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Available structures
PDB Ortholog search: PDBe RCSB
Aliases FERMT3, KIND3, MIG-2, MIG2B, UNC112C, URP2, URP2SF, fermitin family member 3
External IDs MGI: 2147790 HomoloGene: 12877 GeneCards: FERMT3
Genetically Related Diseases
attention deficit hyperactivity disorder[1]
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 11: 64.21 – 64.22 Mb Chr 19: 7 – 7.02 Mb
PubMed search [2] [3]
View/Edit Human View/Edit Mouse

Fermitin family homolog 3) (FERMT3), 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.[4][5][6] 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[7]

FERMT-3 protein sequence


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.[8] 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.[8][9]


FERMT 3 Structure

The FERMT3 protein has a key role in the regulation of hemostasis and thrombosis.[9] This protein may also help maintain the membrane skeleton of erythrocytes.[4] Kindlin 3 is a cytoskeletal signalling protein involved in the activation of the glycoprotein receptor, integrin.[10] Together with the Talin protein it binds cooperatively to beta integrin’s cytoplasmic domain causing tail reorientation, thus altering the molecule’s conformation.[citation needed] Modification of integrin’s conformation serves to dissociate alpha and beta subunits by disrupting their interactions and helping the molecule adopt a high affinity state.[8] FERMT3 functions as a stabilizer of the cytoskeleton and regulates its dynamics in cell and organelle motility.[11][non-primary source needed]

Clinical significance[edit]

FERMT3 mutations can result in autosomal recessive leukocyte adhesion deficiency syndrome-III (LAD-III).[4] a deficiency in beta1, beta2 and beta3 integrin activation in platelets and leukocytes that causes haemorrhaging and recurrent infections.[9] Loss of FERMT3 expression in leukocytes compromises their adhesion to the inflamed endothelia and affects neutrophil granulocyte binding and spreading while selectin mediated rolling is unaffected.[non-primary source needed] It has also been found that FERMT3 lowers Natural Killer cell’s activation threshold, such that a loss of FERMT3 affects single receptor activation of NK cell-mediated cytotoxicity but has no impact on multiple receptors, where the protein deficiency is overcome and target cells are killed.[non-primary source needed]

FERMT3 deficiency on β(2) integrin function depend on both cell type (Natural killer cell or Leukocytes) and the integrin activation stimulus.[12] The prevention of the beta-3 activation is specifically related to LAD-3, causing Glanzmann's thrombasthenia symptoms, a condition in which patients bleed excessively.[13][non-primary source needed] Leukocyte adhesion deficiency is diagnosed clinically and by complete blood counts that reveal leukocytosis with neutrophilia.[12] Management and treatment of this disease aim to control these recurrent infections by antibiotics and blood transfusions, with bone marrow transplantation as the only curative measure.[non-primary source needed] Failure to express the FERMT3 protein disrupts the ability to form clots and coagulate by preventing integrin αIIβ3-mediated platelet aggregation.[9]


  1. ^ "Diseases that are genetically associated with FERMT3 view/edit references on wikidata". 
  2. ^ "Human PubMed Reference:". 
  3. ^ "Mouse PubMed Reference:". 
  4. ^ a b c "Entrez Gene: fermitin family homolog 3 (Drosophila)". 
  5. ^ Weinstein EJ, Bourner M, Head R, Zakeri H, Bauer C, Mazzarella R (April 2003). "URP1: a member of a novel family of PH and FERM domain-containing membrane-associated proteins is significantly over-expressed in lung and colon carcinomas". Biochim. Biophys. Acta. 1637 (3): 207–16. doi:10.1016/S0925-4439(03)00035-8. PMID 12697302. 
  6. ^ Boyd RS, Adam PJ, Patel S, Loader JA, Berry J, Redpath NT, Poyser HR, Fletcher GC, Burgess NA, Stamps AC, Hudson L, Smith P, Griffiths M, Willis TG, Karran EL, Oscier DG, Catovsky D, Terrett JA, Dyer MJ (August 2003). "Proteomic analysis of the cell-surface membrane in chronic lymphocytic leukemia: identification of two novel proteins, BCNP1 and MIG2B". Leukemia. 17 (8): 1605–12. doi:10.1038/sj.leu.2402993. PMID 12886250. 
  7. ^ Malinin NL, Zhang L, Choi J, Ciocea A, Razorenova O, Ma YQ, Podrez EA, Tosi M, Lennon DP, Caplan AI, Shurin SB, Plow EF, Byzova TV (2009). "A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans". Nat. Med. 15 (3): 313–8. doi:10.1038/nm.1917. PMC 2857384Freely accessible. PMID 19234460. 
  8. ^ a b c Ali RH, Khan AA (2014). "Tracing the evolution of FERM domain of Kindlins". Mol. Phylogenet. Evol. 80: 193–204. doi:10.1016/j.ympev.2014.08.008. PMID 25150025. 
  9. ^ a b c d Lai-Cheong JE, Parsons M, McGrath JA (2010). "The role of kindlins in cell biology and relevance to human disease". Int. J. Biochem. Cell Biol. 42 (5): 595–603. doi:10.1016/j.biocel.2009.10.015. PMID 19854292. 
  10. ^ Danen EHJ (2000–13). Integrins: An Overview of Structural and Functional Aspects. Madame Curie Bioscience Database. 
  11. ^ Feigelson SW, Grabovsky V, Manevich-Mendelson E, Pasvolsky R, Shulman Z, Shinder V, Klein E, Etzioni A, Aker M, Alon R (2011). "Kindlin-3 is required for the stabilization of TCR-stimulated LFA-1:ICAM-1 bonds critical for lymphocyte arrest and spreading on dendritic cells". Blood. 117 (26): 7042–52. doi:10.1182/blood-2010-12-322859. PMID 21536861. 
  12. ^ a b Svensson L, Howarth K, McDowall A, Patzak I, Evans R, Ussar S, Moser M, Metin A, Fried M, Tomlinson I, Hogg N (2009). "Leukocyte adhesion deficiency-III is caused by mutations in KINDLIN3 affecting integrin activation". Nat. Med. 15 (3): 306–12. doi:10.1038/nm.1931. PMC 2680140Freely accessible. PMID 19234463. 
  13. ^ Mory A, Feigelson SW, Yarali N, Kilic SS, Bayhan GI, Gershoni-Baruch R, Etzioni A, Alon R (2008). "Kindlin-3: a new gene involved in the pathogenesis of LAD-III". Blood. 112 (6): 2591. doi:10.1182/blood-2008-06-163162. PMID 18779414. 

Further reading[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.