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TMPRSS3 (transmembrane protease, serine 3)

Identity

Other namesDFNB10 (deafness, autosomal recessive 10)
DFNB8 (deafness, autosomal recessive 8)
TADG12 (Tumor associated differentially-expressed gene-12 protein)
ECHOS1
Hugo TMPRSS3
Location 21q22.3
Note Not to be confused with TMPRSS4 (11q23.3), which was originally named TMPRSS3

DNA/RNA

Description 13 exons spanning 24 kb
Transcription Four alternative splice isoforms have been described, producing transcripts of 1.3 kb, 2.1 kb, 2.4 kb and 2.5 kb, respectively

Protein

Description Isoform A (full length) is 454 amino acids; isoforms B and C lack 127 aa at the N-terminus due to alternative splicing; isoform D is 344 aa and has a unique C-terminus due to alternative splicing. The full length isoform comprises an LDL-receptor A domain, a Scavenger receptor (Srcr) domain and a peptidase S1 S6 domain,
Expression Expressed in many fetal and adult tissues
Localisation Transmembrane
Function Transmembrane serine protease; exact function unknown

Mutations

Germinal Insertion, frameshift and missense mutations in the TMPRSS3 gene have been described in familial congenital (DFNB10) and childhood onset (DFNB8) deafness.

Implicated in

Entity Autosomal recessive neurosensory deafness; childhood-onset deafness (DFNB8); Autosomal recessive neurosensory deafness; congenital deafness (DFNB10)
  
Entity Ovarian Cancer
Disease Variant D of TMPRSS3 has been reported to be overexpressed in ovarian carcinomas and has been proposed as a novel diagnostic marker.
Prognosis High expression of variant D is correlated with advanced clinical stages of the disease.
  
Entity Pancreatic Cancer
Disease TMPRSS3 has been reported to be overexpressed in pancreatic cancer. No information on splice variants or prognostic value is available.
  

