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169  structures 1614  species 2  interactions 10300  sequences 1197  architectures

Family: F5_F8_type_C (PF00754)

Summary: F5/8 type C domain

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This is the Wikipedia entry entitled "Discoidin domain". More...

Discoidin domain Edit Wikipedia article

F5/8 type C domain
PDB 1fac EBI.jpg
Structure of the membrane-binding C2 domain of factor VIII.[1]
Identifiers
Symbol F5_F8_type_C
Pfam PF00754
InterPro IPR000421
PROSITE PDOC00988
SCOP 1fac
SUPERFAMILY 1fac
OPM superfamily 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[edit]

AEBP1; BTBD9; CASPR4; CNTNAP1; CNTNAP2; CNTNAP3; CNTNAP4; CNTNAP5; CPXM1; CPXM2; DCBLD1; DCBLD2; DDR1; DDR2; EDIL3; F5; F8; F8B; MFGE8; NRP1; NRP2; RS1; SSPO;

References[edit]

  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. 
  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. 
  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. 
  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. 
  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[edit]

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

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


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F5/8 type C domain Provide feedback

This domain is also known as the discoidin (DS) domain family [1].

Literature references

  1. Baumgartner S, Hofmann K, Chiquet-Ehrismann R, Bucher P; , Protein Sci 1998;7:1626-1631.: The discoidin domain family revisited: new members from prokaryotes and a homology-based fold prediction. PUBMED:9684896 EPMC:9684896


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000421

Blood coagulation factors V and VIII contain a C-terminal, twice repeated, domain of about 150 amino acids, which is called F5/8 type C, FA58C, or C1/C2- like 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 [PUBMED:3092220, PUBMED:8390675, PUBMED:8639264] 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 [PUBMED:3125864]. 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 [PUBMED:2110840, PUBMED:7515064]. It forms an amphipathic alpha-helix, which binds to the membrane [PUBMED:7893714]. FA58C contains two conserved cysteines in most proteins, which link the extremities of the domain by a disulphide bond [PUBMED:8504111, PUBMED:7613471, PUBMED:8856064]. A further disulphide bond is located near the C-terminal of the second FA58C domain in MFGM SWISSPROT [PUBMED:8856064].
  +------------------------------------------------------------------------+
  |                                                               +-+      |
  |                                                               | |      |
  CxPLGxxQITASxxxxxRLxxxWxxxxWxxxxxxQGxxxxxxxxxxxxGNxxxxxxxxxxRxPxcxcLRxExGC
'C': conserved cysteine involved in a disulphide bond.
'c': cysteine involved in a disulphide bond in MFGM SWISSPROT.
'x': any amino acid.
upper case letters: conserved residues.

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan GBD (CL0202), which has the following description:

This large superfamily contains beta sandwich domains with a jelly roll topology. Many of these families are involved in carbohydrate recognition. Despite sharing little sequence similarity they do share a weak sequence motif, with a conserved bulge in the C-terminal beta sheet. The probable role of this bulge is in bending of the beta sheet that contains the bulge. This enables the curvature of the sheet forming the sugar binding site [1].

The clan contains the following 27 members:

Allantoicase APC10 Bac_rhamnosid_N BetaGal_dom4_5 CBM_11 CBM_15 CBM_17_28 CBM_4_9 CBM_6 CIA30 Cleaved_Adhesin DUF642 Endotoxin_C Ephrin_lbd F5_F8_type_C FBA Glyco_hydro_2_N Laminin_N Lyase_N MAM Muskelin_N P_proprotein PA-IL PepX_C PITH Sad1_UNC XRCC1_N

Alignments

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(185)
Full
(10300)
Representative proteomes NCBI
(9293)
Meta
(615)
RP15
(2052)
RP35
(2661)
RP55
(3306)
RP75
(3934)
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Format an alignment

  Seed
(185)
Full
(10300)
Representative proteomes NCBI
(9293)
Meta
(615)
RP15
(2052)
RP35
(2661)
RP55
(3306)
RP75
(3934)
Alignment:
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Sequence:
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  Seed
(185)
Full
(10300)
Representative proteomes NCBI
(9293)
Meta
(615)
RP15
(2052)
RP35
(2661)
RP55
(3306)
RP75
(3934)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_478 (release 2.1)
Previous IDs: none
Type: Domain
Author: Bateman A, Finn RD
Number in seed: 185
Number in full: 10300
Average length of the domain: 125.60 aa
Average identity of full alignment: 16 %
Average coverage of the sequence by the domain: 18.56 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.8 23.8
Trusted cut-off 23.8 23.8
Noise cut-off 23.7 23.7
Model length: 129
Family (HMM) version: 20
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 2 interactions for this family. More...

F5_F8_type_C CUB

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the F5_F8_type_C domain has been found. There are 169 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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