ILK

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: cytoplasm: a core subcellular location for ILK. Reason: Correct core localization.
GO:0007229 integrin-mediated signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: integrin-mediated signaling pathway: a core biological process for ILK. Reason: Core process consistent with ILK's established function.
GO:0005102 signaling receptor binding	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: signaling receptor binding. Reason: Retained as non-core.
GO:0030154 cell differentiation	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: cell differentiation: process annotation for ILK. Reason: Valid but non-core / secondary.
GO:0030674 protein-macromolecule adaptor activity	IBA GO_REF:0000033	ACCEPT	Summary: Protein-macromolecule adaptor activity: ILK's actual molecular function as the scaffold of the IPP (ILK-PINCH-PARVIN) complex linking integrins to the actin cytoskeleton. Reason: Core molecular function for the pseudokinase scaffold. Retain. Supporting Evidence: file:human/ILK/ILK-uniprot.txt Scaffold protein which mediates protein-protein interactions
GO:0005925 focal adhesion	IBA GO_REF:0000033	ACCEPT	Summary: focal adhesion: a core subcellular location for ILK. Reason: Correct core localization.
GO:0007160 cell-matrix adhesion	IBA GO_REF:0000033	ACCEPT	Summary: cell-matrix adhesion: a core biological process for ILK. Reason: Core process consistent with ILK's established function.
GO:0034446 substrate adhesion-dependent cell spreading	IBA GO_REF:0000033	ACCEPT	Summary: substrate adhesion-dependent cell spreading: a core biological process for ILK. Reason: Core process consistent with ILK's established function.
GO:0004672 protein kinase activity	IEA GO_REF:0000002	REMOVE	Summary: Positive 'protein kinase activity' (IEA) propagated from the protein-kinase-superfamily (TKL) signature. ILK is a pseudokinase with a degenerate catalytic site and no kinase activity. Reason: Electronic over-propagation refuted on biological grounds: ILK is established as a catalytically dead scaffold (the curated NOT\|ser/thr kinase). Remove. Supporting Evidence: file:human/ILK/ILK-uniprot.txt Now thought to be a pseudokinase which does not have kinase activity and which functions solely as a scaffold protein
GO:0005524 ATP binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: ATP binding: ILK's pseudokinase domain still binds ATP/Mg despite lacking catalytic activity (IDA). Reason: Real (structurally demonstrated) nucleotide binding but not catalytic; non-core for a scaffold.
GO:0005634 nucleus	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: nucleus: a secondary/broad localization for ILK. Reason: Plausible but non-core (broad term or context-specific).
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: cytoplasm: a core subcellular location for ILK. Reason: Correct core localization.
GO:0005813 centrosome	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: centrosome: a secondary/broad localization for ILK. Reason: Plausible but non-core (broad term or context-specific).
GO:0005886 plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: plasma membrane: a core subcellular location for ILK. Reason: Correct core localization.
GO:0005925 focal adhesion	IEA GO_REF:0000120	ACCEPT	Summary: focal adhesion: a core subcellular location for ILK. Reason: Correct core localization.
GO:0005938 cell cortex	IEA GO_REF:0000044	ACCEPT	Summary: cell cortex: a core subcellular location for ILK. Reason: Correct core localization.
GO:0009653 anatomical structure morphogenesis	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: anatomical structure morphogenesis: process annotation for ILK. Reason: Valid but non-core / secondary.
GO:0030017 sarcomere	IEA GO_REF:0000044	ACCEPT	Summary: sarcomere: a core subcellular location for ILK. Reason: Correct core localization.
GO:0030027 lamellipodium	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: lamellipodium: a secondary/broad localization for ILK. Reason: Plausible but non-core (broad term or context-specific).
GO:0005515 protein binding	IPI PMID:11331308 A new focal adhesion protein that interacts with integrin-li...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:11331308) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005515 protein binding	IPI PMID:11331582 Modulation of integrin signal transduction by ILKAP, a prote...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:11331582) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005515 protein binding	IPI PMID:12432066 Assembly of the PINCH-ILK-CH-ILKBP complex precedes and is e...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:12432066) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005515 protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:16189514) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005515 protein binding	IPI PMID:16936772 Integrin-linked kinase interacts with caspase-9 and -8 in an...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:16936772) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005515 protein binding	IPI PMID:17003112 Posttranslational hydroxylation of ankyrin repeats in Ikappa...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:17003112) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005515 protein binding	IPI PMID:17553790 Interaction of integrin-linked kinase with the kidney chlori...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:17553790) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005515 protein binding	IPI PMID:18339839 Rictor and integrin-linked kinase interact and regulate Akt ...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:18339839) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005515 protein binding	IPI PMID:19074270 The structural basis of integrin-linked kinase-PINCH interac...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:19074270) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005515 protein binding	IPI PMID:21516116 Next-generation sequencing to generate interactome datasets.	MARK AS OVER ANNOTATED	Summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:21516116). Reason: High-throughput protein binding is uninformative about molecular function (curation guideline). Over-annotation.
