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Protein

Prothrombin

Gene

F2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

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.

Catalytic activityi

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

Activity 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
  • enzyme activator activity Source: MGI
  • heparin binding Source: MGI
  • lipopolysaccharide binding Source: MGI
  • peptidase activity Source: MGI
  • serine-type endopeptidase activity Source: MGI
  • signaling receptor binding Source: MGI
  • thrombospondin receptor activity Source: MGI

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processAcute phase, Blood coagulation, Hemostasis
LigandCalcium

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)
R-MMU-977606 Regulation of Complement cascade

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:88380 F2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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...) asparagine1 Publication1
Disulfide bondi130 ↔ 170By similarity
Glycosylationi144N-linked (GlcNAc...) asparagine1
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...) asparagine1 Publication1
Disulfide bondi533 ↔ 5471 Publication
Glycosylationi553N-linked (GlcNAc...) asparagine1 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-CutDBiP19221

Expressioni

Gene expression databases

BgeeiENSMUSG00000027249 Expressed in 70 organ(s), highest expression level in liver
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, 6 interactors
MINTiP19221
STRINGi10090.ENSMUSP00000028681

Chemistry databases

BindingDBiP19221

Structurei

Secondary structure

1618
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

Kringle, Repeat, Signal

Phylogenomic databases

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

Family and domain databases

CDDicd00108 KR, 2 hits
cd00190 Tryp_SPc, 1 hit
Gene3Di2.40.20.10, 2 hits
4.10.140.10, 1 hit
InterProiView protein in InterPro
IPR035972 GLA-like_dom_SF
IPR000294 GLA_domain
IPR000001 Kringle
IPR013806 Kringle-like
IPR018056 Kringle_CS
IPR038178 Kringle_sf
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR003966 Prothrombin/thrombin
IPR018992 Thrombin_light_chain
IPR037111 Thrombin_light_chain_sf
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PANTHERiPTHR24254:SF10 PTHR24254:SF10, 1 hit
PfamiView protein in Pfam
PF00594 Gla, 1 hit
PF00051 Kringle, 2 hits
PF09396 Thrombin_light, 1 hit
PF00089 Trypsin, 1 hit
PIRSFiPIRSF001149 Thrombin, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
PR00001 GLABLOOD
PR01505 PROTHROMBIN
SMARTiView protein in SMART
SM00069 GLA, 1 hit
SM00130 KR, 2 hits
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
SSF57440 SSF57440, 2 hits
SSF57630 SSF57630, 1 hit
PROSITEiView protein in PROSITE
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

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7BX99H7BX99_MOUSE
Prothrombin
F2
617Annotation score:

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

Similar proteinsi

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, 6 interactors
MINTiP19221
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
OMAiHPVCLPD
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)
R-MMU-977606 Regulation of Complement cascade

Miscellaneous databases

ChiTaRSiF2 mouse
EvolutionaryTraceiP19221
PMAP-CutDBiP19221
PROiPR:P19221
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000027249 Expressed in 70 organ(s), highest expression level in liver
CleanExiMM_F2
ExpressionAtlasiP19221 baseline and differential
GenevisibleiP19221 MM

Family and domain databases

CDDicd00108 KR, 2 hits
cd00190 Tryp_SPc, 1 hit
Gene3Di2.40.20.10, 2 hits
4.10.140.10, 1 hit
InterProiView protein in InterPro
IPR035972 GLA-like_dom_SF
IPR000294 GLA_domain
IPR000001 Kringle
IPR013806 Kringle-like
IPR018056 Kringle_CS
IPR038178 Kringle_sf
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR003966 Prothrombin/thrombin
IPR018992 Thrombin_light_chain
IPR037111 Thrombin_light_chain_sf
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PANTHERiPTHR24254:SF10 PTHR24254:SF10, 1 hit
PfamiView protein in Pfam
PF00594 Gla, 1 hit
PF00051 Kringle, 2 hits
PF09396 Thrombin_light, 1 hit
PF00089 Trypsin, 1 hit
PIRSFiPIRSF001149 Thrombin, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
PR00001 GLABLOOD
PR01505 PROTHROMBIN
SMARTiView protein in SMART
SM00069 GLA, 1 hit
SM00130 KR, 2 hits
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
SSF57440 SSF57440, 2 hits
SSF57630 SSF57630, 1 hit
PROSITEiView protein in PROSITE
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
ProtoNetiSearch...

Entry informationi

Entry nameiTHRB_MOUSE
AccessioniPrimary (citable) accession number: P19221
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: November 1, 1990
Last modified: September 12, 2018
This is version 193 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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