SubmitCancel

Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

P19221

- THRB_MOUSE

UniProt

P19221 - THRB_MOUSE

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Prothrombin

Gene
F2, Cf2
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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 activityi

Selective cleavage of Arg-|-Gly bonds in fibrinogen to form fibrin and release fibrinopeptides A and B.

Enzyme regulationi

Inhibited by SERPINA5 By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei200 – 2012Cleavage; by thrombin
Sitei324 – 3252Cleavage; by factor Xa
Sitei360 – 3612Cleavage; by factor Xa
Active sitei403 – 4031Charge relay system By similarity
Active sitei459 – 4591Charge relay system By similarity
Active sitei565 – 5651Charge relay system By similarity

GO - Molecular functioni

  1. calcium ion binding Source: InterPro
  2. peptidase activity Source: MGI
  3. protein binding Source: MGI
  4. serine-type endopeptidase activity Source: MGI
  5. thrombospondin receptor activity Source: Ensembl

GO - Biological processi

  1. acute-phase response Source: UniProtKB-KW
  2. cytosolic calcium ion homeostasis Source: Ensembl
  3. fibrinolysis Source: Ensembl
  4. negative regulation of astrocyte differentiation Source: Ensembl
  5. negative regulation of proteolysis Source: Ensembl
  6. platelet activation Source: MGI
  7. positive regulation of blood coagulation Source: Ensembl
  8. positive regulation of cell growth Source: MGI
  9. positive regulation of cell proliferation Source: MGI
  10. positive regulation of collagen biosynthetic process Source: Ensembl
  11. positive regulation of phosphatidylinositol 3-kinase signaling Source: MGI
  12. positive regulation of phospholipase C-activating G-protein coupled receptor signaling pathway Source: Ensembl
  13. positive regulation of protein phosphorylation Source: Ensembl
  14. positive regulation of reactive oxygen species metabolic process Source: Ensembl
  15. positive regulation of release of sequestered calcium ion into cytosol Source: Ensembl
  16. regulation of cell shape Source: MGI
  17. regulation of gene expression Source: MGI
  18. thrombin receptor signaling pathway Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Acute phase, Blood coagulation, Hemostasis

Keywords - Ligandi

Calcium

Enzyme and pathway databases

ReactomeiREACT_207651. G alpha (q) signalling events.
REACT_220322. Thrombin signalling through proteinase activated receptors (PARs).
REACT_225233. Cell surface interactions at the vascular wall.

Protein family/group databases

MEROPSiS01.217.

Names & Taxonomyi

Protein namesi
Recommended name:
Prothrombin (EC:3.4.21.5)
Alternative name(s):
Coagulation factor II
Cleaved into the following 4 chains:
Gene namesi
Name:F2
Synonyms:Cf2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 2

Organism-specific databases

MGIiMGI:88380. F2.

Subcellular locationi

GO - Cellular componenti

  1. extracellular space Source: Ensembl
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi565 – 5651S → A: Loss of protease activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424 Reviewed predictionAdd
BLAST
Propeptidei25 – 4319PRO_0000028165Add
BLAST
Chaini44 – 618575ProthrombinPRO_0000028166Add
BLAST
Peptidei44 – 200157Activation peptide fragment 1PRO_0000028167Add
BLAST
Peptidei201 – 324124Activation peptide fragment 2PRO_0000028168Add
BLAST
Chaini325 – 36036Thrombin light chainPRO_0000028169Add
BLAST
Chaini361 – 618258Thrombin heavy chainPRO_0000028170Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei50 – 5014-carboxyglutamate1 Publication
Modified residuei51 – 5114-carboxyglutamate1 Publication
Modified residuei58 – 5814-carboxyglutamate1 Publication
Modified residuei60 – 6014-carboxyglutamate1 Publication
Disulfide bondi61 ↔ 66 By similarity
Modified residuei63 – 6314-carboxyglutamate1 Publication
Modified residuei64 – 6414-carboxyglutamate1 Publication
Modified residuei69 – 6914-carboxyglutamate1 Publication
Modified residuei70 – 7014-carboxyglutamate1 Publication
Modified residuei73 – 7314-carboxyglutamate1 Publication
Modified residuei76 – 7614-carboxyglutamate1 Publication
Disulfide bondi91 ↔ 104 By similarity
Disulfide bondi109 ↔ 187 By similarity
Glycosylationi122 – 1221N-linked (GlcNAc...)1 Publication
Disulfide bondi130 ↔ 170 By similarity
Glycosylationi144 – 1441N-linked (GlcNAc...)
Disulfide bondi158 ↔ 182 By similarity
Disulfide bondi215 ↔ 293 By similarity
Disulfide bondi236 ↔ 276 By similarity
Disulfide bondi264 ↔ 288 By similarity
Disulfide bondi333 ↔ 479Interchain (between light and heavy chains) By similarity
Disulfide bondi388 ↔ 4041 Publication
Glycosylationi413 – 4131N-linked (GlcNAc...)1 Publication
Disulfide bondi533 ↔ 5471 Publication
Glycosylationi553 – 5531N-linked (GlcNAc...)1 Publication
Disulfide bondi561 ↔ 5911 Publication

