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Protein

Coagulation factor IX

Gene

F9

Organism
Homo sapiens (Human)
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.6 Publications

Miscellaneous

In 1952, one of the earliest researchers of the disease, Dr. R.G. Macfarlane used the patient's surname, Christmas, to refer to the disease and also to refer to the clotting factor which he called the 'Christmas Factor' At the time Stephen Christmas was a 5-year-old boy. He died in 1993 at the age of 46 from acquired immunodeficiency syndrome contracted through treatment with blood products.

Catalytic activityi

Selective cleavage of Arg-|-Ile bond in factor X to form factor Xa.4 Publications

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 sourcesBy similarity1 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 sourcesBy similarity1 Publication1
Metal bindingi67Calcium 1; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi72Calcium 5 or magnesium 2; via 4-carboxyglutamateCombined sourcesBy similarity1 Publication1
Metal bindingi73Calcium 2; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi73Calcium 3; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi76Calcium 3; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi76Calcium 5 or magnesium 2; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi76Calcium 5; via 4-carboxyglutamateCombined sources1 Publication1
Metal bindingi82Calcium 6 or magnesium 3; via 4-carboxyglutamateBy similarity1
Metal bindingi86Calcium 6 or magnesium 3; via 4-carboxyglutamateBy similarity1
Metal bindingi93Calcium 7Combined sources1 Publication1
Metal bindingi94Calcium 7; via carbonyl oxygenCombined sources1 Publication1
Metal bindingi96Calcium 7Combined sources1 Publication1
Metal bindingi110Calcium 7Combined sources1 Publication1
Metal bindingi111Calcium 7; via carbonyl oxygenCombined sources1 Publication1
Active sitei267Charge relay system2 Publications1
Metal bindingi281Calcium 8Combined sources5 Publications1
Metal bindingi283Calcium 8; via carbonyl oxygenCombined sources5 Publications1
Metal bindingi286Calcium 8; via carbonyl oxygenCombined sources5 Publications1
Metal bindingi288Calcium 8Combined sources5 Publications1
Metal bindingi291Calcium 8Combined sources5 Publications1
Active sitei315Charge relay system1 Publication1
Active sitei411Charge relay system2 Publications1

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • endopeptidase activity Source: UniProtKB
  • serine-type endopeptidase activity Source: BHF-UCL

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

BRENDAi3.4.21.22 2681
ReactomeiR-HSA-140834 Extrinsic Pathway of Fibrin Clot Formation
R-HSA-140837 Intrinsic Pathway of Fibrin Clot Formation
R-HSA-159740 Gamma-carboxylation of protein precursors
R-HSA-159763 Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus
R-HSA-159782 Removal of aminoterminal propeptides from gamma-carboxylated proteins
SABIO-RKiP00740
SIGNORiP00740

Protein family/group databases

MEROPSiS01.214

Names & Taxonomyi

Protein namesi
Recommended name:
Coagulation factor IX1 Publication (EC:3.4.21.224 Publications)
Alternative name(s):
Christmas factor
Plasma thromboplastin component
Short name:
PTC
Cleaved into the following 2 chains:
Gene namesi
Name:F9
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000101981.10
HGNCiHGNC:3551 F9
MIMi300746 gene
neXtProtiNX_P00740

