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ILK (integrin-linked kinase)

Written2014-08Isabel Serrano, Paul McDonald, Shoukat Dedhar
Department of Integrative Oncology, British Columbia Cancer Research Centre of the BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC, Canada, V5Z1L3

Abstract Review on ILK (integrin-linked kinase), with data on DNA, on the protein encoded, and where the gene is implicated.

(Note : for Links provided by Atlas : click)

Identity

Alias_namesintegrin-linked kinase
Other aliasHEL-S-28
ILK-1
ILK-2
P59
p59ILK
HGNC (Hugo) ILK
LocusID (NCBI) 3611
Atlas_Id 460
Location 11p15.4  [Link to chromosome band 11p15]
Location_base_pair Starts at 6603708 and ends at 6610874 bp from pter ( according to hg19-Feb_2009)  [Mapping ILK.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ILK (11p15.4) / GRK3 (22q12.1)ILK (11p15.4) / ILK (11p15.4)ILK (11p15.4) / PABPC1 (8q22.3)
LAMA4 (6q21) / ILK (11p15.4)RBM3 (Xp11.23) / ILK (11p15.4)

DNA/RNA

 
  Chromosome 11, genomic organization of human ILK. The ILK gene is located on chromosome 11 at position 15. Exactly from 6624961 bp to 6632102 bp (7142 bases) (Diagram author: Elena Serrano).
Description According to Entrez-Gene, human ILK maps to locus NC_000011.9. ILK gene contains 13 exons and spans 9.0 kb.
Transcription ILK encodes a predicted 451-amino acid protein with an apparent molecular mass of 59 kD based on SDS-PAGE. Northern blot analysis showed that the 1.8-kb ILK mRNA is widely expressed.
Pseudogene An ILK pseudogene has been found in mice, predicted gene 6263 (Gm6263).

Protein

 
  Functional domains of integrin-linked kinase (ILK). ILK is an intracellular serine/threonine protein kinase with a C-terminal kinase catalytic domain. ILK structure consists in four ankyrin repeats at the N-terminus (residues 33-164), a phosphoinositide-binding motif and a catalytic domain (residues 180-212). The integrin-binding site is in the extreme C-terminus of the kinase domain (residues 293-451) (Diagram author: Elena Serrano).
Description ILK is a widely expressed modular protein composed of three major domains: an N-terminal domain that contains four ankyrin repeats, a central pleckstrin homology (PH)-like domain and a C-terminal kinase domain. The N-terminal ankyrin domain binds to PINCH (particularly interesting new cysteinehistidine protein) - an adaptor protein that complexes with ILK in the cytoplasm prior to active recruitment of ILK to focal adhesion sites - and to ILK-associated protein (ILKAP) - a protein phosphatase 2C (PP2C)-family protein phosphatase that negatively regulates ILK signaling (McDonald et al., 2008a). Adjacent to the ankyrin repeats, a sequence motif present in PH domains binds to the second messenger PI(3,4,5)P3 and a PI3-kinase-dependent kinase activation has been reported (Delcommenne et al., 1998; Boulter and Van Obberghen-Schilling, 2006). The C-terminus kinase domain also interacts with integrins, as well as with the focal adhesion proteins paxillin (Nikolopoulos and Turner, 2001; Nikolopoulos and Turner, 2002) and parvins (Hannigan et al., 2005; Legate et al., 2006), which link ILK, and therefore integrins, to the actin cytoskeleton.
Expression ILK is ubiquitously expressed in most tissues, with predominance at skeletal muscle, heart, kidney and pancreas. Increased expression of ILK is correlated with progression of several tumor types, constituting an attractive therapeutic target in human cancer.
Localisation ILK is generally considered a cytosolic protein localized at focal adhesions, however ILK co-localizes with tubulins and many centrosomal and mitotic spindle associated proteins at centrosomes.
Function Integrin-linked kinase (ILK) (Hannigan et al., 1996) is a multifunctional protein kinase which is implicated in a large number of cellular processes and diseases, participating in signal transduction pathways that control cell survival, differentiation, proliferation and gene expression in mammalian cells (Wu, 2001). ILK, PINCH1 and α-parvin form a ternary complex termed IPP (ILK-PINCH-parvin) that localizes to both focal adhesions (FAs) and fibrillar adhesions (FBs) and is essential for several integrin-dependent functions. The IPP complex, interacts with the cytoplasmic tail of β integrins, resulting in the engagement and organization of the cytoskeleton as well as activation of signalling pathways. Deletion of the genes encoding ILK or PINCH1 similarly blocks maturation of FAs and FBs by downregulating expression or recruitment of tensin and destabilizing α5β1-integrin-cytoskeleton linkages (Legate et al., 2006; Stanchi et al., 2009; Elad et al., 2013). The kinase activity of ILK is stimulated by integrins and soluble mediators, including growth factors and chemokines, and is regulated in a phosphoinositide 3-kinase (PI3K)-dependent manner. The activity of ILK is antagonized by phosphatases such as ILKAP and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) (McDonald et al., 2008a). Important downstream targets of ILK signaling include PKB/Akt, GSK-3, β-catenin, p44/p42 MAP kinases, the myosin light chain (MLC) (Hannigan et al., 2011) and the Hippo pathway through Merlin's phosphatase MYPT1 (Serrano et al., 2013c). AKT is a regulator of cell survival and apoptosis. To become fully activated, PKB/Akt requires phosphorylation at two sites, threonine 308 and serine 473. Phosphorylation at serine 473 depends on PI3K activity (Persad et al., 2001), the rictor-mTOR complex (Sarbassov et al., 2005) and the ILK-Rictor complex (McDonald et al., 2008b). GSK-3 is phosphorylated and inactivated at serine 9 by ILK, regulating the cell cycle through proteolysis of cyclin D1 and activation of the transcription factor AP1 (Troussard et al., 1999). Inactivation of GSK-3 stabilizes β-catenin, whose accumulation is related to deregulation of proliferation, migration and differentiation (Oloumi et al., 2004). ILK can directly phosphorylate MLC on Ser18/thr19 influencing in cell contraction, motility and migration (Deng et al., 2001). ILK function is required in TGFβ-1-induced EMT in mammary epithelial cells, and the ILK/Rictor complex has been identified as a potential molecular target for preventing/reversing EMT (Serrano et al., 2013b). But ILK can also directly regulate EMT by promoting the expression of Snail transcriptionally (McPhee et al., 2008) and via posttranslational modification through GSK-3b.
ILK also localize to centrosomes, where it is recruited by RUVBI1/2, and it regulates mitotic spindle assembly by promoting Aurora A kinase/TACC3/ch-TOG interactions (Fielding et al., 2008) as well as centrosome clustering through the microtubule regulating proteins TACC3 and ch-TOG (Fielding et al., 2011). In addition, ILK regulates microtubule dynamics since overexpression of ILK in HeLa cells is associated with a shorter duration of mitosis and decreased sensitivity to paclitaxel, a chemotherapeutic agent that suppresses microtubule dynamics and conversely, the use of a small molecule inhibitor selective against ILK, QLT-0267, results in suppressed microtubule dynamics (Lim et al., 2013). ILK regulation of microtubules is critical for proper trafficking of caveolin-1-containing vesicles. ILK controls this process by regulating microtubule stability through the recruitment of the scaffold protein IQGAP1 and its downstream effector mDia1 to nascent, cortical adhesion sites. In the absence of ILK, caveolae remain associated with dynamic microtubules, fail to stably fuse with the plasma membrane, and subsequently accumulate in intracellular structures (Wickström et al., 2010).
 
