TISIDB

Summary
Symbol	ILK
Name	integrin-linked kinase
Aliases	HEL-S-28-1; ILK-2; p59ILK; 59 kDa serine/threonine-protein kinase; epididymis secretory protein Li 28; integ ......
Chromosomal Location	11p15.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cell junction, focal adhesion Cell membrane; Peripheral membrane protein; Cytoplasmic side Cell projection, lamellipodium Cytoplasm, myofibril, sarcomere
Domain	PF12796 Ankyrin repeats (3 copies) PF07714 Protein tyrosine kinase
Function	Receptor-proximal protein kinase regulating integrin-mediated signal transduction (PubMed:8538749, PubMed:9736715). May act as a mediator of inside-out integrin signaling. Focal adhesion protein part of the complex ILK-PINCH. This complex is considered to be one of the convergence points of integrin- and growth factor-signaling pathway. Could be implicated in mediating cell architecture, adhesion to integrin substrates and anchorage-dependent growth in epithelial cells. Phosphorylates beta-1 and beta-3 integrin subunit on serine and threonine residues, but also AKT1 and GSK3B (PubMed:8538749, PubMed:9736715).

> Gene Ontology [ TOP ]
Biological Process	GO:0001503 ossification GO:0001558 regulation of cell growth GO:0001649 osteoblast differentiation GO:0001655 urogenital system development GO:0001657 ureteric bud development GO:0001658 branching involved in ureteric bud morphogenesis GO:0001667 ameboidal-type cell migration GO:0001763 morphogenesis of a branching structure GO:0001822 kidney development GO:0001823 mesonephros development GO:0001933 negative regulation of protein phosphorylation GO:0001952 regulation of cell-matrix adhesion GO:0001954 positive regulation of cell-matrix adhesion GO:0003007 heart morphogenesis GO:0003151 outflow tract morphogenesis GO:0006469 negative regulation of protein kinase activity GO:0007050 cell cycle arrest GO:0007160 cell-matrix adhesion GO:0007163 establishment or maintenance of cell polarity GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway GO:0007229 integrin-mediated signaling pathway GO:0007272 ensheathment of neurons GO:0007409 axonogenesis GO:0007422 peripheral nervous system development GO:0007507 heart development GO:0007568 aging GO:0007569 cell aging GO:0007596 blood coagulation GO:0007599 hemostasis GO:0008361 regulation of cell size GO:0008366 axon ensheathment GO:0010001 glial cell differentiation GO:0010656 negative regulation of muscle cell apoptotic process GO:0010657 muscle cell apoptotic process GO:0010658 striated muscle cell apoptotic process GO:0010659 cardiac muscle cell apoptotic process GO:0010660 regulation of muscle cell apoptotic process GO:0010662 regulation of striated muscle cell apoptotic process GO:0010664 negative regulation of striated muscle cell apoptotic process GO:0010665 regulation of cardiac muscle cell apoptotic process GO:0010667 negative regulation of cardiac muscle cell apoptotic process GO:0010720 positive regulation of cell development GO:0010761 fibroblast migration GO:0010769 regulation of cell morphogenesis involved in differentiation GO:0010770 positive regulation of cell morphogenesis involved in differentiation GO:0010810 regulation of cell-substrate adhesion GO:0010811 positive regulation of cell-substrate adhesion GO:0010927 cellular component assembly involved in morphogenesis GO:0010975 regulation of neuron projection development GO:0010976 positive regulation of neuron projection development GO:0014037 Schwann cell differentiation GO:0014044 Schwann cell development GO:0014812 muscle cell migration GO:0014909 smooth muscle cell migration GO:0014910 regulation of smooth muscle cell migration GO:0014912 negative regulation of smooth muscle cell migration GO:0016049 cell growth GO:0016055 Wnt signaling pathway GO:0016358 dendrite development GO:0018105 peptidyl-serine phosphorylation GO:0018209 peptidyl-serine modification GO:0021675 nerve development GO:0021782 glial cell development GO:0022011 myelination in peripheral nervous system GO:0022604 regulation of cell morphogenesis GO:0030111 regulation of Wnt signaling pathway GO:0030168 platelet activation GO:0030177 positive regulation of Wnt signaling pathway GO:0030198 extracellular matrix organization GO:0030278 regulation of ossification GO:0030307 positive regulation of cell growth GO:0030335 positive regulation of cell migration GO:0030336 negative regulation of cell migration GO:0030509 BMP signaling pathway GO:0030510 regulation of BMP signaling pathway GO:0030513 positive regulation of BMP signaling pathway GO:0030516 regulation of axon extension GO:0031346 positive regulation of cell projection organization GO:0031589 cell-substrate adhesion GO:0032288 myelin assembly GO:0032292 peripheral nervous system axon ensheathment GO:0032535 regulation of cellular component size GO:0032956 regulation of actin cytoskeleton organization GO:0032970 regulation of actin filament-based process GO:0033002 muscle cell proliferation GO:0033673 negative regulation of kinase activity GO:0033674 positive regulation of kinase activity GO:0034109 homotypic cell-cell adhesion GO:0034329 cell junction assembly GO:0034330 cell junction organization GO:0034446 substrate adhesion-dependent cell spreading GO:0035088 establishment or maintenance of apical/basal cell polarity GO:0035239 tube morphogenesis GO:0040013 negative regulation of locomotion GO:0040017 positive regulation of locomotion GO:0042063 gliogenesis GO:0042326 negative regulation of phosphorylation GO:0042552 myelination GO:0042692 muscle cell differentiation