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Protein

Transmembrane protease serine 3

Gene

TMPRSS3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Probable serine protease that plays a role in hearing. Acts as a permissive factor for cochlear hair cell survival and activation at the onset of hearing and is required for saccular hair cell survival (By similarity). Activates ENaC (in vitro).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei257Charge relay systemBy similarity1
Active sitei304Charge relay systemBy similarity1
Active sitei401Charge relay systemCurated1

GO - Molecular functioni

  • scavenger receptor activity Source: InterPro
  • serine-type endopeptidase activity Source: UniProtKB
  • sodium channel regulator activity Source: MGI

GO - Biological processi

  • cellular sodium ion homeostasis Source: MGI
  • proteolysis Source: UniProtKB
  • sensory perception of sound Source: Ensembl

Keywordsi

Molecular functionHydrolase, Protease, Serine protease

Protein family/group databases

MEROPSiS01.079

Names & Taxonomyi

Protein namesi
Recommended name:
Transmembrane protease serine 3 (EC:3.4.21.-)
Alternative name(s):
Serine protease TADG-12
Tumor-associated differentially-expressed gene 12 protein
Gene namesi
Name:TMPRSS3
Synonyms:ECHOS1, TADG12
ORF Names:UNQ323/PRO382
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

EuPathDBiHostDB:ENSG00000160183.13
HGNCiHGNC:11877 TMPRSS3
MIMi605511 gene
neXtProtiNX_P57727

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 48CytoplasmicSequence analysisAdd BLAST48
Transmembranei49 – 69Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini70 – 454ExtracellularSequence analysisAdd BLAST385

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Deafness, autosomal recessive, 8 (DFNB8)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
See also OMIM:601072
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_013490103D → G in DFNB8; fails to undergo proteolytic cleavage and is unable to activate ENaC. 2 PublicationsCorresponds to variant dbSNP:rs387906915EnsemblClinVar.1
Natural variantiVAR_013491109R → W in DFNB8; fails to undergo proteolytic cleavage and is unable to activate ENaC. 2 PublicationsCorresponds to variant dbSNP:rs201632198EnsemblClinVar.1
Natural variantiVAR_013494194C → F in DFNB8; fails to undergo proteolytic cleavage and is unable to activate ENaC. 2 Publications1
Natural variantiVAR_025354216R → L in DFNB8; fails to undergo proteolytic cleavage and is unable to activate ENaC. 1 PublicationCorresponds to variant dbSNP:rs137853000EnsemblClinVar.1
Natural variantiVAR_011678251W → C in DFNB8; fails to undergo proteolytic cleavage and is unable to activate ENaC. 2 PublicationsCorresponds to variant dbSNP:rs137852999EnsemblClinVar.1
Natural variantiVAR_011679404P → L in DFNB8; fails to undergo proteolytic cleavage and is unable to activate ENaC. 3 PublicationsCorresponds to variant dbSNP:rs28939084EnsemblClinVar.1
Natural variantiVAR_013495407C → R in DFNB8; fails to undergo proteolytic cleavage and is unable to activate ENaC. 2 PublicationsCorresponds to variant dbSNP:rs773780151Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi401S → A: Fails to undergo proteolytic cleavage and is unable to activate ENaC. 1 Publication1

Keywords - Diseasei

Deafness, Disease mutation, Non-syndromic deafness

Organism-specific databases

DisGeNETi64699
GeneReviewsiTMPRSS3
MalaCardsiTMPRSS3
MIMi601072 phenotype
OpenTargetsiENSG00000160183
Orphaneti90636 Autosomal recessive non-syndromic sensorineural deafness type DFNB
PharmGKBiPA36578

Polymorphism and mutation databases

BioMutaiTMPRSS3
DMDMi13124582

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000886901 – 454Transmembrane protease serine 3Add BLAST454