  ILK interaction partners. Schematic representation of the signal transduction pathways where ILK is implicated. Dark green represents direct interaction, red represents indirect interaction and light brown represents not analysed. Adapted from Widmaier et al., 2012 by Elena Serrano.
Homology The ILK gene is highly conserved in a total of 24 species. The most representatives are human, mouse, chicken, lizard, African clawed frog, zebrafish, fruit fly, worm.

Mutations

Note 1. ILK mutation causes human cardiomyopathy via simultaneous defects in cardiomyocytes and endothelial cells (Knoll et al., 2007).
2. Embryonic lethality was observed in Xenopus laevis (Yasunaga et al., 2005) and mouse (Sakai et al., 2003) models of ILK ablation, and this was attributed to defects in adhesive and migratory mechanics.

Implicated in

Note
  
Entity Melanoma
Note Increased expression of integrin-linked kinase is correlated with melanoma progression and poor patient survival (Dai et al., 2003; Wong et al., 2007). ILK regulates melanoma angiogenesis by activating NF-kB/interleukin-6 signaling pathway (Wani et al., 2011).
  
  
Entity Colon cancer
Note ILK is hyperexpressed in malignant crypts from both the primary and metastatic lesions. Changes in ILK activity coincide with changes on downstream targets, primarily GSK3β. Dysregulation of the ILK-signaling nexus is an important early event in the genesis of human colon cancer (Marotta et al., 2003). ILK expression levels correlated with tumor invasion, grade and stage; higher levels in metastatic tumors (Bravou et al., 2003). Thymosin beta 4 induces colon cancer cell migration and clinical metastasis via enhancing ILK/IQGAP1/Rac1 signal transduction pathway (Tang et al., 2011).
  
  
Entity Gastric cancer
Note ILK might be a novel molecular marker for aggressive gastric cancer. Strong expression of ILK is observed in the majority of primary tumors that were associated with tumor cell invasion and nodal metastasis; no expression in non-neoplastic gastric epithelia (Ito et al., 2003). ILK might be used as a potential therapeutic strategy to combat multi-drug resistance through blocking PI3K-Akt and MAPK-ERK pathways in human gastric carcinoma (Song et al., 2012).
  
  
Entity Lung cancer
Note ILK expression is significantly associated with tumor grade and stage, and lower than 5-year survival. Increased expression of ILK is a poor prognostic factor in patients with non-small cell lung cancer (Takanami 2005; Okamura et al., 2007).
  
  
Entity Anaplastic thyroid cancer
Note ILK is a potential therapeutic target for treating anaplastic thyroid cancer. ILK expression and activity are elevated in human anaplastic thyroid cancer and ILK inhibition leads to growth arrest and apoptosis in vitro and in vivo (Younes et al., 2005).
  
  
Entity Squamous cell carcinoma of head and neck
Note ILK is overexpressed in SCCHN tumor specimens. Targeting ILK with the small-molecule ILK inhibitor QLT0267 inhibits cell growth and induces apoptosis in SCCHN cell lines by reducing ILK activity and Akt phosphorylation (Younes et al., 2007).
  
  
Entity Pancreatic cancer
Note ILK is involved with aggressive capability in pancreatic cancer. Significant association between strong expression of ILK and poor prognosis of pancreatic cancer patients has been observed (Sawai et al., 2006). Silencing ILK could be a potentially useful therapeutic approach for treating pancreatic cancer (Schaeffer et al., 2010; Zhu et al., 2012).
  
  
Entity Ovarian cancer
Note ILK expression is increased with tumor progression; normal epithelium was negative for ILK (Ahmed et al., 2003). ILK gene silencing suppresses tumor growth in human ovarian carcinoma HO-8910 xenografts in mice (Li et al., 2013) and induces apoptosis in ovarian carcinoma SKOV3 cell (Liu et al., 2012).
  
  
Entity Prostate cancer
Note ILK expression is increased with tumor progression. Increased expression of the protein has been demonstrated to be inversely related to the 5-year survival rate in prostate cancer (Graff et al., 2001). ILK stimulates the expression of VEGF by stimulating HIF-1alpha protein expression in a PKB/Akt- and mTOR/FRAP-dependent manner and knockdown of ILK expression with siRNA, or inhibition of ILK activity, results in significant inhibition of HIF-1alpha and VEGF expression (Tan el al., 2004). Compound 22, a novel ILK inhibitor, exhibited high in vitro potency against a panel of prostate and breast cancer cell lines and its therapeutic potential has been suggested by its in vivo efficacy as a single oral agent in suppressing PC-3 xenograft tumor growth (Lee et al., 2011).
  
  
Entity Mesothelioma
Note ILK is expressed in malignant mesothelioma. Normal mesothelial cells and lung parenchyma are negative (Watzka et al., 2008). Evaluating ILK's potential use as a marker of disease progression in malignant pleural mesothelioma has been suggested (Watzka et al., 2013).
  
  
Entity Ewing's sarcoma and primitive neuroectodermal tumor
Note Expression is observed (Chung et al., 1998).
  
  
Entity Glioblastoma
Note The ILK inhibitor, QLT0267, was able to reduce cellular invasion and angiogenesis of glioma cells. Blocking the ILK/Akt pathway is a potential strategy for molecular targeted therapy for gliomas (Kou et al., 2005; Edwards et al., 2008). Expression of insulin-like growth factor-binding protein 2 (IGFBP2), a glioma oncogene emerging as a target for therapeutic intervention, requires ILK to induce cell motility and activate NF-kB (Holmes et al., 2012).
  
