CILK1_MOUSE
ID CILK1_MOUSE Reviewed; 629 AA.
AC Q9JKV2; Q8K138;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Serine/threonine-protein kinase ICK;
DE EC=2.7.11.1 {ECO:0000269|PubMed:24797473};
DE AltName: Full=Intestinal cell kinase;
DE Short=mICK;
DE AltName: Full=MAK-related kinase;
DE Short=MRK;
GN Name=Cilk1; Synonyms=Ick;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|EMBL:AAF37277.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Ileum {ECO:0000269|PubMed:10699974}, and
RC Jejunum {ECO:0000269|PubMed:10699974};
RX PubMed=10699974;
RX DOI=10.1002/(sici)1097-4652(200004)183:1<129::aid-jcp15>3.0.co;2-s;
RA Togawa K., Yan Y.-X., Inomoto T., Slaugenhaupt S.A., Rustgi A.K.;
RT "Intestinal cell kinase (ICK) localizes to the crypt region and requires a
RT dual phosphorylation site found in map kinases.";
RL J. Cell. Physiol. 183:129-139(2000).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon {ECO:0000312|EMBL:AAH28863.1};
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 [3]
RP PROTEIN SEQUENCE OF 152-163, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY,
RP AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-33; 157-THR--TYR-159; GLU-169;
RP TRP-184; LYS-270; LYS-271 AND ARG-272, PHOSPHORYLATION AT THR-157 AND
RP TYR-159, AND MASS SPECTROMETRY.
RX PubMed=15988018; DOI=10.1128/mcb.25.14.6047-6064.2005;
RA Fu Z., Schroeder M.J., Shabanowitz J., Kaldis P., Togawa K., Rustgi A.K.,
RA Hunt D.F., Sturgill T.W.;
RT "Activation of a nuclear Cdc2-related kinase within a mitogen-activated
RT protein kinase-like TDY motif by autophosphorylation and cyclin-dependent
RT protein kinase-activating kinase.";
RL Mol. Cell. Biol. 25:6047-6064(2005).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-157; TYR-159 AND SER-161, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Pancreas, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND SUBCELLULAR LOCATION.
RX PubMed=24797473; DOI=10.1002/embj.201488175;
RA Chaya T., Omori Y., Kuwahara R., Furukawa T.;
RT "ICK is essential for cell type-specific ciliogenesis and the regulation of
RT ciliary transport.";
RL EMBO J. 33:1227-1242(2014).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-33.
RX PubMed=25243405; DOI=10.1371/journal.pone.0108470;
RA Broekhuis J.R., Verhey K.J., Jansen G.;
RT "Regulation of cilium length and intraflagellar transport by the RCK-
RT kinases ICK and MOK in renal epithelial cells.";
RL PLoS ONE 9:E108470-E108470(2014).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND SUBCELLULAR LOCATION.
RX PubMed=24853502; DOI=10.1073/pnas.1323161111;
RA Moon H., Song J., Shin J.O., Lee H., Kim H.K., Eggenschwiller J.T., Bok J.,
RA Ko H.W.;
RT "Intestinal cell kinase, a protein associated with endocrine-cerebro-
RT osteodysplasia syndrome, is a key regulator of cilia length and Hedgehog
RT signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:8541-8546(2014).
RN [8]
RP DEVELOPMENTAL STAGE.
RX PubMed=29539279; DOI=10.1056/nejmoa1700175;
RA Bailey J.N., de Nijs L., Bai D., Suzuki T., Miyamoto H., Tanaka M.,
RA Patterson C., Lin Y.C., Medina M.T., Alonso M.E., Serratosa J.M.,
RA Duron R.M., Nguyen V.H., Wight J.E., Martinez-Juarez I.E., Ochoa A.,
RA Jara-Prado A., Guilhoto L., Molina Y., Yacubian E.M., Lopez-Ruiz M.,
RA Inoue Y., Kaneko S., Hirose S., Osawa M., Oguni H., Fujimoto S.,
RA Grisar T.M., Stern J.M., Yamakawa K., Lakaye B., Delgado-Escueta A.V.;
RT "Variant intestinal-cell kinase in juvenile myoclonic epilepsy.";
RL N. Engl. J. Med. 378:1018-1028(2018).
CC -!- FUNCTION: Has an essential role in ciliogenesis, particularly in
CC neuronal and retinal progenitor cells (PubMed:24797473). Phosphorylates
CC KIF3A (PubMed:24797473). Involved in the control of ciliary length
CC (PubMed:24853502). Regulates the ciliary localization of SHH pathway
CC components as well as the localization of IFT components at ciliary
CC tips (PubMed:24797473, PubMed:24853502). May play a role in cardiac
CC development (By similarity). Regulates intraflagellar transport (IFT)
CC speed and negatively regulates cilium length in a cAMP and mTORC1
CC signaling -dependent manner and this regulation requires its kinase
CC activity (PubMed:25243405). {ECO:0000250|UniProtKB:Q62726,
CC ECO:0000269|PubMed:24797473, ECO:0000269|PubMed:24853502,
CC ECO:0000269|PubMed:25243405}.
