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TMPRSS4 (transmembrane protease, serine 4)

Written2009-10Youngwoo Park
Therapeutic Antibody Research Center, Korea Research Institute of Bioscience, Biotechnology, Daejon, Korea

(Note : for Links provided by Atlas : click)


Alias (NCBI)EC 3.4.21.-
HGNC Alias symbTMPRSS3
HGNC Alias nametransmembrane serine protease 3
 membrane-type serine protease 2
 type II membrane serine protease
 channel-activating serine protease 2
HGNC Previous nametransmembrane protease, serine 4
LocusID (NCBI) 56649
Atlas_Id 42594
Location 11q23.3  [Link to chromosome band 11q23]
Location_base_pair Starts at 118077078 and ends at 118121890 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping TMPRSS4.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
DYNC1H1 (14q32.31)::TMPRSS4 (11q23.3)GRIK4 (11q23.3)::TMPRSS4 (11q23.3)
Note Not to be confused with TMPRSS3 (21q22.3), which was originally named for TMPRSS4 (11q23.3).


Description TMPRSS4 gene approximately extends 41.38 kb-long on chromosome 11 in the region p23.3, containing 13 exons.
Transcription Two alternative splicing variants have been described, producing transcripts of 2.12 kb and 1.98 kb, respectively.


  TMPRSS4 is a 437 amino acid single-pass type II membrane protein. It contains a Serine protease domain at the C-terminus, followed by a Scavenger receptor cysteine-rich domain (SRDR) and a Low Density Lipoprotein Receptor Class A domain. Letters H, D and S in the serine protease domain indicate the position of the three catalytic residues histidine, aspartate and serine, respectively.
Description TMPRSS4 is a 437 amino acid type II transmembrane serine protease (TTSPs) which are expressed at the cell surface and are thus ideally located to regulate cell-cell and cell-matrix interactions.
Expression TMPRSS4 is highly expressed in pancreatic, colon, lung and gastric cancer tissues, and TMPRSS4 is also broadly expressed in a variety of human cancer cell lines, such as NCI-H322, Colo205 and HCT15.
Localisation Membrane; Single-pass type II membrane protein.
Function TMPRSS4 plays a role in invasion, metastasis, migration and adhesion, as well as in the EMT in cancer cells. Loss of E-cadherin transcript, a hallmark of EMT, was induced by TMPRSS4. It also modulates cell growth in a cell type-dependent manner. TMPRSS4 expression is upregulated in lung cancer tissues compared with normal tissues, and various cancer cell lines themselves express TMPRSS4 at various levels.
Homology TMPRSS4 is a type II transmembrane serine protease (TTSPs) which contains a Serine protease domain. Human TTSPs, which consists of 17 members, were grouped into four subfamilies based on similarity in domain structure and phylogenetic analysis of the serine protease domains, namely the matriptase, corin, hepsin/TMPRSS and HAT/DESC subfamilies.

Implicated in

Entity Colon cancer
Oncogenesis TMPRSS4 is an important mediator of invasion, metastasis, migration, adhesion and EMT (epithelial-mesenchymal transition) in human epithelial colon cancer cells and also modulates in vitro cell growth in a cell type- and/or signaling context dependent manner, suggesting that TMPRSS4 may represent a novel therapeutic target for cancer.
TMPRSS4 overexpression induces an EMT associated with SIP1/ZEB2 induction and E-cadherin loss in SW480 cells, and also promotes metastasis of SW480 cells.
TMPRSS4 overexpression is associated with morphological changes and actin cytoskeleton rearrangement.
Entity Pancreatic cancer
Oncogenesis TMPRSS4 is strongly expressed in a subset of pancreatic cancer and various other cancer tissues, and its expression correlates with the metastatic potential of the pancreatic cancer cell lines.


