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13  structures 1408  species 0  interactions 14263  sequences 529  architectures

Family: EF-hand_4 (PF12763)

Summary: Cytoskeletal-regulatory complex EF hand

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.

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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

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

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

View options

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
(13)
Full
(14263)
Representative proteomes UniProt
(25564)
RP15
(1916)
RP35
(5298)
RP55
(11414)
RP75
(16076)
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PP/heatmap 1            

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

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

Format an alignment

  Seed
(13)
Full
(14263)
Representative proteomes UniProt
(25564)
RP15
(1916)
RP35
(5298)
RP55
(11414)
RP75
(16076)
Alignment:
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Sequence:
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Download options

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
(13)
Full
(14263)
Representative proteomes UniProt
(25564)
RP15
(1916)
RP35
(5298)
RP55
(11414)
RP75
(16076)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped 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.

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.

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: 14263
Average length of the domain: 94.40 aa
Average identity of full alignment: 31 %
Average coverage of the sequence by the domain: 16.74 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild --amino -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.3 21.3
Trusted cut-off 21.3 21.3
Noise cut-off 21.2 21.2
Model length: 104
Family (HMM) version: 9
Download: download the raw HMM for this family

Species distribution

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Selections

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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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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 EF-hand_4 domain has been found. There are 13 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
A0A0G2L0S9 View 3D Structure Click here
A0A0G2L0S9 View 3D Structure Click here
A0A0K3AS36 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
A0A1D8PF53 View 3D Structure Click here
A0A1D8PF53 View 3D Structure Click here
A0A2R8QHH3 View 3D Structure Click here
A0A2R8QHH3 View 3D Structure Click here
A0A2R8QHH3 View 3D Structure Click here
A0A2R8RHR6 View 3D Structure Click here
A0A2R8RHR6 View 3D Structure Click here
A0A2R8RHR6 View 3D Structure Click here
A0A2R8RZ08 View 3D Structure Click here
A0A2R8RZ08 View 3D Structure Click here
A0A2R8RZ08 View 3D Structure Click here
A8E7E7 View 3D Structure Click here
A8E7E7 View 3D Structure Click here
B3LF48 View 3D Structure Click here
B4FPT9 View 3D Structure Click here
D3ZJR1 View 3D Structure Click here
D3ZJR1 View 3D Structure Click here
D3ZJR1 View 3D Structure Click here
E7FBC4 View 3D Structure Click here
E9PSY8 View 3D Structure Click here
E9PSY8 View 3D Structure Click here
E9PSY8 View 3D Structure Click here
E9QGV7 View 3D Structure Click here
F1QCM5 View 3D Structure Click here
F1QCM5 View 3D Structure Click here
F1QIJ6 View 3D Structure Click here
F1QIJ6 View 3D Structure Click here
F1QIJ6 View 3D Structure Click here
F1R0Z9 View 3D Structure Click here
F1R0Z9 View 3D Structure Click here
F4HY32 View 3D Structure Click here
G5ECC3 View 3D Structure Click here
I1JJC9 View 3D Structure Click here
I1JST7 View 3D Structure Click here
I1K7B7 View 3D Structure Click here
I1KNI2 View 3D Structure Click here
I1KZX5 View 3D Structure Click here
I1M635 View 3D Structure Click here
I1MFL9 View 3D Structure Click here
I1MR19 View 3D Structure Click here
I1N0J5 View 3D Structure Click here
K7KBT7 View 3D Structure Click here
M0R7A6 View 3D Structure Click here
M0R7A6 View 3D Structure Click here
M9ND00 View 3D Structure Click here
M9ND00 View 3D Structure Click here
O54916 View 3D Structure Click here
O94685 View 3D Structure Click here
P32521 View 3D Structure Click here
P34216 View 3D Structure Click here
P39013 View 3D Structure Click here
P42567 View 3D Structure Click here
P42567 View 3D Structure Click here
P42567 View 3D Structure Click here
Q10172 View 3D Structure Click here
Q10172 View 3D Structure Click here
Q10S92 View 3D Structure Click here
Q15811 View 3D Structure Click here
Q15811 View 3D Structure Click here
Q4V8H8 View 3D Structure Click here
Q54KI4 View 3D Structure Click here
Q54KI4 View 3D Structure Click here
Q54KI4 View 3D Structure Click here
Q54ST5 View 3D Structure Click here
Q55DJ6 View 3D Structure Click here
Q59SR6 View 3D Structure Click here
Q5AHB1 View 3D Structure Click here
Q5AHB1 View 3D Structure Click here
Q5AJ82 View 3D Structure Click here
Q5TYP7 View 3D Structure Click here
Q5VSI7 View 3D Structure Click here
Q60902 View 3D Structure Click here
Q60902 View 3D Structure Click here
Q641Z6 View 3D Structure Click here
Q653F5 View 3D Structure Click here
Q66HW2 View 3D Structure Click here
Q6ET46 View 3D Structure Click here
Q6NY81 View 3D Structure Click here
Q6P3J7 View 3D Structure Click here
Q7XR66 View 3D Structure Click here
Q80XA6 View 3D Structure Click here
Q8BH64 View 3D Structure Click here
Q8IJF4 View 3D Structure Click here
Q8IJF4 View 3D Structure Click here
Q8MQS4 View 3D Structure Click here
Q8MYM6 View 3D Structure Click here
Q8NFH8 View 3D Structure Click here
Q8R3Z7 View 3D Structure Click here
Q8R491 View 3D Structure Click here
Q8T8W3 View 3D Structure Click here
Q94CF0 View 3D Structure Click here
Q96D71 View 3D Structure Click here
Q9BIF4 View 3D Structure Click here
Q9BIF4 View 3D Structure Click here
Q9EQP2 View 3D Structure Click here
Q9H223 View 3D Structure Click here
Q9H4M9 View 3D Structure Click here
Q9HGL2 View 3D Structure Click here
Q9HGL2 View 3D Structure Click here
Q9HGL2 View 3D Structure Click here
Q9LM78 View 3D Structure Click here
Q9NLB8 View 3D Structure Click here
Q9NZM3 View 3D Structure Click here
Q9NZM3 View 3D Structure Click here
Q9NZN3 View 3D Structure Click here
Q9NZN4 View 3D Structure Click here
Q9QXY6 View 3D Structure Click here
Q9UBC2 View 3D Structure Click here
Q9UBC2 View 3D Structure Click here
Q9UBC2 View 3D Structure Click here
Q9USZ7 View 3D Structure Click here
Q9W111 View 3D Structure Click here
Q9W111 View 3D Structure Click here
Q9WVE9 View 3D Structure Click here
Q9WVE9 View 3D Structure Click here
Q9WVK4 View 3D Structure Click here
Q9Z0R4 View 3D Structure Click here
Q9Z0R4 View 3D Structure Click here