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TMPRSS2 transmembrane serine protease 2 [ Homo sapiens (human) ]

Gene ID: 7113, updated on 7-Apr-2024

Summary

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Official Symbol
TMPRSS2provided by HGNC
Official Full Name
transmembrane serine protease 2provided by HGNC
Primary source
HGNC:HGNC:11876
See related
Ensembl:ENSG00000184012 MIM:602060; AllianceGenome:HGNC:11876
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PRSS10
Summary
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]
Annotation information
Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in SARS-CoV-2 infection.
Expression
Biased expression in prostate (RPKM 167.2), colon (RPKM 59.9) and 10 other tissues See more
Orthologs
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Genomic context

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Location:
21q22.3
Exon count:
15
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 21 NC_000021.9 (41464305..41508158, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 21 NC_060945.1 (39852990..39897690, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 21 NC_000021.8 (42836232..42880085, complement)

Chromosome 21 - NC_000021.9Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18472 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13330 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18473 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:42739613-42740114 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18474 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:42740714-42741402 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:42741403-42742089 Neighboring gene melanoma risk locus-associated MPRA allelic enhancer 21:42745414 Neighboring gene melanoma risk locus-associated MPRA allelic enhancers 21:42746568 and 21:42746578 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:42750497-42750998 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:42750999-42751498 Neighboring gene MX dynamin like GTPase 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13332 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18477 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18478 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18479 Neighboring gene MX dynamin like GTPase 1 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr21:42824122-42825321 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:42830117-42830618 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18480 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18481 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:42851654-42852154 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:42852155-42852655 Neighboring gene transmembrane protease serine 2 breakpoint cluster recombination region Neighboring gene TMPRSS2 promoter region Neighboring gene TMPRSS2 repressive element NBS1 Neighboring gene TMPRSS2 repressive element NBS2 Neighboring gene TMPRSS2 repressive element NBS4 Neighboring gene TMPRSS2 androgen receptor-responsive -13 kb enhancer Neighboring gene TMPRSS2 -17 kb enhancer Neighboring gene TMPRSS2 E3 enhancer Neighboring gene uncharacterized LOC124905021 Neighboring gene TMPRSS2 E4 enhancer Neighboring gene small nucleolar RNA SNORA32

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Expression of TMPRSS2 is up-regulated by bacterial flagellin, LPS, and Pam3Cys in human airway cells. Schwerdtner M, et al. Life Sci Alliance, 2023 Aug. PMID 37208193, Free PMC Article
  2. SARS-CoV-2 Infection of Human Neurons Is TMPRSS2 Independent, Requires Endosomal Cell Entry, and Can Be Blocked by Inhibitors of Host Phosphoinositol-5 Kinase. Kettunen P, et al. J Virol, 2023 Apr 27. PMID 37039676, Free PMC Article
  3. TMPRSS2 polymorphism (rs12329760) and the severity of the COVID-19 in Iranian population. Yaghoobi A, et al. PLoS One, 2023. PMID 36795725, Free PMC Article
  4. Polymorphism of tmprss2 (rs12329760) but not ace2 (rs4240157), tmprss11a (rs353163) and cd147 (rs8259) is associated with the severity of COVID-19 in the Ukrainian population. Kaidashev I, et al. Acta Biomed, 2023 Feb 13. PMID 36786264, Free PMC Article
  5. rs12329760 Polymorphism in Transmembrane Serine Protease 2 Gene and Risk of Coronavirus Disease 2019 Mortality. Beheshti Shirazi SS, et al. Biomed Res Int, 2022. PMID 36457338, Free PMC Article

