Scaffold protein ILK

UniProt Q13418 Organism Homo sapiens Gene ILK, ILK1, ILK2

Also known as: ILK, ILK1, ILK2

Function

Scaffold protein which mediates protein-protein interactions during a range of cellular events including focal adhesion assembly, cell adhesion and cell migration. Regulates integrin-mediated signal transduction by contributing to inside-out integrin activation (By similarity). Recruits PARVA and LIMS1/PITCH to form the heterotrimeric IPP (ILK-PINCH-PARVIN) complex which binds to F-actin via the C-terminal tail of LIMS1 and the N-terminal region of PARVA, promoting F-actin filament bundling, a process required to generate force for actin cytoskeleton reorganization and subsequent dynamic cell adhesion events such as cell spreading and migration. Binding to PARVA promotes effective assembly of ILK into focal adhesions while PARVA-bound ILK can simultaneously engage integrin-beta cytoplasmic tails to mediate cell adhesion. Plays a role with PARVG in promoting the cell adhesion and spreading of leukocytes. Acts as an upstream effector of both AKT1/PKB and GSK3. Mediates trafficking of caveolae to the cell surface in an ITGB1-dependent manner by promoting the recruitment of IQGAP1 to the cell cortex which cooperates with its effector DIAPH1 to locally stabilize microtubules and allow stable insertion of caveolae into the plasma membrane (By similarity). Required for the maintenance of mitotic spindle integrity by promoting phosphorylation of TACC3 by AURKA. Associates with chromatin and may act as a negative regulator of transcription when located in the nucleus.

Classification

Family (Pfam): PF12796 Ank_2, PF07714 PK_Tyr_Ser-Thr
InterPro: Ankyrin_rpt, Ankyrin_rpt-contain_sf, Kinase-like_dom_sf, PK_ILK, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ser/Thr_Kinases-Pseudokinases
Functional cluster: Serine/Threonine Protein Kinases

Experimental structures · PDB · 15

2KBX NMR
3F6Q X-ray 1.60A
3IXE X-ray 1.90A
3KMU X-ray 1.80A
3KMW X-ray 2.00A
3REP X-ray 1.80A
4HI8 X-ray 1.20A
4HI9 X-ray 1.20A
6MIB X-ray 1.80A
9D5E X-ray 1.50A
9D5F X-ray 1.50A
9D5G X-ray 1.55A
… and 3 more

A predicted model is available from AlphaFold.

Gene Ontology · 38

Neighborhood · nearest proteins

Nearest neighbours of Scaffold protein ILK: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Scaffold protein ILK 1.00
Scaffold protein ILK 1.00
Scaffold protein ILK 1.00
Scaffold protein ILK 1.00
Scaffold protein ILK 1.00
Scaffold protein ILK 0.98
Integrin-linked protein kinase homolog pat-4 0.91
Integrin-linked protein kinase 1 0.75
Serine/threonine-protein kinase VIK 0.75
Tyrosine-protein kinase HTK16 0.72
Tyrosine-protein kinase CSK 0.72
Tyrosine-protein kinase CSK 0.72

Co-cited proteins · studied together in the literature

LIM and senescent cell antigen-like-containing domain protein 1 5 shared papers
Alpha-parvin 7 shared papers
LIM and senescent cell antigen-like-containing domain protein 2 1 shared papers
LIM domain-containing protein 2 1 shared papers
Beta-parvin 2 shared papers
Laminin subunit alpha-4 1 shared papers
Coiled-coil domain-containing protein 25 1 shared papers
Coiled-coil domain-containing protein 25 1 shared papers
Rho guanine nucleotide exchange factor 6 1 shared papers
Gamma-parvin 1 shared papers
Ephrin type-A receptor 1 1 shared papers
Serine/threonine-protein kinase PAK 1 1 shared papers

Literature · 33 cited papers

ATP allosterically stabilizes integrin-linked kinase for efficient force generation. Proc. Natl. Acad. Sci. U.S.A. · 2022
DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25. Nature · 2020
Non-catalytic signaling by pseudokinase ILK for regulating cell adhesion. Nat. Commun. · 2018
N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
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. Cancer Res. · 2014
N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features. Mol. Cell. Proteomics · 2012
Biochemical, proteomic, structural, and thermodynamic characterizations of integrin-linked kinase (ILK): cross-validation of the pseudokinase. J. Biol. Chem. · 2011
System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
Structural basis for asymmetric association of the betaPIX coiled coil and shank PDZ. J. Mol. Biol. · 2010
The pseudoactive site of ILK is essential for its binding to alpha-parvin and localization to focal adhesions. Mol. Cell · 2009
… and 21 more in the literature graph

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