ID   ILKH_CAEEL              Reviewed;         466 AA.
AC   Q9TZC4; Q9NG00;
DT   14-OCT-2015, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   27-MAR-2024, entry version 178.
DE   RecName: Full=Integrin-linked protein kinase homolog pat-4 {ECO:0000303|PubMed:22761445};
DE            Short=ILK homolog {ECO:0000303|PubMed:12015115};
DE   AltName: Full=Paralyzed and arrested elongation at two-fold protein 4 {ECO:0000303|PubMed:12015115};
GN   Name=pat-4 {ECO:0000312|WormBase:C29F9.7};
GN   ORFNames=C29F9.7 {ECO:0000312|WormBase:C29F9.7};
OS   Caenorhabditis elegans.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN   [1] {ECO:0000312|Proteomes:UP000001940}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX   PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG   The C. elegans sequencing consortium;
RT   "Genome sequence of the nematode C. elegans: a platform for investigating
RT   biology.";
RL   Science 282:2012-2018(1998).
RN   [2] {ECO:0000312|EMBL:CAB77052.1}
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 18-466.
RX   PubMed=10637513; DOI=10.1038/sj.onc.1203258;
RA   Lynch D.K., Ellis C.A., Edwards P.A., Hiles I.D.;
RT   "Integrin-linked kinase regulates phosphorylation of serine 473 of protein
RT   kinase B by an indirect mechanism.";
RL   Oncogene 18:8024-8032(1999).
RN   [3] {ECO:0000305}
RP   FUNCTION, INTERACTION WITH UNC-112 AND UNC-97, SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP   GLU-374.
RX   PubMed=12015115; DOI=10.1016/s0960-9822(02)00810-2;
RA   Mackinnon A.C., Qadota H., Norman K.R., Moerman D.G., Williams B.D.;
RT   "C. elegans PAT-4/ILK functions as an adaptor protein within integrin
RT   adhesion complexes.";
RL   Curr. Biol. 12:787-797(2002).
RN   [4] {ECO:0000305}
RP   INTERACTION WITH PAT-6, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLU-374.
RX   PubMed=12781130; DOI=10.1016/s0960-9822(03)00372-5;
RA   Lin X., Qadota H., Moerman D.G., Williams B.D.;
RT   "C. elegans PAT-6/actopaxin plays a critical role in the assembly of
RT   integrin adhesion complexes in vivo.";
RL   Curr. Biol. 13:922-932(2003).
RN   [5]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=16495308; DOI=10.1242/dev.02300;
RA   Dixon S.J., Alexander M., Fernandes R., Ricker N., Roy P.J.;
RT   "FGF negatively regulates muscle membrane extension in Caenorhabditis
RT   elegans.";
RL   Development 133:1263-1275(2006).
RN   [6]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=16476426; DOI=10.1016/j.yexcr.2006.01.006;
RA   Xu X., Rongali S.C., Miles J.P., Lee K.D., Lee M.;
RT   "pat-4/ILK and unc-112/Mig-2 are required for gonad function in
RT   Caenorhabditis elegans.";
RL   Exp. Cell Res. 312:1475-1483(2006).
RN   [7]
RP   INTERACTION WITH UNC-97, AND SUBCELLULAR LOCATION.
RX   PubMed=17662976; DOI=10.1016/j.ydbio.2007.06.014;
RA   Norman K.R., Cordes S., Qadota H., Rahmani P., Moerman D.G.;
RT   "UNC-97/PINCH is involved in the assembly of integrin cell adhesion
RT   complexes in Caenorhabditis elegans body wall muscle.";
RL   Dev. Biol. 309:45-55(2007).
RN   [8]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=22761445; DOI=10.1074/jbc.m112.354852;
RA   Qadota H., Moerman D.G., Benian G.M.;
RT   "A molecular mechanism for the requirement of PAT-4 (integrin-linked kinase
RT   (ILK)) for the localization of UNC-112 (Kindlin) to integrin adhesion
RT   sites.";
RL   J. Biol. Chem. 287:28537-28551(2012).
RN   [9]
RP   FUNCTION, COMPONENT OF AN INTEGRIN CONTAINING ATTACHMENT COMPLEX, AND
RP   DISRUPTION PHENOTYPE.
RX   PubMed=22253611; DOI=10.1371/journal.pgen.1002471;
RA   Etheridge T., Oczypok E.A., Lehmann S., Fields B.D., Shephard F.,
RA   Jacobson L.A., Szewczyk N.J.;
RT   "Calpains mediate integrin attachment complex maintenance of adult muscle
RT   in Caenorhabditis elegans.";
RL   PLoS Genet. 8:E1002471-E1002471(2012).
