Human Gene F12 (uc003mgo.4) Description and Page Index
Description: Homo sapiens coagulation factor XII (Hageman factor) (F12), mRNA. RefSeq Summary (NM_000505): This gene encodes coagulation factor XII which circulates in blood as a zymogen. This single chain zymogen is converted to a two-chain serine protease with an heavy chain (alpha-factor XIIa) and a light chain. The heavy chain contains two fibronectin-type domains, two epidermal growth factor (EGF)-like domains, a kringle domain and a proline-rich domain, whereas the light chain contains only a catalytic domain. On activation, further cleavages takes place in the heavy chain, resulting in the production of beta-factor XIIa light chain and the alpha-factor XIIa light chain becomes beta-factor XIIa heavy chain. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then to beta-factor XIIa. The active factor XIIa participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. It activates coagulation factors VII and XI. Defects in this gene do not cause any clinical symptoms and the sole effect is that whole-blood clotting time is prolonged. [provided by RefSeq, Jul 2008]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: AB095845.1, M31315.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1968540 [ECO:0000350] ##Evidence-Data-END## ##RefSeq-Attributes-START## RefSeq Select criteria :: based on conservation, expression, longest protein regulatory uORF :: PMID: 19372376 ##RefSeq-Attributes-END## Transcript (Including UTRs) Position: hg19 chr5:176,829,139-176,836,577 Size: 7,439 Total Exon Count: 14 Strand: - Coding Region Position: hg19 chr5:176,829,293-176,836,528 Size: 7,236 Coding Exon Count: 14
ID:FA12_HUMAN DESCRIPTION: RecName: Full=Coagulation factor XII; EC=184.108.40.206; AltName: Full=Hageman factor; Short=HAF; Contains: RecName: Full=Coagulation factor XIIa heavy chain; Contains: RecName: Full=Beta-factor XIIa part 1; Contains: RecName: Full=Beta-factor XIIa part 2; Contains: RecName: Full=Coagulation factor XIIa light chain; Flags: Precursor; 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. CATALYTIC ACTIVITY: Selective cleavage of Arg-|-Ile bonds in factor VII to form factor VIIa and factor XI to form factor XIa. 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. SUBCELLULAR LOCATION: Secreted. PTM: Factor XII is activated by kallikrein in alpha-factor XIIa, which is then further converted by trypsin into beta-factor XIIa. Alpha-factor XIIa is composed of the NH2-terminal heavy chain (Coagulation factor XIIa heavy chain) and the COOH-terminal light chain (Coagulation factor XIIa light chain), connected by a disulfide bond. Beta-factor XIIa is composed of 2 chains linked by a disulfide bond, a light chain (Beta-factor XIIa part 2), corresponding to the COOH-terminal light chain (Coagulation factor XIIa light chain) and a nonapeptide (Beta-factor XIIa part 1). PTM: O- and N-glycosylated. The O-linked polysaccharides were not identified, but are probably the mucin type linked to GalNAc. DISEASE: Defects in F12 are the cause of factor XII deficiency (FA12D) [MIM:234000]; also known as Hageman factor deficiency. This trait is 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. F12 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). DISEASE: Defects in F12 are the cause of hereditary angioedema type 3 (HAE3) [MIM:610618]; also known as estrogen-related HAE or hereditary angioneurotic edema with normal C1 inhibitor concentration and function. HAE is characterized by episodic local subcutaneous edema, and submucosal edema involving the upper respiratory and gastrointestinal tracts. HAE3 occurs exclusively in women and is precipitated or worsened by high estrogen levels (e.g. during pregnancy or treatment with oral contraceptives). It differs from HAE types 1 and 2 in that both concentration and function of C1 inhibitor are normal. SIMILARITY: Belongs to the peptidase S1 family. SIMILARITY: Contains 2 EGF-like domains. SIMILARITY: Contains 1 fibronectin type-I domain. SIMILARITY: Contains 1 fibronectin type-II domain. SIMILARITY: Contains 1 kringle domain. SIMILARITY: Contains 1 peptidase S1 domain. WEB RESOURCE: Name=Wikipedia; Note=Factor XII entry; URL="http://en.wikipedia.org/wiki/Factor_XII"; WEB RESOURCE: Name=F12base; Note=F12 mutation db; URL="http://bioinf.uta.fi/F12base/"; WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/f12/";
Genetic Association Studies of Complex Diseases and Disorders
Activated factor XII levels Ishii K et al. 2000, Activated factor XII levels are dependent on factor XII 46C/T genotypes and factor XII zymogen levels and are associated with vascular risk factors in patients and healthy subjects., Blood coagulation & fibrinolysis. 2000 Apr;11(3):277-84.
atherosclerosis, coronary Santamaria, A. et al. 2004, Homozygosity of the T allele of the 46 C-->T polymorphism in the F12 gene is a risk factor for acute coronary artery disease in the Spanish population., Haematologica. 2004 Jul;89(7):878-9.
We found a 6-fold higher risk of acute CAD associated with the homozygosity of the T allele of the F12, 46C-->T polymorphism in the Spanish population.
Blood Platelets JA Guerrero et al. Haematologica 2011, Novel loci involved in platelet function and platelet count identified by a genome-wide study performed in children., Haematologica.
Our genome-wide association study performed in children, followed by a validation analysis, led us to the identification of new genes potentially relevant in platelet function and biogenesis.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P00748
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.