THRB_RAT
ID THRB_RAT Reviewed; 617 AA.
AC P18292;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Prothrombin;
DE EC=3.4.21.5;
DE AltName: Full=Coagulation factor II;
DE Contains:
DE RecName: Full=Activation peptide fragment 1;
DE Contains:
DE RecName: Full=Activation peptide fragment 2;
DE Contains:
DE RecName: Full=Thrombin light chain;
DE Contains:
DE RecName: Full=Thrombin heavy chain;
DE Flags: Precursor;
GN Name=F2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=2377469; DOI=10.1093/nar/18.14.4251;
RA Dihanich M., Monard D.;
RT "cDNA sequence of rat prothrombin.";
RL Nucleic Acids Res. 18:4251-4251(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 383-617.
RC TISSUE=Liver;
RX PubMed=1557383; DOI=10.1073/pnas.89.7.2779;
RA Banfield D.K., Macgillivray R.T.;
RT "Partial characterization of vertebrate prothrombin cDNAs: amplification
RT and sequence analysis of the B chain of thrombin from nine different
RT species.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:2779-2783(1992).
RN [3]
RP CHARACTERIZATION OF THE TP508 PEPTIDE.
RX PubMed=1373740; DOI=10.1172/jci115737;
RA Carney D.H., Mann R., Redin W.R., Pernia S.D., Berry D., Heggers J.P.,
RA Hayward P.G., Robson M.C., Christie J., Annable C., Fenton W.J. II,
RA Glenn K.C.;
RT "Enhancement of incisional wound healing and neovascularization in normal
RT rats by thrombin and synthetic thrombin receptor-activating peptides.";
RL J. Clin. Invest. 89:1469-1477(1992).
RN [4]
RP CHARACTERIZATION OF THE TP508 PEPTIDE.
RX PubMed=15885490; DOI=10.1016/j.orthres.2004.10.002;
RA Wang H., Li X., Tomin E., Doty S.B., Lane J.M., Carney D.H., Ryaby J.T.;
RT "Thrombin peptide (TP508) promotes fracture repair by up-regulating
RT inflammatory mediators, early growth factors, and increasing
RT angiogenesis.";
RL J. Orthop. Res. 23:671-679(2005).
CC -!- FUNCTION: Thrombin, which cleaves bonds after Arg and Lys, converts
CC fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in
CC complex with thrombomodulin, protein C. Functions in blood homeostasis,
CC inflammation and wound healing.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Selective cleavage of Arg-|-Gly bonds in fibrinogen to form
CC fibrin and release fibrinopeptides A and B.; EC=3.4.21.5;
CC -!- ACTIVITY REGULATION: Inhibited by SERPINA5. {ECO:0000250}.
CC -!- SUBUNIT: Heterodimer (named alpha-thrombin) of a light and a heavy
CC chain; disulfide-linked. Forms a heterodimer with SERPINA5. In plasma,
CC interacts (via N-terminus) with alpha-1-microglobulin; this interaction
CC does not prevent the activation of prothrombin to thrombin.
CC {ECO:0000250|UniProtKB:P00734}.
CC -!- PTM: The gamma-carboxyglutamyl residues, which bind calcium ions,
CC result from the carboxylation of glutamyl residues by a microsomal
CC enzyme, the vitamin K-dependent carboxylase. The modified residues are
CC necessary for the calcium-dependent interaction with a negatively
CC charged phospholipid surface, which is essential for the conversion of
CC prothrombin to thrombin (By similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: Prothrombin is activated on the surface of a
CC phospholipid membrane that binds the amino end of prothrombin and
CC factors Va and Xa in Ca-dependent interactions; factor Xa removes the
CC activation peptide and cleaves the remaining part into light and heavy
CC chains. The activation process starts slowly because factor V itself
CC has to be activated by the initial, small amounts of thrombin.
CC -!- MISCELLANEOUS: Thrombin can itself cleave the N-terminal fragment
CC (fragment 1) of the prothrombin, prior to its activation by factor Xa.
CC -!- MISCELLANEOUS: The peptide TP508 is able to accelerate repair of both
CC soft and hard tissues.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; X52835; CAA37017.1; -; Transcribed_RNA.
DR EMBL; M81397; AAA42240.1; -; mRNA.
DR PIR; S10511; S10511.
DR AlphaFoldDB; P18292; -.
DR SMR; P18292; -.
DR STRING; 10116.ENSRNOP00000022233; -.
DR BindingDB; P18292; -.
DR ChEMBL; CHEMBL3078; -.
DR MEROPS; S01.217; -.
DR GlyGen; P18292; 4 sites.
DR iPTMnet; P18292; -.
DR PhosphoSitePlus; P18292; -.
