TMPRSS2 (transmembrane protease, serine 2)

Written2010-03Youngwoo Park
Therapeutic Antibody Research Center, Korea Research Institute of Bioscience, Biotechnology, Daejon, Korea

(Note : for Links provided by Atlas : click)

1. Identity

Alias_symbol (synonym)
General Information
Other aliasFLJ41954
LocusID (NCBI) 7113
Atlas_Id 42592
Location 21q22.3  [Link to chromosome band 21q22]
Location_base_pair Starts at 41464551 and ends at 41508158 bp from pter ( according to hg19-Feb_2009)  [Mapping TMPRSS2.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)
ARID2 (12q12) / TMPRSS2 (21q22.3)ATF7IP (12p13.1) / TMPRSS2 (21q22.3)ERG (21q22.2) / TMPRSS2 (21q22.3)
ETV1 (7p21.2) / TMPRSS2 (21q22.3)ETV4 (17q21.31) / TMPRSS2 (21q22.3)ETV5 (3q27.2) / TMPRSS2 (21q22.3)
NR4A1 (12q13.13) / TMPRSS2 (21q22.3)TMPRSS2 (21q22.3) / ARFGEF2 (20q13.13)TMPRSS2 (21q22.3) / ATF7IP (12p13.1)
TMPRSS2 (21q22.3) / ERG (21q22.2)TMPRSS2 (21q22.3) / ETV1 (7p21.2)TMPRSS2 (21q22.3) / ETV4 (17q21.31)
TMPRSS2 (21q22.3) / ETV5 (3q27.2)TMPRSS2 (21q22.3) / FKBP5 (6p21.31)TMPRSS2 (21q22.3) / GRHL2 (8q22.3)
TMPRSS2 (21q22.3) / MALAT1 (11q13.1)TMPRSS2 (21q22.3) / SKIL (3q26.2)


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.

3. Protein

  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.

4. Implicated in

Entity 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.

5. Breakpoints


6. Bibliography

Prostate cancer genes associated with TMPRSS2-ERG gene fusion and prognostic of biochemical recurrence in multiple cohorts.
Barwick BG, Abramovitz M, Kodani M, Moreno CS, Nam R, Tang W, Bouzyk M, Seth A, Leyland-Jones B.
Br J Cancer. 2010 Feb 2;102(3):570-6. Epub 2010 Jan 12.
PMID 20068566
Type II transmembrane serine proteases.
Bugge TH, Antalis TM, Wu Q.
J Biol Chem. 2009 Aug 28;284(35):23177-81. Epub 2009 Jun 1. (REVIEW)
PMID 19487698
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. (REVIEW)
PMID 19581128
Cloning of the TMPRSS2 gene, which encodes a novel serine protease with transmembrane, LDLRA, and SRCR domains and maps to 21q22.3.
Paoloni-Giacobino A, Chen H, Peitsch MC, Rossier C, Antonarakis SE.
Genomics. 1997 Sep 15;44(3):309-20.
PMID 9325052
Expression of transmembrane serine protease TMPRSS2 in mouse and human tissues.
Vaarala MH, Porvari KS, Kellokumpu S, Kyllonen AP, Vihko PT.
J Pathol. 2001 Jan;193(1):134-40.
PMID 11169526

7. Citation

This paper should be referenced as such :
Park, Y
TMPRSS2 (transmembrane protease, serine 2)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(12):1163-1165.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 7 ]
  Prostate tumors: an overview
t(3;21)(q26;q22) TMPRSS2/SKIL
t(8;21)(q22;q22) TMPRSS2/GRHL2
t(12;21)(p13;q22) ATF7IP/TMPRSS2
t(12;21)(p13;q22) TMPRSS2/ATF7IP
t(12;21)(q12;q22) ARID2/TMPRSS2
t(20;21)(q13;q22) TMPRSS2/ARFGEF2

