ID ILK_HUMAN Reviewed; 452 AA. AC Q13418; B7Z1I0; B7Z418; D3DQU0; P57043; Q68DZ3; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1998, sequence version 2. DT 27-MAR-2024, entry version 235. DE RecName: Full=Integrin-linked protein kinase {ECO:0000303|PubMed:8538749}; DE EC=2.7.11.1 {ECO:0000303|PubMed:8538749}; DE AltName: Full=59 kDa serine/threonine-protein kinase {ECO:0000303|PubMed:8538749}; DE AltName: Full=Beta-integrin-linked kinase {ECO:0000250|UniProtKB:P57044}; DE AltName: Full=ILK-1 {ECO:0000303|PubMed:10871859}; DE AltName: Full=ILK-2 {ECO:0000303|PubMed:10871859}; DE AltName: Full=p59ILK {ECO:0000303|PubMed:8538749}; GN Name=ILK {ECO:0000312|HGNC:HGNC:6040}; GN Synonyms=ILK1 {ECO:0000303|PubMed:10871859}, ILK2 GN {ECO:0000303|PubMed:10871859}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND AUTOPHOSPHORYLATION. RC TISSUE=Placenta; RX PubMed=8538749; DOI=10.1038/379091a0; RA Hannigan G.E., Leung-Hagesteijn C., Fitz-Gibbon L., Coppolino M.G., RA Radeva G., Filmus J., Bell J.C., Dedhar S.; RT "Regulation of cell adhesion and anchorage-dependent growth by a new beta RT 1-integrin-linked protein kinase."; RL Nature 379:91-96(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=10871859; DOI=10.1038/sj.onc.1203640; RA Janji B., Melchior C., Vallar L., Kieffer N.; RT "Cloning of an isoform of integrin-linked kinase (ILK) that is upregulated RT in HT-144 melanoma cells following TGF-beta1 stimulation."; RL Oncogene 19:3069-3077(2000). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Tadic B., Hannigan G.E.; RT "Integrin-linked kinase genomic sequence."; RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Melchior C., Janji B., Kreis S., Kieffer N.; RT "Structural organisation of the gene encoding integrin-linked kinase 1."; RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). RC TISSUE=Cerebellum, and Colon; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Endometrium; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Cervix; 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 [11] RP FUNCTION, AND MUTAGENESIS OF GLU-359. RX PubMed=9736715; DOI=10.1073/pnas.95.19.11211; RA Delcommenne M., Tan C., Gray V., Rue L., Woodgett J.R., Dedhar S.; RT "Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase RT kinase 3 and protein kinase B/AKT by the integrin-linked kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 95:11211-11216(1998). RN [12] RP REVIEW. RX PubMed=10712922; DOI=10.1016/s0955-0674(99)00083-6; RA Dedhar S.; RT "Cell-substrate interactions and signaling through ILK."; RL Curr. Opin. Cell Biol. 12:250-256(2000). RN [13] RP INTERACTION WITH PARVB, AND SUBCELLULAR LOCATION. RX PubMed=11402068; DOI=10.1083/jcb.153.6.1251; RA Yamaji S., Suzuki A., Sugiyama Y., Koide Y., Yoshida M., Kanamori H., RA Mohri H., Ohno S., Ishigatsubo Y.; RT "A novel integrin-linked kinase-binding protein, affixin, is involved in RT the early stage of cell-substrate interaction."; RL J. Cell Biol. 153:1251-1264(2001). RN [14] RP SUBCELLULAR LOCATION, AND INTERACTION WITH LIMS1 AND LIMS2. RX PubMed=12167643; DOI=10.1074/jbc.m205576200; RA Zhang Y., Chen K., Guo L., Wu C.; RT "Characterization of PINCH-2, a new focal adhesion protein that regulates RT the PINCH-1-ILK interaction, cell spreading, and