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

Involvement in diseasei

Hemophilia B (HEMB)38 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn X-linked blood coagulation disorder characterized by a permanent tendency to hemorrhage, due to factor IX deficiency. It is phenotypically similar to hemophilia A, but patients present with fewer symptoms. Many patients are asymptomatic until the hemostatic system is stressed by surgery or trauma.
See also OMIM:306900
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00652117I → N in HEMB; severe; UK 22. 1
Natural variantiVAR_07397520L → S in HEMB; unknown pathological significance; decreased protein abundance; decreased function in blood coagulation. 1 Publication1
Natural variantiVAR_00652228C → R in HEMB; moderate; HB130. Corresponds to variant dbSNP:rs387906481EnsemblClinVar.1
Natural variantiVAR_01734328C → Y in HEMB; decreased protein abundance; decreased function in blood coagulation. 2 Publications1
Natural variantiVAR_00652330V → I in HEMB. 1
Natural variantiVAR_00652543R → L in HEMB; severe; Bendorf, Beuten, Gleiwitz; impairs removal of propeptide. 2 Publications1
Natural variantiVAR_00652443R → Q in HEMB; severe; San Dimas, Oxford-3, Strasbourg-2; impairs removal of propeptide. 6 PublicationsCorresponds to variant dbSNP:rs1275708479Ensembl.1
Natural variantiVAR_00652643R → W in HEMB; severe; Boxtel, Heiden, Lienen; impairs removal of propeptide. 3 Publications1
Natural variantiVAR_00652745K → N in HEMB; severe; Seattle E. 1
Natural variantiVAR_00652846R → S in HEMB; severe; Cambridge; impaired processing of the propeptide; impaired gamma-carboxylation; decreased protein abundance; loss of function in blood coagulation. 1 Publication1
Natural variantiVAR_00652946R → T in HEMB; severe. 1 Publication1
Natural variantiVAR_00653048N → I in HEMB; severe; Calgary-16. 1
Natural variantiVAR_00653149S → P in HEMB. 1
Natural variantiVAR_01734452L → S in HEMB; severe; Gla mutant. 1 Publication1
Natural variantiVAR_00653253E → A in HEMB; severe; Oxford-B2; Gla mutant. 1
Natural variantiVAR_07397654E → D in HEMB; unknown pathological significance; no effect on protein abundance; loss of function in blood coagulation. 1 Publication1
Natural variantiVAR_00653354E → G in HEMB; severe; HB151; Gla mutant. 1
Natural variantiVAR_00653455F → C in HEMB. 1
Natural variantiVAR_00653558G → A in HEMB; severe; Hong Kong-1. 1
Natural variantiVAR_07397758G → E in HEMB; unknown pathological significance; no effect on protein abundance; loss of function in blood coagulation. 1 Publication1
Natural variantiVAR_00653658G → R in HEMB; severe; Los Angeles-4. 1
Natural variantiVAR_00653762 – 63Missing in HEMB; severe. 2
Natural variantiVAR_00653866E → V in HEMB; moderate. 1
Natural variantiVAR_00653967E → K in HEMB; severe; Nagoya-4; Gla mutant. 1
Natural variantiVAR_00654071F → S in HEMB; severe. 1
Natural variantiVAR_00654173E → K in HEMB; severe; Seattle-3; Gla mutant. 1 PublicationCorresponds to variant dbSNP:rs137852225Ensembl.1
Natural variantiVAR_00654273E → V in HEMB; severe; Chongqing; Gla mutant. 1 PublicationCorresponds to variant dbSNP:rs137852226EnsemblClinVar.1
Natural variantiVAR_01730875R → Q in HEMB; mild. 1 PublicationCorresponds to variant dbSNP:rs137852228EnsemblClinVar.1
Natural variantiVAR_01730979E → D in HEMB. 1 PublicationCorresponds to variant dbSNP:rs137852229EnsemblClinVar.1
Natural variantiVAR_01734584T → R in HEMB; decreased protein abundance; loss of function in blood coagulation. 2 Publications1
Natural variantiVAR_00654391Y → C in HEMB; moderate. 1
Natural variantiVAR_00654493D → G in HEMB; moderate; Alabama. 1 PublicationCorresponds to variant dbSNP:rs137852230EnsemblClinVar.1
