O15393 · TMPS2_HUMAN
- ProteinTransmembrane protease serine 2
- GeneTMPRSS2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids492 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Participates in proteolytic cascades of relevance for the normal physiologic function of the prostate (PubMed:25122198).
Androgen-induced TMPRSS2 activates several substrates that include pro-hepatocyte growth factor/HGF, the protease activated receptor-2/F2RL1 or matriptase/ST14 leading to extracellular matrix disruption and metastasis of prostate cancer cells (PubMed:15537383, PubMed:25122198, PubMed:26018085).
In addition, activates trigeminal neurons and contribute to both spontaneous pain and mechanical allodynia (By similarity).
The cleavage of SARS-COV2 spike glycoprotein occurs between the S2 and S2' site (PubMed:32703818).
Upon SARS-CoV-2 infection, increases syncytia formation by accelerating the fusion process (PubMed:33051876, PubMed:34159616).
Proteolytically cleaves and activates the spike glycoproteins of human coronavirus 229E (HCoV-229E) and human coronavirus EMC (HCoV-EMC) and the fusion glycoproteins F0 of Sendai virus (SeV), human metapneumovirus (HMPV), human parainfluenza 1, 2, 3, 4a and 4b viruses (HPIV). Essential for spread and pathogenesis of influenza A virus (strains H1N1, H3N2 and H7N9); involved in proteolytic cleavage and activation of hemagglutinin (HA) protein which is essential for viral infectivity
Catalytic activity
Features
Showing features for site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 255-256 | Cleavage | ||||
Sequence: RI | ||||||
Active site | 296 | Charge relay system | ||||
Sequence: H | ||||||
Active site | 345 | Charge relay system | ||||
Sequence: D | ||||||
Active site | 441 | Charge relay system | ||||
Sequence: S |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | extracellular exosome | |
Cellular Component | extracellular region | |
Cellular Component | nucleoplasm | |
Cellular Component | plasma membrane | |
Molecular Function | serine-type endopeptidase activity | |
Molecular Function | serine-type peptidase activity | |
Biological Process | positive regulation of viral entry into host cell | |
Biological Process | protein autoprocessing | |
Biological Process | proteolysis | |
Biological Process | viral translation |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameTransmembrane protease serine 2
- EC number
- Alternative names
- Cleaved into 2 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO15393
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Transmembrane protease serine 2 catalytic chain
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-84 | Cytoplasmic | ||||
Sequence: MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQASNPVVCTQPKSPSGTVCTSKTKKA | ||||||
Transmembrane | 85-105 | Helical; Signal-anchor for type II membrane protein | ||||
Sequence: LCITLTLGTFLVGAALAAGLL | ||||||
Topological domain | 106-492 | Extracellular | ||||
Sequence: WKFMGSKCSNSGIECDSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENYGRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLRCIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEKPLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDLVKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLITPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVFTDWIYRQMRADG |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_084541 | 8 | In isoform O15393-2; in dbSNP:rs200291871 | |||
Sequence: G → R | ||||||
Natural variant | VAR_084540 | 8 | In isoform O15393-2; in dbSNP:rs75603675 | |||
Sequence: G → V | ||||||
Natural variant | VAR_084538 | 28 | ||||
Sequence: A → T | ||||||
Natural variant | VAR_084539 | 74 | ||||
Sequence: G → R | ||||||
Natural variant | VAR_027674 | 160 | in dbSNP:rs12329760 | |||
Sequence: V → M | ||||||
Natural variant | VAR_038002 | 254 | ||||
Sequence: S → C | ||||||
Mutagenesis | 255 | Loss of cleavage. | ||||
Sequence: R → Q | ||||||
Natural variant | VAR_038003 | 329 | in dbSNP:rs775137340 | |||
Sequence: E → Q | ||||||
Mutagenesis | 441 | Loss of activity. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_011692 | 449 | in dbSNP:rs1056602 | |||
Sequence: K → N | ||||||
Natural variant | VAR_038004 | 491 | in dbSNP:rs779875214 | |||
Sequence: D → N |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,112 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000027855 | 1-255 | Transmembrane protease serine 2 non-catalytic chain | |||
Sequence: MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQASNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIECDSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENYGRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLRCIACGVNLNSSRQSR | ||||||
Disulfide bond | 113↔126 | |||||
Sequence: CSNSGIECDSSGTC | ||||||
Disulfide bond | 120↔139 | |||||
Sequence: CDSSGTCINPSNWCDGVSHC | ||||||
Disulfide bond | 133↔148 | |||||
Sequence: CDGVSHCPGGEDENRC | ||||||
Disulfide bond | 172↔231 | |||||
Sequence: CQDDWNENYGRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDAC | ||||||
Disulfide bond | 185↔241 | |||||
Sequence: CRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLRC | ||||||
Glycosylation | 213 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 244↔365 | Interchain (between non-catalytic and catalytic chains) | ||||
Sequence: CGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEKPLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDLVKPVC | ||||||
Glycosylation | 249 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Chain | PRO_0000027856 | 256-492 | Transmembrane protease serine 2 catalytic chain | |||
Sequence: IVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEKPLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDLVKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLITPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVFTDWIYRQMRADG | ||||||
Disulfide bond | 281↔297 | |||||
Sequence: CGGSIITPEWIVTAAHC | ||||||
Disulfide bond | 410↔426 | |||||
Sequence: CNSRYVYDNLITPAMIC | ||||||
Disulfide bond | 437↔465 | |||||
Sequence: CQGDSGGPLVTSKNNIWWLIGDTSWGSGC |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Induction
Gene expression databases
Organism-specific databases
Interaction
Subunit
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 112-149 | LDL-receptor class A | ||||
Sequence: KCSNSGIECDSSGTCINPSNWCDGVSHCPGGEDENRCV | ||||||
Domain | 150-242 | SRCR | ||||
Sequence: RLYGPNFILQVYSSQRKSWHPVCQDDWNENYGRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLRCI | ||||||
Domain | 256-489 | Peptidase S1 | ||||
Sequence: IVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEKPLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDLVKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLITPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVFTDWIYRQMR |
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative splicing.