  
Entity Musculoskeletal sarcoma
Note Prognostic factor in osteosarcoma and a novel potential therapeutic target for the treatment of osteosarcoma (Rhee et al., 2013).
  
  
Entity Medulloblastoma
Note Expression is observed (Chung et al., 1998).
  
  
Entity Breast cancer, cancer cell growth and metastasis
Note Epithelial to mesenchymal transition (EMT) causes fibrosis, cancer progression and metastasis. Acquisition of invasive and migratory characteristics in cancer cells results primarily from adopting an EMT phenotype. Overexpression of ILK induces EMT in mammary epithelial cells (Somasiri et al., 2001) and targeting this signaling cascade is an effective strategy for the treatment of fibrotic kidney (Li et al., 2009), lung (Kavvadas et al., 2010) or bladder cancer (Matsui et al., 2011). ILK is a key intracellular mediator of TGFβ-1 induced EMT (Li et al., 2009) through a Snail and Slug mechanism (Serrano et al., 2013b). TGFβ-1 mediated EMT induces an interaction between ILK and Rictor and disruption of this interaction by silencing ILK or using ILK inhibitor molecule, QLT0267, blocks TGFβ-1 induced EMT and partially reverses the mesenchymal phenotype in breast cancer cell lines (Serrano et al., 2013b). ILK promotes lung cancer cell migration and invasion through the induction of EMT process (Chen et al., 2013) and is a therapeutically targetable mediator of ERG-induced EMT and transformation in prostate cancer (Becker-Santos et al., 2012) and in high glucose-induced epithelial-mesenchymal transition of renal tubular cell (Peng et al., 2012). A significant acceleration in mammary tumor incidence and growth was observed in the MMTV-Wnt/ILK mice compared to Wnt alone, showing the cooperation between Wnt1 and ILK transgenes during mammary carcinogenesis (Oloumi et al., 2010). Furthermore, mammary epithelial disruption of ILK in mice results in a profound block in mammary tumor induction (Pontier et al., 2010). ILK plays a critical role in the suppression of the Hippo pathway in breast, colon and prostate cancer cells; inactivation of ILK suppresses YAP activation and tumour growth in vivo (Serrano et al., 2013c). Expression of LIMD2 is associated with the metastatic process of papillary thyroid carcinoma (Cerutti et al., 2007) and has been described to bound directly to the kinase domain of ILK in IPP, a signal transduction pathway strongly linked to cell motility and invasion suggesting that LIMD2 potentiates ILK biological effects (Peng et al., 2014).
  
  
Entity Embryonic development
Note Embryonic lethality was observed in Xenopus laevis (Yasunaga et al., 2005) and mouse (Sakai et al., 2003) models of ILK ablation, and this was attributed to defects in adhesive and migratory mechanics.
  
  
Entity Musculoskeletal system and skin
Note During bone formation, ILK-dependent interactions and downstream signaling effectors are required for proliferation and differentiation of chondrocytes within the growth plate. The kinase activity of ILK is necessary for mechanosensing and signaling in vertebrate skeletal muscle (Postel et al., 2008). ILK is important for proliferation, adhesion, spreading and migration of keratinocytes (Lorenz et al., 2007; Nakrieko et al., 2008). ILK plays an important modulatory role in the normal contribution of hair follicle stem cell progeny to the regenerating epidermis following injury (Nakrieko et al., 2011). ILK and PI3K activation after skin wounding are critical for tissue repair in an HGF-dependent mechanism (Serrano et al., 2012).
Disease Mice with depletion of ILK in chondrocytes suffer from dwarfism and chondrodysplasia (Grashoff et al., 2003; Terpstra et al., 2003). Lack of ILK in skin causes skin blistering and inhibition of hair follicle development (Lorenz et al., 2007; Nakrieko et al., 2008). ILK deficiency in mice leads to retarded wound closure in skin (Serrano et al., 2012).
  
  
Entity Central nervous system
Note The downregulation of ILK expression was found to inhibit axon formation through the elimination or length reduction of the axon. ILK-Akt-GSK3 signaling axis is implicated in the development and function of neurons (Guo et al., 2007).
Disease ILK deletion in the central nervous system leads to Cobblestone lissencephaly (Niewmierzycka et al., 2005) and to cerebellar development and loss of NGF signaling (Mills et al., 2006).
  
  
Entity Kidney
Note ILK function is required for epithelial to mesenchymal transition and adhesion and in the maintenance of glomerular filtration barrier. Human mesangial cells exposed to abnormal collagen I are protected against apoptosis by a complex mechanism involving integrin β1/ILK/AKT-dependent NFkB activation with consequent Bcl-xL overexpression, that opposes a simultaneously activated ILK/GSK-3β-dependent Bim expression and this dual mechanism may play a role in the progression of glomerular dysfunction (del Nogal et al., 2012). ILK plays a key role in the regulation of renal inflammation by modulating the canonical NF-kB pathway, and suggest a potential therapeutic target for inflammatory renal diseases (Alique et al., 2014). ILK regulates expression of tubular water channel aquaporin-2 (AQP2) and its apical membrane presence in the renal tubule, polyuria and decreased urine osmolality were present in ILK conditional-knockdown (cKD-ILK) adult mice compared with nondepleted ILK littermates pointing ILK as a therapeutic target in nephrogenic diabetes insipidus (Cano-Penalver et al., 2014).
Disease Fibrosis; proteinuria (Dai et al., 2006; El-Aouni et al., 2006).
  
