| IED ID | IndEnz0002009341 |
| Enzyme Type ID | protease009341 |
| Protein Name |
Vitamin K-dependent protein C EC 3.4.21.69 Anticoagulant protein C Autoprothrombin IIA Blood coagulation factor XIV Cleaved into: Vitamin K-dependent protein C light chain; Vitamin K-dependent protein C heavy chain; Activation peptide |
| Gene Name | PROC |
| 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 | MWQLTSLLLFVATWGISGTPAPLDSVFSSSERAHQVLRIRKRANSFLEELRHSSLERECIEEICDFEEAKEIFQNVDDTLAFWSKHVDGDQCLVLPLEHPCASLCCGHGTCIDGIGSFSCDCRSGWEGRFCQREVSFLNCSLDNGGCTHYCLEEVGWRRCSCAPGYKLGDDLLQCHPAVKFPCGRPWKRMEKKRSHLKRDTEDQEDQVDPRLIDGKMTRRGDSPWQVVLLDSKKKLACGAVLIHPSWVLTAAHCMDESKKLLVRLGEYDLRRWEKWELDLDIKEVFVHPNYSKSTTDNDIALLHLAQPATLSQTIVPICLPDSGLAERELNQAGQETLVTGWGYHSSREKEAKRNRTFVLNFIKIPVVPHNECSEVMSNMVSENMLCAGILGDRQDACEGDSGGPMVASFHGTWFLVGLVSWGEGCGLLHNYGVYTKVSRYLDWIHGHIRDKEAPQKSWAP |
| Enzyme Length | 461 |
| Uniprot Accession Number | P04070 |
| Absorption | |
| Active Site | ACT_SITE 253; /note=Charge relay system; ACT_SITE 299; /note=Charge relay system; ACT_SITE 402; /note=Charge relay system |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Degradation of blood coagulation factors Va and VIIIa.; EC=3.4.21.69; |
| DNA Binding | |
| EC Number | 3.4.21.69 |
| Enzyme Function | FUNCTION: Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a protective effect on the endothelial cell barrier function (PubMed:25651845). {ECO:0000269|PubMed:25618265, ECO:0000269|PubMed:25651845}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Alternative sequence (2); Beta strand (25); Chain (3); Disulfide bond (12); Domain (4); Erroneous termination (1); Glycosylation (5); Helix (9); Modified residue (11); Natural variant (93); Peptide (1); Propeptide (1); Sequence conflict (2); Signal peptide (1); Site (1); Turn (4) |
| Keywords | 3D-structure;Alternative splicing;Blood coagulation;Calcium;Cleavage on pair of basic residues;Direct protein sequencing;Disease variant;Disulfide bond;EGF-like domain;Endoplasmic reticulum;Gamma-carboxyglutamic acid;Glycoprotein;Golgi apparatus;Hemostasis;Hydrolase;Hydroxylation;Phosphoprotein;Protease;Reference proteome;Repeat;Secreted;Serine protease;Signal;Thrombophilia;Zymogen |
| Interact With | A8MQ03; P51511 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:25618265}. Golgi apparatus {ECO:0000269|PubMed:22531345, ECO:0000269|PubMed:25748729}. Endoplasmic reticulum {ECO:0000269|PubMed:22531345, ECO:0000269|PubMed:25748729}. |
| Modified Residue | MOD_RES 48; /note="4-carboxyglutamate"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:2991887"; MOD_RES 49; /note="4-carboxyglutamate"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:2991887"; MOD_RES 56; /note="4-carboxyglutamate"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:2991887"; MOD_RES 58; /note="4-carboxyglutamate"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:2991887"; MOD_RES 61; /note="4-carboxyglutamate"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:2991887"; MOD_RES 62; /note="4-carboxyglutamate"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:2991887"; MOD_RES 67; /note="4-carboxyglutamate"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:2991887"; MOD_RES 68; /note="4-carboxyglutamate"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:2991887"; MOD_RES 71; /note="4-carboxyglutamate"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:2991887"; MOD_RES 113; /note="(3R)-3-hydroxyaspartate"; /evidence="ECO:0000269|PubMed:2991887"; MOD_RES 347; /note="Phosphoserine; by FAM20C"; /evidence="ECO:0000269|PubMed:26091039" |
| Post Translational Modification | PTM: The vitamin K-dependent, enzymatic carboxylation of some Glu residues allows the modified protein to bind calcium.; PTM: N- and O-glycosylated. Partial (70%) N-glycosylation of Asn-371 with an atypical N-X-C site produces a higher molecular weight form referred to as alpha. The lower molecular weight form, not N-glycosylated at Asn-371, is beta. O-glycosylated with core 1 or possibly core 8 glycans. {ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:1694179, ECO:0000269|PubMed:22171320, ECO:0000269|PubMed:2991887}.; PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. {ECO:0000269|PubMed:1544894, ECO:0000269|PubMed:2991887}.; PTM: May be phosphorylated on a Ser or Thr in a region (AA 25-30) of the propeptide. |
| Signal Peptide | SIGNAL 1..18; /evidence=ECO:0000255 |
| Structure 3D | X-ray crystallography (7) |
| Cross Reference PDB | 1AUT; 1LQV; 3F6U; 3JTC; 4DT7; 6M3B; 6M3C; |
| Mapped Pubmed ID | 10026158; 10068650; 10364092; 10781579; 10917896; 11238108; 11252894; 11513608; 11686318; 11761087; 11994010; 12029084; 12034704; 12052963; 12063259; 12067914; 12091344; 12091346; 12193972; 12195699; 12200374; 12407115; 12482406; 12540965; 12563316; 12588872; 12609838; 12871399; 12960605; 14517747; 14660667; 14675098; 14976057; 14982929; 15114590; 15116250; 15152000; 15178554; 15248212; 15308562; 15319291; 15337738; 15486064; 15505101; 15516929; 15582990; 15634335; 15665002; 15670041; 15705565; 15710622; 15769747; 15841323; 16095499; 16105054; 16113785; 16113807; 16113841; 16146761; 16246255; 16418283; 16420659; 16601829; 16607073; 16765424; 16867987; 16887970; 16935856; 17048007; 17054378; 17080006; 17107352; 17170365; 17254565; 17255099; 17284699; 17343367; 17549291; 17557119; 17569089; 17635713; 17646160; 17649706; 17677000; 17704111; 17849052; 17890957; 17932312; 17982464; 18045665; 18089851; 18160601; 18184931; 18198180; 18247057; 18329782; 18376272; 18424361; 18424440; 18451327; 18457995; 18489431; 18496716; 18521487; 18612533; 18680534; 18680736; 18702832; 18768782; 18779332; 18824642; 18953177; 18954896; 18974842; 19004141; 19052924; 19116273; 19129726; 19132190; 19190829; 19244160; 19244161; 19248107; 19279234; 19350118; 19373522; 1939075; 19404546; 19506951; 19535131; 19546541; 19587380; 19625989; 19644401; 19680809; 19682239; 19686413; 19691480; 19765701; 19774219; 19794411; 19874463; 19892996; 19913121; 19922983; 19924026; 19958090; 20066740; 20077116; 20127387; 20128871; 20156643; 20180321; 20187890; 2019570; 20334530; 20404340; 20409682; 20452482; 20485444; 20492471; 20499136; 20501981; 20628086; 20664913; 20673868; 20675283; 20802025; 20815936; 20873219; 20881312; 21044954; 21173154; 21176144; 21228323; 21392254; 21430357; 21474669; 21486865; 21575129; 21627595; 21777953; 21822632; 21826371; 21900206; 21901152; 22106258; 22109555; 22167755; 22168450; 22236035; 22236082; 22245244; 22371115; 22398431; 22425321; 22443383; 22447930; 22477541; 22535660; 22627591; 22664011; 22682140; 22690042; 22750541; 22817391; 22918506; 22944127; 22951146; 22964764; 22976599; 23174622; 23224054; 23312776; 23339473; 23377316; 23387557; 23389250; 23412516; 23454357; 23480827; 23484147; 23879866; 24051141; 2405901; 24096826; 24115609; 24158116; 24177324; 24233386; 24251463; 24410881; 24660539; 24759138; 24816905; 24911457; 24921658; 24951429; 2502206; 2505252; 25115555; 25149909; 25196808; 2538457; 25586317; 25643747; 25667200; 25730025; 25879167; 26082331; 26250584; 26354831; 26552309; 26663133; 26800564; 27172833; 27215212; 27345772; 2742826; 27456888; 27517348; 27561318; 27794481; 27882376; 28082259; 28111891; 28174134; 28186585; 28211163; 28294177; 28376316; 28408624; 28468828; 28607330; 2866798; 28834159; 28861852; 29218739; 29303701; 29363996; 29890521; 30159948; 3082357; 30865333; 31142255; 31254973; 31338992; 3134349; 31399531; 31680443; 31821907; 32532974; 32717757; 32781781; 32833261; 32924112; 32964666; 33812436; 34077937; 34112885; 34261859; 468991; 6323392; 7479820; 7499257; 7749828; 7831652; 8144529; 8338946; 8400292; 8473289; 8530480; 8947506; 9218519; 9888880; |
| Motif | |
| Gene Encoded By | |
| Mass | 52,071 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.21.69; |