Factor XI

Coagulation factor XI (plasma thromboplastin antecedent)
PDB rendering based on 1xx9.
Available structures: 1xx9, 1xxd, 1xxf, 1zhm, 1zhp, 1zhr, 1zjd, 1zlr, 1zmj, 1zml, 1zmn, 1zom, 1zpb, 1zpc, 1zpz, 1zrk, 1zsj, 1zsk, 1zsl, 1ztj, 1ztk, 1ztl, 2f83, 2fda, 2j8j, 2j8l
Identifiers
Symbols	F11; FXI; MGC141891
External IDs	OMIM: 264900 MGI: 99481 HomoloGene: 86654
Gene ontology Molecular function: • coagulation factor IXa activity • coagulation factor XIa activity • heparin binding • peptidase activity Cellular component: • extracellular region • membrane Biological process: • proteolysis • blood coagulation
RNA expression pattern
More reference expression data
Orthologs
	Human	Mouse
Entrez	2160	109821
Ensembl	ENSG00000088926	ENSMUSG00000031645
Uniprot	P03951	Q9DAT3
Refseq	NM_019559 (mRNA) NP_062505 (protein)	NM_028066 (mRNA) NP_082342 (protein)
Location	Chr 4: 187.42 - 187.45 Mb	Chr 8: 46.74 - 46.76 Mb
Pubmed search	[1]	[2]

Factor XI or plasma thromboplastin antecedent is the zymogen form of factor XIa, one of the enzymes of the coagulation cascade. Like many other coagulation factors, it is a serine protease. In humans, Factor XI is encoded by the F11 gene.^[1][2][3][4]

Physiology

Factor XI (FXI) is produced by the liver and circulates as a homo-dimer in its inactive form.^[5] The plasma half-life of FXI is approximately 52 hours. The zymogen factor is activated into factor XIa by factor XIIa (FXIIa), thrombin, and it is also autocatalytic, and FXI is a member of the "contact pathway" due to activation by FXIIa (with includes HMWK, prekallikrein, factor XII, factor XI and factor IX).^[6]

Factor XIa activates factor IX by selectively cleaving arg-ala and arg-val peptide bonds. Factor IXa, in turn, activates factor X.

Inhibitors of factor XIa include protein Z-dependent protease inhibitor (ZPI, a member of the serine protease inhibitor/serpin class of proteins), which is independent of protein Z (its action on factor X, however, is protein Z-dependent, hence its name).

Protein structure and molecular biology

Although synthesized as a single polypeptide chain, FXI circulates as a homodimer. Every chain has a relative molecular mass of approximately 80000. Typical plasma concentrations of FXI are 5 mg/l, corresponding to a plasma concentration (of FXI dimers) of approximately 30nM. The FXI gene is 23kb in length, has 15 exons, and is found on chromosome 4q32-35.^[2][3]

Role in disease

Deficiency of factor XI causes the rare Haemophilia C; this mainly occurs in Ashkenazi Jews and is believed to affect approximately 8% of that population, of both sexes. The condition has been described in other populations at around 1% of cases. It is an autosomal recessive disorder. There is little spontaneous bleeding, but surgical procedures may cause excessive blood loss, and prophylaxis is required.^[7]

Low levels of factor XI also occur in many other disease states, including Noonan syndrome.

High levels of factor XI have been implicated in thrombosis, although it is uncertain what determines these levels and how serious the procoagulant state is.

References

Further reading

v • d • e PDB Gallery 1xx9: Crystal Structure of the FXIa Catalytic Domain in Complex with EcotinM84R   1xxd: Crystal Structure of the FXIa Catalytic Domain in Complex with mutated Ecotin   1xxf: Crystal Structure of the FXIa Catalytic Domain in Complex with Ecotin Mutant (EcotinP)   1zhm: Crystal Structure of the Catalytic Domain of the Coagulation Factor XIa in Complex with Benzamidine (S434A-T475A-K437 Mutant)   1zhp: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with Benzamidine (S434A-T475A-K505 Mutant)   1zhr: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with Benzamidine (S434A-T475A-C482S-K437A Mutant)   1zjd: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with Kunitz Protease Inhibitor Domain of Protease Nexin II   1zlr: Factor XI catalytic domain complexed with 2-guanidino-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl nicotinate   1zmj: Crystal Structure of the Catalytic Domain of Factor XI in complex with 4-(guanidinomethyl)-phenylboronic acid   1zml: Crystal Structure of the Catalytic Domain of Factor XI in complex with (R)-1-(4-(4-(hydroxymethyl)-1,3,2-dioxaborolan-2-yl)phenethyl)guanidine   1zmn: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with (R)-1-(4-(4-(hydroxymethyl)-1,3,2-dioxaborolan-2-yl)phenyl)guanidine   1zom: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in complex with a peptidomimetic Inhibitor   1zpb: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with 4-Methyl-pentanoic acid {1-[4-guanidino-1-(thiazole-2-carbonyl)-butylcarbamoyl]-2-methyl-propyl}-amide   1zpc: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with 2-[2-(3-Chloro-phenyl)-2-hydroxy-acetylamino]-N-[4-guanidino-1-(thiazole-2-carbonyl)-butyl]-3-methyl-butyramide   1zpz: Factor XI catalytic domain complexed with N-((R)-1-(4-bromophenyl)ethyl)urea-Asn-Val-Arg-alpha-ketothiazole   1zrk: Factor XI complexed with 3-hydroxypropyl 3-(7-amidinonaphthalene-1-carboxamido)benzenesulfonate   1zsj: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in complex with N-(7-Carbamimidoyl-naphthalen-1-yl)-3-hydroxy-2-methyl-benzamide   1zsk: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with 6-Carbamimidoyl-4-(3-hydroxy-2-methyl-benzoylamino)-naphthalene-2-carboxylic acid methyl ester   1zsl: Factor XI complexed with a pyrimidinone inhibitor   1ztj: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with 2-(5-Benzylamino-2-methylsulfanyl-6-oxo-6H-pyrimidin-1-yl)-N-[4-guanidino-1-(thiazole-2-carbonyl)-butyl]-acetamide   1ztk: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with 2-(5-Amino-6-oxo-2-m-tolyl-6H-pyrimidin-1-yl)-N-[4-guanidino-1-(thiazole-2-carbonyl)-butyl]-acetamide   1ztl: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with N-[4-Guanidino-1-(thiazole-2-carbonyl)-butyl]-2-{6-oxo-5-[(quinolin-8-ylmethyl)-amino]-2-m-tolyl-6H-pyrimidin-1-yl}-acetamide   2f83: Crystal structure at 2.9 Angstroms resolution of human plasma coagulation factor XI zymogen   2fda: Crystal Structure of the Catalytic Domain of Human Coagulation Factor XIa in Complex with alpha-Ketothiazole Arginine Derived Ligand