GO:0005515 protein binding	IPI PMID:21643011 Phosphorylation and interaction of myopodin by integrin-link...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:21643011) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005515 protein binding	IPI PMID:22939624 Quantitative analysis of HSP90-client interactions reveals p...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:22939624) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005515 protein binding	IPI PMID:23414517 A human skeletal muscle interactome centered on proteins inv...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:23414517) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005515 protein binding	IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein...	MARK AS OVER ANNOTATED	Summary: Specific protein interaction (PMID:23455922) consistent with ILK's scaffold/adapter role. Reason: Large-scale standardized AP-MS protein-complex study; high-throughput generic protein binding, grouped with the other HT-screen over-annotations for consistency.
GO:0005515 protein binding	IPI PMID:23877428 Interaction of smoothened with integrin-linked kinase in pri...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:23877428) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:25416956). Reason: High-throughput protein binding is uninformative about molecular function (curation guideline). Over-annotation.
GO:0005515 protein binding	IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:25502805) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005515 protein binding	IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:25852190) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005515 protein binding	IPI PMID:26496610 A human interactome in three quantitative dimensions organiz...	MARK AS OVER ANNOTATED	Summary: Specific protein interaction (PMID:26496610) consistent with ILK's scaffold/adapter role. Reason: Large-scale quantitative interactome study ('A human interactome in three quantitative dimensions'); generic protein binding from a high-throughput screen is uninformative about molecular function. Grouped with the other HT-screen over-annotations.
GO:0005515 protein binding	IPI PMID:26972000 Substrate-Trapped Interactors of PHD3 and FIH Cluster in Dis...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:26972000) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:28514442). Reason: High-throughput protein binding is uninformative about molecular function (curation guideline). Over-annotation.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	MARK AS OVER ANNOTATED	Summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:31515488). Reason: High-throughput protein binding is uninformative about molecular function (curation guideline). Over-annotation.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:32296183). Reason: High-throughput protein binding is uninformative about molecular function (curation guideline). Over-annotation.
GO:0005515 protein binding	IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:32707033) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:33961781). Reason: High-throughput protein binding is uninformative about molecular function (curation guideline). Over-annotation.
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:35271311) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005515 protein binding	IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:36931259) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:40205054). Reason: High-throughput protein binding is uninformative about molecular function (curation guideline). Over-annotation.
GO:0003151 outflow tract morphogenesis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: outflow tract morphogenesis: process annotation for ILK. Reason: Valid but non-core / secondary.
GO:0007229 integrin-mediated signaling pathway	IEA GO_REF:0000120	ACCEPT	Summary: integrin-mediated signaling pathway: a core biological process for ILK. Reason: Core process consistent with ILK's established function.
GO:0030513 positive regulation of BMP signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of BMP signaling pathway: process annotation for ILK. Reason: Valid but non-core / secondary.
GO:0045669 positive regulation of osteoblast differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of osteoblast differentiation: process annotation for ILK. Reason: Valid but non-core / secondary.
GO:0070836 caveola assembly	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: caveola assembly: process annotation for ILK. Reason: Valid but non-core / secondary.
GO:0072697 protein localization to cell cortex	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: protein localization to cell cortex: process annotation for ILK. Reason: ILK's primary site is focal adhesions, not the broad cell cortex; keep as non-core for consistency with the caveola assembly annotation.
GO:0005925 focal adhesion	NAS PMID:35089438 Integrin-linked kinase (ILK): the known vs. the unknown and ...	ACCEPT	Summary: focal adhesion: a core subcellular location for ILK. Reason: Correct core localization.
GO:0051017 actin filament bundle assembly	IDA PMID:30367047 Non-catalytic signaling by pseudokinase ILK for regulating c...	KEEP AS NON CORE	Summary: actin filament bundle assembly: process annotation for ILK. Reason: Valid but non-core / secondary.
GO:0051639 actin filament network formation	IDA PMID:30367047 Non-catalytic signaling by pseudokinase ILK for regulating c...	KEEP AS NON CORE	Summary: actin filament network formation: process annotation for ILK. Reason: Valid but non-core / secondary.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: cytosol: a core subcellular location for ILK. Reason: Correct core localization.
GO:0005925 focal adhesion	IDA GO_REF:0000052	ACCEPT	Summary: focal adhesion: a core subcellular location for ILK. Reason: Correct core localization.
GO:0005886 plasma membrane	EXP PMID:11402068 A novel integrin-linked kinase-binding protein, affixin, is ...	ACCEPT	Summary: plasma membrane: a core subcellular location for ILK. Reason: Correct core localization.
GO:0007229 integrin-mediated signaling pathway	ISS PMID:20675382 CYR61 regulates BMP-2-dependent osteoblast differentiation t...	ACCEPT	Summary: integrin-mediated signaling pathway: a core biological process for ILK. Reason: Core process consistent with ILK's established function.
GO:0000785 chromatin	IDA PMID:17420447 Phosphorylation-dependent regulation of nuclear localization...	KEEP AS NON CORE	Summary: chromatin: a secondary/broad localization for ILK. Reason: Plausible but non-core (broad term or context-specific).
GO:0005634 nucleus	IDA PMID:17420447 Phosphorylation-dependent regulation of nuclear localization...	KEEP AS NON CORE	Summary: nucleus: a secondary/broad localization for ILK. Reason: Plausible but non-core (broad term or context-specific).
GO:0005737 cytoplasm	IDA PMID:17420447 Phosphorylation-dependent regulation of nuclear localization...	ACCEPT	Summary: cytoplasm: a core subcellular location for ILK. Reason: Correct core localization.
