[1]	NUCLEOTIDE SEQUENCE [MRNA]. DOI=10.1016/0022-2836(88)90331-2; PubMed=3379642 [NCBI, ExPASy, EBI, Israel, Japan] Irwin D.M., Robertson K.A., Macgillivray R.T.A.; "Structure and evolution of the bovine prothrombin gene."; J. Mol. Biol. 200:31-45(1988).
[2]	NUCLEOTIDE SEQUENCE [MRNA]. DOI=10.1021/bi00303a007; PubMed=6326805 [NCBI, ExPASy, EBI, Israel, Japan] McGillivray R.T.A., Davie E.W.; "Characterization of bovine prothrombin mRNA and its translation product."; Biochemistry 23:1626-1634(1984).
[3]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. STRAIN=Hereford; TISSUE=Fetal liver; NIH - Mammalian Gene Collection (MGC) project; Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[4]	PROTEIN SEQUENCE OF 44-625, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-120; ASN-144 AND ASN-419. Magnusson S., Sottrup-Jensen L., Petersen T.E., Claeys H.; (In) Hemker H.C., Veltkamp J.J. (eds.); Boerhaave symposium on prothrombin and related coagulation factors, pp.25-46, Leiden University Press, Leiden (1975).
[5]	GENE STRUCTURE. DOI=10.1021/bi00345a018; PubMed=3000440 [NCBI, ExPASy, EBI, Israel, Japan] Irwin D.M., Ahern K.G., Pearson G.D., McGillivray R.T.A.; "Characterization of the bovine prothrombin gene."; Biochemistry 24:6854-6861(1985).
[6]	X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF ACTIVATION PEPTIDE 1. DOI=10.1021/bi00362a001; PubMed=3741841 [NCBI, ExPASy, EBI, Israel, Japan] Park C.H., Tulinsky A.; "Three-dimensional structure of the kringle sequence: structure of prothrombin fragment 1."; Biochemistry 25:3977-3982(1986).
[7]	X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF ACTIVATION PEPTIDE 1. DOI=10.1016/0022-2836(91)90025-2; PubMed=1856869 [NCBI, ExPASy, EBI, Israel, Japan] Seshadri T.-P., Tulinsky A., Skrzypczak-Jankun E., Park C.H.; "Structure of bovine prothrombin fragment 1 refined at 2.25-A resolution."; J. Mol. Biol. 220:481-494(1991).
[8]	X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF ACTIVATION PEPTIDE 1 IN COMPLEX WITH CALCIUM IONS, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-120 AND ASN-144. DOI=10.1021/bi00124a016; PubMed=1547238 [NCBI, ExPASy, EBI, Israel, Japan] Soriano-Garcia M., Padmanabhan K., de Vos A.M., Tulinsky A.; "The Ca2+ ion and membrane binding structure of the Gla domain of Ca-prothrombin fragment 1."; Biochemistry 31:2554-2566(1992).
[9]	X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH FIBRINOGEN. PubMed=1560020 [NCBI, ExPASy, EBI, Israel, Japan] Martin P.D., Robertson W., Turk D., Huber R., Bode W., Edwards B.F.P.; "The structure of residues 7-16 of the A alpha-chain of human fibrinogen bound to bovine thrombin at 2.3-A resolution."; J. Biol. Chem. 267:7911-7920(1992).
[10]	X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 318-625 IN COMPLEX WITH HIRUDIN. PubMed=1517214 [NCBI, ExPASy, EBI, Israel, Japan] Vitali J., Martin P.D., Malkowski M.G., Robertson W.D., Lazar J.B., Winant R.C., Johnson P.H., Edwards B.F.P.; "The structure of a complex of bovine alpha-thrombin and recombinant hirudin at 2.8-A resolution."; J. Biol. Chem. 267:17670-17678(1992).
[11]	X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS). DOI=10.1016/0022-2836(92)91054-S; PubMed=1518046 [NCBI, ExPASy, EBI, Israel, Japan] Brandstetter H., Turk D., Hoeffken H.W., Grosse D., Stuerzebecher J., Martin P.D., Edwards B.F.P., Bode W.; "Refined 2.3 A X-ray crystal structure of bovine thrombin complexes formed with the benzamidine and arginine-based thrombin inhibitors NAPAP, 4-TAPAP and MQPA. A starting point for improving antithrombotics."; J. Mol. Biol. 226:1085-1089(1992).
[12]	X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF COMPLEX WITH ORNITHODORIN. PubMed=8947023 [NCBI, ExPASy, EBI, Israel, Japan] van de Locht A., Stubbs M.T., Bode W., Friedrich T., Bollschweiler C., Hoffken W., Huber R.; "The ornithodorin-thrombin crystal structure, a key to the TAP enigma?"; EMBO J. 15:6011-6017(1996).
[13]	X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF COMPLEX WITH TRIABIN. DOI=10.1073/pnas.94.22.11845; PubMed=9342325 [NCBI, ExPASy, EBI, Israel, Japan] Fuentes-Prior P., Noeske-Jungblut C., Donner P., Schleuning W.-D., Huber R., Bode W.; "Structure of the thrombin complex with triabin, a lipocalin-like exosite-binding inhibitor derived from a triatomine bug."; Proc. Natl. Acad. Sci. U.S.A. 94:11845-11850(1997).
[14]	X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 44-190 IN COMPLEX WITH CALCIUM AND LYSOPHOSPHATIDYLSERINE. DOI=10.1038/nsb971; PubMed=12923575 [NCBI, ExPASy, EBI, Israel, Japan] Huang M., Rigby A.C., Morelli X., Grant M.A., Huang G., Furie B., Seaton B., Furie B.C.; "Structural basis of membrane binding by Gla domains of vitamin K-dependent proteins."; Nat. Struct. Biol. 10:751-756(2003).

