UniProt functional annotation for P00748



	UniProt functional annotation for P00748

UniProt code: P00748.

Organism: Homo sapiens (Human).

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

Function: Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then trypsin cleaves it to beta-factor XIIa. Alpha-factor XIIa activates factor XI to factor XIa. {ECO:0000269|PubMed:21304106}.

Catalytic activity: Reaction=Selective cleavage of Arg-|-Ile bonds in factor VII to form factor VIIa and factor XI to form factor XIa.; EC=3.4.21.38;

Subunit: Interacts with HRG; the interaction, which is enhanced in the presence of zinc ions and inhibited by heparin-binding, inhibits factor XII autoactivation and contact-initiated coagulation. {ECO:0000269|PubMed:21304106}.

Subcellular location: Secreted.

Ptm: Factor XII is activated by kallikrein in alpha-factor XIIa, which is further converted by trypsin into beta-factor XIIa. Alpha-factor XIIa is composed of an NH2-terminal heavy chain, called coagulation factor XIIa heavy chain, and a COOH-terminal light chain, called coagulation factor XIIa light chain, connected by a disulfide bond. Beta-factor XIIa is composed of 2 chains linked by a disulfide bond, an N-terminal nonapeptide, called beta-factor XIIa part 1, and coagulation factor XIIa light chain, also known in this context as beta-factor XIIa part 2.

Ptm: O- and N-glycosylated. The O-linked polysaccharides were not identified, but are probably the mucin type linked to GalNAc. {ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:1544894, ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:3886654}.

Disease: Factor XII deficiency (FA12D) [MIM:234000]: An asymptomatic anomaly of in vitro blood coagulation. Its diagnosis is based on finding a low plasma activity of the factor in coagulating assays. It is usually only accidentally discovered through pre-operative blood tests. Factor XII deficiency is divided into two categories, a cross- reacting material (CRM)-negative group (negative F12 antigen detection) and a CRM-positive group (positive F12 antigen detection). {ECO:0000269|PubMed:10361128, ECO:0000269|PubMed:11776307, ECO:0000269|PubMed:15205584, ECO:0000269|PubMed:15617741, ECO:0000269|PubMed:2510163, ECO:0000269|PubMed:2882793, ECO:0000269|PubMed:8049433, ECO:0000269|PubMed:8528215, ECO:0000269|PubMed:9354665}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Hereditary angioedema 3 (HAE3) [MIM:610618]: A hereditary angioedema occurring only in women. Hereditary angioedema is an autosomal dominant disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. Hereditary angioedema type 3 differs from types 1 and 2 in that both concentration and function of C1 esterase inhibitor are normal. Hereditary angioedema type 3 is precipitated or worsened by high estrogen levels (e.g., during pregnancy or treatment with oral contraceptives). {ECO:0000269|PubMed:16638441, ECO:0000269|PubMed:17186468}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE- ProRule:PRU00274}.

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 XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then trypsin cleaves it to beta-factor XIIa. Alpha-factor XIIa activates factor XI to factor XIa. {ECO:0000269\|PubMed:21304106}.


Catalytic activity:		Reaction=Selective cleavage of Arg-\|-Ile bonds in factor VII to form factor VIIa and factor XI to form factor XIa.; EC=3.4.21.38;
Subunit:		Interacts with HRG; the interaction, which is enhanced in the presence of zinc ions and inhibited by heparin-binding, inhibits factor XII autoactivation and contact-initiated coagulation. {ECO:0000269\|PubMed:21304106}.
Subcellular location:		Secreted.
Ptm:		Factor XII is activated by kallikrein in alpha-factor XIIa, which is further converted by trypsin into beta-factor XIIa. Alpha-factor XIIa is composed of an NH2-terminal heavy chain, called coagulation factor XIIa heavy chain, and a COOH-terminal light chain, called coagulation factor XIIa light chain, connected by a disulfide bond. Beta-factor XIIa is composed of 2 chains linked by a disulfide bond, an N-terminal nonapeptide, called beta-factor XIIa part 1, and coagulation factor XIIa light chain, also known in this context as beta-factor XIIa part 2.
Ptm:		O- and N-glycosylated. The O-linked polysaccharides were not identified, but are probably the mucin type linked to GalNAc. {ECO:0000269\|PubMed:14760718, ECO:0000269\|PubMed:1544894, ECO:0000269\|PubMed:16335952, ECO:0000269\|PubMed:3886654}.
Disease:		Factor XII deficiency (FA12D) [MIM:234000]: An asymptomatic anomaly of in vitro blood coagulation. Its diagnosis is based on finding a low plasma activity of the factor in coagulating assays. It is usually only accidentally discovered through pre-operative blood tests. Factor XII deficiency is divided into two categories, a cross- reacting material (CRM)-negative group (negative F12 antigen detection) and a CRM-positive group (positive F12 antigen detection). {ECO:0000269\|PubMed:10361128, ECO:0000269\|PubMed:11776307, ECO:0000269\|PubMed:15205584, ECO:0000269\|PubMed:15617741, ECO:0000269\|PubMed:2510163, ECO:0000269\|PubMed:2882793, ECO:0000269\|PubMed:8049433, ECO:0000269\|PubMed:8528215, ECO:0000269\|PubMed:9354665}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Hereditary angioedema 3 (HAE3) [MIM:610618]: A hereditary angioedema occurring only in women. Hereditary angioedema is an autosomal dominant disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. Hereditary angioedema type 3 differs from types 1 and 2 in that both concentration and function of C1 esterase inhibitor are normal. Hereditary angioedema type 3 is precipitated or worsened by high estrogen levels (e.g., during pregnancy or treatment with oral contraceptives). {ECO:0000269\|PubMed:16638441, ECO:0000269\|PubMed:17186468}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the peptidase S1 family. {ECO:0000255\|PROSITE- ProRule:PRU00274}.