TMPS5_HUMAN
ID TMPS5_HUMAN Reviewed; 457 AA.
AC Q9H3S3;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Transmembrane protease serine 5;
DE EC=3.4.21.-;
DE AltName: Full=Spinesin;
GN Name=TMPRSS5;
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].
RC TISSUE=Brain;
RX PubMed=11741986; DOI=10.1074/jbc.m103645200;
RA Yamaguchi N., Okui A., Yamada T., Nakazato H., Mitsui S.;
RT "Spinesin/TMPRSS5, a novel transmembrane serine protease, cloned from human
RT spinal cord.";
RL J. Biol. Chem. 277:6806-6812(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, VARIANTS VAL-31; GLN-46; VAL-249; SER-317;
RP SER-337 AND LEU-369, AND CHARACTERIZATION OF VARIANTS SER-317 AND LEU-369.
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).
CC -!- FUNCTION: May play a role in hearing. {ECO:0000269|PubMed:17918732}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass type II
CC membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Brain-specific. Predominantly expressed in neurons,
CC in their axons, and at the synapses of motoneurons in the spinal cord.
CC -!- DISEASE: Note=Defects in TMPRSS5 may be a cause of deafness.
CC {ECO:0000269|PubMed:17918732}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; AB028140; BAB20375.1; -; mRNA.
DR EMBL; AP002436; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP003402; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS44735.1; -.
DR RefSeq; NP_001275678.1; NM_001288749.1.
DR RefSeq; NP_001275679.1; NM_001288750.1.
DR RefSeq; NP_001275680.1; NM_001288751.1.
DR RefSeq; NP_001275681.1; NM_001288752.1.
DR RefSeq; NP_110397.2; NM_030770.3.
DR AlphaFoldDB; Q9H3S3; -.
DR SMR; Q9H3S3; -.
DR BioGRID; 123345; 54.
DR IntAct; Q9H3S3; 2.
DR STRING; 9606.ENSP00000299882; -.
DR MEROPS; S01.313; -.
DR GlyGen; Q9H3S3; 5 sites.
DR PhosphoSitePlus; Q9H3S3; -.
DR BioMuta; TMPRSS5; -.
DR DMDM; 296452845; -.
DR MassIVE; Q9H3S3; -.
DR PaxDb; Q9H3S3; -.
DR PeptideAtlas; Q9H3S3; -.
DR PRIDE; Q9H3S3; -.
DR ProteomicsDB; 80747; -.
DR Antibodypedia; 2582; 326 antibodies from 31 providers.
DR DNASU; 80975; -.
DR Ensembl; ENST00000299882.11; ENSP00000299882.5; ENSG00000166682.13.
DR GeneID; 80975; -.
DR KEGG; hsa:80975; -.
DR MANE-Select; ENST00000299882.11; ENSP00000299882.5; NM_030770.4; NP_110397.2.
DR UCSC; uc001poc.6; human.
DR CTD; 80975; -.
DR DisGeNET; 80975; -.
DR GeneCards; TMPRSS5; -.
DR HGNC; HGNC:14908; TMPRSS5.
DR HPA; ENSG00000166682; Group enriched (brain, choroid plexus).
DR MIM; 606751; gene.
DR neXtProt; NX_Q9H3S3; -.
DR OpenTargets; ENSG00000166682; -.
DR PharmGKB; PA37920; -.
DR VEuPathDB; HostDB:ENSG00000166682; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000159163; -.
DR InParanoid; Q9H3S3; -.
DR OMA; CSERWNS; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; Q9H3S3; -.
DR TreeFam; TF351678; -.
DR PathwayCommons; Q9H3S3; -.
DR SignaLink; Q9H3S3; -.
DR BioGRID-ORCS; 80975; 4 hits in 1067 CRISPR screens.
DR ChiTaRS; TMPRSS5; human.
DR GenomeRNAi; 80975; -.
DR Pharos; Q9H3S3; Tbio.
