ILK_HUMAN
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 03-AUG-2022, entry version 226.
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},
GN ILK2 {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 -!- 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};
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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. [Q13418-3]
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; 267.
DR CORUM; Q13418; -.
DR DIP; DIP-38657N; -.
DR IntAct; Q13418; 211.
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; Q13418; -.
DR PeptideAtlas; Q13418; -.
DR PRIDE; Q13418; -.
DR ProteomicsDB; 59396; -. [Q13418-1]
DR ProteomicsDB; 6331; -.
DR ProteomicsDB; 6564; -.
DR Antibodypedia; 23909; 833 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 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; NMADAKF; -.
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; 291 hits in 1128 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 204 other tissues.
DR ExpressionAtlas; Q13418; baseline and differential.
DR Genevisible; Q13418; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
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: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:0018105; P:peptidyl-serine phosphorylation; 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: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:1901224; P:positive regulation of NIK/NF-kappaB signaling; IMP:CAFA.
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:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; IEA:Ensembl.
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; -; 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 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; unknown pathological significance;
FT 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
