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 27-MAR-2024, entry version 194. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 63. DR IntAct; Q9UPZ9; 33. 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 CPTAC; non-CPTAC-2976; -. DR CPTAC; non-CPTAC-2977; -. DR EPD; Q9UPZ9; -. DR jPOST; Q9UPZ9; -. DR MassIVE; Q9UPZ9; -. DR PaxDb; 9606-ENSP00000349458; -. DR PeptideAtlas; Q9UPZ9; -. DR ProteomicsDB; 85480; -. [Q9UPZ9-1] DR ProteomicsDB; 85481; -. [Q9UPZ9-2] DR Antibodypedia; 605; 326 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 AGR; HGNC:21219; -. 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; 5478252at2759; -. DR PhylomeDB; Q9UPZ9; -. DR TreeFam; TF328769; -. DR PathwayCommons; Q9UPZ9; -. DR SignaLink; Q9UPZ9; -. DR SIGNOR; Q9UPZ9; -. DR BioGRID-ORCS; 22858; 14 hits in 1184 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 188 other cell types or tissues. DR ExpressionAtlas; Q9UPZ9; baseline and differential. 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 CDD; cd07830; STKc_MAK_like; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR24055; MITOGEN-ACTIVATED PROTEIN KINASE; 1. DR PANTHER; PTHR24055:SF260; SERINE_THREONINE-PROTEIN KINASE ICK; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; Q9UPZ9; HS. 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; uncertain 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; uncertain significance; FT 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; uncertain significance; impairs FT mitosis, cell-cycle exit and radial neuroblast migration, FT while promoting apoptosis, when tested in a heterologous FT 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 //