GO:0005813 centrosome	IDA PMID:18283114 Integrin-linked kinase localizes to the centrosome and regul...	KEEP AS NON CORE	Summary: centrosome: a secondary/broad localization for ILK. Reason: Plausible but non-core (broad term or context-specific).
GO:0007052 mitotic spindle organization	IMP PMID:18283114 Integrin-linked kinase localizes to the centrosome and regul...	KEEP AS NON CORE	Summary: mitotic spindle organization: process annotation for ILK. Reason: Valid but non-core / secondary.
GO:0000287 magnesium ion binding	IDA PMID:20005845 The pseudoactive site of ILK is essential for its binding to...	KEEP AS NON CORE	Summary: Magnesium ion binding (IDA) by the pseudokinase domain, associated with ATP binding. Reason: Real but non-core (no catalytic role).
GO:0004674 protein serine/threonine kinase activity	IDA NOT PMID:20005845 The pseudoactive site of ILK is essential for its binding to...	ACCEPT	Summary: NOT: ILK does not have protein serine/threonine kinase activity. Structural and biochemical work established it as a pseudokinase scaffold (UniProt now names it 'Scaffold protein ILK'). Reason: Correct, important negation supported by direct evidence (IDA). Retain. Supporting Evidence: file:human/ILK/ILK-uniprot.txt Now thought to be a pseudokinase which does not have kinase activity and which functions solely as a scaffold protein
GO:0004674 protein serine/threonine kinase activity	IDA NOT PMID:21524996 Biochemical, proteomic, structural, and thermodynamic charac...	ACCEPT	Summary: NOT: ILK does not have protein serine/threonine kinase activity. Structural and biochemical work established it as a pseudokinase scaffold (UniProt now names it 'Scaffold protein ILK'). Reason: Correct, important negation supported by direct evidence (IDA). Retain. Supporting Evidence: file:human/ILK/ILK-uniprot.txt Now thought to be a pseudokinase which does not have kinase activity and which functions solely as a scaffold protein
GO:0005178 integrin binding	IDA PMID:20005845 The pseudoactive site of ILK is essential for its binding to...	ACCEPT	Summary: Integrin binding (IDA): ILK binds integrin beta cytoplasmic tails, central to its focal-adhesion scaffold role. Reason: Core, experimentally supported interaction defining ILK's adhesion function.
GO:0005515 protein binding	IPI PMID:20005845 The pseudoactive site of ILK is essential for its binding to...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:20005845) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005524 ATP binding	IDA PMID:20005845 The pseudoactive site of ILK is essential for its binding to...	KEEP AS NON CORE	Summary: ATP binding: ILK's pseudokinase domain still binds ATP/Mg despite lacking catalytic activity (IDA). Reason: Real (structurally demonstrated) nucleotide binding but not catalytic; non-core for a scaffold.
GO:0005524 ATP binding	IDA PMID:21524996 Biochemical, proteomic, structural, and thermodynamic charac...	KEEP AS NON CORE	Summary: ATP binding: ILK's pseudokinase domain still binds ATP/Mg despite lacking catalytic activity (IDA). Reason: Real (structurally demonstrated) nucleotide binding but not catalytic; non-core for a scaffold.
GO:0043123 positive regulation of canonical NF-kappaB signal transduction	IMP PMID:21343177 Thymosin beta4 inhibits TNF-alpha-induced NF-kappaB activati...	KEEP AS NON CORE	Summary: positive regulation of canonical NF-kappaB signal transduction: process annotation for ILK. Reason: Valid but non-core / secondary.
GO:1900026 positive regulation of substrate adhesion-dependent cell spreading	IGI PMID:30254023 Kindlin-2 interacts with a highly conserved surface of ILK t...	ACCEPT	Summary: positive regulation of substrate adhesion-dependent cell spreading: a core biological process for ILK. Reason: Core process consistent with ILK's established function.
GO:0000902 cell morphogenesis	IMP PMID:30254023 Kindlin-2 interacts with a highly conserved surface of ILK t...	KEEP AS NON CORE	Summary: cell morphogenesis: process annotation for ILK. Reason: Valid but non-core / secondary.
GO:0005515 protein binding	IPI PMID:30254023 Kindlin-2 interacts with a highly conserved surface of ILK t...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:30254023) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0005925 focal adhesion	IDA PMID:30254023 Kindlin-2 interacts with a highly conserved surface of ILK t...	ACCEPT	Summary: focal adhesion: a core subcellular location for ILK. Reason: Correct core localization.
GO:0005515 protein binding	IPI PMID:15817463 Actopaxin interacts with TESK1 to regulate cell spreading on...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:15817463) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0033209 tumor necrosis factor-mediated signaling pathway	IMP PMID:21343177 Thymosin beta4 inhibits TNF-alpha-induced NF-kappaB activati...	KEEP AS NON CORE	Summary: tumor necrosis factor-mediated signaling pathway: process annotation for ILK. Reason: Valid but non-core / secondary.
GO:0009967 positive regulation of signal transduction	IMP PMID:10637513 Integrin-linked kinase regulates phosphorylation of serine 4...	KEEP AS NON CORE	Summary: positive regulation of signal transduction: process annotation for ILK. Reason: Valid but non-core / secondary.
