Jump to content

Factor XI: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
m →Structure: Journal cites:, added 1 PMC using AWB (12061)
Jdevola (talk | contribs)
303 edits
m →Structure: typos ~~~~
Line 15: Line 15:
The FXI gene is 23kb in length, has 15 exons, and is found on chromosome 4q32-35.<ref name="pmid2827746"/><ref name="pmid2612218"/>
The FXI gene is 23kb in length, has 15 exons, and is found on chromosome 4q32-35.<ref name="pmid2827746"/><ref name="pmid2612218"/>


Factor XI consists of four [[PAN domain|apple domain]]s, that creates a disk-like platform around the base of a fifth, catalytic [[serine protease]] domain.
Factor XI consists of four [[PAN domain|apple domain]]s, that create a disk-like platform around the base of a fifth, catalytic [[serine protease]] domain.
One contains a binding sites for [[thrombin]], another for [[high molecular weight kininogen]], a third one for [[factor IX]], [[heparin]] and [[glycoprotein Ib]] and the fourth is implicated in forming the factor XI homodimer, including a [[cysteine]] redisude that creates a [[disulfide bond]].
One contains a binding site for [[thrombin]], another for [[high molecular weight kininogen]], a third one for [[factor IX]], [[heparin]] and [[glycoprotein Ib]] and the fourth is implicated in forming the factor XI homodimer, including a [[cysteine]] residue that creates a [[disulfide bond]].


In the homodimer, the apple domains create two disk-like platforms connected together in an angle, with the catalytic domains sticking out at each side of the dimer.
In the homodimer, the apple domains create two disk-like platforms connected together at an angle, with the catalytic domains sticking out at each side of the dimer.


Activation by thrombin or [[factor XII]]a is achieved by cleavage of Arg369-Ile370 peptide bonds on both subunits of the dimer. This results in a partial detachment of the catalytic domain from the disk-like apple domains, still linked to the forth domain with a disulfide bond, but now farther from the third domain.
Activation by thrombin or [[factor XII]]a is achieved by cleavage of Arg369-Ile370 peptide bonds on both subunits of the dimer. This results in a partial detachment of the catalytic domain from the disk-like apple domains, still linked to the forth domain with a disulfide bond, but now farther from the third domain.
This is thought to expose the factor IX binding site of the third apple domain, allowing factor XI's protease activity on it.
This is thought that this exposes the factor IX binding site of the third apple domain, allowing factor XI's protease activity on it.
<ref>{{cite journal|vauthors=Emsley J, McEwan PA, Gailani D | title=Structure and function of factor XI | journal=Blood | date = Apr 2010 | volume= 115 | issue= 13 | pages= 2569–77 | pmid=20110423 | doi=10.1182/blood-2009-09-199182 | pmc=4828079}}</ref>
<ref>{{cite journal|vauthors=Emsley J, McEwan PA, Gailani D | title=Structure and function of factor XI | journal=Blood | date = Apr 2010 | volume= 115 | issue= 13 | pages= 2569–77 | pmid=20110423 | doi=10.1182/blood-2009-09-199182 | pmc=4828079}}</ref>


Revision as of 13:46, 19 January 2017

F11
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesF11, FXI, coagulation factor XI, PTA, factor XI
External IDsOMIM: 264900; MGI: 99481; HomoloGene: 86654; GeneCards: F11; OMA:F11 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

2160

109821

Ensembl

ENSG00000088926

ENSMUSG00000031645

UniProt

P03951

Q91Y47

RefSeq (mRNA)

NM_000128
NM_019559
NM_001354804

NM_028066

RefSeq (protein)

NP_000119
NP_001341733

NP_082342

Location (UCSC)Chr 4: 186.27 – 186.29 MbChr 8: 45.69 – 45.72 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5][6][7][8]

Function

Factor XI (FXI) is produced by the liver and circulates as a homo-dimer in its inactive form.[9] 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).[10]

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.[6][7]

Factor XI consists of four apple domains, that create a disk-like platform around the base of a fifth, catalytic serine protease domain. One contains a binding site for thrombin, another for high molecular weight kininogen, a third one for factor IX, heparin and glycoprotein Ib and the fourth is implicated in forming the factor XI homodimer, including a cysteine residue that creates a disulfide bond.

In the homodimer, the apple domains create two disk-like platforms connected together at an angle, with the catalytic domains sticking out at each side of the dimer.

Activation by thrombin or factor XIIa is achieved by cleavage of Arg369-Ile370 peptide bonds on both subunits of the dimer. This results in a partial detachment of the catalytic domain from the disk-like apple domains, still linked to the forth domain with a disulfide bond, but now farther from the third domain. This is thought that this exposes the factor IX binding site of the third apple domain, allowing factor XI's protease activity on it. [11]

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.[12]

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.

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000088926 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031645 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ a b 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.
  7. ^ a b 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.
  8. ^ 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.
  9. ^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  10. ^ 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.
  11. ^ Emsley J, McEwan PA, Gailani D (Apr 2010). "Structure and function of factor XI". Blood. 115 (13): 2569–77. doi:10.1182/blood-2009-09-199182. PMC 4828079. PMID 20110423.
  12. ^ 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.

Further reading

  • The MEROPS online database for peptidases and their inhibitors: S01.213
Retrieved from "https://en.wikipedia.org/w/index.php?title=Factor_XI&oldid=760855519"