ILK_MOUSE
ID ILK_MOUSE Reviewed; 452 AA.
AC O55222; Q78KK2;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Integrin-linked protein kinase {ECO:0000312|MGI:MGI:1195267};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q13418};
DE AltName: Full=59 kDa serine/threonine-protein kinase {ECO:0000250|UniProtKB:Q13418};
DE AltName: Full=Beta-integrin-linked kinase {ECO:0000250|UniProtKB:P57044};
DE AltName: Full=ILK-1 {ECO:0000250|UniProtKB:Q13418};
DE AltName: Full=ILK-2 {ECO:0000250|UniProtKB:Q13418};
DE AltName: Full=p59ILK {ECO:0000250|UniProtKB:Q13418};
GN Name=Ilk {ECO:0000312|MGI:MGI:1195267};
GN Synonyms=ILK1 {ECO:0000250|UniProtKB:Q13418},
GN ILK2 {ECO:0000250|UniProtKB:Q13418};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Heart;
RX PubMed=9366252; DOI=10.1016/s0167-4889(97)00089-x;
RA Li F., Liu J., Mayne R., Wu C.;
RT "Identification and characterization of a mouse protein kinase that is
RT highly homologous to human integrin-linked kinase.";
RL Biochim. Biophys. Acta 1358:215-220(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP INTERACTION WITH TGFB1I1.
RX PubMed=16737959; DOI=10.1074/jbc.m513111200;
RA Mori K., Asakawa M., Hayashi M., Imura M., Ohki T., Hirao E.,
RA Kim-Kaneyama J.-R., Nose K., Shibanuma M.;
RT "Oligomerizing potential of a focal adhesion LIM protein Hic-5 organizing a
RT nuclear-cytoplasmic shuttling complex.";
RL J. Biol. Chem. 281:22048-22061(2006).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=18325335; DOI=10.1016/j.febslet.2008.01.064;
RA Matsuda C., Kameyama K., Suzuki A., Mishima W., Yamaji S., Okamoto H.,
RA Nishino I., Hayashi Y.K.;
RT "Affixin activates Rac1 via betaPIX in C2C12 myoblast.";
RL FEBS Lett. 582:1189-1196(2008).
RN [5]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH FERMT2.
RX PubMed=18483218; DOI=10.1101/gad.469408;
RA Montanez E., Ussar S., Schifferer M., Bosl M., Zent R., Moser M.,
RA Fassler R.;
RT "Kindlin-2 controls bidirectional signaling of integrins.";
RL Genes Dev. 22:1325-1330(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-426, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Receptor-proximal protein kinase regulating integrin-mediated
CC signal transduction. May act as a mediator of inside-out integrin
CC signaling. Focal adhesion protein part of the complex ILK-PINCH. This
CC complex is considered to be one of the convergence points of
CC integrin- and growth factor-signaling pathway. Could be implicated in
CC mediating cell architecture, adhesion to integrin substrates and
CC anchorage-dependent growth in epithelial cells. Regulates cell motility
CC by forming a complex with PARVB. Phosphorylates beta-1 and beta-3
CC integrin subunit on serine and threonine residues, but also AKT1 and
CC GSK3B. {ECO:0000250|UniProtKB:Q13418}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:Q13418};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:Q13418};
CC -!- ACTIVITY REGULATION: Stimulated rapidly but transiently by both cell
CC fibronectin interactions, as well as by insulin, in a PI3-K-dependent
CC manner, likely via the binding of PtdIns(3,4,5)P3 with a PH-like domain
CC of ILK. The protein kinase activity is stimulated by LIMD2.
CC {ECO:0000250|UniProtKB:Q13418}.
CC -!- SUBUNIT: Interacts with the cytoplasmic domain of ITGB1. Could also
CC interact with integrin ITGB2, ITGB3 and/or ITGB5. Interacts (via ANK
CC repeats) with LIMS1 and LIMS2. Interacts with PARVA (via C-terminus)
CC and PARVB; these compete for the same binding site (By similarity).
CC Interacts probably also with TGFB1I1 (PubMed:16737959). Interacts (via
CC ANK repeats) with EPHA1 (via SAM domain); stimulated by EFNA1 but
CC independent of the kinase activity of EPHA1 (By similarity). Interacts
CC with FERMT2 (PubMed:18483218). Interacts with LIMD2; leading to
CC activate the protein kinase activity. Interacts with PXN/PAXILLIN (via
CC LD motif 4). Interacts with CCDC25 (via cytoplasmic region); initiating
CC the ILK-PARVB cascade to induce cytoskeleton rearrangement and
CC directional migration of cells (By similarity).
CC {ECO:0000250|UniProtKB:Q13418, ECO:0000269|PubMed:16737959,
CC ECO:0000269|PubMed:18483218}.
