Summary: Human growth factor-like EGF
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hEGF, or human growth factor-like EGF, domains have six conserved residues disulfide-bonded into the characteristic 'ababcc' pattern. They are involved in growth and proliferation of cells, in proteins of the Notch/Delta pathway, neurogulin and selectins. hEGFs are also found in mosaic proteins with four-disulfide laminin EGFs such as aggrecan and perlecan. The core fold of the EGF domain consists of two small beta-hairpins packed against each other. Two major structural variants have been identified based on the structural context of the C-terminal Cys residue of disulfide 'c' in the C-terminal hairpin: hEGFs and cEGFs. In hEGFs the C-terminal thiol resides in the beta-turn, resulting in shorter loop-lengths between the Cys residues of disulfide 'c', typically C[8-9]XC. These shorter loop-lengths are also typical of the four-disulfide EGF domains, laminin ad integrin. Tandem hEGF domains have six linking residues between terminal cysteines of adjacent domains. hEGF domains may or may not bind calcium in the linker region. hEGF domains with the consensus motif CXD4X[F,Y]XCXC are hydroxylated exclusively in the Asp residue.
Internal database links
|Similarity to PfamA using HHSearch:||DSL EGF EGF_2 cEGF EGF_3|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR013032A sequence of about thirty to forty amino-acid residues long found in the sequence of epidermal growth factor (EGF) has been shown [PUBMED:, PUBMED:3282918, PUBMED:6607417, PUBMED:2288911, PUBMED:6334307] to be present, in a more or less conserved form, in a large number of other, mostly animal proteins. The list of proteins currently known to contain one or more copies of an EGF-like pattern is large and varied. The functional significance of EGF domains in what appear to be unrelated proteins is not yet clear. However, a common feature is that these repeats are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted (exception: prostaglandin G/H synthase). The EGF domain includes six cysteine residues which have been shown (in EGF) to be involved in disulphide bonds. The main structure is a two-stranded beta-sheet followed by a loop to a C-terminal short two-stranded sheet. Subdomains between the conserved cysteines vary in length. This entry represents a conserved site in the EGF-like domain.
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
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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
We make a range of alignments for each Pfam-A family:
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Curation and family details
|Seed source:||Wouters M|
|Author:||Wouters M, Coggill P|
|Number in seed:||521|
|Number in full:||6130|
|Average length of the domain:||13.00 aa|
|Average identity of full alignment:||50 %|
|Average coverage of the sequence by the domain:||2.13 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||2|
|Download:||download the raw HMM for this family|
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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 hEGF domain has been found. There are 11 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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