Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Coagulation factor IX

Gene

F9

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi47 – 471Calcium 1; via carbonyl oxygenCombined sources1 Publication
Metal bindingi48 – 481Calcium 2Combined sources1 Publication
Metal bindingi53 – 531Calcium 1; via 4-carboxyglutamateCombined sources1 Publication
Metal bindingi53 – 531Calcium 2; via 4-carboxyglutamateCombined sources1 Publication
Metal bindingi54 – 541Calcium 2; via 4-carboxyglutamateCombined sources1 Publication
Metal bindingi54 – 541Calcium 3; via 4-carboxyglutamateCombined sources1 Publication
Metal bindingi61 – 611Calcium 4 or magnesium 1; via 4-carboxyglutamateCombined sourcesBy similarity1 Publication
Metal bindingi63 – 631Calcium 1; via 4-carboxyglutamateCombined sources1 Publication
Metal bindingi63 – 631Calcium 2; via 4-carboxyglutamateCombined sources1 Publication
Metal bindingi63 – 631Calcium 3; via 4-carboxyglutamateCombined sources1 Publication
Metal bindingi66 – 661Calcium 4 or magnesium 1; via 4-carboxyglutamateCombined sourcesBy similarity1 Publication
Metal bindingi67 – 671Calcium 1; via 4-carboxyglutamateCombined sources1 Publication
Metal bindingi72 – 721Calcium 5 or magnesium 2; via 4-carboxyglutamateCombined sourcesBy similarity1 Publication
Metal bindingi73 – 731Calcium 2; via 4-carboxyglutamateCombined sources1 Publication
Metal bindingi73 – 731Calcium 3; via 4-carboxyglutamateCombined sources1 Publication
Metal bindingi76 – 761Calcium 3; via 4-carboxyglutamateCombined sources1 Publication
Metal bindingi76 – 761Calcium 5 or magnesium 2; via 4-carboxyglutamateCombined sources1 Publication
Metal bindingi76 – 761Calcium 5; via 4-carboxyglutamateCombined sources1 Publication
Metal bindingi82 – 821Calcium 6 or magnesium 3; via 4-carboxyglutamateBy similarity
Metal bindingi86 – 861Calcium 6 or magnesium 3; via 4-carboxyglutamateBy similarity
Metal bindingi93 – 931Calcium 7Combined sources1 Publication
Metal bindingi94 – 941Calcium 7; via carbonyl oxygenCombined sources1 Publication
Metal bindingi96 – 961Calcium 7Combined sources1 Publication
Metal bindingi110 – 1101Calcium 7Combined sources1 Publication
Metal bindingi111 – 1111Calcium 7; via carbonyl oxygenCombined sources1 Publication
Sitei191 – 1922Cleavage; by factor XIa
Sitei226 – 2272Cleavage; by factor XIa
Active sitei267 – 2671Charge relay system2 Publications
Metal bindingi281 – 2811Calcium 8Combined sources5 Publications
Metal bindingi283 – 2831Calcium 8; via carbonyl oxygenCombined sources5 Publications
Metal bindingi286 – 2861Calcium 8; via carbonyl oxygenCombined sources5 Publications
Metal bindingi288 – 2881Calcium 8Combined sources5 Publications
Metal bindingi291 – 2911Calcium 8Combined sources5 Publications
Active sitei315 – 3151Charge relay system1 Publication
Active sitei411 – 4111Charge relay system2 Publications

GO - Molecular functioni

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

GO - Biological processi

  • blood coagulation Source: UniProtKB
  • blood coagulation, extrinsic pathway Source: Reactome
  • blood coagulation, intrinsic pathway Source: Reactome
  • cellular protein metabolic process Source: Reactome
  • peptidyl-glutamic acid carboxylation Source: Reactome
  • post-translational protein modification Source: Reactome
  • proteolysis Source: UniProtKB
  • zymogen activation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Blood coagulation, Hemostasis

Keywords - Ligandi

Calcium, Magnesium, Metal-binding

Enzyme and pathway databases

BRENDAi3.4.21.22. 2681.
ReactomeiREACT_1050. Gamma-carboxylation of protein precursors.
REACT_1573. Extrinsic Pathway of Fibrin Clot Formation.
REACT_1906. Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus.
REACT_326. Intrinsic Pathway of Fibrin Clot Formation.
REACT_733. Removal of aminoterminal propeptides from gamma-carboxylated proteins.
SABIO-RKP00740.

