DegronMD - O15393(TMPRSS2)

FUNCTION: Plasma membrane-anchored serine protease that 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:26018085, PubMed:25122198). In addition, activates trigeminal neurons and contribute to both spontaneous pain and mechanical allodynia (By similarity). {ECO:0000250|UniProtKB:Q9JIQ8, ECO:0000269|PubMed:15537383, ECO:0000269|PubMed:25122198, ECO:0000269|PubMed:26018085}.; FUNCTION: (Microbial infection) Facilitates human coronaviruses SARS-CoV and SARS-CoV-2 infections via two independent mechanisms, proteolytic cleavage of ACE2 receptor which promotes viral uptake, and cleavage of coronavirus spike glycoproteins which activates the glycoprotein for host cell entry (PubMed:24227843, PubMed:32142651, PubMed:32404436, PubMed:34159616, PubMed:33051876). Upon SARS-CoV-2 infection, increases syncytia formation by accelerating the fusion process (PubMed:34159616, PubMed:33051876). 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. {ECO:0000269|PubMed:21068237, ECO:0000269|PubMed:21325420, ECO:0000269|PubMed:23536651, ECO:0000269|PubMed:23966399, ECO:0000269|PubMed:24027332, ECO:0000269|PubMed:24227843, ECO:0000269|PubMed:32142651, ECO:0000269|PubMed:32404436, ECO:0000269|PubMed:33051876, ECO:0000269|PubMed:34159616}. View more >>

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GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.S7L	DO233020	GACA	ICGC	IGPYYE	LIG_APCC_ABBA_1	11:16	Mutation rewiring degron network	0.2222
p.P3A	DO233035	GACA	ICGC	IGPYYE	LIG_APCC_ABBA_1	11:16	Mutation rewiring degron network	0.1111
p.G8R	DO50967	LICA	ICGC	IGPYYE	LIG_APCC_ABBA_1	11:16	Mutation rewiring degron network	0.25
p.E9G	DO25320	LUAD	ICGC	IGPYYE	LIG_APCC_ABBA_1	11:16	Mutation rewiring degron network	0.2778
p.L3F	DO36394	READ	ICGC	IGPYYE	LIG_APCC_ABBA_1	11:16	Mutation rewiring degron network	0.1111
p.E23K	ACH-001550	Skin Cancer	CCLE	IGPYYE	LIG_APCC_ABBA_1	11:16	Mutation rewiring degron network	0.1389
p.E23K	MCC13	skin	COSMIC	IGPYYE	LIG_APCC_ABBA_1	11:16	Mutation rewiring degron network	0.1389

DegronMD: protein-targeted degradation, mutation and drug response to degrons

TMPRSS2

UniProt ID: O15393

Entrez ID: 7113

Protein name: Transmembrane protease serine 2 (EC 3.4.21.-) (Serine protease 10) [Cleaved into: Transmembrane protease serine 2 non-catalytic chain; Transmembrane protease serine 2 catalytic chain]

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for TMPRSS2 in