RN   [10]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP   STAGE.
RX   PubMed=23283987; DOI=10.1091/mbc.e12-06-0478;
RA   Warner A., Xiong G., Qadota H., Rogalski T., Vogl A.W., Moerman D.G.,
RA   Benian G.M.;
RT   "CPNA-1, a copine domain protein, is located at integrin adhesion sites and
RT   is required for myofilament stability in Caenorhabditis elegans.";
RL   Mol. Biol. Cell 24:601-616(2013).
RN   [11]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=24314125; DOI=10.1111/acel.12189;
RA   Kumsta C., Ching T.T., Nishimura M., Davis A.E., Gelino S., Catan H.H.,
RA   Yu X., Chu C.C., Ong B., Panowski S.H., Baird N., Bodmer R., Hsu A.L.,
RA   Hansen M.;
RT   "Integrin-linked kinase modulates longevity and thermotolerance in C.
RT   elegans through neuronal control of HSF-1.";
RL   Aging Cell 13:419-430(2014).
RN   [12]
RP   INTERACTION WITH UNC-112, AND MUTAGENESIS OF PRO-257.
RX   PubMed=24692564; DOI=10.1074/jbc.m114.556308;
RA   Qadota H., Luo Y., Matsunaga Y., Park A.S., Gernert K.M., Benian G.M.;
RT   "Suppressor mutations suggest a surface on PAT-4 (Integrin-linked Kinase)
RT   that interacts with UNC-112 (Kindlin).";
RL   J. Biol. Chem. 289:14252-14262(2014).
CC   -!- FUNCTION: Probable pseudokinase that acts as an adapter protein
CC       (PubMed:12015115, PubMed:23283987). Component of an integrin containing
CC       attachment complex, which is required for muscle development and
CC       maintenance (PubMed:22253611). Involved in the assembly of dense bodies
CC       and M lines during body wall muscle development by recruiting several
CC       of their components including integrin pat-3, cpna-1, unc-89 and unc-
CC       112 to integrin-mediated attachment sites (PubMed:12015115,
CC       PubMed:23283987). Plays a role in distal tip cell (DTC) migration and
CC       in oocyte development probably by regulating the actin cytoskeleton
CC       (PubMed:16476426). During the formation of neuromuscular junctions at
CC       the larval stage, negatively regulates membrane protrusion from body
CC       wall muscles (PubMed:16495308). May be involved in thermotolerance and
CC       lifespan (PubMed:24314125). {ECO:0000269|PubMed:12015115,
CC       ECO:0000269|PubMed:16476426, ECO:0000269|PubMed:16495308,
CC       ECO:0000269|PubMed:22253611, ECO:0000269|PubMed:23283987,
CC       ECO:0000269|PubMed:24314125}.
CC   -!- SUBUNIT: Interacts (via protein kinase domain) with unc-112 (via N-
CC       terminus) (PubMed:12015115, PubMed:24692564). Interacts (via ANK
CC       repeats) with unc-97 (via first LIM domain) (PubMed:12015115,
CC       PubMed:17662976). Interacts (via protein kinase domain) with pat-6 (via
CC       C-terminus CH domain) (PubMed:12781130). May form a complex with unc-
CC       112, unc-97 and pat-6 (PubMed:12781130, PubMed:17662976,
CC       PubMed:24692564). Does not interact with integrin pat-3
CC       (PubMed:12015115). Component of an integrin containing attachment
CC       complex, composed of at least pat-2, pat-3, pat-4, pat-6, unc-52, unc-
CC       97 and unc-112 (PubMed:22253611). {ECO:0000269|PubMed:12015115,
CC       ECO:0000269|PubMed:12781130, ECO:0000269|PubMed:17662976,
CC       ECO:0000269|PubMed:24692564, ECO:0000305|PubMed:22253611}.
CC   -!- INTERACTION:
CC       Q9TZC4; O16785: pat-6; NbExp=4; IntAct=EBI-1564527, EBI-328106;
CC       Q9TZC4; Q18685: unc-112; NbExp=5; IntAct=EBI-1564527, EBI-1564809;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere, M line
CC       {ECO:0000269|PubMed:12015115, ECO:0000269|PubMed:23283987}. Basal cell
CC       membrane {ECO:0000269|PubMed:12015115, ECO:0000269|PubMed:17662976};
CC       Peripheral membrane protein {ECO:0000269|PubMed:12015115,
CC       ECO:0000269|PubMed:24314125}. Note=Colocalizes in dense bodies and M
CC       lines with integrin pat-3. Localization to muscle attachment sites is
CC       regulated by pat-2, unc-52 and unc-112 (PubMed:12015115). Co-localizes
CC       with pat-3 and pat-6 at body wall muscle attachment sites
CC       (PubMed:12781130, PubMed:17662976). {ECO:0000269|PubMed:12015115,
CC       ECO:0000269|PubMed:12781130, ECO:0000269|PubMed:17662976}.
