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Protein

Prothrombin

Gene

F2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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).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)DescriptionActionsGraphical viewLength
Active sitei403Charge relay systemBy similarity1
Active sitei459Charge relay systemBy similarity1
Active sitei565Charge relay systemBy similarity1

GO - Molecular functioni

  • calcium ion binding Source: InterPro
  • peptidase activity Source: MGI
  • receptor binding Source: MGI
  • serine-type endopeptidase activity Source: MGI
  • thrombospondin receptor activity Source: MGI

GO - Biological processi

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

ReactomeiR-MMU-140837. Intrinsic Pathway of Fibrin Clot Formation.
R-MMU-140875. Common Pathway of Fibrin Clot Formation.
R-MMU-159740. Gamma-carboxylation of protein precursors.
R-MMU-159763. Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus.
R-MMU-159782. Removal of aminoterminal propeptides from gamma-carboxylated proteins.
R-MMU-202733. Cell surface interactions at the vascular wall.
R-MMU-375276. Peptide ligand-binding receptors.
R-MMU-381426. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
R-MMU-416476. G alpha (q) signalling events.
R-MMU-456926. Thrombin signalling through proteinase activated receptors (PARs).
R-MMU-76009. Platelet Aggregation (Plug Formation).

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
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:88380. F2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi565S → A: Loss of protease activity. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL1075308.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
PropeptideiPRO_000002816525 – 43Add BLAST19
ChainiPRO_000002816644 – 618ProthrombinAdd BLAST575
PeptideiPRO_000002816744 – 200Activation peptide fragment 1Add BLAST157
PeptideiPRO_0000028168201 – 324Activation peptide fragment 2Add BLAST124
ChainiPRO_0000028169325 – 360Thrombin light chainAdd BLAST36
ChainiPRO_0000028170361 – 618Thrombin heavy chainAdd BLAST258

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei504-carboxyglutamatePROSITE-ProRule annotation1 Publication1
Modified residuei514-carboxyglutamatePROSITE-ProRule annotation1 Publication1
Modified residuei584-carboxyglutamatePROSITE-ProRule annotation1 Publication1
Modified residuei604-carboxyglutamatePROSITE-ProRule annotation1 Publication1
Disulfide bondi61 ↔ 66By similarity
Modified residuei634-carboxyglutamatePROSITE-ProRule annotation1 Publication1
Modified residuei644-carboxyglutamatePROSITE-ProRule annotation1 Publication1
Modified residuei694-carboxyglutamatePROSITE-ProRule annotation1 Publication1
Modified residuei704-carboxyglutamatePROSITE-ProRule annotation1 Publication1
Modified residuei734-carboxyglutamatePROSITE-ProRule annotation1 Publication1
Modified residuei764-carboxyglutamatePROSITE-ProRule annotation1 Publication1
Disulfide bondi91 ↔ 104By similarity
Disulfide bondi109 ↔ 187By similarity
Glycosylationi122N-linked (GlcNAc...)1 Publication1
Disulfide bondi130 ↔ 170By similarity
Glycosylationi144N-linked (GlcNAc...)1
Disulfide bondi158 ↔ 182By similarity
Disulfide bondi215 ↔ 293By similarity
Disulfide bondi236 ↔ 276By similarity
Disulfide bondi264 ↔ 288By similarity
Disulfide bondi333 ↔ 479Interchain (between light and heavy chains)PROSITE-ProRule annotation
Disulfide bondi388 ↔ 4041 Publication
Glycosylationi413N-linked (GlcNAc...)1 Publication1
Disulfide bondi533 ↔ 5471 Publication
Glycosylationi553N-linked (GlcNAc...)1 Publication1
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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei200 – 201Cleavage; by thrombin2
Sitei324 – 325Cleavage; by factor Xa2
Sitei360 – 361Cleavage; by factor Xa2

Keywords - PTMi

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

Proteomic databases

PaxDbiP19221.
PeptideAtlasiP19221.
PRIDEiP19221.

PTM databases

iPTMnetiP19221.
PhosphoSitePlusiP19221.
SwissPalmiP19221.

Miscellaneous databases

PMAP-CutDBP19221.

