Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
Symbol FERMT3 contributors: mct - updated : 12-09-2018
HGNC name fermitin family homolog 3 (Drosophila)
HGNC id 23151
Corresponding disease
LAD3 leukocyte adhesion deficiency 3
Location 11q13.1      Physical location : 63.974.151 - 63.991.363
Synonym name
  • kindlin 3
  • UNC-112 related protein 2
  • MIG2-like protein
  • FERM domain–containing, beta-integrin tail–binding protein
  • Synonym symbol(s) KIND3, MGC10966, MIG2B, URP2, MIG-2, UNC112C, URP2SF
    TYPE functioning gene
    STRUCTURE 17.21 kb     15 Exon(s)
    MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 splicing 2558 75.4 663 brain 2008 18280249
  • short form, URP2SF
  • 15 splicing 2570 75.9 667 leukocytes 2008 18280249
    long form, URP2LF
    - - - - - - 2013 23595985
  • four-residue insert in the PH domain at a critical site that influences phosphoinositide binding
  • correct functioning of the FERMT3 PH domain is central to the role that FERMT3 performs in guiding lymphocyte adhesion and motility behavior
    Rna function
  • mRNA detected in endothelial cells
  • Type restricted
       expressed in (based on citations)
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoietic   specific Homo sapiens
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte Homo sapiens
    Blood/Hematopoieticmature hematopoietic Homo sapiens
    Blood/Hematopoieticplatelet Homo sapiens
    Cardiovascularendothelial cell Homo sapiens
    Lymphoid/ImmuneB cell Homo sapiens
    cell lineage
    cell lines
    at STAGE
    physiological period pregnancy
    Text placenta
  • F0, F1, F2, and F3 subdomains with in addition a pleckstrin homology (PH)5 domain inserted in the F2 domain
  • a pleckstrin homology PH domain having binding affinity for phosphoinositide, and having a major role in membrane association of FERMT3 that is enhanced by the binding of ITGB2 to ICAM1
  • two plasma-membrane-binding ezrin/radixin/moesin domains
  • lipid interactions of the 83-AAs F1 loop, with an isolated N-terminal peptide fragment, or EK21, containing a poly-Lys sequence motif, important for membrane interactions
  • two C-terminal FERM domains, similar with that of talin, and this bipartite FERM (four point one protein, ezrin, radixin, moesin) domain is interrupted by a pleckstrin homology domain
    intraspecies homolog to FERMT1, FERMT2
  • kindlin family
  • CATEGORY chaperone/stress , regulatory
        plasma membrane,junction
  • associated with the B cell membrane but is then further recruited in a PH-dependent manner following an adhesion event
  • basic FUNCTION
  • essential element for platelet integrin activation in hemostasis and thrombosis
  • focal adhesion proteins, acting as a transcriptional repressor in NF-kappaB signaling pathway
  • regulating cell apoptotic pathway
  • cytoplasmic component of cell-ECM adhesions that bind to beta-integrin cytoplasmic tails directly and cooperate with talin in integrin activation
  • essential role for integrin signalling and cell-ECM adhesion regulation
  • is more critical to ITGB2 than to ITGB1-adhesive functions in human lymphocytes
  • focal adhesion proteins implicated in integrin activation
  • essential to activate the ITGB1, ITGB2, ITGB3
  • plays a role in integrin-mediated adhesion of endothelial cells
  • required to activate leukocyte and platelet integrins
  • FERMT3-mediated signaling from multiple integrin classes is required for osteoclast-mediated bone resorption
  • selectively contributes to a final TCR-triggered outside-in stabilization of bonds generated between chemokine-primed ITGB2 molecules and cell-surface ICAM1
  • is also required for integrin outside-in signaling, and it may interact with cytoplasmic protein(s) that modulate cell spreading
  • plays a role in integrin alphaLbeta2 outside-in signaling, and it can induce integrin alphaLbeta2 micro-clustering
  • critical for hemostasis, immunity, and bone metabolism via its role in integrin activation
  • critical role in integrin activation and focal adhesion assembly
  • main activator and binding partner of integrins in hematopoietic cells, that can be cleaved by calpain in an activation-dependent manner
  • integrin-binding focal adhesion adaptor absent in patients with leukocyte and platelet adhesion deficiency syndrome and critical for firm integrin-dependent leukocyte adhesion
  • FERMT3-stabilized integrin adhesions, although essential for lymphocyte arrest on blood vessels and interstitial motility, are not obligatory for leukocyte diapedesis
  • promotes firm adhesion of T cells to primary brain microvascular endothelial cells
  • regulates integrin activation and adhesion reinforcement of effector T cells
  • major regulator of integrin function in hematopoietic cells
  • influences breast cancer progression by influencing the crosstalk between ITGB1 and TWIST to increase VEGFA production
  • CELLULAR PROCESS cell life, cell death/apoptosis
    nucleotide, transcription, regulation
    a component
  • forms a ternary complex with the Talin and ITGB1 cytoplasmic tails
    small molecule
  • interact with integrin beta tails
  • interact with many components of cell–ECM adhesions-such as migfilin and integrin-linked kinase-to promote cytoskeletal reorganization
  • key lymphocyte function-associated antigen-1 (ITGB2) coactivator
  • interacts with the receptor for activated-C kinase 1 (GNB2L1), a scaffold protein that folds into a seven-blade propeller
  • enriched within focal clusters of high-affinity ITGB2, which promoted physical linkage with ORAI1
  • binds PI(3,4,5)P3 through the PH domain and contributes to the association of FERMT3 with the B cell membrane
  • binding of ITGB2 to ICAM1 has a downstream effect in the recruitment of kindlin 3 to the membrane that is PH-dependent
  • role of FERMT3 phosphorylation in ITGB3 activation, providing a basis for functional differences between FERMT3 and the two other kindlin paralogs
  • FERMT3-mediated integrin adhesion is dispensable for quiescent but essential for activated hematopoietic stem cells
  • interacts with the ribosome and regulates MYC expression required for proliferation of chronic myeloid leukemia cells
  • cell & other
    corresponding disease(s) LAD3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    results in severe bleeding and resistance to arterial thrombosis
    resulting in postnatal lethality
    Variant & Polymorphism
    Candidate gene
    Therapy target
  • kindlin-3-deficient mice develop severe osteopetrosis because of profound adhesion and spreading defects in bone-resorbing osteoclasts
  • mice lacking Kindlin-3 in T cells were immunized with an autoantigen to induce experimental autoimmune encephalitis (EAE), a model of multiple sclerosis, and autoreactive Kindlin-3–null T cells extravasate only when the brain microvasculature expresses high integrin ligand levels
  • kindlin-3-null mice, which die perinatally of severe bleeding and leukocyte adhesion deficiency, mice expressing as little as 5p100 of kindlin-3 were viable and protected from spontaneous bleeding and infections