DR PRO; PR:Q9H3S3; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9H3S3; protein.
DR Bgee; ENSG00000166682; Expressed in tibial nerve and 107 other tissues.
DR ExpressionAtlas; Q9H3S3; baseline and differential.
DR Genevisible; Q9H3S3; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; IMP:UniProtKB.
DR GO; GO:0005044; F:scavenger receptor activity; IEA:InterPro.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IMP:UniProtKB.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 1.
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 Pfam; PF15494; SRCR_2; 1.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF56487; SSF56487; 1.
DR PROSITE; PS00420; SRCR_1; 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; Disulfide bond; Glycoprotein; Hydrolase; Membrane; Protease;
KW Reference proteome; Serine protease; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..457
FT /note="Transmembrane protease serine 5"
FT /id="PRO_0000088694"
FT TOPO_DOM 1..49
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 50..70
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 71..457
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 112..207
FT /note="SRCR"
FT DOMAIN 218..453
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 258
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 308
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 405
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT SITE 217..218
FT /note="Cleavage"
FT /evidence="ECO:0000255"
FT CARBOHYD 163
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 170
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 195
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 319
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 375
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 135..196
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 148..206
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 209..328
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 243..259
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 342..411
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 374..390
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 401..429
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT VARIANT 31
FT /note="D -> V (in patients with sporadic hearing loss)"
FT /evidence="ECO:0000269|PubMed:17918732"
FT /id="VAR_038005"
FT VARIANT 46
FT /note="R -> Q (in dbSNP:rs11601425)"
FT /evidence="ECO:0000269|PubMed:17918732"
FT /id="VAR_038006"
FT VARIANT 125
FT /note="V -> M (in dbSNP:rs7939917)"
FT /id="VAR_038007"
FT VARIANT 249
FT /note="A -> V (in dbSNP:rs1263487635)"
FT /evidence="ECO:0000269|PubMed:17918732"
FT /id="VAR_038008"
FT VARIANT 317
FT /note="A -> S (in patients with sporadic hearing loss; no
FT detectable proteolytic activity in a yeast-based protease
FT assay)"
FT /evidence="ECO:0000269|PubMed:17918732"
FT /id="VAR_038009"
FT VARIANT 337
FT /note="P -> S"
FT /evidence="ECO:0000269|PubMed:17918732"
FT /id="VAR_038010"
FT VARIANT 369
FT /note="F -> L (reduced proteolytic activity in a yeast-
FT based protease assay; dbSNP:rs7110736)"
FT /evidence="ECO:0000269|PubMed:17918732"
FT /id="VAR_038011"
FT CONFLICT 428
FT /note="G -> A (in Ref. 1; BAB20375)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 457 AA; 49560 MW; 64406AB4985C4637 CRC64;
MSLMLDDQPP MEAQYAEEGP GPGIFRAEPG DQQHPISQAV CWRSMRRGCA VLGALGLLAG
AGVGSWLLVL YLCPAASQPI SGTLQDEEIT LSCSEASAEE ALLPALPKTV SFRINSEDFL
LEAQVRDQPR WLLVCHEGWS PALGLQICWS LGHLRLTHHK GVNLTDIKLN SSQEFAQLSP
RLGGFLEEAW QPRNNCTSGQ VVSLRCSECG ARPLASRIVG GQSVAPGRWP WQASVALGFR
HTCGGSVLAP RWVVTAAHCM HSFRLARLSS WRVHAGLVSH SAVRPHQGAL VERIIPHPLY
SAQNHDYDVA LLRLQTALNF SDTVGAVCLP AKEQHFPKGS RCWVSGWGHT HPSHTYSSDM
LQDTVVPLFS TQLCNSSCVY SGALTPRMLC AGYLDGRADA CQGDSGGPLV CPDGDTWRLV
GVVSWGRGCA EPNHPGVYAK VAEFLDWIHD TAQDSLL
