SH2 domain

No Pfam abstract.

InterPro entry IPR000980

The Src homology 2 (SH2) domain is a protein domain of about 100 amino-acid residues first identified as a conserved sequence region between the oncoproteins Src and Fps PUBMED:3025655. Similar sequences were later found in many other intracellular signal-transducing proteins PUBMED:1377638. SH2 domains function as regulatory modules of intracellular signalling cascades by interacting with high affinity to phosphotyrosine-containing target peptides in a sequence-specific, SH2 domains recognise between 3-6 residues C-terminal to the phosphorylated tyrosine in a fashion that differs from one SH2 domain to another, and strictly phosphorylation-dependent manner PUBMED:7883800, PUBMED:15335710, PUBMED:14731533, PUBMED:7531822. They are found in a wide variety of protein contexts e.g., in association with catalytic domains of phospholipase Cy (PLCy) and the non-receptor protein tyrosine kinases; within structural proteins such as fodrin and tensin; and in a group of small adaptor molecules, i.e Crk and Nck. The domains are frequently found as repeats in a single protein sequence and will then often bind both mono- and di-phosphorylated substrates.

The structure of the SH2 domain belongs to the alpha+beta class, its overall shape forming a compact flattened hemisphere. The core structural elements comprise a central hydrophobic anti-parallel beta-sheet, flanked by 2 short alpha-helices. The loop between strands 2 and 3 provides many of the binding interactions with the phosphate group of its phosphopeptide ligand, and is hence designated the phosphate binding loop, the phosphorylated ligand binds perpendicular to the beta-sheet and typically interacts with the phosphate binding loop and a hydrophobic binding pocket that interacts with a pY+3 side chain. The N- and C-termini of the domain are close together in space and on the opposite face from the phosphopeptide binding surface and it has been speculated that this has facilitated their integration into surface-exposed regions of host proteins PUBMED:11911873.

Gene Ontology

External database links

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

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Very large alignments can often cause problems for the formatting tool above. If you find that downloading or viewing a large alignment is problematic, you can also download a gzip-compressed, Stockholm-format file containing the seed or full alignment for this family.

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

The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER2.

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. 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 or full alignments.

Note: You can also download the data files for the seed, full, NCBI or metagenomics trees.

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

HMM information

There are 8 interactions for this family. More...

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the MSD 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 SH2 domain has been found.