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
ProteomesiUP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:3551. F9.

Subcellular locationi

GO - Cellular componenti

  • endoplasmic reticulum lumen Source: Reactome
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
  • extracellular space Source: UniProtKB
  • Golgi lumen Source: Reactome
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Hemophilia B (HEMB)36 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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti17 – 171I → N in HEMB; severe; UK 22.
VAR_006521
Natural varianti28 – 281C → R in HEMB; moderate; HB130.
VAR_006522
Natural varianti28 – 281C → Y in HEMB. 1 Publication
VAR_017343
Natural varianti30 – 301V → I in HEMB.
VAR_006523
Natural varianti43 – 431R → L in HEMB; severe; Bendorf, Beuten, Gleiwitz; impairs removal of propeptide. 2 Publications
VAR_006525
Natural varianti43 – 431R → Q in HEMB; severe; San Dimas, Oxford-3, Strasbourg-2; impairs removal of propeptide. 6 Publications
VAR_006524
Natural varianti43 – 431R → W in HEMB; severe; Boxtel, Heiden, Lienen; impairs removal of propeptide. 3 Publications
VAR_006526
Natural varianti45 – 451K → N in HEMB; severe; Seattle E.
VAR_006527
Natural varianti46 – 461R → S in HEMB; severe; Cambridge.
VAR_006528
Natural varianti46 – 461R → T in HEMB; severe. 1 Publication
VAR_006529
Natural varianti48 – 481N → I in HEMB; severe; Calgary-16.
VAR_006530
Natural varianti49 – 491S → P in HEMB.
VAR_006531
Natural varianti52 – 521L → S in HEMB; severe; Gla mutant. 1 Publication
VAR_017344
Natural varianti53 – 531E → A in HEMB; severe; Oxford-B2; Gla mutant.
VAR_006532
Natural varianti54 – 541E → G in HEMB; severe; HB151; Gla mutant.
VAR_006533
Natural varianti55 – 551F → C in HEMB.
VAR_006534
Natural varianti58 – 581G → A in HEMB; severe; Hong Kong-1.
VAR_006535
Natural varianti58 – 581G → R in HEMB; severe; Los Angeles-4.
VAR_006536
Natural varianti62 – 632Missing in HEMB; severe.
VAR_006537
Natural varianti66 – 661E → V in HEMB; moderate.
VAR_006538
Natural varianti67 – 671E → K in HEMB; severe; Nagoya-4; Gla mutant.
VAR_006539
Natural varianti71 – 711F → S in HEMB; severe.
VAR_006540
Natural varianti73 – 731E → K in HEMB; severe; Seattle-3; Gla mutant. 1 Publication
VAR_006541
Natural varianti73 – 731E → V in HEMB; severe; Chongqing; Gla mutant. 1 Publication
VAR_006542
Natural varianti75 – 751R → Q in HEMB; mild. 1 Publication
VAR_017308
Natural varianti79 – 791E → D in HEMB. 1 Publication
VAR_017309
Natural varianti84 – 841T → R in HEMB. 1 Publication
VAR_017345
Natural varianti91 – 911Y → C in HEMB; moderate.
VAR_006543
Natural varianti93 – 931D → G in HEMB; moderate; Alabama. 1 Publication
VAR_006544
Natural varianti96 – 961Q → P in HEMB; severe; New London.
VAR_006545
Natural varianti97 – 971C → S in HEMB.
VAR_006546
Natural varianti101 – 1011P → R in HEMB.
VAR_006547
Natural varianti102 – 1021C → R in HEMB; severe; Basel.
VAR_006548
Natural varianti106 – 1061G → D in HEMB. 1 Publication
VAR_017346
Natural varianti106 – 1061G → S in HEMB; mild; Durham. 2 Publications
VAR_006549
Natural varianti108 – 1081C → S in HEMB.
VAR_006550
Natural varianti110 – 1101D → N in HEMB; severe; Oxford-D1.
VAR_006551
Natural varianti112 – 1121I → S in HEMB.
VAR_006552
Natural varianti113 – 1131N → K in HEMB; mild. 1 Publication
VAR_006553
Natural varianti115 – 1151Y → C in HEMB; severe. 1 Publication
VAR_006554
Natural varianti119 – 1191C → F in HEMB; severe.
