Download Gene Section TMPRSS4 (transmembrane protease, serine 4) Atlas of Genetics and Cytogenetics

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Mini Review
TMPRSS4 (transmembrane protease, serine 4)
Youngwoo Park
Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejon,
Korea (YP)
Published in Atlas Database: October 2009
Online updated version : http://AtlasGeneticsOncology.org/Genes/TMPRSS4ID42594ch11q23.html
DOI: 10.4267/2042/44830
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
Protein
Other names: EC 3.4.21.-; MT-SP2; TMPRSS3
HGNC (Hugo): TMPRSS4
Location: 11q23.3
Note: Not to be confused with TMPRSS3 (21q22.3),
which was originally named for TMPRSS4 (11q23.3).
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
DNA/RNA
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.
Description
TMPRSS4 gene approximately extends 41.38 kb-long
on chromosome 11 in the region p23.3, containing 13
exons.
Localisation
Membrane; single-pass type II membrane protein.
Transcription
Function
Two alternative splicing variants have been described,
producing transcripts of 2.12 kb and 1.98 kb,
respectively.
TMPRSS4 plays a role in invasion, metastasis,
migration and adhesion, as well as in the EMT in
cancer cells.
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.
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(8)
785
TMPRSS4 (transmembrane protease, serine 4)
Park Y
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.
metastasis, migration, adhesion and EMT (epithelialmesenchymal 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.
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.
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.
Implicated in
Colon cancer
Oncogenesis
TMPRSS4 is an important mediator of invasion,
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.emblheidelberg.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.
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(8)
786
TMPRSS4 (transmembrane protease, serine 4)
Park Y
Choi SY, Shin HC, Kim SY, Park YW. Role of TMPRSS4
during cancer progression. Drug News Perspect. 2008
Oct;21(8):417-23
References
Wallrapp C, Hähnel S, Müller-Pillasch F, Burghardt B, Iwamura
T, Ruthenbürger M, Lerch MM, Adler G, Gress TM. A novel
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pancreatic cancer. Cancer Res. 2000 May 15;60(10):2602-6
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. TMPRSS4
promotes invasion, migration and metastasis of human tumor
cells by facilitating an epithelial-mesenchymal transition.
Oncogene. 2008 Apr 17;27(18):2635-47
Jarzab B, Wiench M, Fujarewicz K, Simek K, Jarzab M, OczkoWojciechowska M, Wloch J, Czarniecka A, Chmielik E, Lange
D, Pawlaczek A, Szpak S, Gubala E, Swierniak A. Gene
expression profile of papillary thyroid cancer: sources of
variability and diagnostic implications. Cancer Res. 2005 Feb
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Li BH, Yang XZ, Li PD, Yuan Q, Liu XH, Yuan J, Zhang WJ. IL4/Stat6 activities correlate with apoptosis and metastasis in
colon cancer cells. Biochem Biophys Res Commun. 2008 May
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Kebebew E, Peng M, Reiff E, Duh QY, Clark OH, McMillan A.
ECM1 and TMPRSS4 are diagnostic markers of malignant
thyroid neoplasms and improve the accuracy of fine needle
aspiration biopsy. Ann Surg. 2005 Sep;242(3):353-61;
discussion 361-3
Chaipan C, Kobasa D, Bertram S, Glowacka I, Steffen I,
Tsegaye TS, Takeda M, Bugge TH, Kim S, Park Y, Marzi A,
Pöhlmann S. Proteolytic activation of the 1918 influenza virus
hemagglutinin. J Virol. 2009 Apr;83(7):3200-11
Yamada H, Shinmura K, Tsuneyoshi T, Sugimura H. Effect of
splice-site polymorphisms of the TMPRSS4, NPHP4 and
ORCTL4 genes on their mRNA expression. J Genet. 2005
Aug;84(2):131-6
Choi SY, Bertram S, Glowacka I, Park YW, Pöhlmann S. Type
II transmembrane serine proteases in cancer and viral
infections. Trends Mol Med. 2009 Jul;15(7):303-12
This article should be referenced as such:
Kebebew E, Peng M, Reiff E, McMillan A. Diagnostic and
extent of disease multigene assay for malignant thyroid
neoplasms. Cancer. 2006 Jun 15;106(12):2592-7
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(8)
Park Y. TMPRSS4 (transmembrane protease, serine 4). Atlas
Genet Cytogenet Oncol Haematol. 2010; 14(8):785-787.
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