Expressioni

Gene expression databases

BgeeiENSMUSG00000027249.
CleanExiMM_F2.
ExpressionAtlasiP19221. baseline and differential.
GenevisibleiP19221. MM.

Interactioni

Subunit structurei

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

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-60968N.
IntActiP19221. 4 interactors.
MINTiMINT-4137721.
STRINGi10090.ENSMUSP00000028681.

Chemistry databases

BindingDBiP19221.

Structurei

Secondary structure

1618
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi323 – 326Combined sources4
Turni331 – 334Combined sources4
Turni337 – 339Combined sources3
Helixi340 – 342Combined sources3
Helixi349 – 354Combined sources6
Beta strandi375 – 380Combined sources6
Turni381 – 384Combined sources4
Beta strandi385 – 400Combined sources16
Helixi402 – 404Combined sources3
Helixi408 – 410Combined sources3
Helixi416 – 418Combined sources3
Beta strandi419 – 424Combined sources6
Beta strandi427 – 430Combined sources4
Turni433 – 435Combined sources3
Beta strandi437 – 446Combined sources10
Turni452 – 454Combined sources3
Beta strandi461 – 467Combined sources7
Helixi483 – 489Combined sources7
Beta strandi495 – 500Combined sources6
Beta strandi504 – 507Combined sources4
Helixi512 – 515Combined sources4
Beta strandi521 – 527Combined sources7
Helixi530 – 535Combined sources6
Beta strandi545 – 548Combined sources4
Beta strandi554 – 556Combined sources3
Helixi562 – 564Combined sources3
Beta strandi568 – 572Combined sources5
Turni574 – 576Combined sources3
Beta strandi579 – 587Combined sources9
Helixi591 – 593Combined sources3
Beta strandi596 – 602Combined sources7
Helixi604 – 606Combined sources3
Helixi607 – 617Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP19221.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini44 – 90GlaPROSITE-ProRule annotationAdd BLAST47
Domaini109 – 187Kringle 1PROSITE-ProRule annotationAdd BLAST79
Domaini215 – 292Kringle 2PROSITE-ProRule annotationAdd BLAST78
Domaini361 – 615Peptidase S1PROSITE-ProRule annotationAdd BLAST255

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni548 – 570High affinity receptor-binding region which is also known as the TP508 peptideBy similarityAdd BLAST23

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation
Contains 1 Gla (gamma-carboxy-glutamate) domain.PROSITE-ProRule annotation
Contains 2 kringle domains.PROSITE-ProRule annotation
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Kringle, Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IKPN. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000119133.
HOGENOMiHOG000251824.
HOVERGENiHBG108381.
InParanoidiP19221.
KOiK01313.
OMAiGIECQLW.
OrthoDBiEOG091G0AH5.
PhylomeDBiP19221.
TreeFamiTF327329.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
Gene3Di4.10.140.10. 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.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR003966. Prothrombin/thrombin.
IPR018992. Thrombin_light_chain.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PANTHERiPTHR24254:SF10. PTHR24254:SF10. 1 hit.
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