VAR_006555
Natural varianti119 – 1191C → R in HEMB; Iran. 1 Publication
VAR_006556
Natural varianti124 – 1241E → K in HEMB. 1 Publication
VAR_017347
Natural varianti125 – 1251G → E in HEMB.
VAR_006557
Natural varianti125 – 1251G → R in HEMB. 1 Publication
VAR_017348
Natural varianti125 – 1251G → V in HEMB. 1 Publication
VAR_006558
Natural varianti129 – 1302Missing in HEMB.
VAR_006559
Natural varianti134 – 1341C → Y in HEMB. 1 Publication
VAR_017349
Natural varianti136 – 1361I → T in HEMB; mild.
VAR_006560
Natural varianti139 – 1391G → D in HEMB; severe.
VAR_006561
Natural varianti139 – 1391G → S in HEMB.
VAR_006562
Natural varianti155 – 1551C → F in HEMB; severe. 1 Publication
VAR_006563
Natural varianti160 – 1601G → E in HEMB; mild.
VAR_006564
Natural varianti167 – 1671Q → H in HEMB; mild.
VAR_006565
Natural varianti169 – 1691S → C in HEMB. 1 Publication
VAR_017350
Natural varianti170 – 1701C → F in HEMB. 1 Publication
VAR_017351
Natural varianti178 – 1781C → R in HEMB.
VAR_006566
Natural varianti178 – 1781C → W in HEMB; severe.
VAR_006567
Natural varianti191 – 1911R → C in HEMB; moderate; Albuquerque, Cardiff-1. 1 Publication
VAR_006569
Natural varianti191 – 1911R → H in HEMB; moderate; Chapel-Hill, Chicago-2. 2 Publications
VAR_006568
Natural varianti226 – 2261R → G in HEMB; severe; Madrid. 2 Publications
VAR_006571
Natural varianti226 – 2261R → Q in HEMB; severe; Hilo and Novara. 3 Publications
VAR_006572
Natural varianti226 – 2261R → W in HEMB; severe; Nagoya-1, Dernbach, Deventer, Idaho. 3 Publications
VAR_006570
Natural varianti227 – 2271V → D in HEMB; mild.
VAR_006573
Natural varianti227 – 2271V → F in HEMB; Milano. 1 Publication
VAR_017310
Natural varianti228 – 2281V → F in HEMB; severe; Kashihara. 1 Publication
VAR_017311
Natural varianti228 – 2281V → L in HEMB; mild; Cardiff-2. 1 Publication
VAR_006574
Natural varianti241 – 2411Q → H in HEMB. 1 Publication
VAR_006575
Natural varianti241 – 2411Q → K in HEMB. 1 Publication
VAR_017352
Natural varianti252 – 2521C → S in HEMB; severe. 1 Publication
VAR_017312
Natural varianti252 – 2521C → Y in HEMB. 1 Publication
VAR_017353
Natural varianti253 – 2531G → E in HEMB; severe.
VAR_006576
Natural varianti253 – 2531G → R in HEMB; severe; Luanda. 1 Publication
VAR_006577
Natural varianti265 – 2651A → T in HEMB; mild.
VAR_006578
Natural varianti268 – 2681C → W in HEMB; moderate. 1 Publication
VAR_017313
Natural varianti279 – 2791A → T in HEMB; mild. 2 Publications
VAR_006579
Natural varianti283 – 2831N → D in HEMB; severe.
VAR_006580
Natural varianti286 – 2861Missing in HEMB; severe.
VAR_006581
Natural varianti291 – 2911E → V in HEMB; Monschau. 1 Publication
VAR_017314
Natural varianti294 – 2941R → G in HEMB; severe.
VAR_006582
Natural varianti294 – 2941R → Q in HEMB; mild to moderate; Dreihacken, Penafiel and Seattle-4. 5 Publications
VAR_006583
Natural varianti302 – 3021H → R in HEMB. 1 Publication
VAR_006584
Natural varianti306 – 3061N → S in HEMB; mild. 1 Publication
VAR_017315
Natural varianti316 – 3161I → F in HEMB. 1 Publication
VAR_006585
Natural varianti318 – 3181L → R in HEMB. 1 Publication
VAR_017354
Natural varianti321 – 3211L → Q in HEMB; severe.
VAR_006586
Natural varianti333 – 3331P → H in HEMB; severe.
VAR_006587
Natural varianti333 – 3331P → T in HEMB. 1 Publication
VAR_017355
Natural varianti342 – 3421T → K in HEMB; mild.
VAR_006588
Natural varianti342 – 3421T → M in HEMB; moderate. 3 Publications
VAR_006589
Natural varianti344 – 3441I → L in HEMB. 1 Publication