migration."; RL J. Biol. Chem. 277:38328-38338(2002). RN [15] RP INTERACTION WITH PARVA AND PARVB. RX PubMed=15284246; DOI=10.1074/jbc.m401563200; RA Zhang Y., Chen K., Tu Y., Wu C.; RT "Distinct roles of two structurally closely related focal adhesion RT proteins, alpha-parvins and beta-parvins, in regulation of cell morphology RT and survival."; RL J. Biol. Chem. 279:41695-41705(2004). RN [16] RP INTERACTION WITH PARVA AND PXN. RX PubMed=15817463; DOI=10.1074/jbc.m500752200; RA LaLonde D.P., Brown M.C., Bouverat B.P., Turner C.E.; RT "Actopaxin interacts with TESK1 to regulate cell spreading on RT fibronectin."; RL J. Biol. Chem. 280:21680-21688(2005). RN [17] RP INTERACTION WITH EPHA1. RX PubMed=19118217; DOI=10.1242/jcs.036467; RA Yamazaki T., Masuda J., Omori T., Usui R., Akiyama H., Maru Y.; RT "EphA1 interacts with integrin-linked kinase and regulates cell morphology RT and motility."; RL J. Cell Sci. 122:243-255(2009). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [20] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [21] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [22] RP INTERACTION WITH LIMD2, AND ACTIVITY REGULATION. RX PubMed=24590809; DOI=10.1158/0008-5472.can-13-1275; RA Peng H., Talebzadeh-Farrooji M., Osborne M.J., Prokop J.W., McDonald P.C., RA Karar J., Hou Z., He M., Kebebew E., Orntoft T., Herlyn M., Caton A.J., RA Fredericks W., Malkowicz B., Paterno C.S., Carolin A.S., Speicher D.W., RA Skordalakes E., Huang Q., Dedhar S., Borden K.L., Rauscher F.J. III; RT "LIMD2 is a small LIM-only protein overexpressed in metastatic lesions that RT regulates cell motility and tumor progression by directly binding to and RT activating the integrin-linked kinase."; RL Cancer Res. 74:1390-1403(2014). RN [23] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [24] RP FUNCTION, AND INTERACTION WITH CCDC25. RX PubMed=32528174; DOI=10.1038/s41586-020-2394-6; RA Yang L., Liu Q., Zhang X., Liu X., Zhou B., Chen J., Huang D., Li J., RA Li H., Chen F., Liu J., Xing Y., Chen X., Su S., Song E.; RT "DNA of neutrophil extracellular traps promotes cancer metastasis via RT CCDC25."; RL Nature 583:133-138(2020). RN [25] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 1-174 IN COMPLEX WITH LIMS1, RP DOMAIN ANK REPEATS, AND MUTAGENESIS OF HIS-99. RX PubMed=19074270; DOI=10.1073/pnas.0811415106; RA Chiswell B.P., Zhang R., Murphy J.W., Boggon T.J., Calderwood D.A.; RT "The structural basis of integrin-linked kinase-PINCH interactions."; RL Proc. Natl. Acad. Sci. U.S.A. 105:20677-20682(2008). RN [26] RP STRUCTURE BY NMR OF 1-171 IN COMPLEX WITH LIMS1, AND DOMAIN ANK REPEATS. RX PubMed=19117955; DOI=10.1074/jbc.m805319200; RA Yang Y., Wang X., Hawkins C.A., Chen K., Vaynberg J., Mao X., Tu Y., RA Zuo X., Wang J., Wang Y.-X., Wu C., Tjandra N., Qin J.; RT "Structural basis of focal adhesion localization of LIM-only adaptor PINCH RT by integrin-linked kinase."; RL J. Biol. Chem. 284:5836-5844(2009). RN [27] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 183-452 IN COMPLEX WITH PARVA, AND RP INTERACTION WITH PARVA. RX PubMed=20005845; DOI=10.1016/j.molcel.2009.11.028; RA Fukuda K., Gupta S., Chen K., Wu C., Qin J.; RT "The pseudoactive site of ILK is essential for its binding to alpha-parvin RT and localization