CILK1_HUMAN
ID CILK1_HUMAN Reviewed; 632 AA.
AC Q9UPZ9; A7MD41; O75985; Q5THL2; Q8IYH8; Q9BX17; Q9NYX3;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Serine/threonine-protein kinase ICK;
DE EC=2.7.11.1 {ECO:0000269|PubMed:10699974};
DE AltName: Full=Ciliogenesis associated kinase 1 {ECO:0000305};
DE AltName: Full=Intestinal cell kinase;
DE Short=hICK;
DE AltName: Full=Laryngeal cancer kinase 2;
DE Short=LCK2;
DE AltName: Full=MAK-related kinase;
DE Short=MRK;
GN Name=CILK1; Synonyms=ICK, KIAA0936;
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 {ECO:0000312|EMBL:AAF37278.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, ACTIVITY REGULATION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-33;
RP LYS-34; LYS-36; LYS-38; THR-157 AND TYR-159, AND PHOSPHORYLATION AT THR-157
RP AND TYR-159.
RC TISSUE=Colon {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]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Cervix carcinoma;
RX PubMed=12103360; DOI=10.1016/s1389-0344(02)00002-3;
RA Yang T., Jiang Y., Chen J.;
RT "The identification and subcellular localization of human MRK.";
RL Biomol. Eng. 19:1-4(2002).
RN [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain {ECO:0000312|EMBL:BAA76780.2};
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [4] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5] {ECO:0000305}
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain {ECO:0000312|EMBL:AAH35807.1};
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 [7]
RP SUBCELLULAR LOCATION (ISOFORM 2).
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT ECO
RP GLN-272.
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 [11]
RP FUNCTION, AND CHARACTERIZATION OF VARIANT ECO GLN-272.
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 [12]
RP VARIANTS [LARGE SCALE ANALYSIS] TYR-115; ILE-320; LYS-471; GLN-476 AND
RP THR-615.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [13]
RP VARIANT ECO GLN-272, CHARACTERIZATION OF VARIANT ECO GLN-272, CATALYTIC
RP ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=19185282; DOI=10.1016/j.ajhg.2008.12.017;
RA Lahiry P., Wang J., Robinson J.F., Turowec J.P., Litchfield D.W.,
RA Lanktree M.B., Gloor G.B., Puffenberger E.G., Strauss K.A., Martens M.B.,
RA Ramsay D.A., Rupar C.A., Siu V., Hegele R.A.;
RT "A multiplex human syndrome implicates a key role for intestinal cell
RT kinase in development of central nervous, skeletal, and endocrine
RT systems.";
RL Am. J. Hum. Genet. 84:134-147(2009).
RN [14]
RP INVOLVEMENT IN EJM10, VARIANTS EJM10 LEU-102; GLU-220; THR-305;
RP 369-PRO--LEU-373 DEL; THR-615 AND ARG-632 DEL, CHARACTERIZATION OF VARIANT
RP ECO GLN-272, VARIANT ILE-320, AND CHARACTERIZATION OF VARIANTS EJM10
RP GLU-220; THR-305; THR-615 AND ARG-632 DEL.
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: Required for ciliogenesis (PubMed:24797473). Phosphorylates
CC KIF3A (By similarity). 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 (By similarity). May play a key role in the development of
CC multiple organ systems and particularly in cardiac development (By
CC similarity). Regulates intraflagellar transport (IFT) speed and
CC negatively regulates cilium length in a cAMP and mTORC1 signaling-
CC dependent manner and this regulation requires its kinase activity (By
CC similarity). {ECO:0000250|UniProtKB:Q62726,
CC ECO:0000250|UniProtKB:Q9JKV2, ECO:0000269|PubMed:24797473,
CC ECO:0000269|PubMed:24853502}.
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:10699974, ECO:0000269|PubMed:19185282};
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:10699974,
CC ECO:0000269|PubMed:19185282};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10699974};
CC -!- INTERACTION:
CC Q9UPZ9; P08238: HSP90AB1; NbExp=3; IntAct=EBI-6381479, EBI-352572;
CC Q9UPZ9; Q9NRG4: SMYD2; NbExp=2; IntAct=EBI-6381479, EBI-1055671;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12103360,
CC ECO:0000269|PubMed:19185282}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q62726}. Cell projection, cilium
CC {ECO:0000269|PubMed:24797473}. Cytoplasm, cytoskeleton, cilium basal
CC body {ECO:0000250|UniProtKB:Q9JKV2}. Note=Also found at the ciliary tip
CC (PubMed:24797473). Nuclear localization has been observed with a GFP-
CC tagged construct in transfected HeLa cells (PubMed:12103360,
CC PubMed:19185282). {ECO:0000269|PubMed:12103360,
CC ECO:0000269|PubMed:19185282, ECO:0000269|PubMed:24797473}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:15988018}. Note=Predominant cytoplasmic
CC localization has been observed with a N-terminally GFP-tagged
CC construct. {ECO:0000269|PubMed:15988018}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:10699974};
CC IsoId=Q9UPZ9-1; Sequence=Displayed;
CC Name=2 {ECO:0000305};
CC IsoId=Q9UPZ9-2; Sequence=VSP_050752, VSP_050753;
CC -!- TISSUE SPECIFICITY: Expressed in heart, brain, placenta, pancreas,
CC thymus, prostate, testis, ovary, small intestine and colon, with
CC highest levels in placenta and testis. Not detected in spleen. Also
CC expressed in many cancer cell lines. {ECO:0000269|PubMed:10699974,
CC ECO:0000269|PubMed:12103360}.