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi73 ↔ 85By similarity
Disulfide bondi79 ↔ 98By similarity
Disulfide bondi92 ↔ 107By similarity
Disulfide bondi129 ↔ 194By similarity
Disulfide bondi142 ↔ 204By similarity
Disulfide bondi207 ↔ 324By similarity
Glycosylationi221N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi242 ↔ 258By similarity
Disulfide bondi338 ↔ 407By similarity
Disulfide bondi370 ↔ 386By similarity
Disulfide bondi397 ↔ 425By similarity

Post-translational modificationi

Undergoes autoproteolytic activation.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei216 – 217CleavageSequence analysis2

Keywords - PTMi

Autocatalytic cleavage, Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiP57727
PeptideAtlasiP57727
PRIDEiP57727
ProteomicsDBi57016
57017 [P57727-2]
57018 [P57727-3]
57019 [P57727-4]
57020 [P57727-5]

PTM databases

iPTMnetiP57727
PhosphoSitePlusiP57727

Expressioni

Tissue specificityi

Expressed in many tissues including fetal cochlea. Isoform T is found at increased levels in some carcinomas.

Gene expression databases

BgeeiENSG00000160183
CleanExiHS_TMPRSS3
ExpressionAtlasiP57727 baseline and differential
GenevisibleiP57727 HS

Interactioni

Protein-protein interaction databases

BioGridi122236, 38 interactors
IntActiP57727, 4 interactors
STRINGi9606.ENSP00000291532

Structurei

3D structure databases

ProteinModelPortaliP57727
SMRiP57727
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini72 – 108LDL-receptor class APROSITE-ProRule annotationAdd BLAST37
Domaini109 – 205SRCRPROSITE-ProRule annotationAdd BLAST97
Domaini217 – 449Peptidase S1PROSITE-ProRule annotationAdd BLAST233

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3627 Eukaryota
COG5640 LUCA
GeneTreeiENSGT00760000118962
HOGENOMiHOG000251822
HOVERGENiHBG013304
InParanoidiP57727
KOiK09634
OMAiCVYDLYL
OrthoDBiEOG091G0DF7
PhylomeDBiP57727
TreeFamiTF351678

Family and domain databases

CDDicd00112 LDLa, 1 hit
cd00190 Tryp_SPc, 1 hit
Gene3Di3.10.250.10, 1 hit
InterProiView protein in InterPro
IPR036055 LDL_receptor-like_sf
IPR023415 LDLR_class-A_CS
IPR002172 LDrepeatLR_classA_rpt
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR001190 SRCR
IPR017448 SRCR-like_dom
IPR036772 SRCR-like_dom_sf
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PfamiView protein in Pfam
PF00057 Ldl_recept_a, 1 hit
PF15494 SRCR_2, 1 hit
PF00089 Trypsin, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00192 LDLa, 1 hit
SM00202 SR, 1 hit
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
SSF56487 SSF56487, 1 hit
SSF57424 SSF57424, 1 hit
PROSITEiView protein in PROSITE
PS01209 LDLRA_1, 1 hit
PS50068 LDLRA_2, 1 hit
PS00420 SRCR_1, 1 hit
PS50287 SRCR_2, 1 hit
PS50240 TRYPSIN_DOM, 1 hit
PS00134 TRYPSIN_HIS, 1 hit
PS00135 TRYPSIN_SER, 1 hit

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform A (identifier: P57727-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGENDPPAVE APFSFRSLFG LDDLKISPVA PDADAVAAQI LSLLPLKFFP
60 70 80 90 100
IIVIGIIALI LALAIGLGIH FDCSGKYRCR SSFKCIELIA RCDGVSDCKD
110 120 130 140 150
GEDEYRCVRV GGQNAVLQVF TAASWKTMCS DDWKGHYANV ACAQLGFPSY
160 170 180 190 200
VSSDNLRVSS LEGQFREEFV SIDHLLPDDK VTALHHSVYV REGCASGHVV
210 220 230 240 250
TLQCTACGHR RGYSSRIVGG NMSLLSQWPW QASLQFQGYH LCGGSVITPL
260 270 280 290 300
WIITAAHCVY DLYLPKSWTI QVGLVSLLDN PAPSHLVEKI VYHSKYKPKR
310 320 330 340 350
LGNDIALMKL AGPLTFNEMI QPVCLPNSEE NFPDGKVCWT SGWGATEDGA
360 370 380 390 400
GDASPVLNHA AVPLISNKIC NHRDVYGGII SPSMLCAGYL TGGVDSCQGD
410 420 430 440 450
SGGPLVCQER RLWKLVGATS FGIGCAEVNK PGVYTRVTSF LDWIHEQMER