  
Entity Heart
Note ILK plays a central role in protecting the mammalian heart against cardiomyopathy and failure. Thymosin beta4 activates ILK and promotes cardiac cell function and regeneration after infarction (Bock-Marquette et al., 2004; Srivastava et al., 2007). The heart uses the Integrin-ILK-beta-parvin network to sense mechanical stretch (Bendig et al., 2006). Deletion of ILK results in disaggregation of cardiomyocytes, associated with disruption of adhesion signaling through the beta1-integrin/FAK (focal adhesion kinase) complex (White et al., 2006). ILK is implicated in cardiac hypertrophy and contractility and is a novel cardiotropic factor that promotes recruitment of human fetal heart cells to a cardiomyogenic fate (Traister et al., 2012). Increased expression of integrin-linked kinase improves cardiac function and decreases mortality in dilated cardiomyopathy model of rats (Gu et al., 2012). In Drosophila, severely compromised integrin/ILK pathway function is detrimental for the heart, but fine-tuned moderate reduction maintains youthful cardiac performance, suggesting a dual role for this complex in regulating cardiac integrity and aging (Nishimura et al., 2014).
Disease Cardiomyogenesis
  
  
Entity Blood vessels
Note ILK closely regulates capillary formation and the survival of progenitor and differentiated endothelial cells. In endothelial cells, VEGF stimulates ILK activity, and inhibition of ILK expression or activity results in the inhibition of VEGF-mediated endothelial cell migration, capillary formation in vitro, and angiogenesis in vivo (Tan et al., 2004). ILK controls postnatal vasculogenesis by recruitment of endothelial progenitor cells to ischemic tissue (Lee et al., 2006). ILK acts as a regulatory partner of eNOS in vivo that prevents eNOS uncoupling, and suggest ILK as a therapeutic target for prevention of endothelial dysfunction related to shear stress-induced vascular diseases (Herranz et al., 2012). ILK regulates retinal vascular endothelial proliferation, migration and tube formation and targeting ILK may be a potentially useful therapeutic approach for treating ocular neovascularization (Xie et al., 2013). Deletion of ILK in mice leads to increased vascular content and increased activity of sGC (soluble Guanylyl Cyclase) and PKG (Protein Kinase G), resulting in a more intense vasodilatory response to nitric oxide donors (Serrano et al., 2013a).
Disease Tumor angiogenesis (Tan et al., 2004).
  

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Koul D, Shen R, Bergh S, Lu Y, de Groot JF, Liu TJ, Mills GB, Yung WK.
Mol Cancer Ther. 2005 Nov;4(11):1681-8.
PMID 16275989
 
Identification and characterization of a novel integrin-linked kinase inhibitor.
Lee SL, Hsu EC, Chou CC, Chuang HC, Bai LY, Kulp SK, Chen CS.
J Med Chem. 2011 Sep 22;54(18):6364-74. doi: 10.1021/jm2007744. Epub 2011 Aug 24.
PMID 21823616
 
Integrin-linked kinase, a hypoxia-responsive molecule, controls postnatal vasculogenesis by recruitment of endothelial progenitor cells to ischemic tissue.
Lee SP, Youn SW, Cho HJ, Li L, Kim TY, Yook HS, Chung JW, Hur J, Yoon CH, Park KW, Oh BH, Park YB, Kim HS.
Circulation. 2006 Jul 11;114(2):150-9. Epub 2006 Jul 3.
PMID 16818815
 
ILK, PINCH and parvin: the tIPP of integrin signalling.
Legate KR, Montanez E, Kudlacek O, Fassler R.
Nat Rev Mol Cell Biol. 2006 Jan;7(1):20-31. (REVIEW)
PMID 16493410
 
Silencing of integrin-linked kinase suppresses in vivo tumorigenesis of human ovarian carcinoma cells.
Li Q, Li C, Zhang YY, Chen W, Lv JL, Sun J, You QS.
Mol Med Rep. 2013 Mar;7(3):1050-4. doi: 10.3892/mmr.2013.1285. Epub 2013 Jan 22.
PMID 23340803
 
Inhibition of integrin-linked kinase attenuates renal interstitial fibrosis.
Li Y, Tan X, Dai C, Stolz DB, Wang D, Liu Y.
J Am Soc Nephrol. 2009 Sep;20(9):1907-18. doi: 10.1681/ASN.2008090930. Epub 2009 Jun 18.
PMID 19541809
 
Integrin-linked kinase regulates interphase and mitotic microtubule dynamics.
Lim S, Kawamura E, Fielding AB, Maydan M, Dedhar S.
PLoS One. 2013;8(1):e53702. doi: 10.1371/journal.pone.0053702. Epub 2013 Jan 21.
PMID 23349730
 
Silencing of the integrin-linked kinase gene induces the apoptosis in ovarian carcinoma.
Liu Q, Xiao L, Yuan D, Shi X, Li P.
J Recept Signal Transduct Res. 2012 Apr;32(2):120-7. doi: 10.3109/10799893.2012.660534. Epub 2012 Mar 2.
PMID 22384810
 
Integrin-linked kinase is required for epidermal and hair follicle morphogenesis.
Lorenz K, Grashoff C, Torka R, Sakai T, Langbein L, Bloch W, Aumailley M, Fassler R.
J Cell Biol. 2007 May 7;177(3):501-13.
PMID 17485490
 
Characterisation of integrin-linked kinase signalling in sporadic human colon cancer.
Marotta A, Parhar K, Owen D, Dedhar S, Salh B.
Br J Cancer. 2003 Jun 2;88(11):1755-62.
PMID 12771992
 
The importance of integrin-linked kinase in the regulation of bladder cancer invasion.
Matsui Y, Assi K, Ogawa O, Raven PA, Dedhar S, Gleave ME, Salh B, So AI.
Int J Cancer. 2012 Feb 1;130(3):521-31. doi: 10.1002/ijc.26008. Epub 2011 May 28.
PMID 21351095
 
Rictor and integrin-linked kinase interact and regulate Akt phosphorylation and cancer cell survival.
McDonald PC, Oloumi A, Mills J, Dobreva I, Maidan M, Gray V, Wederell ED, Bally MB, Foster LJ, Dedhar S.
Cancer Res. 2008b Mar 15;68(6):1618-24. doi: 10.1158/0008-5472.CAN-07-5869.
PMID 18339839
 
Integrin-linked kinase regulates E-cadherin expression through PARP-1.
McPhee TR, McDonald PC, Oloumi A, Dedhar S.
Dev Dyn. 2008 Oct;237(10):2737-47. doi: 10.1002/dvdy.21685.
PMID 18773488
 
Critical role of integrin-linked kinase in granule cell precursor proliferation and cerebellar development.
Mills J, Niewmierzycka A, Oloumi A, Rico B, St-Arnaud R, Mackenzie IR, Mawji NM, Wilson J, Reichardt LF, Dedhar S.
J Neurosci. 2006 Jan 18;26(3):830-40.
PMID 16421303
 
Targeted inactivation of integrin-linked kinase in hair follicle stem cells reveals an important modulatory role in skin repair after injury.
Nakrieko KA, Rudkouskaya A, Irvine TS, D'Souza SJ, Dagnino L.
Mol Biol Cell. 2011 Jul 15;22(14):2532-40. doi: 10.1091/mbc.E11-01-0035. Epub 2011 May 18.
PMID 21593206
 