CC -!- INTERACTION:
CC O55222; Q9EPC1: Parva; NbExp=7; IntAct=EBI-6690138, EBI-6690233;
CC O55222; Q9ES46: Parvb; NbExp=3; IntAct=EBI-6690138, EBI-6914996;
CC O55222; Q9WUD1: Stub1; NbExp=7; IntAct=EBI-6690138, EBI-773027;
CC O55222; P48059: LIMS1; Xeno; NbExp=4; IntAct=EBI-6690138, EBI-306928;
CC O55222; Q9NVD7: PARVA; Xeno; NbExp=2; IntAct=EBI-6690138, EBI-747655;
CC -!- SUBCELLULAR LOCATION: Cell junction, focal adhesion
CC {ECO:0000269|PubMed:18325335, ECO:0000269|PubMed:18483218}. Cell
CC membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250};
CC Cytoplasmic side {ECO:0000250|UniProtKB:Q13418}. Cytoplasm, myofibril,
CC sarcomere {ECO:0000250|UniProtKB:Q13418}. Cell projection,
CC lamellipodium {ECO:0000269|PubMed:18325335}.
CC -!- TISSUE SPECIFICITY: Highly expressed in lung, heart, kidney, liver,
CC brain, spleen and skeletal muscle. Weakly expressed in testis.
CC -!- DOMAIN: A PH-like domain is involved in phosphatidylinositol phosphate
CC binding. {ECO:0000250|UniProtKB:Q13418}.
CC -!- PTM: Autophosphorylated on serine residues.
CC {ECO:0000250|UniProtKB:Q13418}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; U94479; AAB94646.1; -; mRNA.
DR EMBL; BC003737; AAH03737.1; -; mRNA.
DR CCDS; CCDS21659.1; -.
DR RefSeq; NP_001155196.1; NM_001161724.1.
DR RefSeq; NP_034692.2; NM_010562.2.
DR AlphaFoldDB; O55222; -.
DR BMRB; O55222; -.
DR SMR; O55222; -.
DR BioGRID; 200649; 17.
DR CORUM; O55222; -.
DR DIP; DIP-41971N; -.
DR IntAct; O55222; 49.
DR MINT; O55222; -.
DR STRING; 10090.ENSMUSP00000033182; -.
DR iPTMnet; O55222; -.
DR PhosphoSitePlus; O55222; -.
DR SwissPalm; O55222; -.
DR EPD; O55222; -.
DR jPOST; O55222; -.
DR MaxQB; O55222; -.
DR PaxDb; O55222; -.
DR PeptideAtlas; O55222; -.
DR PRIDE; O55222; -.
DR ProteomicsDB; 269477; -.
DR Antibodypedia; 23909; 833 antibodies from 44 providers.
DR DNASU; 16202; -.
DR Ensembl; ENSMUST00000033182; ENSMUSP00000033182; ENSMUSG00000030890.
DR Ensembl; ENSMUST00000163389; ENSMUSP00000130341; ENSMUSG00000030890.
DR GeneID; 16202; -.
DR KEGG; mmu:16202; -.
DR UCSC; uc009izb.2; mouse.
DR CTD; 3611; -.
DR MGI; MGI:1195267; Ilk.
DR VEuPathDB; HostDB:ENSMUSG00000030890; -.
DR eggNOG; KOG0195; Eukaryota.
DR GeneTree; ENSGT00940000155956; -.
DR HOGENOM; CLU_000288_7_5_1; -.
DR InParanoid; O55222; -.
DR OMA; NMADAKF; -.
DR OrthoDB; 740146at2759; -.
DR PhylomeDB; O55222; -.
DR TreeFam; TF315194; -.
DR BRENDA; 2.7.10.2; 3474.
DR Reactome; R-MMU-446343; Localization of the PINCH-ILK-PARVIN complex to focal adhesions.
DR Reactome; R-MMU-446353; Cell-extracellular matrix interactions.
DR BioGRID-ORCS; 16202; 13 hits in 78 CRISPR screens.
DR ChiTaRS; Ilk; mouse.
DR PRO; PR:O55222; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; O55222; protein.
DR Bgee; ENSMUSG00000030890; Expressed in placenta labyrinth and 271 other tissues.
DR ExpressionAtlas; O55222; baseline and differential.
DR Genevisible; O55222; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0005911; C:cell-cell junction; ISO:MGI.
DR GO; GO:0043034; C:costamere; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0043198; C:dendritic shaft; ISO:MGI.
DR GO; GO:0005925; C:focal adhesion; IDA:MGI.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0030017; C:sarcomere; IEA:UniProtKB-SubCell.
DR GO; GO:0001725; C:stress fiber; ISO:MGI.
