TMPRSS4 (transmembrane protease, serine 4)

2009-10-01   Youngwoo Park 

Therapeutic Antibody Research Center, Korea Research Institute of Bioscience, Biotechnology, Daejon, Korea

Identity

HGNC
LOCATION
11q23.3
LOCUSID
ALIAS
CAP2,CAPH2,MT-SP2,TMPRSS3
FUSION GENES

DNA/RNA

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.

Proteins

Atlas Image
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.
Atlas Image
Multidomain structure of human TTSPs. Human TTSPs 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. Consensus domains are shown above. Each diagram was drawn using the web-based SMART software (http://smart.embl-heidelberg.de) with TTSP amino acid sequences obtained from GenBank.
Abbreviations: CUB, Cls/Clr, urchin embryonic growth factor and bone morphogenic protein-1 domain; DESC1, differentially expressed squamous cell carcinoma gene 1; FRZ, frizzled domain; HAT, human airway trypsin-like protease; LDLA, low-density lipoprotein receptor domain class A; MAM, a meprin, A5 antigen and receptor protein phosphatase m domain; MSPL, mosaic serine protease long-form; Polyserase-1, polyserine protease-1; SEA, a single sea urchin sperm protein, enteropeptidase, agrin domain; SR, scavenger receptor cysteine-rich domain; TM, transmembrane domain. Letters H, D and S in the serine protease domain (active) indicate the position of the three catalytic residues histidine, aspartate and serine, respectively. Letter A in the serine protease domain (inactive) indicates a serine to alanine exchange.

Implicated in

Entity name
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 name
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.

Bibliography

Pubmed IDLast YearTitleAuthors
191582462009Proteolytic activation of the 1918 influenza virus hemagglutinin.Chaipan C et al
195811282009Type II transmembrane serine proteases in cancer and viral infections.Choi SY et al
190343472008Role of TMPRSS4 during cancer progression.Choi SY et al
157350492005Gene expression profile of papillary thyroid cancer: sources of variability and diagnostic implications.Jarzab B et al
179683092008TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial-mesenchymal transition.Jung H et al
166887752006Diagnostic and extent of disease multigene assay for malignant thyroid neoplasms.Kebebew E et al
182949572008IL-4/Stat6 activities correlate with apoptosis and metastasis in colon cancer cells.Li BH et al
108251292000A novel transmembrane serine protease (TMPRSS3) overexpressed in pancreatic cancer.Wallrapp C et al
161317122005Effect of splice-site polymorphisms of the TMPRSS4, NPHP4 and ORCTL4 genes on their mRNA expression.Yamada H et al

Other Information

Locus ID:

NCBI: 56649
MIM: 606565
HGNC: 11878
Ensembl: ENSG00000137648

Variants:

dbSNP: 56649
ClinVar: 56649
TCGA: ENSG00000137648
COSMIC: TMPRSS4

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000137648ENST00000437212Q9NRS4
ENSG00000137648ENST00000517483E5RJR8
ENSG00000137648ENST00000517544H0YBM5
ENSG00000137648ENST00000519236G3V124
ENSG00000137648ENST00000522151E5RIH1
ENSG00000137648ENST00000522307E7ESG9
ENSG00000137648ENST00000522824Q9NRS4
ENSG00000137648ENST00000523251Q9NRS4
ENSG00000137648ENST00000524218H0YAX8
ENSG00000137648ENST00000534111Q9NRS4
ENSG00000137648ENST00000616579A0A087WTU6
ENSG00000137648ENST00000618855Q9NRS4

Expression (GTEx)

0
10
20
30
40
50
60
70
80

Pathways

PathwaySourceExternal ID
Influenza AKEGGko05164
Influenza AKEGGhsa05164

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
191582462009Proteolytic activation of the 1918 influenza virus hemagglutinin.99
206311232010TMPRSS2 and TMPRSS4 facilitate trypsin-independent spread of influenza virus in Caco-2 cells.77
179683092008TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial-mesenchymal transition.57
201182002010TMPRSS4 induces invasion and epithelial-mesenchymal transition through upregulation of integrin alpha5 and its signaling pathways.42
324044362020TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes.29
244344352014TMPRSS4 regulates levels of integrin α5 in NSCLC through miR-205 activity to promote metastasis.26
220679042011Overexpression of TMPRSS4 in non-small cell lung cancer is associated with poor prognosis in patients with squamous histology.24
216373072011Radiation enhances long-term metastasis potential of residual hepatocellular carcinoma in nude mice through TMPRSS4-induced epithelial-mesenchymal transition.23
252444002015Transmembrane protease serine 4 promotes thyroid cancer proliferation via CREB phosphorylation.17
234200632013Prognostic value of TMPRSS4 expression in patients with breast cancer.16

Citation

Youngwoo Park

TMPRSS4 (transmembrane protease, serine 4)

Atlas Genet Cytogenet Oncol Haematol. 2009-10-01

Online version: http://atlasgeneticsoncology.org/gene/42594/tmprss4