| IED ID | IndEnz0002012004 |
| Enzyme Type ID | protease012004 |
| Protein Name |
Prothrombin EC 3.4.21.5 Coagulation factor II Cleaved into: Activation peptide fragment 1; Activation peptide fragment 2; Thrombin light chain; Thrombin heavy chain |
| Gene Name | F2 |
| 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 | MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE |
| Enzyme Length | 622 |
| Uniprot Accession Number | P00734 |
| Absorption | |
| Active Site | ACT_SITE 406; /note=Charge relay system; ACT_SITE 462; /note=Charge relay system; ACT_SITE 568; /note=Charge relay system |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by SERPINA5. {ECO:0000269|PubMed:6323392}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Selective cleavage of Arg-|-Gly bonds in fibrinogen to form fibrin and release fibrinopeptides A and B.; EC=3.4.21.5; |
| DNA Binding | |
| EC Number | 3.4.21.5 |
| Enzyme Function | FUNCTION: Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing. {ECO:0000269|PubMed:2856554}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Beta strand (40); Chain (3); Disulfide bond (12); Domain (4); Glycosylation (3); Helix (18); Modified residue (10); Natural variant (13); Peptide (2); Propeptide (1); Region (1); Sequence conflict (24); Signal peptide (1); Site (3); Turn (14) |
| Keywords | 3D-structure;Acute phase;Blood coagulation;Calcium;Cleavage on pair of basic residues;Direct protein sequencing;Disease variant;Disulfide bond;Gamma-carboxyglutamic acid;Glycoprotein;Hemostasis;Hydrolase;Kringle;Pharmaceutical;Protease;Reference proteome;Repeat;Secreted;Serine protease;Signal;Thrombophilia;Zymogen |
| Interact With | P05067; P07204; Q846V4; P01008 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted, extracellular space. |
| Modified Residue | MOD_RES 49; /note="4-carboxyglutamate"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:3759958, ECO:0000269|PubMed:6305407"; MOD_RES 50; /note="4-carboxyglutamate"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:3759958, ECO:0000269|PubMed:6305407"; MOD_RES 57; /note="4-carboxyglutamate"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:6305407"; MOD_RES 59; /note="4-carboxyglutamate"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:6305407"; MOD_RES 62; /note="4-carboxyglutamate"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:6305407"; MOD_RES 63; /note="4-carboxyglutamate"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:6305407"; MOD_RES 68; /note="4-carboxyglutamate"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:6305407"; MOD_RES 69; /note="4-carboxyglutamate"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:6305407"; MOD_RES 72; /note="4-carboxyglutamate"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:6305407"; MOD_RES 75; /note="4-carboxyglutamate"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:6305407" |