Proteolytic activation of the 1918 influenza virus hemagglutinin.
Chaipan C, Kobasa D, Bertram S, Glowacka I, Steffen I, Tsegaye TS, Takeda M, Bugge TH, Kim S, Park Y, Marzi A, Pohlmann S.
J Virol. 2009 Apr;83(7):3200-11. Epub 2009 Jan 21.
PMID 19158246
Type II transmembrane serine proteases in cancer and viral infections.
Choi SY, Bertram S, Glowacka I, Park YW, Pohlmann S.
Trends Mol Med. 2009 Jul;15(7):303-12. Epub 2009 Jul 4.
PMID 19581128
Role of TMPRSS4 during cancer progression.
Choi SY, Shin HC, Kim SY, Park YW.
Drug News Perspect. 2008 Oct;21(8):417-23. (REVIEW)
PMID 19034347
Gene expression profile of papillary thyroid cancer: sources of variability and diagnostic implications.
Jarzab B, Wiench M, Fujarewicz K, Simek K, Jarzab M, Oczko-Wojciechowska M, Wloch J, Czarniecka A, Chmielik E, Lange D, Pawlaczek A, Szpak S, Gubala E, Swierniak A.
Cancer Res. 2005 Feb 15;65(4):1587-97.
PMID 15735049
TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial-mesenchymal transition.
Jung H, Lee KP, Park SJ, Park JH, Jang YS, Choi SY, Jung JG, Jo K, Park DY, Yoon JH, Park JH, Lim DS, Hong GR, Choi C, Park YK, Lee JW, Hong HJ, Kim S, Park YW.
Oncogene. 2008 Apr 17;27(18):2635-47. Epub 2007 Oct 29.
PMID 17968309
Diagnostic and extent of disease multigene assay for malignant thyroid neoplasms.
Kebebew E, Peng M, Reiff E, McMillan A.
Cancer. 2006 Jun 15;106(12):2592-7.
PMID 16688775
IL-4/Stat6 activities correlate with apoptosis and metastasis in colon cancer cells.
Li BH, Yang XZ, Li PD, Yuan Q, Liu XH, Yuan J, Zhang WJ.
Biochem Biophys Res Commun. 2008 May 2;369(2):554-60. Epub 2008 Feb 21.
PMID 18294957
A novel transmembrane serine protease (TMPRSS3) overexpressed in pancreatic cancer.
Wallrapp C, Hahnel S, Muller-Pillasch F, Burghardt B, Iwamura T, Ruthenburger M, Lerch MM, Adler G, Gress TM.
Cancer Res. 2000 May 15;60(10):2602-6.
PMID 10825129
Effect of splice-site polymorphisms of the TMPRSS4, NPHP4 and ORCTL4 genes on their mRNA expression.
Yamada H, Shinmura K, Tsuneyoshi T, Sugimura H.
J Genet. 2005 Aug;84(2):131-6.
PMID 16131712