GO:0005515 protein binding	IPI PMID:20926685 The roles of two distinct regions of PINCH-1 in the regulati...	KEEP AS NON CORE	Summary: Specific protein interaction (PMID:20926685) consistent with ILK's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative.
GO:0070527 platelet aggregation	HMP PMID:23382103 Platelet proteome analysis reveals integrin-dependent aggreg...	KEEP AS NON CORE	Summary: platelet aggregation: process annotation for ILK. Reason: Valid but non-core / secondary.
GO:0005925 focal adhesion	HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome...	ACCEPT	Summary: focal adhesion: a core subcellular location for ILK. Reason: Correct core localization.
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	KEEP AS NON CORE	Summary: membrane: a secondary/broad localization for ILK. Reason: Plausible but non-core (broad term or context-specific).
GO:0005829 cytosol	TAS Reactome:R-HSA-432897	ACCEPT	Summary: cytosol: a core subcellular location for ILK. Reason: Correct core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-446391	ACCEPT	Summary: cytosol: a core subcellular location for ILK. Reason: Correct core localization.
GO:0019901 protein kinase binding	IPI PMID:19118217 EphA1 interacts with integrin-linked kinase and regulates ce...	KEEP AS NON CORE	Summary: Protein kinase binding (IPI): ILK scaffolds/associates with kinases at adhesions. Reason: Specific interaction supporting the scaffold role; non-core.
GO:0034446 substrate adhesion-dependent cell spreading	IMP PMID:19118217 EphA1 interacts with integrin-linked kinase and regulates ce...	ACCEPT	Summary: substrate adhesion-dependent cell spreading: a core biological process for ILK. Reason: Core process consistent with ILK's established function.
GO:0045893 positive regulation of DNA-templated transcription	IMP PMID:20018240 Type I collagen promotes epithelial-mesenchymal transition t...	KEEP AS NON CORE	Summary: positive regulation of DNA-templated transcription: process annotation for ILK. Reason: Valid but non-core / secondary.
GO:0090263 positive regulation of canonical Wnt signaling pathway	IMP PMID:20018240 Type I collagen promotes epithelial-mesenchymal transition t...	KEEP AS NON CORE	Summary: positive regulation of canonical Wnt signaling pathway: process annotation for ILK. Reason: Valid but non-core / secondary.
GO:0007160 cell-matrix adhesion	TAS PMID:8538749 Regulation of cell adhesion and anchorage-dependent growth b...	ACCEPT	Summary: cell-matrix adhesion: a core biological process for ILK. Reason: Core process consistent with ILK's established function.
GO:0007229 integrin-mediated signaling pathway	IDA PMID:9366252 Identification and characterization of a mouse protein kinas...	ACCEPT	Summary: integrin-mediated signaling pathway: a core biological process for ILK. Reason: Core process consistent with ILK's established function.

📄 View Raw YAML

# yaml-language-server: $schema=../../../src/ai_gene_review/schema/gene_review.yaml
id: Q13418
gene_symbol: ILK
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: ILK (integrin-linked kinase; now annotated by UniProt as 'Scaffold protein ILK') is a focal-adhesion
  protein of the protein-kinase superfamily that is catalytically dead - a pseudokinase. Rather than phosphorylating
  substrates, it functions as the central scaffold of the heterotrimeric IPP (ILK-PINCH-PARVIN) complex,
  linking integrin cytoplasmic tails to the actin cytoskeleton and coordinating cell-matrix adhesion,
  spreading, and integrin/growth-factor signaling. Its pseudokinase domain still binds ATP/Mg but performs
  no catalysis. ILK is essential for focal-adhesion organization, actin filament assembly, and is implicated
  in cardiac/muscle function and cancer.
alternative_products:
- name: '1'
  id: Q13418-1
- name: '2'
  id: Q13418-2
  sequence_note: VSP_054920
- name: '3'
  id: Q13418-3
  sequence_note: VSP_055925
existing_annotations:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: 'cytoplasm: a core subcellular location for ILK.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0007229
    label: integrin-mediated signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: 'integrin-mediated signaling pathway: a core biological process for ILK.'
    action: ACCEPT
    reason: Core process consistent with ILK's established function.
- term:
    id: GO:0005102
    label: signaling receptor binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: signaling receptor binding.
    action: KEEP_AS_NON_CORE
    reason: Retained as non-core.
- term:
    id: GO:0030154
    label: cell differentiation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: 'cell differentiation: process annotation for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core / secondary.
- term:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: 'Protein-macromolecule adaptor activity: ILK''s actual molecular function as the scaffold
      of the IPP (ILK-PINCH-PARVIN) complex linking integrins to the actin cytoskeleton.'
    action: ACCEPT
    reason: Core molecular function for the pseudokinase scaffold. Retain.
    supported_by:
    - reference_id: file:human/ILK/ILK-uniprot.txt
      supporting_text: Scaffold protein which mediates protein-protein interactions
- term:
    id: GO:0005925
    label: focal adhesion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: 'focal adhesion: a core subcellular location for ILK.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0007160
    label: cell-matrix adhesion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: 'cell-matrix adhesion: a core biological process for ILK.'
    action: ACCEPT
    reason: Core process consistent with ILK's established function.
