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19  structures 201  species 0  interactions 1009  sequences 15  architectures

Family: ITAM (PF02189)

Summary: Immunoreceptor tyrosine-based activation motif

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

This is the Wikipedia entry entitled "Immunoreceptor tyrosine-based activation motif". More...

Immunoreceptor tyrosine-based activation motif Edit Wikipedia article

An immunoreceptor tyrosine-based activation motif (ITAM) is a conserved sequence of four amino acids that is repeated twice in the cytoplasmic tails of certain cell surface proteins of the immune system. The motif contains a tyrosine separated from a leucine by any two other amino acids, giving the signature YxxL. Two of these signatures are typically separated by between 7 and 12 amino acids in the tail of the molecule (YxxLx(7-12)YxxL). ITAMs are important for signal transduction in immune cells. Hence, they are found in the tails of important cell signaling molecules such as the CD3-, ζ-chains of the T cell receptor complex, the CD79-alpha and -beta chains of the B cell receptor complex, and certain Fc receptors. The tyrosine residues within these motifs become phosphorylated following interaction of the receptor molecules with their ligands and form docking sites for other proteins involved in the signaling pathways of the cell.

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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.

Immunoreceptor tyrosine-based activation motif Provide feedback

T cell receptor (TCR) is a complex multi-protein cell surface receptor composed of the ligand-sensing TCR heterodimer and three signaling subunits. These signaling subunits contain cytoplasmic immunoreceptor tyrosine-based activation motifs (ITAMs) with a consensus sequence of YxxL/Ix6-12YxxL/I. The two tyrosines are phosphorylated by a Src kinase, Lck or Fyn. Binding of the dually phosphorylated ITAM peptide reorients the two SH2 domains relative to each other, destabilizing inhibitory interactions made by the linker connecting the SH2 and kinase domains [1].

Literature references

  1. Xu C, Gagnon E, Call ME, Schnell JR, Schwieters CD, Carman CV, Chou JJ, Wucherpfennig KW;, Cell. 2008;135:702-713.: Regulation of T cell receptor activation by dynamic membrane binding of the CD3epsilon cytoplasmic tyrosine-based motif. PUBMED:19013279 EPMC:19013279


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003110

Phosphorylated immunoreceptor signalling motifs (ITAMs) exhibit unique abilities to bind and activate Lyn and Syk tyrosine kinases [ PUBMED:7594458 ]. Motif may be dually phosphorylated on tyrosine that links antigen receptors to downstream signalling machinery.

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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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...

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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.

  Seed
(18)
Full
(1009)
Representative proteomes UniProt
(1482)
RP15
(43)
RP35
(173)
RP55
(589)
RP75
(960)
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PP/heatmap 1 View           

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

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

Format an alignment

  Seed
(18)
Full
(1009)
Representative proteomes UniProt
(1482)
RP15
(43)
RP35
(173)
RP55
(589)
RP75
(960)
Alignment:
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Sequence:
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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.

  Seed
(18)
Full
(1009)
Representative proteomes UniProt
(1482)
RP15
(43)
RP35
(173)
RP55
(589)
RP75
(960)
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: Alignment kindly provided by SMART
Previous IDs: none
Type: Motif
Sequence Ontology: SO:0001067
Author: SMART, El-Gebali S
Number in seed: 18
Number in full: 1009
Average length of the domain: 20 aa
Average identity of full alignment: 38 %
Average coverage of the sequence by the domain: 13.21 %

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 22.2 22.2
Trusted cut-off 22.2 22.2
Noise cut-off 22.1 22.1
Model length: 20
Family (HMM) version: 18
Download: download the raw HMM for this family

Species distribution

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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 ITAM domain has been found. There are 19 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
D4A5M2 View 3D Structure Click here
F1MAC3 View 3D Structure Click here
O70153 View 3D Structure Click here
P04234 View 3D Structure Click here
P04235 View 3D Structure Click here
P07766 View 3D Structure Click here
P09693 View 3D Structure Click here
P0CAN6 View 3D Structure Click here
P11911 View 3D Structure Click here
P11912 View 3D Structure Click here
P11942 View 3D Structure Click here
P15530 View 3D Structure Click here
P18438 View 3D Structure Click here
P18439 View 3D Structure Click here
P19377 View 3D Structure Click here
P20411 View 3D Structure Click here
P20491 View 3D Structure Click here
P20963 View 3D Structure Click here
P22646 View 3D Structure Click here
P24161 View 3D Structure Click here
P27597 View 3D Structure Click here
P29328 View 3D Structure Click here
P29329 View 3D Structure Click here
P30273 View 3D Structure Click here
P40293 View 3D Structure Click here
Q07249 View 3D Structure Click here
Q28072 View 3D Structure Click here
Q28074 View 3D Structure Click here
Q4V7G0 View 3D Structure Click here
Q5PXD3 View 3D Structure Click here
Q5R1Q1 View 3D Structure Click here
Q64159 View 3D Structure Click here
Q764N2 View 3D Structure Click here
Q7YRN2 View 3D Structure Click here
Q8SPW1 View 3D Structure Click here
Q95LI5 View 3D Structure Click here
Q95LI7 View 3D Structure Click here
Q95LI8 View 3D Structure Click here
Q9BDR7 View 3D Structure Click here
Q9TUF8 View 3D Structure Click here