Factor VIII

F8
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesF8, AHF, DXS1253E, F8B, F8C, FVIII, HEMA, coagulation factor VIII, THPH13
External IDsOMIM: 300841; MGI: 88383; HomoloGene: 49153; GeneCards: F8; OMA:F8 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000132
NM_019863

NM_001161373
NM_001161374
NM_007977

RefSeq (protein)

NP_000123
NP_063916

NP_001154845
NP_001154846
NP_032003

Location (UCSC)Chr X: 154.84 – 155.03 MbChr X: 74.22 – 74.43 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Coagulation factor VIII (Factor VIII, FVIII, also known as anti-hemophilic factor (AHF)) is an essential blood clotting protein. In humans, it is encoded by F8 gene.[5][6] Defects in this gene result in hemophilia A, an X-linked bleeding disorder.[7]

Factor VIII is produced in the liver's sinusoidal cells and endothelial cells outside the liver throughout the body. This protein circulates in the bloodstream in an inactive form, bound to another molecule called von Willebrand factor, until an injury that damages blood vessels occurs.[8] In response to injury, coagulation factor VIII is activated and separates from von Willebrand factor. The active protein (sometimes written as coagulation factor VIIIa) interacts with another coagulation factor called factor IX. This interaction sets off a chain of additional chemical reactions that form a blood clot.[8]

Factor VIII participates in blood coagulation; it is a cofactor for factor IXa, which, in the presence of Ca2+ and phospholipids, forms a complex that converts factor X to the activated form Xa. The factor VIII gene produces two alternatively spliced transcripts. Transcript variant 1 encodes a large glycoprotein, isoform a, which circulates in plasma and associates with von Willebrand factor in a noncovalent complex. This protein undergoes multiple cleavage events. Transcript variant 2 encodes a putative small protein, isoform b, which consists primarily of the phospholipid binding domain of factor VIIIc. This binding domain is essential for coagulant activity.[9]

People with high levels of factor VIII are at increased risk for deep vein thrombosis and pulmonary embolism.[10] Copper is a required cofactor for factor VIII and copper deficiency is known to increase the activity of factor VIII.[11]

Factor VIII is available as a medication that is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.[12]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000185010Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031196Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Toole JJ, Knopf JL, Wozney JM, Sultzman LA, Buecker JL, Pittman DD, et al. (1984). "Molecular cloning of a cDNA encoding human antihaemophilic factor". Nature. 312 (5992): 342–347. Bibcode:1984Natur.312..342T. doi:10.1038/312342a0. PMID 6438528. S2CID 4313575.
  6. ^ Truett MA, Blacher R, Burke RL, Caput D, Chu C, Dina D, et al. (October 1985). "Characterization of the polypeptide composition of human factor VIII:C and the nucleotide sequence and expression of the human kidney cDNA". DNA. 4 (5): 333–349. doi:10.1089/dna.1985.4.333. PMID 3935400.
  7. ^ Antonarakis SE (July 1995). "Molecular genetics of coagulation factor VIII gene and hemophilia A". Thrombosis and Haemostasis. 74 (1): 322–328. doi:10.1055/s-0038-1642697. PMID 8578479. S2CID 23435953.
  8. ^ a b "NIH: F8 – coagulation factor VIII". National Institutes of Health.
  9. ^ "Entrez Gene: F8 coagulation factor VIII, procoagulant component (hemophilia A)".
  10. ^ Jenkins PV, Rawley O, Smith OP, O'Donnell JS (June 2012). "Elevated factor VIII levels and risk of venous thrombosis". British Journal of Haematology. 157 (6): 653–663. doi:10.1111/j.1365-2141.2012.09134.x. PMID 22530883.
  11. ^ Milne DB, Nielsen FH (March 1996). "Effects of a diet low in copper on copper-status indicators in postmenopausal women". The American Journal of Clinical Nutrition. 63 (3): 358–364. doi:10.1093/ajcn/63.3.358. PMID 8602593.
  12. ^ "19th WHO Model List of Essential Medicines" (PDF). WHO. April 2015. Retrieved May 10, 2015.