Integrin-linked kinase deletion from mouse cortex results in cortical lamination defects resembling cobblestone lissencephaly.
Niewmierzycka A, Mills J, St-Arnaud R, Dedhar S, Reichardt LF.
J Neurosci. 2005 Jul 27;25(30):7022-31.
PMID 16049178
 
Molecular dissection of actopaxin-integrin-linked kinase-Paxillin interactions and their role in subcellular localization.
Nikolopoulos SN, Turner CE.
Biol Chem. 2002 Jan 11;277(2):1568-75. Epub 2001 Nov 1.
PMID 11694518
 
A dual role for integrin-linked kinase and β1-integrin in modulating cardiac aging.
Nishimura M, Kumsta C, Kaushik G, Diop SB, Ding Y, Bisharat-Kernizan J, Catan H, Cammarato A, Ross RS, Engler AJ, Bodmer R, Hansen M, Ocorr K.
Aging Cell. 2014 Jun;13(3):431-40. doi: 10.1111/acel.12193. Epub 2014 Jan 9.
PMID 24400780
 
Prognostic value of integrin beta1-ILK-pAkt signaling pathway in non-small cell lung cancer.
Okamura M, Yamaji S, Nagashima Y, Nishikawa M, Yoshimoto N, Kido Y, Iemoto Y, Aoki I, Ishigatsubo Y.
Hum Pathol. 2007 Jul;38(7):1081-91. Epub 2007 Apr 18.
PMID 17442374
 
Cooperative signaling between Wnt1 and integrin-linked kinase induces accelerated breast tumor development.
Oloumi A, Maidan M, Lock FE, Tearle H, McKinney S, Muller WJ, Aparicio SA, Dedhar S.
Breast Cancer Res. 2010;12(3):R38. doi: 10.1186/bcr2592. Epub 2010 Jun 21.
PMID 20565980
 
Regulation of E-cadherin expression and beta-catenin/Tcf transcriptional activity by the integrin-linked kinase.
Oloumi A, McPhee T, Dedhar S.
Biochim Biophys Acta. 2004 Apr 1;1691(1):1-15. (REVIEW)
PMID 15053919
 
LIMD2 is a small LIM-only protein overexpressed in metastatic lesions that regulates cell motility and tumor progression by directly binding to and activating the integrin-linked kinase.
Peng H, Talebzadeh-Farrooji M, Osborne MJ, Prokop JW, McDonald PC, Karar J, Hou Z, He M, Kebebew E, Orntoft T, Herlyn M, Caton AJ, Fredericks W, Malkowicz B, Paterno CS, Carolin AS, Speicher DW, Skordalakes E, Huang Q, Dedhar S, Borden KL, Rauscher FJ 3rd.
Cancer Res. 2014 Mar 1;74(5):1390-403. doi: 10.1158/0008-5472.CAN-13-1275.
PMID 24590809
 
Rhein inhibits integrin-linked kinase expression and regulates matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio in high glucose-induced epithelial-mesenchymal transition of renal tubular cell.
Peng L, Yang J, Ning C, Zhang J, Xiao X, He D, Wang X, Li Z, Fu S, Ning J.
Biol Pharm Bull. 2012;35(10):1676-85.
PMID 23037158
 
Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and amino acids arginine 211 and serine 343.
Persad S, Attwell S, Gray V, Mawji N, Deng JT, Leung D, Yan J, Sanghera J, Walsh MP, Dedhar S.
J Biol Chem. 2001 Jul 20;276(29):27462-9. Epub 2001 Apr 19.
PMID 11313365
 
Integrin-linked kinase has a critical role in ErbB2 mammary tumor progression: implications for human breast cancer.
Pontier SM, Huck L, White DE, Rayment J, Sanguin-Gendreau V, Hennessy B, Zuo D, St-Arnaud R, Mills GB, Dedhar S, Marshall CJ, Muller WJ.
Oncogene. 2010 Jun 10;29(23):3374-85. doi: 10.1038/onc.2010.86. Epub 2010 Mar 22.
PMID 20305688
 
Zebrafish integrin-linked kinase is required in skeletal muscles for strengthening the integrin-ECM adhesion complex.
Postel R, Vakeel P, Topczewski J, Knoll R, Bakkers J.
Dev Biol. 2008 Jun 1;318(1):92-101. doi: 10.1016/j.ydbio.2008.03.024. Epub 2008 Mar 26.
PMID 18436206
 
Role of integrin-linked kinase in osteosarcoma progression.
Rhee SH, Han I, Lee MR, Cho HS, Oh JH, Kim HS.
J Orthop Res. 2013 Oct;31(10):1668-75. doi: 10.1002/jor.22409. Epub 2013 Jun 19.
PMID 23784942
 
Integrin-linked kinase (ILK) is required for polarizing the epiblast, cell adhesion, and controlling actin accumulation.
Sakai T, Li S, Docheva D, Grashoff C, Sakai K, Kostka G, Braun A, Pfeifer A, Yurchenco PD, Fassler R.
Genes Dev. 2003 Apr 1;17(7):926-40.
PMID 12670870
 
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex.
Sarbassov DD, Guertin DA, Ali SM, Sabatini DM.
Science. 2005 Feb 18;307(5712):1098-101.
PMID 15718470
 
Integrin-linked kinase activity is associated with interleukin-1 alpha-induced progressive behavior of pancreatic cancer and poor patient survival.
Sawai H, Okada Y, Funahashi H, Matsuo Y, Takahashi H, Takeyama H, Manabe T.
Oncogene. 2006 Jun 1;25(23):3237-46. Epub 2006 Jan 16.
PMID 16407822
 
Tumor expression of integrin-linked kinase (ILK) correlates with the expression of the E-cadherin repressor snail: an immunohistochemical study in ductal pancreatic adenocarcinoma.
Schaeffer DF, Assi K, Chan K, Buczkowski AK, Chung SW, Scudamore CH, Weiss A, Salh B, Owen DA.
Virchows Arch. 2010 Mar;456(3):261-8. doi: 10.1007/s00428-009-0866-z. Epub 2010 Jan 21.
PMID 20091050
 