See all (355) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Expression of the SARS-CoV-2 Receptor ACE2 and Protease TMPRSS2 in Ocular Hypertension Eyes of Nonhuman Primate and Human.
    Title: Expression of the SARS-CoV-2 Receptor ACE2 and Protease TMPRSS2 in Ocular Hypertension Eyes of Nonhuman Primate and Human.
  2. Host genetics and the profile of COVID-19 in indigenous people from the Brazilian Amazon: A pilot study with variants of the ACE1, ACE2 and TMPRSS2 genes.
    Title: Host genetics and the profile of COVID-19 in indigenous people from the Brazilian Amazon: A pilot study with variants of the ACE1, ACE2 and TMPRSS2 genes.
  3. Increased ACE2 and TMPRSS2 expression in ulcerative colitis.
    Title: Increased ACE2 and TMPRSS2 expression in ulcerative colitis.
  4. Evaluation of relationship between TMPRSS2 p.(Val197Met) variant and COVID-19 susceptibility and severity.
    Title: Evaluation of relationship between TMPRSS2 p.(Val197Met) variant and COVID-19 susceptibility and severity.
  5. The relationship between the clinical course of SARS-CoV-2 infections and ACE2 and TMPRSS2 expression and polymorphisms.
    Title: The relationship between the clinical course of SARS-CoV-2 infections and ACE2 and TMPRSS2 expression and polymorphisms.
  6. Genetic association of ACE2 and TMPRSS2 polymorphisms with COVID-19 severity; a single centre study from Egypt.
    Title: Genetic association of ACE2 and TMPRSS2 polymorphisms with COVID-19 severity; a single centre study from Egypt.
  7. Genetic polymorphisms of ACE1, ACE2, IFTM3, TMPRSS2 and TNFalpha genes associated with susceptibility and severity of SARS-CoV-2 infection: a systematic review and meta-analysis.
    Title: Genetic polymorphisms of ACE1, ACE2, IFTM3, TMPRSS2 and TNFα genes associated with susceptibility and severity of SARS-CoV-2 infection: a systematic review and meta-analysis.
  8. Conformational response to ligand binding of TMPRSS2, a protease involved in SARS-CoV-2 infection: Insights through computational modeling.
    Title: Conformational response to ligand binding of TMPRSS2, a protease involved in SARS-CoV-2 infection: Insights through computational modeling.
  9. SARS-CoV-2 Omicron entry is type II transmembrane serine protease-mediated in human airway and intestinal organoid models.
    Title: SARS-CoV-2 Omicron entry is type II transmembrane serine protease-mediated in human airway and intestinal organoid models.
  10. Human TMPRSS2 non-catalytic ectodomain and SARS-CoV-2 S2' subunit interaction mediated SARS-CoV-2 endocytosis: a model proposal with virtual screening for potential drug molecules to inhibit this interaction.
    Title: Human TMPRSS2 non-catalytic ectodomain and SARS-CoV-2 S2' subunit interaction mediated SARS-CoV-2 endocytosis: a model proposal with virtual screening for potential drug molecules to inhibit this interaction.
Submit: New GeneRIF Correction See all GeneRIFs (325)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.
EBI GWAS Catalog
Genome-wide association study combining pathway analysis for typical sporadic amyotrophic lateral sclerosis in Chinese Han populations.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ41954

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables serine-type endopeptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables serine-type endopeptidase activity TAS
Traceable Author Statement
more info
  
enables serine-type peptidase activity TAS
Traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in positive regulation of viral entry into host cell IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein autoprocessing IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein autoprocessing IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in proteolysis IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of viral translation TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in extracellular exosome HDA PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
transmembrane protease serine 2
Names
epitheliasin
serine protease 10
transmembrane protease, serine 2
NP_001128571.1
NP_001369649.1
NP_005647.3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_047085.2 RefSeqGene

    Range
    27959..71812
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_1368

mRNA and Protein(s)

  1. NM_001135099.1 → NP_001128571.1  transmembrane protease serine 2 isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    AA904080, AF270487, BC051839, DC382934
    Consensus CDS
    CCDS54486.1
    UniProtKB/TrEMBL
    Q96T73
    Related
    ENSP00000381588.3, ENST00000398585.7
    Conserved Domains (3) summary
    cd00112
    Location:150 → 185
    LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
    cd00190
    Location:293 → 524
    Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
    pfam15494
    Location:190 → 283
    SRCR_2; Scavenger receptor cysteine-rich domain

  2. NM_001382720.1 → NP_001369649.1  transmembrane protease serine 2 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AP001610
    Consensus CDS
    CCDS93100.1
    UniProtKB/TrEMBL
    A0A7I2V474, C9JKZ3
    Related
    ENSP00000503877.1, ENST00000678171.1
    Conserved Domains (3) summary
    cd00112
    Location:113 → 148
    LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
    cd00190
    Location:256 → 487
    Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
    pfam15494
    Location:153 → 246
    SRCR_2; Scavenger receptor cysteine-rich domain

  3. NM_005656.4 → NP_005647.3  transmembrane protease serine 2 isoform 2

    See identical proteins and their annotated locations for NP_005647.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) has an alternate 5' exon and uses a downstream AUG start codon, as compared to variant 1. The resulting isoform (2) has a shorter N-terminus, as compared to isoform 1.
    Source sequence(s)
    AF270487, AP001610, BC051839, BP276431
    Consensus CDS
    CCDS33564.1
    UniProtKB/Swiss-Prot
    A8K6Z8, B2R8E5, B7Z459, D3DSJ2, F8WES1, O15393, Q6GTK7, Q9BXX1
    UniProtKB/TrEMBL
    Q96T73
    Related
    ENSP00000330330.5, ENST00000332149.10
    Conserved Domains (3) summary
    cd00112
    Location:113 → 148
    LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
    cd00190
    Location:256 → 487
    Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
    pfam15494
    Location:153 → 246
    SRCR_2; Scavenger receptor cysteine-rich domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000021.9 Reference GRCh38.p14 Primary Assembly

    Range
    41464305..41508158 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060945.1 Alternate T2T-CHM13v2.0

    Range
    39852990..39897690 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O15393.3 GenPept UniProtKB/Swiss-Prot:O15393

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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