        10         20         30         40         50
MSHVRGLGLP GCLALAALVS LVHSQHVFLA PQQALSLLQR VRRANSGFLE
60 70 80 90 100
ELRKGNLERE CVEEQCSYEE AFEALESPQD TDVFWAKYTV CDSVRKPRET
110 120 130 140 150
FMDCLEGRCA MDLGVNYLGT VNVTHTGIQC QLWRSRYPHK PEINSTTHPG
160 170 180 190 200
ADLKENFCRN PDSSTTGPWC YTTDPTVRRE ECSVPVCGQE GRTTVVMTPR
210 220 230 240 250
SGGSKDNLSP PLGQCLTERG RLYQGNLAVT TLGSPCLPWN SLPAKTLSKY
260 270 280 290 300
QDFDPEVKLV ENFCRNPDWD EEGAWCYVAG QPGDFEYCNL NYCEEAVGEE
310 320 330 340 350
NYDVDESIAG RTTDAEFHTF FNEKTFGLGE ADCGLRPLFE KKSLKDTTEK
360 370 380 390 400
ELLDSYIDGR IVEGWDAEKG IAPWQVMLFR KSPQELLCGA SLISDRWVLT
410 420 430 440 450
AAHCILYPPW DKNFTENDLL VRIGKHSRTR YERNVEKISM LEKIYVHPRY
460 470 480 490 500
NWRENLDRDI ALLKLKKPVP FSDYIHPVCL PDKQTVTSLL RAGYKGRVTG
510 520 530 540 550
WGNLRETWTT NINEIQPSVL QVVNLPIVER PVCKASTRIR ITDNMFCAGF
560 570 580 590 600
KVNDTKRGDA CEGDSGGPFV MKSPFNNRWY QMGIVSWGEG CDRKGKYGFY
610
THVFRLKRWI QKVIDQFG
Length:618
Mass (Da):70,269
Last modified:November 1, 1990 - v1
Checksum:iB89F719AAFD601E0
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52308 mRNA. Translation: CAA36548.1.
BC013662 mRNA. Translation: AAH13662.1.
M81394 mRNA. Translation: AAA40435.1.
CCDSiCCDS16434.1.
PIRiA35827.
RefSeqiNP_034298.1. NM_010168.3.
UniGeneiMm.89048.

Genome annotation databases

EnsembliENSMUST00000028681; ENSMUSP00000028681; ENSMUSG00000027249.
GeneIDi14061.
KEGGimmu:14061.
UCSCiuc008kwg.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52308 mRNA. Translation: CAA36548.1.
BC013662 mRNA. Translation: AAH13662.1.
M81394 mRNA. Translation: AAA40435.1.
CCDSiCCDS16434.1.
PIRiA35827.
RefSeqiNP_034298.1. NM_010168.3.
UniGeneiMm.89048.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-60968N.
IntActiP19221. 4 interactors.
MINTiMINT-4137721.
STRINGi10090.ENSMUSP00000028681.

Chemistry databases

BindingDBiP19221.
ChEMBLiCHEMBL1075308.

Protein family/group databases

MEROPSiS01.217.

PTM databases

iPTMnetiP19221.
PhosphoSitePlusiP19221.
SwissPalmiP19221.

Proteomic databases

PaxDbiP19221.
PeptideAtlasiP19221.
PRIDEiP19221.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000028681; ENSMUSP00000028681; ENSMUSG00000027249.
GeneIDi14061.
KEGGimmu:14061.
UCSCiuc008kwg.2. mouse.

Organism-specific databases

CTDi2147.
MGIiMGI:88380. F2.

Phylogenomic databases

eggNOGiENOG410IKPN. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000119133.
HOGENOMiHOG000251824.
HOVERGENiHBG108381.
InParanoidiP19221.
KOiK01313.
OMAiGIECQLW.
OrthoDBiEOG091G0AH5.
PhylomeDBiP19221.
TreeFamiTF327329.

Enzyme and pathway databases

ReactomeiR-MMU-140837. Intrinsic Pathway of Fibrin Clot Formation.
R-MMU-140875. Common Pathway of Fibrin Clot Formation.
R-MMU-159740. Gamma-carboxylation of protein precursors.
R-MMU-159763. Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus.
R-MMU-159782. Removal of aminoterminal propeptides from gamma-carboxylated proteins.
R-MMU-202733. Cell surface interactions at the vascular wall.
R-MMU-375276. Peptide ligand-binding receptors.
R-MMU-381426. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
R-MMU-416476. G alpha (q) signalling events.
R-MMU-456926. Thrombin signalling through proteinase activated receptors (PARs).
R-MMU-76009. Platelet Aggregation (Plug Formation).

Miscellaneous databases

EvolutionaryTraceiP19221.
PMAP-CutDBP19221.
PROiP19221.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000027249.
CleanExiMM_F2.
ExpressionAtlasiP19221. baseline and differential.
GenevisibleiP19221. MM.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
Gene3Di4.10.140.10. 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.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR003966. Prothrombin/thrombin.
IPR018992. Thrombin_light_chain.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PANTHERiPTHR24254:SF10. PTHR24254:SF10. 1 hit.
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]
ProtoNetiSearch...

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: November 30, 2016
This is version 180 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.