Comments

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 (By similarity).
CATALYTIC ACTIVITY: Selective cleavage of Arg-|-Gly bonds in fibrinogen to form fibrin and release fibrinopeptides A and B.
INTERACTION:
Q4W8J9:coa (xeno); NbExp=2; IntAct=EBI-990806, EBI-990838;
SUBCELLULAR LOCATION: Secreted, extracellular space.
TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma.
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.
MISCELLANEOUS: Prothrombin 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.
MISCELLANEOUS: Thrombin can itself cleave the N-terminal fragment (fragment 1) of the prothrombin, prior to its activation by factor Xa.
SIMILARITY: Belongs to the peptidase S1 family [view classification].
SIMILARITY: Contains 1 Gla (gamma-carboxy-glutamate) domain.
SIMILARITY: Contains 2 kringle domains.
SIMILARITY: Contains 1 peptidase S1 domain [view classification].

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

V00135; CAA23451.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
J00041; AAA30781.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC105201; AAI05202.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

S02537; TBBO.

NP_776302.1; -.

3D structure databases

PDB

1A0H; X-ray; 3.20 A; A/D=208-366, B/E=367-625.	[ExPASy / RCSB / EBI]
1AVG; X-ray; 2.60 A; H=367-625, L=326-366.	[ExPASy / RCSB / EBI]
1BBR; X-ray; 2.30 A; E=517-625, H=367-516, J/L/M=318-366, K/N=367-625.	[ExPASy / RCSB / EBI]
1ETR; X-ray; 2.20 A; H=367-625, L=318-366.	[ExPASy / RCSB / EBI]
1ETS; X-ray; 2.30 A; H=367-625, L=318-366.	[ExPASy / RCSB / EBI]
1ETT; X-ray; 2.50 A; H=367-625, L=318-366.	[ExPASy / RCSB / EBI]
1HRT; X-ray; 2.80 A; H=367-625, L=318-366.	[ExPASy / RCSB / EBI]
1ID5; X-ray; 2.50 A; H=367-622, L=318-366.	[ExPASy / RCSB / EBI]
1MKW; X-ray; 2.30 A; H=367-625, K=318-625, L=318-366.	[ExPASy / RCSB / EBI]
1MKX; X-ray; 2.20 A; H=367-625, K=318-625, L=318-366.	[ExPASy / RCSB / EBI]
1NL1; X-ray; 1.90 A; A=44-190.	[ExPASy / RCSB / EBI]
1NL2; X-ray; 2.30 A; A=44-189.	[ExPASy / RCSB / EBI]
1TBQ; X-ray; 3.10 A; H/K=367-625, J/L=318-366.	[ExPASy / RCSB / EBI]
1TBR; X-ray; 2.60 A; H/K=367-625, J/L=318-366.	[ExPASy / RCSB / EBI]
1TOC; X-ray; 3.10 A; A/C/E/G=318-366, B/D/F/H=367-625.	[ExPASy / RCSB / EBI]
1UCY; X-ray; 2.20 A; E=517-625, H=367-516, J/L/M=318-366, K/N=367-625.	[ExPASy / RCSB / EBI]
1UVT; X-ray; 2.50 A; H=367-625, L=318-366.	[ExPASy / RCSB / EBI]
1UVU; X-ray; 2.80 A; H=367-625, L=318-366.	[ExPASy / RCSB / EBI]
1VIT; X-ray; 3.20 A; F=367-516, G=517-625, H=367-625, L/M=318-366.	[ExPASy / RCSB / EBI]
1YCP; X-ray; 2.50 A; H=367-625, J/L=318-366, K=367-516, M=517-625.	[ExPASy / RCSB / EBI]
2A1D; X-ray; 3.50 A; A/E=326-366, B/F=367-625.	[ExPASy / RCSB / EBI]
2HPP; X-ray; 3.30 A; P=214-292.	[ExPASy / RCSB / EBI]
2ODY; X-ray; 2.35 A; A/C=318-366, B/D=367-625.	[ExPASy / RCSB / EBI]
2PF1; X-ray; 2.80 A; A=44-199.	[ExPASy / RCSB / EBI]
2PF2; X-ray; 2.20 A; A=44-199.	[ExPASy / RCSB / EBI]
2SPT; X-ray; 2.50 A; A=44-188.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