8. External links

HGNC (Hugo)TMPRSS2   11876
Entrez_Gene (NCBI)TMPRSS2  7113  transmembrane serine protease 2
AliasesPP9284; PRSS10
GeneCards (Weizmann)TMPRSS2
Ensembl hg19 (Hinxton)ENSG00000184012 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000184012 [Gene_View] &nbspENSG00000184012 [Sequence]  chr21:41464551-41508158 [Contig_View]  TMPRSS2 [Vega]
ICGC DataPortalENSG00000184012
Genatlas (Paris)TMPRSS2
Genetics Home Reference (NIH)TMPRSS2
Genomic and cartography
GoldenPath hg38 (UCSC)TMPRSS2  -     chr21:41464551-41508158 -  21q22.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)TMPRSS2  -     21q22.3   [Description]    (hg19-Feb_2009)
EnsemblTMPRSS2 - 21q22.3 [CytoView hg19]  TMPRSS2 - 21q22.3 [CytoView hg38]
Mapping of homologs : NCBITMPRSS2 [Mapview hg19]  TMPRSS2 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AA904080 AF123453 AF270487 AF318374 AF329454
RefSeq transcript (Entrez)NM_001135099 NM_005656
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)TMPRSS2
Cluster EST : UnigeneHs.439309 [ NCBI ]
CGAP (NCI)Hs.439309
Alternative Splicing GalleryENSG00000184012
Gene Expression Viewer (FireBrowse)TMPRSS2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets] &nbsp [Normal Tissue Atlas] &nbsp[carcinoma Classsification] &nbsp[NCI60]
GenevestigatorExpression in : [tissues] &nbsp[cell-lines] &nbsp[cancer] &nbsp[perturbations] &nbsp
BioGPS (Tissue expression)7113
GTEX Portal (Tissue expression)TMPRSS2
Human Protein AtlasENSG00000184012-TMPRSS2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO15393   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO15393  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO15393
Splice isoforms : SwissVarO15393
Catalytic activity : Enzyme3.4.21.- [ Enzyme-Expasy ]   3.4.21.-3.4.21.- [ IntEnz-EBI ]   3.4.21.- [ BRENDA ]   3.4.21.- [ KEGG ]   
Domaine pattern : Prosite (Expaxy)LDLRA_1 (PS01209)    LDLRA_2 (PS50068)    SRCR_2 (PS50287)    TRYPSIN_DOM (PS50240)    TRYPSIN_HIS (PS00134)    TRYPSIN_SER (PS00135)   
Domains : Interpro (EBI)LDL_receptor-like_sf    LDLR_class-A_CS    LDrepeatLR_classA_rpt    Peptidase_S1_PA    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)TMPRSS2
DMDM Disease mutations7113
Blocks (Seattle)TMPRSS2
Human Protein Atlas [tissue]ENSG00000184012-TMPRSS2 [tissue]
Peptide AtlasO15393
IPIIPI00006212   IPI00383276   IPI00871690   IPI00789736   IPI00927365   IPI00953138   
Protein Interaction databases
IntAct (EBI)O15393
Ontologies - Pathways
Ontology : AmiGOserine-type endopeptidase activity  scavenger receptor activity  protein binding  plasma membrane  integral component of plasma membrane  proteolysis  receptor-mediated endocytosis  serine-type peptidase activity  protein autoprocessing  protein autoprocessing  positive regulation of viral entry into host cell  extracellular exosome  
Ontology : EGO-EBIserine-type endopeptidase activity  scavenger receptor activity  protein binding  plasma membrane  integral component of plasma membrane  proteolysis  receptor-mediated endocytosis  serine-type peptidase activity  protein autoprocessing  protein autoprocessing  positive regulation of viral entry into host cell  extracellular exosome  
Pathways : KEGGInfluenza A    Transcriptional misregulation in cancer   
Atlas of Cancer Signalling NetworkTMPRSS2
Wikipedia pathwaysTMPRSS2
Orthology - Evolution
GeneTree (enSembl)ENSG00000184012
Phylogenetic Trees/Animal Genes : TreeFamTMPRSS2
Homologs : HomoloGeneTMPRSS2
Homology/Alignments : Family Browser (UCSC)TMPRSS2
Gene fusions - Rearrangements
Fusion : MitelmanARID2/TMPRSS2 [12q12/21q22.3] &nbsp[t(12;21)(q12;q22)]  
Fusion : MitelmanATF7IP/TMPRSS2 [12p13.1/21q22.3] &nbsp[t(12;21)(p13;q22)]  
