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14  structures 1497  species 0  interactions 17638  sequences 575  architectures

Family: EF-hand_4 (PF12763)

Summary: Cytoskeletal-regulatory complex EF hand

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Cytoskeletal-regulatory complex EF hand Provide feedback

This is an efhand family from the N-terminal of actin cytoskeleton-regulatory complex END3 and similar proteins from fungi and closely related species.

Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000261

The EH (for Eps15 Homology) domain is a protein-protein interaction module of approximately 95 residues which was originally identified as a repeated sequence present in three copies at the N terminus of the tyrosine kinase substrates Eps15 and Eps15R [ PUBMED:7568168 , PUBMED:11911876 ]. The EH domain was subsequently found in several proteins implicated in endocytosis, vesicle transport and signal transduction in organisms ranging from yeast to mammals. EH domains are present in one to three copies and they may include calcium-binding domains of the EF-hand type [ PUBMED:9397678 , PUBMED:10021353 ]. Eps15 is divided into three domains: domain I contains signatures of a regulatory domain, including a candidate tyrosine phosphorylation site and EF-hand-type calcium-binding domains, domain II presents the characteristic heptad repeats of coiled-coil rod-like proteins, and domain III displays a repeated aspartic acid-proline-phenylalanine motif similar to a consensus sequence of several methylases [ PUBMED:7689153 ].

EH domains have been shown to bind specifically but with moderate affinity to peptides containing short, unmodified motifs through predominantly hydrophobic interactions. The target motifs are divided into three classes: class I consists of the concensus Asn-Pro-Phe (NPF) sequence; class II consists of aromatic and hydrophobic di- and tripeptide motifs, including the Phe-Trp (FW), Trp-Trp (WW), and Ser-Trp-Gly (SWG) motifs; and class III contains the His-(Thr/Ser)-Phe motif (HTF/HSF) [ PUBMED:9303539 , PUBMED:9822599 ]. The structure of several EH domains has been solved by NMR spectroscopy. The fold consists of two helix-loop-helix characteristic of EF-hand domains, connected by a short antiparallel beta-sheet. The target peptide is bound in a hydrophobic pocket between two alpha helices. Sequence analysis and structural data indicate that not all the EF-hands are capable of binding calcium because of substitutions of the calcium-liganding residues in the loop [ PUBMED:9721102 , PUBMED:10757979 , PUBMED:11389591 ].

This domain is often implicated in the regulation of protein transport/sorting and membrane trafficking. Messenger RNA translation initiation and cytoplasmic poly(A) tail shortening require the poly(A)-binding protein (PAB) in yeast. The PAB-dependent poly(A) ribonuclease (PAN) is organised into distinct domains containing repeated sequence elements [ PUBMED:1339314 ].

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


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.

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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.

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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_51079 (release 24.0)
Previous IDs: efhand_3;
Type: Family
Sequence Ontology: SO:0100021
Author: Wood V , Coggill P
Number in seed: 13
Number in full: 17638
Average length of the domain: 94.50 aa
Average identity of full alignment: 32 %
Average coverage of the sequence by the domain: 16.63 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild --amino -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.0 22.0
Trusted cut-off 22.0 22.0
Noise cut-off 21.9 21.9
Model length: 104
Family (HMM) version: 10
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 EF-hand_4 domain has been found. There are 14 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
A0A0G2JZY3 View 3D Structure Click here
A0A0G2K1L4 View 3D Structure Click here
A0A0G2L0S9 View 3D Structure Click here
A0A0K3AS36 View 3D Structure Click here
A0A0P0X1C3 View 3D Structure Click here
A0A0R0IZ12 View 3D Structure Click here
A0A1D6GU10 View 3D Structure Click here
A0A1D6GWT6 View 3D Structure Click here
A0A1D6JMN9 View 3D Structure Click here
A0A1D6LUR9 View 3D Structure Click here
A0A1D6PJG6 View 3D Structure Click here
A0A1D8PF53 View 3D Structure Click here
A0A2R8QHH3 View 3D Structure Click here
A0A2R8RHR6 View 3D Structure Click here
A0A2R8RZ08 View 3D Structure Click here
A1CD74 View 3D Structure Click here
A1CPG1 View 3D Structure Click here
A1D2B8 View 3D Structure Click here
A1DC51 View 3D Structure Click here
A1DDY6 View 3D Structure Click here
A2QRG2 View 3D Structure Click here
A2R180 View 3D Structure Click here
A2RA84 View 3D Structure Click here
A3LN86 View 3D Structure Click here
A3LPY4 View 3D Structure Click here
A3M008 View 3D Structure Click here
A4QST9 View 3D Structure Click here
A4R8N4 View 3D Structure Click here
A5DBE7 View 3D Structure Click here
A5DF78 View 3D Structure Click here
A5DP36 View 3D Structure Click here
A5DVD6 View 3D Structure Click here
A5DXI9 View 3D Structure Click here
A5DZL0 View 3D Structure Click here
A6R7X5 View 3D Structure Click here
A6RFP4 View 3D Structure Click here
A7E7N7 View 3D Structure Click here
A7EKZ0 View 3D Structure Click here
A7TEE6 View 3D Structure Click here
A7TSV7 View 3D Structure Click here