PDBsum

1A0H; -.
1AVG; -.
1BBR; -.
1ETR; -.
1ETS; -.
1ETT; -.
1HRT; -.
1ID5; -.
1MKW; -.
1MKX; -.
1NL1; -.
1NL2; -.
1TBQ; -.
1TBR; -.
1TOC; -.
1UCY; -.
1UVT; -.
1UVU; -.
1VIT; -.
1YCP; -.
2A1D; -.
2HPP; -.
2ODY; -.
2PF1; -.
2PF2; -.
2SPT; -.

ModBase

P00735.

Protein-protein interaction databases

DIP

DIP:6099N; -.

IntAct

P00735; -.

Protein family/group databases

MEROPS

S01.217; -.

Ontologies

GO:0005515;	Molecular function: protein binding (inferred from physical interaction from IntAct).
QuickGo view.

Family and domain databases

InterPro

IPR002383; Coagulation_factor_Gla.
IPR000001; Kringle.
IPR001254; Peptidase_S1_S6.
IPR001314; Peptidase_S1A.
IPR012051; Peptidase_S1A_pr.
IPR003966; Peptidase_S1A_prothrombin.
IPR000294; VitK_dep_GLA.
Graphical view of domain structure.

Gene3D

G3DSA:2.40.20.10; Kringle; 2.

PANTHER

PTHR19355:SF61; Peptidase_S1A_pr; 1.

Pfam

PF00594; Gla; 1.
PF00051; Kringle; 2.
PF00089; Trypsin; 1.
Pfam graphical view of domain structure.

PIRSF

PIRSF001149; Thrombin; 1.

PRINTS

PR00722; CHYMOTRYPSIN.
PR00001; GLABLOOD.
PR00018; KRINGLE.
PR01505; PROTHROMBIN.

ProDom

PD000395; Kringle; 2.
[Domain structure / List of seq. sharing at least 1 domain]

SMART

SM00069; GLA; 1.
SM00130; KR; 2.
SM00020; Tryp_SPc; 1.
SMART graphical view of domain structure.

PROSITE

PS00011; GLA_1; 1.
PS50998; GLA_2; 1.
PS00021; KRINGLE_1; 2.
PS50070; KRINGLE_2; 2.
PS50240; TRYPSIN_DOM; 1.
PS00134; TRYPSIN_HIS; 1.
PS00135; TRYPSIN_SER; 1.
PROSITE graphical view of domain structure (profiles).

Genome annotation databases

Ensembl

ENSBTAG00000007148; Bos taurus. [Contig view]

GeneID

280685; -.

KEGG

bta:280685; -.

Phylogenomic databases

HOVERGEN

P00735; -.

