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FLASH GENE

Symbol

ILK

contributors: mct/pgu - updated : 07-01-2016

HGNC name	integrin-linked kinase
HGNC id	6040

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

RNA

TRANSCRIPTS	type	messenger

text	all transcripts encoding the same protein

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004517 13 - 1817 NP_004508 - 452 - 2004 14990992 NM_001014794 13 - 1771 NP_001014794 - 452 - 2004 14990992 NM_001014795 12 - 1931 NP_001014795 - 452 - 2004 14990992

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol blood / hematopoietic spleen       highly Cardiovascular heart       highly Digestive liver       highly Endocrine pancreas       highly Nervous brain       highly Reproductive male system prostate     highly Respiratory lung       lowly Urinary kidney       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Connective bone       Epithelial secretory glandular endocrine   Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic monocyte

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed 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 cancer reproductive ovary targeting ILK and ITGB4 abrogates the invasive potential of ovarian cancer cancer urinary   could be served as a novel potential therapy target for human bladder cancer

ANIMAL & CELL MODELS