Post-translational modificationi

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.

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Gamma-carboxyglutamic acid, Glycoprotein, Zymogen

Proteomic databases

MaxQBiP19221.
PaxDbiP19221.
PRIDEiP19221.

PTM databases

PhosphoSiteiP19221.

Miscellaneous databases

PMAP-CutDBP19221.

Expressioni

Gene expression databases

ArrayExpressiP19221.
BgeeiP19221.
CleanExiMM_F2.
GenevestigatoriP19221.

Interactioni

Subunit structurei

Heterodimer (named alpha-thrombin) of a light and a heavy chain; disulfide-linked. Forms a heterodimer with SERPINA5 By similarity.1 Publication

Protein-protein interaction databases

IntActiP19221. 3 interactions.
MINTiMINT-4137721.
STRINGi10090.ENSMUSP00000028681.

Structurei

Secondary structure

1
618
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi323 – 3264
Turni331 – 3344
Turni337 – 3393
Helixi340 – 3423
Helixi349 – 3546
Beta strandi375 – 3806
Turni381 – 3844
Beta strandi385 – 40016
Helixi402 – 4043
Helixi408 – 4103
Helixi416 – 4183
Beta strandi419 – 4246
Beta strandi427 – 4304
Turni433 – 4353
Beta strandi437 – 44610
Turni452 – 4543
Beta strandi461 – 4677
Helixi483 – 4897
Beta strandi495 – 5006
Beta strandi504 – 5074
Helixi512 – 5154
Beta strandi521 – 5277
Helixi530 – 5356
Beta strandi545 – 5484
Beta strandi554 – 5563
Helixi562 – 5643
Beta strandi568 – 5725
Turni574 – 5763
Beta strandi579 – 5879
Helixi591 – 5933
Beta strandi596 – 6027
Helixi604 – 6063
Helixi607 – 61711

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2OCVX-ray2.20A319-346[»]
B361-618[»]
2PUXX-ray2.00A317-360[»]
B361-618[»]
2PV9X-ray3.50A317-360[»]
B361-618[»]
3EDXX-ray2.40A/C/E317-360[»]
B/D/F361-618[»]
3HK3X-ray1.94A317-360[»]
B361-618[»]
3HK6X-ray3.20A/C317-360[»]
B/D361-618[»]
3HKIX-ray2.20A/D317-360[»]
B/E361-618[»]
ProteinModelPortaliP19221.
SMRiP19221. Positions 44-618.

Miscellaneous databases

EvolutionaryTraceiP19221.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini44 – 9047GlaAdd
BLAST
Domaini109 – 18779Kringle 1Add
BLAST
Domaini215 – 29278Kringle 2Add
BLAST
Domaini361 – 615255Peptidase S1Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni548 – 57023High affinity receptor-binding region which is also known as the TP508 peptide By similarityAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase S1 family.
Contains 2 kringle domains.

Keywords - Domaini

Kringle, Repeat, Signal

Phylogenomic databases

eggNOGiCOG5640.
HOGENOMiHOG000251824.
HOVERGENiHBG108381.
InParanoidiP19221.
KOiK01313.
OMAiGIECQLW.
PhylomeDBiP19221.
TreeFamiTF327329.