| Post Translational Modification | PTM: The gamma-carboxyglutamyl residues, which bind calcium ions, result from the carboxylation of glutamyl residues by a microsomal enzyme, the vitamin K-dependent carboxylase. The modified residues are necessary for the calcium-dependent interaction with a negatively charged phospholipid surface, which is essential for the conversion of prothrombin to thrombin. {ECO:0000269|PubMed:3759958, ECO:0000269|PubMed:6305407}.; PTM: N-glycosylated. N-glycan heterogeneity at Asn-121: Hex3HexNAc3 (minor), Hex4HexNAc3 (minor) and Hex5HexNAc4 (major). At Asn-143: Hex4HexNAc3 (minor) and Hex5HexNAc4 (major). {ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:22171320, ECO:0000269|PubMed:873923}. |
| Signal Peptide | SIGNAL 1..24; /evidence=ECO:0000255 |
| Structure 3D | NMR spectroscopy (2); X-ray crystallography (389) |
| Cross Reference PDB | 1A2C; 1A3B; 1A3E; 1A46; 1A4W; 1A5G; 1A61; 1ABI; 1ABJ; 1AD8; 1AE8; 1AFE; 1AHT; 1AI8; 1AIX; 1AWF; 1AWH; 1AY6; 1B5G; 1B7X; 1BA8; 1BB0; 1BCU; 1BHX; 1BMM; 1BMN; 1BTH; 1C1U; 1C1V; 1C1W; 1C4U; 1C4V; 1C4Y; 1C5L; 1C5N; 1C5O; 1CA8; 1D3D; 1D3P; 1D3Q; 1D3T; 1D4P; 1D6W; 1D9I; 1DE7; 1DIT; 1DM4; 1DOJ; 1DWB; 1DWC; 1DWD; 1DWE; 1DX5; 1E0F; 1EB1; 1EOJ; 1EOL; 1FPC; 1FPH; 1G30; 1G32; 1G37; 1GHV; 1GHW; 1GHX; 1GHY; 1GJ4; 1GJ5; 1H8D; 1H8I; 1HAG; 1HAH; 1HAI; 1HAO; 1HAP; 1HBT; 1HDT; 1HGT; 1HLT; 1HUT; 1HXE; 1HXF; 1IHS; 1IHT; 1JMO; 1JOU; 1JWT; 1K21; 1K22; 1KTS; 1KTT; 1LHC; 1LHD; 1LHE; 1LHF; 1LHG; 1MH0; 1MU6; 1MU8; 1MUE; 1NM6; 1NO9; 1NRN; 1NRO; 1NRP; 1NRQ; 1NRR; 1NRS; 1NT1; 1NU7; 1NU9; 1NY2; 1NZQ; 1O0D; 1O2G; 1O5G; 1OOK; 1OYT; 1P8V; 1PPB; 1QBV; 1QHR; 1QJ1; 1QJ6; 1QJ7; 1QUR; 1RD3; 1RIW; 1SB1; 1SFQ; 1SG8; 1SGI; 1SHH; 1SL3; 1SR5; 1T4U; 1T4V; 1TA2; 1TA6; 1TB6; 1TBZ; 1THP; 1THR; 1THS; 1TMB; 1TMT; 1TMU; 1TOM; 1TQ0; 1TQ7; 1TWX; 1UMA; 1UVS; 1VR1; 1VZQ; 1W7G; 1WAY; 1WBG; 1XM1; 1XMN; 1YPE; 1YPG; 1YPJ; 1YPK; 1YPL; 1YPM; 1Z71; 1Z8I; 1Z8J; 1ZGI; 1ZGV; 1ZRB; 2A0Q; 2A2X; 2A45; 2AFQ; 2ANK; 2ANM; 2B5T; 2BDY; 2BVR; 2BVS; 2BVX; 2BXT; 2BXU; 2C8W; 2C8X; 2C8Y; 2C8Z; 2C90; 2C93; 2CF8; 2CF9; 2CN0; 2FEQ; 2FES; 2GDE; 2GP9; 2H9T; 2HGT; 2HNT; 2HPP; 2HPQ; 2HWL; 2JH0; 2JH5; 2JH6; 2OD3; 2PGB; 2PGQ; 2PKS; 2PW8; 2R2M; 2THF; 2UUF; 2UUJ; 2UUK; 2V3H; 2V3O; 2ZC9; 2ZDA; 2ZDV; 2ZF0; 2ZFF; 2ZFP; 2ZFQ; 2ZFR; 2ZG0; 2ZGB; 2ZGX; 2ZHE; 2ZHF; 2ZHQ; 2ZHW; 2ZI2; 2ZIQ; 2ZNK; 2ZO3; 3B23; 3B9F; 3BEF; 3BEI; 3BF6; 3BIU; 3BIV; 3BV9; 3C1K; 3C27; 3D49; 3DA9; 3DD2; 3DHK; 3DT0; 3DUX; 3E6P; 3EE0; 3EGK; 3EQ0; 3F68; 3GIC; 3GIS; 3HAT; 3HKJ; 3HTC; 3JZ1; 3JZ2; 3K65; 3LDX; 3LU9; 3NXP; 3P17; 3P6Z; 3P70; 3PMH; 3PO1; 3QDZ; 3QGN; 3QLP; 3QTO; 3QTV; 3QWC; 3QX5; 3R3G; 3RLW; 3RLY; 3RM0; 3RM2; 3RML; 3RMM; 3RMN; 3RMO; 3S7H; 3S7K; 3SHA; 3SHC; 3SI3; 3SI4; 3SQE; 3SQH; 3SV2; 3T5F; 3TU7; 3U69; 3U8O; 3U8R; 3U8T; 3U98; 3U9A; 3UTU; 3UWJ; 3VXE; 3VXF; 4AX9; 4AYV; 4AYY; 4AZ2; 4BAH; 4BAK; 4BAM; 4BAN; 4BAO; 4BAQ; 4BOH; 4CH2; 4CH8; 4DIH; 4DII; 4DT7; 4DY7; 4E05; 4E06; 4E7R; 4H6S; 4H6T; 4HFP; 4HTC; 4HZH; 4I7Y; 4LOY; 4LXB; 4LZ1; 4LZ4; 4MLF; 4NZQ; 4O03; 4RKJ; 4RKO; 4RN6; 4THN; 4UD9; 4UDW; 4UE7; 4UEH; 4UFD; 4UFE; 4UFF; 4UFG; 4YES; 5A2M; 5AF9; 5AFY; 5AFZ; 5AHG; 5CMX; 5DO4; 5E8E; 5EDK; 5EDM; 5EW1; 5EW2; 5GDS; 5GIM; 5JDU; 5JFD; 5JZY; 5L6N; 5MJT; 5MLS; 5MM6; 5NHU; 5TO3; 5Z5W; 5Z5X; 6BJR; 6C2W; 6EO6; 6EO7; 6EO8; 6EO9; 6V5T; 7KME; 8KME; |
| Mapped Pubmed ID | 10068650; 10079109; 10089309; 10191087; 10210187; 10212123; 10350471; 10387040; 10504391; 10543954; 10694407; 10695772; 10713516; 10739244; 10739913; 10761923; 10779411; 10781579; 10823287; 10887932; 10910914; 10917896; 10956659; 11053836; 11060016; 11212093; 11252894; 11292354; 11342132; 11383586; 11427721; 11434083; 11454529; 11471205; 11513608; 11568114; 11676542; 11720865; 11728531; 11731301; 11738570; 11739083; 11742625; 11748101; 11820731; 11833835; 11884127; 11960487; 12038776; 12169660; 12205081; 12212242; 12379487; 12439143; 12466191; 12480694; 12570369; 12598231; 12615788; 12657281; 12679024; 12738509; 12742021; 12757770; 12781189; 12800172; 12855810; 12855811; 12873514; 12885234; 12907439; 1304349; 1445905; 14523329; 14523451; 14669168; 14691232; 14701945; 14706682; 14978285; 14982929; 15051174; 15075325; 15096570; 15109703; 15137772; 15152000; 15163182; 15174051; 15203120; 15203151; 15252033; 15299700; 15299843; 15311268; 15311269; 15522303; 15548541; 15572256; 15630502; 15658854; 15705787; 15707890; 15790048; 15801822; 1587268; 15890651; 15892865; 15911253; 15994914; 15998637; 16137886; 16201969; 16230339; 16230340; 16290930; 16294249; 16320685; 16374786; 16420563; 16460939; 16472842; 16480269; 16517159; 16533041; 1672265; 16754659; 16881367; 16882823; 16895415; 16938111; 16954215; 16962697; 16963292; 16973611; 17001711; 17047378; 17100732; 17107352; 17113632; 17155964; 17156138; 17290027; 17307838; 17316730; 17336062; 17341023; 17408404; 17428793; 17506785; 17510305; 17598008; 17636263; 17642517; 17889527; 17901324; 17902081; 17955562; 18019535; 18250335; 18315550; 1851341; 18577758; 18854941; 18971322; 1905813; 1920434; 19240027; 1930190; 19318721; 19332154; 19336370; 19371038; 1939071; 1942057; 19473969; 19520086; 19538716; 19559392; 19586901; 19591822; 19656282; 1973901; 19846563; 20156458; 2019570; 20236938; 20953506; 20974933; 2104766; 2109644; 21206024; 21536369; 21555542; 21555742; 21707111; 21715374; 21932952; 21988832; 22049947; 22053189; 2226434; 22366545; 22457833; 22535660; 22612268; 22618708; 22669903; 22726924; 22802338; 22907907; 23223529; 23290007; 23300094; 23467412; 23712263; 23775088; 2384594; 23951260; 24113284; 24128303; 24175584; 24311581; 24316004; 24821807; 2502206; 2505252; 25241761; 25268757; 2538457; 25664608; 26005532; 26270568; 26365066; 26469093; 26673709; 26762840; 26763231; 27347732; 2742826; 27566147; 27899589; 28294177; 28363953; 28592490; 2866798; 28837178; 29440720; 29684204; 30018388; 3052293; 30591525; 3082357; 3086311; 3134349; 31633354; 32358061; 3863104; 468991; 7238875; 7547884; 7574675; 7756983; 7853394; 7893672; 7947765; 7966150; 8052958; 8102368; 8136362; 8272424; 8338946; 8367461; 8376390; 8387813; 8407908; 8473289; 8473305; 8530480; 8605148; 8615752; 8637015; 8664309; 8745399; 8817670; 8868478; 8900153; 8913620; 8916933; 8939759; 9033393; 9058715; 9087410; 9108691; 9217260; 9226718; 9232642; 9282798; 9408029; 9409269; 9438869; 9446674; 9459334; 9468142; 9469622; 9521099; 9559654; 9576847; 9578548; 9618465; 9622548; 9703466; 9724521; 9733491; 9772168; 9869153; 9888880; |
| Motif | |
| Gene Encoded By | |
| Mass | 70,037 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.21.5; |