DR jPOST; P18292; -.
DR PaxDb; P18292; -.
DR PRIDE; P18292; -.
DR UCSC; RGD:61996; rat.
DR RGD; 61996; F2.
DR eggNOG; ENOG502QTSX; Eukaryota.
DR InParanoid; P18292; -.
DR PhylomeDB; P18292; -.
DR Reactome; R-RNO-140837; Intrinsic Pathway of Fibrin Clot Formation.
DR Reactome; R-RNO-140875; Common Pathway of Fibrin Clot Formation.
DR Reactome; R-RNO-159740; Gamma-carboxylation of protein precursors.
DR Reactome; R-RNO-159763; Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus.
DR Reactome; R-RNO-159782; Removal of aminoterminal propeptides from gamma-carboxylated proteins.
DR Reactome; R-RNO-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-RNO-375276; Peptide ligand-binding receptors.
DR Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-RNO-416476; G alpha (q) signalling events.
DR Reactome; R-RNO-456926; Thrombin signalling through proteinase activated receptors (PARs).
DR Reactome; R-RNO-76009; Platelet Aggregation (Plug Formation).
DR PRO; PR:P18292; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:1905370; C:serine-type endopeptidase complex; ISO:RGD.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0008201; F:heparin binding; ISO:RGD.
DR GO; GO:0001530; F:lipopolysaccharide binding; ISO:RGD.
DR GO; GO:0008233; F:peptidase activity; ISO:RGD.
DR GO; GO:0004252; F:serine-type endopeptidase activity; ISO:RGD.
DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD.
DR GO; GO:0070053; F:thrombospondin receptor activity; ISO:RGD.
DR GO; GO:0006953; P:acute-phase response; IEA:UniProtKB-KW.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; ISO:RGD.
DR GO; GO:0007596; P:blood coagulation; IDA:RGD.
DR GO; GO:0072377; P:blood coagulation, common pathway; ISO:RGD.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISO:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
DR GO; GO:0051838; P:cytolysis by host of symbiont cells; ISO:RGD.
DR GO; GO:0042730; P:fibrinolysis; ISO:RGD.
DR GO; GO:0048712; P:negative regulation of astrocyte differentiation; ISO:RGD.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; ISO:RGD.
DR GO; GO:0045861; P:negative regulation of proteolysis; ISO:RGD.
DR GO; GO:0070945; P:neutrophil-mediated killing of gram-negative bacterium; ISO:RGD.
DR GO; GO:0030168; P:platelet activation; ISO:RGD.
DR GO; GO:0030194; P:positive regulation of blood coagulation; IMP:RGD.
DR GO; GO:0030307; P:positive regulation of cell growth; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; ISO:RGD.
DR GO; GO:0090218; P:positive regulation of lipid kinase activity; ISO:RGD.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:RGD.
DR GO; GO:1900738; P:positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; ISO:RGD.
DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; ISO:RGD.
DR GO; GO:0006508; P:proteolysis; ISO:RGD.
DR GO; GO:0008360; P:regulation of cell shape; ISO:RGD.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0014854; P:response to inactivity; IEP:RGD.
DR GO; GO:1904016; P:response to Thyroglobulin triiodothyronine; IEP:RGD.
DR GO; GO:1905225; P:response to thyrotropin-releasing hormone; IEP:RGD.
DR GO; GO:0097068; P:response to thyroxine; IEP:RGD.
DR GO; GO:0009611; P:response to wounding; ISO:RGD.
DR GO; GO:0031638; P:zymogen activation; ISO:RGD.
DR CDD; cd00108; KR; 2.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 2.40.20.10; -; 2.
DR Gene3D; 4.10.140.10; -; 1.
DR InterPro; IPR035972; GLA-like_dom_SF.
DR InterPro; IPR000294; GLA_domain.
DR InterPro; IPR000001; Kringle.
DR InterPro; IPR013806; Kringle-like.
DR InterPro; IPR018056; Kringle_CS.
DR InterPro; IPR038178; Kringle_sf.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR003966; Prothrombin/thrombin.
DR InterPro; IPR018992; Thrombin_light_chain.
DR InterPro; IPR037111; Thrombin_light_chain_sf.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR PANTHER; PTHR24254:SF10; PTHR24254:SF10; 1.
DR Pfam; PF00594; Gla; 1.
DR Pfam; PF00051; Kringle; 2.
DR Pfam; PF09396; Thrombin_light; 1.
DR Pfam; PF00089; Trypsin; 1.
DR PIRSF; PIRSF001149; Thrombin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR PRINTS; PR00001; GLABLOOD.
DR PRINTS; PR01505; PROTHROMBIN.
DR SMART; SM00069; GLA; 1.
