UniProt functional annotation for P00451



	UniProt functional annotation for P00451

UniProt code: P00451.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa.

Subunit: Interacts with VWF/vWF. vWF binding is essential for the stabilization of F8 in circulation. {ECO:0000269|PubMed:1554716, ECO:0000269|PubMed:9218428}.

Subcellular location: Secreted, extracellular space.

Domain: Domain F5/8 type C 2 is responsible for phospholipid-binding and essential for factor VIII activity.

Ptm: Sulfation on Tyr-1699 is essential for binding vWF. {ECO:0000269|PubMed:10368977, ECO:0000269|PubMed:1554716, ECO:0000269|PubMed:1898735}.

Disease: Hemophilia A (HEMA) [MIM:306700]: A disorder of blood coagulation characterized by a permanent tendency to hemorrhage. About 50% of patients have severe hemophilia resulting in frequent spontaneous bleeding into joints, muscles and internal organs. Less severe forms are characterized by bleeding after trauma or surgery. {ECO:0000269|PubMed:10215414, ECO:0000269|PubMed:10338101, ECO:0000269|PubMed:10404764, ECO:0000269|PubMed:10408784, ECO:0000269|PubMed:10554831, ECO:0000269|PubMed:10612839, ECO:0000269|PubMed:10691849, ECO:0000269|PubMed:10800171, ECO:0000269|PubMed:10886198, ECO:0000269|PubMed:10896236, ECO:0000269|PubMed:10910910, ECO:0000269|PubMed:10910913, ECO:0000269|PubMed:11298607, ECO:0000269|PubMed:11341489, ECO:0000269|PubMed:11410838, ECO:0000269|PubMed:11442643, ECO:0000269|PubMed:11442647, ECO:0000269|PubMed:11554935, ECO:0000269|PubMed:11748850, ECO:0000269|PubMed:11857744, ECO:0000269|PubMed:11858487, ECO:0000269|PubMed:12195713, ECO:0000269|PubMed:12199686, ECO:0000269|PubMed:12203998, ECO:0000269|PubMed:12325022, ECO:0000269|PubMed:12351418, ECO:0000269|PubMed:12406074, ECO:0000269|PubMed:12614369, ECO:0000269|PubMed:12871415, ECO:0000269|PubMed:12930394, ECO:0000269|PubMed:1301194, ECO:0000269|PubMed:1301932, ECO:0000269|PubMed:1301960, ECO:0000269|PubMed:1349567, ECO:0000269|PubMed:1356412, ECO:0000269|PubMed:15682412, ECO:0000269|PubMed:15810915, ECO:0000269|PubMed:1639429, ECO:0000269|PubMed:16805874, ECO:0000269|PubMed:18184865, ECO:0000269|PubMed:1851341, ECO:0000269|PubMed:1908096, ECO:0000269|PubMed:1908817, ECO:0000269|PubMed:1973901, ECO:0000269|PubMed:2104766, ECO:0000269|PubMed:2105106, ECO:0000269|PubMed:2105906, ECO:0000269|PubMed:2106480, ECO:0000269|PubMed:2107542, ECO:0000269|PubMed:21371196, ECO:0000269|PubMed:2495245, ECO:0000269|PubMed:2498882, ECO:0000269|PubMed:2499363, ECO:0000269|PubMed:2506948, ECO:0000269|PubMed:2510835, ECO:0000269|PubMed:25550078, ECO:0000269|PubMed:26278069, ECO:0000269|PubMed:2833855, ECO:0000269|PubMed:2835904, ECO:0000269|PubMed:3012775, ECO:0000269|PubMed:3122181, ECO:0000269|PubMed:7579394, ECO:0000269|PubMed:7759074, ECO:0000269|PubMed:7794769, ECO:0000269|PubMed:8322269, ECO:0000269|PubMed:8449505, ECO:0000269|PubMed:8639447, ECO:0000269|PubMed:8644728, ECO:0000269|PubMed:8759905, ECO:0000269|PubMed:9029040, ECO:0000269|PubMed:9326186, ECO:0000269|PubMed:9341862, ECO:0000269|PubMed:9450898, ECO:0000269|PubMed:9452104, ECO:0000269|PubMed:9569180, ECO:0000269|PubMed:9569189, ECO:0000269|PubMed:9603440, ECO:0000269|PubMed:9792405, ECO:0000269|PubMed:9829908, ECO:0000269|PubMed:9886318}. Note=The disease is caused by variants affecting the gene represented in this entry. Of particular interest for the understanding of the function of F8 is the category of CRM (cross-reacting material) positive patients (approximately 5%) that have considerable amount of F8 in their plasma (at least 30% of normal), but the protein is non-functional; i.e. the F8 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.

Pharmaceutical: Available under the names Kogenate (Bayer) and Recombinate (Baxter and American Home Products). Used to treat hemophilia A.

Similarity: Belongs to the multicopper oxidase family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa.