- term:
    id: GO:0034446
    label: substrate adhesion-dependent cell spreading
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: 'substrate adhesion-dependent cell spreading: a core biological process for ILK.'
    action: ACCEPT
    reason: Core process consistent with ILK's established function.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Positive 'protein kinase activity' (IEA) propagated from the protein-kinase-superfamily (TKL)
      signature. ILK is a pseudokinase with a degenerate catalytic site and no kinase activity.
    action: REMOVE
    reason: 'Electronic over-propagation refuted on biological grounds: ILK is established as a catalytically
      dead scaffold (the curated NOT|ser/thr kinase). Remove.'
    supported_by:
    - reference_id: file:human/ILK/ILK-uniprot.txt
      supporting_text: Now thought to be a pseudokinase which does not have kinase activity and which
        functions solely as a scaffold protein
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: 'ATP binding: ILK''s pseudokinase domain still binds ATP/Mg despite lacking catalytic activity
      (IDA).'
    action: KEEP_AS_NON_CORE
    reason: Real (structurally demonstrated) nucleotide binding but not catalytic; non-core for a scaffold.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'nucleus: a secondary/broad localization for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'cytoplasm: a core subcellular location for ILK.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'centrosome: a secondary/broad localization for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'plasma membrane: a core subcellular location for ILK.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0005925
    label: focal adhesion
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: 'focal adhesion: a core subcellular location for ILK.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0005938
    label: cell cortex
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'cell cortex: a core subcellular location for ILK.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0009653
    label: anatomical structure morphogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: 'anatomical structure morphogenesis: process annotation for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core / secondary.
- term:
    id: GO:0030017
    label: sarcomere
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'sarcomere: a core subcellular location for ILK.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0030027
    label: lamellipodium
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: 'lamellipodium: a secondary/broad localization for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11331308
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:11331308) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11331582
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:11331582) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12432066
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:12432066) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16189514
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:16189514) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16936772
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:16936772) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17003112
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:17003112) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17553790
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:17553790) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18339839
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:18339839) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19074270
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:19074270) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21516116
  qualifier: enables
  review:
    summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:21516116).
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput protein binding is uninformative about molecular function (curation guideline).
      Over-annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21643011
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:21643011) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22939624
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:22939624) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23414517
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:23414517) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23455922
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:23455922) consistent with ILK's scaffold/adapter role.
    action: MARK_AS_OVER_ANNOTATED
    reason: Large-scale standardized AP-MS protein-complex study; high-throughput generic protein binding,
      grouped with the other HT-screen over-annotations for consistency.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23877428
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:23877428) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:25416956).
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput protein binding is uninformative about molecular function (curation guideline).
      Over-annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25502805
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:25502805) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25852190
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:25852190) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26496610
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:26496610) consistent with ILK's scaffold/adapter role.
    action: MARK_AS_OVER_ANNOTATED
    reason: Large-scale quantitative interactome study ('A human interactome in three quantitative dimensions');
      generic protein binding from a high-throughput screen is uninformative about molecular function.
      Grouped with the other HT-screen over-annotations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26972000
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:26972000) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:28514442).
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput protein binding is uninformative about molecular function (curation guideline).
      Over-annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:31515488).
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput protein binding is uninformative about molecular function (curation guideline).
      Over-annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:32296183).
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput protein binding is uninformative about molecular function (curation guideline).
      Over-annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32707033
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:32707033) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:33961781).
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput protein binding is uninformative about molecular function (curation guideline).
      Over-annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:35271311) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36931259
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:36931259) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:40205054).
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput protein binding is uninformative about molecular function (curation guideline).
      Over-annotation.
- term:
    id: GO:0003151
    label: outflow tract morphogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'outflow tract morphogenesis: process annotation for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core / secondary.
- term:
    id: GO:0007229
    label: integrin-mediated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: 'integrin-mediated signaling pathway: a core biological process for ILK.'
    action: ACCEPT
    reason: Core process consistent with ILK's established function.
- term:
    id: GO:0030513
    label: positive regulation of BMP signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'positive regulation of BMP signaling pathway: process annotation for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core / secondary.
- term:
    id: GO:0045669
    label: positive regulation of osteoblast differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'positive regulation of osteoblast differentiation: process annotation for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core / secondary.
- term:
    id: GO:0070836
    label: caveola assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'caveola assembly: process annotation for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core / secondary.
- term:
    id: GO:0072697
    label: protein localization to cell cortex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'protein localization to cell cortex: process annotation for ILK.'
    action: KEEP_AS_NON_CORE
    reason: ILK's primary site is focal adhesions, not the broad cell cortex; keep as non-core for consistency
      with the caveola assembly annotation.
- term:
    id: GO:0005925
    label: focal adhesion
  evidence_type: NAS
  original_reference_id: PMID:35089438
  qualifier: located_in
  review:
    summary: 'focal adhesion: a core subcellular location for ILK.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0051017
    label: actin filament bundle assembly
  evidence_type: IDA
  original_reference_id: PMID:30367047
  qualifier: involved_in
  review:
    summary: 'actin filament bundle assembly: process annotation for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core / secondary.