VAR_017356
Natural varianti351 – 3511G → D in HEMB.
VAR_006590
Natural varianti356 – 3561W → C in HEMB; severe.
VAR_006591
Natural varianti357 – 3571G → E in HEMB; severe; Amagasaki. 1 Publication
VAR_006592
Natural varianti357 – 3571G → R in HEMB. 1 Publication
VAR_017316
Natural varianti362 – 3621K → E in HEMB; moderate.
VAR_006593
Natural varianti363 – 3631G → W in HEMB.
VAR_006594
Natural varianti366 – 3661A → D in HEMB.
VAR_006595
Natural varianti379 – 3791R → G in HEMB; moderate. 1 Publication
VAR_006596
Natural varianti379 – 3791R → Q in HEMB; severe; Iceland-1, London and Sesimbra. 3 Publications
VAR_006597
Natural varianti382 – 3821C → Y in HEMB.
VAR_006598
Natural varianti383 – 3831L → F in HEMB. 1 Publication
VAR_017358
Natural varianti383 – 3831L → I in HEMB. 1 Publication
VAR_017357
Natural varianti387 – 3871K → E in HEMB; mild. 1 Publication
VAR_006599
Natural varianti390 – 3901I → F in HEMB; severe.
VAR_006600
Natural varianti394 – 3941M → K in HEMB.
VAR_006601
Natural varianti395 – 3951F → I in HEMB. 1 Publication
VAR_017359
Natural varianti395 – 3951F → L in HEMB. 1 Publication
VAR_017360
Natural varianti396 – 3961C → F in HEMB. 1 Publication
VAR_017361
Natural varianti396 – 3961C → S in HEMB; severe.
VAR_006602
Natural varianti397 – 3971A → P in HEMB; mild; Hong Kong-11. 1 Publication
VAR_017317
Natural varianti404 – 4041R → T in HEMB.
VAR_006603
Natural varianti407 – 4071C → R in HEMB. 1 Publication
VAR_017362
Natural varianti407 – 4071C → S in HEMB; severe.
VAR_006604
Natural varianti410 – 4101D → H in HEMB; Mechtal. 1 Publication
VAR_017318
Natural varianti411 – 4111S → G in HEMB; Varel. 1 Publication
VAR_017320
Natural varianti411 – 4111S → I in HEMB; Schmallenberg. 1 Publication
VAR_017319
Natural varianti412 – 4121G → E in HEMB. 1 Publication
VAR_017363
Natural varianti413 – 4131G → R in HEMB; moderate to severe. 2 Publications
VAR_006605
Natural varianti414 – 4141P → T in HEMB; Bergamo. 2 Publications
VAR_017321
Natural varianti419 – 4191V → E in HEMB; moderately severe. 2 Publications
VAR_006606
Natural varianti424 – 4241F → V in HEMB. 1 Publication
VAR_006607
Natural varianti426 – 4261T → P in HEMB; severe; Barcelos. 1 Publication
VAR_006608
Natural varianti430 – 4301S → T in HEMB.
VAR_006609
Natural varianti431 – 4311W → G in HEMB.
VAR_006610
Natural varianti431 – 4311W → R in HEMB; moderate.
VAR_006611
Natural varianti432 – 4321G → S in HEMB; severe.
VAR_006612
Natural varianti432 – 4321G → V in HEMB; severe. 1 Publication
VAR_006613
Natural varianti433 – 4331E → A in HEMB.
VAR_006614
Natural varianti433 – 4331E → K in HEMB.
VAR_006615
Natural varianti435 – 4351C → Y in HEMB. 1 Publication
VAR_017364
Natural varianti436 – 4361A → V in HEMB; moderately severe; Niigata. 1 Publication
VAR_006616
Natural varianti442 – 4421G → E in HEMB. 1 Publication
VAR_017365
Natural varianti442 – 4421G → R in HEMB; severe; Angers. 1 Publication
VAR_017322
Natural varianti443 – 4431I → T in HEMB; moderately severe; Long Beach, Los Angeles and Vancouver. 2 Publications
VAR_017323
Natural varianti445 – 4451T → TIYT in HEMB; severe; Lousada.
VAR_006617
Natural varianti449 – 4491R → Q in HEMB; mild. 1 Publication
VAR_006618
Natural varianti449 – 4491R → W in HEMB; mild. 1 Publication
VAR_006619
Natural varianti450 – 4501Y → C in HEMB; severe. 1 Publication
VAR_006620
Natural varianti453 – 4531W → R in HEMB. 1 Publication
VAR_017324
Natural varianti454 – 4541I → T in HEMB; Italy. 1 Publication
VAR_006621