Fusion : MitelmanTMPRSS2/ARFGEF2 [21q22.3/20q13.13] &nbsp[t(20;21)(q13;q22)]  
Fusion : MitelmanTMPRSS2/ATF7IP [21q22.3/12p13.1] &nbsp[t(12;21)(p13;q22)]  
Fusion : MitelmanTMPRSS2/ERG [21q22.3/21q22.2] &nbsp[del(21)(q22q22)]  [t(17;21)(q21;q22)]  
[t(1;21)(q32;q22)]  [t(21;21)(q22;q22)]  [t(7;21)(p21;q22)]  
Fusion : MitelmanTMPRSS2/ETV1 [21q22.3/7p21.2] &nbsp[del(21)(q22q22)]  [t(17;21)(q21;q22)]  
[t(21;21)(q22;q22)]  [t(7;21)(p21;q22)]  
Fusion : MitelmanTMPRSS2/ETV4 [21q22.3/17q21.31] &nbsp[del(21)(q22q22)]  [t(17;21)(q21;q22)]  
[t(21;21)(q22;q22)]  [t(7;21)(p21;q22)]  
Fusion : MitelmanTMPRSS2/ETV5 [21q22.3/3q27.2] &nbsp[t(3;21)(q27;q22)]  
Fusion : MitelmanTMPRSS2/GRHL2 [21q22.3/8q22.3] &nbsp[t(8;21)(q22;q22)]  
Fusion : COSMICTMPRSS2 [ERG]  -  116 [118]  [fusion_121]  [fusion_123]  [fusion_124]  [fusion_125]  [fusion_126]  [fusion_127]  [fusion_128]  
[fusion_129]  [fusion_130]  [fusion_135]  [fusion_138]  [fusion_139]  [fusion_16]  [fusion_17]  [fusion_18]  [fusion_21]  [fusion_23]  
[fusion_24]  [fusion_25]  [fusion_26]  [fusion_27]  [fusion_28]  [fusion_29]  [fusion_30]  [fusion_36]  [fusion_38]  [fusion_39]  
[fusion_40]  [fusion_41]  [fusion_736]  
Fusion : COSMICTMPRSS2 [ETV1]  -  115 [122]  [fusion_134]  [fusion_14]  [fusion_15]  [fusion_22]  [fusion_33]  [fusion_34]  
Fusion : COSMICTMPRSS2 [ETV4]  -  144 [212]  [fusion_213]  [fusion_214]  [fusion_44]  
Fusion : COSMICTMPRSS2 [ETV5]  -  1159 [1160]  [fusion_1163]  [fusion_1164]  
Fusion PortalARID2 12q12 TMPRSS2 21q22.3 BRCA
Fusion PortalATF7IP 12p13.1 TMPRSS2 21q22.3 PRAD
Fusion PortalTMPRSS2 21q22.3 ARFGEF2 20q13.13 PRAD
Fusion PortalTMPRSS2 21q22.3 ATF7IP 12p13.1 PRAD
Fusion PortalTMPRSS2 21q22.3 ERG 21q22.2 PRAD
Fusion PortalTMPRSS2 21q22.3 ETV4 17q21.31 PRAD
Fusion PortalTMPRSS2 21q22.3 GRHL2 8q22.3 PRAD
Fusion : TICdbTMPRSS2 [21q22.3]  -  ERG [21q22.2]
Fusion : TICdbTMPRSS2 [21q22.3]  -  ETV1 [7p21.2]
Fusion : TICdbTMPRSS2 [21q22.3]  -  ETV4 [17q21.31]
Fusion : TICdbTMPRSS2 [21q22.3]  -  ETV5 [3q27.2]
Fusion Cancer (Beijing)NR4A1 [12q13.13]  -  TMPRSS2 [21q22.3]  [FUSC004214]
Fusion Cancer (Beijing)TMPRSS2 [21q22.3]  -  ERG [21q22.2]  [FUSC004187]  [FUSC004187]  [FUSC004187]  [FUSC004187]  [FUSC004187]
Fusion : QuiverTMPRSS2
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTMPRSS2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TMPRSS2
Exome Variant ServerTMPRSS2
ExAC (Exome Aggregation Consortium)ENSG00000184012
GNOMAD BrowserENSG00000184012
Varsome BrowserTMPRSS2
Genetic variants : HAPMAP7113
Genomic Variants (DGV)TMPRSS2 [DGVbeta]
DECIPHERTMPRSS2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisTMPRSS2 
ICGC Data PortalTMPRSS2 
TCGA Data PortalTMPRSS2 
Broad Tumor PortalTMPRSS2
OASIS PortalTMPRSS2 [ Somatic mutations - Copy number]
Cancer Gene: CensusTMPRSS2 
Somatic Mutations in Cancer : COSMICTMPRSS2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDTMPRSS2
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch TMPRSS2
DgiDB (Drug Gene Interaction Database)TMPRSS2
DoCM (Curated mutations)TMPRSS2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TMPRSS2 (select a term)
NCG5 (London)TMPRSS2
Cancer3DTMPRSS2(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry TMPRSS2
NextProtO15393 [Medical]
Target ValidationTMPRSS2
Huge Navigator TMPRSS2 [HugePedia]
snp3D : Map Gene to Disease7113
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7113
Chemical/Pharm GKB GenePA36577
Clinical trialTMPRSS2
canSAR (ICR)TMPRSS2 (select the gene name)
DataMed IndexTMPRSS2
PubMed166 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 : Thu Jan 17 19:10:22 CET 2019

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