CC -!- PTM: Autophosphorylated on serine and threonine residues.
CC Phosphorylation at Thr-157 increases kinase activity.
CC {ECO:0000269|PubMed:10699974}.
CC -!- DISEASE: Endocrine-cerebroosteodysplasia (ECO) [MIM:612651]: Previously
CC unidentified neonatal lethal recessive disorder with multiple anomalies
CC involving the endocrine, cerebral, and skeletal systems.
CC {ECO:0000269|PubMed:19185282, ECO:0000269|PubMed:24797473,
CC ECO:0000269|PubMed:24853502, ECO:0000269|PubMed:29539279}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Juvenile myoclonic epilepsy 10 (EJM10) [MIM:617924]: A form of
CC juvenile myoclonic epilepsy, a subtype of idiopathic generalized
CC epilepsy generally characterized by afebrile seizures with onset in
CC adolescence (rather than in childhood) and myoclonic jerks, which
CC usually occur after awakening and are triggered by sleep deprivation
CC and fatigue. EJM10 is an autosomal dominant seizure disorder with
CC variable manifestations, even within families. Affected individuals
CC have febrile, myoclonic, tonic-clonic, or absence seizures, although
CC several seizure types can occur in the same individual. Some patients
CC have onset of seizures in the first years of life.
CC {ECO:0000269|PubMed:29539279}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA76780.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF225919; AAF37278.1; -; mRNA.
DR EMBL; AF152469; AAG43364.1; -; mRNA.
DR EMBL; AB023153; BAA76780.2; ALT_INIT; mRNA.
DR EMBL; AL031178; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL162581; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX04400.1; -; Genomic_DNA.
DR EMBL; BC035807; AAH35807.1; -; mRNA.
DR EMBL; BC136420; AAI36421.1; -; mRNA.
DR EMBL; BC136421; AAI36422.1; -; mRNA.
DR EMBL; BC152464; AAI52465.1; -; mRNA.
DR CCDS; CCDS4949.1; -. [Q9UPZ9-1]
DR RefSeq; NP_055735.1; NM_014920.3. [Q9UPZ9-1]
DR RefSeq; NP_057597.2; NM_016513.4. [Q9UPZ9-1]
DR RefSeq; XP_016865977.1; XM_017010488.1.
DR RefSeq; XP_016865978.1; XM_017010489.1.
DR RefSeq; XP_016865979.1; XM_017010490.1.
DR RefSeq; XP_016865980.1; XM_017010491.1.
DR RefSeq; XP_016865981.1; XM_017010492.1.
DR AlphaFoldDB; Q9UPZ9; -.
DR SMR; Q9UPZ9; -.
DR BioGRID; 116527; 55.
DR IntAct; Q9UPZ9; 32.
DR MINT; Q9UPZ9; -.
DR STRING; 9606.ENSP00000349458; -.
DR BindingDB; Q9UPZ9; -.
DR ChEMBL; CHEMBL1163126; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q9UPZ9; -.
DR iPTMnet; Q9UPZ9; -.
DR PhosphoSitePlus; Q9UPZ9; -.
DR BioMuta; ICK; -.
DR DMDM; 48428273; -.
DR EPD; Q9UPZ9; -.
DR jPOST; Q9UPZ9; -.
DR MassIVE; Q9UPZ9; -.
DR PaxDb; Q9UPZ9; -.
DR PeptideAtlas; Q9UPZ9; -.
DR PRIDE; Q9UPZ9; -.
DR ProteomicsDB; 85480; -. [Q9UPZ9-1]
DR ProteomicsDB; 85481; -. [Q9UPZ9-2]
DR Antibodypedia; 605; 300 antibodies from 24 providers.
DR DNASU; 22858; -.
DR Ensembl; ENST00000356971.3; ENSP00000349458.3; ENSG00000112144.16. [Q9UPZ9-1]
DR Ensembl; ENST00000676107.1; ENSP00000501692.1; ENSG00000112144.16. [Q9UPZ9-1]
DR GeneID; 22858; -.
DR KEGG; hsa:22858; -.
