Coagulation factor VIII precursor - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P00451 (FA8_HUMAN)

Last modified July 7, 2009. Version 144. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Coagulation factor VIII
Alternative name(s):
    Procoagulant component
    Antihemophilic factor
      Short name=AHF
Cleaved into the following 4 chains:
    1- Recommended name:
            Factor VIIIa heavy chain, 200 kDa isoform
    2- Recommended name:
            Factor VIIIa heavy chain, 92 kDa isoform
    3- Recommended name:
            Factor VIII B chain
    4- Recommended name:
            Factor VIIIa light chain

Gene names

Name:	F8
Synonyms:	F8C

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	2351 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Factor VIII, along with calcium and phospholipid, acts as a cofactor for factor IXa when it converts factor X to the activated form, factor Xa.
Subunit structure	Interacts with vWF. vWF binding is essential for the stabilization of F8 in circulation. Ref.9 Ref.10
Subcellular location	Secreted › extracellular space.
Domain	Domain F5/8 type C 2 is responsible for phospholipid-binding and essential for factor VIII activity.
Post-translational modification	Sulfation on Tyr-1699 is essential for binding vWF.
Involvement in disease	Defects in F8 are the cause of hemophilia A (HEMA) [MIM:306700]. HEMA is a common recessive X-linked coagulation disorder. The frequency of hemophilia A is 1-2 in 10,000 male births in all ethnic groups. About 50% of patients have severe hemophilia A with F8C activity less than 1% of normal; they have frequent spontaneous bleeding into joints, muscles and internal organs. Moderately severe hemophilia A occurs in about 10% of patients; F8C activity is 2-5% of normal, and there is bleeding after minor trauma. Mild hemophilia A, which occurs in 30-40% of patients, is associated with F8C activity of 5-30% and bleeding occurs only after significant trauma or surgery. Of particular interest for the understanding of the function of F8C is the category of CRM (cross-reacting material) positive patients (approximately 5%) that have considerable amount of F8C in their plasma (at least 30% of normal), but the protein is non-functional; i.e., the F8C activity is much less than the plasma protein level. CRM-reduced is another category of patients in which the F8C antigen and activity are reduced to approximately the same level. Most mutations are CRM negative, and probably affect the folding and stability of the protein. Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.45 Ref.46 Ref.47 Ref.48 Ref.49 Ref.50 Ref.51 Ref.52 Ref.53 Ref.54 Ref.55 Ref.56 Ref.57 Ref.58 Ref.59 Ref.60 Ref.61 Ref.62 Ref.63 Ref.64 Ref.65 Ref.66 Ref.67 Ref.68 Ref.69 Ref.70 Ref.71 Ref.72 Ref.73 Ref.74 Ref.75 Ref.76 Ref.77 Ref.78 Ref.79 Ref.81 Ref.82 Ref.83 Ref.84 Ref.85 Ref.86 Ref.87 Ref.88 Ref.89 Ref.90 Ref.91 Ref.92 Ref.93 Ref.94
Pharmaceutical use	Available under the names Kogenate (Bayer) and Recombinate (Baxter and American Home Products). Used to treat hemophilia A.
Sequence similarities	Belongs to the multicopper oxidase family. Contains 3 F5/8 type A domains. Contains 2 F5/8 type C domains. Contains 6 plastocyanin-like domains.
Mass spectrometry	Molecular mass is 1367.6 Da from positions 356 - 378. Determined by ESI. Nonsulfated. Ref.7 Molecular mass is 1407.4 Da from positions 356 - 378. Determined by ESI. Sulfated. Ref.7 Molecular mass is 2975.4 Da from positions 400 - 424. Determined by ESI. Nonsulfated. Ref.7 Molecular mass is 3024 Da from positions 727 - 752. Determined by ESI. Nonsulfated. Ref.7 Molecular mass is 3104 Da from positions 727 - 752. Determined by ESI. Monosulfated. Ref.7 Molecular mass is 3183.5 Da from positions 727 - 752. Determined by ESI. Disulfated. Ref.7 Molecular mass is 3262.5 Da from positions 727 - 752. Determined by ESI. Trisulfated. Ref.7 Molecular mass is 2460.9 Da from positions 1672 - 1692. Determined by ESI. Nonsulfated. Ref.7 Molecular mass is 2540.7 Da from positions 1672 - 1692. Determined by ESI. Sulfated. Ref.7 Molecular mass is 2000.7 Da from positions 1691 - 1708. Determined by ESI. Nonsulfated. Ref.7 Molecular mass is 2080.7 Da from positions 1691 - 1708. Determined by ESI. Sulfated. Ref.7

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Ontologies

Keywords
Biological process	Acute phase Blood coagulation
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation Hemophilia
Domain	Repeat Signal
Ligand	Calcium Metal-binding
PTM	Disulfide bond Glycoprotein Sulfation
Technical term	3D-structure Complete proteome Direct protein sequencing Pharmaceutical
Gene Ontology (GO)
Biological process	acute-phase response Inferred from electronic annotation. Source: UniProtKB-KW blood coagulation Traceable author statement. Source: ProtInc cell adhesion Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from Experiment. Source: Reactome platelet alpha granule lumen Inferred from Experiment. Source: Reactome
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW copper ion binding Inferred from electronic annotation. Source: InterPro oxidoreductase activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

Chain

20 – 2351

2332

Coagulation factor VIII

PRO_0000002967

Chain

20 – 1332

1313

Factor VIIIa heavy chain, 200 kDa isoform

PRO_0000002968

Chain

20 – 759

740

Factor VIIIa heavy chain, 92 kDa isoform

PRO_0000002969

Chain

760 – 1332

573

Factor VIII B chain

PRO_0000002970

Chain

1668 – 2351

684

Factor VIIIa light chain

PRO_0000002971

Regions

Domain

20 – 348

329

F5/8 type A 1

Domain

20 – 198

179

Plastocyanin-like 1

Domain

206 – 348

143

Plastocyanin-like 2

Domain

399 – 730

332

F5/8 type A 2

Domain

399 – 573

175

Plastocyanin-like 3

Domain

583 – 730

148

Plastocyanin-like 4

Domain

1713 – 2040

328

F5/8 type A 3

Domain

1713 – 1877

165

Plastocyanin-like 5

Domain

1887 – 2040

154

Plastocyanin-like 6

Domain

2040 – 2188

149

F5/8 type C 1

Domain

2193 – 2345

153

F5/8 type C 2

Region

760 – 1667

908

Sites

Site

391 – 392

Cleavage; by thrombin

Site

759 – 760

Cleavage; by thrombin

Site

1332 – 1333

Cleavage (activation)

Site

1667 – 1668

Cleavage (activation)

Site

1708 – 1709

Cleavage; by thrombin

Amino acid modifications

Modified residue

365

Sulfotyrosine

Modified residue

737

Sulfotyrosine

Modified residue

738

Sulfotyrosine

Modified residue

742

Sulfotyrosine

Modified residue

1683

Sulfotyrosine

Modified residue

1699

Sulfotyrosine

Glycosylation