GO:0043062 extracellular structure organization GO:0043206 extracellular fibril organization GO:0043405 regulation of MAP kinase activity GO:0043406 positive regulation of MAP kinase activity GO:0043410 positive regulation of MAPK cascade GO:0043491 protein kinase B signaling GO:0043523 regulation of neuron apoptotic process GO:0043524 negative regulation of neuron apoptotic process GO:0045197 establishment or maintenance of epithelial cell apical/basal polarity GO:0045445 myoblast differentiation GO:0045661 regulation of myoblast differentiation GO:0045663 positive regulation of myoblast differentiation GO:0045666 positive regulation of neuron differentiation GO:0045667 regulation of osteoblast differentiation GO:0045669 positive regulation of osteoblast differentiation GO:0045773 positive regulation of axon extension GO:0045778 positive regulation of ossification GO:0045785 positive regulation of cell adhesion GO:0045786 negative regulation of cell cycle GO:0045860 positive regulation of protein kinase activity GO:0045927 positive regulation of growth GO:0048588 developmental cell growth GO:0048638 regulation of developmental growth GO:0048639 positive regulation of developmental growth GO:0048659 smooth muscle cell proliferation GO:0048660 regulation of smooth muscle cell proliferation GO:0048662 negative regulation of smooth muscle cell proliferation GO:0048667 cell morphogenesis involved in neuron differentiation GO:0048675 axon extension GO:0048754 branching morphogenesis of an epithelial tube GO:0048813 dendrite morphogenesis GO:0048814 regulation of dendrite morphogenesis GO:0050769 positive regulation of neurogenesis GO:0050770 regulation of axonogenesis GO:0050772 positive regulation of axonogenesis GO:0050773 regulation of dendrite development GO:0050775 positive regulation of dendrite morphogenesis GO:0050817 coagulation GO:0050878 regulation of body fluid levels GO:0051147 regulation of muscle cell differentiation GO:0051149 positive regulation of muscle cell differentiation GO:0051259 protein oligomerization GO:0051271 negative regulation of cellular component movement GO:0051272 positive regulation of cellular component movement GO:0051291 protein heterooligomerization GO:0051348 negative regulation of transferase activity GO:0051402 neuron apoptotic process GO:0051493 regulation of cytoskeleton organization GO:0051896 regulation of protein kinase B signaling GO:0051897 positive regulation of protein kinase B signaling GO:0051962 positive regulation of nervous system development GO:0060070 canonical Wnt signaling pathway GO:0060560 developmental growth involved in morphogenesis GO:0060562 epithelial tube morphogenesis GO:0060675 ureteric bud morphogenesis GO:0060828 regulation of canonical Wnt signaling pathway GO:0060993 kidney morphogenesis GO:0061138 morphogenesis of a branching epithelium GO:0061245 establishment or maintenance of bipolar cell polarity GO:0061326 renal tubule development GO:0061333 renal tubule morphogenesis GO:0061351 neural precursor cell proliferation GO:0061387 regulation of extent of cell growth GO:0061564 axon development GO:0070527 platelet aggregation GO:0070997 neuron death GO:0071772 response to BMP GO:0071773 cellular response to BMP stimulus GO:0071900 regulation of protein serine/threonine kinase activity GO:0071902 positive regulation of protein serine/threonine kinase activity GO:0072001 renal system development GO:0072006 nephron development GO:0072009 nephron epithelium development GO:0072028 nephron morphogenesis GO:0072073 kidney epithelium development GO:0072078 nephron tubule morphogenesis GO:0072080 nephron tubule development GO:0072088 nephron epithelium morphogenesis GO:0072163 mesonephric epithelium development GO:0072164 mesonephric tubule development GO:0072171 mesonephric tubule morphogenesis GO:0090066 regulation of anatomical structure size GO:0090092 regulation of transmembrane receptor protein serine/threonine kinase signaling pathway GO:0090100 positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway GO:0090263 positive regulation of canonical Wnt signaling pathway GO:0090287 regulation of cellular response to growth factor stimulus GO:0097435 fibril organization GO:0198738 cell-cell signaling by wnt GO:1900006 positive regulation of dendrite development GO:1901214 regulation of neuron death GO:1901215 negative regulation of neuron death GO:1990138 neuron projection extension GO:2000146 negative regulation of cell motility GO:2000147 positive regulation of cell motility GO:2000177 regulation of neural precursor cell proliferation GO:2000178 negative regulation of neural precursor cell proliferation
Molecular Function	GO:0004674 protein serine/threonine kinase activity GO:0005178 integrin binding GO:0017124 SH3 domain binding GO:0050839 cell adhesion molecule binding
Cellular Component	GO:0001725 stress fiber GO:0005924 cell-substrate adherens junction GO:0005925 focal adhesion GO:0015629 actin cytoskeleton GO:0030016 myofibril GO:0030017 sarcomere GO:0030027 lamellipodium GO:0030055 cell-substrate junction GO:0030424 axon GO:0030425 dendrite GO:0031252 cell leading edge GO:0032432 actin filament bundle GO:0033267 axon part GO:0042641 actomyosin GO:0043025 neuronal cell body GO:0043034 costamere GO:0043195 terminal bouton GO:0043198 dendritic shaft GO:0043292 contractile fiber GO:0043679 axon terminus GO:0044297 cell body GO:0044306 neuron projection terminus GO:0044449 contractile fiber part GO:0097517 contractile actin filament bundle GO:0098793 presynapse

