FERMT3


Description

The FERMT3 (FERM domain containing kindlin 3) is a protein-coding gene located on chromosome 11.

FERMT3 (Fermitin family homolog 3), also known as kindlin-3 (KIND3), MIG2-like protein (MIG2B), or unc-112-related protein 2 (URP2), is a protein that in humans is encoded by the FERMT3 gene. The kindlin family of proteins, member of the B4.1 superfamily, comprises three conserved protein homologues, kindlin 1, 2, and 3. They each contain a bipartite FERM domain comprising four subdomains F0, F1, F2, and F3 that show homology with the FERM head (H) domain of the cytoskeletal Talin protein. Kindlins have been linked to Kindler syndrome, leukocyte adhesion deficiency, cancer and other acquired human diseases. They are essential in the organisation of focal adhesions that mediate cell-extracellular matrix junctions and are involved in other cellular compartments that control cell-cell contacts and nucleus functioning. Therefore, they are responsible for cell to cell crosstalk via cell-cell contacts and integrin mediated cell adhesion through focal adhesion proteins and as specialised adhesion structures of hematopoietic cells they are also present in podosome's F actin surrounding ring structure. Isoform 2 may act as a repressor of NF-kappa-B and apoptosis. It has been suggested that the evolutionary source of a single ancestral Kindlin protein is the earliest metazoa, the Parazoa. Within vertebrates, these ancestral proteins were subjected to duplication processes in order to arrive at the actual Kindlin family. In comparison with other members of the B4.1 superfamily of proteins, the FERM domains in Kindlin homologues have a greater degree of conservation. The presence of an inserted pleckstrin homology domain within the FERM domain, suggests that the metazoan evolution of the FERM domain is the origination from a proto-talin protein in unicellular or proto-multicellular organisms.

FERMT3 plays a central role in cell adhesion in hematopoietic cells (PubMed:19234463, PubMed:26359933). FERMT3 acts by activating the integrin beta-1-3 (ITGB1, ITGB2 and ITGB3) (By similarity). FERMT3 is required for integrin-mediated platelet adhesion and leukocyte adhesion to endothelial cells (PubMed:19234460). FERMT3 is required for activation of integrin beta-2 (ITGB2) in polymorphonuclear granulocytes (PMNs) (By similarity).

FERMT3 is also known as KIND3, MIG-2, MIG2B, UNC112C, URP2, URP2SF.

Associated Diseases


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