TM11D_HUMAN
ID TM11D_HUMAN Reviewed; 418 AA.
AC O60235; Q08AF6;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Transmembrane protease serine 11D;
DE EC=3.4.21.-;
DE AltName: Full=Airway trypsin-like protease;
DE Contains:
DE RecName: Full=Transmembrane protease serine 11D non-catalytic chain;
DE Contains:
DE RecName: Full=Transmembrane protease serine 11D catalytic chain;
DE Flags: Precursor;
GN Name=TMPRSS11D; Synonyms=HAT;
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].
RX PubMed=9565616; DOI=10.1074/jbc.273.19.11895;
RA Yamaoka K., Masuda K., Ogawa H., Takagi K., Umemoto N., Yasuoka S.;
RT "Cloning and characterization of the cDNA for human airway trypsin-like
RT protease.";
RL J. Biol. Chem. 273:11895-11901(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP PROTEIN SEQUENCE OF 187-206, AND CHARACTERIZATION.
RX PubMed=9070615; DOI=10.1165/ajrcmb.16.3.9070615;
RA Yasuoka S., Ohnishi T., Kawano S., Tsuchihashi S., Ogawara M., Masuda K.,
RA Yamaoka K., Takahashi M., Sano T.;
RT "Purification, characterization, and localization of a novel trypsin-like
RT protease found in the human airway.";
RL Am. J. Respir. Cell Mol. Biol. 16:300-308(1997).
RN [4]
RP FUNCTION.
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 [5]
RP FUNCTION.
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).
CC -!- FUNCTION: May play some biological role in the host defense system on
CC the mucous membrane independently of or in cooperation with other
CC substances in airway mucous or bronchial secretions. Plays a role in
CC the proteolytic processing of ACE2. Proteolytically cleaves and
CC activates the human coronavirus 229E (HCoV-229E) spike glycoprotein
CC which facilitate virus-cell membrane fusions; spike proteins are
CC synthesized and maintained in precursor intermediate folding states and
CC proteolysis permits the refolding and energy release required to create
CC stable virus-cell linkages and membrane coalescence. Preferentially
CC cleaves the C-terminal side of arginine residues at the P1 position of
CC certain peptides, cleaving Boc-Phe-Ser-Arg-4-methylcoumaryl-7-amide
CC most efficiently and having an optimum pH of 8.6 with this substrate.
CC {ECO:0000269|PubMed:23536651, ECO:0000269|PubMed:24227843}.
CC -!- ACTIVITY REGULATION: Strongly inhibited by diisopropyl fluorophosphate,
CC leupeptin, antipain, aprotinin, and soybean trypsin inhibitor, but
CC hardly inhibited by secretory leukocyte protease inhibitor at 10
CC microM.
CC -!- SUBUNIT: Monomer.
CC -!- INTERACTION:
CC O60235; O43765: SGTA; NbExp=3; IntAct=EBI-7639969, EBI-347996;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane
CC protein. Note=Activated by cleavage and secreted.
CC -!- SUBCELLULAR LOCATION: [Transmembrane protease serine 11D catalytic
CC chain]: Secreted. Note=Activated by cleavage and secreted.
CC -!- TISSUE SPECIFICITY: Located in the cells of the submucosal serous
CC glands of the bronchi and trachea.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; AB002134; BAA28691.1; -; mRNA.
DR EMBL; BC125195; AAI25196.1; -; mRNA.
DR EMBL; BC125196; AAI25197.1; -; mRNA.
DR CCDS; CCDS3518.1; -.
DR RefSeq; NP_004253.1; NM_004262.2.
DR AlphaFoldDB; O60235; -.
DR SMR; O60235; -.
DR BioGRID; 114803; 7.
DR IntAct; O60235; 3.
DR MINT; O60235; -.
DR STRING; 9606.ENSP00000283916; -.
DR BindingDB; O60235; -.
DR ChEMBL; CHEMBL1795138; -.
DR GuidetoPHARMACOLOGY; 2420; -.
DR MEROPS; S01.047; -.
DR GlyGen; O60235; 1 site.
DR BioMuta; TMPRSS11D; -.
DR MassIVE; O60235; -.
DR MaxQB; O60235; -.
DR PaxDb; O60235; -.
