CTRO_HUMAN
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 03-AUG-2022, entry version 202.
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};
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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; 1429.
DR IntAct; O14578; 15.
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 BioMuta; CIT; -.
DR EPD; O14578; -.
DR jPOST; O14578; -.
DR MassIVE; O14578; -.
DR MaxQB; O14578; -.
DR PaxDb; O14578; -.
DR PeptideAtlas; O14578; -.
DR PRIDE; O14578; -.
DR ProteomicsDB; 48094; -. [O14578-1]
DR ProteomicsDB; 48095; -. [O14578-2]
DR ProteomicsDB; 48096; -. [O14578-3]
DR ProteomicsDB; 48097; -. [O14578-4]
DR Antibodypedia; 18910; 181 antibodies from 23 providers.
DR DNASU; 11113; -.
DR Ensembl; ENST00000261833.11; ENSP00000261833.7; ENSG00000122966.17. [O14578-1]
DR Ensembl; ENST00000392521.7; ENSP00000376306.2; ENSG00000122966.17. [O14578-4]
DR Ensembl; ENST00000612548.4; ENSP00000482318.1; ENSG00000122966.17. [O14578-2]
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 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; 759391at2759; -.
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; 264 hits in 1127 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 159 other tissues.
DR ExpressionAtlas; O14578; baseline and differential.
DR Genevisible; O14578; HS.
DR GO; GO:0032154; C:cleavage furrow; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0031985; C:Golgi cisterna; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0030496; C:midbody; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
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:0031032; P:actomyosin structure organization; IBA:GO_Central.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0048699; P:generation of neurons; ISS:UniProtKB.
DR GO; GO:0007030; P:Golgi organization; IEA:Ensembl.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
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:0018107; P:peptidyl-threonine phosphorylation; IBA:GO_Central.
DR GO; GO:0032467; P:positive regulation of cytokinesis; IMP:UniProtKB.
DR GO; GO:0008064; P:regulation of actin polymerization or depolymerization; IEA:Ensembl.
DR CDD; cd00029; C1; 1.
DR CDD; cd05601; STKc_CRIK; 1.
DR Gene3D; 2.30.29.30; -; 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; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR22988:SF26; PTHR22988:SF26; 2.
DR Pfam; PF00780; CNH; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00069; Pkinase; 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; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57889; SSF57889; 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.
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