CC   -!- TISSUE SPECIFICITY: Expressed in body wall muscle.
CC       {ECO:0000269|PubMed:12015115, ECO:0000269|PubMed:23283987}.
CC   -!- DEVELOPMENTAL STAGE: Expression starts in body wall muscles at the 1.5-
CC       fold embryonic stage. {ECO:0000269|PubMed:12015115,
CC       ECO:0000269|PubMed:23283987}.
CC   -!- DOMAIN: The protein kinase domain is predicted to be catalytically
CC       inactive. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC   -!- DISRUPTION PHENOTYPE: Embryonic lethality due to 1.5 fold stage-onset
CC       paralysis. Mutant embryos have defects in maintaining polarization of
CC       several components involved in the assembly of dense bodies and M
CC       lines, such as integrin pat-3, unc-89 and unc-112 to muscle attachment
CC       sites (PubMed:12015115). RNAi-mediated knockdown causes sterility
CC       resulting from oocyte accumulation in the proximal gonad and distal tip
CC       cell (DTC) migration defects (33 percent of animals). Actin
CC       cytoskeleton in the proximal gonad appears disorganized
CC       (PubMed:16476426). RNAi-mediated knockdown results in impaired
CC       mobility, mitochondrial fragmentation and disrupted integrin attachment
CC       complexes in muscle (PubMed:22253611). This leads to degradation of
CC       muscle proteins in the cytosol, myofibrillar defects and disruption of
CC       sarcomere organization (PubMed:22253611). RNAi-mediated knockdown in
CC       hatched embryos but not in adults causes adult-onset paralysis
CC       characterized by the collapse of myosin filaments in body wall muscles
CC       and a decrease in pharyngeal pumping (PubMed:24314125). In L1 larval
CC       stage, results in the formation of large myosin aggregates in body wall
CC       muscle cells (PubMed:22761445). In L4 larval stage, causes ectopic
CC       membrane extensions from body wall muscles (PubMed:16495308). In
CC       adults, causes an increase in lifespan, resistance to heat stress and
CC       increased expression of stress response factors hsf-1, sod-3, hsp-16.2
CC       and gst-4 (PubMed:24314125). {ECO:0000269|PubMed:12015115,
CC       ECO:0000269|PubMed:16476426, ECO:0000269|PubMed:16495308,
CC       ECO:0000269|PubMed:22253611, ECO:0000269|PubMed:22761445,
CC       ECO:0000269|PubMed:24314125}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC       protein kinase family. {ECO:0000305}.
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DR   EMBL; BX284603; CCD66066.1; -; Genomic_DNA.
DR   EMBL; AJ249344; CAB77052.1; -; mRNA.
DR   PIR; T33574; T33574.
DR   RefSeq; NP_497139.1; NM_064738.5.
DR   AlphaFoldDB; Q9TZC4; -.
DR   SMR; Q9TZC4; -.
DR   IntAct; Q9TZC4; 4.
DR   STRING; 6239.C29F9.7.1; -.
DR   EPD; Q9TZC4; -.
DR   PaxDb; 6239-C29F9-7; -.
DR   PeptideAtlas; Q9TZC4; -.
DR   EnsemblMetazoa; C29F9.7.1; C29F9.7.1; WBGene00003931.
DR   GeneID; 175175; -.
DR   KEGG; cel:CELE_C29F9.7; -.
DR   UCSC; C29F9.7; c. elegans.
DR   AGR; WB:WBGene00003931; -.
DR   WormBase; C29F9.7; CE19706; WBGene00003931; pat-4.
DR   eggNOG; KOG0195; Eukaryota.
DR   GeneTree; ENSGT00940000155956; -.
DR   HOGENOM; CLU_000288_7_5_1; -.
DR   InParanoid; Q9TZC4; -.
DR   OMA; MQVRVWL; -.
DR   OrthoDB; 2127408at2759; -.
DR   PhylomeDB; Q9TZC4; -.
DR   Reactome; R-CEL-446343; Localization of the PINCH-ILK-PARVIN complex to focal adhesions.
