Protein: P00734

UniprotKB AC UniprotKB ID Gene name Full name Species Curated set
P00734 (Uniprot) THRB_HUMAN F2 Prothrombin human Yes
Uniprot: 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.
Dissimilar Functions Manual Curation

Function 1: Thrombin protease (cleaves fibrinogen to produce fibrin in the blood-clotting cascade).

Function 2: Ligand for cell surface receptor (ligand for G-protein coupled receptor PAR1 activation of this receptor causes platelets to stick together).

Publications (PMID): 1672265

Biological Processes
Module ID (MoonGO) GO ID (BP) GO Name
22 GO:0019538 protein metabolic process
22 GO:0007165 signal transduction
199 GO:0006464 cellular protein modification process
199 GO:0060255 regulation of macromolecule metabolic process
199 GO:0007165 signal transduction
429 GO:0016070 RNA metabolic process
429 GO:0034645 cellular macromolecule biosynthetic process
429 GO:0044271 cellular nitrogen compound biosynthetic process
429 GO:0019538 protein metabolic process
429 GO:0010468 regulation of gene expression
429 GO:0010556 regulation of macromolecule biosynthetic process
429 GO:0019219 regulation of nucleobase-containing compound metabolic process
430 GO:0019538 protein metabolic process
431 GO:0019538 protein metabolic process
431 GO:0060255 regulation of macromolecule metabolic process
Cellular Components
Module ID (MoonGO) GO ID (CC) GO Name
22 GO:0005576 extracellular region
22 GO:0005886 plasma membrane
22 GO:0031982 vesicle
199 GO:0012505 endomembrane system
199 GO:0005576 extracellular region
199 GO:0070013 intracellular organelle lumen
235 GO:0012505 endomembrane system
235 GO:0016021 integral component of membrane
429 GO:0070013 intracellular organelle lumen
429 GO:0005634 nucleus
431 GO:0005829 cytosol
GO ID (BP) GO Name Evidence Code (GO EC)
GO:0001934 positive regulation of protein phosphorylation IDA
GO:0006465 signal peptide processing TAS
GO:0006508 proteolysis TAS
GO:0006888 ER to Golgi vesicle-mediated transport TAS
GO:0006953 acute-phase response IEA
GO:0007166 cell surface receptor signaling pathway IDA
GO:0007186 G-protein coupled receptor signaling pathway TAS
GO:0007275 multicellular organism development TAS
GO:0007596 blood coagulation TAS
GO:0007597 blood coagulation, intrinsic pathway TAS
GO:0008284 positive regulation of cell proliferation IEA
GO:0008360 regulation of cell shape IEA
GO:0009611 response to wounding IDA
GO:0010469 regulation of receptor activity IEA
GO:0010544 negative regulation of platelet activation TAS
GO:0014068 positive regulation of phosphatidylinositol 3-kinase signaling IEA
GO:0017187 peptidyl-glutamic acid carboxylation TAS
GO:0030168 platelet activation TAS
GO:0030193 regulation of blood coagulation TAS
GO:0030194 positive regulation of blood coagulation IDA
GO:0030307 positive regulation of cell growth IEA
GO:0030449 regulation of complement activation TAS
GO:0032967 positive regulation of collagen biosynthetic process IDA
GO:0042730 fibrinolysis IDA
GO:0044267 cellular protein metabolic process TAS
GO:0045861 negative regulation of proteolysis IDA
GO:0048712 negative regulation of astrocyte differentiation IDA
GO:0050900 leukocyte migration TAS
GO:0051281 positive regulation of release of sequestered calcium ion into cytosol IDA
GO:0051480 regulation of cytosolic calcium ion concentration IDA
GO:0051838 cytolysis by host of symbiont cells IDA
GO:0051918 negative regulation of fibrinolysis TAS
GO:0061844 antimicrobial humoral immune response mediated by antimicrobial peptide IDA
GO:0070945 neutrophil mediated killing of gram-negative bacterium IDA
GO:0090218 positive regulation of lipid kinase activity IDA
GO:1900016 negative regulation of cytokine production involved in inflammatory response IDA
GO:1900182 positive regulation of protein localization to nucleus IDA
GO:1900738 positive regulation of phospholipase C-activating G-protein coupled receptor signaling pathway IDA
GO:2000366 positive regulation of STAT protein import into nucleus NAS
GO:2000379 positive regulation of reactive oxygen species metabolic process IDA
GO ID (CC) GO Name Evidence Code (GO EC)
GO:0005576 extracellular region TAS
GO:0005615 extracellular space IDA
GO:0005788 endoplasmic reticulum lumen TAS
GO:0005796 Golgi lumen TAS
GO:0005886 plasma membrane TAS
GO:0009897 external side of plasma membrane IDA
GO:0070062 extracellular exosome IDA
GO:0072562 blood microparticle IDA
No pairs of PrOnto dissimilar CC GO terms found.
PMID Article Title
266717 Amino acid sequence of human prothrombin fragments 1 and 2.
873923 Primary structure of human prethrombin 2 and alpha-thrombin.
1349838 Detection of a single base substitution of the gene for prothrombin Tokushima. The application of PCR-SSCP for the genetic and molecular analysis of dysprothrombinemia.
1354985 Prothrombin Salakta: substitution of glutamic acid-466 by alanine reduces the fibrinogen clotting activity and the esterase activity.
1421398 Prothrombin Himi: a compound heterozygote for two dysfunctional prothrombin molecules (Met-337-->Thr and Arg-388-->His).
2369893 Crystal structure of the thrombin-hirudin complex: a novel mode of serine protease inhibition.
2374926 The structure of a complex of recombinant hirudin and human alpha-thrombin.
2583108 The refined 1.9 A crystal structure of human alpha-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment.