External links

Nomenclature
HugoTMPRSS3
GDBTMPRSS3
Entrez_GeneTMPRSS3  64699  transmembrane protease, serine 3
Cards
AtlasTMPRSS3ID42593ch21q22
GeneCardsTMPRSS3
EnsemblTMPRSS3 [Search_View]   ENSG00000160183 [Gene_View]
GenatlasTMPRSS3
GeneLynxTMPRSS3
eGenomeTMPRSS3
euGene64699
Genomic and cartography
GoldenPathTMPRSS3  -  21q22.3   chr21:42665069-42683596 -  21q22.3   [Description]    (hg18-Mar_2006)
EnsemblTMPRSS3 - 21q22.3 [CytoView]
NCBIMapview
OMIMDisease map [OMIM]
HomoloGeneTMPRSS3
Gene and transcription
GenbankAB038157 [ ENTREZ ]
GenbankAB038158 [ ENTREZ ]
GenbankAB038159 [ ENTREZ ]
GenbankAB038160 [ ENTREZ ]
GenbankAF201380 [ ENTREZ ]
RefSeqNM_024022 [ SRS ]    NM_024022 [ ENTREZ ]
RefSeqNM_032401 [ SRS ]    NM_032401 [ ENTREZ ]
RefSeqNM_032404 [ SRS ]    NM_032404 [ ENTREZ ]
RefSeqNM_032405 [ SRS ]    NM_032405 [ ENTREZ ]
RefSeqAC_000064 [ SRS ]    AC_000064 [ ENTREZ ]
RefSeqNC_000021 [ SRS ]    NC_000021 [ ENTREZ ]
RefSeqNT_030188 [ SRS ]    NT_030188 [ ENTREZ ]
RefSeqNW_927384 [ SRS ]    NW_927384 [ ENTREZ ]
AceViewTMPRSS3 AceView - NCBI
UnigeneHs.208600 [ SRS ]    Hs.208600 [ NCBI ]     HS208600 [ spliceNest ]
Fast-db3416 (alternative variants)
Protein : pattern, domain, 3D structure
SwissProtP57727 [ SRS]    P57727 [ EXPASY ]     P57727 [ INTERPRO ]
PrositePS01209 LDLRA_1 [ SRS ]    PS01209 LDLRA_1 [ Expasy ]
PrositePS50068 LDLRA_2 [ SRS ]    PS50068 LDLRA_2 [ Expasy ]
PrositePS00420 SRCR_1 [ SRS ]    PS00420 SRCR_1 [ Expasy ]
PrositePS50287 SRCR_2 [ SRS ]    PS50287 SRCR_2 [ Expasy ]
PrositePS50240 TRYPSIN_DOM [ SRS ]    PS50240 TRYPSIN_DOM [ Expasy ]
PrositePS00134 TRYPSIN_HIS [ SRS ]    PS00134 TRYPSIN_HIS [ Expasy ]
PrositePS00135 TRYPSIN_SER [ SRS ]    PS00135 TRYPSIN_SER [ Expasy ]
InterproIPR002172 LDL_rcpt_classA_cys-rich [ SRS ]    IPR002172 LDL_rcpt_classA_cys-rich [ EBI ]
InterproIPR001254 Peptidase_S1_S6 [ SRS ]    IPR001254 Peptidase_S1_S6 [ EBI ]
InterproIPR001314 Peptidase_S1A [ SRS ]    IPR001314 Peptidase_S1A [ EBI ]
InterproIPR001190 Srcr_rcpt [ SRS ]    IPR001190 Srcr_rcpt [ EBI ]
CluSTrP57727
PfamPF00530 SRCR [ SRS ]    PF00530 SRCR [ Sanger ]    pfam00530 [ NCBI-CDD ]
PfamPF00089 Trypsin [ SRS ]    PF00089 Trypsin [ Sanger ]    pfam00089 [ NCBI-CDD ]
SmartSM00192 LDLa [EMBL]
SmartSM00202 SR [EMBL]
SmartSM00020 Tryp_SPc [EMBL]
BlocksP57727
HPRD05696
Protein Interaction databases
DIPP57727
IntActP57727
Polymorphism : SNP, mutations, diseases
OMIM601072;605316;605511    [ map ]   
GENECLINICS601072;605316;605511
SNPTMPRSS3 [dbSNP-NCBI]  
SNPNM_024022 [SNP-NCI]  
SNPNM_032401 [SNP-NCI]  
SNPNM_032404 [SNP-NCI]  
SNPNM_032405 [SNP-NCI]  
SNPTMPRSS3 [GeneSNPs - Utah]  TMPRSS3] [HGBASE - SRS]
HAPMAPTMPRSS3 [HAPMAP]  
HGMDTMPRSS3
General knowledge
Family BrowserTMPRSS3 [UCSC Family Browser]
SOURCENM_024022
SOURCENM_032401
SOURCENM_032404
SOURCENM_032405
SMDHs.208600
SAGEHs.208600
Enzyme3.4.21.- [ Enzyme-SRS ]   3.4.21.- [ Brenda-SRS ]   3.4.21.- [ KEGG ]   3.4.21.- [ WIT ]
GOcatalytic activity [Amigo]  catalytic activity
GOserine-type endopeptidase activity [Amigo]  serine-type endopeptidase activity
GOserine-type endopeptidase activity [Amigo]  serine-type endopeptidase activity
GOscavenger receptor activity [Amigo]  scavenger receptor activity
GOendoplasmic reticulum [Amigo]  endoplasmic reticulum
GOendoplasmic reticulum membrane [Amigo]  endoplasmic reticulum membrane
GOproteolysis [Amigo]  proteolysis
GOproteolysis [Amigo]  proteolysis
GOcellular sodium ion homeostasis [Amigo]  cellular sodium ion homeostasis
GOsensory perception of sound [Amigo]  sensory perception of sound
GOpeptidase activity [Amigo]  peptidase activity
GOmembrane [Amigo]  membrane
GOintegral to membrane [Amigo]  integral to membrane
GOintegral to membrane [Amigo]  integral to membrane
GOsodium channel regulator activity [Amigo]  sodium channel regulator activity
PubGeneTMPRSS3
TreeFamTMPRSS3
CTD64699 [Comparative ToxicoGenomics Database]
Other databases
Probes
ProbeTMPRSS3 Related clones (RZPD - Berlin)
PubMed
PubMed20 Pubmed reference(s) in LocusLink