Other

LinkHub

P00735; -.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Acute phase; Blood coagulation; Calcium; Cleavage on pair of basic residues; Direct protein sequencing; Gamma-carboxyglutamic acid; Glycoprotein; Hydrolase; Kringle; Protease; Repeat; Secreted; Serine protease; Signal; Zymogen.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`SIGNAL`	`1 24`	`24`	`Potential.`
`PROPEP`	`25 43`	`19`		`PRO_0000028153`
`CHAIN`	`44 625`	`582`	`Prothrombin.`	`PRO_0000028154`
`PEPTIDE`	`44 199`	`156`	`Activation peptide fragment 1.`	`PRO_0000028155`
`PEPTIDE`	`200 317`	`118`	`Activation peptide fragment 2.`	`PRO_0000028156`
`CHAIN`	`318 366`	`49`	`Thrombin light chain.`	`PRO_0000028157`
`CHAIN`	`367 625`	`259`	`Thrombin heavy chain.`	`PRO_0000028158`
`DOMAIN`	`44 90`	`47`	`Gla.`
`DOMAIN`	`109 187`	`79`	`Kringle 1.`
`DOMAIN`	`214 292`	`79`	`Kringle 2.`
`DOMAIN`	`367 621`	`255`	`Peptidase S1.`
`REGION`	`554 576`	`23`	`High affinity receptor-binding region which is also known as the TP508 peptide (By similarity).`
`ACT_SITE`	`409 409`		`Charge relay system.`
`ACT_SITE`	`465 465`		`Charge relay system.`
`ACT_SITE`	`571 571`		`Charge relay system.`
`SITE`	`199 200`	`2`	`Cleavage; by thrombin.`
`SITE`	`317 318`	`2`	`Cleavage; by factor Xa.`
`SITE`	`366 367`	`2`	`Cleavage; by factor Xa.`
`MOD_RES`	`50 50`		`4-carboxyglutamate.`
`MOD_RES`	`51 51`		`4-carboxyglutamate.`
`MOD_RES`	`58 58`		`4-carboxyglutamate.`
`MOD_RES`	`60 60`		`4-carboxyglutamate.`
`MOD_RES`	`63 63`		`4-carboxyglutamate.`
`MOD_RES`	`64 64`		`4-carboxyglutamate.`
`MOD_RES`	`69 69`		`4-carboxyglutamate.`
`MOD_RES`	`70 70`		`4-carboxyglutamate.`
`MOD_RES`	`73 73`		`4-carboxyglutamate.`
`MOD_RES`	`76 76`		`4-carboxyglutamate.`
`CARBOHYD`	`120 120`		`N-linked (GlcNAc...).`
`CARBOHYD`	`144 144`		`N-linked (GlcNAc...).`
`CARBOHYD`	`419 419`		`N-linked (GlcNAc...).`
`DISULFID`	`61 66`
`DISULFID`	`91 104`
`DISULFID`	`109 187`
`DISULFID`	`130 170`
`DISULFID`	`158 182`
`DISULFID`	`214 292`
`DISULFID`	`235 275`
`DISULFID`	`263 287`
`DISULFID`	`339 485`		`Interchain (between light and heavy chains).`
`DISULFID`	`394 410`
`DISULFID`	`539 553`
`DISULFID`	`567 597`
`VARIANT`	`600 600`	`1`	`D -> N.`
`CONFLICT`	`231 231`		`S -> H (in Ref. 2; AAA30781).`
`CONFLICT`	`249 249`		`D -> H (in Ref. 2; AAA30781).`
`CONFLICT`	`288 288`		`D -> N (in Ref. 4; AA sequence).`
`CONFLICT`	`353 353`		`Q -> E (in Ref. 4; AA sequence).`
`CONFLICT`	`355 355`		`E -> Q (in Ref. 4; AA sequence).`
`CONFLICT`	`358 358`		`L -> P (in Ref. 3; AAI05202).`
`CONFLICT`	`549 550`		`DN -> ND (in Ref. 4; AA sequence).`
`STRAND`	`47 49`	`3`
`HELIX`	`50 52`	`3`
`HELIX`	`57 61`	`5`
`HELIX`	`68 74`	`7`
`HELIX`	`78 90`	`13`
`TURN`	`91 93`	`3`
`HELIX`	`98 106`	`9`
`STRAND`	`108 110`	`3`
`STRAND`	`137 139`	`3`
`TURN`	`145 147`	`3`
`STRAND`	`168 174`	`7`
`STRAND`	`179 181`	`3`
`STRAND`	`192 194`	`3`
`HELIX`	`217 219`	`3`
`STRAND`	`238 240`	`3`
`HELIX`	`243 246`	`4`
`STRAND`	`274 276`	`3`
`STRAND`	`278 280`	`3`
`STRAND`	`284 286`	`3`
`STRAND`	`291 293`	`3`
`STRAND`	`310 313`	`4`
`STRAND`	`321 323`	`3`
`TURN`	`328 330`	`3`
`TURN`	`337 340`	`4`
`TURN`	`343 345`	`3`
`HELIX`	`346 348`	`3`
`HELIX`	`355 362`	`8`
`STRAND`	`381 386`	`6`
`TURN`	`387 390`	`4`
`STRAND`	`391 398`	`8`
`STRAND`	`400 406`	`7`
`HELIX`	`408 410`	`3`
`HELIX`	`414 416`	`3`
`TURN`	`422 424`	`3`
`STRAND`	`425 430`	`6`
`STRAND`	`434 436`	`3`
`HELIX`	`439 441`	`3`
`STRAND`	`442 445`	`4`
`STRAND`	`447 452`	`6`
`TURN`	`458 461`	`4`
`STRAND`	`467 473`	`7`
`HELIX`	`489 495`	`7`
`STRAND`	`501 508`	`8`
`STRAND`	`527 533`	`7`
`HELIX`	`536 541`	`6`
`STRAND`	`551 554`	`4`
`HELIX`	`558 560`	`3`
`STRAND`	`574 578`	`5`
`TURN`	`580 582`	`3`
`STRAND`	`585 593`	`9`
`STRAND`	`595 598`