Integrin-linked kinase (ILK) modulates wound healing through regulation of hepatocyte growth factor (HGF).
Serrano I, Diez-Marques ML, Rodriguez-Puyol M, Herrero-Fresneda I, Raimundo Garcia del M, Dedhar S, Ruiz-Torres MP, Rodriguez-Puyol D.
Exp Cell Res. 2012 Nov 15;318(19):2470-81. doi: 10.1016/j.yexcr.2012.08.001. Epub 2012 Aug 23.
PMID 22971619
 
Overexpression of the integrin-linked kinase mesenchymally transforms mammary epithelial cells.
Somasiri A, Howarth A, Goswami D, Dedhar S, Roskelley CD.
J Cell Sci. 2001 Mar;114(Pt 6):1125-36.
PMID 11228156
 
Role of integrin-linked kinase in multi-drug resistance of human gastric carcinoma SGC7901/DDP cells.
Song W, Jiang R, Zhao CM.
Asian Pac J Cancer Prev. 2012;13(11):5619-25.
PMID 23317227
 
Thymosin beta4 is cardioprotective after myocardial infarction.
Srivastava D, Saxena A, Michael Dimaio J, Bock-Marquette I.
Ann N Y Acad Sci. 2007 Sep;1112:161-70. Epub 2007 Jun 28.
PMID 17600280
 
Molecular dissection of the ILK-PINCH-parvin triad reveals a fundamental role for the ILK kinase domain in the late stages of focal-adhesion maturation.
Stanchi F, Grashoff C, Nguemeni Yonga CF, Grall D, Fassler R, Van Obberghen-Schilling E.
J Cell Sci. 2009 Jun 1;122(Pt 11):1800-11. doi: 10.1242/jcs.044602. Epub 2009 May 12.
PMID 19435803
 
Increased expression of integrin-linked kinase is associated with shorter survival in non-small cell lung cancer.
Takanami I.
BMC Cancer. 2005 Jan 5;5:1.
PMID 15631637
 
Regulation of tumor angiogenesis by integrin-linked kinase (ILK).
Tan C, Cruet-Hennequart S, Troussard A, Fazli L, Costello P, Sutton K, Wheeler J, Gleave M, Sanghera J, Dedhar S.
Cancer Cell. 2004 Jan;5(1):79-90.
PMID 14749128
 
Thymosin beta 4 induces colon cancer cell migration and clinical metastasis via enhancing ILK/IQGAP1/Rac1 signal transduction pathway.
Tang MC, Chan LC, Yeh YC, Chen CY, Chou TY, Wang WS, Su Y.
Cancer Lett. 2011 Sep 28;308(2):162-71. doi: 10.1016/j.canlet.2011.05.001. Epub 2011 May 28.
PMID 21621326
 
Reduced chondrocyte proliferation and chondrodysplasia in mice lacking the integrin-linked kinase in chondrocytes.
Terpstra L, Prud'homme J, Arabian A, Takeda S, Karsenty G, Dedhar S, St-Arnaud R.
J Cell Biol. 2003 Jul 7;162(1):139-48. Epub 2003 Jun 30.
PMID 12835312
 
ILK induces cardiomyogenesis in the human heart.
Traister A, Aafaqi S, Masse S, Dai X, Li M, Hinek A, Nanthakumar K, Hannigan G, Coles JG.
PLoS One. 2012;7(5):e37802. doi: 10.1371/journal.pone.0037802. Epub 2012 May 29.
PMID 22666394
 
Cell-extracellular matrix interactions stimulate the AP-1 transcription factor in an integrin-linked kinase- and glycogen synthase kinase 3-dependent manner.
Troussard AA, Tan C, Yoganathan TN, Dedhar S.
Mol Cell Biol. 1999 Nov;19(11):7420-7.
PMID 10523630
 
Integrin-linked kinase regulates melanoma angiogenesis by activating NF-kB/interleukin-6 signaling pathway.
Wani AA, Jafarnejad SM, Zhou J, Li G.
Oncogene. 2011 Jun 16;30(24):2778-88. doi: 10.1038/onc.2010.644. Epub 2011 Jan 31.
PMID 21278793
 
Serum concentration of integrin-linked kinase in malignant pleural mesothelioma and after asbestos exposure.
Watzka SB, Posch F, Pass HI, Flores RM, Hannigan GE, Bernhard D, Weber M, Mueller MR.
Eur J Cardiothorac Surg. 2013 May;43(5):940-5. doi: 10.1093/ejcts/ezs521. Epub 2012 Oct 7.
PMID 23045294
 
Reactivity of integrin-linked kinase in human mesothelial cell proliferation.
Watzka SB, Setinek U, Huber M, Cantonati H, Lax F, Watson S, Weigel G, Muller MR.
Interact Cardiovasc Thorac Surg. 2008 Feb;7(1):107-10. Epub 2007 Nov 29.
PMID 18048409
 
Targeted ablation of ILK from the murine heart results in dilated cardiomyopathy and spontaneous heart failure.
White DE, Coutu P, Shi YF, Tardif JC, Nattel S, St Arnaud R, Dedhar S, Muller WJ.
Genes Dev. 2006 Sep 1;20(17):2355-60.
PMID 16951252
 
Integrin-linked kinase controls microtubule dynamics required for plasma membrane targeting of caveolae.
Wickstrom SA, Lange A, Hess MW, Polleux J, Spatz JP, Kruger M, Pfaller K, Lambacher A, Bloch W, Mann M, Huber LA, Fassler R.
Dev Cell. 2010 Oct 19;19(4):574-88. doi: 10.1016/j.devcel.2010.09.007.
PMID 20951348
 
Integrin-linked kinase at a glance.
Widmaier M, Rognoni E, Radovanac K, Azimifar SB, Fassler R.
J Cell Sci. 2012 Apr 15;125(Pt 8):1839-43. doi: 10.1242/jcs.093864.
PMID 22637643
 
The role of integrin-linked kinase in melanoma cell migration, invasion, and tumor growth.
Wong RP, Ng P, Dedhar S, Li G.
Mol Cancer Ther. 2007 Jun;6(6):1692-700.
PMID 17575101
 
ILK interactions.
Wu C.
J Cell Sci. 2001 Jul;114(Pt 14):2549-50. (REVIEW)
PMID 11683382
 
Targeting of integrin-linked kinase with small interfering RNA inhibits VEGF-induced angiogenesis in retinal endothelial cells.
Xie W, Zhao M, Zhou W, Guo L, Huang L, Yu W, Li X.
Ophthalmic Res. 2013;49(3):139-49. doi: 10.1159/000345070. Epub 2012 Dec 18.
PMID 23258222
 
