Summary

Integrin, beta chain

Integrins have been found in animals and their homologues have also been found in cyanobacteria, probably due to horizontal gene transfer [1]. The sequences repeats have been trimmed due to an overlap with EGF.

Literature references

May AP, Ponting CP; , Trends Biochem Sci 1999;24:12-13.: Integrin alpha- and beta 4-subunit-domain homologues in cyanobacterial proteins. PUBMED:10087915

InterPro entry IPR002369

Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton and activate many intracellular signalling pathways PUBMED:12297042, PUBMED:12361595. The integrin receptors are composed of alpha and beta subunit heterodimers. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a vWA domain inserted within the integrin domain at the N terminus.

Most integrins recognise relatively short peptide motifs, and in general require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits PUBMED:12234368. There are at least 18 types of alpha and 8 types of beta subunits recognised in humans PUBMED:14689578. Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule PUBMED:2467745. Each association of alpha and beta subunits has its own binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activate or inhibit another.

The structure of unliganded alphaV beta3 showed the molecule to be folded, with the head bent over towards the C termini of the legs which would normally be inserted into the membrane PUBMED:12714499. The head comprises a beta propeller domain at the end terminus of the alphaV subunit and an I/A domain inserted into a loop on the top of the hybrid domain in the beta subunit. The I/A domain consists of a Rossman fold with a core of beta parallel sheets surrounded by amphipathic alpha helices.

Integrins are important therapeutic targets in conditions such as atherosclerosis, thrombosis, cancer and asthma PUBMED:2199285.

At the N-terminus of the beta subunit is a cysteine-containing domain reminiscent of that found in presenillins and semaphorins, which has hence been termed the PSI domain. C-terminal to the PSI domain is an A-domain, which has been predicted to adopt a Rossmann fold similar to that of the alpha subunit, but with additional loops between the second and third beta strands PUBMED:9009218. The murine gene Pactolus shares significant similarity with the beta subunit PUBMED:9535848, but lacks either one or both of the inserted loops. The C-terminal portion of the beta subunit extracellular domain contains an internally disulphide-bonded cysteine-rich region, while the intracellular tail contains putative sites of interaction with a variety of intracellular signalling and cytoskeletal proteins, such as focal adhesion kinase and alpha-actinin respectively PUBMED:9818167. Integrin cytoplasmic domains are normally less than 50 amino acids in length, with the beta-subunit sequences exhibiting greater homology to each other than the alpha-subunit sequences. This is consistent with current evidence that the beta subunit is the principal site for binding of cytoskeletal and signalling molecules, whereas the alpha subunit has a regulatory role. The first 20 amino acids of the beta-subunit cytoplasmic domain are also alpha helical, but the final 25 residues are disordered and, apart from a turn that follows a conserved NPxY motif, appear to lack defined structure, suggesting that this is adopted on effector binding. The two membrane-proximal helices mediate the link between the subunits via a series of hydrophobic and electrostatic contacts.

Gene Ontology

Cellular component	integrin complex (GO:0008305)
Molecular function	receptor activity (GO:0004872)
Molecular function	binding (GO:0005488)
Biological process	cell-matrix adhesion (GO:0007160)
	cell adhesion (GO:0007155)
	integrin-mediated signaling pathway (GO:0007229)

External database links

PANDIT:	PF00362
PROSITE:	PDOC00216
SCOP:	1jv2
SYSTERS:	Integrin_beta

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

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...

View options

Alignment:	Seed (48) Full (310) NCBI (698) Metagenomics (1)
Viewer:

Formatting options

Alignment:	Seed (48) Full (310)
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

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.

Pfam alignments:	Seed (48) Full (310) NCBI (698) Metagenomics (1)
Full length sequences	Full-sequences (310)

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 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. 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.

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

Seed source:

Prosite

Previous IDs:

integrin_B;

Type:

Family

Author:

Finn RD

Number in seed:

48

Number in full:

310

Average length of the domain:

330.30 aa

Average identity of full alignment:

41 %

Average coverage of the sequence by the domain:

50.76 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 9421015 -E 1000 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	25.7	25.7
Trusted cut-off	28.2	29.3
Noise cut-off	25.4	25.6

Model length:

425

Family (HMM) version:

11

Download:

download the raw HMM for this family

Species distribution

Tree controls

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The tree shows the occurrence of this domain across different species. More...

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

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Interactions

There are 3 interactions for this family. More...

Integrin_B_tail EGF_2 FG-GAP

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 Integrin_beta domain has been found.

Loading structure mapping...

Family: Integrin_beta (PF00362)

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