UniProt functional annotation for Q13418



	UniProt functional annotation for Q13418

UniProt code: Q13418.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Receptor-proximal protein kinase regulating integrin-mediated signal transduction (PubMed:8538749, PubMed:9736715). May act as a mediator of inside-out integrin signaling (PubMed:10712922). Focal adhesion protein part of the complex ILK-PINCH (PubMed:10712922). This complex is considered to be one of the convergence points of integrin- and growth factor-signaling pathway (PubMed:10712922). Could be implicated in mediating cell architecture, adhesion to integrin substrates and anchorage-dependent growth in epithelial cells (PubMed:10712922). Regulates cell motility by forming a complex with PARVB (PubMed:32528174). Phosphorylates beta-1 and beta-3 integrin subunit on serine and threonine residues, but also AKT1 and GSK3B (PubMed:8538749, PubMed:9736715). {ECO:0000269|PubMed:32528174, ECO:0000269|PubMed:8538749, ECO:0000269|PubMed:9736715, ECO:0000303|PubMed:10712922}.

Catalytic activity: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:8538749};

Catalytic activity: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:8538749};

Activity regulation: Stimulated rapidly but transiently by both cell fibronectin interactions, as well as by insulin, in a PI3-K-dependent manner, likely via the binding of PtdIns(3,4,5)P3 with a PH-like domain of ILK. The protein kinase activity is stimulated by LIMD2 (PubMed:24590809). {ECO:0000269|PubMed:24590809}.

Subunit: Interacts with the cytoplasmic domain of ITGB1 (PubMed:10712922). Could also interact with integrin ITGB2, ITGB3 and/or ITGB5 (PubMed:10712922). Interacts (via ANK repeats) with LIMS1 and LIMS2 (PubMed:12167643, PubMed:19074270, PubMed:19117955). Interacts with PARVA (via C-terminus) and PARVB; these compete for the same binding site (PubMed:11402068, PubMed:15284246, PubMed:15817463, PubMed:20005845, PubMed:20117114). Interacts probably also with TGFB1I1 (By similarity). Interacts (via ANK repeats) with EPHA1 (via SAM domain); stimulated by EFNA1 but independent of the kinase activity of EPHA1 (PubMed:19118217). Interacts with FERMT2 (By similarity). Interacts with LIMD2; leading to activate the protein kinase activity (PubMed:24590809). Interacts with PXN/PAXILLIN (via LD motif 4) (PubMed:15817463). Interacts with CCDC25 (via cytoplasmic region); initiating the ILK-PARVB cascade to induce cytoskeleton rearrangement and directional migration of cells (PubMed:32528174). {ECO:0000250|UniProtKB:O55222, ECO:0000269|PubMed:11402068, ECO:0000269|PubMed:12167643, ECO:0000269|PubMed:15284246, ECO:0000269|PubMed:15817463, ECO:0000269|PubMed:19074270, ECO:0000269|PubMed:19117955, ECO:0000269|PubMed:19118217, ECO:0000269|PubMed:20005845, ECO:0000269|PubMed:20117114, ECO:0000269|PubMed:24590809, ECO:0000269|PubMed:32528174, ECO:0000303|PubMed:10712922}.

Subcellular location: Cell junction, focal adhesion {ECO:0000269|PubMed:11402068, ECO:0000269|PubMed:12167643}. Cell membrane; Peripheral membrane protein; Cytoplasmic side {ECO:0000269|PubMed:11402068}. Cell projection, lamellipodium {ECO:0000250|UniProtKB:O55222}. Cytoplasm, myofibril, sarcomere {ECO:0000269|PubMed:11402068}.

Tissue specificity: Highly expressed in heart followed by skeletal muscle, pancreas and kidney. Weakly expressed in placenta, lung and liver.

Domain: A PH-like domain is involved in phosphatidylinositol phosphate binding. {ECO:0000269|PubMed:19074270, ECO:0000269|PubMed:19117955}.

Ptm: Autophosphorylated on serine residues. {ECO:0000269|PubMed:8538749}.

Similarity: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. {ECO:0000305}.