to focal adhesions."; RL Mol. Cell 36:819-830(2009). RN [28] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 183-452 IN COMPLEX WITH PARVA, AND RP INTERACTION WITH PARVA. RX PubMed=20117114; DOI=10.1016/j.jmb.2010.01.048; RA Im Y.J., Kang G.B., Lee J.H., Park K.R., Song H.E., Kim E., Song W.K., RA Park D., Eom S.H.; RT "Structural basis for asymmetric association of the betaPIX coiled coil and RT shank PDZ."; RL J. Mol. Biol. 397:457-466(2010). RN [29] RP VARIANT VAL-262. RX PubMed=17646580; DOI=10.1161/circulationaha.107.689984; RA Knoell R., Postel R., Wang J., Kraetzner R., Hennecke G., Vacaru A.M., RA Vakeel P., Schubert C., Murthy K., Rana B.K., Kube D., Knoell G., RA Schaefer K., Hayashi T., Holm T., Kimura A., Schork N., Toliat M.R., RA Nuernberg P., Schultheiss H.P., Schaper W., Schaper J., Bos E., RA Den Hertog J., van Eeden F.J., Peters P.J., Hasenfuss G., Chien K.R., RA Bakkers J.; RT "Laminin-alpha4 and integrin-linked kinase mutations cause human RT cardiomyopathy via simultaneous defects in cardiomyocytes and endothelial RT cells."; RL Circulation 116:515-525(2007). CC -!- FUNCTION: Receptor-proximal protein kinase regulating integrin-mediated CC signal transduction (PubMed:8538749, PubMed:9736715). May act as a CC mediator of inside-out integrin signaling (PubMed:10712922). Focal CC adhesion protein part of the complex ILK-PINCH (PubMed:10712922). This CC complex is considered to be one of the convergence points of CC integrin- and growth factor-signaling pathway (PubMed:10712922). Could CC be implicated in mediating cell architecture, adhesion to integrin CC substrates and anchorage-dependent growth in epithelial cells CC (PubMed:10712922). Regulates cell motility by forming a complex with CC PARVB (PubMed:32528174). Phosphorylates beta-1 and beta-3 integrin CC subunit on serine and threonine residues, but also AKT1 and GSK3B CC (PubMed:8538749, PubMed:9736715). {ECO:0000269|PubMed:32528174, CC ECO:0000269|PubMed:8538749, ECO:0000269|PubMed:9736715, CC ECO:0000303|PubMed:10712922}. 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:0000269|PubMed:8538749}; 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:0000269|PubMed:8538749}; 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 (PubMed:24590809). {ECO:0000269|PubMed:24590809}. CC -!- SUBUNIT: Interacts with the cytoplasmic domain of ITGB1 CC (PubMed:10712922). Could also interact with integrin ITGB2, ITGB3 CC and/or ITGB5 (PubMed:10712922). Interacts (via ANK repeats) with LIMS1 CC and LIMS2 (PubMed:12167643, PubMed:19074270, PubMed:19117955). CC Interacts with PARVA (via C-terminus) and PARVB; these compete for the CC same binding site (PubMed:11402068, PubMed:15284246, PubMed:15817463, CC PubMed:20005845, PubMed:20117114). Interacts probably also with TGFB1I1 CC (By similarity). Interacts (via ANK repeats) with EPHA1 (via SAM CC domain); stimulated by EFNA1 but independent of the kinase activity of CC EPHA1 (PubMed:19118217). Interacts with FERMT2 (By similarity). CC Interacts with LIMD2; leading to activate the protein kinase activity CC (PubMed:24590809). Interacts with PXN/PAXILLIN (via LD motif 4) CC (PubMed:15817463). Interacts with CCDC25 (via cytoplasmic region); CC initiating the ILK-PARVB cascade to induce cytoskeleton rearrangement CC and directional migration of cells (PubMed:32528174). CC {ECO:0000250|UniProtKB:O55222, ECO:0000269|PubMed:11402068, CC ECO:0000269|PubMed:12167643, ECO:0000269|PubMed:15284246, CC ECO:0000269|PubMed:15817463, ECO:0000269|PubMed:19074270, CC ECO:0000269|PubMed:19117955, ECO:0000269|PubMed:19118217, CC ECO:0000269|PubMed:20005845, ECO:0000269|PubMed:20117114, CC ECO:0000269|PubMed:24590809, ECO:0000269|PubMed:32528174, CC ECO:0000303|PubMed:10712922}. CC -!