Xenopus ILK (integrin-linked kinase) is required for morphogenetic movements during gastrulation.
Yasunaga T, Kusakabe M, Yamanaka H, Hanafusa H, Masuyama N, Nishida E.
Genes Cells. 2005 Apr;10(4):369-79.
PMID 15773899
 
Integrin-linked kinase is a potential therapeutic target for anaplastic thyroid cancer.
Younes MN, Kim S, Yigitbasi OG, Mandal M, Jasser SA, Dakak Yazici Y, Schiff BA, El-Naggar A, Bekele BN, Mills GB, Myers JN.
Mol Cancer Ther. 2005 Aug;4(8):1146-56.
PMID 16093430
 
Effects of the integrin-linked kinase inhibitor QLT0267 on squamous cell carcinoma of the head and neck.
Younes MN, Yigitbasi OG, Yazici YD, Jasser SA, Bucana CD, El-Naggar AK, Mills GB, Myers JN.
Arch Otolaryngol Head Neck Surg. 2007 Jan;133(1):15-23.
PMID 17224516
 
Silencing of the integrin-linked kinase gene suppresses the proliferation, migration and invasion of pancreatic cancer cells (Panc-1).
Zhu XY, Liu N, Liu W, Song SW, Guo KJ.
Genet Mol Biol. 2012 Apr;35(2):538-44. doi: 10.1590/S1415-47572012005000028. Epub 2012 May 17.
PMID 22888305
 
Balance between apoptosis or survival induced by changes in extracellular-matrix composition in human mesangial cells: a key role for ILK-NFkB pathway.
del Nogal M, Luengo A, Olmos G, Lasa M, Rodriguez-Puyol D, Rodriguez-Puyol M, Calleros L.
Apoptosis. 2012 Dec;17(12):1261-74. doi: 10.1007/s10495-012-0769-3.
PMID 23054083
 

Citation

This paper should be referenced as such :
Isabel Serrano, Paul McDonald, Shoukat Dedhar
ILK (integrin-linked kinase)
Atlas Genet Cytogenet Oncol Haematol. 2015;19(5):324-332.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/ILKID460ch11p15.html


