PROSITE documentation PDOC00216Integrins beta chain EGF (I-EGF) domain signature and profile
Integrins [1,2] are a large family of cell surface receptors that mediate cell to cell as well as cell to matrix adhesion. Some integrins recognize the R-G-D sequence (see <PDOC00016>) in their extracellular matrix protein ligand. Structurally, integrins consist of a dimer of an α and a β chain. Each subunit has a large N-terminal extracellular domain followed by a transmembrane domain and a short C-terminal cytoplasmic region. Some receptors share a common β chain while having different α chains. The sequence of a number of different β chains has been determined and are listed below:
- Integrin β-1, which associates with α-1 to form a laminin receptor, with α-2 to form a collagen receptor, with α-4 to interact with VCAM-1, with α-5 to form a fibronectin receptor, and with α-8.
- Integrin β-2, which associates with α-L (LFA-1) to interact with ICAM-1, and with α-M (MAC-1) or α-X (p150,95) to form the receptor for the iC3b fragment of the third complement component.
- Integrin β-3, which associates with α-IIB to form a receptor for fibrinogen, fibronectin, vitronectin and VWF, and with α-V to form a vitronectin receptor.
- Integrin β-4, which associates with α-6.
- Integrin β-5, which associates with α-V.
- Integrin β-6 [3].
- Integrin β-7 [4].
- Integrin β-8, which associates with α-V [5].
- The Drosophila myospheroid protein, a probable integrin β chain.
The C-terminus of the extracellular region of all the integrin β chains has four cysteine-rich tandem repeats of forty amino acids, which are variants of the EGF-like domain (see <PDOC00021>), termed integrin- or I-EGF domains. The I-EGF domain is a small globular domain mainly composed by loops with a small anti-parallel β-sheet constituted of two β-strands (see <PDB:1L3Y>. The structure is stabilized by four disulfide bonds between the first and fifth, second and fourth, third and sixth, and seventh and eighth Cys residues. Three disulfide bonds are shared with classical EGF-like domains. The disulfide unique to I-EGF domains links the N-terminus to the turn between the two β-strands. Compared to classical EGF-like modules with three disulfide bonds, the I-EGF module is less elongated, with a nosecone-like shape. The anti-parallel sheet between the two β-strands is shortened because four highly conserved residues among classical EGF-like modules are deleted in I-EGF modules. I-EGF repeats in the integrin β subunit stalk region relay activation signals to the ligand-binding headpiece [5,6].
We have developed a pattern from a section of the I-EGF domain that includes five of the conserved cysteines. We also developed a profile which covers the entire I-EGF domain.
Note:The pattern will not pick up the first of the four repeats, the spacing of the cysteine residues being different in that repeat. The profile does not detect the highly degenerated first repeat found in Integrin β-8.
Last update:July 2024 / Text revised; profile added.
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PROSITE methods (with tools and information) covered by this documentation:
1 | Authors | Hynes R.O. |
Title | Integrins: a family of cell surface receptors. | |
Source | Cell 48:549-554(1987). | |
PubMed ID | 3028640 |
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Title | Integrins and other cell adhesion molecules. | |
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PubMed ID | 2199285 |
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Title | Complete amino acid sequence of a novel integrin beta subunit (beta 6) identified in epithelial cells using the polymerase chain reaction. | |
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PubMed ID | 2365683 |
4 | Authors | Erle D.J. Rueegg C. Sheppard D. Pytela R. |
Title | Complete amino acid sequence of an integrin beta subunit (beta 7) identified in leukocytes. | |
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PubMed ID | 2040616 |
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Title | Cloning and expression of a divergent integrin subunit beta 8. | |
Source | J. Biol. Chem. 266:19650-19658(1991). | |
PubMed ID | 1918072 |
6 | Authors | Beglova N. Blacklow S.C. Takagi J. Springer T.A. |
Title | Cysteine-rich module structure reveals a fulcrum for integrin rearrangement upon activation. | |
Source | Nat. Struct. Biol. 9:282-287(2002). | |
PubMed ID | 11896403 | |
DOI | 10.1038/nsb779 |
7 | Authors | Xiong J.-P. Stehle T. Diefenbach B. Zhang R. Dunker R. Scott D.L. Joachimiak A. Goodman S.L. Arnaout M.A. |
Title | Crystal structure of the extracellular segment of integrin alpha Vbeta3. | |
Source | Science 294:339-345(2001). | |
PubMed ID | 11546839 | |
DOI | 10.1126/science.1064535 |
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