- INTERACTION: CC Q13418; Q14790: CASP8; NbExp=2; IntAct=EBI-747644, EBI-78060; CC Q13418; P55211: CASP9; NbExp=2; IntAct=EBI-747644, EBI-516799; CC Q13418; Q9NWT6: HIF1AN; NbExp=2; IntAct=EBI-747644, EBI-745632; CC Q13418; P08238: HSP90AB1; NbExp=2; IntAct=EBI-747644, EBI-352572; CC Q13418; Q9H0C8: ILKAP; NbExp=3; IntAct=EBI-747644, EBI-2620298; CC Q13418; P48059: LIMS1; NbExp=14; IntAct=EBI-747644, EBI-306928; CC Q13418; P48059-3: LIMS1; NbExp=3; IntAct=EBI-747644, EBI-12864460; CC Q13418; Q9NVD7: PARVA; NbExp=23; IntAct=EBI-747644, EBI-747655; CC Q13418; Q9HBI0: PARVG; NbExp=12; IntAct=EBI-747644, EBI-3921217; CC Q13418; Q6R327: RICTOR; NbExp=8; IntAct=EBI-747644, EBI-1387196; CC Q13418; Q9BWU0: SLC4A1AP; NbExp=8; IntAct=EBI-747644, EBI-1999704; CC Q13418; Q9UMS6: SYNPO2; NbExp=6; IntAct=EBI-747644, EBI-3453434; CC Q13418; P14373: TRIM27; NbExp=4; IntAct=EBI-747644, EBI-719493; CC Q13418; P62258: YWHAE; NbExp=2; IntAct=EBI-747644, EBI-356498; CC -!- SUBCELLULAR LOCATION: Cell junction, focal adhesion CC {ECO:0000269|PubMed:11402068, ECO:0000269|PubMed:12167643}. Cell CC membrane; Peripheral membrane protein; Cytoplasmic side CC {ECO:0000269|PubMed:11402068}. Cell projection, lamellipodium CC {ECO:0000250|UniProtKB:O55222}. Cytoplasm, myofibril, sarcomere CC {ECO:0000269|PubMed:11402068}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q13418-1; Sequence=Displayed; CC Name=2; CC IsoId=Q13418-2; Sequence=VSP_054920; CC Name=3; CC IsoId=Q13418-3; Sequence=VSP_055925; CC -!- TISSUE SPECIFICITY: Highly expressed in heart followed by skeletal CC muscle, pancreas and kidney. Weakly expressed in placenta, lung and CC liver. CC -!- DOMAIN: A PH-like domain is involved in phosphatidylinositol phosphate CC binding. {ECO:0000269|PubMed:19074270, ECO:0000269|PubMed:19117955}. CC -!- PTM: Autophosphorylated on serine residues. CC {ECO:0000269|PubMed:8538749}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr CC protein kinase family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U40282; AAC16892.1; -; mRNA. DR EMBL; AJ277481; CAB94832.1; ALT_SEQ; mRNA. DR EMBL; AF244139; AAF74449.1; -; Genomic_DNA. DR EMBL; AJ404847; CAB99253.1; -; Genomic_DNA. DR EMBL; AK293474; BAH11516.1; -; mRNA. DR EMBL; AK296628; BAH12404.1; -; mRNA. DR EMBL; CR407673; CAG28601.1; -; mRNA. DR EMBL; CR749220; CAH18077.1; -; mRNA. DR EMBL; AC091564; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471064; EAW68688.1; -; Genomic_DNA. DR EMBL; CH471064; EAW68689.1; -; Genomic_DNA. DR EMBL; CH471064; EAW68690.1; -; Genomic_DNA. DR EMBL; BC001554; AAH01554.1; -; mRNA. DR CCDS; CCDS60712.1; -. [Q13418-2] DR CCDS; CCDS60713.1; -. [Q13418-3] DR CCDS; CCDS7768.1; -. [Q13418-1] DR PIR; S68455; S68455. DR RefSeq; NP_001014794.1; NM_001014794.2. [Q13418-1] DR RefSeq; NP_001014795.1; NM_001014795.2. [Q13418-1] DR