External links

Nomenclature
HGNC (Hugo)ILK   6040
LRG (Locus Reference Genomic)LRG_444
Cards
AtlasILKID460ch11p15
Entrez_Gene (NCBI)ILK  3611  integrin linked kinase
AliasesHEL-S-28; ILK-1; ILK-2; P59; 
p59ILK
GeneCards (Weizmann)ILK
Ensembl hg19 (Hinxton)ENSG00000166333 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000166333 [Gene_View]  chr11:6603708-6610874 [Contig_View]  ILK [Vega]
ICGC DataPortalENSG00000166333
TCGA cBioPortalILK
AceView (NCBI)ILK
Genatlas (Paris)ILK
WikiGenes3611
SOURCE (Princeton)ILK
Genetics Home Reference (NIH)ILK
Genomic and cartography
GoldenPath hg38 (UCSC)ILK  -     chr11:6603708-6610874 +  11p15.4   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)ILK  -     11p15.4   [Description]    (hg19-Feb_2009)
EnsemblILK - 11p15.4 [CytoView hg19]  ILK - 11p15.4 [CytoView hg38]
Mapping of homologs : NCBIILK [Mapview hg19]  ILK [Mapview hg38]
OMIM602366   
Gene and transcription
Genbank (Entrez)AB209416 AK293474 AK296628 AK314843 BC001554
RefSeq transcript (Entrez)NM_001014794 NM_001014795 NM_001278441 NM_001278442 NM_004517
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)ILK
Cluster EST : UnigeneHs.706355 [ NCBI ]
CGAP (NCI)Hs.706355
Alternative Splicing GalleryENSG00000166333
Gene ExpressionILK [ NCBI-GEO ]   ILK [ EBI - ARRAY_EXPRESS ]   ILK [ SEEK ]   ILK [ MEM ]
Gene Expression Viewer (FireBrowse)ILK [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)3611
GTEX Portal (Tissue expression)ILK
Human Protein AtlasENSG00000166333-ILK [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ13418   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ13418  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ13418
Splice isoforms : SwissVarQ13418
Catalytic activity : Enzyme2.7.11.1 [ Enzyme-Expasy ]   2.7.11.12.7.11.1 [ IntEnz-EBI ]   2.7.11.1 [ BRENDA ]   2.7.11.1 [ KEGG ]   
PhosPhoSitePlusQ13418
Domaine pattern : Prosite (Expaxy)ANK_REP_REGION (PS50297)    ANK_REPEAT (PS50088)    PROTEIN_KINASE_DOM (PS50011)   
Domains : Interpro (EBI)Ankyrin_rpt    Ankyrin_rpt-contain_dom    Kinase-like_dom    Prot_kinase_dom    Ser-Thr/Tyr_kinase_cat_dom   
Domain families : Pfam (Sanger)Ank_2 (PF12796)    Pkinase_Tyr (PF07714)   
Domain families : Pfam (NCBI)pfam12796    pfam07714   
Domain families : Smart (EMBL)ANK (SM00248)  
Conserved Domain (NCBI)ILK
DMDM Disease mutations3611
Blocks (Seattle)ILK
PDB (SRS)2KBX    3F6Q    3IXE    3KMU    3KMW    3REP    4HI8    4HI9   
PDB (PDBSum)2KBX    3F6Q    3IXE    3KMU    3KMW    3REP    4HI8    4HI9   
PDB (IMB)2KBX    3F6Q    3IXE    3KMU    3KMW    3REP    4HI8    4HI9   
PDB (RSDB)2KBX    3F6Q    3IXE    3KMU    3KMW    3REP    4HI8    4HI9   
Structural Biology KnowledgeBase2KBX    3F6Q    3IXE    3KMU    3KMW    3REP    4HI8    4HI9   
SCOP (Structural Classification of Proteins)2KBX    3F6Q    3IXE    3KMU    3KMW    3REP    4HI8    4HI9   
CATH (Classification of proteins structures)2KBX    3F6Q    3IXE    3KMU    3KMW    3REP    4HI8    4HI9   
SuperfamilyQ13418
Human Protein Atlas [tissue]ENSG00000166333-ILK [tissue]
Peptide AtlasQ13418
HPRD03842
IPIIPI00013219   IPI01012931   IPI01008768   IPI00985172   IPI00984656   IPI00556543   IPI00985220   IPI00922759   
Protein Interaction databases
DIP (DOE-UCLA)Q13418
IntAct (EBI)Q13418
FunCoupENSG00000166333
BioGRIDILK
STRING (EMBL)ILK
ZODIACILK
Ontologies - Pathways
QuickGOQ13418
Ontology : AmiGOMAPK cascade  branching involved in ureteric bud morphogenesis  stress fiber  positive regulation of cell-matrix adhesion  outflow tract morphogenesis  protein serine/threonine kinase activity  signal transducer activity  integrin binding  protein binding  ATP binding  nucleoplasm  cytoplasm  cytosol  cytosol  plasma membrane  cell-cell junction  focal adhesion  focal adhesion  protein phosphorylation  negative regulation of protein kinase activity  cell cycle arrest  cell-matrix adhesion  integrin-mediated signaling pathway  multicellular organism development  cell aging  cell proliferation  positive regulation of cell proliferation  negative regulation of cardiac muscle cell apoptotic process  fibroblast migration  negative regulation of smooth muscle cell migration  membrane  SH3 domain binding  peptidyl-serine phosphorylation  protein kinase binding  nerve development  myelination in peripheral nervous system  sarcomere  lamellipodium  cell junction  positive regulation of cell migration  positive regulation of BMP signaling pathway  myelin assembly  regulation of actin cytoskeleton organization  tumor necrosis factor-mediated signaling pathway  cell junction assembly  substrate adhesion-dependent cell spreading  positive regulation of phosphorylation  neuronal cell body  costamere  terminal bouton  dendritic shaft  protein complex  positive regulation of MAP kinase activity  protein kinase B signaling  negative regulation of neuron apoptotic process  establishment or maintenance of epithelial cell apical/basal polarity  positive regulation of myoblast differentiation  positive regulation of osteoblast differentiation  positive regulation of axon extension  positive regulation of transcription, DNA-templated  negative regulation of smooth muscle cell proliferation  neuron projection morphogenesis  positive regulation of dendrite morphogenesis  protein heterooligomerization  positive regulation of protein kinase B signaling  platelet aggregation  positive regulation of canonical Wnt signaling pathway  supramolecular fiber organization  positive regulation of NIK/NF-kappaB signaling  negative regulation of neural precursor cell proliferation  
Ontology : EGO-EBIMAPK cascade  branching involved in ureteric bud morphogenesis  stress fiber  positive regulation of cell-matrix adhesion  outflow tract morphogenesis  protein serine/threonine kinase activity  signal transducer activity  integrin binding  protein binding  ATP binding  nucleoplasm  cytoplasm  cytosol  cytosol  plasma membrane  cell-cell junction  focal adhesion  focal adhesion  protein phosphorylation  negative regulation of protein kinase activity  cell cycle arrest  cell-matrix adhesion  integrin-mediated signaling pathway  multicellular organism development  cell aging  cell proliferation  positive regulation of cell proliferation  negative regulation of cardiac muscle cell apoptotic process  fibroblast migration  negative regulation of smooth muscle cell migration  membrane  SH3 domain binding  peptidyl-serine phosphorylation  protein kinase binding  nerve development  myelination in peripheral nervous system  sarcomere  lamellipodium  cell junction  positive regulation of cell migration  positive regulation of BMP signaling pathway  myelin assembly  regulation of actin cytoskeleton organization  tumor necrosis factor-mediated signaling pathway  cell junction assembly  substrate adhesion-dependent cell spreading  positive regulation of phosphorylation  neuronal cell body  costamere  terminal bouton  dendritic shaft  protein complex  positive regulation of MAP kinase activity  protein kinase B signaling  negative regulation of neuron apoptotic process  establishment or maintenance of epithelial cell apical/basal polarity  positive regulation of myoblast differentiation  positive regulation of osteoblast differentiation  positive regulation of axon extension  positive regulation of transcription, DNA-templated  negative regulation of smooth muscle cell proliferation  neuron projection morphogenesis  positive regulation of dendrite morphogenesis  protein heterooligomerization  positive regulation of protein kinase B signaling  platelet aggregation  positive regulation of canonical Wnt signaling pathway  supramolecular fiber organization  positive regulation of NIK/NF-kappaB signaling  negative regulation of neural precursor cell proliferation  
Pathways : BIOCARTAPTEN dependent cell cycle arrest and apoptosis [Genes]   
Pathways : KEGGPPAR signaling pathway    Focal adhesion    Bacterial invasion of epithelial cells    Endometrial cancer   
REACTOMEQ13418 [protein]
REACTOME PathwaysR-HSA-446353 [pathway]   
NDEx NetworkILK
Atlas of Cancer Signalling NetworkILK
Wikipedia pathwaysILK
Orthology - Evolution
OrthoDB3611
GeneTree (enSembl)ENSG00000166333
Phylogenetic Trees/Animal Genes : TreeFamILK
HOVERGENQ13418
HOGENOMQ13418
Homologs : HomoloGeneILK
Homology/Alignments : Family Browser (UCSC)ILK
Gene fusions - Rearrangements
Tumor Fusion PortalILK
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerILK [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)ILK
dbVarILK
ClinVarILK
1000_GenomesILK 
Exome Variant ServerILK
ExAC (Exome Aggregation Consortium)ENSG00000166333
GNOMAD BrowserENSG00000166333
Genetic variants : HAPMAP3611
Genomic Variants (DGV)ILK [DGVbeta]
DECIPHERILK [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisILK 
Mutations
ICGC Data PortalILK 
TCGA Data PortalILK 
Broad Tumor PortalILK
OASIS PortalILK [ Somatic mutations - Copy number]
Mutations and Diseases : HGMDILK
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch ILK
DgiDB (Drug Gene Interaction Database)ILK
DoCM (Curated mutations)ILK (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)ILK (select a term)
intoGenILK
NCG5 (London)ILK
Cancer3DILK(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM602366   
Orphanet
DisGeNETILK
MedgenILK
Genetic Testing Registry ILK
NextProtQ13418 [Medical]
TSGene3611
GENETestsILK
Target ValidationILK
Huge Navigator ILK [HugePedia]
snp3D : Map Gene to Disease3611
BioCentury BCIQILK
ClinGenILK
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD3611
Chemical/Pharm GKB GenePA29855
Clinical trialILK
Miscellaneous
canSAR (ICR)ILK (select the gene name)
Probes
Litterature
PubMed267 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineILK
EVEXILK
GoPubMedILK
iHOPILK
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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