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FLASH GENE
Symbol ILK contributors: mct/pgu - updated : 07-01-2013
HGNC name integrin-linked kinase
HGNC id 6040
Location 11p15.4      Physical location : 6.624.963 - 6.632.097
Synonym name 59 kDa serine/threonine-protein kinase
Synonym symbol(s) p59, PAT-4, DKFZp686F1765, ILK-1, ILK-2, ILK1, ILK2, p59ILK
EC.number 2.7.11.1
DNA
TYPE functioning gene
SPECIAL FEATURE overlapping, gene in gene
text the last coding exon containing the entire 3'UTR of ILK overlaps with the complementary 3'UTR sequence of TAF2H
STRUCTURE 7.14 kb     13 Exon(s)
10 Kb 5' upstream gene genomic sequence study
text structure a TATA-less and CAAT-less promoter with typical features of housekeeping genes
MAPPING cloned Y linked N status provisional
Map see TPP1
Physical map
OR52X1P 11p15.3 olfactory receptor, family 52, subfamily X, member 1 pseudogene LOC196335 11p15.4 similar to Olfactory receptor 56B4 LOC390088 11 similar to seven transmembrane helix receptor LOC390089 11 hypothetical gene supported by AF359415 LOC255725 11p15.4 similar to seven transmembrane helix receptor LOC120787 11p15.4 similar to seven transmembrane helix receptor MGC34805 11p15.4 hypothetical protein MGC34805 DKFZP566M1046 11p15.4 hypothetical protein DKFZp566M1046 CNGA4 11p15.4 cyclic nucleotide gated channel alpha 4 CCKBR 11p15.4 cholecystokinin B receptor PRKCDBP 11p15.5-p15.4 protein kinase C, delta binding protein SMPD1 11p15.3 sphingomyelin phosphodiesterase 1, acid lysosomal (acid sphingomyelinase) APBB1 11p15.5 amyloid beta (A4) precursor protein-binding, family B, member 1 (Fe65) HPX 11p15.5 hemopexin TRIM3 11p15.5 tripartite motif-containing 3 ARFIP2 11p15 ADP-ribosylation factor interacting protein 2 (arfaptin 2) FXC1 11p15.2-p15.5 fracture callus 1 homolog (rat) LOC390090 11 similar to voltage-dependent anion channel 1 FLJ35709 11p15.4 hypothetical protein FLJ35709 LOC387749 11 hypothetical gene supported by BX647806 LOC196337 11p15.4 hypothetical protein LOC196337 LOC387750 11 similar to SI:zC220F6.1 (novel protein similar to human dynein heavy chain (DHC)) FLJ32752 11p15.4 hypothetical protein FLJ32752 KIAA0409 11p15.5-p15.2 hypothetical protein FLJ32752 ILK 11p15.3 integrin-linked kinase TAF10 11p15.3 TAF10 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 30kDa CLN2 11p15.3 ceroid-lipofuscinosis, neuronal 2, late infantile (Jansky-Bielschowsky disease) PCDH16 11p15.4 protocadherin 16 dachsous-like (Drosophila) MRPL17 11p15.5-p15.4 mitochondrial ribosomal protein L17 LOC387751 11 similar to very large inducible GTPase-1 LOC338755 11p15.4 similar to Olfactory receptor 2AG1 (HT3) LOC144125 11p15.4 similar to Olfactory receptor 2AG1 (HT3) OR6A1 11p15.5 olfactory receptor, family 6, subfamily A, member 1 JCG6 11p15.4 olfactory receptor-like protein JCG6 LOC341276 11p15.4 similar to hP4 olfactory receptor LOC283297 11p15.4 similar to Olfactory receptor 10A4 (HP2) (Olfactory receptor-like protein JCG5) LOC120776 11p15.4 similar to seven transmembrane helix receptor OR10A4P 11 olfactory receptor, family 10, subfamily A, member 4 pseudogene LOC120775 11p15.4 similar to Olfactory receptor 2D3 ZNF215 11p15.4 zinc finger protein 215
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
  • 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