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Literature summary extracted from

  • Emsley, J.; McEwan, P.A.; Gailani, D.
    Structure and function of factor XI (2010), Blood, 115, 2569-2577.
    View publication on PubMedView publication on EuropePMC

Activating Compound

EC Number Activating Compound Comment Organism Structure
3.4.21.27 activated factor IX autoactivation, cleavage of FXI at the Arg369-Ile370 bond. activated factor IX is part of a feedback loop that sustains thrombin generation through FIX activation to consolidate coagulation Homo sapiens
3.4.21.27 activated factor XII activated factor XII-mediated activation of FXI appears to play a central role in formation of pathologic thrombi in murine thrombosis models Mus musculus
3.4.21.27 activated factor XII cleaves FXI at the Arg369-Ile370 bond Homo sapiens
3.4.21.27 alpha-thrombin cleaves FXI at the Arg369-Ile370 bond Homo sapiens
3.4.21.27 meizothrombin cleaves FXI at the Arg369-Ile370 bond Homo sapiens
3.4.21.27 additional information platelets may play a role in FXI activation. FXI binding to platelets is not enhanced by kininogen Homo sapiens
3.4.21.27 thrombin activates FXI. FXI activation by thrombin is enhanced by charged substances, such as dextran sulfate or heparin. Thrombin binds to the A1 domain of FXI, with residues Glu66, Lys83, and Gln84 forming part of the binding site. The dimer is required for optimal FXI activation by thrombin Mus musculus

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
3.4.21.27 full-length zymogen FXI, and the isolated active protease domain of activated factor IX in complex with natural and synthetic inhibitors. Intimate linkage of the apple domains into a disk-like platform around the base of the catalytic domain Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
3.4.21.27 C398Y exhibits a dominant negative effect when coexpressed with wild-type FXI and is associated with FXI deficiency that may be inherited in a dominant manner Homo sapiens
3.4.21.27 G104R this mutation in the PK A2 domain associated with CRM+ PK deficiency causes decreased kininogen binding Homo sapiens
3.4.21.27 G155E is a rare example of a mutation causing CRM+ FXI deficieny Homo sapiens
3.4.21.27 G400V exhibits a dominant negative effect when coexpressed with wild-type FXI and is associated with FXI deficiency that may be inherited in a dominant manner Homo sapiens
3.4.21.27 additional information FXI with substitutions for Cys321 still form stable dimers. The Cys321-Cys321 interchain bond forms poorly in FXI with a single alanine substitution of Leu284, Ile290, or Tyr329 Homo sapiens
3.4.21.27 S225F exhibits a dominant negative effect when coexpressed with wild-type FXI and is associated with FXI deficiency that may be inherited in a dominant manner Homo sapiens
3.4.21.27 S248A binds platelets with reduced affinity compared with wild-type Homo sapiens
3.4.21.27 S248N binds platelets with 5fold reduced affinity compared with wild-type, the A3 domain is probably not affected significantly, as FXI-Asn248 is secreted, activated by activated factor XII, and activates FIX similar to wild-type activated factor IX. Is associated with bleeding and defective FXI binding to platelets but does not affect the activated partial thromboplastin time assay, which does not contain platelets Homo sapiens
3.4.21.27 S248Q binds platelets with reduced affinity compared with wild-type Homo sapiens
3.4.21.27 W569S exhibits a dominant negative effect when coexpressed with wild-type FXI and is associated with FXI deficiency that may be inherited in a dominant manner Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.4.21.27 additional information Arg184 may be part of a switch that holds FXI in an inactive conformation in the zymogen Homo sapiens

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
3.4.21.27 Zn2+ in the presence of zinc ions, kininogen is required for optimal FXI binding to GP1b on activated platelets in suspension, enhancing the binding stoichiometry by approximately 2fold Homo sapiens

Organism

EC Number Organism UniProt Comment Textmining
3.4.21.27 Homo sapiens P03951
-
-
3.4.21.27 Mus musculus
-
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
3.4.21.27 blood
-
 Homo sapiens
-
3.4.21.27 blood plasma
-
 Mus musculus
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.4.21.27 factor IX + H2O
-
 Homo sapiens activated factor IX + ?
-
 ?
3.4.21.27 kininogen + H2O
-
 Homo sapiens ?
-
 ?
3.4.21.27 additional information FXI contains 4 apple domains that form a disk structure with extensive interfaces at the base of the catalytic domain. Binding of FXI to platelets requires residues in the FXI A3 domain. Platelets bind and spread on glass coated with FXI Homo sapiens ?
-
 ?
3.4.21.27 additional information platelets bind and spread on glass coated with FXI. Platelets from ApoER2-deficient mice do not bind FXI Mus musculus ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
3.4.21.27 factor XI
-
 Mus musculus
3.4.21.27 factor XI
-
 Homo sapiens
3.4.21.27 FXI
-
 Mus musculus
3.4.21.27 FXI
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
3.4.21.27 malfunction congenital FXI deficiency is associated with a variable, mild to moderate bleeding disorder. Severe deficiency is prevalent in people of Jewish ancestry. The severe mutation Glu117Stop encodes a truncated protein, and homozygotes lack plasma FXI antigen. The more subtle missense mutation Phe283Leu causes a defect in FXI dimer formation. Most cases of FXI deficiency are associated with low plasma levels of FXI protein. Deficiency or inhibition of FXI interferes with platelet accumulation in growing thrombi. A4 domain mutations associated with FXI deficiency interfere with dimerization. FXI-deficient plasma exhibits a prolonged activated partial thromboplastin clotting time Homo sapiens
3.4.21.27 malfunction mice lacking FIX, FXI, or FXII on a background of low tissue factor expression have a severe bleeding disorder but are viable. Superimposing FIX or FXI deficiency on the low tissue factor background results in death in utero from bleeding Mus musculus
3.4.21.27 physiological function FXI is the zymogen of a blood coagulation protease, factor XIa (activated factor IX), that contributes to hemostasis through activation of factor IX. Almost all FXI circulate in a complex with kininogen Homo sapiens