DR PeptideAtlas; O60235; -.
DR PRIDE; O60235; -.
DR ProteomicsDB; 49261; -.
DR Antibodypedia; 12680; 157 antibodies from 28 providers.
DR DNASU; 9407; -.
DR Ensembl; ENST00000283916.11; ENSP00000283916.6; ENSG00000153802.12.
DR GeneID; 9407; -.
DR KEGG; hsa:9407; -.
DR MANE-Select; ENST00000283916.11; ENSP00000283916.6; NM_004262.3; NP_004253.1.
DR UCSC; uc003hdq.4; human.
DR CTD; 9407; -.
DR DisGeNET; 9407; -.
DR GeneCards; TMPRSS11D; -.
DR HGNC; HGNC:24059; TMPRSS11D.
DR HPA; ENSG00000153802; Group enriched (cervix, esophagus, lymphoid tissue, salivary gland, vagina).
DR MIM; 605369; gene.
DR neXtProt; NX_O60235; -.
DR OpenTargets; ENSG00000153802; -.
DR PharmGKB; PA142670728; -.
DR VEuPathDB; HostDB:ENSG00000153802; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000161719; -.
DR HOGENOM; CLU_006842_19_0_1; -.
DR InParanoid; O60235; -.
DR OMA; WGYQCGV; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; O60235; -.
DR TreeFam; TF351684; -.
DR BRENDA; 3.4.21.B61; 2681.
DR PathwayCommons; O60235; -.
DR SignaLink; O60235; -.
DR BioGRID-ORCS; 9407; 9 hits in 1067 CRISPR screens.
DR ChiTaRS; TMPRSS11D; human.
DR GeneWiki; TMPRSS11D; -.
DR GenomeRNAi; 9407; -.
DR Pharos; O60235; Tchem.
DR PRO; PR:O60235; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; O60235; protein.
DR Bgee; ENSG00000153802; Expressed in tongue squamous epithelium and 134 other tissues.
DR ExpressionAtlas; O60235; baseline and differential.
DR Genevisible; O60235; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:ProtInc.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0008233; F:peptidase activity; TAS:ProtInc.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0007585; P:respiratory gaseous exchange by respiratory system; TAS:ProtInc.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 3.30.70.960; -; 1.
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 Pfam; PF01390; SEA; 1.
DR Pfam; PF00089; Trypsin; 1.
DR PIRSF; PIRSF037941; TMPRSS11ABCDE; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00200; SEA; 1.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF82671; SSF82671; 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 Cell membrane; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hydrolase; Membrane; Protease; Reference proteome; Secreted;
KW Serine protease; Signal-anchor; Transmembrane; Transmembrane helix;
KW Zymogen.
FT CHAIN 1..186
FT /note="Transmembrane protease serine 11D non-catalytic
FT chain"
FT /id="PRO_0000027885"
FT CHAIN 187..418
FT /note="Transmembrane protease serine 11D catalytic chain"
FT /id="PRO_0000027886"
FT TOPO_DOM 1..20
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 21..41
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 42..418
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 46..163
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 144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 173..292
FT /note="Interchain (between non-catalytic and catalytic
FT chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
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"
SQ SEQUENCE 418 AA; 46263 MW; F4BC1DB020CFBBD0 CRC64;
MYRPARVTST SRFLNPYVVC FIVVAGVVIL AVTIALLVYF LAFDQKSYFY RSSFQLLNVE
YNSQLNSPAT QEYRTLSGRI ESLITKTFKE SNLRNQFIRA HVAKLRQDGS GVRADVVMKF
QFTRNNNGAS MKSRIESVLR QMLNNSGNLE INPSTEITSL TDQAAANWLI NECGAGPDLI
TLSEQRILGG TEAEEGSWPW QVSLRLNNAH HCGGSLINNM WILTAAHCFR SNSNPRDWIA
TSGISTTFPK LRMRVRNILI HNNYKSATHE NDIALVRLEN SVTFTKDIHS VCLPAATQNI
PPGSTAYVTG WGAQEYAGHT VPELRQGQVR IISNDVCNAP HSYNGAILSG MLCAGVPQGG
VDACQGDSGG PLVQEDSRRL WFIVGIVSWG DQCGLPDKPG VYTRVTAYLD WIRQQTGI
