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Protein

Coagulation factor IX

Gene

F9

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca2+ ions, phospholipids, and factor VIIIa.1 Publication

Catalytic activityi

Selective cleavage of Arg-|-Ile bond in factor X to form factor Xa.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi47Calcium 1; via carbonyl oxygenCombined sources1 Publication1
Metal bindingi48Calcium 2Combined sources1 Publication1
Metal bindingi53Calcium 1; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi53Calcium 2; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi54Calcium 2; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi54Calcium 3; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi61Calcium 4 or magnesium 1; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi63Calcium 1; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi63Calcium 2; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi63Calcium 3; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi66Calcium 4 or magnesium 1; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi67Calcium 1; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi72Calcium 5 or magnesium 2; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi73Calcium 2; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi73Calcium 3; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi76Calcium 3; via 4-carboxyglutamateBy similarity1
Metal bindingi76Calcium 5 or magnesium 2; via 4-carboxyglutamateBy similarity1
Metal bindingi82Calcium 6 or magnesium 3; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi86Calcium 6 or magnesium 3; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi93Calcium 7By similarity1
Metal bindingi94Calcium 7; via carbonyl oxygenBy similarity1
Metal bindingi96Calcium 7By similarity1
Metal bindingi110Calcium 7By similarity1
Metal bindingi111Calcium 7; via carbonyl oxygenBy similarity1
Active sitei268Charge relay systemBy similarity1
Metal bindingi282Calcium 8By similarity1
Metal bindingi284Calcium 8; via carbonyl oxygenBy similarity1
Metal bindingi289Calcium 8By similarity1
Metal bindingi292Calcium 8By similarity1
Active sitei316Charge relay systemBy similarity1
Active sitei412Charge relay systemBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processBlood coagulation, Hemostasis
LigandCalcium, Magnesium, Metal-binding

Enzyme and pathway databases

ReactomeiR-BTA-140834 Extrinsic Pathway of Fibrin Clot Formation
R-BTA-140837 Intrinsic Pathway of Fibrin Clot Formation
R-BTA-159740 Gamma-carboxylation of protein precursors
R-BTA-159763 Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus
R-BTA-159782 Removal of aminoterminal propeptides from gamma-carboxylated proteins
SABIO-RKiP00741

Protein family/group databases

MEROPSiS01.214

Names & Taxonomyi

Protein namesi
Recommended name:
Coagulation factor IX (EC:3.4.21.22)
Alternative name(s):
Christmas factor
Cleaved into the following 2 chains:
Gene namesi
Name:F9
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome X

Organism-specific databases

VGNCiVGNC:28691 F9

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

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Keywords - Diseasei

Hemophilia

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
ChainiPRO_000002774126 – 462Coagulation factor IXAdd BLAST437
PropeptideiPRO_000043308429 – 46By similarityAdd BLAST18
ChainiPRO_000002774247 – 192Coagulation factor IXa light chainAdd BLAST146
PropeptideiPRO_0000027743193 – 227Activation peptideAdd BLAST35
ChainiPRO_0000027744228 – 462Coagulation factor IXa heavy chainAdd BLAST235

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei534-carboxyglutamatePROSITE-ProRule annotationCombined sources2 Publications1
Modified residuei544-carboxyglutamatePROSITE-ProRule annotationCombined sources2 Publications1
Modified residuei614-carboxyglutamatePROSITE-ProRule annotationCombined sources2 Publications1
Modified residuei634-carboxyglutamatePROSITE-ProRule annotationCombined sources2 Publications1
Disulfide bondi64 ↔ 69Combined sources1 Publication
Modified residuei664-carboxyglutamatePROSITE-ProRule annotationCombined sources2 Publications1
Modified residuei674-carboxyglutamatePROSITE-ProRule annotationCombined sources2 Publications1
Modified residuei724-carboxyglutamatePROSITE-ProRule annotationCombined sources2 Publications1
Modified residuei734-carboxyglutamatePROSITE-ProRule annotationCombined sources2 Publications1
Modified residuei764-carboxyglutamatePROSITE-ProRule annotationCombined sources2 Publications1
Modified residuei794-carboxyglutamatePROSITE-ProRule annotationCombined sources2 Publications1
Modified residuei824-carboxyglutamatePROSITE-ProRule annotationCombined sources2 Publications1
Glycosylationi85O-linked (GalNAc...) threonineBy similarity1
Modified residuei864-carboxyglutamatePROSITE-ProRule annotationCombined sources2 Publications1
Disulfide bondi97 ↔ 108By similarity
GlycosylationiCAR_00000899O-linked (Glc...) serine; alternate3 Publications1
Glycosylationi99O-linked (Xyl...) serine; alternateBy similarity3 Publications1
Disulfide bondi102 ↔ 117By similarity
Modified residuei110(3R)-3-hydroxyaspartate1 Publication1
Modified residuei114PhosphoserineBy similarity1
Disulfide bondi119 ↔ 128By similarity
Disulfide bondi134 ↔ 145By similarity
Disulfide bondi141 ↔ 155By similarity
Disulfide bondi157 ↔ 170By similarity
Disulfide bondi178 ↔ 336Interchain (between light and heavy chains)By similarity
Modified residuei202SulfotyrosineBy similarity1
Glycosylationi204N-linked (GlcNAc...) asparagine1 Publication1
Modified residuei205PhosphoserineBy similarity1
Glycosylationi214N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi219N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi253 ↔ 269By similarity
Glycosylationi307N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi383 ↔ 397By similarity
Disulfide bondi408 ↔ 436By similarity

