ILK_CAVPO
ID ILK_CAVPO Reviewed; 451 AA.
AC P57044;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Integrin-linked protein kinase {ECO:0000250|UniProtKB:Q13418};
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:0000303|Ref.1};
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:0000250|UniProtKB:Q13418};
GN Synonyms=ILK1 {ECO:0000250|UniProtKB:Q13418},
GN ILK2 {ECO:0000250|UniProtKB:Q13418};
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Ishii T.;
RT "Guinea pig beta-integrin-linked kinase.";
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). 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 (By similarity). Interacts with LIMD2; leading to activate
CC the protein kinase activity. Interacts with PXN/PAXILLIN (via LD motif
CC 4). Interacts with CCDC25 (via cytoplasmic region); initiating the ILK-
CC PARVB cascade to induce cytoskeleton rearrangement and directional
CC migration of cells (By similarity). {ECO:0000250|UniProtKB:O55222,
CC ECO:0000250|UniProtKB:Q13418}.
CC -!- SUBCELLULAR LOCATION: Cell junction, focal adhesion
CC {ECO:0000250|UniProtKB:Q13418}. Cell membrane
CC {ECO:0000250|UniProtKB:Q13418}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q13418}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q13418}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:O55222}. Cytoplasm, myofibril, sarcomere
CC {ECO:0000250|UniProtKB:Q13418}.
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; AF256520; AAF70501.1; -; mRNA.
DR RefSeq; NP_001166442.1; NM_001172971.1.
DR AlphaFoldDB; P57044; -.
DR BMRB; P57044; -.
DR SMR; P57044; -.
DR STRING; 10141.ENSCPOP00000011264; -.
DR GeneID; 100135559; -.
DR KEGG; cpoc:100135559; -.
DR CTD; 3611; -.
DR eggNOG; KOG0195; Eukaryota.
DR HOGENOM; CLU_000288_7_5_1; -.
DR InParanoid; P57044; -.
DR OrthoDB; 740146at2759; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
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:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
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 2: Evidence at transcript 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..451
FT /note="Integrin-linked protein kinase"
FT /id="PRO_0000086019"
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..445
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 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 425
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O55222"
SQ SEQUENCE 451 AA; 51308 MW; 88EF22C4517DD52B CRC64;
MDDIFTQCRE GNAVAVRLWL DNTENDLNQG DDHGFSPLHW ACREGRSAVV EMLIMRGARI
NVMNRGDDTP LHLAASHGHR DIVQKLLQYK ADINAVNEHG NVPLHYACFW GQDQVAEDLV
ANGALVSICN KYGEMPMDKA KAPLRELLRE RAEKMGQNLN RIPYKDTFWK GTTRTRPRNG
TLNKHSGIDF KQLNFLAKLN ENHSGELWKG RWQGNDIVVK VLKVRDWSTR KSRDFNEECP
RLRIFSHPNV LPVLGACQSP PAPHPTLITH WMPYGSLYNV LHEGTNFVVD QSQAVKFALD
MARGMAFLHT LEPLIPRHAL NSRSVMIDED MTARISMADV KFSFQCPGRM YAPAWVAPEA
LQKKPEDTNR RSADMWSFAV LLWELVTREV PFADLSNMEI GMKVALEGRP TIPPGISPHV
CKLMKICMNE DPAKRPKFDM IVPILEKMQD K
