TMPRSS2 (transmembrane protease, serine 2)

2010-03-01   Youngwoo Park 

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

Identity

HGNC
LOCATION
21q22.3
LOCUSID
ALIAS
PRSS10
FUSION GENES

DNA/RNA

Atlas Image

Description

TMPRSS2 gene approximately extends 43.59 kb-long on chromosome 21 in the region q22.3, containing 14 exons.

Transcription

Two alternative splicing variants have been described, producing transcripts of 3.25 kb and 3.21 kb, respectively.

Proteins

Atlas Image
TMPRSS2 is a 492 amino acid single-pass type II membrane protein. It contains a Serine protease domain (aa 255-492) of the S1 family, followed by a Scavenger receptor cysteine-rich domain (SRDR, aa 149-242) of group A; an LDL receptor class A (LDLRA, aa 113-148) domain forms a binding site for calcium; a predicted transmembrane domain (aa 84-106). Letters H, D and S in the serine protease domain indicate the position of the three catalytic residues histidine, aspartate and serine, respectively.

Description

TMPRSS2 is a 492 amino acid type II transmembrane serine proteases (TTSPs) which are expressed at the cell surface and are thus ideally located to regulate cell-cell and cell-matrix interactions.

Expression

TMPRSS2 is expressed in normal and diseased human tissues. Especially, TMPRSS2 is highly expressed in small intestine, but also in lower levels in several other tissues. Also expressed in prostate, colon, stomach and salivary gland.

Localisation

Subcellular location: Cell membrane; Single-pass type II membrane protein.
Activated by cleavage and secreted.

Function

This gene was demonstrated to be up-regulated by androgenic hormones in prostate cancer cells and down-regulated in androgen-independent prostate cancer tissue. To containing intra- and extracellular domains, TMPRSS2 could work as a receptor for specific ligand(s) mediating signals between the environment and the cell. TMPRSS2 has been proposed to regulate epithelial sodium currents in the lung through proteolytic cleavage of the epithelial sodium channel and inflammatory responses in the prostate via the proteolytic activation of PAR-2.

Homology

TTPs (type II transmembrane serine proteases) contain an integral transmembrane domain and remain cell-surface-associated, even after proteolytic activation of the protease zymogen. 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 below. 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
Prostate cancer
Prognosis
TMPRSS2 was originally reported to be a small intestine-associated serine protease. Later, however, its gene turned out to be expressed mainly in the prostate in an androgen dependent manner.
In the prostate adenocarcinoma, TMPRSS2-EGR fusion mRNAs is highly expressed. Because of its location on the surface of prostatic cells, TMPRSS2 is a potential new diagnostic marker for prostate cancer.

Breakpoints

Atlas Image

Bibliography

Pubmed IDLast YearTitleAuthors
200685662010Prostate cancer genes associated with TMPRSS2-ERG gene fusion and prognostic of biochemical recurrence in multiple cohorts.Barwick BG et al
194876982009Type II transmembrane serine proteases.Bugge TH et al
195811282009Type II transmembrane serine proteases in cancer and viral infections.Choi SY et al
93250521997Cloning of the TMPRSS2 gene, which encodes a novel serine protease with transmembrane, LDLRA, and SRCR domains and maps to 21q22.3.Paoloni-Giacobino A et al
111695262001Expression of transmembrane serine protease TMPRSS2 in mouse and human tissues.Vaarala MH et al

Other Information

Locus ID:

NCBI: 7113
MIM: 602060
HGNC: 11876
Ensembl: ENSG00000184012

Variants:

dbSNP: 7113
ClinVar: 7113
TCGA: ENSG00000184012
COSMIC: TMPRSS2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000184012ENST00000332149O15393
ENSG00000184012ENST00000398585O15393
ENSG00000184012ENST00000424093C9J5Y1
ENSG00000184012ENST00000454499C9JKZ3
ENSG00000184012ENST00000455813C9JB05
ENSG00000184012ENST00000458356O15393

Expression (GTEx)

0
50
100
150
200

Pathways

PathwaySourceExternal ID
Influenza AKEGGko05164
Influenza AKEGGhsa05164
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
321426512020SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor.1161
169735942006Proteolytic activation of influenza viruses by serine proteases TMPRSS2 and HAT from human airway epithelium.164
213254202011Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response.162
165851602006TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer.160
199331092009Induced chromosomal proximity and gene fusions in prostate cancer.155
240273322013Middle East respiratory syndrome coronavirus infection mediated by the transmembrane serine protease TMPRSS2.120
210682372011A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry.118
227367902012The TMPRSS2:ERG rearrangement, ERG expression, and prostate cancer outcomes: a cohort study and meta-analysis.102
181722982008Characterization of TMPRSS2:ETV5 and SLC45A3:ETV5 gene fusions in prostate cancer.101
191582462009Proteolytic activation of the 1918 influenza virus hemagglutinin.99

Citation

Youngwoo Park

TMPRSS2 (transmembrane protease, serine 2)

Atlas Genet Cytogenet Oncol Haematol. 2010-03-01

Online version: http://atlasgeneticsoncology.org/gene/42592/tmprss2id42592ch21q22