TMPRSS2

Protein identityUniProt · HPA

UniProt accession

O15393

Gene

TMPRSS2

Ensembl

ENSG00000184012

Chromosome

21

Canonical length

492 aa

Protein class

Cancer-related genes, Enzymes, Predicted intracellular proteins, Predicted membrane proteins, Predicted secreted proteins, Transporters

Subcellular location

Plasma membrane

Secretome location

Secreted in other tissues

OverviewNCBI Gene

This gene encodes a protein that belongs to the serine protease family. The encoded protein contains a type II transmembrane domain, a receptor class A domain, a scavenger receptor cysteine-rich domain and a protease domain. Serine proteases are known to be involved in many physiological and pathological processes. This gene was demonstrated to be up-regulated by androgenic hormones in prostate cancer cells and down-regulated in androgen-independent prostate cancer tissue. The protease domain of this protein is thought to be cleaved and secreted into cell media after autocleavage. This protein also facilitates entry of viruses into host cells by proteolytically cleaving and activating viral envelope glycoproteins. Viruses found to use this protein for cell entry include Influenza virus and the human coronaviruses HCoV-229E, MERS-CoV, SARS-CoV and SARS-CoV-2 (COVID-19 virus). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2020]

Canonical amino-acid sequenceUniProt

492 residues, UniProt reviewed canonical sequence.

>O15393|TMPRSS2
     1  MALNSGSPPA IGPYYENHGY QPENPYPAQP TVVPTVYEVH PAQYYPSPVP QYAPRVLTQA
    61  SNPVVCTQPK SPSGTVCTSK TKKALCITLT LGTFLVGAAL AAGLLWKFMG SKCSNSGIEC
   121  DSSGTCINPS NWCDGVSHCP GGEDENRCVR LYGPNFILQV YSSQRKSWHP VCQDDWNENY
   181  GRAACRDMGY KNNFYSSQGI VDDSGSTSFM KLNTSAGNVD IYKKLYHSDA CSSKAVVSLR
   241  CIACGVNLNS SRQSRIVGGE SALPGAWPWQ VSLHVQNVHV CGGSIITPEW IVTAAHCVEK
   301  PLNNPWHWTA FAGILRQSFM FYGAGYQVEK VISHPNYDSK TKNNDIALMK LQKPLTFNDL
   361  VKPVCLPNPG MMLQPEQLCW ISGWGATEEK GKTSEVLNAA KVLLIETQRC NSRYVYDNLI
   421  TPAMICAGFL QGNVDSCQGD SGGPLVTSKN NIWWLIGDTS WGSGCAKAYR PGVYGNVMVF
   481  TDWIYRQMRA DG

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TMPRSS2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.33

Highest tissue expression

263 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.94

gnomAD pLI

0

gnomAD missense Z

0.4

DepMap mean gene effect

-0.04

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• entry receptor-mediated virion attachment to host cell
• positive regulation of viral entry into host cell
• protein autoprocessing
• proteolysis

Molecular functions

• serine-type endopeptidase activity
• serine-type peptidase activity

Cellular components

• extracellular exosome
• extracellular region
• nucleoplasm
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• SRCR domain
• Serine proteases, trypsin domain
• Peptidase S1A, chymotrypsin family
• Low-density lipoprotein (LDL) receptor class A repeat
• Peptidase S1, PA clan
• Serine proteases, trypsin family, histidine active site
• Low-density lipoprotein (LDL) receptor class A, conserved site
• Serine proteases, trypsin family, serine active site
• LDL receptor-like superfamily
• SRCR-like domain superfamily
• Trypsin
• Scavenger receptor cysteine-rich domain

KeywordsUniProt

• Autocatalytic cleavage
• Cell membrane
• Disulfide bond
• Glycoprotein
• Host-virus interaction
• Hydrolase
• Membrane
• Protease
• Secreted
• Serine protease
• Signal-anchor
• Transmembrane
• Transmembrane helix
• Zymogen

InteractionsUniProt · HPA

Protein binding partners of TMPRSS2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ACE2