DR MANE-Select; ENST00000676107.1; ENSP00000501692.1; NM_014920.5; NP_055735.1.
DR UCSC; uc003pbh.3; human. [Q9UPZ9-1]
DR CTD; 22858; -.
DR DisGeNET; 22858; -.
DR GeneCards; CILK1; -.
DR HGNC; HGNC:21219; CILK1.
DR HPA; ENSG00000112144; Low tissue specificity.
DR MalaCards; CILK1; -.
DR MIM; 612325; gene.
DR MIM; 612651; phenotype.
DR MIM; 617924; phenotype.
DR neXtProt; NX_Q9UPZ9; -.
DR OpenTargets; ENSG00000112144; -.
DR Orphanet; 199332; Endocrine-cerebro-osteodysplasia syndrome.
DR Orphanet; 307; Juvenile myoclonic epilepsy.
DR VEuPathDB; HostDB:ENSG00000112144; -.
DR eggNOG; KOG0661; Eukaryota.
DR GeneTree; ENSGT00940000158807; -.
DR HOGENOM; CLU_000288_181_25_1; -.
DR InParanoid; Q9UPZ9; -.
DR OrthoDB; 76933at2759; -.
DR PhylomeDB; Q9UPZ9; -.
DR TreeFam; TF328769; -.
DR PathwayCommons; Q9UPZ9; -.
DR SignaLink; Q9UPZ9; -.
DR SIGNOR; Q9UPZ9; -.
DR BioGRID-ORCS; 22858; 12 hits in 1109 CRISPR screens.
DR ChiTaRS; ICK; human.
DR GeneWiki; ICK_(gene); -.
DR GenomeRNAi; 22858; -.
DR Pharos; Q9UPZ9; Tchem.
DR PRO; PR:Q9UPZ9; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9UPZ9; protein.
DR Bgee; ENSG00000112144; Expressed in adrenal tissue and 186 other tissues.
DR ExpressionAtlas; Q9UPZ9; baseline and differential.
DR Genevisible; Q9UPZ9; HS.
DR GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB.
DR GO; GO:0097546; C:ciliary base; ISS:UniProtKB.
DR GO; GO:0097542; C:ciliary tip; IMP:UniProtKB.
DR GO; GO:0005929; C:cilium; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0035720; P:intraciliary anterograde transport; ISS:UniProtKB.
DR GO; GO:0035721; P:intraciliary retrograde transport; ISS:UniProtKB.
DR GO; GO:0042073; P:intraciliary transport; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:UniProtKB.
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 Alternative splicing; ATP-binding; Cell projection;
KW Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton;
KW Developmental protein; Disease variant; Epilepsy; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..632
FT /note="Serine/threonine-protein kinase ICK"
FT /id="PRO_0000086007"
FT DOMAIN 4..284
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000305"
FT REGION 290..344
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 457..481
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 582..632
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 314..328
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 330..344
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 462..480
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:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:10699974"
FT MOD_RES 157
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:10699974"
FT MOD_RES 159
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:10699974"
FT MOD_RES 161
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JKV2"
FT VAR_SEQ 278..292
FT /note="ALRYPYFQVGHPLGS -> VFFHFLVITFISNSE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_050752"
FT VAR_SEQ 293..632
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_050753"
FT VARIANT 98
FT /note="P -> L (in dbSNP:rs1493105)"
FT /id="VAR_053931"
FT VARIANT 102
FT /note="I -> L (in EJM10; unknown pathological significance;
FT dbSNP:rs748539319)"
FT /evidence="ECO:0000269|PubMed:29539279"
FT /id="VAR_080554"
FT VARIANT 115
FT /note="F -> Y (in a renal clear cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042001"
FT VARIANT 220
FT /note="K -> E (in EJM10; impairs mitosis, cell-cycle exit
FT and radial neuroblast migration, while promoting apoptosis,
FT when tested in a heterologous system)"
FT /evidence="ECO:0000269|PubMed:29539279"
FT /id="VAR_080555"
FT VARIANT 272
FT /note="R -> Q (in ECO; significantly impairs kinase
FT activity; decreased localization at the ciliary tips;
FT impaired ciliogenesis; results in abnormally elongated
FT cilia; impairs mitosis, cell-cycle exit and radial