RefSeq; NP_001265370.1; NM_001278441.1. [Q13418-2] DR RefSeq; NP_001265371.1; NM_001278442.1. [Q13418-3] DR RefSeq; NP_004508.1; NM_004517.3. [Q13418-1] DR RefSeq; XP_005252961.1; XM_005252904.4. [Q13418-1] DR RefSeq; XP_005252962.1; XM_005252905.2. DR RefSeq; XP_011518367.1; XM_011520065.1. [Q13418-1] DR PDB; 2KBX; NMR; -; A=1-171. DR PDB; 3F6Q; X-ray; 1.60 A; A=1-170. DR PDB; 3IXE; X-ray; 1.90 A; A=1-174. DR PDB; 3KMU; X-ray; 1.80 A; A=183-452. DR PDB; 3KMW; X-ray; 2.00 A; A=183-452. DR PDB; 3REP; X-ray; 1.80 A; A=183-452. DR PDB; 4HI8; X-ray; 1.20 A; A=1-174. DR PDB; 4HI9; X-ray; 1.20 A; A=1-174. DR PDB; 6MIB; X-ray; 1.80 A; A=182-452. DR PDBsum; 2KBX; -. DR PDBsum; 3F6Q; -. DR PDBsum; 3IXE; -. DR PDBsum; 3KMU; -. DR PDBsum; 3KMW; -. DR PDBsum; 3REP; -. DR PDBsum; 4HI8; -. DR PDBsum; 4HI9; -. DR PDBsum; 6MIB; -. DR AlphaFoldDB; Q13418; -. DR BMRB; Q13418; -. DR SMR; Q13418; -. DR BioGRID; 109824; 306. DR CORUM; Q13418; -. DR DIP; DIP-38657N; -. DR IntAct; Q13418; 214. DR MINT; Q13418; -. DR STRING; 9606.ENSP00000379975; -. DR BindingDB; Q13418; -. DR ChEMBL; CHEMBL5247; -. DR GuidetoPHARMACOLOGY; 2041; -. DR GlyGen; Q13418; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q13418; -. DR MetOSite; Q13418; -. DR PhosphoSitePlus; Q13418; -. DR SwissPalm; Q13418; -. DR BioMuta; ILK; -. DR DMDM; 9973397; -. DR OGP; Q13418; -. DR EPD; Q13418; -. DR jPOST; Q13418; -. DR MassIVE; Q13418; -. DR MaxQB; Q13418; -. DR PaxDb; 9606-ENSP00000379975; -. DR PeptideAtlas; Q13418; -. DR ProteomicsDB; 59396; -. [Q13418-1] DR ProteomicsDB; 6331; -. DR ProteomicsDB; 6564; -. DR Pumba; Q13418; -. DR Antibodypedia; 23909; 952 antibodies from 44 providers. DR DNASU; 3611; -. DR Ensembl; ENST00000299421.9; ENSP00000299421.4; ENSG00000166333.14. [Q13418-1] DR Ensembl; ENST00000396751.6; ENSP00000379975.2; ENSG00000166333.14. [Q13418-1] DR Ensembl; ENST00000420936.6; ENSP00000403487.2; ENSG00000166333.14. [Q13418-1] DR Ensembl; ENST00000528995.5; ENSP00000435323.1; ENSG00000166333.14. [Q13418-2] DR Ensembl; ENST00000532063.5; ENSP00000434492.2; ENSG00000166333.14. [Q13418-3] DR GeneID; 3611; -. DR KEGG; hsa:3611; -. DR MANE-Select; ENST00000299421.9; ENSP00000299421.4; NM_004517.4; NP_004508.1. DR UCSC; uc010rap.3; human. [Q13418-1] DR AGR; HGNC:6040; -. DR CTD; 3611; -. DR DisGeNET; 3611; -. DR GeneCards; ILK; -. DR HGNC; HGNC:6040; ILK. DR HPA; ENSG00000166333; Low tissue specificity. DR MIM; 602366; gene. DR neXtProt; NX_Q13418; -. DR OpenTargets; ENSG00000166333; -. DR PharmGKB; PA29855; -. DR VEuPathDB; HostDB:ENSG00000166333; -. DR eggNOG; KOG0195; Eukaryota. DR GeneTree; ENSGT00940000155956; -. DR HOGENOM; CLU_000288_7_35_1; -. DR InParanoid; Q13418; -. DR OMA; NEHGNAP; -. DR OrthoDB; 2127408at2759; -. DR PhylomeDB; Q13418; -. DR TreeFam; TF315194; -. DR BRENDA; 2.7.10.2; 2681. DR PathwayCommons; Q13418; -. DR Reactome; R-HSA-446343; Localization of the PINCH-ILK-PARVIN complex to focal adhesions. DR Reactome; R-HSA-446353; Cell-extracellular matrix interactions. DR SignaLink; Q13418; -. DR SIGNOR; Q13418; -. DR BioGRID-ORCS; 3611; 314 hits in 1209 CRISPR screens. DR ChiTaRS; ILK; human. DR EvolutionaryTrace; Q13418; -. DR GeneWiki; Integrin-linked_kinase; -. DR GenomeRNAi; 3611; -. DR Pharos; Q13418; Tchem. DR