Mutations in position 43 (Oxford-3, San Dimas) and 46 (Cambridge) prevents cleavage of the propeptide, mutation in position 93 (Alabama) probably fails to bind to cell membranes, mutation in position 191 (Chapel-Hill) or in position 226 (Nagoya OR Hilo) prevent cleavage of the activation peptide.

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti384 – 3841R → L in THPH8; factor IX Padua; higher specific activity than wild-type. 1 Publication
VAR_062999

Pharmaceutical usei

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

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi305 – 3051Y → F: Strongly increases enzyme activity with a synthetic peptide substrate; when associated with T-311; A-365 and T-391. 1 Publication
Mutagenesisi311 – 3111K → T: Strongly increases enzyme activity with a synthetic peptide substrate; when associated with F-305; A-365 and T-391. 1 Publication
Mutagenesisi312 – 3121Y → A: Strongly decreases enzyme activity with a synthetic peptide substrate. 1 Publication
Mutagenesisi391 – 3911Y → T: Strongly increases enzyme activity with a synthetic peptide substrate; when associated with F-305; T-311 and A-365. 1 Publication

Keywords - Diseasei

Disease mutation, Hemophilia, Thrombophilia

Organism-specific databases

MIMi300807. phenotype.
306900. phenotype.
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

DrugBankiDB00025. Antihemophilic Factor.
DB00170. Menadione.

Polymorphism and mutation databases

BioMutaiF9.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2828Sequence AnalysisAdd
BLAST
Propeptidei29 – 46181 PublicationPRO_0000027755Add
BLAST
Chaini47 – 461415Coagulation factor IXPRO_0000027756Add
BLAST
Chaini47 – 191145Coagulation factor IXa light chainPRO_0000027757Add
BLAST
Propeptidei192 – 22635Activation peptidePRO_0000027758Add
BLAST
Chaini227 – 461235Coagulation factor IXa heavy chainPRO_0000027759Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei53 – 5314-carboxyglutamatePROSITE-ProRule annotationBy similarity
Modified residuei54 – 5414-carboxyglutamatePROSITE-ProRule annotationBy similarity
Modified residuei61 – 6114-carboxyglutamatePROSITE-ProRule annotationBy similarity
Modified residuei63 – 6314-carboxyglutamatePROSITE-ProRule annotationBy similarity
Disulfide bondi64 ↔ 69By similarity
Modified residuei66 – 6614-carboxyglutamatePROSITE-ProRule annotationBy similarity
Modified residuei67 – 6714-carboxyglutamatePROSITE-ProRule annotationBy similarity
Modified residuei72 – 7214-carboxyglutamatePROSITE-ProRule annotationBy similarity
Modified residuei73 – 7314-carboxyglutamatePROSITE-ProRule annotationBy similarity
Modified residuei76 – 7614-carboxyglutamatePROSITE-ProRule annotationBy similarity
Modified residuei79 – 7914-carboxyglutamatePROSITE-ProRule annotationBy similarity
Modified residuei82 – 8214-carboxyglutamatePROSITE-ProRule annotationBy similarity
Glycosylationi85 – 851O-linked (GalNAc...)1 Publication
Modified residuei86 – 8614-carboxyglutamatePROSITE-ProRule annotationBy similarity
Disulfide bondi97 ↔ 108Combined sources2 Publications
Glycosylationi99 – 991O-linked (Glc...); alternate2 PublicationsCAR_000009
Glycosylationi99 – 991O-linked (Xyl...); alternate1 Publication
Disulfide bondi102 ↔ 117Combined sources2 Publications
Glycosylationi107 – 1071O-linked (Fuc...)1 PublicationCAR_000010
Modified residuei110 – 1101(3R)-3-hydroxyaspartate1 Publication
Modified residuei114 – 1141Phosphoserine1 Publication
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 residuei201 – 2011Sulfotyrosine1 Publication
Glycosylationi203 – 2031N-linked (GlcNAc...)Sequence Analysis
Modified residuei204 – 2041Phosphoserine2 Publications
Modified residuei205 – 2051Phosphothreonine1 Publication
Glycosylationi205 – 2051O-linked (GalNAc...)2 Publications
Glycosylationi213 – 2131N-linked (GlcNAc...)Sequence Analysis
Glycosylationi215 – 2151O-linked (GalNAc...)2 Publications
Glycosylationi225 – 2251O-linked (GalNAc...)1 Publication
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.

Keywords - PTMi

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

Proteomic databases

PaxDbiP00740.
PeptideAtlasiP00740.
PRIDEiP00740.

PTM databases

PhosphoSiteiP00740.
UniCarbKBiP00740.

Miscellaneous databases

PMAP-CutDBP00740.

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

BgeeiP00740.
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

Protein-protein interaction databases

BioGridi108456. 10 interactions.
DIPiDIP-58520N.
IntActiP00740. 1 interaction.
STRINGi9606.ENSP00000218099.