DR   Reactome; R-CEL-446353; Cell-extracellular matrix interactions.
DR   PRO; PR:Q9TZC4; -.
DR   Proteomes; UP000001940; Chromosome III.
DR   Bgee; WBGene00003931; Expressed in pharyngeal muscle cell (C elegans) and 4 other cell types or tissues.
DR   GO; GO:0005912; C:adherens junction; IDA:WormBase.
DR   GO; GO:0009925; C:basal plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005925; C:focal adhesion; IBA:GO_Central.
DR   GO; GO:0008305; C:integrin complex; IDA:WormBase.
DR   GO; GO:0031430; C:M band; IDA:UniProtKB.
DR   GO; GO:0055120; C:striated muscle dense body; IDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR   GO; GO:0005178; F:integrin binding; IPI:UniProtKB.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:WormBase.
DR   GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:UniProtKB.
DR   GO; GO:0007160; P:cell-matrix adhesion; IBA:GO_Central.
DR   GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:WormBase.
DR   GO; GO:0007229; P:integrin-mediated signaling pathway; IGI:WormBase.
DR   GO; GO:0007005; P:mitochondrion organization; IMP:UniProtKB.
DR   GO; GO:0046716; P:muscle cell cellular homeostasis; IMP:UniProtKB.
DR   GO; GO:0030239; P:myofibril assembly; IMP:WormBase.
DR   GO; GO:1904951; P:positive regulation of establishment of protein localization; IMP:UniProtKB.
DR   GO; GO:0040017; P:positive regulation of locomotion; IMP:UniProtKB.
DR   GO; GO:1904901; P:positive regulation of myosin II filament organization; IMP:UniProtKB.
DR   GO; GO:1903829; P:positive regulation of protein localization; IMP:UniProtKB.
DR   GO; GO:0060298; P:positive regulation of sarcomere organization; IMP:UniProtKB.
DR   GO; GO:0032956; P:regulation of actin cytoskeleton organization; IMP:UniProtKB.
DR   GO; GO:0055002; P:striated muscle cell development; IMP:UniProtKB.
DR   GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IBA:GO_Central.
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; PF00023; Ank; 1.
DR   Pfam; PF12796; Ank_2; 1.
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.
PE   1: Evidence at protein level;
KW   ANK repeat; Cell adhesion; Cell membrane; Cytoplasm; Membrane;
KW   Reference proteome; Repeat.
FT   CHAIN           1..466
FT                   /note="Integrin-linked protein kinase homolog pat-4"
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000434505"
FT   REPEAT          50..79
FT                   /note="ANK 1"
FT                   /evidence="ECO:0000255"
FT   REPEAT          83..112
FT                   /note="ANK 2"
FT                   /evidence="ECO:0000255"
FT   REPEAT          116..145
FT                   /note="ANK 3"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          210..465
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MUTAGEN         257
FT                   /note="P->L: Restores the interaction with unc-112 when
FT                   mutated at 'Asp-382' and the localization of mutated
FT                   unc-112 to integrin adhesion sites in body wall muscles."
FT                   /evidence="ECO:0000269|PubMed:24692564"
FT   MUTAGEN         374
FT                   /note="E->K: No effect on the interaction with unc-112 or
FT                   pat-6."
FT                   /evidence="ECO:0000269|PubMed:12015115,
FT                   ECO:0000269|PubMed:12781130"
SQ   SEQUENCE   466 AA;  52260 MW;  0D13147657A0DF11 CRC64;
     MSLSTHYHAH KPNVPIIMED VFGWVREGNA FQVRVWLDDH EHDLNVGDDH AFSLLHWAAK
     GGHVAIAEML LSRGARVNST NMGDDTSLHL AAAHGHRQIV VKLLSRKADV NATNEHGMTP
     LHYACFWGYE QIAEDLISCG AAVNVCNKKG MTPLDVCQPM CKNTILEIAQ EHGQSPNDRV
     PFKDTTWKGT KSRTRDATLS RYTGVDVSSL NLITKIAESH SGELWRGKWQ GNDIVARILN
     VQEVTARISR DFQTEFPALR IFAHPNICAV LAAANQPPNL VIISQYMPFG SLYNVLHEQS
     SVVIDHGQAV RFALDIARGM SYLHSLDPML LRFYLSSKHV VVDEELTAKL SMADTKFSFQ
     EVGKAYSPAW MSPEALSRAP EDLNIRAADM WSFAILLWEL NTREVPFSDL PPMECGMKIA
     LEGLRVHIPP GIARNMNRLM NICMNEDPGR RPNFDQIIPI LERMIL
//