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FLASH GENE
Symbol ILK contributors: mct/pgu - updated : 07-01-2016
HGNC name integrin-linked kinase
HGNC id 6040
RNA
TRANSCRIPTS type messenger
text all transcripts encoding the same protein
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
13 - 1817 - 452 - 2004 14990992
13 - 1771 - 452 - 2004 14990992
12 - 1931 - 452 - 2004 14990992
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
blood / hematopoieticspleen   highly
Cardiovascularheart   highly
Digestiveliver   highly
Endocrinepancreas   highly
Nervousbrain   highly
Reproductivemale systemprostate  highly
Respiratorylung   lowly
Urinarykidney   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoieticbone marrow   
Connectivebone   
Epithelialsecretoryglandularendocrine 
Muscularstriatumskeletal  
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticmonocyte
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period pregnancy
Text placenta lowly
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • five ankyrin-like repeats (ankyrin repeat domain bound to the LIMS1 LIM1 domain)
  • a PH-like domain (involved in phosphatidylinositol phosphate binding)
  • a kinase domain, including proline-rich regions, appeared to interact physically with the Src homology 3 domain of SRC, and indispensable for regulation of diverse cell-adhesion-dependent processes ,
  • an unusual pseudoactive site that is incapable of catalyzing phosphorylation
  • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine Ilk
    homolog to Drosophila ilk
    homolog to C.elegans pat-4
    Homologene
    FAMILY
  • protein kinase superfamily
  • TKL Ser/Thr protein kinase family
  • CATEGORY enzyme , receptor membrane serine/threonine kinase
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus
    text
  • localizes to multiple sites, including the cytoplasm, and imported into the nucleus through sequences in its N-terminus, via active transport mechanisms that involve nuclear pore complexes
  • basic FUNCTION
  • serine/threonine kinase (phosphorylating beta-1 and beta-3 integrin subunit, AKT1 and GSK3B)
  • regulating integrin-mediated signal transduction and cell adhesion
  • mediating cell architecture
  • having a critical function in the organization of centrosomal protein complexes during mitotic spindle assembly and DNA segregation
  • plays key roles in a variety of cell functions, including cell proliferation, adhesion and migration
  • can be rapidly exported into the cytoplasm through a CRM1-dependent pathway, and its export is enhanced by the type 2C protein phosphatase ILKAP
  • involved in signal transduction by integrin-mediated cell adhesion that leads to dynamic actin reorganization
  • plays a pivotal role in connecting transmembrane receptor integrin to the actin cytoskeleton and thereby regulating
  • diverse cell-adhesion-dependent processes
  • distinct pseudokinase that mechanically couples integrin and PARVA for mediating cell adhesion
  • roles in regulating actin cytoskeletal reorganization, survival, proliferation, cell migration, invasion and epithelial to mesenchymal transition, and is therefore essential to normal cell physiology
  • also regulates the microtubule cytoskeleton and is involved in mitotic spindle organization
  • performs crucial roles in the control of intestinal cell and crypt-villus axis homeostasis-especially with regard to basement membrane fibronectin deposition-as well as cell proliferation, spreading, and migration
  • critically involved in actin and mitotic microtubule organization, is required for centrosome clustering
  • important role to the integrin/ILK complex for caveolar trafficking to the cell surface
  • scaffolding protein with central roles in tissue development and homeostasis
  • might be involved in the development of bladder cancer
  • role of ILK and ELMO2 in the integration of adhesion and migration pathways
  • possible role for ILK in the progression of Clear Cell Renal Carcinoma
  • intracellular effector of cell-matrix interactions, regulating many cellular processes, including growth, proliferation, survival, differentiation, migration, invasion and angiogenesis
  • exogenous expression of ELMO2 or RHOG stabilizes microtubules, but only if ILK is also present
  • costamere genes, such as ILK, are involved in the control of muscle fiber characteristics
  • CELLULAR PROCESS cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • signaling pathway consisting of PRKCA and integrin-linked kinase (ILK) mediates the negative guidance effects of high concentration of SHH on retinal ganglion cell (RGC) axons
  • a component
  • acts as a central component of a heterotrimer (the PINCH-ILK-parvin complex) at ECM adhesions mediating interactions with a large number of proteins via multiple sites including its pseudoactive site
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
  • protein
  • binding to cytoplasmic domain of beta-1 integrin
  • LIMS1 and LIMS2
  • beta2, beta3 and beta5 subunit of integrin
  • PARVA, PARVB, PARVG and ILKAP
  • interacting with TMSB4X, TMSB4Y
  • interacting with RICTOR (ILK and rictor colocalized in membrane ruffles and leading edges of cancer cells)
  • signaling connection from ILK to cofilin for dynamic actin polymerization during cell adhesion, depending on the activity of ILK-associated SRC
  • ILK interacts with the regulatory region of the CNKSR3 gene chromatin to negatively modulate its expression
  • ILKAP is a pivotal modulator of ILK subcellular distribution and activity in the keratinocytes
  • interaction between EPHA1 and ILK
  • interaction with ELMO2 and RHOG is essential for the ability of ILK to induce front-rear cell polarity
  • performs its centrosome clustering activity in a focal adhesion-independent, but centrosome-dependent, manner through the microtubule regulating proteins TACC3 and CKAP5
  • ELMO2 is an ILK-binding protein in epidermal keratinocytes
  • new role for ADAM12L in mediating the functional association of ILK with ITGB1 to regulate cell adhesion/survival through a PI3K/Akt signaling pathway
  • modulates wound healing through regulation of hepatocyte growth factor (HGF)
  • cell & other
  • binding to phosphatidylinositol phosphate (via the PH-like domain)
  • REGULATION
    activated by cell fibronectin interaction and by insulin in PI(3)K dependent manner
    chemokine monocyte chemoattractant protein-1 (in leukocytes)
    by growth factors, cytokines and hormones
    inhibited by ILKAP
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    2 novel amino acid residue-altering mutations (2828C>T [Pro943Leu] and 3217C>T [Arg1073X]) in the integrin-interacting domain of the LAMA4 gene and 1 mutation (785C>T [Ala262Val]) in the ILK gene in dilated cardiomyopathy
    tumoral     --over  
    in various tumors independent of TGF-beta 1
    tumoral     --over  
    during liver oncogenesis and cirrhosis correlates with activation of Akt but not with other conventional ILK targets
    tumoral     --over  
    is associated with tumor progression and a poor (CRC)prognosis in colorectal patients
    tumoral     --over  
    promotes cellular transformation, cell survival, epithelial mesenchymal transition (EMT), and metastasis of hormonal cancer cells while inhibition of ILK1 reduces tumor growth and progression
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker may represent a novel potential prognostic marker for patients with CRC
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    potential role therapeutic of the anti-mitotic effects of genetic or pharmacological inhibition of ILK
    cancer  
    inhibiting ILK offers a selective means of targeting cancer cells
    cancerreproductiveovary
    targeting ILK and ITGB4 abrogates the invasive potential of ovarian cancer
    cancerurinary 
    could be served as a novel potential therapy target for human bladder cancer
    ANIMAL & CELL MODELS