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2  structures 596  species 0  interactions 14361  sequences 1161  architectures

Family: Ephrin_rec_like (PF07699)

Summary: Tyrosine-protein kinase ephrin type A/B receptor-like

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Tyrosine-protein kinase ephrin type A/B receptor-like Provide feedback

This family has repeats of a region rich in cysteines. It is found in various ephrin type A and B receptors, which have tyrosine kinase activity.

Literature references

  1. Li E, Hristova K;, Biochemistry. 2006;45:6241-6251.: Role of receptor tyrosine kinase transmembrane domains in cell signaling and human pathologies. PUBMED:16700535 EPMC:16700535


Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR011641

Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity [ PUBMED:3291115 ]:

  • Serine/threonine-protein kinases
  • Tyrosine-protein kinases
  • Dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)

Protein kinase function is evolutionarily conserved from Escherichia coli to human [ PUBMED:12471243 ]. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation [ PUBMED:12368087 ]. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [ PUBMED:15078142 ], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [ PUBMED:15320712 ].

This entry represents a domain found in various ephrin type A and B receptors, which have tyrosine kinase activity.

Tyrosine-protein kinases can transfer a phosphate group from ATP to a tyrosine residue in a protein. These enzymes can be divided into two main groups [ PUBMED:12471243 ]:

  • Receptor tyrosine kinases (RTK), which are transmembrane proteins involved in signal transduction; they play key roles in growth, differentiation, metabolism, adhesion, motility, death and oncogenesis [ PUBMED:19275641 ]. RTKs are composed of 3 domains: an extracellular domain (binds ligand), a transmembrane (TM) domain, and an intracellular catalytic domain (phosphorylates substrate). The TM domain plays an important role in the dimerisation process necessary for signal transduction [ PUBMED:16700535 ].

  • Cytoplasmic / non-receptor tyrosine kinases, which act as regulatory proteins, playing key roles in cell differentiation, motility, proliferation, and survival. For example, the Src-family of protein-tyrosine kinases [ PUBMED:15845350 ].

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

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
(28)
Full
(14361)
Representative proteomes UniProt
(36457)
RP15
(4343)
RP35
(7129)
RP55
(13272)
RP75
(16553)
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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
(28)
Full
(14361)
Representative proteomes UniProt
(36457)
RP15
(4343)
RP35
(7129)
RP55
(13272)
RP75
(16553)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

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
(28)
Full
(14361)
Representative proteomes UniProt
(36457)
RP15
(4343)
RP35
(7129)
RP55
(13272)
RP75
(16553)
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: He QY, Liu XH
Previous IDs: GCC2_GCC3;
Type: Family
Sequence Ontology: SO:0100021
Author: He QY, Liu XH, Studholme DJ
Number in seed: 28
Number in full: 14361
Average length of the domain: 46.50 aa
Average identity of full alignment: 29 %
Average coverage of the sequence by the domain: 7.46 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.1 23.1
Trusted cut-off 23.1 23.1
Noise cut-off 23.0 23.0
Model length: 48
Family (HMM) version: 15
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

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 Ephrin_rec_like domain has been found. There are 2 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.

Loading structure mapping...

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
A0A0G2JVB2 View 3D Structure Click here
A0A0G2JVB2 View 3D Structure Click here
A0A0G2JVB2 View 3D Structure Click here
A0A0G2JY48 View 3D Structure Click here
A0A0R4IBT9 View 3D Structure Click here
A0A0R4IBT9 View 3D Structure Click here
A0A0R4IBT9 View 3D Structure Click here
A0A2R8Q191 View 3D Structure Click here
A0A2R8Q191 View 3D Structure Click here
A0A2R8Q191 View 3D Structure Click here
A0A2R8QG72 View 3D Structure Click here
A0A2R8QH20 View 3D Structure Click here
A2CEJ3 View 3D Structure Click here
C0H518 View 3D Structure Click here
D3ZDH4 View 3D Structure Click here
D3ZH39 View 3D Structure Click here
D3ZZK3 View 3D Structure Click here
E7FCH1 View 3D Structure Click here
E7FCH1 View 3D Structure Click here
E7FCH1 View 3D Structure Click here
F1LV96 View 3D Structure Click here
F1LV96 View 3D Structure Click here
F1LV96 View 3D Structure Click here
F1M987 View 3D Structure Click here
F1M987 View 3D Structure Click here
F1M987 View 3D Structure Click here
F1Q9D9 View 3D Structure Click here
F1QJD4 View 3D Structure Click here
H2FLH1 View 3D Structure Click here
H2FLH1 View 3D Structure Click here
H2FLH1 View 3D Structure Click here
H2FLH1 View 3D Structure Click here
M0RDA4 View 3D Structure Click here
O08644 View 3D Structure Click here
O08680 View 3D Structure Click here
O15197 View 3D Structure Click here
O73878 View 3D Structure Click here
P0C0K7 View 3D Structure Click here
P21709 View 3D Structure Click here
P29319 View 3D Structure Click here
P29320 View 3D Structure Click here
P29323 View 3D Structure Click here
P54753 View 3D Structure Click here
P54754 View 3D Structure Click here
P54757 View 3D Structure Click here
P54758 View 3D Structure Click here
P54760 View 3D Structure Click here
P54761 View 3D Structure Click here
P54763 View 3D Structure Click here
P54764 View 3D Structure Click here
Q03137 View 3D Structure Click here
Q15375 View 3D Structure Click here
Q54MZ1 View 3D Structure Click here
Q5G872 View 3D Structure Click here
Q5G872 View 3D Structure Click here
Q5G872 View 3D Structure Click here
Q5VSJ4 View 3D Structure Click here
Q60750 View 3D Structure Click here
Q62413 View 3D Structure Click here
Q66PY1 View 3D Structure Click here
Q66PY1 View 3D Structure Click here
Q66PY1 View 3D Structure Click here
Q6NZL8 View 3D Structure Click here
Q6NZL8 View 3D Structure Click here
Q6NZL8 View 3D Structure Click here
Q8IBR8 View 3D Structure Click here
Q8IBR8 View 3D Structure Click here
Q8IBR8 View 3D Structure Click here
Q8IWY4 View 3D Structure Click here
Q8IWY4 View 3D Structure Click here
Q8IWY4 View 3D Structure Click here
Q8IX30 View 3D Structure Click here
Q8IX30 View 3D Structure Click here
Q8IX30 View 3D Structure Click here
Q9JJS0 View 3D Structure Click here
Q9JJS0 View 3D Structure Click here
Q9JJS0 View 3D Structure Click here
Q9NQ36 View 3D Structure Click here
Q9NQ36 View 3D Structure Click here
Q9NQ36 View 3D Structure Click here
Q9UF33 View 3D Structure Click here

trRosetta Structure

The structural model below was generated by the Baker group with the trRosetta software using the Pfam UniProt multiple sequence alignment.

The InterPro website shows the contact map for the Pfam SEED alignment. Hovering or clicking on a contact position will highlight its connection to other residues in the alignment, as well as on the 3D structure.

Improved protein structure prediction using predicted inter-residue orientations. Jianyi Yang, Ivan Anishchenko, Hahnbeom Park, Zhenling Peng, Sergey Ovchinnikov, David Baker Proceedings of the National Academy of Sciences Jan 2020, 117 (3) 1496-1503; DOI: 10.1073/pnas.1914677117;