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FLASH GENE

Symbol

TMPRSS2

contributors: mct/pgu - updated : 02-04-2020

HGNC name	transmembrane protease, serine 2
HGNC id	11876

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	43.85 kb     14 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	cytosine-phosphate-guanine/HTF
	Binding site   enhancer   HRE
text structure	initiator-like element and potential regulatory element including SREBP, SP1, ERE
	androgen-responsive promoter elements
	an enhancer at 13 kb upstream of the TMPRSS2 transcription start site is crucial for the androgen regulation of the TMPRSS2 gene, and the GATA-2 binding sites are involved in the enhancer activity

MAPPING

cloned

Y

linked

N

status

provisional

Map	cen - ERG - MX1 - TMPRSS2 - D21S56 - qter
Authors	PMID: 9325052

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005656 14 - 3450 NP_005647 53.7 492 - 2015 2637904 NM_001135099 14 - 3250 NP_001128571 57.6 529 in lung-derived cell lines and tissues 2015 2637904 TMPRSS2 isoform 1 colocalizes with HA and cleaves and activates hemagglutinin (HA) having extended N-terminal cytoplasmic domain (isoform 1) activates the SARS-CoV spike protein for cathepsin L-independent entry into target cells is expressed in viral target cells and might contribute to viral activation in the host

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine small intestine     highly   intestine large intestine colon   highly   stomach       lowly Nervous brain       highly Reproductive male system prostate     highly Urinary bladder       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine

cells

System Cell Pubmed Species Stage Rna symbol Reproductive epithelial cell

cell lineage
cell lines	cells of epithelial prostate carcinoid
fluid/secretion

at STAGE

physiological period

fetal

Text	lung, kidney

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a serine protease domain of the S1 family
	a scavenger receptor cysteine rich (SRCR) domain
	an LDL receptor class A (LDLRA) domain
	a predicted transmembrane domain

HOMOLOGY

intraspecies

homolog to enteropeptidase gene

Homologene

FAMILY	serine protease, peptidase family
	peptidase S1 family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm
text	type II transmembrane-bound serine protease

basic FUNCTION	may contribute to prostate tumour metastasis via the activation of F2RL1
	important role for TMPRSS2 and possibly TMPRSS4 in influenza virus replication and highlight the former protease as a potential therapeutic target
	TMPRSS2 and TMPRSS11D are expressed by important influenza and SARS-coronavirus target cells and could thus support viral spread in the human host
	TMPRSS2 and TMPRSS11D can cleave and activate the spike protein (S) of the severe acute respiratory syndrome coronavirus (SARS-CoV) for membrane fusion
	plays a major role in in vivo replication of emerging H7N9 and seasonal influenza viruses
	cleaves and activates the influenza virus and coronavirus surface protein
	activate the SARS- and MERS-CoV S proteins for cathepsin B/L-independent host cell entry, presumably by cleaving the S proteins at or close to the cell surface
	activates HCV infection at the postbinding and entry stage
	HPN and TMPRSS2 colocalize on the cell surface with the secreted serine proteases KLK4 and KLK14, only in membrane protrusions, suggesting that reciprocal proteolytic interactions occur in defined cellular structures that are important during cancer dissemination for cell migration, invasion and survival
	is a novel membrane-anchored mediator in cancer pain
	SARS-2-S employs TMPRSS2 for S protein priming in human lung cells
	may also play an important role in SARS-CoV-2 cell entry
	TMPRSS2 is also likely to be a key protease for SARS-CoV-2 replication

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	TMPRSS2 and potentially related proteases promote SARS-CoV entry by two separate mechanisms: ACE2 cleavage, which might promote viral uptake, and SARS-S cleavage, which activates the S protein for membrane fusion
	TMPRSS2 was found to compete with the metalloprotease ADAM17 for ACE2 processing, but only cleavage by TMPRSS2 resulted in augmented SARS-S-driven entry
	role for inflammation-induced oxidative stress in the formation of DNA breaks leading to recurrent TMPRSS2-ERG gene fusions
	in contrast with HPN, TMPRSS2 degrades KLK14, and TMPRSS2 cleavage is mediated by KLK14

cell & other

REGULATION

activated by

androgens

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in prostate carcinoma, with down-regulation of KLK11 gene in advanced and more aggressive tumors may open the feasibility of being used as biomarkers distinguishing the tumor aggressiveness tumoral fusion       with ERG, ETV1 and ETV4 in prostate cancer tumoral somatic mutation translocation     Loss of PTEN and concomitant activation of AKTcould act in partnership with the TMPRSS2-ERG fusion protein to promote progression to prostate cancer tumoral fusion       TMPRSS2-ERG gene fusions were observed in 44p 100 of prostate cancer, and over 90p100 of these fusions occurred in ERG exons 3 or 4

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	development of the TMPRSS2-ERG fusion gene is a noninvasive tumor marker for therapy assessment, risk stratification, and relapse detection to improve personalized therapy strategies for patients with prostate cancer
	urinary TMPRSS2:ERG might become a valuable test not only for diagnosing PCa but also for distinguishing the aggressive tumors from the indolent ones
Therapy target
	System Type Disorder Pubmed immunology infectious   TMPRSS2-related therapeutic agents may be a promising countermeasure against the current and new outbreaks of CoVs

ANIMAL & CELL MODELS

Tmprss2 plays a crucial role in viral spread within the airway of murine models infected by SARS-CoV and MERS-CoV and in the resulting immunopathology