Family and domain databases

Gene3Di2.40.20.10. 2 hits.
4.10.140.10. 1 hit.
4.10.740.10. 1 hit.
InterProiIPR017857. Coagulation_fac_subgr_Gla_dom.
IPR000294. GLA_domain.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR003966. Prothrombin/thrombin.
IPR018992. Thrombin_light_chain.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamiPF00594. Gla. 1 hit.
PF00051. Kringle. 2 hits.
PF09396. Thrombin_light. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF001149. Thrombin. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
PR00001. GLABLOOD.
PR01505. PROTHROMBIN.
SMARTiSM00069. GLA. 1 hit.
SM00130. KR. 2 hits.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF57440. SSF57440. 2 hits.
SSF57630. SSF57630. 1 hit.
PROSITEiPS00011. GLA_1. 1 hit.
PS50998. GLA_2. 1 hit.
PS00021. KRINGLE_1. 2 hits.
PS50070. KRINGLE_2. 2 hits.
PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P19221-1 [UniParc]FASTAAdd to Basket

« Hide

MSHVRGLGLP GCLALAALVS LVHSQHVFLA PQQALSLLQR VRRANSGFLE    50
ELRKGNLERE CVEEQCSYEE AFEALESPQD TDVFWAKYTV CDSVRKPRET 100
FMDCLEGRCA MDLGVNYLGT VNVTHTGIQC QLWRSRYPHK PEINSTTHPG 150
ADLKENFCRN PDSSTTGPWC YTTDPTVRRE ECSVPVCGQE GRTTVVMTPR 200
SGGSKDNLSP PLGQCLTERG RLYQGNLAVT TLGSPCLPWN SLPAKTLSKY 250
QDFDPEVKLV ENFCRNPDWD EEGAWCYVAG QPGDFEYCNL NYCEEAVGEE 300
NYDVDESIAG RTTDAEFHTF FNEKTFGLGE ADCGLRPLFE KKSLKDTTEK 350
ELLDSYIDGR IVEGWDAEKG IAPWQVMLFR KSPQELLCGA SLISDRWVLT 400
AAHCILYPPW DKNFTENDLL VRIGKHSRTR YERNVEKISM LEKIYVHPRY 450
NWRENLDRDI ALLKLKKPVP FSDYIHPVCL PDKQTVTSLL RAGYKGRVTG 500
WGNLRETWTT NINEIQPSVL QVVNLPIVER PVCKASTRIR ITDNMFCAGF 550
KVNDTKRGDA CEGDSGGPFV MKSPFNNRWY QMGIVSWGEG CDRKGKYGFY 600
THVFRLKRWI QKVIDQFG 618
Length:618
Mass (Da):70,269
Last modified:November 1, 1990 - v1
Checksum:iB89F719AAFD601E0
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X52308 mRNA. Translation: CAA36548.1.
BC013662 mRNA. Translation: AAH13662.1.
M81394 mRNA. Translation: AAA40435.1.
CCDSiCCDS16434.1.
PIRiA35827.
RefSeqiNP_034298.1. NM_010168.2.
UniGeneiMm.89048.

Genome annotation databases

EnsembliENSMUST00000028681; ENSMUSP00000028681; ENSMUSG00000027249.
GeneIDi14061.
KEGGimmu:14061.
UCSCiuc008kwg.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X52308 mRNA. Translation: CAA36548.1 .
BC013662 mRNA. Translation: AAH13662.1 .
M81394 mRNA. Translation: AAA40435.1 .
CCDSi CCDS16434.1.
PIRi A35827.
RefSeqi NP_034298.1. NM_010168.2.
UniGenei Mm.89048.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2OCV X-ray 2.20 A 319-346 [» ]
B 361-618 [» ]
2PUX X-ray 2.00 A 317-360 [» ]
B 361-618 [» ]
2PV9 X-ray 3.50 A 317-360 [» ]
B 361-618 [» ]
3EDX X-ray 2.40 A/C/E 317-360 [» ]
B/D/F 361-618 [» ]
3HK3 X-ray 1.94 A 317-360 [» ]
B 361-618 [» ]
3HK6 X-ray 3.20 A/C 317-360 [» ]
B/D 361-618 [» ]
3HKI X-ray 2.20 A/D 317-360 [» ]
B/E 361-618 [» ]
ProteinModelPortali P19221.
SMRi P19221. Positions 44-618.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P19221. 3 interactions.
MINTi MINT-4137721.
STRINGi 10090.ENSMUSP00000028681.

Chemistry

ChEMBLi CHEMBL1075308.

Protein family/group databases

MEROPSi S01.217.

PTM databases

PhosphoSitei P19221.

Proteomic databases

MaxQBi P19221.
PaxDbi P19221.
PRIDEi P19221.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000028681 ; ENSMUSP00000028681 ; ENSMUSG00000027249 .
GeneIDi 14061.
KEGGi mmu:14061.
UCSCi uc008kwg.1. mouse.