PRO; PR:Q13418; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q13418; Protein. DR Bgee; ENSG00000166333; Expressed in body of uterus and 206 other cell types or tissues. DR ExpressionAtlas; Q13418; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005925; C:focal adhesion; IDA:ARUK-UCL. DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0030017; C:sarcomere; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IEA:Ensembl. DR GO; GO:0000902; P:cell morphogenesis; IMP:ARUK-UCL. DR GO; GO:0030030; P:cell projection organization; IEA:Ensembl. 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; IEA:Ensembl. DR GO; GO:0010761; P:fibroblast migration; IEA:Ensembl. DR GO; GO:0007229; P:integrin-mediated signaling pathway; IDA:MGI. DR GO; GO:0022011; P:myelination in peripheral nervous system; IEA:Ensembl. DR GO; GO:2000178; P:negative regulation of neural precursor cell proliferation; IEA:Ensembl. DR GO; GO:0021675; P:nerve development; IEA:Ensembl. DR GO; GO:0061351; P:neural precursor cell proliferation; IEA:Ensembl. DR GO; GO:0003151; P:outflow tract morphogenesis; IEA:Ensembl. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IEA:Ensembl. DR GO; GO:0070527; P:platelet aggregation; HMP:UniProtKB. DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IEA:Ensembl. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IMP:CAFA. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IEA:Ensembl. DR GO; GO:0042327; P:positive regulation of phosphorylation; IMP:UniProtKB. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB. DR GO; GO:0009967; P:positive regulation of signal transduction; IMP:UniProtKB. DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IGI:ARUK-UCL. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IMP:UniProtKB. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IMP:CAFA. DR CDD; cd14057; PK_ILK; 1. DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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 PANTHER; PTHR23257:SF967; INTEGRIN-LINKED PROTEIN KINASE; 1. DR PANTHER; PTHR23257; SERINE-THREONINE PROTEIN KINASE; 1. DR Pfam; PF12796; Ank_2; 2. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR PIRSF; PIRSF000654; Integrin-linked_kinase; 1. DR SMART; SM00248; ANK; 3. DR SUPFAM; SSF48403; Ankyrin repeat; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS50297; ANK_REP_REGION; 1. DR PROSITE; PS50088; ANK_REPEAT; 3. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR Genevisible; Q13418; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ANK repeat; ATP-binding; KW Cell junction; Cell membrane; Cell projection; Cytoplasm; Kinase; Membrane; KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat; KW Serine/threonine-protein kinase; Transferase. FT CHAIN 1..452 FT /note="Integrin-linked protein kinase" FT /id="PRO_0000086020" 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:0000269|PubMed:12167643" FT REGION 180..212 FT /note="PH-like; mediates interaction with TGFB1I1" 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:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378" FT MOD_RES 186 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 426 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:O55222" FT VAR_SEQ 1..134 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055925" FT