- term:
    id: GO:0051639
    label: actin filament network formation
  evidence_type: IDA
  original_reference_id: PMID:30367047
  qualifier: involved_in
  review:
    summary: 'actin filament network formation: process annotation for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core / secondary.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: 'cytosol: a core subcellular location for ILK.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0005925
    label: focal adhesion
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: 'focal adhesion: a core subcellular location for ILK.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: EXP
  original_reference_id: PMID:11402068
  qualifier: located_in
  review:
    summary: 'plasma membrane: a core subcellular location for ILK.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0007229
    label: integrin-mediated signaling pathway
  evidence_type: ISS
  original_reference_id: PMID:20675382
  qualifier: involved_in
  review:
    summary: 'integrin-mediated signaling pathway: a core biological process for ILK.'
    action: ACCEPT
    reason: Core process consistent with ILK's established function.
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: IDA
  original_reference_id: PMID:17420447
  qualifier: located_in
  review:
    summary: 'chromatin: a secondary/broad localization for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:17420447
  qualifier: located_in
  review:
    summary: 'nucleus: a secondary/broad localization for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:17420447
  qualifier: located_in
  review:
    summary: 'cytoplasm: a core subcellular location for ILK.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IDA
  original_reference_id: PMID:18283114
  qualifier: located_in
  review:
    summary: 'centrosome: a secondary/broad localization for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0007052
    label: mitotic spindle organization
  evidence_type: IMP
  original_reference_id: PMID:18283114
  qualifier: involved_in
  review:
    summary: 'mitotic spindle organization: process annotation for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core / secondary.
- term:
    id: GO:0000287
    label: magnesium ion binding
  evidence_type: IDA
  original_reference_id: PMID:20005845
  qualifier: enables
  review:
    summary: Magnesium ion binding (IDA) by the pseudokinase domain, associated with ATP binding.
    action: KEEP_AS_NON_CORE
    reason: Real but non-core (no catalytic role).
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:20005845
  qualifier: enables
  negated: true
  review:
    summary: 'NOT: ILK does not have protein serine/threonine kinase activity. Structural and biochemical
      work established it as a pseudokinase scaffold (UniProt now names it ''Scaffold protein ILK'').'
    action: ACCEPT
    reason: Correct, important negation supported by direct evidence (IDA). Retain.
    supported_by: &id001
    - reference_id: file:human/ILK/ILK-uniprot.txt
      supporting_text: Now thought to be a pseudokinase which does not have kinase activity and which
        functions solely as a scaffold protein
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:21524996
  qualifier: enables
  negated: true
  review:
    summary: 'NOT: ILK does not have protein serine/threonine kinase activity. Structural and biochemical
      work established it as a pseudokinase scaffold (UniProt now names it ''Scaffold protein ILK'').'
    action: ACCEPT
    reason: Correct, important negation supported by direct evidence (IDA). Retain.
    supported_by: *id001
- term:
    id: GO:0005178
    label: integrin binding
  evidence_type: IDA
  original_reference_id: PMID:20005845
  qualifier: enables
  review:
    summary: 'Integrin binding (IDA): ILK binds integrin beta cytoplasmic tails, central to its focal-adhesion
      scaffold role.'
    action: ACCEPT
    reason: Core, experimentally supported interaction defining ILK's adhesion function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20005845
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:20005845) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IDA
  original_reference_id: PMID:20005845
  qualifier: enables
  review:
    summary: 'ATP binding: ILK''s pseudokinase domain still binds ATP/Mg despite lacking catalytic activity
      (IDA).'
    action: KEEP_AS_NON_CORE
    reason: Real (structurally demonstrated) nucleotide binding but not catalytic; non-core for a scaffold.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IDA
  original_reference_id: PMID:21524996
  qualifier: enables
  review:
    summary: 'ATP binding: ILK''s pseudokinase domain still binds ATP/Mg despite lacking catalytic activity
      (IDA).'
    action: KEEP_AS_NON_CORE
    reason: Real (structurally demonstrated) nucleotide binding but not catalytic; non-core for a scaffold.
- term:
    id: GO:0043123
    label: positive regulation of canonical NF-kappaB signal transduction
  evidence_type: IMP
  original_reference_id: PMID:21343177
  qualifier: involved_in
  review:
    summary: 'positive regulation of canonical NF-kappaB signal transduction: process annotation for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core / secondary.
- term:
    id: GO:1900026
    label: positive regulation of substrate adhesion-dependent cell spreading
  evidence_type: IGI
  original_reference_id: PMID:30254023
  qualifier: involved_in
  review:
    summary: 'positive regulation of substrate adhesion-dependent cell spreading: a core biological process
      for ILK.'
    action: ACCEPT
    reason: Core process consistent with ILK's established function.
- term:
    id: GO:0000902
    label: cell morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:30254023
  qualifier: acts_upstream_of_or_within
  review:
    summary: 'cell morphogenesis: process annotation for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core / secondary.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30254023
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:30254023) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0005925
    label: focal adhesion
  evidence_type: IDA
  original_reference_id: PMID:30254023
  qualifier: located_in
  review:
    summary: 'focal adhesion: a core subcellular location for ILK.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15817463
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:15817463) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0033209
    label: tumor necrosis factor-mediated signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:21343177
  qualifier: involved_in
  review:
    summary: 'tumor necrosis factor-mediated signaling pathway: process annotation for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core / secondary.