Organism-specific databases

CTDi 2147.
MGIi MGI:88380. F2.

Phylogenomic databases

eggNOGi COG5640.
HOGENOMi HOG000251824.
HOVERGENi HBG108381.
InParanoidi P19221.
KOi K01313.
OMAi GIECQLW.
PhylomeDBi P19221.
TreeFami TF327329.

Enzyme and pathway databases

Reactomei REACT_207651. G alpha (q) signalling events.
REACT_220322. Thrombin signalling through proteinase activated receptors (PARs).
REACT_225233. Cell surface interactions at the vascular wall.

Miscellaneous databases

ChiTaRSi F2. mouse.
EvolutionaryTracei P19221.
NextBioi 285028.
PMAP-CutDB P19221.
PROi P19221.
SOURCEi Search...

Gene expression databases

ArrayExpressi P19221.
Bgeei P19221.
CleanExi MM_F2.
Genevestigatori P19221.

Family and domain databases

Gene3Di 2.40.20.10. 2 hits.
4.10.140.10. 1 hit.
4.10.740.10. 1 hit.
InterProi IPR017857. Coagulation_fac_subgr_Gla_dom.
IPR000294. GLA_domain.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR003966. Prothrombin/thrombin.
IPR018992. Thrombin_light_chain.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view ]
Pfami PF00594. Gla. 1 hit.
PF00051. Kringle. 2 hits.
PF09396. Thrombin_light. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view ]
PIRSFi PIRSF001149. Thrombin. 1 hit.
PRINTSi PR00722. CHYMOTRYPSIN.
PR00001. GLABLOOD.
PR01505. PROTHROMBIN.
SMARTi SM00069. GLA. 1 hit.
SM00130. KR. 2 hits.
SM00020. Tryp_SPc. 1 hit.
[Graphical view ]
SUPFAMi SSF50494. SSF50494. 1 hit.
SSF57440. SSF57440. 2 hits.
SSF57630. SSF57630. 1 hit.
PROSITEi PS00011. GLA_1. 1 hit.
PS50998. GLA_2. 1 hit.
PS00021. KRINGLE_1. 2 hits.
PS50070. KRINGLE_2. 2 hits.
PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Characterization of the cDNA coding for mouse prothrombin and localization of the gene on mouse chromosome 2."
    Friezner Degen S.J., Schaffer L.A., Jamison C.S., Grant S.G., Fitzgibbon J.J., Pai J.-A., Chapman V.M., Elliott R.W.
    DNA Cell Biol. 9:487-498(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], GAMMA-CARBOXYGLUTAMATION AT GLU-50; GLU-51; GLU-58; GLU-60; GLU-63; GLU-64; GLU-69; GLU-70; GLU-73 AND GLU-76.
    Strain: C57BL/6.
    Tissue: Liver.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Liver.
  3. "Partial characterization of vertebrate prothrombin cDNAs: amplification and sequence analysis of the B chain of thrombin from nine different species."
    Banfield D.K., Macgillivray R.T.
    Proc. Natl. Acad. Sci. U.S.A. 89:2779-2783(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 384-618.
    Tissue: Liver.
  4. "Enhanced analysis of the mouse plasma proteome using cysteine-containing tryptic glycopeptides."
    Bernhard O.K., Kapp E.A., Simpson R.J.
    J. Proteome Res. 6:987-995(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-122; ASN-413 AND ASN-553.
    Strain: C57BL/6.
    Tissue: Plasma.
  5. Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 319-618, DISULFIDE BONDS.
  6. "Crystal structures of murine thrombin in complex with the extracellular fragments of murine protease-activated receptors PAR3 and PAR4."
    Bah A., Chen Z.-W., Bush-Pelc L.A., Mathews F.S., Di Cera E.
    Proc. Natl. Acad. Sci. U.S.A. 104:11603-11608(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 317-618 OF MUTANT ALA-565 IN COMPLEXES WITH PAR3/F2RL2 AND PAR4/F2RL3, MUTAGENESIS OF SER-565.

Entry informationi

Entry nameiTHRB_MOUSE
AccessioniPrimary (citable) accession number: P19221
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: November 1, 1990
Last modified: September 3, 2014
This is version 157 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.
Thrombin can itself cleave the N-terminal fragment (fragment 1) of the prothrombin, prior to its activation by factor Xa.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi