Factor XI

Coagulation factor XI

PDB rendering based on 1xx9.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
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, 3BG8, 3SOR, 3SOS, 4CR5, 4CR9, 4CRA, 4CRB, 4CRC, 4CRD, 4CRE, 4CRF, 4CRG, 4NA7, 4NA8, 4TY6, 4TY7, 4WXI, 4X6M, 4X6N, 4X6O, 4X6P

Identifiers

Symbols

F11 ; FXI

External IDs

OMIM: 264900 MGI: 99481 HomoloGene: 86654 ChEMBL: 2820 GeneCards: F11 Gene

EC number

3.4.21.27

Gene ontology
Molecular function	• serine-type endopeptidase activity • protein binding • heparin binding
Cellular component	• extracellular region • extracellular space • plasma membrane • membrane • extracellular exosome
Biological process	• blood coagulation • blood coagulation, intrinsic pathway • plasminogen activation • positive regulation of fibrinolysis
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 4:
186.27 – 186.29 Mb

Chr 8:
45.24 – 45.26 Mb

PubMed search

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]

Function

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 FXIa itself; due to its activation by FXIIa, FXI is a member of the "contact pathway" (which 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).

Structure

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 μg/mL, corresponding to a plasma concentration (of FXI dimers) of approximately 30 nM. 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 hemophilia C; this mainly occurs in Ashkenazi Jews and is believed to affect approximately 8% of that population. Less commonly, hemophilia C can be found in Jews of Iraqi ancestry and in Israeli Arabs. 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

↑ Fujikawa K, Chung DW, Hendrickson LE, Davie EW (May 1986). "Amino acid sequence of human factor XI, a blood coagulation factor with four tandem repeats that are highly homologous with plasma prekallikrein". Biochemistry 25 (9): 2417–24. doi:10.1021/bi00357a018. PMID 3636155.
1 2 Asakai R, Davie EW, Chung DW (Nov 1987). "Organization of the gene for human factor XI". Biochemistry 26 (23): 7221–8. doi:10.1021/bi00397a004. PMID 2827746.
1 2 Kato A, Asakai R, Davie EW, Aoki N (1989). "Factor XI gene (F11) is located on the distal end of the long arm of human chromosome 4". Cytogenetics and Cell Genetics 52 (1-2): 77–8. doi:10.1159/000132844. PMID 2612218.
↑ Buetow KH, Shiang R, Yang P, Nakamura Y, Lathrop GM, White R, Wasmuth JJ, Wood S, Berdahl LD, Leysens NJ (May 1991). "A detailed multipoint map of human chromosome 4 provides evidence for linkage heterogeneity and position-specific recombination rates". American Journal of Human Genetics 48 (5): 911–25. PMC 1683054. PMID 1673289.
↑ Wu W, Sinha D, Shikov S, Yip CK, Walz T, Billings PC, Lear JD, Walsh PN (Jul 2008). "Factor XI homodimer structure is essential for normal proteolytic activation by factor XIIa, thrombin, and factor XIa". The Journal of Biological Chemistry 283 (27): 18655–64. doi:10.1074/jbc.M802275200. PMC 2441546. PMID 18441012.
↑ Walsh PN (Jul 2001). "Roles of platelets and factor XI in the initiation of blood coagulation by thrombin". Thrombosis and Haemostasis 86 (1): 75–82. PMID 11487044.
↑ Bolton-Maggs PH (Jun 1996). "Factor XI deficiency". Baillière's Clinical Haematology 9 (2): 355–68. doi:10.1016/S0950-3536(96)80068-0. PMID 8800510.

External links

The MEROPS online database for peptidases and their inhibitors: S01.213

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

Proteins involved in coagulation

Coagulation factors

Primary hemostasis	vWF platelet membrane glycoproteins: Ib (A B IX) IIb/IIIa (IIb IIIa) VI

Intrinsic pathway	HMWK/Bradykinin Prekallikrein/Kallikrein XII "Hageman" XI IX VIII

Extrinsic pathway	III "Tissue factor" VII

Common pathway	X V II "(Pro)thrombin" I "Fibrin" Fibrinogen (FGA, FGG) XIII

Coagulation inhibitors

Thrombolysis/fibrinolysis

Endopeptidases: serine proteases/serine endopeptidases (EC 3.4.21)

Digestive enzymes	Enteropeptidase Trypsin Chymotrypsin Elastase Neutrophil Pancreatic

Coagulation	factors: Thrombin Factor VIIa Factor IXa Factor Xa Factor XIa Factor XIIa Kallikrein PSA KLK1 KLK2 KLK3 KLK4 KLK5 KLK6 KLK7 KLK8 KLK9 KLK10 KLK11 KLK12 KLK13 KLK14 KLK15 fibrinolysis: Plasmin Plasminogen activator Tissue plasminogen activator Urinary plasminogen activator

Complement system	Factor B Factor D Factor I MASP MASP1 MASP2 C3-convertase

Other immune system	Chymase Granzyme Tryptase Proteinase 3/Myeloblastin

Venombin	Ancrod Batroxobin

Other	Acrosin Prolyl endopeptidase Pronase Proprotein convertases 1 2 Prostasin Reelin Subtilisin/Furin Streptokinase S1P Cathepsin A G

Proteins: enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases(list) EC2 Transferases(list) EC3 Hydrolases(list) EC4 Lyases(list) EC5 Isomerases(list) EC6 Ligases(list)

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