- term:
    id: GO:0009967
    label: positive regulation of signal transduction
  evidence_type: IMP
  original_reference_id: PMID:10637513
  qualifier: involved_in
  review:
    summary: 'positive regulation of signal transduction: process annotation for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core / secondary.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20926685
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:20926685) consistent with ILK's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0070527
    label: platelet aggregation
  evidence_type: HMP
  original_reference_id: PMID:23382103
  qualifier: involved_in
  review:
    summary: 'platelet aggregation: process annotation for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core / secondary.
- term:
    id: GO:0005925
    label: focal adhesion
  evidence_type: HDA
  original_reference_id: PMID:21423176
  qualifier: located_in
  review:
    summary: 'focal adhesion: a core subcellular location for ILK.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: 'membrane: a secondary/broad localization for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-432897
  qualifier: located_in
  review:
    summary: 'cytosol: a core subcellular location for ILK.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-446391
  qualifier: located_in
  review:
    summary: 'cytosol: a core subcellular location for ILK.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0019901
    label: protein kinase binding
  evidence_type: IPI
  original_reference_id: PMID:19118217
  qualifier: enables
  review:
    summary: 'Protein kinase binding (IPI): ILK scaffolds/associates with kinases at adhesions.'
    action: KEEP_AS_NON_CORE
    reason: Specific interaction supporting the scaffold role; non-core.
- term:
    id: GO:0034446
    label: substrate adhesion-dependent cell spreading
  evidence_type: IMP
  original_reference_id: PMID:19118217
  qualifier: involved_in
  review:
    summary: 'substrate adhesion-dependent cell spreading: a core biological process for ILK.'
    action: ACCEPT
    reason: Core process consistent with ILK's established function.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IMP
  original_reference_id: PMID:20018240
  qualifier: involved_in
  review:
    summary: 'positive regulation of DNA-templated transcription: process annotation for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core / secondary.
- term:
    id: GO:0090263
    label: positive regulation of canonical Wnt signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:20018240
  qualifier: involved_in
  review:
    summary: 'positive regulation of canonical Wnt signaling pathway: process annotation for ILK.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core / secondary.
- term:
    id: GO:0007160
    label: cell-matrix adhesion
  evidence_type: TAS
  original_reference_id: PMID:8538749
  qualifier: involved_in
  review:
    summary: 'cell-matrix adhesion: a core biological process for ILK.'
    action: ACCEPT
    reason: Core process consistent with ILK's established function.
- term:
    id: GO:0007229
    label: integrin-mediated signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:9366252
  qualifier: acts_upstream_of_or_within
  review:
    summary: 'integrin-mediated signaling pathway: a core biological process for ILK.'
    action: ACCEPT
    reason: Core process consistent with ILK's established function.
references:
- id: GO_REF:0000002
  title: GO annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified annotations to orthologs by curator judgment
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: GO annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
  findings: []
- id: GO_REF:0000052
  title: GO annotation based on curation of immunofluorescence data (HPA)
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl
    Compara
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on inter-ontology links
  findings: []
- id: GO_REF:0000117
  title: Automatic GO annotation from UniProtKB-KW mapping
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: file:human/ILK/ILK-uniprot.txt
  title: UniProt entry for ILK
  findings: []
- id: PMID:10637513
  title: Integrin-linked kinase regulates phosphorylation of serine 473 of protein kinase B by an indirect
    mechanism.
  findings: []
- id: PMID:11331308
  title: A new focal adhesion protein that interacts with integrin-linked kinase and regulates cell adhesion
    and spreading.
  findings: []
- id: PMID:11331582
  title: Modulation of integrin signal transduction by ILKAP, a protein phosphatase 2C associating with
    the integrin-linked kinase, ILK1.
  findings: []
- id: PMID:11402068
  title: A novel integrin-linked kinase-binding protein, affixin, is involved in the early stage of cell-substrate
    interaction.
  findings: []
- id: PMID:12432066
  title: Assembly of the PINCH-ILK-CH-ILKBP complex precedes and is essential for localization of each
    component to cell-matrix adhesion sites.
  findings: []
- id: PMID:15817463
  title: Actopaxin interacts with TESK1 to regulate cell spreading on fibronectin.
  findings: []
- id: PMID:16189514
  title: Towards a proteome-scale map of the human protein-protein interaction network.
  findings: []
- id: PMID:16936772
  title: Integrin-linked kinase interacts with caspase-9 and -8 in an adhesion-dependent manner for promoting
    radiation-induced apoptosis in human leukemia cells.
  findings: []
- id: PMID:17003112
  title: Posttranslational hydroxylation of ankyrin repeats in IkappaB proteins by the hypoxia-inducible
    factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH).
  findings: []
- id: PMID:17420447
  title: Phosphorylation-dependent regulation of nuclear localization and functions of integrin-linked
    kinase.
  findings: []
- id: PMID:17553790
  title: Interaction of integrin-linked kinase with the kidney chloride/bicarbonate exchanger, kAE1.
  findings: []
- id: PMID:18283114
  title: Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization.
  findings: []
- id: PMID:18339839
  title: Rictor and integrin-linked kinase interact and regulate Akt phosphorylation and cancer cell survival.
  findings: []
- id: PMID:19074270
  title: The structural basis of integrin-linked kinase-PINCH interactions.
  findings: []
- id: PMID:19118217
  title: EphA1 interacts with integrin-linked kinase and regulates cell morphology and motility.