2719946 Substitution of valine for glycine-558 in the congenital dysthrombin thrombin Quick II alters primary substrate specificity.
2825773 Nucleotide sequence of the gene for human prothrombin.
2856554 Synthetic peptides bind to high-affinity thrombin receptors and modulate thrombin mitogenesis.
3242619 Identification of the primary structural defect in the dysthrombin thrombin Quick I: substitution of cysteine for arginine-382.
3567158 Prothrombin Tokushima, a replacement of arginine-418 by tryptophan that impairs the fibrinogen clotting activity of derived thrombin Tokushima.
3759958 Prothrombin fragment 1 X 2 X 3, a major product of prothrombin activation in human plasma.
3771562 Molecular defect of prothrombin Barcelona. Substitution of cysteine for arginine at residue 273.
3801671 Prothrombin Tokushima: characterization of dysfunctional thrombin derived from a variant of human prothrombin.
6305407 Characterization of the complementary deoxyribonucleic acid and gene coding for human prothrombin.
6323392 Mechanism of inhibition of activated protein C by protein C inhibitor.
6405779 Determination of the amino acid substitution in human prothrombin type 3 (157 Glu leads to Lys) and the localization of a third thrombin cleavage site.
7792730 Prothrombin Frankfurt: a dysfunctional prothrombin characterized by substitution of Glu-466 by Ala.
7865694 Prothrombin Padua I: incomplete activation due to an amino acid substitution at a factor Xa cleavage site.
8071320 Crystallographic structure of human gamma-thrombin.
8073540 Isolation and partial characterization of crystal matrix protein as a potent inhibitor of calcium oxalate crystal aggregation: evidence of activation peptide of human prothrombin.
8251938 Changes in interactions in complexes of hirudin derivatives and human alpha-thrombin due to different crystal forms.
9214615 The thrombin E192Q-BPTI complex reveals gross structural rearrangements: implications for the interaction with antithrombin and thrombomodulin.
10051558 Unexpected crucial role of residue 225 in serine proteases.
10391209 Characterization of single-nucleotide polymorphisms in coding regions of human genes.
11493008 Inhibition of human alpha-thrombin by a phosphonate tripeptide proceeds via a metastable pentacoordinated phosphorus intermediate.
11506076 Thrombophilic gene mutations and recurrent spontaneous abortion: prothrombin mutation increases the risk in the first trimester.
14702039 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14760718 Screening for N-glycosylated proteins by liquid chromatography mass spectrometry.
14962227 Prothrombin Shanghai: hypoprothrombinaemia caused by substitution of Gla29 by Gly.
15489334 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15534175 Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls.
15885491 rhBMP-2, rhVEGF(165), rhPTN and thrombin-related peptide, TP508 induce chemotaxis of human osteoblasts and microvascular endothelial cells.
16335952 Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.
16763681 Multipolar interactions in the D pocket of thrombin: large differences between tricyclic imide and lactam inhibitors.
17244316 Thrombin peptide Chrysalin stimulates healing of diabetic foot ulcers in a placebo-controlled phase I/II study.
17685615 Crystal structure of a biosynthetic sulfo-hirudin complexed to thrombin.
18291642 Structure-based design of novel groups for use in the P1 position of thrombin inhibitor scaffolds. Part 2: N-acetamidoimidazoles.
18362344 Molecular basis of thrombin recognition by protein C inhibitor revealed by the 1.6-A structure of the heparin-bridged complex.
19139490 A strategy for precise and large scale identification of core fucosylated glycoproteins.
19159218 Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.
19838169 Enrichment of glycopeptides for glycan structure and attachment site identification.
22028381 Quantitative detection of single amino acid polymorphisms by targeted proteomics.
22171320 Human urinary glycoproteomics; attachment site specific analysis of N-and O-linked glycosylations by CID and ECD.
24275569 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
OMIM ID Disease Name
188050 Thrombophilia due to thrombin defect
601367 Ischemic stroke
613679 Factor II deficiency
614390 Pregnancy loss, recurrent, 2
Domain Name Domain ID Source
TBHU A29351 PIR
Kringle IPR000001 InterPro
GLA_domain IPR000294 InterPro
Trypsin_dom IPR001254 InterPro
Peptidase_S1A IPR001314 InterPro
Prothrombin/thrombin IPR003966 InterPro
Peptidase_S1_PA IPR009003 InterPro
Kringle-like IPR013806 InterPro
Kringle_CS IPR018056 InterPro
TRYPSIN_HIS IPR018114 InterPro
Thrombin_light_chain IPR018992 InterPro
TRYPSIN_SER IPR033116 InterPro
GLA-like_dom_SF IPR035972 InterPro
Thrombin_light_chain_sf IPR037111 InterPro
Kringle_sf IPR038178 InterPro
Kringle PF00051 Pfam
Trypsin PF00089 Pfam
Gla PF00594 Pfam
Thrombin_light PF09396 Pfam
Thrombin PIRSF001149 PIRSF
GLABLOOD PR00001 PRINTS
CHYMOTRYPSIN PR00722 PRINTS
PROTHROMBIN PR01505 PRINTS
GLA_1 PS00011 PROSITE
KRINGLE_1 PS00021 PROSITE
TRYPSIN_HIS PS00134 PROSITE
TRYPSIN_SER PS00135 PROSITE
KRINGLE_2 PS50070 PROSITE
TRYPSIN_DOM PS50240 PROSITE
GLA_2 PS50998 PROSITE
PTHR24254:SF10 PTHR24254:SF10 PANTHER
Tryp_SPc SM00020 SMART
GLA SM00069 SMART
KR SM00130 SMART
SSF50494 SSF50494 SUPFAM
SSF57440 SSF57440 SUPFAM
SSF57630 SSF57630 SUPFAM
Tryp_SPc cd00190 CDD