Natural variantiVAR_00654596Q → P in HEMB; severe; New London. Corresponds to variant dbSNP:rs137852231EnsemblClinVar.1
Natural variantiVAR_00654697C → S in HEMB. 1
Natural variantiVAR_006547101P → R in HEMB. 1
Natural variantiVAR_006548102C → R in HEMB; severe; Basel. 1
Natural variantiVAR_017346106G → D in HEMB. 1 Publication1
Natural variantiVAR_006549106G → S in HEMB; mild; Durham. 2 PublicationsCorresponds to variant dbSNP:rs137852233EnsemblClinVar.1
Natural variantiVAR_006550108C → S in HEMB. 1
Natural variantiVAR_006551110D → N in HEMB; severe; Oxford-D1. Corresponds to variant dbSNP:rs137852274EnsemblClinVar.1
Natural variantiVAR_006552112I → S in HEMB. 1
Natural variantiVAR_006553113N → K in HEMB; mild. 1 Publication1
Natural variantiVAR_006554115Y → C in HEMB; severe. 1 Publication1
Natural variantiVAR_006555119C → F in HEMB; severe. 1
Natural variantiVAR_006556119C → R in HEMB; Iran. 1 Publication1
Natural variantiVAR_017347124E → K in HEMB. 1 Publication1
Natural variantiVAR_006557125G → E in HEMB. 1
Natural variantiVAR_017348125G → R in HEMB. 1 Publication1
Natural variantiVAR_006558125G → V in HEMB. 1 Publication1
Natural variantiVAR_006559129 – 130Missing in HEMB. 2
Natural variantiVAR_017349134C → Y in HEMB. 1 Publication1
Natural variantiVAR_006560136I → T in HEMB; mild. 1
Natural variantiVAR_073978138N → H in HEMB; unknown pathological significance; decreased protein abundance; decreased function in blood coagulation. 1 Publication1
Natural variantiVAR_006561139G → D in HEMB; severe. 1
Natural variantiVAR_006562139G → S in HEMB. 1
Natural variantiVAR_006563155C → F in HEMB; severe. 1 PublicationCorresponds to variant dbSNP:rs1330705989Ensembl.1
Natural variantiVAR_006564160G → E in HEMB; mild. 1
Natural variantiVAR_006565167Q → H in HEMB; mild. 1
Natural variantiVAR_017350169S → C in HEMB. 1 Publication1
Natural variantiVAR_017351170C → F in HEMB. 1 Publication1
Natural variantiVAR_006566178C → R in HEMB. 1
Natural variantiVAR_006567178C → W in HEMB; severe. 1
Natural variantiVAR_006569191R → C in HEMB; moderate; Albuquerque, Cardiff-1. 1 PublicationCorresponds to variant dbSNP:rs137852237EnsemblClinVar.1
Natural variantiVAR_006568191R → H in HEMB; moderate; Chapel-Hill, Chicago-2. 2 PublicationsCorresponds to variant dbSNP:rs137852238EnsemblClinVar.1
Natural variantiVAR_006571226R → G in HEMB; severe; Madrid. 2 Publications1
Natural variantiVAR_006572226R → Q in HEMB; severe; Hilo and Novara; no effect on protein abundance; loss of function in blood coagulation. 4 PublicationsCorresponds to variant dbSNP:rs137852241EnsemblClinVar.1
Natural variantiVAR_006570226R → W in HEMB; severe; Nagoya-1, Dernbach, Deventer, Idaho. 3 PublicationsCorresponds to variant dbSNP:rs137852240EnsemblClinVar.1
Natural variantiVAR_006573227V → D in HEMB; mild. 1
Natural variantiVAR_017310227V → F in HEMB; Milano. 1 PublicationCorresponds to variant dbSNP:rs137852242Ensembl.1
Natural variantiVAR_017311228V → F in HEMB; severe; Kashihara. 1 PublicationCorresponds to variant dbSNP:rs137852243EnsemblClinVar.1
Natural variantiVAR_006574228V → L in HEMB; mild; Cardiff-2. 1 PublicationCorresponds to variant dbSNP:rs137852243EnsemblClinVar.1
Natural variantiVAR_006575241Q → H in HEMB. 1 PublicationCorresponds to variant dbSNP:rs1182648920Ensembl.1
Natural variantiVAR_017352241Q → K in HEMB. 1 Publication1
Natural variantiVAR_017312252C → S in HEMB; severe. 1 PublicationCorresponds to variant dbSNP:rs267606792EnsemblClinVar.1
Natural variantiVAR_017353252C → Y in HEMB. 1 Publication1
Natural variantiVAR_006576253G → E in HEMB; severe. 1
Natural variantiVAR_006577253G → R in HEMB; severe; Luanda. 1 Publication1