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:15988018, ECO:0000269|PubMed:24797473};
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:15988018,
CC ECO:0000269|PubMed:24797473};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:24797473};
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q62726}. Cell projection, cilium
CC {ECO:0000269|PubMed:24797473, ECO:0000269|PubMed:25243405}. Nucleus
CC {ECO:0000269|PubMed:15988018, ECO:0000269|PubMed:25243405}. Cytoplasm,
CC cytoskeleton, cilium basal body {ECO:0000269|PubMed:24853502}.
CC Note=Also found at the ciliary tip (PubMed:24797473). Predominant
CC nuclear localization has been observed with a N-terminally GFP-tagged
CC construct in transfected COS-7 cells (PubMed:15988018).
CC {ECO:0000269|PubMed:15988018, ECO:0000269|PubMed:24797473}.
CC -!- TISSUE SPECIFICITY: Highly expressed in colon and lung, lower levels
CC present in heart, esophagus, stomach, small intestine and ovary.
CC Localizes to the crypt region of large and small intestine.
CC {ECO:0000269|PubMed:10699974}.
CC -!- DEVELOPMENTAL STAGE: At 14.5 dpc, expressed in the brain cortex,
CC including the cortical plate, intermediate zone, and ventricular and
CC subventricular zones. {ECO:0000269|PubMed:29539279}.
CC -!- PTM: Autophosphorylated on serine and threonine residues.
CC Phosphorylation at Thr-157 by CDK7/Cak1p increases kinase activity.
CC {ECO:0000269|PubMed:15988018}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice manifest hydrocephalus,
CC polydactyly, and delayed skeletal development. At cellular levels, ICK
CC knockout results in abnormally elongated cilia and compromised SHH
CC signaling. {ECO:0000269|PubMed:24853502}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
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DR EMBL; AF225918; AAF37277.1; -; mRNA.
DR EMBL; BC028863; AAH28863.1; -; mRNA.
DR CCDS; CCDS40697.1; -.
DR RefSeq; NP_001157252.1; NM_001163780.1.
DR RefSeq; NP_064371.2; NM_019987.2.
DR RefSeq; XP_006511367.1; XM_006511304.2.
DR AlphaFoldDB; Q9JKV2; -.
DR SMR; Q9JKV2; -.
DR STRING; 10090.ENSMUSP00000048234; -.
DR iPTMnet; Q9JKV2; -.
DR PhosphoSitePlus; Q9JKV2; -.
DR jPOST; Q9JKV2; -.
DR MaxQB; Q9JKV2; -.
DR PaxDb; Q9JKV2; -.
DR PRIDE; Q9JKV2; -.
DR ProteomicsDB; 267186; -.
DR ABCD; Q9JKV2; 1 sequenced antibody.
DR Antibodypedia; 605; 300 antibodies from 24 providers.
DR DNASU; 56542; -.
DR Ensembl; ENSMUST00000044551; ENSMUSP00000048234; ENSMUSG00000009828.
DR Ensembl; ENSMUST00000118869; ENSMUSP00000112961; ENSMUSG00000009828.
DR GeneID; 56542; -.
DR KEGG; mmu:56542; -.
DR UCSC; uc009qtt.2; mouse.
DR CTD; 22858; -.
DR MGI; MGI:1934157; Cilk1.
DR VEuPathDB; HostDB:ENSMUSG00000009828; -.
DR eggNOG; KOG0661; Eukaryota.
DR GeneTree; ENSGT00940000158807; -.
DR InParanoid; Q9JKV2; -.
DR OMA; RYTNIRQ; -.
DR OrthoDB; 76933at2759; -.
DR PhylomeDB; Q9JKV2; -.
DR TreeFam; TF328769; -.
DR BioGRID-ORCS; 56542; 4 hits in 75 CRISPR screens.
DR PRO; PR:Q9JKV2; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q9JKV2; protein.
DR Bgee; ENSMUSG00000009828; Expressed in trigeminal ganglion and 237 other tissues.
DR ExpressionAtlas; Q9JKV2; baseline and differential.
DR Genevisible; Q9JKV2; MM.
DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
DR GO; GO:0097546; C:ciliary base; IDA:UniProtKB.
DR GO; GO:0097542; C:ciliary tip; IMP:UniProtKB.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0001650; C:fibrillar center; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:MGI.
DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:UniProtKB.
DR GO; GO:0035720; P:intraciliary anterograde transport; IMP:UniProtKB.