DR SMART; SM00130; KR; 2.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57440; SSF57440; 2.
DR SUPFAM; SSF57630; SSF57630; 1.
DR PROSITE; PS00011; GLA_1; 1.
DR PROSITE; PS50998; GLA_2; 1.
DR PROSITE; PS00021; KRINGLE_1; 2.
DR PROSITE; PS50070; KRINGLE_2; 2.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW Acute phase; Blood coagulation; Calcium;
KW Cleavage on pair of basic residues; Disulfide bond;
KW Gamma-carboxyglutamic acid; Glycoprotein; Hemostasis; Hydrolase; Kringle;
KW Protease; Reference proteome; Repeat; Serine protease; Signal; Zymogen.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..43
FT /id="PRO_0000028177"
FT CHAIN 44..617
FT /note="Prothrombin"
FT /id="PRO_0000028178"
FT PEPTIDE 44..200
FT /note="Activation peptide fragment 1"
FT /id="PRO_0000028179"
FT PEPTIDE 201..323
FT /note="Activation peptide fragment 2"
FT /id="PRO_0000028180"
FT CHAIN 324..359
FT /note="Thrombin light chain"
FT /id="PRO_0000028181"
FT CHAIN 360..617
FT /note="Thrombin heavy chain"
FT /id="PRO_0000028182"
FT DOMAIN 44..90
FT /note="Gla"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463"
FT DOMAIN 109..187
FT /note="Kringle 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 215..292
FT /note="Kringle 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 360..614
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 547..569
FT /note="High affinity receptor-binding region which is also
FT known as the TP508 peptide"
FT ACT_SITE 402
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 458
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 564
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT SITE 200..201
FT /note="Cleavage; by thrombin"
FT SITE 323..324
FT /note="Cleavage; by factor Xa"
FT SITE 359..360
FT /note="Cleavage; by factor Xa"
FT MOD_RES 50
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00735,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 51
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00735,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 58
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00735,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 60
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00735,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 63
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00735,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 64
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00735,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 69
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00735,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 70
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00735,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 73
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00735,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 76
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00735,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT CARBOHYD 120
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 412
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 552
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 61..66
FT /evidence="ECO:0000250"
FT DISULFID 91..104
FT /evidence="ECO:0000250"
FT DISULFID 109..187
FT /evidence="ECO:0000250"
FT DISULFID 130..170
FT /evidence="ECO:0000250"
FT DISULFID 158..182
FT /evidence="ECO:0000250"
FT DISULFID 215..292
FT /evidence="ECO:0000250"
FT DISULFID 236..276
FT /evidence="ECO:0000250"
FT DISULFID 264..287
FT /evidence="ECO:0000250"
FT DISULFID 332..478
FT /note="Interchain (between light and heavy chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121,
FT ECO:0000255|PROSITE-ProRule:PRU00274, ECO:0000255|PROSITE-
FT ProRule:PRU00463"
FT DISULFID 387..403
FT /evidence="ECO:0000250"
FT DISULFID 532..546
FT /evidence="ECO:0000250"
FT DISULFID 560..590
FT /evidence="ECO:0000250"
SQ SEQUENCE 617 AA; 70412 MW; AD27D1B71445DB1D CRC64;
MLHVRGLGLP GCLALAALAS LVHSQHVFLA PQQALSLLQR VRRANSGFLE ELRKGNLERE
CVEEQCSYEE AFEALESPQD TDVFWAKYTV CDSVRKPRET FMDCLEGRCA MDLGLNYHGN
VSVTHTGIEC QLWRSRYPHR PDINSTTHPG ADLKENFCRN PDSSTSGPWC YTTDPTVRRE
ECSIPVCGQE GRTTVKMTPR SRGSKENLSP PLGECLLERG RLYQGNLAVT TLGSPCLAWD
SLPTKTLSKY QNFDPEVKLV QNFCRNPDRD EEGAWCFVAQ QPGFEYCSLN YCDEAVGEEN
HDGDESIAGR TTDAEFHTFF DERTFGLGEA DCGLRPLFEK KSLTDKTEKE LLDSYIDGRI
VEGWDAEKGI APWQVMLFRK SPQELLCGAS LISDRWVLTA AHCILYPPWD KNFTENDLLV
RIGKHSRTRY ERNVEKISML EKIYIHPRYN WRENLDRDIA LLKLKKPVPF SDYIHPVCLP
DKQTVTSLLQ AGYKGRVTGW GNLRETWTTN INEIQPSVLQ VVNLPIVERP VCKASTRIRI
TDNMFCAGFK VNDTKRGDAC EGDSGGPFVM KSPYNHRWYQ MGIVSWGEGC DRNGKYGFYT
HVFRLKRWMQ KVIDQHR