Structurei

Secondary structure

1
461
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi50 – 523Combined sources
Helixi60 – 645Combined sources
Beta strandi65 – 673Combined sources
Helixi71 – 755Combined sources
Beta strandi78 – 803Combined sources
Helixi81 – 9010Combined sources
Turni96 – 994Combined sources
Beta strandi107 – 1115Combined sources
Beta strandi114 – 1185Combined sources
Turni125 – 1284Combined sources
Turni134 – 1363Combined sources
Helixi137 – 1404Combined sources
Beta strandi142 – 1476Combined sources
Beta strandi149 – 1513Combined sources
Beta strandi153 – 1564Combined sources
Beta strandi161 – 1633Combined sources
Beta strandi165 – 1684Combined sources
Beta strandi170 – 1767Combined sources
Beta strandi187 – 1893Combined sources
Beta strandi241 – 2488Combined sources
Beta strandi252 – 2587Combined sources
Beta strandi261 – 2644Combined sources
Helixi266 – 2683Combined sources
Beta strandi271 – 2733Combined sources
Beta strandi276 – 2805Combined sources
Beta strandi282 – 2865Combined sources
Beta strandi292 – 30110Combined sources
Turni303 – 3064Combined sources
Beta strandi307 – 3104Combined sources
Turni311 – 3144Combined sources
Beta strandi317 – 3237Combined sources
Helixi339 – 3479Combined sources
Beta strandi350 – 36011Combined sources
Beta strandi370 – 3778Combined sources
Helixi379 – 3846Combined sources
Beta strandi394 – 3985Combined sources
Beta strandi414 – 4196Combined sources
Beta strandi422 – 43110Combined sources
Beta strandi433 – 4364Combined sources
Beta strandi442 – 4465Combined sources
Helixi447 – 4504Combined sources
Helixi451 – 4577Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1CFHNMR-A47-93[»]
1CFINMR-A47-93[»]
1EDMX-ray1.50B/C92-130[»]
1IXANMR-A92-130[»]
1MGXNMR-A47-93[»]
1NL0X-ray2.20G47-91[»]
1RFNX-ray2.80A227-461[»]
B133-188[»]
2WPHX-ray1.50E133-191[»]
S227-461[»]
2WPIX-ray1.99E133-191[»]
S227-461[»]
2WPJX-ray1.60E133-191[»]
S227-461[»]
2WPKX-ray2.21E133-191[»]
S227-461[»]
2WPLX-ray1.82E133-191[»]
S227-461[»]
2WPMX-ray2.00E133-191[»]
S227-461[»]
3KCGX-ray1.70H227-461[»]
L131-188[»]
3LC3X-ray1.90A/C227-461[»]
B/D133-188[»]
3LC5X-ray2.62A227-461[»]
B133-188[»]
4YZUX-ray1.41A227-461[»]
B131-191[»]
4Z0KX-ray1.41A227-461[»]
B131-191[»]
4ZAEX-ray1.86A227-461[»]
B131-191[»]
ProteinModelPortaliP00740.
SMRiP00740. Positions 47-191, 227-461.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP00740.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini47 – 9246GlaPROSITE-ProRule annotationAdd
BLAST
Domaini93 – 12937EGF-like 1; calcium-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini130 – 17142EGF-like 2PROSITE-ProRule annotationAdd
BLAST
Domaini227 – 459233Peptidase S1PROSITE-ProRule annotationAdd
BLAST

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
Contains 2 EGF-like domains.PROSITE-ProRule annotation
Contains 1 Gla (gamma-carboxy-glutamate) domain.PROSITE-ProRule annotation
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Repeat, Signal

Phylogenomic databases

eggNOGiCOG5640.
GeneTreeiENSGT00760000118890.
HOGENOMiHOG000251821.
HOVERGENiHBG013304.
InParanoidiP00740.
KOiK01321.
OMAiMKGKYGI.
OrthoDBiEOG75B84T.
PhylomeDBiP00740.
TreeFamiTF327329.

Family and domain databases

Gene3Di4.10.740.10. 1 hit.
InterProiIPR017857. Coagulation_fac_subgr_Gla_dom.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR000294. GLA_domain.
IPR012224. Pept_S1A_FX.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamiPF00008. EGF. 1 hit.
PF00594. Gla. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF001143. Factor_X. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
PR00001. GLABLOOD.
SMARTiSM00181. EGF. 1 hit.
SM00179. EGF_CA. 1 hit.
SM00069. GLA. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF57630. SSF57630. 1 hit.
PROSITEiPS00010. 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.
[Graphical view]