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa03320 PPAR signaling pathway hsa04360 Axon guidance hsa04510 Focal adhesion
Reactome	R-HSA-446728: Cell junction organization R-HSA-1500931: Cell-Cell communication R-HSA-446353: Cell-extracellular matrix interactions R-HSA-446343: Localization of the PINCH-ILK-PARVIN complex to focal adhesions

Summary
Symbol	ILK
Name	integrin-linked kinase
Aliases	HEL-S-28-1; ILK-2; p59ILK; 59 kDa serine/threonine-protein kinase; epididymis secretory protein Li 28; integ ......
Chromosomal Location	11p15.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ILK and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

[ TOP ]

Literatures describing the relation between ILK and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26921343	Lung Carcinoma	Promote immunity (infiltration, T cell function)	Here, we used viable human lung tumor slices and autologous tumor antigen-specific T-lymphocyte clones to provide evidence that CD103 is directly involved in T-lymphocyte recruitment within epithelial tumor islets and intratumoral early T-cell signaling. Mechanistic investigations revealed that TGFβ bound to its receptors (TGFBR), which promoted the recruitment and phosphorylation of integrin-linked kinase (ILK) by TGFBR1. We further show that ILK interacted with the CD103 intracellular domain, resulting in protein kinase B (PKB)/AKT activation, thereby initiating integrin inside-out signaling.

Summary
Symbol	ILK
Name	integrin-linked kinase
Aliases	HEL-S-28-1; ILK-2; p59ILK; 59 kDa serine/threonine-protein kinase; epididymis secretory protein Li 28; integ ......
Chromosomal Location	11p15.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

[ TOP ]

Statistical results of ILK in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	logFC: -2.62; FDR: 0.04630	Resistant to T cell-mediated killing
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	ILK
Name	integrin-linked kinase
Aliases	HEL-S-28-1; ILK-2; p59ILK; 59 kDa serine/threonine-protein kinase; epididymis secretory protein Li 28; integ ......
Chromosomal Location	11p15.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the expression difference of ILK in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.109	0.6
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.321	0.908
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.421	0.832
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.252	0.769
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.234	0.916
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.873	0.764
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.038	0.928
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.234	0.902
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.337	0.873
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.322	0.887
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.828	0.807
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.173	0.0274

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of ILK in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	3.7	0.27
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	3.7	0.314
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	ILK
Name	integrin-linked kinase
Aliases	HEL-S-28-1; ILK-2; p59ILK; 59 kDa serine/threonine-protein kinase; epididymis secretory protein Li 28; integ ......
Chromosomal Location	11p15.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ILK. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	ILK
Name	integrin-linked kinase
Aliases	HEL-S-28-1; ILK-2; p59ILK; 59 kDa serine/threonine-protein kinase; epididymis secretory protein Li 28; integ ......
Chromosomal Location	11p15.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ILK. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ILK. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ILK
Name	integrin-linked kinase
Aliases	HEL-S-28-1; ILK-2; p59ILK; 59 kDa serine/threonine-protein kinase; epididymis secretory protein Li 28; integ ......
Chromosomal Location	11p15.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ILK. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	ILK
Name	integrin-linked kinase
Aliases	HEL-S-28-1; ILK-2; p59ILK; 59 kDa serine/threonine-protein kinase; epididymis secretory protein Li 28; integ ......
Chromosomal Location	11p15.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ILK expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ILK
Name	integrin-linked kinase
Aliases	HEL-S-28-1; ILK-2; p59ILK; 59 kDa serine/threonine-protein kinase; epididymis secretory protein Li 28; integ ......
Chromosomal Location	11p15.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ILK and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ILK
Name	integrin-linked kinase
Aliases	HEL-S-28-1; ILK-2; p59ILK; 59 kDa serine/threonine-protein kinase; epididymis secretory protein Li 28; integ ......
Chromosomal Location	11p15.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ILK collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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