ILKH_CAEEL
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 03-AUG-2022, entry version 171.
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; -.
DR EPD; Q9TZC4; -.
DR PaxDb; Q9TZC4; -.
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 CTD; 175175; -.
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; NMADAKF; -.
DR OrthoDB; 740146at2759; -.
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 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:0048815; P:hermaphrodite genitalia morphogenesis; IMP:UniProtKB.
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:1903356; P:positive regulation of distal tip cell migration; IMP:UniProtKB.
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:0060279; P:positive regulation of ovulation; 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:0045987; P:positive regulation of smooth muscle contraction; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:WormBase.
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; -; 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; 1.
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 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 unc-
FT 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
