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49  structures 264  species 6  interactions 24503  sequences 2919  architectures

Family: EGF_CA (PF07645)

Summary: Calcium-binding EGF domain

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This is the Wikipedia entry entitled "Calcium-binding EGF domain". More...

Calcium-binding EGF domain Edit Wikipedia article

Calcium-binding EGF domain
PDB 1szb EBI.jpg
crystal structure of the human mbl-associated protein 19 (map19)
Identifiers
Symbol EGF_CA
Pfam PF07645
Pfam clan CL0001
InterPro IPR013091

In molecular biology, the calcium-binding EGF domain is a conserved domain of about forty amino-acid residues found in epidermal growth factor (EGF). This domain is present in a large number of membrane-bound and extracellular, mostly animal, proteins.[1][2][3][4][5] Many of these proteins require calcium for their biological function and a calcium-binding site has been found at the N-terminus of some EGF-like domains.[6] Calcium-binding may be crucial for numerous protein-protein interactions.

For human coagulation factor IX it has been shown that the calcium-ligands form a pentagonal bipyramid.[7] The first, third and fourth conserved negatively charged or polar residues are side chain ligands. The latter is possibly hydroxylated.[6] A conserved aromatic residue, as well as the second conserved negative residue, are thought to be involved in stabilising the calcium-binding site.

As in non-calcium binding EGF-like domains, there are six conserved cysteines and the structure of both types is very similar as calcium-binding induces only strictly local structural changes.[6]

References[edit]

  1. ^ Davis CG (May 1990). "The many faces of epidermal growth factor repeats". New Biol. 2 (5): 410–9. PMID 2288911. 
  2. ^ Blomquist MC, Hunt LT, Barker WC (December 1984). "Vaccinia virus 19-kilodalton protein: relationship to several mammalian proteins, including two growth factors". Proc. Natl. Acad. Sci. U.S.A. 81 (23): 7363–7. doi:10.1073/pnas.81.23.7363. PMC 392146. PMID 6334307. 
  3. ^ Barker WC, Johnson GC, Hunt LT, George DG, Tsugita A (June 1986). "[Similar domains in different proteins: detection and significance]". Tanpakushitsu Kakusan Koso (in Japanese) (29 Suppl): 54–68. PMID 3534958. 
  4. ^ Doolittle RF, Feng DF, Johnson MS (1984). "Computer-based characterization of epidermal growth factor precursor". Nature 307 (5951): 558–60. doi:10.1038/307558a0. PMID 6607417. 
  5. ^ Appella E, Weber IT, Blasi F (April 1988). "Structure and function of epidermal growth factor-like regions in proteins". FEBS Lett. 231 (1): 1–4. doi:10.1016/0014-5793(88)80690-2. PMID 3282918. 
  6. ^ a b c Selander-Sunnerhagen M, Ullner M, Persson E, Teleman O, Stenflo J, Drakenberg T (September 1992). "How an epidermal growth factor (EGF)-like domain binds calcium. High resolution NMR structure of the calcium form of the NH2-terminal EGF-like domain in coagulation factor X". J. Biol. Chem. 267 (27): 19642–9. PMID 1527084. 
  7. ^ Rao Z, Handford P, Mayhew M, Knott V, Brownlee GG, Stuart D (July 1995). "The structure of a Ca(2+)-binding epidermal growth factor-like domain: its role in protein-protein interactions". Cell 82 (1): 131–41. doi:10.1016/0092-8674(95)90059-4. PMID 7606779. 

This article incorporates text from the public domain Pfam and InterPro IPR013091

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Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001881

A sequence of about forty amino-acid residues found in epidermal growth factor (EGF) has been shown [PUBMED:2288911, PUBMED:6334307, PUBMED:3534958, PUBMED:6607417, PUBMED:3282918, PUBMED:] to be present in a large number of membrane-bound and extracellular, mostly animal, proteins. Many of these proteins require calcium for their biological function and a calcium-binding site has been found at the N terminus of some EGF-like domains [PUBMED:1527084]. Calcium-binding may be crucial for numerous protein-protein interactions.

For human coagulation factor IX it has been shown [PUBMED:7606779] that the calcium-ligands form a pentagonal bipyramid. The first, third and fourth conserved negatively charged or polar residues are side chain ligands. The latter is possibly hydroxylated (see aspartic acid and asparagine hydroxylation site) [PUBMED:1527084]. A conserved aromatic residue, as well as the second conserved negative residue, are thought to be involved in stabilising the calcium-binding site.

As in non-calcium binding EGF-like domains, there are six conserved cysteines and the structure of both types is very similar as calcium-binding induces only strictly local structural changes [PUBMED:1527084].

                             +------------------+        +---------+
                             |                  |        |         |
               nxnnC-x(3,14)-C-x(3,7)-CxxbxxxxaxC-x(1,6)-C-x(8,13)-Cx
                   |                  | 
                   +------------------+
'n': negatively charged or polar residue [DEQN]
'b': possibly beta-hydroxylated residue [DN]
'a': aromatic amino acid
'C': cysteine, involved in disulphide bond
'x': any amino acid.

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 EGF (CL0001), which has the following description:

Members of this clan all belong to the EGF superfamily. This particular superfamily is characterised as having least 6 cysteines residues. These cysteine form disulphide bonds, in the order 1-3, 2-4, 5-6, which are essential for the stability of the EGF fold. These disulphide bonds are stacked in a ladder-like arrangement. The Laminin EGF family is distinguished by having an an additional disulphide bond. The function of the domains within this family remains unclear, but they are though to largely perform a structural role. More often than not, there domains are arranged a tandem repeats in extracellular proteins.

The clan contains the following 13 members:

cEGF DSL EGF EGF_2 EGF_3 EGF_alliinase EGF_CA EGF_MSP1_1 FOLN FXa_inhibition hEGF Laminin_EGF Tme5_EGF_like

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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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
(18)
Full
(24503)
Representative proteomes NCBI
(30190)
Meta
(160)
RP15
(4262)
RP35
(5341)
RP55
(9307)
RP75
(14019)
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Format an alignment

  Seed
(18)
Full
(24503)
Representative proteomes NCBI
(30190)
Meta
(160)
RP15
(4262)
RP35
(5341)
RP55
(9307)
RP75
(14019)
Alignment:
Format:
Order:
Sequence:
Gaps:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(18)
Full
(24503)
Representative proteomes NCBI
(30190)
Meta
(160)
RP15
(4262)
RP35
(5341)
RP55
(9307)
RP75
(14019)
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.

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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_330 (release 10.0)
Previous IDs: none
Type: Domain
Author: Bateman A
Number in seed: 18
Number in full: 24503
Average length of the domain: 41.60 aa
Average identity of full alignment: 36 %
Average coverage of the sequence by the domain: 11.43 %

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 21.0 21.0
Trusted cut-off 21.0 21.0
Noise cut-off 20.9 20.9
Model length: 42
Family (HMM) version: 10
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 6 interactions for this family. More...

CUB TSP_3 EGF TB EGF_CA Ldl_recept_b

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 EGF_CA domain has been found. There are 49 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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