| IED ID | IndEnz0002001382 |
| Enzyme Type ID | protease001382 |
| 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 |
| Gene Name | TMPRSS2 PRSS10 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQASNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIECDSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENYGRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLRCIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEKPLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDLVKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLITPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVFTDWIYRQMRADG |
| Enzyme Length | 492 |
| Uniprot Accession Number | O15393 |
| Absorption | |
| Active Site | ACT_SITE 296; /note=Charge relay system; /evidence=ECO:0000250; ACT_SITE 345; /note=Charge relay system; /evidence=ECO:0000250; ACT_SITE 441; /note=Charge relay system |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.21.- |
| Enzyme Function | 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}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Alternative sequence (1); Chain (2); Disulfide bond (9); Domain (3); Glycosylation (2); Mutagenesis (2); Natural variant (9); Sequence conflict (5); Site (1); Topological domain (2); Transmembrane (1) |
| Keywords | 3D-structure;Alternative splicing;Autocatalytic cleavage;Cell membrane;Disulfide bond;Glycoprotein;Hydrolase;Membrane;Protease;Reference proteome;Secreted;Serine protease;Signal-anchor;Transmembrane;Transmembrane helix;Zymogen |
| Interact With | Q9BYF1; P01009; Q15848; Q86W74-2; P29972; O95393; Q12982; Q12983; Q6PL45-2; Q86Z23; O14523; Q9BXR6; Q9BXN2-6; Q9NWW5; Q96FZ5; Q6PI25; Q8TBE1; Q4LDR2; Q07325; Q9BQA9; P81534; P56851; Q9UKR5; Q92520; Q96IV6; P24593; Q6ZSS7; O75425; Q9NZG7; Q9UHJ9-5; Q9Y342; P26678; P60201-2; Q04941; Q13635-3; P53801; O00767; Q96IW7; Q9Y6D0; P11686; P78382; Q9NVC3; B2RUZ4; O15400; Q9UNK0; P17152; A0PK00; Q5BJH2-2; A2RU14; Q9H0R3; Q8NBD8; Q9BU79; Q9H2L4; Q9BSE2; Q8N2M4; Q8N661; P01375; Q5BVD1; O00526; O95183; Q9BQB6; O95159 |
| Induction | INDUCTION: By androgenic hormones in vivo. {ECO:0000269|PubMed:25122198}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20382709, ECO:0000269|PubMed:21068237}; Single-pass type II membrane protein {ECO:0000269|PubMed:20382709, ECO:0000269|PubMed:21068237}.; SUBCELLULAR LOCATION: [Transmembrane protease serine 2 catalytic chain]: Secreted {ECO:0000269|PubMed:20382709}. Note=Activated by cleavage and secreted. {ECO:0000269|PubMed:11245484, ECO:0000269|PubMed:20382709}. |
| Modified Residue | |
| Post Translational Modification | PTM: Proteolytically processed; by an autocatalytic mechanism. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 7MEQ; |
| Mapped Pubmed ID | 15065083; 15474033; 16575875; 16585160; 16820092; 16973594; 17032499; 17367471; 17390040; 17584912; 17632455; 17654723; 17804708; 18065961; 18172298; 18385909; 18474293; 18483239; 18519767; 18519769; 18562527; 18583469; 18676740; 18694509; 18922926; 19029822; 19158246; 19190343; 19242826; 19396154; 19465903; 19494719; 19584163; 19597533; 19649210; 19664128; 19762545; 19933109; 20068566; 20118910; 20442300; 20631123; 20798944; 20800881; 20878952; 20926566; 21040948; 21169414; 21377967; 21394739; 21499238; 21584900; 21600800; 21676887; 21677539; 21680704; 21731703; 21743434; 21743959; 21802835; 21937078; 22076164; 22222211; 22313860; 22496216; 22558251; 22674214; 22736790; 22860005; 22930729; 23192872; 23352841; 23447416; 23472063; 23535644; 23701505; 23850495; 24072184; 24109594; 24186205; 24195515; 24292212; 24297949; 24418414; 24777847; 24789172; 24824408; 24926821; 24931216; 24961351; 24997128; 25007891; 25015038; 25043536; 25175909; 25203900; 25263440; 25728532; 25734995; 25754347; 25852077; 25933120; 25939480; 25977336; 26026052; 26251449; 26379044; 26424596; 26503111; 26615022; 26774207; 26978019; 27028521; 27144529; 27277342; 27285981; 27320318; 27377958; 27500376; 27550352; 27630329; 27733646; 27798103; 27814612; 27926866; 28004109; 28050800; 28364793; 28445989; 28633309; 28783165; 28845585; 29127096; 29277318; 29346775; 29773553; 30078722; 30430607; 30538195; 30718921; 31391268; 31405024; 32143573; 32150281; 32229180; 32246845; 32329629; 32333601; 32362314; 32410502; 32441816; 32467600; 32468052; 32480226; 32501810; 32532959; 32573479; 32620366; 32658591; 32661206; 32664879; 32675312; 32691890; 32703421; 32703818; 32705281; 32726325; 32759995; 32768580; 32776522; 32828550; 32829149; 32831324; 32840422; 32842606; 32851697; 32861070; 32861340; 32871104; 32873700; 32967703; 32978525; 32980345; 33046696; 33061814; 33081421; 33104520; 33141952; 33180746; 33188579; 33207245; 33243086; 33245471; 33268377; 33278516; 33289868; 33301988; 33315943; 33351362; 33358483; 33375616; 33401657; 33407110; 33421977; 33531686; 33536584; 33558541; 33565463; 33609069; 33635001; 33649313; 33707526; 33752217; 33789993; 33812037; 33828231; 33844653; 33880519; 33880537; 33921689; 33958627; 34001248; 34045511; 34160253; 34160563; 34168096; 34210968; 34257580; 34284028; 34293134; 34293137; 34341114; 34356057; 34378968; 34407143; 34416267; 34418496; 34445373; 34588322; 34590312; 34635581; 34719202; 34807954; 34811561; 34953136; 35022007; |
| Motif | |
| Gene Encoded By | |
| Mass | 53,859 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.21.B60; |