O15393-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length492
- Mass (Da)53,859
- Last updated2006-10-03 v3
- ChecksumC05B5531C8A311C7
O15393-2
- Name2
- Differences from canonical
- 1-1: M → MPPAPPGGESGCEERGAAGHIEHSRYLSLLDAVDNSKM
Computationally mapped potential isoform sequences
There are 10 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
C9J5Y1 | C9J5Y1_HUMAN | TMPRSS2 | 452 | ||
C9JKZ3 | C9JKZ3_HUMAN | TMPRSS2 | 489 | ||
C9JB05 | C9JB05_HUMAN | TMPRSS2 | 79 | ||
A0A7I2YQ98 | A0A7I2YQ98_HUMAN | TMPRSS2 | 47 | ||
A0A7I2V3D1 | A0A7I2V3D1_HUMAN | TMPRSS2 | 384 | ||
A0A7I2V474 | A0A7I2V474_HUMAN | TMPRSS2 | 498 | ||
A0A7I2V509 | A0A7I2V509_HUMAN | TMPRSS2 | 410 | ||
A0A7I2V5F9 | A0A7I2V5F9_HUMAN | TMPRSS2 | 232 | ||
A0A7I2V5N2 | A0A7I2V5N2_HUMAN | TMPRSS2 | 423 | ||
A0A7I2V650 | A0A7I2V650_HUMAN | TMPRSS2 | 545 |
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_045083 | 1 | in isoform 2 | |||
Sequence: M → MPPAPPGGESGCEERGAAGHIEHSRYLSLLDAVDNSKM | ||||||
Sequence conflict | 26 | in Ref. 4; BAF84502 | ||||
Sequence: Y → H | ||||||
Sequence conflict | 62 | in Ref. 4; BAH12445 | ||||
Sequence: N → S | ||||||
Sequence conflict | 163 | in Ref. 4; BAF84502 | ||||
Sequence: S → P | ||||||
Sequence conflict | 242 | in Ref. 1; AAC51784 | ||||
Sequence: I → L | ||||||
Sequence conflict | 489-491 | in Ref. 1; AAC51784 | ||||
Sequence: RAD → KAN |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U75329 EMBL· GenBank· DDBJ | AAC51784.1 EMBL· GenBank· DDBJ | mRNA | ||
AF123453 EMBL· GenBank· DDBJ | AAD37117.1 EMBL· GenBank· DDBJ | mRNA | ||
AF270487 EMBL· GenBank· DDBJ | AAK29280.1 EMBL· GenBank· DDBJ | mRNA | ||
AK291813 EMBL· GenBank· DDBJ | BAF84502.1 EMBL· GenBank· DDBJ | mRNA | ||
AK296860 EMBL· GenBank· DDBJ | BAH12445.1 EMBL· GenBank· DDBJ | mRNA | ||
AK313338 EMBL· GenBank· DDBJ | BAG36142.1 EMBL· GenBank· DDBJ | mRNA | ||
AK222784 EMBL· GenBank· DDBJ | BAD96504.1 EMBL· GenBank· DDBJ | mRNA | ||
AP001610 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471079 EMBL· GenBank· DDBJ | EAX09597.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471079 EMBL· GenBank· DDBJ | EAX09598.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC051839 EMBL· GenBank· DDBJ | AAH51839.1 EMBL· GenBank· DDBJ | mRNA |