{PDOC00216} {PS00243; I_EGF_1} {PS52047; I_EGF_2} {BEGIN} ***************************************************************** * Integrins 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 ) in their extracellular matrix protein ligand. Structurally, integrins consist of a dimer of an alpha and a beta 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 beta chain while having different alpha chains. The sequence of a number of different beta chains has been determined and are listed below: - Integrin beta-1, which associates with alpha-1 to form a laminin receptor, with alpha-2 to form a collagen receptor, with alpha-4 to interact with VCAM-1, with alpha-5 to form a fibronectin receptor, and with alpha-8. - Integrin beta-2, which associates with alpha-L (LFA-1) to interact with ICAM-1, and with alpha-M (MAC-1) or alpha-X (p150,95) to form the receptor for the iC3b fragment of the third complement component. - Integrin beta-3, which associates with alpha-IIB to form a receptor for fibrinogen, fibronectin, vitronectin and VWF, and with alpha-V to form a vitronectin receptor. - Integrin beta-4, which associates with alpha-6. - Integrin beta-5, which associates with alpha-V. - Integrin beta-6 [3]. - Integrin beta-7 [4]. - Integrin beta-8, which associates with alpha-V [5]. - The Drosophila myospheroid protein, a probable integrin beta chain. The C-terminus of the extracellular region of all the integrin beta chains has four cysteine-rich tandem repeats of forty amino acids, which are variants of the EGF-like domain (see ), termed integrin- or I-EGF domains. The I-EGF domain is a small globular domain mainly composed by loops with a small anti-parallel beta-sheet constituted of two beta-strands (see . 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 beta- 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 beta-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 beta 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. -Consensus pattern: C-x-[GNQ]-x(1,3)-G-x-C-x-C-x(2)-C-x-C [The 5 C's may be involved in disulfide bonds] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -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 beta-8. -Last update: July 2024 / Text revised; profile added. [ 1] Hynes R.O. "Integrins: a family of cell surface receptors." Cell 48:549-554(1987). PubMed=3028640 [ 2] Albelda S.M., Buck C.A. "Integrins and other cell adhesion molecules." FASEB J. 4:2868-2880(1990). PubMed=2199285 [ 3] Sheppard D., Rozzo C., Starr L., Quaranta V., Erle D.J., Pytela R. "Complete amino acid sequence of a novel integrin beta subunit (beta 6) identified in epithelial cells using the polymerase chain reaction." J. Biol. Chem. 265:11502-11507(1990). PubMed=2365683 [ 4] Erle D.J., Rueegg C., Sheppard D., Pytela R. "Complete amino acid sequence of an integrin beta subunit (beta 7) identified in leukocytes." J. Biol. Chem. 266:11009-11016(1991). PubMed=2040616 [ 5] Moyle M., Napier M.A., McLean J.W. "Cloning and expression of a divergent integrin subunit beta 8." J. Biol. Chem. 266:19650-19658(1991). PubMed=1918072 [ 6] Beglova N., Blacklow S.C., Takagi J., Springer T.A. "Cysteine-rich module structure reveals a fulcrum for integrin rearrangement upon activation." Nat. Struct. Biol. 9:282-287(2002). PubMed=11896403; DOI=10.1038/nsb779 [ 7] Xiong J.-P., Stehle T., Diefenbach B., Zhang R., Dunker R., Scott D.L., Joachimiak A., Goodman S.L., Arnaout M.A. "Crystal structure of the extracellular segment of integrin alpha Vbeta3." Science 294:339-345(2001). PubMed=11546839; DOI=10.1126/science.1064535 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}