DR GO; GO:0035721; P:intraciliary retrograde transport; IMP:UniProtKB.
DR GO; GO:0042073; P:intraciliary transport; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:MGI.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell projection; Cilium biogenesis/degradation; Cytoplasm;
KW Cytoskeleton; Developmental protein; Direct protein sequencing; Kinase;
KW Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..629
FT /note="Serine/threonine-protein kinase ICK"
FT /id="PRO_0000086008"
FT DOMAIN 4..284
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000305"
FT REGION 292..376
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 455..483
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 581..629
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 328..343
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 125
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 10..18
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P06493,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 33
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9NYX3,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 157
FT /note="Phosphothreonine; by CDK7"
FT /evidence="ECO:0000269|PubMed:15988018,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 159
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:15988018,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 161
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15988018"
FT MUTAGEN 33
FT /note="K->M: No effect on cilium length."
FT /evidence="ECO:0000269|PubMed:25243405"
FT MUTAGEN 33
FT /note="K->R: Loss of kinase activity; no effect on nuclear
FT subcellular location."
FT /evidence="ECO:0000269|PubMed:15988018"
FT MUTAGEN 157..159
FT /note="TDY->ADF: Loss of kinase activity and of
FT autophosphorylation; loss of phosphorylation by CDK7; no
FT effect on nuclear subcellular location."
FT /evidence="ECO:0000269|PubMed:15988018"
FT MUTAGEN 157
FT /note="T->A: Loss of kinase activity; loss of
FT phosphorylation by CDK7; no effect on autophosphorylation."
FT /evidence="ECO:0000269|PubMed:15988018"
FT MUTAGEN 159
FT /note="Y->F: Loss of kinase activity and of
FT autophosphorylation; no effect on phosphorylation by CDK7."
FT /evidence="ECO:0000269|PubMed:15988018"
FT MUTAGEN 169
FT /note="E->A: Complete loss of kinase activity and of
FT nuclear localization."
FT /evidence="ECO:0000269|PubMed:15988018"
FT MUTAGEN 184
FT /note="W->A: Complete loss of kinase activity and of
FT nuclear localization."
FT /evidence="ECO:0000269|PubMed:15988018"
FT MUTAGEN 270
FT /note="K->A: Partial loss of autocatalytic kinase activity.
FT Complete loss of kinase activity and of nuclear
FT localization; when associated with A-271 and A-272."
FT /evidence="ECO:0000269|PubMed:15988018"
FT MUTAGEN 271
FT /note="K->A: Partial loss of kinase activity. Complete loss
FT of kinase activity and of nuclear localization; when
FT associated with A-270 and A-272."
FT /evidence="ECO:0000269|PubMed:15988018"
FT MUTAGEN 272
FT /note="R->A: Complete loss of kinase activity and of
FT nuclear localization. Complete loss of kinase activity and
FT of nuclear localization; when associated with A-270 and A-
FT 272."
FT /evidence="ECO:0000269|PubMed:15988018"
FT CONFLICT 533
FT /note="S -> R (in Ref. 1; AAF37277)"
FT /evidence="ECO:0000305"
FT CONFLICT 616
FT /note="H -> L (in Ref. 1; AAF37277)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 629 AA; 70592 MW; 43E863847C5FD9C5 CRC64;
MNRYTTIKQL GDGTYGSVLL GRSIESGELI AIKKMKRKFY SWEECMNLRE VKSLKKLNHA
NIVKLKEVIR ENDHLYFIFE YMKENLYQLI KERNKLFPES AIRNIMYQIL QGLAFIHKHG
FFHRDLKPEN LLCMGPELVK IADFGLAREI RSRPPYTDYV STRWYRAPEV LLRSTNYSSP
IDIWAVGCIM AEVYTLRPLF PGASEIDTIF KICQVLGTPK KTDWPEGYQL SSAMNFLWPQ
CIPNNLKTLI PNASSEAIQL LRDLLQWDPK KRPTASQALR YPYFQIGHPL GIISKDSGKP
QREVQDKTGP PPYIKPAPPA QAPAKAYTLI SSRPSQASQP PQHSVHPYKG DVSRTEQLSH
VQEGKPSPPF FPSLHNKNLQ PKILASLEQK NGEIKPKSRR RWGLISRSTK GSDDWADLDD
LDFSPSLTRI DVKNKKRQSD DTLCRFESVL DLKPSESVGT GTTVSTQASS QRRDTPTLQS
SAKQHYLKHS RYLPGINIRN GVLPNPGKDF LPSNSWSSSG LSGKSSGTVS VVSKITSVGS
GSASSSGLTG SYIPSFLKKE IGSVMQRVQL APLAAPPPGY SSLKAVRPHP GRPFFHTQPR
STPGLIPRPP AAQPVHGRID WSSKYPSRR