  findings: []
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
- id: PMID:20005845
  title: The pseudoactive site of ILK is essential for its binding to alpha-Parvin and localization to
    focal adhesions.
  findings: []
- id: PMID:20018240
  title: Type I collagen promotes epithelial-mesenchymal transition through ILK-dependent activation of
    NF-kappaB and LEF-1.
  findings: []
- id: PMID:20675382
  title: CYR61 regulates BMP-2-dependent osteoblast differentiation through the {alpha}v{beta}3 integrin/integrin-linked
    kinase/ERK pathway.
  findings: []
- id: PMID:20926685
  title: The roles of two distinct regions of PINCH-1 in the regulation of cell attachment and spreading.
  findings: []
- id: PMID:21343177
  title: Thymosin beta4 inhibits TNF-alpha-induced NF-kappaB activation, IL-8 expression, and the sensitizing
    effects by its partners PINCH-1 and ILK.
  findings: []
- id: PMID:21423176
  title: Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative
    regulation of focal adhesion maturation.
  findings: []
- id: PMID:21516116
  title: Next-generation sequencing to generate interactome datasets.
  findings: []
- id: PMID:21524996
  title: 'Biochemical, proteomic, structural, and thermodynamic characterizations of integrin-linked kinase
    (ILK): cross-validation of the pseudokinase.'
  findings: []
- id: PMID:21643011
  title: Phosphorylation and interaction of myopodin by integrin-link kinase lead to suppression of cell
    growth and motility in prostate cancer cells.
  findings: []
- id: PMID:22939624
  title: Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition.
  findings: []
- id: PMID:23382103
  title: Platelet proteome analysis reveals integrin-dependent aggregation defects in patients with myelodysplastic
    syndromes.
  findings: []
- id: PMID:23414517
  title: 'A human skeletal muscle interactome centered on proteins involved in muscular dystrophies: LGMD
    interactome.'
  findings: []
- id: PMID:23455922
  title: Interlaboratory reproducibility of large-scale human protein-complex analysis by standardized
    AP-MS.
  findings: []
- id: PMID:23877428
  title: Interaction of smoothened with integrin-linked kinase in primary cilia mediates Hedgehog signalling.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:25502805
  title: A massively parallel pipeline to clone DNA variants and examine molecular phenotypes of human
    disease mutations.
  findings: []
- id: PMID:25852190
  title: Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential
    targets for combination therapy.
  findings: []
- id: PMID:26496610
  title: A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
  findings: []
- id: PMID:26972000
  title: Substrate-Trapped Interactors of PHD3 and FIH Cluster in Distinct Signaling Pathways.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease networks.
  findings: []
- id: PMID:30254023
  title: Kindlin-2 interacts with a highly conserved surface of ILK to regulate focal adhesion localization
    and cell spreading.
  findings: []
- id: PMID:30367047
  title: Non-catalytic signaling by pseudokinase ILK for regulating cell adhesion.
  findings: []
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the allele frequency
    spectrum in human populations.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32707033
  title: Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:35089438
  title: 'Integrin-linked kinase (ILK): the known vs. the unknown and perspectives.'
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:36931259
  title: A central chaperone-like role for 14-3-3 proteins in human cells.
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: PMID:8538749
  title: Regulation of cell adhesion and anchorage-dependent growth by a new beta 1-integrin-linked protein
    kinase.
  findings: []
- id: PMID:9366252
  title: Identification and characterization of a mouse protein kinase that is highly homologous to human
    integrin-linked kinase.
  findings: []
- id: Reactome:R-HSA-432897
  title: Reactome pathway
  findings: []
- id: Reactome:R-HSA-446391
  title: Reactome pathway
  findings: []
aliases:
- ILK1
- ILK2
- P59-ILK
- Integrin-linked protein kinase
- Scaffold protein ILK
core_functions:
- description: Catalytically dead pseudokinase that acts as the scaffold of the IPP (ILK-PINCH-PARVIN)
    complex at focal adhesions, coupling integrins to the actin cytoskeleton and coordinating cell-matrix
    adhesion and spreading.
  molecular_function:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  directly_involved_in:
  - id: GO:0007229
    label: integrin-mediated signaling pathway
  - id: GO:0007160
    label: cell-matrix adhesion
  locations:
  - id: GO:0005925
    label: focal adhesion
  supported_by:
  - reference_id: file:human/ILK/ILK-uniprot.txt
    supporting_text: Now thought to be a pseudokinase which does not have kinase activity and which functions
      solely as a scaffold protein
suggested_questions:
- question: Given ILK is a pseudokinase, are any residual phenotypes attributed to 'ILK kinase activity'
    in older literature explained entirely by its scaffolding of bona fide kinases?
suggested_experiments:
- hypothesis: ILK's adhesion functions are scaffold-dependent and kinase-activity-independent.
  description: Rescue ILK-null cells with wild-type vs IPP-binding-deficient ILK and assess focal-adhesion
    assembly and spreading.

Gene Description

Existing Annotations Review

Core Functions

Catalytically dead pseudokinase that acts as the scaffold of the IPP (ILK-PINCH-PARVIN) complex at focal adhesions, coupling integrins to the actin cytoskeleton and coordinating cell-matrix adhesion and spreading.

References

Suggested Questions for Experts

Suggested Experiments

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