FT neuroblast migration, while promoting apoptosis, when
FT tested in a heterologous system; loss of nuclear
FT localization; dbSNP:rs118203918)"
FT /evidence="ECO:0000269|PubMed:19185282,
FT ECO:0000269|PubMed:24797473, ECO:0000269|PubMed:24853502,
FT ECO:0000269|PubMed:29539279"
FT /id="VAR_057994"
FT VARIANT 305
FT /note="K -> T (in EJM10; impairs mitosis, cell-cycle exit
FT and radial neuroblast migration, while promoting apoptosis,
FT when tested in a heterologous system; dbSNP:rs765078446)"
FT /evidence="ECO:0000269|PubMed:29539279"
FT /id="VAR_080556"
FT VARIANT 320
FT /note="V -> I (in dbSNP:rs33936662)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:29539279"
FT /id="VAR_042002"
FT VARIANT 369..373
FT /note="Missing (in EJM10; unknown pathological
FT significance; dbSNP:rs201964851)"
FT /evidence="ECO:0000269|PubMed:29539279"
FT /id="VAR_080557"
FT VARIANT 471
FT /note="T -> K (in dbSNP:rs56164633)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042003"
FT VARIANT 476
FT /note="R -> Q (in dbSNP:rs55895113)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042004"
FT VARIANT 615
FT /note="A -> T (in EJM10; unknown pathological significance;
FT impairs mitosis, cell-cycle exit and radial neuroblast
FT migration, while promoting apoptosis, when tested in a
FT heterologous system; dbSNP:rs55932059)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:29539279"
FT /id="VAR_042005"
FT VARIANT 632
FT /note="Missing (in EJM10; impairs mitosis, cell-cycle exit
FT and radial neuroblast migration, while promoting apoptosis,
FT when tested in a heterologous system)"
FT /evidence="ECO:0000269|PubMed:29539279"
FT /id="VAR_080558"
FT MUTAGEN 33
FT /note="K->R: Loss of activity and autophosphorylation; when
FT associated with R-34; R-36 and R-38."
FT /evidence="ECO:0000269|PubMed:10699974"
FT MUTAGEN 34
FT /note="K->R: Loss of activity and autophosphorylation; when
FT associated with R-33; R-36 and R-38."
FT /evidence="ECO:0000269|PubMed:10699974"
FT MUTAGEN 36
FT /note="K->R: Loss of activity and autophosphorylation; when
FT associated with R-33; R-34 and R-38."
FT /evidence="ECO:0000269|PubMed:10699974"
FT MUTAGEN 38
FT /note="K->R: Loss of activity and autophosphorylation; when
FT associated with R-33; R-34 and R-36."
FT /evidence="ECO:0000269|PubMed:10699974"
FT MUTAGEN 157
FT /note="T->A: Reduction of activity and loss of
FT autophosphorylation. Loss of activity and
FT autophosphorylation; when associated with F-159."
FT /evidence="ECO:0000269|PubMed:10699974"
FT MUTAGEN 159
FT /note="Y->F: Reduction of activity and loss of
FT autophosphorylation. Loss of activity and
FT autophosphorylation; when associated with A-157."
FT /evidence="ECO:0000269|PubMed:10699974"
FT CONFLICT 48
FT /note="L -> Q (in Ref. 1; AAF37278)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="H -> L (in Ref. 1; AAF37278)"
FT /evidence="ECO:0000305"
FT CONFLICT 310
FT /note="K -> R (in Ref. 1; AAF37278)"
FT /evidence="ECO:0000305"
FT CONFLICT 598..599
FT /note="FH -> LD (in Ref. 1; AAF37278)"
FT /evidence="ECO:0000305"
FT CONFLICT 629
FT /note="A -> P (in Ref. 1; AAF37278)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 632 AA; 71427 MW; F4C22C6CCD5878D2 CRC64;
MNRYTTIRQL GDGTYGSVLL GRSIESGELI AIKKMKRKFY SWEECMNLRE VKSLKKLNHA
NVVKLKEVIR ENDHLYFIFE YMKENLYQLI KERNKLFPES AIRNIMYQIL QGLAFIHKHG
FFHRDLKPEN LLCMGPELVK IADFGLAREI RSKPPYTDYV STRWYRAPEV LLRSTNYSSP
IDVWAVGCIM AEVYTLRPLF PGASEIDTIF KICQVLGTPK KTDWPEGYQL SSAMNFRWPQ
CVPNNLKTLI PNASSEAVQL LRDMLQWDPK KRPTASQALR YPYFQVGHPL GSTTQNLQDS
EKPQKGILEK AGPPPYIKPV PPAQPPAKPH TRISSRQHQA SQPPLHLTYP YKAEVSRTDH
PSHLQEDKPS PLLFPSLHNK HPQSKITAGL EHKNGEIKPK SRRRWGLISR STKDSDDWAD
LDDLDFSPSL SRIDLKNKKR QSDDTLCRFE SVLDLKPSEP VGTGNSAPTQ TSYQRRDTPT
LRSAAKQHYL KHSRYLPGIS IRNGILSNPG KEFIPPNPWS SSGLSGKSSG TMSVISKVNS
VGSSSTSSSG LTGNYVPSFL KKEIGSAMQR VHLAPIPDPS PGYSSLKAMR PHPGRPFFHT
QPRSTPGLIP RPPAAQPVHG RTDWASKYAS RR