Bibliography

Novel mutations of TMPRSS3 in four DFNB8/B10 families segregating congenital autosomal recessive deafness.
Ben-Yosef T, Wattenhofer M, Riazuddin S, Ahmed ZM, Scott HS, Kudoh J, Shibuya K, Antonarakis SE, Bonne-Tamir B, Radhakrishna U, Naz S, Ahmed Z, Riazuddin S, Pandya A, Nance WE, Wilcox ER, Friedman TB, Morell RJ
Journal of medical genetics. 2001 ; 38 (6) : 396-400.
PMID 11424922
 
Insertion of beta-satellite repeats identifies a transmembrane protease causing both congenital and childhood onset autosomal recessive deafness.
Scott HS, Kudoh J, Wattenhofer M, Shibuya K, Berry A, Chrast R, Guipponi M, Wang J, Kawasaki K, Asakawa S, Minoshima S, Younus F, Mehdi SQ, Radhakrishna U, Papasavvas MP, Gehrig C, Rossier C, Korostishevsky M, Gal A, Shimizu N, Bonne-Tamir B, Antonarakis SE
Nature genetics. 2001 ; 27 (1) : 59-63.
PMID 11137999
 
Mutations in the TMPRSS3 gene are a rare cause of childhood nonsyndromic deafness in Caucasian patients.
Wattenhofer M, Di Iorio MV, Rabionet R, Dougherty L, Pampanos A, Schwede T, Montserrat-Sentis B, Arbones ML, Iliades T, Pasquadibisceglie A, D'Amelio M, Alwan S, Rossier C, Dahl HH, Petersen MB, Estivill X, Gasparini P, Scott HS, Antonarakis SE
Journal of molecular medicine (Berlin, Germany). 2002 ; 80 (2) : 124-131.
PMID 11907649
 
Highly expressed genes in pancreatic ductal adenocarcinomas: a comprehensive characterization and comparison of the transcription profiles obtained from three major technologies.
Iacobuzio-Donahue CA, Ashfaq R, Maitra A, Adsay NV, Shen-Ong GL, Berg K, Hollingsworth MA, Cameron JL, Yeo CJ, Kern SE, Goggins M, Hruban RH
Cancer research. 2003 ; 63 (24) : 8614-8622.
PMID 14695172
 
Pathogenic mutations but not polymorphisms in congenital and childhood onset autosomal recessive deafness disrupt the proteolytic activity of TMPRSS3.
Lee YJ, Park D, Kim SY, Park WJ
Journal of medical genetics. 2003 ; 40 (8) : 629-631.
PMID 12920079
 
Characterization of a new full length TMPRSS3 isoform and identification of mutant alleles responsible for nonsyndromic recessive deafness in Newfoundland and Pakistan.
Ahmed ZM, Li XC, Powell SD, Riazuddin S, Young TL, Ramzan K, Ahmad Z, Luscombe S, Dhillon K, MacLaren L, Ploplis B, Shotland LI, Ives E, Riazuddin S, Friedman TB, Morell RJ, Wilcox ER
BMC medical genetics. 2004 ; 5 : page 24.
PMID 15447792
 
The transmembrane protease serine (TMPRSS3/TADG-12) D variant: a potential candidate for diagnosis and therapeutic intervention in ovarian cancer.
Sawasaki T, Shigemasa K, Gu L, Beard JB, O'Brien TJ
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2004 ; 25 (3) : 141-148.
PMID 15361711
 
A novel TMPRSS3 missense mutation in a DFNB8/10 family prevents proteolytic activation of the protein.
Wattenhofer M, Sahin-Calapoglu N, Andreasen D, Kalay E, Caylan R, Braillard B, Fowler-Jaeger N, Reymond A, Rossier BC, Karaguzel A, Antonarakis SE
Human genetics. 2005 ; 117 (6) : 528-535.
PMID 16021470
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written07-2005Malte Buchholz, Thomas M Gress
Universität Ulm, Abteilung Innere Medizin I, Robert-Koch-Str. 8,89081 Ulm, Germany

Citation

This paper should be referenced as such :
Buchholz M, Gress TM . TMPRSS3 (transmembrane protease, serine 3). Atlas Genet Cytogenet Oncol Haematol. July 2005 .
URL : http://AtlasGeneticsOncology.org/Genes/TMPRSS3ID42593ch21q22.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Jul 2 08:27:42 2008


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