Natural variantiVAR_006578265A → T in HEMB; mild. 1
Natural variantiVAR_017313268C → W in HEMB; moderate. 1 PublicationCorresponds to variant dbSNP:rs137852246EnsemblClinVar.1
Natural variantiVAR_006579279A → T in HEMB; mild. 2 PublicationsCorresponds to variant dbSNP:rs137852247EnsemblClinVar.1
Natural variantiVAR_006580283N → D in HEMB; severe. 1
Natural variantiVAR_073979284Missing in HEMB; severe; decreased protein abundance; loss of function in blood coagulation. 1 Publication1
Natural variantiVAR_006581286Missing in HEMB; severe. 1
Natural variantiVAR_017314291E → V in HEMB; Monschau. 1 PublicationCorresponds to variant dbSNP:rs137852279EnsemblClinVar.1
Natural variantiVAR_006582294R → G in HEMB; severe. 1
Natural variantiVAR_006583294R → Q in HEMB; mild to moderate; Dreihacken, Penafiel and Seattle-4. 5 PublicationsCorresponds to variant dbSNP:rs137852249EnsemblClinVar.1
Natural variantiVAR_073980296V → M in HEMB; unknown pathological significance; decreased protein abundance; decreased function in blood coagulation. 1 Publication1
Natural variantiVAR_006584302H → R in HEMB. 1 Publication1
Natural variantiVAR_017315306N → S in HEMB; mild. 1 PublicationCorresponds to variant dbSNP:rs137852251EnsemblClinVar.1
Natural variantiVAR_006585316I → F in HEMB. 1 Publication1
Natural variantiVAR_017354318L → R in HEMB. 1 PublicationCorresponds to variant dbSNP:rs1222227572Ensembl.1
Natural variantiVAR_006586321L → Q in HEMB; severe. 1
Natural variantiVAR_073981328N → K in HEMB; unknown pathological significance; decreased protein abundance; decreased function in blood coagulation. 1 Publication1
Natural variantiVAR_073982328N → Y in HEMB; moderate; decreased protein abundance; decreased function in blood coagulation. 1 Publication1
Natural variantiVAR_006587333P → H in HEMB; severe. 1
Natural variantiVAR_017355333P → T in HEMB. 1 Publication1
Natural variantiVAR_006588342T → K in HEMB; mild. 1
Natural variantiVAR_006589342T → M in HEMB; moderate. 3 PublicationsCorresponds to variant dbSNP:rs137852254EnsemblClinVar.1
Natural variantiVAR_017356344I → L in HEMB. 1 Publication1
Natural variantiVAR_006590351G → D in HEMB. 1
Natural variantiVAR_006591356W → C in HEMB; severe. 1
Natural variantiVAR_006592357G → E in HEMB; severe; Amagasaki. 1 PublicationCorresponds to variant dbSNP:rs137852275EnsemblClinVar.1
Natural variantiVAR_017316357G → R in HEMB. 1 PublicationCorresponds to variant dbSNP:rs137852257EnsemblClinVar.1
Natural variantiVAR_006593362K → E in HEMB; moderate. 1
Natural variantiVAR_006594363G → W in HEMB. 1
Natural variantiVAR_006595366A → D in HEMB. 1
Natural variantiVAR_006596379R → G in HEMB; moderate. 1 Publication1
Natural variantiVAR_006597379R → Q in HEMB; severe; Iceland-1, London and Sesimbra. 3 PublicationsCorresponds to variant dbSNP:rs137852259EnsemblClinVar.1
Natural variantiVAR_006598382C → Y in HEMB. 1
Natural variantiVAR_017358383L → F in HEMB. 1 Publication1
Natural variantiVAR_017357383L → I in HEMB. 1 Publication1
Natural variantiVAR_006599387K → E in HEMB; mild. 1 Publication1
Natural variantiVAR_006600390I → F in HEMB; severe. 1
Natural variantiVAR_006601394M → K in HEMB. 1
Natural variantiVAR_017359395F → I in HEMB. 1 Publication1
Natural variantiVAR_017360395F → L in HEMB. 1 Publication1
Natural variantiVAR_017361396C → F in HEMB. 1 Publication1
Natural variantiVAR_006602396C → S in HEMB; severe. Corresponds to variant dbSNP:rs137852273EnsemblClinVar.1
Natural variantiVAR_017317397A → P in HEMB; mild; Hong Kong-11. 1 PublicationCorresponds to variant dbSNP:rs137852281EnsemblClinVar.1
Natural variantiVAR_006603404R → T in HEMB. 1
Natural variantiVAR_017362407C → R in HEMB. 1 Publication1
