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P19221 (THRB_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Prothrombin

EC=3.4.21.5
Alternative name(s):
Coagulation factor II
Gene names
Name:F2
Synonyms:Cf2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length618 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (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.

Enzyme regulation

Inhibited by SERPINA5 By similarity.

Subunit structure

Heterodimer (named alpha-thrombin) of a light and a heavy chain; disulfide-linked. Forms a heterodimer with SERPINA5 By similarity. Ref.5

Post-translational modification

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.

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

Sequence similarities

Belongs to the peptidase S1 family.

Contains 1 Gla (gamma-carboxy-glutamate) domain.

Contains 2 kringle domains.

Contains 1 peptidase S1 domain.

Ontologies

Keywords
   Biological processAcute phase
Blood coagulation
Hemostasis
   DomainKringle
Repeat
Signal
   LigandCalcium
   Molecular functionHydrolase
Protease
Serine protease
   PTMCleavage on pair of basic residues
Disulfide bond
Gamma-carboxyglutamic acid
Glycoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processacute-phase response

Inferred from electronic annotation. Source: UniProtKB-KW

cytosolic calcium ion homeostasis

Inferred from electronic annotation. Source: Ensembl

fibrinolysis

Inferred from electronic annotation. Source: Ensembl

negative regulation of astrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of proteolysis

Inferred from electronic annotation. Source: Ensembl

platelet activation

Inferred from direct assay PubMed 17380206. Source: MGI

positive regulation of blood coagulation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell growth

Inferred from genetic interaction PubMed 18398001. Source: MGI

positive regulation of cell proliferation

Inferred from genetic interaction PubMed 18398001. Source: MGI

positive regulation of collagen biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of phosphatidylinositol 3-kinase signaling

Inferred from genetic interaction PubMed 18398001. Source: MGI

positive regulation of phospholipase C-activating G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of reactive oxygen species metabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of release of sequestered calcium ion into cytosol

Inferred from electronic annotation. Source: Ensembl

regulation of cell shape

Inferred from genetic interaction PubMed 18398001. Source: MGI

regulation of gene expression

Inferred from direct assay PubMed 16720835. Source: MGI

thrombin receptor signaling pathway

Inferred from sequence orthology PubMed 18398001. Source: MGI

   Cellular_componentextracellular space

Inferred from electronic annotation. Source: Ensembl

   Molecular_functioncalcium ion binding

Inferred from electronic annotation. Source: InterPro

peptidase activity

Inferred from mutant phenotype PubMed 18305483. Source: MGI

protein binding

Inferred from physical interaction PubMed 7608171. Source: MGI

serine-type endopeptidase activity

Inferred from direct assay PubMed 18398001. Source: MGI

thrombospondin receptor activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Propeptide25 – 4319
PRO_0000028165
Chain44 – 618575Prothrombin
PRO_0000028166
Peptide44 – 200157Activation peptide fragment 1
PRO_0000028167
Peptide201 – 324124Activation peptide fragment 2
PRO_0000028168
Chain325 – 36036Thrombin light chain
PRO_0000028169
Chain361 – 618258Thrombin heavy chain
PRO_0000028170

Regions

Domain44 – 9047Gla
Domain109 – 18779Kringle 1
Domain215 – 29278Kringle 2
Domain361 – 615255Peptidase S1
Region548 – 57023High affinity receptor-binding region which is also known as the TP508 peptide By similarity

Sites

Active site4031Charge relay system By similarity
Active site4591Charge relay system By similarity
Active site5651Charge relay system By similarity
Site200 – 2012Cleavage; by thrombin
Site324 – 3252Cleavage; by factor Xa
Site360 – 3612Cleavage; by factor Xa

Amino acid modifications

Modified residue5014-carboxyglutamate Ref.1
Modified residue5114-carboxyglutamate Ref.1
Modified residue5814-carboxyglutamate Ref.1
Modified residue6014-carboxyglutamate Ref.1
Modified residue6314-carboxyglutamate Ref.1
Modified residue6414-carboxyglutamate Ref.1
Modified residue6914-carboxyglutamate Ref.1
Modified residue7014-carboxyglutamate Ref.1
Modified residue7314-carboxyglutamate Ref.1
Modified residue7614-carboxyglutamate Ref.1
Glycosylation1221N-linked (GlcNAc...) Ref.4
Glycosylation1441N-linked (GlcNAc...)
Glycosylation4131N-linked (GlcNAc...) Ref.4
Glycosylation5531N-linked (GlcNAc...) Ref.4
Disulfide bond61 ↔ 66 By similarity
Disulfide bond91 ↔ 104 By similarity
Disulfide bond109 ↔ 187 By similarity
Disulfide bond130 ↔ 170 By similarity
Disulfide bond158 ↔ 182 By similarity
Disulfide bond215 ↔ 293 By similarity
Disulfide bond236 ↔ 276 By similarity
Disulfide bond264 ↔ 288 By similarity
Disulfide bond333 ↔ 479Interchain (between light and heavy chains) By similarity
Disulfide bond388 ↔ 404 Ref.5
Disulfide bond533 ↔ 547 Ref.5
Disulfide bond561 ↔ 591 Ref.5

Experimental info

Mutagenesis5651S → A: Loss of protease activity. Ref.6

Secondary structure

.............................................................. 618
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P19221 [UniParc].