DLKT
Length:454
Mass (Da):49,405
Last modified:February 21, 2001 - v2
Checksum:i57ECC3678F7D6AFF
GO
Isoform B (identifier: P57727-2) [UniParc]FASTAAdd to basket
Also known as: C

The sequence of this isoform differs from the canonical sequence as follows:
     1-127: Missing.

Show »
Length:327
Mass (Da):35,760
Checksum:iCF6A6505C4B9A6B9
GO
Isoform D (identifier: P57727-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     318-454: EMIQPVCLPN...HEQMERDLKT → GTSGSLCGSAALPLFQEDLQLLIEAFL

Show »
Length:344
Mass (Da):37,497
Checksum:iFCE5335794AF9712
GO
Isoform T (identifier: P57727-4) [UniParc]FASTAAdd to basket
Also known as: Truncated, TADG-12V

The sequence of this isoform differs from the canonical sequence as follows:
     261-293: DLYLPKSWTIQVGLVSLLDNPAPSHLVEKIVYH → EIVAPRERADRRGRKLLCWRKPTKMKGPRPSHS
     294-454: Missing.

Show »
Length:293
Mass (Da):32,230
Checksum:iCF9C0540F570B900
GO
Isoform E (identifier: P57727-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     350-350: Missing.

Show »
Length:453
Mass (Da):49,334
Checksum:i90D46870BFA39B86
GO
Isoform 6 (identifier: P57727-6) [UniParc]FASTAAdd to basket
Also known as: TMPRSS3e

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MQAVGPKPLP...DVRGPEIVTM

Note: Has a predicted N-terminal signal sequence, indicating it may be secreted. Expressed in retina, lung, liver, pancreas, placenta and kidney.
Show »
Length:538
Mass (Da):58,324
Checksum:iEC7E6FDAA5B7ED9B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti46 – 54LKFFPIIVI → FEVFSQSSSL in AAG37012 (PubMed:11068177).Curated9
Sequence conflicti90A → T in AAG37012 (PubMed:11068177).Curated1
Sequence conflicti369 – 395ICNHR…TGGVD → DLQPQGRVRWHHLPLHALRG LPDGWRWN in AAG37012 (PubMed:11068177).CuratedAdd BLAST27
Sequence conflicti427E → D in AAG37012 (PubMed:11068177).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01078153V → I2 PublicationsCorresponds to variant dbSNP:rs928302EnsemblClinVar.1
Natural variantiVAR_013490103D → G in DFNB8; fails to undergo proteolytic cleavage and is unable to activate ENaC. 2 PublicationsCorresponds to variant dbSNP:rs387906915EnsemblClinVar.1
Natural variantiVAR_013491109R → W in DFNB8; fails to undergo proteolytic cleavage and is unable to activate ENaC. 2 PublicationsCorresponds to variant dbSNP:rs201632198EnsemblClinVar.1
Natural variantiVAR_013492111G → S1 PublicationCorresponds to variant dbSNP:rs35227181EnsemblClinVar.1
Natural variantiVAR_013493173D → N1 PublicationCorresponds to variant dbSNP:rs766000719Ensembl.1
Natural variantiVAR_013494194C → F in DFNB8; fails to undergo proteolytic cleavage and is unable to activate ENaC. 2 Publications1
Natural variantiVAR_025354216R → L in DFNB8; fails to undergo proteolytic cleavage and is unable to activate ENaC. 1 PublicationCorresponds to variant dbSNP:rs137853000EnsemblClinVar.1
Natural variantiVAR_011678251W → C in DFNB8; fails to undergo proteolytic cleavage and is unable to activate ENaC. 2 PublicationsCorresponds to variant dbSNP:rs137852999EnsemblClinVar.1
Natural variantiVAR_013101253I → V1 PublicationCorresponds to variant dbSNP:rs2839500EnsemblClinVar.1
Natural variantiVAR_011679404P → L in DFNB8; fails to undergo proteolytic cleavage and is unable to activate ENaC. 3 PublicationsCorresponds to variant dbSNP:rs28939084EnsemblClinVar.1
Natural variantiVAR_013495407C → R in DFNB8; fails to undergo proteolytic cleavage and is unable to activate ENaC. 2 PublicationsCorresponds to variant dbSNP:rs773780151Ensembl.1
Natural variantiVAR_013496426A → T1 PublicationCorresponds to variant dbSNP:rs56264519EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0053911 – 127Missing in isoform B. 1 PublicationAdd BLAST127
Alternative sequenceiVSP_0476951M → MQAVGPKPLPTLLCGGRTGH RTARVLSFLIRSCPCEPGKG CVYGKPVTLWPTISSVVPST FLGLGNYEVEVEAEPDVRGP EIVTM in isoform 6. 1 Publication1
Alternative sequenceiVSP_005393261 – 293DLYLP…KIVYH → EIVAPRERADRRGRKLLCWR KPTKMKGPRPSHS in isoform T. 1 PublicationAdd BLAST33
Alternative sequenceiVSP_005394294 – 454Missing in isoform T. 1 PublicationAdd BLAST161
Alternative sequenceiVSP_005392318 – 454EMIQP…RDLKT → GTSGSLCGSAALPLFQEDLQ LLIEAFL in isoform D. 1 PublicationAdd BLAST137
Alternative sequenceiVSP_013184350Missing in isoform E. 4 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF201380 mRNA Translation: AAG37012.1
AB038157 mRNA Translation: BAB20077.1
AB038158 mRNA Translation: BAB20078.1
AB038159 mRNA Translation: BAB20079.1
AB038160 mRNA Translation: BAB20080.1
AY633572 mRNA Translation: AAT66641.1
AY358458 mRNA Translation: AAQ88823.1
AK172842 mRNA Translation: BAD18806.1
AP001623 Genomic DNA No translation available.
CH471079 Genomic DNA Translation: EAX09564.1
CH471079 Genomic DNA Translation: EAX09566.1
BC074846 mRNA Translation: AAH74846.1
BC074847 mRNA Translation: AAH74847.1
CCDSiCCDS13686.1 [P57727-1]
CCDS42939.1 [P57727-3]
CCDS58790.1 [P57727-5]
RefSeqiNP_001243246.1, NM_001256317.1 [P57727-5]
NP_076927.1, NM_024022.2 [P57727-1]
NP_115780.1, NM_032404.2 [P57727-2]
NP_115781.1, NM_032405.1 [P57727-3]
UniGeneiHs.208600

Genome annotation databases

EnsembliENST00000291532; ENSP00000291532; ENSG00000160183 [P57727-1]
ENST00000398397; ENSP00000381434; ENSG00000160183 [P57727-3]
ENST00000433957; ENSP00000411013; ENSG00000160183 [P57727-1]
ENST00000644384; ENSP00000494414; ENSG00000160183 [P57727-5]
GeneIDi64699
KEGGihsa:64699
UCSCiuc002zbc.4 human [P57727-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTMPS3_HUMAN
AccessioniPrimary (citable) accession number: P57727
Secondary accession number(s): D3DSJ6, Q5USC7, Q6ZMC3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: February 21, 2001
Last modified: June 20, 2018
This is version 172 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

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