DR GO; GO:0043195; C:terminal bouton; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005178; F:integrin binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0017124; F:SH3 domain binding; ISO:MGI.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IDA:MGI.
DR GO; GO:0000902; P:cell morphogenesis; ISO:MGI.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0030030; P:cell projection organization; IMP:MGI.
DR GO; GO:0007160; P:cell-matrix adhesion; IBA:GO_Central.
DR GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; IMP:MGI.
DR GO; GO:0010761; P:fibroblast migration; IMP:MGI.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISO:MGI.
DR GO; GO:0032288; P:myelin assembly; ISO:MGI.
DR GO; GO:0022011; P:myelination in peripheral nervous system; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; ISO:MGI.
DR GO; GO:2000178; P:negative regulation of neural precursor cell proliferation; IMP:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISO:MGI.
DR GO; GO:0014912; P:negative regulation of smooth muscle cell migration; ISO:MGI.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0021675; P:nerve development; IMP:MGI.
DR GO; GO:0061351; P:neural precursor cell proliferation; IMP:MGI.
DR GO; GO:0048812; P:neuron projection morphogenesis; ISO:MGI.
DR GO; GO:0003151; P:outflow tract morphogenesis; IMP:CACAO.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IMP:MGI.
DR GO; GO:0045773; P:positive regulation of axon extension; ISO:MGI.
DR GO; GO:0050772; P:positive regulation of axonogenesis; ISO:MGI.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IMP:BHF-UCL.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISO:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; ISO:MGI.
DR GO; GO:2000774; P:positive regulation of cellular senescence; ISO:MGI.
DR GO; GO:0050775; P:positive regulation of dendrite morphogenesis; ISO:MGI.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0045663; P:positive regulation of myoblast differentiation; ISO:MGI.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IMP:BHF-UCL.
DR GO; GO:0042327; P:positive regulation of phosphorylation; ISO:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0009967; P:positive regulation of signal transduction; ISO:MGI.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0043491; P:protein kinase B signaling; IMP:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISO:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; ISO:MGI.
DR GO; GO:0001558; P:regulation of cell growth; ISO:MGI.
DR GO; GO:0014044; P:Schwann cell development; IMP:MGI.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; ISO:MGI.
DR GO; GO:0097435; P:supramolecular fiber organization; ISO:MGI.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; ISO:MGI.
DR CDD; cd14057; PK_ILK; 1.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR035692; PK_ILK.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR Pfam; PF12796; Ank_2; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR SMART; SM00248; ANK; 3.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 3.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW Acetylation; ANK repeat; ATP-binding; Cell junction; Cell membrane;
KW Cell projection; Cytoplasm; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..452
FT /note="Integrin-linked protein kinase"
FT /id="PRO_0000086022"
FT REPEAT 2..30
FT /note="ANK 1"
FT REPEAT 31..63
FT /note="ANK 2"
FT REPEAT 64..96
FT /note="ANK 3"
FT REPEAT 97..129
FT /note="ANK 4"
FT REPEAT 130..174
FT /note="ANK 5"
FT DOMAIN 193..446
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 33..139
FT /note="Interaction with LIMS1"
FT /evidence="ECO:0000250"
FT REGION 180..212
FT /note="PH-like; mediates interaction with TGFB1I1"
FT /evidence="ECO:0000269|PubMed:16737959"
FT BINDING 199..207
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 220
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q13418"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13418"
FT MOD_RES 426
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 93
FT /note="I -> T (in Ref. 1; AAB94646)"
FT /evidence="ECO:0000305"
FT CONFLICT 413
FT /note="I -> V (in Ref. 1; AAB94646)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 452 AA; 51373 MW; F41960CF8EC503A7 CRC64;
MDDIFTQCRE GNAVAVRLWL DNTENDLNQG DDHGFSPLHW ACREGRSAVV EMLIMRGARI
NVMNRGDDTP LHLAASHGHR DIVQKLLQYK ADINAVNEHG NVPLHYACFW GQDQVAEDLV
ANGALVSICN KYGEMPVDKA KAPLRELLRE RAEKMGQNLN RIPYKDTFWK GTTRTRPRNG
TLNKHSGIDF KQLNFLAKLN ENHSGELWKG RWQGNDIVVK VLKVRDWSTR KSRDFNEECP
RLRIFSHPNV LPVLGACQAP PAPHPTLITH WMPYGSLYNV LHEGTNFVVD QSQAVKFALD
MARGMAFLHT LEPLIPRHAL NSRSVMIDED MTARISMADV KFSFQCPGRM YAPAWVAPEA
LQKKPEDTNR RSADMWSFAV LLWELVTREV PFADLSNMEI GMKVALEGLR PTIPPGISPH
VCKLMKICMN EDPAKRPKFD MIVPILEKMQ DK