This paper should be referenced as such :
Park, Y
TMPRSS4 (transmembrane protease, serine 4)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(8):785-787.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)TMPRSS4   11878
Entrez_Gene (NCBI)TMPRSS4    transmembrane serine protease 4
GeneCards (Weizmann)TMPRSS4
Ensembl hg19 (Hinxton)ENSG00000137648 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000137648 [Gene_View]  ENSG00000137648 [Sequence]  chr11:118077078-118121890 [Contig_View]  TMPRSS4 [Vega]
ICGC DataPortalENSG00000137648
Genatlas (Paris)TMPRSS4
Genetics Home Reference (NIH)TMPRSS4
Genomic and cartography
GoldenPath hg38 (UCSC)TMPRSS4  -     chr11:118077078-118121890 +  11q23.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)TMPRSS4  -     11q23.3   [Description]    (hg19-Feb_2009)
GoldenPathTMPRSS4 - 11q23.3 [CytoView hg19]  TMPRSS4 - 11q23.3 [CytoView hg38]
Genome Data Viewer NCBITMPRSS4 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AF179224 AF216312 AK172766 AK290361 AK296855
RefSeq transcript (Entrez)NM_001083947 NM_001173551 NM_001173552 NM_001290094 NM_001290096 NM_019894 NM_183247
Consensus coding sequences : CCDS (NCBI)TMPRSS4
Gene Expression Viewer (FireBrowse)TMPRSS4 [ Firebrowse - Broad ]
GenevisibleExpression of TMPRSS4 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)56649
GTEX Portal (Tissue expression)TMPRSS4
Human Protein AtlasENSG00000137648-TMPRSS4 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9NRS4   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9NRS4  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9NRS4
Catalytic activity : Enzyme3.4.21.- [ Enzyme-Expasy ]   3.4.21.-3.4.21.- [ IntEnz-EBI ]   3.4.21.- [ BRENDA ]   3.4.21.- [ KEGG ]   [ MEROPS ]
Domaine pattern : Prosite (Expaxy)SRCR_2 (PS50287)    TRYPSIN_DOM (PS50240)    TRYPSIN_HIS (PS00134)    TRYPSIN_SER (PS00135)   
Domains : Interpro (EBI)LDL_receptor-like_sf    LDrepeatLR_classA_rpt    Peptidase_S1_PA    Peptidase_S1_PA_chymotrypsin    Peptidase_S1A    SRCR    SRCR-like_dom    SRCR-like_dom_sf    Trypsin_dom    TRYPSIN_HIS    TRYPSIN_SER   
Domain families : Pfam (Sanger)SRCR_2 (PF15494)    Trypsin (PF00089)   
Domain families : Pfam (NCBI)pfam15494    pfam00089   
Domain families : Smart (EMBL)LDLa (SM00192)  SR (SM00202)  Tryp_SPc (SM00020)  
Conserved Domain (NCBI)TMPRSS4
AlphaFold pdb e-kbQ9NRS4   
Human Protein Atlas [tissue]ENSG00000137648-TMPRSS4 [tissue]
Protein Interaction databases
IntAct (EBI)Q9NRS4
Ontologies - Pathways
Ontology : AmiGOserine-type endopeptidase activity  scavenger receptor activity  protein binding  extracellular space  plasma membrane  proteolysis  proteolysis  endocytosis  serine-type peptidase activity  response to wounding  regulation of gene expression  integral component of membrane  protein processing  secretory granule  negative regulation of growth rate  positive regulation of viral entry into host cell  
Ontology : EGO-EBIserine-type endopeptidase activity  scavenger receptor activity  protein binding  extracellular space  plasma membrane  proteolysis  proteolysis  endocytosis  serine-type peptidase activity  response to wounding  regulation of gene expression  integral component of membrane  protein processing  secretory granule  negative regulation of growth rate  positive regulation of viral entry into host cell  
Pathways : KEGGInfluenza A   
Atlas of Cancer Signalling NetworkTMPRSS4
Wikipedia pathwaysTMPRSS4
Orthology - Evolution
GeneTree (enSembl)ENSG00000137648
Phylogenetic Trees/Animal Genes : TreeFamTMPRSS4
Homologs : HomoloGeneTMPRSS4
Homology/Alignments : Family Browser (UCSC)TMPRSS4
Gene fusions - Rearrangements
Fusion : MitelmanGRIK4::TMPRSS4 [11q23.3/11q23.3]  
Fusion : QuiverTMPRSS4
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTMPRSS4 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TMPRSS4
Exome Variant ServerTMPRSS4
GNOMAD BrowserENSG00000137648
Varsome BrowserTMPRSS4
ACMGTMPRSS4 variants
Genomic Variants (DGV)TMPRSS4 [DGVbeta]
DECIPHERTMPRSS4 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisTMPRSS4 
ICGC Data PortalTMPRSS4 
TCGA Data PortalTMPRSS4 
Broad Tumor PortalTMPRSS4
OASIS PortalTMPRSS4 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTMPRSS4  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DTMPRSS4
Mutations and Diseases : HGMDTMPRSS4
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)TMPRSS4
DoCM (Curated mutations)TMPRSS4
CIViC (Clinical Interpretations of Variants in Cancer)TMPRSS4
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry TMPRSS4
NextProtQ9NRS4 [Medical]
Target ValidationTMPRSS4
Huge Navigator TMPRSS4 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDTMPRSS4
Pharm GKB GenePA36579
Clinical trialTMPRSS4
DataMed IndexTMPRSS4
PubMed58 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:29:40 CEST 2021

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