Subunit:		Interacts with VWF/vWF. vWF binding is essential for the stabilization of F8 in circulation. {ECO:0000269\|PubMed:1554716, ECO:0000269\|PubMed:9218428}.
Subcellular location:		Secreted, extracellular space.
Domain:		Domain F5/8 type C 2 is responsible for phospholipid-binding and essential for factor VIII activity.
Ptm:		Sulfation on Tyr-1699 is essential for binding vWF. {ECO:0000269\|PubMed:10368977, ECO:0000269\|PubMed:1554716, ECO:0000269\|PubMed:1898735}.
Disease:		Hemophilia A (HEMA) [MIM:306700]: A disorder of blood coagulation characterized by a permanent tendency to hemorrhage. About 50% of patients have severe hemophilia resulting in frequent spontaneous bleeding into joints, muscles and internal organs. Less severe forms are characterized by bleeding after trauma or surgery. {ECO:0000269\|PubMed:10215414, ECO:0000269\|PubMed:10338101, ECO:0000269\|PubMed:10404764, ECO:0000269\|PubMed:10408784, ECO:0000269\|PubMed:10554831, ECO:0000269\|PubMed:10612839, ECO:0000269\|PubMed:10691849, ECO:0000269\|PubMed:10800171, ECO:0000269\|PubMed:10886198, ECO:0000269\|PubMed:10896236, ECO:0000269\|PubMed:10910910, ECO:0000269\|PubMed:10910913, ECO:0000269\|PubMed:11298607, ECO:0000269\|PubMed:11341489, ECO:0000269\|PubMed:11410838, ECO:0000269\|PubMed:11442643, ECO:0000269\|PubMed:11442647, ECO:0000269\|PubMed:11554935, ECO:0000269\|PubMed:11748850, ECO:0000269\|PubMed:11857744, ECO:0000269\|PubMed:11858487, ECO:0000269\|PubMed:12195713, ECO:0000269\|PubMed:12199686, ECO:0000269\|PubMed:12203998, ECO:0000269\|PubMed:12325022, ECO:0000269\|PubMed:12351418, ECO:0000269\|PubMed:12406074, ECO:0000269\|PubMed:12614369, ECO:0000269\|PubMed:12871415, ECO:0000269\|PubMed:12930394, ECO:0000269\|PubMed:1301194, ECO:0000269\|PubMed:1301932, ECO:0000269\|PubMed:1301960, ECO:0000269\|PubMed:1349567, ECO:0000269\|PubMed:1356412, ECO:0000269\|PubMed:15682412, ECO:0000269\|PubMed:15810915, ECO:0000269\|PubMed:1639429, ECO:0000269\|PubMed:16805874, ECO:0000269\|PubMed:18184865, ECO:0000269\|PubMed:1851341, ECO:0000269\|PubMed:1908096, ECO:0000269\|PubMed:1908817, ECO:0000269\|PubMed:1973901, ECO:0000269\|PubMed:2104766, ECO:0000269\|PubMed:2105106, ECO:0000269\|PubMed:2105906, ECO:0000269\|PubMed:2106480, ECO:0000269\|PubMed:2107542, ECO:0000269\|PubMed:21371196, ECO:0000269\|PubMed:2495245, ECO:0000269\|PubMed:2498882, ECO:0000269\|PubMed:2499363, ECO:0000269\|PubMed:2506948, ECO:0000269\|PubMed:2510835, ECO:0000269\|PubMed:25550078, ECO:0000269\|PubMed:26278069, ECO:0000269\|PubMed:2833855, ECO:0000269\|PubMed:2835904, ECO:0000269\|PubMed:3012775, ECO:0000269\|PubMed:3122181, ECO:0000269\|PubMed:7579394, ECO:0000269\|PubMed:7759074, ECO:0000269\|PubMed:7794769, ECO:0000269\|PubMed:8322269, ECO:0000269\|PubMed:8449505, ECO:0000269\|PubMed:8639447, ECO:0000269\|PubMed:8644728, ECO:0000269\|PubMed:8759905, ECO:0000269\|PubMed:9029040, ECO:0000269\|PubMed:9326186, ECO:0000269\|PubMed:9341862, ECO:0000269\|PubMed:9450898, ECO:0000269\|PubMed:9452104, ECO:0000269\|PubMed:9569180, ECO:0000269\|PubMed:9569189, ECO:0000269\|PubMed:9603440, ECO:0000269\|PubMed:9792405, ECO:0000269\|PubMed:9829908, ECO:0000269\|PubMed:9886318}. Note=The disease is caused by variants affecting the gene represented in this entry. Of particular interest for the understanding of the function of F8 is the category of CRM (cross-reacting material) positive patients (approximately 5%) that have considerable amount of F8 in their plasma (at least 30% of normal), but the protein is non-functional; i.e. the F8 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.
Pharmaceutical:		Available under the names Kogenate (Bayer) and Recombinate (Baxter and American Home Products). Used to treat hemophilia A.
Similarity:		Belongs to the multicopper oxidase family. {ECO:0000305}.