> P (in Ref. 1; AAD41463)" FT /evidence="ECO:0000305" FT CONFLICT 327 FT /note="A -> V (in Ref. 1; AAD41463)" FT /evidence="ECO:0000305" SQ SEQUENCE 418 AA; 47226 MW; 97784C1ABCA9B1D1 CRC64; MMYRTVGFGT RSRNLKPWMI AVLIVLSLTV VAVTIGLLVH FLVFDQKKEY YHGSFKILDP QINNNFGQSN TYQLKDLRET TENLVDEIFI DSAWKKNYIK NQVVRLTPEE DGVKVDVIMV FQFPSTEQRA VREKKIQSIL NQKIRNLRAL PINASSVQVN AMSSSTGELT VQASCGKRVV PLNVNRIASG VIAPKAAWPW QASLQYDNIH QCGATLISNT WLVTAAHCFQ KYKNPHQWTV SFGTKINPPL MKRNVRRFII HEKYRSAARE YDIAVVQVSS RVTFSDDIRQ ICLPEASASF QPNLTVHITG FGALYYGGES QNDLREARVK IISDDVCKQP QVYGNDIKPG MFCAGYMEGI YDACRGDSGG PLVTRDLKDT WYLIGIVSWG DNCGQKDKPG VYTQVTYYRN WIASKTGI //