Sequence caution: Sequence=CAB94832.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact. Was originally thought to be distinct gene (ILK2) (PubMed:10871859).; Evidence={ECO:0000305|PubMed:10871859};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Receptor-proximal protein kinase regulating integrin-mediated signal transduction (PubMed:8538749, PubMed:9736715). May act as a mediator of inside-out integrin signaling (PubMed:10712922). Focal adhesion protein part of the complex ILK-PINCH (PubMed:10712922). This complex is considered to be one of the convergence points of integrin- and growth factor-signaling pathway (PubMed:10712922). Could be implicated in mediating cell architecture, adhesion to integrin substrates and anchorage-dependent growth in epithelial cells (PubMed:10712922). Regulates cell motility by forming a complex with PARVB (PubMed:32528174). Phosphorylates beta-1 and beta-3 integrin subunit on serine and threonine residues, but also AKT1 and GSK3B (PubMed:8538749, PubMed:9736715). {ECO:0000269\|PubMed:32528174, ECO:0000269\|PubMed:8538749, ECO:0000269\|PubMed:9736715, ECO:0000303\|PubMed:10712922}.


Catalytic activity:		Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269\|PubMed:8538749};
Catalytic activity:		Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269\|PubMed:8538749};
Activity regulation:		Stimulated rapidly but transiently by both cell fibronectin interactions, as well as by insulin, in a PI3-K-dependent manner, likely via the binding of PtdIns(3,4,5)P3 with a PH-like domain of ILK. The protein kinase activity is stimulated by LIMD2 (PubMed:24590809). {ECO:0000269\|PubMed:24590809}.
Subunit:		Interacts with the cytoplasmic domain of ITGB1 (PubMed:10712922). Could also interact with integrin ITGB2, ITGB3 and/or ITGB5 (PubMed:10712922). Interacts (via ANK repeats) with LIMS1 and LIMS2 (PubMed:12167643, PubMed:19074270, PubMed:19117955). Interacts with PARVA (via C-terminus) and PARVB; these compete for the same binding site (PubMed:11402068, PubMed:15284246, PubMed:15817463, PubMed:20005845, PubMed:20117114). Interacts probably also with TGFB1I1 (By similarity). Interacts (via ANK repeats) with EPHA1 (via SAM domain); stimulated by EFNA1 but independent of the kinase activity of EPHA1 (PubMed:19118217). Interacts with FERMT2 (By similarity). Interacts with LIMD2; leading to activate the protein kinase activity (PubMed:24590809). Interacts with PXN/PAXILLIN (via LD motif 4) (PubMed:15817463). Interacts with CCDC25 (via cytoplasmic region); initiating the ILK-PARVB cascade to induce cytoskeleton rearrangement and directional migration of cells (PubMed:32528174). {ECO:0000250\|UniProtKB:O55222, ECO:0000269\|PubMed:11402068, ECO:0000269\|PubMed:12167643, ECO:0000269\|PubMed:15284246, ECO:0000269\|PubMed:15817463, ECO:0000269\|PubMed:19074270, ECO:0000269\|PubMed:19117955, ECO:0000269\|PubMed:19118217, ECO:0000269\|PubMed:20005845, ECO:0000269\|PubMed:20117114, ECO:0000269\|PubMed:24590809, ECO:0000269\|PubMed:32528174, ECO:0000303\|PubMed:10712922}.
Subcellular location:		Cell junction, focal adhesion {ECO:0000269\|PubMed:11402068, ECO:0000269\|PubMed:12167643}. Cell membrane; Peripheral membrane protein; Cytoplasmic side {ECO:0000269\|PubMed:11402068}. Cell projection, lamellipodium {ECO:0000250\|UniProtKB:O55222}. Cytoplasm, myofibril, sarcomere {ECO:0000269\|PubMed:11402068}.
Tissue specificity:		Highly expressed in heart followed by skeletal muscle, pancreas and kidney. Weakly expressed in placenta, lung and liver.
Domain:		A PH-like domain is involved in phosphatidylinositol phosphate binding. {ECO:0000269\|PubMed:19074270, ECO:0000269\|PubMed:19117955}.
Ptm:		Autophosphorylated on serine residues. {ECO:0000269\|PubMed:8538749}.
Similarity:		Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. {ECO:0000305}.
Sequence caution:		Sequence=CAB94832.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact. Was originally thought to be distinct gene (ILK2) (PubMed:10871859).; Evidence={ECO:0000305\|PubMed:10871859};