Discoidin domain

Discoidin domain
F5/8 type C domain
PDB 1fac EBI.jpg
Structure of the membrane-binding C2 domain of factor VIII.[1]
Symbol F5_F8_type_C
Pfam PF00754
InterPro IPR000421
SCOP 1fac
OPM family 48
OPM protein 1sdd

Discoidin domain (also known as F5/8 type C domain, or C2-like domain) is major domain of many blood coagulation factors.

Blood coagulation factors V and VIII contain a C-terminal, twice repeated, domain of about 150 amino acids, which is often called "C2-like domain" (that is unrelated to C2 domain). In the Dictyostelium discoideum (Slime mold) cell adhesion protein discoidin, a related domain, named discoidin I-like domain, DLD, or DS, has been found which shares a common C-terminal region of about 110 amino acids with the FA58C domain, but whose N-terminal 40 amino acids are much less conserved. Similar domains have been detected in other extracellular and membrane proteins.[2][3][4] In coagulation factors V and VIII the repeated domains compose part of a larger functional domain which promotes binding to anionic phospholipids on the surface of platelets and endothelial cells.[5] The C-terminal domain of the second FA58C repeat (C2) of coagulation factor VIII has been shown to be responsible for phosphatidylserine-binding and essential for activity.[6][7] It forms an amphipathic alpha-helix, which binds to the membrane.[8] FA58C contains two conserved cysteines in most proteins, which link the extremities of the domain by a disulfide bond.[9][10][11] A further disulfide bond is located near the C-terminal of the second FA58C domain in MFGM Q08431.[11]

Human proteins containing this domain



  1. ^ Veeraraghavan S, Baleja JD, Gilbert GE (June 1998). "Structure and topography of the membrane-binding C2 domain of factor VIII in the presence of dodecylphosphocholine micelles". Biochem. J. 332 ( Pt 2) (Pt 2): 549–55. PMC 1219512. PMID 9601086. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1219512. 
  2. ^ Davie EW, Kane WH (1986). "Cloning of a cDNA coding for human factor V, a blood coagulation factor homologous to factor VIII and ceruloplasmin". Proc. Natl. Acad. Sci. U.S.A. 83 (18): 6800–6804. doi:10.1073/pnas.83.18.6800. PMC 386597. PMID 3092220. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=386597. 
  3. ^ Rutter WJ, Edman JC, Johnson JD (1993). "A receptor tyrosine kinase found in breast carcinoma cells has an extracellular discoidin I-like domain". Proc. Natl. Acad. Sci. U.S.A. 90 (12): 5677–5681. doi:10.1073/pnas.90.12.5677. PMC 46784. PMID 8390675. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=46784. 
  4. ^ Couto JR, Taylor MR, Godwin SG, Ceriani RL, Peterson JA (1996). "Cloning and sequence analysis of human breast epithelial antigen BA46 reveals an RGD cell adhesion sequence presented on an epidermal growth factor-like domain". DNA Cell Biol. 15 (4): 281–286. doi:10.1089/dna.1996.15.281. PMID 8639264. 
  5. ^ Davie EW, Kane WH (1988). "Blood coagulation factors V and VIII: structural and functional similarities and their relationship to hemorrhagic and thrombotic disorders". Blood 71 (3): 539–555. PMID 3125864. 
  6. ^ Foster PA, Fulcher CA, Houghten RA, Zimmerman TS (1990). "Synthetic factor VIII peptides with amino acid sequences contained within the C2 domain of factor VIII inhibit factor VIII binding to phosphatidylserine". Blood 75 (10): 1999–2004. PMID 2110840. 
  7. ^ Kane WH, Peterson JA, Ortel TL, Quinn-Allen MA, Keller FG, Larocca D (1994). "Localization of functionally important epitopes within the second C-type domain of coagulation factor V using recombinant chimeras". J. Biol. Chem. 269 (22): 15898–15905. PMID 7515064. 
  8. ^ Baleja JD, Gilbert GE (1995). "Membrane-binding peptide from the C2 domain of factor VIII forms an amphipathic structure as determined by NMR spectroscopy". Biochemistry 34 (9): 3022–3031. doi:10.1021/bi00009a033. PMID 7893714. 
  9. ^ Mann KG, Xue J, Kalafatis M (1993). "Determination of the disulfide bridges in factor Va light chain". Biochemistry 32 (22): 5917–5923. doi:10.1021/bi00071a002. PMID 8504111. 
  10. ^ Fujikawa K, McMullen BA, Davie EW, Hedner U, Ezban M (1995). "Locations of disulfide bonds and free cysteines in the heavy and light chains of recombinant human factor VIII (antihemophilic factor A)". Protein Sci. 4 (4): 740–746. doi:10.1002/pro.5560040413. PMC 2143093. PMID 7613471. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2143093. 
  11. ^ a b Petersen TE, Hvarregaard J, AndersenMH, Berglund L, Rasmussen JT (1996). "Characterization of glycoprotein PAS-6/7 from membranes of bovine milk fat globules". Eur. J. Biochem. 240 (3): 628–636. doi:10.1111/j.1432-1033.1996.0628h.x. PMID 8856064. 

Further reading

The discoidin domain family revisited: new members from prokaryotes and a homology-based fold prediction. Baumgartner S, Hofmann K, Chiquet-Ehrismann R, Bucher P; Protein Sci 1998;7:1626-1631. PubMed

This article includes text from the public domain Pfam and InterPro IPR000421