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88  structures 704  species 0  interactions 162547  sequences 11629  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

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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Calcium-binding EGF domain Provide feedback

No Pfam abstract.

Internal 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 ] 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 ].

                             +------------------+        +---------+
                             |                  |        |         |
                   |                  | 

'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

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

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 cysteine residues. These cysteines 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 thought to largely perform a structural role. More often than not, these domains are arranged in tandem repeats in extracellular proteins.

The clan contains the following 22 members:

cEGF CFC DSL EGF EGF_2 EGF_3 EGF_alliinase EGF_CA EGF_MSP1_1 EGF_Tenascin Ephrin_rec_like Fibrillin_U_N FOLN FXa_inhibition Gla hEGF I-EGF_1 Laminin_EGF Plasmod_Pvs28 Sushi Sushi_2 Tme5_EGF_like


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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB 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.

Representative proteomes UniProt
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

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Representative proteomes UniProt

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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.

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

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...


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.

Note: You can also download the data file for the tree.

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
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 18
Number in full: 162547
Average length of the domain: 41.60 aa
Average identity of full alignment: 36 %
Average coverage of the sequence by the domain: 11.44 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.0 16.3
Trusted cut-off 27.0 16.3
Noise cut-off 26.9 16.2
Model length: 42
Family (HMM) version: 18
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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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 EGF_CA domain has been found. There are 88 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 sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A096LNW5 View 3D Structure Click here
A0A096MJG4 View 3D Structure Click here
A0A0G2JSI4 View 3D Structure Click here
A0A0G2JTG3 View 3D Structure Click here
A0A0G2JVB2 View 3D Structure Click here
A0A0G2JXD2 View 3D Structure Click here
A0A0G2JYM7 View 3D Structure Click here
A0A0G2JZH3 View 3D Structure Click here
A0A0G2K2R5 View 3D Structure Click here
A0A0G2K538 View 3D Structure Click here
A0A0G2K5M0 View 3D Structure Click here
A0A0G2KB47 View 3D Structure Click here
A0A0G2KDJ5 View 3D Structure Click here
A0A0G2KR67 View 3D Structure Click here
A0A0G2KTB7 View 3D Structure Click here
A0A0G2KWA4 View 3D Structure Click here
A0A0G2L836 View 3D Structure Click here
A0A0P0VM56 View 3D Structure Click here
A0A0P0W972 View 3D Structure Click here
A0A0P0W976 View 3D Structure Click here
A0A0P0W996 View 3D Structure Click here
A0A0P0XM28 View 3D Structure Click here
A0A0P0XNG3 View 3D Structure Click here
A0A0P0XQC9 View 3D Structure Click here
A0A0P0XQF5 View 3D Structure Click here
A0A0P0XRK8 View 3D Structure Click here
A0A0P0XRM4 View 3D Structure Click here
A0A0P0XS43 View 3D Structure Click here
A0A0P0XS49 View 3D Structure Click here
A0A0P0Y5N5 View 3D Structure Click here
A0A0P0YA14 View 3D Structure Click here
A0A0R0GDX2 View 3D Structure Click here
A0A0R4I9N1 View 3D Structure Click here
A0A0R4IAF3 View 3D Structure Click here
A0A0R4IBT9 View 3D Structure Click here
A0A0R4IKQ6 View 3D Structure Click here
A0A0R4IL08 View 3D Structure Click here
A0A0R4IL35 View 3D Structure Click here
A0A0R4IN59 View 3D Structure Click here
A0A0R4IYY9 View 3D Structure Click here