Contents

Search

coagulation factor VIII; antihemophilic factor; AHF; procoagulant component; contains: factor VIIIa heavy chain, 200 kD & 92 isoforms; factor VIII B chain; factor VIIIa light chain (F8, F8C)

Function: - coagulation factor, intrinsic pathway - zymogen activated by thrombin to factor VIIIa - factor VIII, along with Ca+2 & phospholipid, acts as a cofactor for factor IXa when it converts factor X to the activated form, factor Xa - in the circulating blood, it is mainly bound to vWF - sulfation on Tyr-1699 is essential for binding vWF - vWF binding is essential for stabilization of F8 in circulation Structure: - domain F5/8 type C 2 is responsible for phospholipid- binding & essential for factor VIII activity - 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 - subunits contain domains homologous to factor V & to ceruloplasmin Compartment: secreted, extracellular space Expression: - synthesized by vascular endothelium & released into the bloodstream Pharmacology: see antihemophilic factor. Pathology: deficiency associated with hemophilia A Laboratory: - F8 gene mutation

Interactions

molecular events

Related

coagulation cascade coagulation factor VIII alloantibody coagulation factor VIII autoantibody (acquired hemophilia) coagulation factor VIIIa F8 gene mutation; hemophilia A genotyping factor VIII intron 22 protein (CpG island protein) hemophilia A; factor VIII deficiency von Willebrand factor; vWF; ristocetin cofactor; factor VIII related antigen; contains: von Willebrand antigen 2 (VWF, F8VWF)

Specific

antihemophilic factor (coagulation factor VIII, AHF-M, Hemofil, Humate-P, Monoclate-P) Factor Viii Parenteral recombinant factor VIII Fc fusion protein; recombinant antihemophilic factor Fc fusion protein; recombinant antihemophilic factor Fc-VWF-XTEN fusion protein-ehtl (Eloctate, Altuviiio) recombinant factor VIII; turoctocog alfa; (Factorate, Recombinate, Xyntha, Kogenate FS, Kovaltry, NovoEight) Refacto

General

coagulation factor glycoprotein multisubunit protein protein precursor

Properties

SIZE: entity length = 2351 aa MW = 267 kD COMPARTMENT: plasma MOTIF: signal sequence {1-19} F5/8 type A 1 {20-348} MOTIF: Plastocyanin-like 1 {20-198} N-glycosylation site {N60} cysteine residue {C172} MODIFICATION: cysteine residue {C198} cysteine residue {C198} MODIFICATION: cysteine residue {C172} Plastocyanin-like 2 {206-348} N-glycosylation site {N258} cysteine residue {C267} MODIFICATION: cysteine residue {C348} cysteine residue {C348} MODIFICATION: cysteine residue {C267} proteolytic site {391-392} F5/8 type A 2 {399-730} MOTIF: Plastocyanin-like 3 {399-573} cysteine residue {C547} MODIFICATION: cysteine residue {C573} cysteine residue {C573} MODIFICATION: cysteine residue {C547} Plastocyanin-like 4 {583-730} N-glycosylation site {N601} cysteine residue {C649} MODIFICATION: cysteine residue {C730} cysteine residue {C730} MODIFICATION: cysteine residue {C649} proteolytic site {759-760} B {760-1667} MOTIF: N-glycosylation site {N776} N-glycosylation site {N803} N-glycosylation site {N847} N-glycosylation site {N919} N-glycosylation site {N962} N-glycosylation site {N982} N-glycosylation site {N1020} N-glycosylation site {N1024} N-glycosylation site {N1074} N-glycosylation site {N1085} N-glycosylation site {N1204} N-glycosylation site {N1274} N-glycosylation site {N1278} N-glycosylation site {N1301} N-glycosylation site {N1319} proteolytic site {1332-1333} N-glycosylation site {N1431} N-glycosylation site {N1461} proteolytic site {1667-1668} proteolytic site {1708-1709} F5/8 type A 3 {1713-2040} MOTIF: Plastocyanin-like 5 {1713-1877} N-glycosylation site {N1829} cysteine residue {C1851} MODIFICATION: cysteine residue {C1877} cysteine residue {C1877} MODIFICATION: cysteine residue {C1851} Plastocyanin-like 6 {1887-2040} cysteine residue {C1918} MODIFICATION: cysteine residue {C1922} cysteine residue {C1922} MODIFICATION: cysteine residue {C1918} coagulation factors 5/8 type C domain (FA58C) {2040-2188} MOTIF: cysteine residue {C2040} MODIFICATION: cysteine residue {C2188} N-glycosylation site {N2137} cysteine residue {C2188} MODIFICATION: cysteine residue {C2040} coagulation factors 5/8 type C domain (FA58C) {2193-2345} MOTIF: cysteine residue {C2193} MODIFICATION: cysteine residue {C2345} cysteine residue {C2345} MODIFICATION: cysteine residue {C2193} PRECURSOR-FOR: coagulation factor VIIIa MISC-INFO: elimination route LIVER CONCENTRATION 0.1-0.2 UG/ML 1/2life 4-24 HOURS

Database Correlations

OMIM correlations UniProt P00451 PFAM correlations Entrez Gene 2157 Kegg hsa:2157

References

  1. Walker FJ, Fay PJ. Regulation of blood coagulation by the protein C system. FASEB J. 1992 May;6(8):2561-7. Review. PMID: 1317308
  2. Andrews BS. Is the WKS motif the tissue-factor binding site for coagulation factor VII? Trends Biochem Sci. 1991 Jan;16(1):31-6. Review. PMID: 2053135
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 18, American College of Physicians, Philadelphia 1998, 2018.
  4. Wikipedia: Factor VIII http://en.wikipedia.org/wiki/Factor_VIII
  5. UniProt :accession P00451
  6. HAMsters; Note: factor VIII mutation db http://hadb.org.uk/WebPages/main/main.htm
  7. GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/F8
  8. SeattleSNPs http://pga.gs.washington.edu/data/f8/

Component-of

factor VIII/von Willebrand factor; vWF-rich factor VIII molecular complex