Last modified November 1, 1990. Version 1.
Checksum: B89F719AAFD601E0

FASTA61870,269
        10         20         30         40         50         60 
MSHVRGLGLP GCLALAALVS LVHSQHVFLA PQQALSLLQR VRRANSGFLE ELRKGNLERE 

        70         80         90        100        110        120 
CVEEQCSYEE AFEALESPQD TDVFWAKYTV CDSVRKPRET FMDCLEGRCA MDLGVNYLGT 

       130        140        150        160        170        180 
VNVTHTGIQC QLWRSRYPHK PEINSTTHPG ADLKENFCRN PDSSTTGPWC YTTDPTVRRE 

       190        200        210        220        230        240 
ECSVPVCGQE GRTTVVMTPR SGGSKDNLSP PLGQCLTERG RLYQGNLAVT TLGSPCLPWN 

       250        260        270        280        290        300 
SLPAKTLSKY QDFDPEVKLV ENFCRNPDWD EEGAWCYVAG QPGDFEYCNL NYCEEAVGEE 

       310        320        330        340        350        360 
NYDVDESIAG RTTDAEFHTF FNEKTFGLGE ADCGLRPLFE KKSLKDTTEK ELLDSYIDGR 

       370        380        390        400        410        420 
IVEGWDAEKG IAPWQVMLFR KSPQELLCGA SLISDRWVLT AAHCILYPPW DKNFTENDLL 

       430        440        450        460        470        480 
VRIGKHSRTR YERNVEKISM LEKIYVHPRY NWRENLDRDI ALLKLKKPVP FSDYIHPVCL 

       490        500        510        520        530        540 
PDKQTVTSLL RAGYKGRVTG WGNLRETWTT NINEIQPSVL QVVNLPIVER PVCKASTRIR 

       550        560        570        580        590        600 
ITDNMFCAGF KVNDTKRGDA CEGDSGGPFV MKSPFNNRWY QMGIVSWGEG CDRKGKYGFY 

       610 
THVFRLKRWI QKVIDQFG 

« Hide

References

« Hide 'large scale' references
[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]"Structural basis of Na+ activation mimicry in murine thrombin."
Marino F., Chen Z.-W., Ergenekan C.E., Bush-Pelc L.A., Mathews F.S., Di Cera E.
J. Biol. Chem. 282:16355-16361(2007) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X52308 mRNA. Translation: CAA36548.1.
BC013662 mRNA. Translation: AAH13662.1.
M81394 mRNA. Translation: AAA40435.1.
CCDSCCDS16434.1.
PIRA35827.
RefSeqNP_034298.1. NM_010168.2.
UniGeneMm.89048.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalP19221.
SMRP19221. Positions 44-618.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP19221. 3 interactions.
MINTMINT-4137721.
STRING10090.ENSMUSP00000028681.

Chemistry

ChEMBLCHEMBL1075308.

Protein family/group databases

MEROPSS01.217.

PTM databases

PhosphoSiteP19221.

Proteomic databases

MaxQBP19221.
PaxDbP19221.
PRIDEP19221.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000028681; ENSMUSP00000028681; ENSMUSG00000027249.
GeneID14061.
KEGGmmu:14061.
UCSCuc008kwg.1. mouse.

Organism-specific databases

CTD2147.
MGIMGI:88380. F2.

Phylogenomic databases

eggNOGCOG5640.
HOGENOMHOG000251824.
HOVERGENHBG108381.
InParanoidP19221.
KOK01313.
OMAGIECQLW.
PhylomeDBP19221.
TreeFamTF327329.

Gene expression databases

ArrayExpressP19221.
BgeeP19221.
CleanExMM_F2.
GenevestigatorP19221.

Family and domain databases

Gene3D2.40.20.10. 2 hits.
4.10.140.10. 1 hit.
4.10.740.10. 1 hit.
InterProIPR017857. 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]
PfamPF00594. Gla. 1 hit.
PF00051. Kringle. 2 hits.
PF09396. Thrombin_light. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFPIRSF001149. Thrombin. 1 hit.
PRINTSPR00722. CHYMOTRYPSIN.
PR00001. GLABLOOD.
PR01505. PROTHROMBIN.
SMARTSM00069. GLA. 1 hit.
SM00130. KR. 2 hits.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF50494. SSF50494. 1 hit.
SSF57440. SSF57440. 2 hits.
SSF57630. SSF57630. 1 hit.
PROSITEPS00011. 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]
ProtoNetSearch...

Other

ChiTaRSF2. mouse.
EvolutionaryTraceP19221.
NextBio285028.
PMAP-CutDBP19221.
PROP19221.
SOURCESearch...

Entry information

Entry nameTHRB_MOUSE
AccessionPrimary (citable) accession number: P19221
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: November 1, 1990
Last modified: July 9, 2014
This is version 156 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot