ID DCLK2_HUMAN Reviewed; 766 AA. AC Q8N568; C9J5Q9; Q59GC8; Q8N399; DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 4. DT 29-MAY-2024, entry version 177. DE RecName: Full=Serine/threonine-protein kinase DCLK2; DE EC=2.7.11.1; DE AltName: Full=CaMK-like CREB regulatory kinase 2; DE Short=CL2; DE Short=CLICK-II; DE Short=CLICK2; DE AltName: Full=Doublecortin domain-containing protein 3B; DE AltName: Full=Doublecortin-like and CAM kinase-like 2; DE AltName: Full=Doublecortin-like kinase 2; GN Name=DCLK2; Synonyms=DCAMKL2, DCDC3B, DCK2; 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 [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 68-766 (ISOFORM 3). RC TISSUE=Amygdala; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP GENE FAMILY. RX PubMed=16869982; DOI=10.1186/1471-2164-7-188; RA Reiner O., Coquelle F.M., Peter B., Levy T., Kaplan A., Sapir T., Orr I., RA Barkai N., Eichele G., Bergmann S.; RT "The evolving doublecortin (DCX) superfamily."; RL BMC Genomics 7:188-188(2006). RN [5] RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=18075264; DOI=10.1159/000109861; RA Tuy F.P.D., Saillour Y., Kappeler C., Chelly J., Francis F.; RT "Alternative transcripts of Dclk1 and Dclk2 and their expression in RT doublecortin knockout mice."; RL Dev. Neurosci. 30:171-186(2008). RN [6] RP REVIEW, AND GENE FAMILY. RX PubMed=20236041; DOI=10.2174/187152410790780118; RA Dijkmans T.F., van Hooijdonk L.W.A., Fitzsimons C.P., Vreugdenhil E.; RT "The doublecortin gene family and disorders of neuronal structure."; RL Cent. Nerv. Syst. Agents Med. Chem. 10:32-46(2010). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-61 AND SER-362, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; 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 [8] RP VARIANTS [LARGE SCALE ANALYSIS] CYS-119; HIS-372 AND VAL-583. 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 [9] RP VARIANT MET-212. RX PubMed=25512093; DOI=10.1002/humu.22744; RA Peeters K., Bervoets S., Chamova T., Litvinenko I., De Vriendt E., RA Bichev S., Kancheva D., Mitev V., Kennerson M., Timmerman V., De Jonghe P., RA Tournev I., MacMillan J., Jordanova A.; RT "Novel mutations in the DYNC1H1 tail domain refine the genetic and clinical RT spectrum of dyneinopathies."; RL Hum. Mutat. 36:287-291(2015). CC -!- FUNCTION: Protein kinase with a significantly reduced C(a2+)/CAM CC affinity and dependence compared to other members of the CaMK family. CC May play a role in the down-regulation of CRE-dependent gene activation CC probably by phosphorylation of the CREB coactivator CRTC2/TORC2 and the CC resulting retention of TORC2 in the cytoplasm (By similarity). CC {ECO:0000250}. 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: Binds to and stabilizes microtubules. Interacts with CC MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK9/JNK2, PPP1R9B/NEURABIN-2 and CC actin. {ECO:0000250}. CC -!- INTERACTION: CC Q8N568; Q96M94: KLHL15; NbExp=3; IntAct=EBI-2930406, EBI-2510129; CC Q8N568; P62258: YWHAE; NbExp=3; IntAct=EBI-2930406, EBI-356498; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Note=Colocalizes with CC microtubules. {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q8N568-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8N568-2; Sequence=VSP_012794; CC Name=3; CC IsoId=Q8N568-3; Sequence=VSP_012793; CC -!- TISSUE SPECIFICITY: Expressed in the brain, heart and eyes. CC {ECO:0000269|PubMed:18075264}. CC -!- DEVELOPMENTAL STAGE: Expressed in fetal brain, and, to a lower extent, CC in fetal kidney. {ECO:0000269|PubMed:18075264}. CC -!- DOMAIN: The doublecortin domains are involved in the colocalization CC with microtubules. {ECO:0000250}. CC -!- PTM: Autophosphorylated. {ECO:0000250}. CC -!- MISCELLANEOUS: [Isoform 2]: By homology to mouse isoform 2. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr CC protein kinase family. CaMK subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD92418.1; 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; AB209181; BAD92418.1; ALT_INIT; mRNA. DR EMBL; AC093748; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC105343; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC108934; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC118064; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL834498; CAD39156.1; -; mRNA. DR CCDS; CCDS34076.1; -. [Q8N568-1] DR CCDS; CCDS47142.2; -. [Q8N568-3] DR CCDS; CCDS93647.1; -. [Q8N568-2] DR RefSeq; NP_001035350.2; NM_001040260.3. [Q8N568-1] DR RefSeq; NP_001035351.4; NM_001040261.4. [Q8N568-3] DR RefSeq; XP_005262843.1; XM_005262786.2. DR AlphaFoldDB; Q8N568; -. DR SMR; Q8N568; -. DR BioGRID; 127929; 29. DR IntAct; Q8N568; 28. DR MINT; Q8N568; -. DR STRING; 9606.ENSP00000303887; -. DR BindingDB; Q8N568; -. DR ChEMBL; CHEMBL5519; -. DR DrugBank; DB12010; Fostamatinib. DR DrugCentral; Q8N568; -. DR GuidetoPHARMACOLOGY; 2006; -. DR iPTMnet; Q8N568; -. DR PhosphoSitePlus; Q8N568; -. DR BioMuta; DCLK2; -. DR DMDM; 296439470; -. DR EPD; Q8N568; -. DR jPOST; Q8N568; -. DR MassIVE; Q8N568; -. DR MaxQB; Q8N568; -. DR PaxDb; 9606-ENSP00000303887; -. DR PeptideAtlas; Q8N568; -. DR ProteomicsDB; 72008; -. [Q8N568-1] DR ProteomicsDB; 72009; -. [Q8N568-2] DR ProteomicsDB; 72010; -. [Q8N568-3] DR Pumba; Q8N568; -. DR Antibodypedia; 16499; 196 antibodies from 34 providers. DR DNASU; 166614; -. DR Ensembl; ENST00000296550.12; ENSP00000296550.7; ENSG00000170390.16. [Q8N568-1] DR Ensembl; ENST00000302176.8; ENSP00000303887.8; ENSG00000170390.16. [Q8N568-3] DR Ensembl; ENST00000506325.5; ENSP00000427235.1; ENSG00000170390.16. [Q8N568-2] DR GeneID; 166614; -. DR KEGG; hsa:166614; -. DR MANE-Select; ENST00000296550.12; ENSP00000296550.7; NM_001040260.4; NP_001035350.2. DR UCSC; uc003ilm.5; human. [Q8N568-1] DR AGR; HGNC:19002; -. DR CTD; 166614; -. DR DisGeNET; 166614; -. DR GeneCards; DCLK2; -. DR HGNC; HGNC:19002; DCLK2. DR HPA; ENSG00000170390; Tissue enhanced (brain, retina). DR MIM; 613166; gene. DR neXtProt; NX_Q8N568; -. DR OpenTargets; ENSG00000170390; -. DR PharmGKB; PA162383366; -. DR VEuPathDB; HostDB:ENSG00000170390; -. DR eggNOG; KOG0032; Eukaryota. DR GeneTree; ENSGT00940000154895; -. DR InParanoid; Q8N568; -. DR OMA; LMTECKV; -. DR OrthoDB; 2956627at2759; -. DR PhylomeDB; Q8N568; -. DR TreeFam; TF318770; -. DR PathwayCommons; Q8N568; -. DR SignaLink; Q8N568; -. DR BioGRID-ORCS; 166614; 14 hits in 1182 CRISPR screens. DR ChiTaRS; DCLK2; human. DR GenomeRNAi; 166614; -. DR Pharos; Q8N568; Tchem. DR PRO; PR:Q8N568; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; Q8N568; Protein. DR Bgee; ENSG00000170390; Expressed in oocyte and 121 other cell types or tissues. DR ExpressionAtlas; Q8N568; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW. DR GO; GO:0015630; C:microtubule cytoskeleton; IEA:TreeGrafter. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0008017; F:microtubule binding; IEA:Ensembl. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW. DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl. DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro. DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central. DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; IEA:Ensembl. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0034504; P:protein localization to nucleus; IEA:Ensembl. DR GO; GO:0021860; P:pyramidal neuron development; IEA:Ensembl. DR CDD; cd17141; DCX1_DCLK2; 1. DR CDD; cd17069; DCX2; 1. DR CDD; cd14184; STKc_DCKL2; 1. DR Gene3D; 3.10.20.230; Doublecortin domain; 2. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR003533; Doublecortin_dom. DR InterPro; IPR036572; Doublecortin_dom_sf. 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; PTHR24347; SERINE/THREONINE-PROTEIN KINASE; 1. DR PANTHER; PTHR24347:SF376; SERINE_THREONINE-PROTEIN KINASE DCLK2; 1. DR Pfam; PF03607; DCX; 2. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00537; DCX; 2. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF89837; Doublecortin (DC); 2. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS50309; DC; 2. 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; Cytoplasm; Cytoskeleton; Kinase; KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat; KW Serine/threonine-protein kinase; Transferase. FT CHAIN 1..766 FT /note="Serine/threonine-protein kinase DCLK2" FT /id="PRO_0000085922" FT DOMAIN 72..158 FT /note="Doublecortin 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00072" FT DOMAIN 197..280 FT /note="Doublecortin 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00072" FT DOMAIN 394..651 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 1..45 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 300..378 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 707..766 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 7..23 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 27..42 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 300..368 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 716..753 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 515 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 400..408 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 423 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 61 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 362 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 647 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q5MPA9" FT MOD_RES 666 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q5MPA9" FT VAR_SEQ 321 FT /note="V -> VKRGGHYSSAYSTAKSPV (in isoform 3)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_012793" FT VAR_SEQ 353 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_012794" FT VARIANT 119 FT /note="G -> C (in dbSNP:rs56327537)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040441" FT VARIANT 212 FT /note="V -> M (found in a patient with hereditary motor and FT sensory neuropathy; uncertain significance; FT dbSNP:rs759398144)" FT /evidence="ECO:0000269|PubMed:25512093" FT /id="VAR_073158" FT VARIANT 372 FT /note="R -> H (in dbSNP:rs34386880)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040442" FT VARIANT 583 FT /note="I -> V (in dbSNP:rs35745104)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040443" FT CONFLICT 694 FT /note="A -> V (in Ref. 3; CAD39156)" FT /evidence="ECO:0000305" FT CONFLICT 748 FT /note="P -> C (in Ref. 1; BAD92418 and 3; CAD39156)" FT /evidence="ECO:0000305" SQ SEQUENCE 766 AA; 83606 MW; 024F3223874AE83C CRC64; MASTRSIELE HFEERDKRPR PGSRRGAPSS SGGSSSSGPK GNGLIPSPAH SAHCSFYRTR TLQALSSEKK AKKARFYRNG DRYFKGLVFA ISSDRFRSFD ALLIELTRSL SDNVNLPQGV RTIYTIDGSR KVTSLDELLE GESYVCASNE PFRKVDYTKN INPNWSVNIK GGTSRALAAA SSVKSEVKES KDFIKPKLVT VIRSGVKPRK AVRILLNKKT AHSFEQVLTD ITEAIKLDSG VVKRLCTLDG KQVTCLQDFF GDDDVFIACG PEKFRYAQDD FVLDHSECRV LKSSYSRSSA VKYSGSKSPG PSRRSKSPAS VNGTPSSQLS TPKSTKSSSS SPTSPGSFRG LKQISAHGRS SSNVNGGPEL DRCISPEGVN GNRCSESSTL LEKYKIGKVI GDGNFAVVKE CIDRSTGKEF ALKIIDKAKC CGKEHLIENE VSILRRVKHP NIIMLVEEME TATELFLVME LVKGGDLFDA ITSSTKYTER DGSAMVYNLA NALRYLHGLS IVHRDIKPEN LLVCEYPDGT KSLKLGDFGL ATVVEGPLYT VCGTPTYVAP EIIAETGYGL KVDIWAAGVI TYILLCGFPP FRSENNLQED LFDQILAGKL EFPAPYWDNI TDSAKELISQ MLQVNVEARC TAGQILSHPW VSDDASQENN MQAEVTGKLK QHFNNALPKQ NSTTTGVSVI MNTALDKEGQ IFCSKHCQDS GRPGMEPISP VPPSVEEIPV PGEAVPAPTP PESPTPHPPP AAPGGERAGT WRRHRD //