VAR_SEQ 118..206 FT /note="DLVANGALVSICNKYGEMPVDKAKAPLRELLRERAEKMGQNLNRIPYKDTFW FT KGTTRTRPRNGTLNKHSGIDFKQLNFLTKLNENHSGE -> SGQRRWARISTVFHTRTH FT SGRGPPALGP (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054920" FT VARIANT 262 FT /note="A -> V (found in a patient with severe dilated FT cardiomyopathy; uncertain significance; dbSNP:rs387907366)" FT /evidence="ECO:0000269|PubMed:17646580" FT /id="VAR_069753" FT MUTAGEN 99 FT /note="H->D: Alters interaction with LIMS1." FT /evidence="ECO:0000269|PubMed:19074270" FT MUTAGEN 359 FT /note="E->K: Inactivation of ILK." FT /evidence="ECO:0000269|PubMed:9736715" FT HELIX 4..10 FT /evidence="ECO:0007829|PDB:4HI8" FT HELIX 13..21 FT /evidence="ECO:0007829|PDB:4HI8" FT HELIX 37..43 FT /evidence="ECO:0007829|PDB:4HI8" FT HELIX 47..55 FT /evidence="ECO:0007829|PDB:4HI8" FT HELIX 70..76 FT /evidence="ECO:0007829|PDB:4HI8" FT HELIX 80..88 FT /evidence="ECO:0007829|PDB:4HI8" FT HELIX 92..94 FT /evidence="ECO:0007829|PDB:2KBX" FT HELIX 103..109 FT /evidence="ECO:0007829|PDB:4HI8" FT HELIX 113..121 FT /evidence="ECO:0007829|PDB:4HI8" FT STRAND 126..128 FT /evidence="ECO:0007829|PDB:4HI8" FT STRAND 131..133 FT /evidence="ECO:0007829|PDB:2KBX" FT HELIX 136..139 FT /evidence="ECO:0007829|PDB:4HI8" FT HELIX 142..154 FT /evidence="ECO:0007829|PDB:4HI8" FT TURN 167..169 FT /evidence="ECO:0007829|PDB:4HI9" FT HELIX 190..192 FT /evidence="ECO:0007829|PDB:3KMU" FT STRAND 194..202 FT /evidence="ECO:0007829|PDB:3KMU" FT STRAND 205..212 FT /evidence="ECO:0007829|PDB:3KMU" FT STRAND 215..222 FT /evidence="ECO:0007829|PDB:3KMU" FT HELIX 229..238 FT /evidence="ECO:0007829|PDB:3KMU" FT HELIX 239..242 FT /evidence="ECO:0007829|PDB:3KMU" FT STRAND 255..257 FT /evidence="ECO:0007829|PDB:3KMU" FT TURN 259..261 FT /evidence="ECO:0007829|PDB:3KMU" FT STRAND 262..264 FT /evidence="ECO:0007829|PDB:3KMU" FT STRAND 266..270 FT /evidence="ECO:0007829|PDB:3KMU" FT HELIX 277..282 FT /evidence="ECO:0007829|PDB:3KMU" FT HELIX 291..308 FT /evidence="ECO:0007829|PDB:3KMU" FT STRAND 311..313 FT /evidence="ECO:0007829|PDB:3KMU" FT STRAND 324..327 FT /evidence="ECO:0007829|PDB:3KMU" FT STRAND 333..336 FT /evidence="ECO:0007829|PDB:3KMU" FT HELIX 337..339 FT /evidence="ECO:0007829|PDB:3KMU" FT HELIX 353..355 FT /evidence="ECO:0007829|PDB:3KMU" FT HELIX 358..362 FT /evidence="ECO:0007829|PDB:3KMU" FT HELIX 365..367 FT /evidence="ECO:0007829|PDB:3KMU" FT HELIX 370..387 FT /evidence="ECO:0007829|PDB:3KMU" FT TURN 391..394 FT /evidence="ECO:0007829|PDB:3KMU" FT HELIX 397..406 FT /evidence="ECO:0007829|PDB:3KMU" FT HELIX 419..428 FT /evidence="ECO:0007829|PDB:3KMU" FT HELIX 433..435 FT /evidence="ECO:0007829|PDB:3KMU" FT HELIX 439..449 FT /evidence="ECO:0007829|PDB:3KMU" SQ SEQUENCE 452 AA; 51419 MW; E37DC2AD5311A1C2 CRC64; MDDIFTQCRE GNAVAVRLWL DNTENDLNQG DDHGFSPLHW ACREGRSAVV EMLIMRGARI NVMNRGDDTP LHLAASHGHR DIVQKLLQYK ADINAVNEHG NVPLHYACFW GQDQVAEDLV ANGALVSICN KYGEMPVDKA KAPLRELLRE RAEKMGQNLN RIPYKDTFWK GTTRTRPRNG TLNKHSGIDF KQLNFLTKLN ENHSGELWKG RWQGNDIVVK VLKVRDWSTR KSRDFNEECP RLRIFSHPNV LPVLGACQSP PAPHPTLITH WMPYGSLYNV LHEGTNFVVD QSQAVKFALD MARGMAFLHT LEPLIPRHAL NSRSVMIDED MTARISMADV KFSFQCPGRM YAPAWVAPEA LQKKPEDTNR RSADMWSFAV LLWELVTREV PFADLSNMEI GMKVALEGLR PTIPPGISPH VCKLMKICMN EDPAKRPKFD MIVPILEKMQ DK //