Post-translational modificationi

Activated by factor XIa, which excises the activation peptide. The propeptide can also be removed by snake venom protease.By similarity
The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.1 Publication
Predominantly O-glucosylated at Ser-99 by POGLUT1 in vitro.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei192 – 193Cleavage; by factor XIa2
Sitei227 – 228Cleavage; by factor XIa2

Keywords - PTMi

Disulfide bond, Gamma-carboxyglutamic acid, Glycoprotein, Hydroxylation, Phosphoprotein, Sulfation, Zymogen

Proteomic databases

PaxDbiP00741
PRIDEiP00741

PTM databases

GlyConnecti97
iPTMnetiP00741
UniCarbKBiP00741

Miscellaneous databases

PMAP-CutDBiP00741

Expressioni

Tissue specificityi

Detected in blood plasma (at protein level) (PubMed:12695512).1 Publication

Gene expression databases

BgeeiENSBTAG00000004003 Expressed in 2 organ(s), highest expression level in liver
ExpressionAtlasiP00741 baseline and differential

Interactioni

Subunit structurei

Heterodimer of a light chain and a heavy chain; disulfide-linked, Interacts with SERPINC1 (By similarity). Interacts with the heterodimeric snake venom coagulation factor IX-binding protein (PubMed:12695512).By similarity1 Publication

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000005227

Structurei

Secondary structure

1462
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP00741
SMRiP00741
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP00741

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini47 – 92GlaPROSITE-ProRule annotationAdd BLAST46
Domaini93 – 129EGF-like 1; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini130 – 171EGF-like 2PROSITE-ProRule annotationAdd BLAST42
Domaini228 – 460Peptidase S1PROSITE-ProRule annotationAdd BLAST233

Domaini

Calcium binds to the gamma-carboxyglutamic acid (Gla) residues in the Gla domain (PubMed:12695512). Calcium can also bind, with stronger affinity, to another site beyond the Gla domain (By similarity). Under physiological ion concentrations, Ca2+ is displaced by Mg2+ from some of the gammaglutamate residues in the N-terminal Gla domain. This leads to a subtle conformation change that may affect the interaction with its binding protein (PubMed:12695512).By similarity1 Publication

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Signal

Phylogenomic databases

eggNOGiENOG410IGPV Eukaryota
COG5640 LUCA
GeneTreeiENSGT00760000118890
HOGENOMiHOG000251821
HOVERGENiHBG013304
InParanoidiP00741
OMAiVTPICIA
OrthoDBiEOG091G0AH5
TreeFamiTF327329

Family and domain databases

CDDicd00190 Tryp_SPc, 1 hit
Gene3Di4.10.740.10, 1 hit
InterProiView protein in InterPro
IPR017857 Coagulation_fac-like_Gla_dom
IPR035694 Coagulation_factor_IX
IPR001881 EGF-like_Ca-bd_dom
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR000152 EGF-type_Asp/Asn_hydroxyl_site
IPR018097 EGF_Ca-bd_CS
IPR035972 GLA-like_dom_SF
IPR000294 GLA_domain
IPR012224 Pept_S1A_FX
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PANTHERiPTHR44064:SF4 PTHR44064:SF4, 1 hit
PfamiView protein in Pfam
PF00008 EGF, 1 hit
PF00594 Gla, 1 hit
PF00089 Trypsin, 1 hit
PIRSFiPIRSF001143 Factor_X, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
PR00001 GLABLOOD
SMARTiView protein in SMART
SM00181 EGF, 2 hits
SM00179 EGF_CA, 1 hit
SM00069 GLA, 1 hit
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
SSF57630 SSF57630, 1 hit
PROSITEiView protein in PROSITE
PS00010 ASX_HYDROXYL, 1 hit
PS00022 EGF_1, 1 hit
PS01186 EGF_2, 2 hits
PS50026 EGF_3, 1 hit
PS01187 EGF_CA, 1 hit
PS00011 GLA_1, 1 hit
PS50998 GLA_2, 1 hit
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

P00741-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MWCLNMIMAE SPGLVTICLL GYLLSAECTV FLDRENATKI LHRPKRYNSG
60 70 80 90 100
KLEEFVRGNL ERECKEEKCS FEEAREVFEN TEKTTEFWKQ YVDGDQCESN
110 120 130 140 150
PCLNGGMCKD DINSYECWCQ AGFEGTNCEL DATCSIKNGR CKQFCKRDTD
160 170 180 190 200
NKVVCSCTDG YRLAEDQKSC EPAVPFPCGR VSVSHISKKL TRAETIFSNT
210 220 230 240 250
NYENSSEAEI IWDNVTQSNQ SFDEFSRVVG GEDAERGQFP WQVLLHGEIA
260 270 280 290 300
AFCGGSIVNE KWVVTAAHCI KPGVKITVVA GEHNTEKPEP TEQKRNVIRA
310 320 330 340 350
IPYHSYNASI NKYSHDIALL ELDEPLELNS YVTPICIADR DYTNIFLKFG
360 370 380 390 400
YGYVSGWGKV FNRGRSASIL QYLKVPLVDR ATCLRSTKFS IYSHMFCAGY
410 420 430 440 450
HEGGKDSCQG DSGGPHVTEV EGTSFLTGII SWGEECAMKG KYGIYTKVSR
460
YVNWIKEKTK LT
Length:462
Mass (Da):52,046
Last modified:May 27, 2015 - v2
Checksum:i415B2A7BD6EA256A
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F1MBC5F1MBC5_BOVIN
Coagulation factor IX
F9
324Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti110D → T AA sequence (PubMed:291916).Curated1
Sequence conflicti347L → S AA sequence (PubMed:291916).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DAAA02067809 Genomic DNA No translation available.
DAAA02067810 Genomic DNA No translation available.
J00007 mRNA Translation: AAA30520.1
PIRiA14757 KFBO
RefSeqiXP_005227591.1, XM_005227534.3
UniGeneiBt.13106

Genome annotation databases

EnsembliENSBTAT00000005227; ENSBTAP00000005227; ENSBTAG00000004003

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DAAA02067809 Genomic DNA No translation available.
DAAA02067810 Genomic DNA No translation available.
J00007 mRNA Translation: AAA30520.1
PIRiA14757 KFBO
RefSeqiXP_005227591.1, XM_005227534.3
UniGeneiBt.13106

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1J34X-ray1.55C47-92[»]
1J35X-ray1.80C47-92[»]
ProteinModelPortaliP00741
SMRiP00741
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000005227

Protein family/group databases

MEROPSiS01.214

PTM databases

GlyConnecti97
iPTMnetiP00741
UniCarbKBiP00741

Proteomic databases

PaxDbiP00741
PRIDEiP00741

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000005227; ENSBTAP00000005227; ENSBTAG00000004003

Organism-specific databases

CTDi2158
VGNCiVGNC:28691 F9

Phylogenomic databases

eggNOGiENOG410IGPV Eukaryota
COG5640 LUCA
GeneTreeiENSGT00760000118890
HOGENOMiHOG000251821
HOVERGENiHBG013304
InParanoidiP00741
OMAiVTPICIA
OrthoDBiEOG091G0AH5
TreeFamiTF327329

Enzyme and pathway databases

ReactomeiR-BTA-140834 Extrinsic Pathway of Fibrin Clot Formation
R-BTA-140837 Intrinsic Pathway of Fibrin Clot Formation
R-BTA-159740 Gamma-carboxylation of protein precursors
R-BTA-159763 Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus
R-BTA-159782 Removal of aminoterminal propeptides from gamma-carboxylated proteins
SABIO-RKiP00741

Miscellaneous databases

EvolutionaryTraceiP00741
PMAP-CutDBiP00741

Gene expression databases

BgeeiENSBTAG00000004003 Expressed in 2 organ(s), highest expression level in liver
ExpressionAtlasiP00741 baseline and differential

Family and domain databases

CDDicd00190 Tryp_SPc, 1 hit
Gene3Di4.10.740.10, 1 hit
InterProiView protein in InterPro
IPR017857 Coagulation_fac-like_Gla_dom
IPR035694 Coagulation_factor_IX
IPR001881 EGF-like_Ca-bd_dom
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR000152 EGF-type_Asp/Asn_hydroxyl_site
IPR018097 EGF_Ca-bd_CS
IPR035972 GLA-like_dom_SF
IPR000294 GLA_domain
IPR012224 Pept_S1A_FX
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PANTHERiPTHR44064:SF4 PTHR44064:SF4, 1 hit
PfamiView protein in Pfam
PF00008 EGF, 1 hit
PF00594 Gla, 1 hit
PF00089 Trypsin, 1 hit
PIRSFiPIRSF001143 Factor_X, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
PR00001 GLABLOOD
SMARTiView protein in SMART
SM00181 EGF, 2 hits
SM00179 EGF_CA, 1 hit
SM00069 GLA, 1 hit
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
SSF57630 SSF57630, 1 hit
PROSITEiView protein in PROSITE
PS00010 ASX_HYDROXYL, 1 hit
PS00022 EGF_1, 1 hit
PS01186 EGF_2, 2 hits
PS50026 EGF_3, 1 hit
PS01187 EGF_CA, 1 hit
PS00011 GLA_1, 1 hit
PS50998 GLA_2, 1 hit
PS50240 TRYPSIN_DOM, 1 hit
PS00134 TRYPSIN_HIS, 1 hit
PS00135 TRYPSIN_SER, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiFA9_BOVIN
AccessioniPrimary (citable) accession number: P00741
Secondary accession number(s): F1MFL4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: May 27, 2015
Last modified: September 12, 2018
This is version 186 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, 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
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Main funding by: National Institutes of Health

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