Natural variantiVAR_006604407C → S in HEMB; severe. 1
Natural variantiVAR_017318410D → H in HEMB; Mechtal. 1 PublicationCorresponds to variant dbSNP:rs137852278EnsemblClinVar.1
Natural variantiVAR_017320411S → G in HEMB; Varel. 1 PublicationCorresponds to variant dbSNP:rs137852277EnsemblClinVar.1
Natural variantiVAR_017319411S → I in HEMB; Schmallenberg. 1 PublicationCorresponds to variant dbSNP:rs137852276EnsemblClinVar.1
Natural variantiVAR_017363412G → E in HEMB. 1 PublicationCorresponds to variant dbSNP:rs1233706534Ensembl.1
Natural variantiVAR_006605413G → R in HEMB; moderate to severe. 2 PublicationsCorresponds to variant dbSNP:rs1306658513Ensembl.1
Natural variantiVAR_017321414P → T in HEMB; Bergamo; increased protein abundance; loss of function in blood coagulation. 3 PublicationsCorresponds to variant dbSNP:rs137852265EnsemblClinVar.1
Natural variantiVAR_006606419V → E in HEMB; moderately severe. 2 PublicationsCorresponds to variant dbSNP:rs137852280EnsemblClinVar.1
Natural variantiVAR_006607424F → V in HEMB. 1 Publication1
Natural variantiVAR_006608426T → P in HEMB; severe; Barcelos. 1 Publication1
Natural variantiVAR_006609430S → T in HEMB. 1
Natural variantiVAR_006610431W → G in HEMB. 1
Natural variantiVAR_006611431W → R in HEMB; moderate. 1
Natural variantiVAR_006612432G → S in HEMB; severe. 1
Natural variantiVAR_006613432G → V in HEMB; severe. 1 Publication1
Natural variantiVAR_006614433E → A in HEMB. 1
Natural variantiVAR_006615433E → K in HEMB. Corresponds to variant dbSNP:rs767828752Ensembl.1
Natural variantiVAR_017364435C → Y in HEMB. 1 Publication1
Natural variantiVAR_006616436A → V in HEMB; moderately severe; Niigata. 1 PublicationCorresponds to variant dbSNP:rs137852266EnsemblClinVar.1
Natural variantiVAR_017365442G → E in HEMB. 1 Publication1
Natural variantiVAR_017322442G → R in HEMB; severe; Angers. 1 PublicationCorresponds to variant dbSNP:rs137852267EnsemblClinVar.1
Natural variantiVAR_017323443I → T in HEMB; moderately severe; Long Beach, Los Angeles and Vancouver. 2 PublicationsCorresponds to variant dbSNP:rs137852268EnsemblClinVar.1
Natural variantiVAR_006617445T → TIYT in HEMB; severe; Lousada. 1
Natural variantiVAR_073983447V → VYTKV in HEMB; reduced protein abundance; loss of function in blood coagulation. 1 Publication1
Natural variantiVAR_006618449R → Q in HEMB; mild. 1 PublicationCorresponds to variant dbSNP:rs143018900Ensembl.1
Natural variantiVAR_006619449R → W in HEMB; mild. 1 PublicationCorresponds to variant dbSNP:rs757996262Ensembl.1
Natural variantiVAR_006620450Y → C in HEMB; severe. 1 Publication1
Natural variantiVAR_017324453W → R in HEMB. 1 PublicationCorresponds to variant dbSNP:rs137852269EnsemblClinVar.1
Natural variantiVAR_006621454I → T in HEMB; Italy. 1 Publication1
Mutations in position 43 (Oxford-3, San Dimas) and 46 (Cambridge) prevents cleavage of the propeptide (PubMed:12588353, PubMed:2738071, PubMed:3009023, PubMed:8295821, PubMed:9169594, PubMed:9600455, PubMed:25251685). Mutation in position 93 (Alabama) probably fails to bind to cell membranes (PubMed:3790720). Mutation in position 191 (Chapel-Hill) or in position 226 (Nagoya or Hilo) prevent cleavage of the activation peptide (PubMed:6603618, PubMed:8076946, PubMed:12588353, PubMed:2162822, PubMed:25251685, PubMed:2713493).12 Publications
Thrombophilia, X-linked, due to factor IX defect (THPH8)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA hemostatic disorder characterized by a tendency to thrombosis.
See also OMIM:300807
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_062999384R → L in THPH8; factor IX Padua; higher specific activity than wild-type. 1 PublicationCorresponds to variant dbSNP:rs137852283EnsemblClinVar.1

Pharmaceutical usei

Available under the name BeneFix (Baxter and American Home Products). Used to treat hemophilia B.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi305Y → F: Strongly increases enzyme activity with a synthetic peptide substrate; when associated with T-311; A-365 and T-391. 1 Publication1
Mutagenesisi311K → T: Strongly increases enzyme activity with a synthetic peptide substrate; when associated with F-305; A-365 and T-391. 1 Publication1
Mutagenesisi312Y → A: Strongly decreases enzyme activity with a synthetic peptide substrate. 1 Publication1
Mutagenesisi391Y → T: Strongly increases enzyme activity with a synthetic peptide substrate; when associated with F-305; T-311 and A-365. 1 Publication1

Keywords - Diseasei

Disease mutation, Hemophilia, Thrombophilia

Organism-specific databases

DisGeNETi2158
GeneReviewsiF9
MalaCardsiF9
MIMi300807 phenotype
306900 phenotype
OpenTargetsiENSG00000101981
Orphaneti169799 Mild hemophilia B
169796 Moderately severe hemophilia B
169793 Severe hemophilia B
177929 Symptomatic form of hemophilia B in female carriers
PharmGKBiPA27954

Protein family/group databases

Allergomei9616 Hom s Factor IX

Chemistry databases

ChEMBLiCHEMBL2016
DrugBankiDB00025 Antihemophilic Factor (Recombinant)
DB13150 Coagulation factor VII human
DB00170 Menadione
DB05131 TTP889
GuidetoPHARMACOLOGYi2364

Polymorphism and mutation databases

BioMutaiF9

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 28Sequence analysisAdd BLAST28
PropeptideiPRO_000002775529 – 461 PublicationAdd BLAST18
ChainiPRO_000002775647 – 461Coagulation factor IXAdd BLAST415
ChainiPRO_000002775747 – 191Coagulation factor IXa light chainAdd BLAST145
PropeptideiPRO_0000027758192 – 226Activation peptideAdd BLAST35
ChainiPRO_0000027759227 – 461Coagulation factor IXa heavy chainAdd BLAST235

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei534-carboxyglutamatePROSITE-ProRule annotationBy similarity1
Modified residuei544-carboxyglutamatePROSITE-ProRule annotationBy similarity1
Modified residuei614-carboxyglutamatePROSITE-ProRule annotationBy similarity1
Modified residuei634-carboxyglutamatePROSITE-ProRule annotationBy similarity1
Disulfide bondi64 ↔ 69By similarity
Modified residuei664-carboxyglutamatePROSITE-ProRule annotationBy similarity1
Modified residuei674-carboxyglutamatePROSITE-ProRule annotationBy similarity1
Modified residuei724-carboxyglutamatePROSITE-ProRule annotationBy similarity1
Modified residuei734-carboxyglutamatePROSITE-ProRule annotationBy similarity1
Modified residuei764-carboxyglutamatePROSITE-ProRule annotationBy similarity1
Modified residuei794-carboxyglutamatePROSITE-ProRule annotationBy similarity1
Modified residuei824-carboxyglutamatePROSITE-ProRule annotationBy similarity1
Glycosylationi85O-linked (GalNAc...) threonine1 Publication1
Modified residuei864-carboxyglutamatePROSITE-ProRule annotationBy similarity1
Disulfide bondi97 ↔ 108Combined sources2 Publications
GlycosylationiCAR_00000999O-linked (Glc...) serine; alternate4 Publications1
Glycosylationi99O-linked (Xyl...) serine; alternate3 Publications1
Disulfide bondi102 ↔ 117Combined sources2 Publications
GlycosylationiCAR_000010107O-linked (Fuc...) serine2 Publications1
Modified residuei110(3R)-3-hydroxyaspartate1 Publication1
Modified residuei114Phosphoserine1 Publication1
Disulfide bondi119 ↔ 128Combined sources2 Publications
Disulfide bondi134 ↔ 145Combined sources4 Publications
Disulfide bondi141 ↔ 155Combined sources4 Publications
Disulfide bondi157 ↔ 170Combined sources4 Publications
Disulfide bondi178 ↔ 335Interchain (between light and heavy chains)Combined sources4 Publications
Modified residuei201Sulfotyrosine1 Publication1
Glycosylationi203N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei204Phosphoserine2 Publications1
Modified residuei205Phosphothreonine; alternate1 Publication1
Glycosylationi205O-linked (GalNAc...) threonine; alternate2 Publications1
Glycosylationi213N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi215O-linked (GalNAc...) threonine2 Publications1
Glycosylationi225O-linked (GalNAc...) threonine1 Publication1
Disulfide bondi252 ↔ 268Combined sources4 Publications
Disulfide bondi382 ↔ 396Combined sources4 Publications
Disulfide bondi407 ↔ 435Combined sources4 Publications

