Discoidin domain explained

Discoidin domain (also known as F5/8 type C domain, or C2-like domain) is major protein 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 the 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.[1] [2] [3] 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.[4] 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.[5] [6] FA58C contains two conserved cysteines in most proteins, which link the extremities of the domain by a disulfide bond.[7] [8] [9] A further disulfide bond is located near the C-terminal of the second FA58C domain in MFGM .

Human proteins containing this domain

AEBP1

BTBD9; CASPR4; CNTNAP1; CNTNAP2; CNTNAP3; CNTNAP4; CNTNAP5; CPXM1; CPXM2; DCBLD1; DCBLD2; DDR1; DDR2; EDIL3;F5
  • F8; F8B; MFGE8; NRP1; NRP2; RS1; SSPO; UNC13A

    • References

    Notes

    Further reading

    Baumgartner . S. . Hofmann . K. . Chiquet-Ehrismann . P. . Bucher . R. . The discoidin domain family revisited: New members from prokaryotes and a homology-based fold prediction . 10.1002/pro.5560070717 . Protein Science . 7 . 7 . 1626–1631 . 1998 . 9684896 . 2144056 .

    Notes and References

    1. Davie EW, Kane WH . Cloning of a cDNA coding for human factor V, a blood coagulation factor homologous to factor VIII and ceruloplasmin . 83 . 18 . 6800–6804 . 1986 . 3092220 . Proc. Natl. Acad. Sci. U.S.A. . 10.1073/pnas.83.18.6800 . 386597. free .
    2. Rutter WJ, Edman JC, Johnson JD . 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 . 1993 . 8390675 . 10.1073/pnas.90.12.5677 . 46784. free .
    3. Couto JR, Taylor MR, Godwin SG, Ceriani RL, Peterson JA . 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 . 1996 . 8639264 . 10.1089/dna.1996.15.281.
    4. Davie EW, Kane WH . Blood coagulation factors V and VIII: structural and functional similarities and their relationship to hemorrhagic and thrombotic disorders . Blood . 71 . 3 . 539–555 . 1988 . 10.1182/blood.V71.3.539.539 . 3125864. free .
    5. Foster PA, Fulcher CA, Houghten RA, Zimmerman TS . 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 . 1990 . 10.1182/blood.V75.10.1999.1999 . 2110840. free .
    6. Kane WH, Peterson JA, Ortel TL, Quinn-Allen MA, Keller FG, Larocca D . 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 . 1994 . 10.1016/S0021-9258(17)40765-4 . 7515064. free .
    7. Mann KG, Xue J, Kalafatis M . Determination of the disulfide bridges in factor Va light chain . Biochemistry . 32 . 22 . 5917–5923 . 1993 . 8504111 . 10.1021/bi00071a002.
    8. Fujikawa K, McMullen BA, Davie EW, Hedner U, Ezban M . 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 . 1995 . 7613471 . 2143093 . 10.1002/pro.5560040413.
    9. Petersen TE, Hvarregaard J, AndersenMH, Berglund L, Rasmussen JT . Characterization of glycoprotein PAS-6/7 from membranes of bovine milk fat globules . Eur. J. Biochem. . 240 . 3 . 628–636 . September 1996. 8856064 . 10.1111/j.1432-1033.1996.0628h.x. free .

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