MGP Database

New search | Record Overview | Ontology/Pathway Information | Domain Information | UniProt Annotations | Related Proteins
MGP001004

UniProt Annotations

Entry Information
Gene Namecoagulation factor II (thrombin)
Protein EntryTHRB_HUMAN
UniProt IDP00734
SpeciesHuman
Comments
Comment typeDescription
Catalytic ActivitySelective cleavage of Arg-|-Gly bonds in fibrinogen to form fibrin and release fibrinopeptides A and B.
DiseaseFactor II deficiency (FA2D) [MIM:613679]: A very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels. {ECO:0000269|PubMed:1349838, ECO:0000269|PubMed:1354985, ECO:0000269|PubMed:1421398, ECO:0000269|PubMed:14962227, ECO:0000269|PubMed:2719946, ECO:0000269|PubMed:3242619, ECO:0000269|PubMed:3567158, ECO:0000269|PubMed:3771562, ECO:0000269|PubMed:3801671, ECO:0000269|PubMed:6405779, ECO:0000269|PubMed:7792730, ECO:0000269|PubMed:7865694}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseIschemic stroke (ISCHSTR) [MIM:601367]: A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. {ECO:0000269|PubMed:15534175}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
DiseasePregnancy loss, recurrent, 2 (RPRGL2) [MIM:614390]: A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions. {ECO:0000269|PubMed:11506076}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
DiseaseThrombophilia due to thrombin defect (THPH1) [MIM:188050]: A multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=The disease is caused by mutations affecting the gene represented in this entry. A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis.
Enzyme RegulationInhibited by SERPINA5. {ECO:0000269|PubMed:6323392}.
FunctionThrombin, 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}.
InteractionQ846V4:- (xeno); NbExp=5; IntAct=EBI-297094, EBI-989571; P07204:THBD; NbExp=4; IntAct=EBI-297094, EBI-941422;
MiscellaneousIt is not known whether 1 or 2 smaller activation peptides, with additional cleavage after Arg-314, are released in natural blood clotting.
MiscellaneousProthrombin is activated on the surface of a phospholipid membrane that binds the amino end of prothrombin and factors Va and Xa in Ca-dependent interactions; factor Xa removes the activation peptide and cleaves the remaining part into light and heavy chains. The activation process starts slowly because factor V itself has to be activated by the initial, small amounts of thrombin.
MiscellaneousThe cleavage after Arg-198, observed in vitro, does not occur in plasma.
MiscellaneousThrombin can itself cleave the N-terminal fragment (fragment 1) of the prothrombin, prior to its activation by factor Xa.
PharmaceuticalThe peptide TP508 also known as Chrysalin (Orthologic) could be used to accelerate repair of both soft and hard tissues.
PtmN-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}.
PtmThe 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}.
SimilarityBelongs to the peptidase S1 family. {ECO:0000255|PROSITE-ProRule:PRU00274}.
SimilarityContains 1 Gla (gamma-carboxy-glutamate) domain. {ECO:0000255|PROSITE-ProRule:PRU00463}.
SimilarityContains 1 peptidase S1 domain. {ECO:0000255|PROSITE- ProRule:PRU00274}.
SimilarityContains 2 kringle domains. {ECO:0000255|PROSITE- ProRule:PRU00121}.
Subcellular LocationSecreted, extracellular space.
SubunitHeterodimer (named alpha-thrombin) of a light and a heavy chain; disulfide-linked. Forms a heterodimer with SERPINA5. {ECO:0000269|PubMed:11493008, ECO:0000269|PubMed:16763681, ECO:0000269|PubMed:17685615, ECO:0000269|PubMed:18291642, ECO:0000269|PubMed:18362344, ECO:0000269|PubMed:2369893, ECO:0000269|PubMed:2374926}.
Tissue SpecificityExpressed by the liver and secreted in plasma.
Web ResourceName=SeattleSNPs; URL="http://pga.gs.washington.edu/data/f2/";
Web ResourceName=Wikipedia; Note=Thrombin entry; URL="http://en.wikipedia.org/wiki/Thrombin";
  logo