Post-translational modificationi

Activated by factor XIa, which excises the activation peptide (PubMed:9169594, PubMed:1730085). The propeptide can also be removed by snake venom protease (PubMed:20004170, PubMed:20080729).6 Publications
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. Xylosylation at this site is minor.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei191 – 192Cleavage; by factor XIa2
Sitei226 – 227Cleavage; by factor XIa2

Keywords - PTMi

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

Proteomic databases

PaxDbiP00740
PeptideAtlasiP00740
PRIDEiP00740
ProteomicsDBi51274

PTM databases

GlyConnecti96
iPTMnetiP00740
PhosphoSitePlusiP00740
UniCarbKBiP00740

Miscellaneous databases

PMAP-CutDBiP00740

Expressioni

Tissue specificityi

Detected in blood plasma (at protein level) (PubMed:3857619, PubMed:8295821, PubMed:2592373, PubMed:9169594, PubMed:19846852). Synthesized primarily in the liver and secreted in plasma.3 Publications

Gene expression databases

BgeeiENSG00000101981 Expressed in 31 organ(s), highest expression level in liver
CleanExiHS_F9
GenevisibleiP00740 HS

Interactioni

Subunit structurei

Heterodimer of a light chain and a heavy chain; disulfide-linked (PubMed:20121198, PubMed:20121197, PubMed:20080729). Interacts with SERPINC1.5 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi108456, 39 interactors
DIPiDIP-58520N
ELMiP00740
IntActiP00740, 4 interactors
MINTiP00740
STRINGi9606.ENSP00000218099

Chemistry databases

BindingDBiP00740

Structurei

Secondary structure

1461
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP00740
SMRiP00740
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP00740

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
Domaini227 – 459Peptidase S1PROSITE-ProRule annotationAdd BLAST233

Domaini

Calcium binds to the gamma-carboxyglutamic acid (Gla) residues in the Gla domain. Calcium can also bind, with stronger affinity, to another site beyond the Gla domain (PubMed:6425296). 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 (By similarity).By similarity3 Publications

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IGPV Eukaryota
COG5640 LUCA
GeneTreeiENSGT00760000118890
HOGENOMiHOG000251821
HOVERGENiHBG013304
InParanoidiP00740
KOiK01321
OMAiSYECWCQ
OrthoDBiEOG091G0AH5
PhylomeDBiP00740
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

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: P00740-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MQRVNMIMAE SPGLITICLL GYLLSAECTV FLDHENANKI LNRPKRYNSG
60 70 80 90 100
KLEEFVQGNL ERECMEEKCS FEEAREVFEN TERTTEFWKQ YVDGDQCESN
110 120 130 140 150
PCLNGGSCKD DINSYECWCP FGFEGKNCEL DVTCNIKNGR CEQFCKNSAD
160 170 180 190 200
NKVVCSCTEG YRLAENQKSC EPAVPFPCGR VSVSQTSKLT RAETVFPDVD
210 220 230 240 250
YVNSTEAETI LDNITQSTQS FNDFTRVVGG EDAKPGQFPW QVVLNGKVDA
260 270 280 290 300
FCGGSIVNEK WIVTAAHCVE TGVKITVVAG EHNIEETEHT EQKRNVIRII
310 320 330 340 350
PHHNYNAAIN KYNHDIALLE LDEPLVLNSY VTPICIADKE YTNIFLKFGS
360 370 380 390 400
GYVSGWGRVF HKGRSALVLQ YLRVPLVDRA TCLRSTKFTI YNNMFCAGFH
410 420 430 440 450
EGGRDSCQGD SGGPHVTEVE GTSFLTGIIS WGEECAMKGK YGIYTKVSRY
460
VNWIKEKTKL T
Length:461
Mass (Da):51,778
Last modified:June 7, 2005 - v2
Checksum:iC4720C1234477EF5
GO
Isoform 2 (identifier: P00740-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     93-130: Missing.

Show »
Length:423
Mass (Da):47,618
Checksum:i2556B3F27FB23A77
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength