ID CTRO_HUMAN Reviewed; 2027 AA. AC O14578; Q2M5E1; Q6XUH8; Q86UQ9; Q9UPZ7; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 04-JAN-2005, sequence version 2. DT 24-JAN-2024, entry version 210. DE RecName: Full=Citron Rho-interacting kinase; DE Short=CRIK; DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P49025}; DE AltName: Full=Serine/threonine-protein kinase 21; GN Name=CIT; Synonyms=CRIK, KIAA0949, STK21; 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; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Huang C.Q., Wu S.L., Shan Y.X., Liu S., Xiao P.J.; RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Mao Y., Xie Y., Wu Q.; RT "Cloning and characterizing a novel human CRIK-SK gene."; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4). RX PubMed=15983625; DOI=10.1038/sj.mp.4001703; RA Lyons-Warren A., Chang J.J., Balkissoon R., Kamiya A., Garant M., RA Nurnberger J., Scheftner W., Reich T., McMahon F., Kelsoe J., Gershon E., RA Coryell W., Byerley W., Berrettini W., Depaulo R., McInnis M., Sawa A.; RT "Evidence of association between bipolar disorder and Citron on chromosome RT 12q24."; RL Mol. Psychiatry 10:807-809(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain; 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 [5] RP SEQUENCE REVISION. RA Ohara O., Nagase T., Kikuno R.; RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [7] RP FUNCTION, AND INTERACTION WITH KIF14. RX PubMed=16431929; DOI=10.1083/jcb.200511061; RA Gruneberg U., Neef R., Li X., Chan E.H.Y., Chalamalasetty R.B., Nigg E.A., RA Barr F.A.; RT "KIF14 and citron kinase act together to promote efficient cytokinesis."; RL J. Cell Biol. 172:363-372(2006). RN [8] RP FUNCTION. RX PubMed=16236794; DOI=10.1091/mbc.e05-06-0569; RA Kamijo K., Ohara N., Abe M., Uchimura T., Hosoya H., Lee J.S., Miki T.; RT "Dissecting the role of Rho-mediated signaling in contractile ring RT formation."; RL Mol. Biol. Cell 17:43-55(2006). RN [9] RP INTERACTION WITH TTC3. RX PubMed=17488780; DOI=10.1242/jcs.000703; RA Berto G., Camera P., Fusco C., Imarisio S., Ambrogio C., Chiarle R., RA Silengo L., Di Cunto F.; RT "The Down syndrome critical region protein TTC3 inhibits neuronal RT differentiation via RhoA and Citron kinase."; RL J. Cell Sci. 120:1859-1867(2007). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-440, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-433 AND SER-440, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [13] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1721, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-440, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [16] RP FUNCTION IN PHOSPHORYLATION OF MYL9/MLC2. RX PubMed=21457715; DOI=10.1016/j.febslet.2011.03.054; RA Tan I., Lai J., Yong J., Li S.F., Leung T.; RT "Chelerythrine perturbs lamellar actomyosin filaments by selective RT inhibition of myotonic dystrophy kinase-related Cdc42-binding kinase."; RL FEBS Lett. 585:1260-1268(2011). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-440, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [18] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-433; SER-440; SER-480; RP SER-582; SER-1940; SER-1993 AND THR-2013, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [20] RP FUNCTION, INVOLVEMENT IN MCPH17, VARIANTS MCPH17 VAL-106; GLN-126 AND RP VAL-230, AND CHARACTERIZATION OF VARIANTS MCPH17 VAL-106; GLN-126 AND RP VAL-230. RX PubMed=27453578; DOI=10.1016/j.ajhg.2016.07.004; RA Li H., Bielas S.L., Zaki M.S., Ismail S., Farfara D., Um K., Rosti R.O., RA Scott E.C., Tu S., Chi N.C., Gabriel S., Erson-Omay E.Z., RA Ercan-Sencicek A.G., Yasuno K., Caglayan A.O., Kaymakcalan H., Ekici B., RA Bilguvar K., Gunel M., Gleeson J.G.; RT "Biallelic mutations in Citron kinase Link mitotic cytokinesis to human RT primary microcephaly."; RL Am. J. Hum. Genet. 99:501-510(2016). RN [21] RP INVOLVEMENT IN MCPH17. RX PubMed=27453579; DOI=10.1016/j.ajhg.2016.07.003; RA Harding B.N., Moccia A., Drunat S., Soukarieh O., Tubeuf H., Chitty L.S., RA Verloes A., Gressens P., El Ghouzzi V., Joriot S., Di Cunto F., Martins A., RA Passemard S., Bielas S.L.; RT "Mutations in Citron kinase cause recessive microlissencephaly with RT multinucleated neurons."; RL Am. J. Hum. Genet. 99:511-520(2016). RN [22] RP INVOLVEMENT IN MCPH17. RX PubMed=27503289; DOI=10.1007/s00439-016-1722-2; RA Shaheen R., Hashem A., Abdel-Salam G.M., Al-Fadhli F., Ewida N., RA Alkuraya F.S.; RT "Mutations in CIT, encoding citron rho-interacting serine/threonine kinase, RT cause severe primary microcephaly in humans."; RL Hum. Genet. 135:1191-1197(2016). RN [23] RP INVOLVEMENT IN MCPH17. RX PubMed=27519304; DOI=10.1007/s00439-016-1724-0; RA Basit S., Al-Harbi K.M., Alhijji S.A., Albalawi A.M., Alharby E., RA Eldardear A., Samman M.I.; RT "CIT, a gene involved in neurogenic cytokinesis, is mutated in human RT primary microcephaly."; RL Hum. Genet. 135:1199-1207(2016). RN [24] RP VARIANTS [LARGE SCALE ANALYSIS] GLU-7; GLN-9 AND PHE-183. 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). CC -!- FUNCTION: Plays a role in cytokinesis. Required for KIF14 localization CC to the central spindle and midbody. Putative RHO/RAC effector that CC binds to the GTP-bound forms of RHO and RAC1. It probably binds p21 CC with a tighter specificity in vivo. Displays serine/threonine protein CC kinase activity. Plays an important role in the regulation of CC cytokinesis and the development of the central nervous system. CC Phosphorylates MYL9/MLC2. {ECO:0000269|PubMed:16236794, CC ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:21457715, CC ECO:0000269|PubMed:27453578}. 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 -!- 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; CC -!- SUBUNIT: Directly interacts with KIF14 depending on the activation CC state (stronger interaction with the kinase-dead form). Homodimer (By CC similarity). Interacts with TTC3. {ECO:0000250, CC ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:17488780}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=Long; CC IsoId=O14578-1; Sequence=Displayed; CC Name=2; Synonyms=Short, CRIK-SK; CC IsoId=O14578-2; Sequence=VSP_012434, VSP_012435; CC Name=3; CC IsoId=O14578-3; Sequence=VSP_014507, VSP_014508, VSP_014509; CC Name=4; CC IsoId=O14578-4; Sequence=VSP_043301; CC -!- DISEASE: Microcephaly 17, primary, autosomal recessive (MCPH17) CC [MIM:617090]: A form of microcephaly, a disease defined as a head CC circumference more than 3 standard deviations below the age, sex and CC ethnically matched mean. Brain weight is markedly reduced and the CC cerebral cortex is disproportionately small. MCPH17 is a severe form CC characterized by lissencephaly, enlarged ventricles, agenesis of the CC corpus callosum, cerebellar hypoplasia, and brainstem hypoplasia. CC Patients manifest delayed psychomotor development, intellectual CC disability, spasticity, axial hypotonia, and dysmorphic features. CC {ECO:0000269|PubMed:27453578, ECO:0000269|PubMed:27453579, CC ECO:0000269|PubMed:27503289, ECO:0000269|PubMed:27519304}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr CC protein kinase family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA76793.2; 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; AY257469; AAP13528.1; -; mRNA. DR EMBL; AY209000; AAP43922.1; -; mRNA. DR EMBL; AY681966; AAV87216.1; -; mRNA. DR EMBL; AB023166; BAA76793.2; ALT_INIT; mRNA. DR EMBL; AC002563; AAB71327.1; -; Genomic_DNA. DR EMBL; AC079317; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC004813; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS55891.1; -. [O14578-4] DR CCDS; CCDS9192.1; -. [O14578-1] DR RefSeq; NP_001193928.1; NM_001206999.1. [O14578-4] DR RefSeq; NP_009105.1; NM_007174.2. [O14578-1] DR AlphaFoldDB; O14578; -. DR SMR; O14578; -. DR BioGRID; 116290; 1435. DR IntAct; O14578; 17. DR MINT; O14578; -. DR STRING; 9606.ENSP00000376306; -. DR BindingDB; O14578; -. DR ChEMBL; CHEMBL5579; -. DR DrugBank; DB12010; Fostamatinib. DR DrugCentral; O14578; -. DR GlyGen; O14578; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O14578; -. DR PhosphoSitePlus; O14578; -. DR SwissPalm; O14578; -. DR BioMuta; CIT; -. DR CPTAC; CPTAC-2811; -. DR CPTAC; CPTAC-3078; -. DR EPD; O14578; -. DR jPOST; O14578; -. DR MassIVE; O14578; -. DR MaxQB; O14578; -. DR PaxDb; 9606-ENSP00000376306; -. DR PeptideAtlas; O14578; -. DR ProteomicsDB; 48094; -. [O14578-1] DR ProteomicsDB; 48095; -. [O14578-2] DR ProteomicsDB; 48096; -. [O14578-3] DR ProteomicsDB; 48097; -. [O14578-4] DR Pumba; O14578; -. DR Antibodypedia; 18910; 194 antibodies from 23 providers. DR DNASU; 11113; -. DR Ensembl; ENST00000261833.11; ENSP00000261833.7; ENSG00000122966.18. [O14578-1] DR Ensembl; ENST00000392521.7; ENSP00000376306.2; ENSG00000122966.18. [O14578-4] DR GeneID; 11113; -. DR KEGG; hsa:11113; -. DR MANE-Select; ENST00000392521.7; ENSP00000376306.2; NM_001206999.2; NP_001193928.1. [O14578-4] DR UCSC; uc001txi.3; human. [O14578-1] DR AGR; HGNC:1985; -. DR CTD; 11113; -. DR DisGeNET; 11113; -. DR GeneCards; CIT; -. DR HGNC; HGNC:1985; CIT. DR HPA; ENSG00000122966; Tissue enhanced (brain). DR MalaCards; CIT; -. DR MIM; 605629; gene. DR MIM; 617090; phenotype. DR neXtProt; NX_O14578; -. DR OpenTargets; ENSG00000122966; -. DR Orphanet; 2512; Autosomal recessive primary microcephaly. DR PharmGKB; PA26522; -. DR VEuPathDB; HostDB:ENSG00000122966; -. DR eggNOG; KOG0612; Eukaryota. DR eggNOG; KOG0976; Eukaryota. DR GeneTree; ENSGT01030000234517; -. DR HOGENOM; CLU_000288_63_5_1; -. DR InParanoid; O14578; -. DR OMA; ASSAWIT; -. DR OrthoDB; 3490126at2759; -. DR PhylomeDB; O14578; -. DR TreeFam; TF101140; -. DR PathwayCommons; O14578; -. DR Reactome; R-HSA-5625900; RHO GTPases activate CIT. DR Reactome; R-HSA-8980692; RHOA GTPase cycle. DR Reactome; R-HSA-9013026; RHOB GTPase cycle. DR Reactome; R-HSA-9013106; RHOC GTPase cycle. DR Reactome; R-HSA-9013149; RAC1 GTPase cycle. DR SignaLink; O14578; -. DR SIGNOR; O14578; -. DR BioGRID-ORCS; 11113; 290 hits in 1207 CRISPR screens. DR ChiTaRS; CIT; human. DR GeneWiki; CIT_(gene); -. DR GenomeRNAi; 11113; -. DR Pharos; O14578; Tchem. DR PRO; PR:O14578; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; O14578; Protein. DR Bgee; ENSG00000122966; Expressed in lateral nuclear group of thalamus and 161 other cell types or tissues. DR ExpressionAtlas; O14578; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:FlyBase. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0030165; F:PDZ domain binding; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:FlyBase. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB. DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IDA:FlyBase. DR GO; GO:0097110; F:scaffold protein binding; IDA:BHF-UCL. DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW. DR GO; GO:0001223; F:transcription coactivator binding; IPI:FlyBase. DR GO; GO:0048699; P:generation of neurons; ISS:UniProtKB. DR GO; GO:0000278; P:mitotic cell cycle; ISS:UniProtKB. DR GO; GO:0000281; P:mitotic cytokinesis; IMP:UniProtKB. DR GO; GO:0035331; P:negative regulation of hippo signaling; IMP:FlyBase. DR GO; GO:0051402; P:neuron apoptotic process; IMP:UniProtKB. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0032467; P:positive regulation of cytokinesis; IMP:UniProtKB. DR CDD; cd20814; CRIK; 1. DR CDD; cd05601; STKc_CRIK; 1. DR Gene3D; 1.10.287.1490; -; 1. DR Gene3D; 1.20.5.340; -; 1. DR Gene3D; 3.30.60.20; -; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR000961; AGC-kinase_C. DR InterPro; IPR046349; C1-like_sf. DR InterPro; IPR017405; Citron_Rho-interacting_kinase. DR InterPro; IPR001180; CNH_dom. DR InterPro; IPR037708; CRIK_dom. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR002219; PE/DAG-bd. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR001849; PH_domain. DR InterPro; IPR017892; Pkinase_C. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR22988:SF71; CITRON RHO-INTERACTING KINASE; 1. DR PANTHER; PTHR22988; MYOTONIC DYSTROPHY S/T KINASE-RELATED; 1. DR Pfam; PF00780; CNH; 1. DR Pfam; PF00169; PH; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF00433; Pkinase_C; 1. DR PIRSF; PIRSF038145; Citron_Rho-interacting_kinase; 1. DR SMART; SM00109; C1; 1. DR SMART; SM00036; CNH; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00133; S_TK_X; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF57889; Cysteine-rich domain; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS51285; AGC_KINASE_CTER; 1. DR PROSITE; PS50219; CNH; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. DR Genevisible; O14578; HS. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; ATP-binding; Cell cycle; Cell division; KW Coiled coil; Cytoplasm; Developmental protein; Differentiation; KW Disease variant; Kinase; Metal-binding; Mitosis; Neurogenesis; KW Nucleotide-binding; Phosphoprotein; Primary microcephaly; KW Reference proteome; Serine/threonine-protein kinase; SH3-binding; KW Transferase; Zinc; Zinc-finger. FT CHAIN 1..2027 FT /note="Citron Rho-interacting kinase" FT /id="PRO_0000085908" FT DOMAIN 97..360 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 361..431 FT /note="AGC-kinase C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618" FT DOMAIN 1443..1563 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT DOMAIN 1591..1881 FT /note="CNH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00795" FT ZN_FING 1362..1411 FT /note="Phorbol-ester/DAG-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226" FT REGION 1091..1302 FT /note="Interaction with Rho/Rac" FT REGION 1290..1310 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1322..1351 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1905..2012 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 453..1297 FT /evidence="ECO:0000255" FT MOTIF 1953..1958 FT /note="SH3-binding" FT /evidence="ECO:0000255" FT COMPBIAS 1913..1927 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1951..1999 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 221 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 103..111 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 126 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES 433 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 440 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 480 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 582 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1196 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P49025" FT MOD_RES 1721 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 1940 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1993 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 2013 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..467 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:10231032" FT /id="VSP_014507" FT VAR_SEQ 481..482 FT /note="EV -> GG (in isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_012434" FT VAR_SEQ 483..2027 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_012435" FT VAR_SEQ 694 FT /note="E -> EERRHSLENKVKRLETMERRENRLKDDIQTKSQQIQQMADKIL (in FT isoform 4)" FT /evidence="ECO:0000303|PubMed:15983625" FT /id="VSP_043301" FT VAR_SEQ 1239..1253 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:10231032" FT /id="VSP_014508" FT VAR_SEQ 1919 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:10231032" FT /id="VSP_014509" FT VARIANT 7 FT /note="G -> E (in dbSNP:rs36054900)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040417" FT VARIANT 9 FT /note="R -> Q (in dbSNP:rs56193743)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040418" FT VARIANT 106 FT /note="G -> V (in MCPH17; impairs kinase activity; exhibits FT abnormal mitotic cytokinesis; exhibits multipolar spindles; FT increases the neurons apoptotic process; FT dbSNP:rs886037892)" FT /evidence="ECO:0000269|PubMed:27453578" FT /id="VAR_077442" FT VARIANT 126 FT /note="K -> Q (in MCPH17; impairs kinase activity; exhibits FT abnormal mitotic cytokinesis; exhibits multipolar spindles; FT increases the neurons apoptotic process; FT dbSNP:rs886037893)" FT /evidence="ECO:0000269|PubMed:27453578" FT /id="VAR_077443" FT VARIANT 183 FT /note="L -> F" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040419" FT VARIANT 230 FT /note="D -> V (in MCPH17; impairs kinase activity; exhibits FT abnormal mitotic cytokinesis; exhibits multipolar spindles; FT increases the neurons apoptotic process; FT dbSNP:rs886037894)" FT /evidence="ECO:0000269|PubMed:27453578" FT /id="VAR_077444" FT CONFLICT 12 FT /note="L -> S (in Ref. 2; AAP43922)" FT /evidence="ECO:0000305" FT CONFLICT 56 FT /note="F -> L (in Ref. 2; AAP43922)" FT /evidence="ECO:0000305" FT CONFLICT 218 FT /note="V -> L (in Ref. 2; AAP43922)" FT /evidence="ECO:0000305" SQ SEQUENCE 2027 AA; 231431 MW; 6B1D8C3F661F357B CRC64; MLKFKYGARN PLDAGAAEPI ASRASRLNLF FQGKPPFMTQ QQMSPLSREG ILDALFVLFE ECSQPALMKI KHVSNFVRKY SDTIAELQEL QPSAKDFEVR SLVGCGHFAE VQVVREKATG DIYAMKVMKK KALLAQEQVS FFEEERNILS RSTSPWIPQL QYAFQDKNHL YLVMEYQPGG DLLSLLNRYE DQLDENLIQF YLAELILAVH SVHLMGYVHR DIKPENILVD RTGHIKLVDF GSAAKMNSNK MVNAKLPIGT PDYMAPEVLT VMNGDGKGTY GLDCDWWSVG VIAYEMIYGR SPFAEGTSAR TFNNIMNFQR FLKFPDDPKV SSDFLDLIQS LLCGQKERLK FEGLCCHPFF SKIDWNNIRN SPPPFVPTLK SDDDTSNFDE PEKNSWVSSS PCQLSPSGFS GEELPFVGFS YSKALGILGR SESVVSGLDS PAKTSSMEKK LLIKSKELQD SQDKCHKMEQ EMTRLHRRVS EVEAVLSQKE VELKASETQR SLLEQDLATY ITECSSLKRS LEQARMEVSQ EDDKALQLLH DIREQSRKLQ EIKEQEYQAQ VEEMRLMMNQ LEEDLVSARR RSDLYESELR ESRLAAEEFK RKATECQHKL LKAKDQGKPE VGEYAKLEKI NAEQQLKIQE LQEKLEKAVK ASTEATELLQ NIRQAKERAE RELEKLQNRE DSSEGIRKKL VEAEELEEKH REAQVSAQHL EVHLKQKEQH YEEKIKVLDN QIKKDLADKE TLENMMQRHE EEAHEKGKIL SEQKAMINAM DSKIRSLEQR IVELSEANKL AANSSLFTQR NMKAQEEMIS ELRQQKFYLE TQAGKLEAQN RKLEEQLEKI SHQDHSDKNR LLELETRLRE VSLEHEEQKL ELKRQLTELQ LSLQERESQL TALQAARAAL ESQLRQAKTE LEETTAEAEE EIQALTAHRD EIQRKFDALR NSCTVITDLE EQLNQLTEDN AELNNQNFYL SKQLDEASGA NDEIVQLRSE VDHLRREITE REMQLTSQKQ TMEALKTTCT MLEEQVMDLE ALNDELLEKE RQWEAWRSVL GDEKSQFECR VRELQRMLDT EKQSRARADQ RITESRQVVE LAVKEHKAEI LALQQALKEQ KLKAESLSDK LNDLEKKHAM LEMNARSLQQ KLETERELKQ RLLEEQAKLQ QQMDLQKNHI FRLTQGLQEA LDRADLLKTE RSDLEYQLEN IQVLYSHEKV KMEGTISQQT KLIDFLQAKM DQPAKKKKGL FSRRKEDPAL PTQVPLQYNE LKLALEKEKA RCAELEEALQ KTRIELRSAR EEAAHRKATD HPHPSTPATA RQQIAMSAIV RSPEHQPSAM SLLAPPSSRR KESSTPEEFS RRLKERMHHN IPHRFNVGLN MRATKCAVCL DTVHFGRQAS KCLECQVMCH PKCSTCLPAT CGLPAEYATH FTEAFCRDKM NSPGLQTKEP SSSLHLEGWM KVPRNNKRGQ QGWDRKYIVL EGSKVLIYDN EAREAGQRPV EEFELCLPDG DVSIHGAVGA SELANTAKAD VPYILKMESH PHTTCWPGRT LYLLAPSFPD KQRWVTALES VVAGGRVSRE KAEADAKLLG NSLLKLEGDD RLDMNCTLPF SDQVVLVGTE EGLYALNVLK NSLTHVPGIG AVFQIYIIKD LEKLLMIAGE ERALCLVDVK KVKQSLAQSH LPAQPDISPN IFEAVKGCHL FGAGKIENGL CICAAMPSKV VILRYNENLS KYCIRKEIET SEPCSCIHFT NYSILIGTNK FYEIDMKQYT LEEFLDKNDH SLAPAVFAAS SNSFPVSIVQ VNSAGQREEY LLCFHEFGVF VDSYGRRSRT DDLKWSRLPL AFAYREPYLF VTHFNSLEVI EIQARSSAGT PARAYLDIPN PRYLGPAISS GAIYLASSYQ DKLRVICCKG NLVKESGTEH HRGPSTSRSS PNKRGPPTYN EHITKRVASS PAPPEGPSHP REPSTPHRYR EGRTELRRDK SPGRPLEREK SPGRMLSTRR ERSPGRLFED SSRGRLPAGA VRTPLSQVNK VWDQSSV //