DCLK2_HUMAN
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 03-AUG-2022, entry version 167.
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 -!- 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};
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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 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. [Q8N568-2]
DR AlphaFoldDB; Q8N568; -.
DR SMR; Q8N568; -.
DR BioGRID; 127929; 10.
DR IntAct; Q8N568; 21.
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; Q8N568; -.
DR PeptideAtlas; Q8N568; -.
DR PRIDE; Q8N568; -.
DR ProteomicsDB; 72008; -. [Q8N568-1]
DR ProteomicsDB; 72009; -. [Q8N568-2]
DR ProteomicsDB; 72010; -. [Q8N568-3]
DR Antibodypedia; 16499; 180 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 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; 330091at2759; -.
DR PhylomeDB; Q8N568; -.
DR TreeFam; TF318770; -.
DR PathwayCommons; Q8N568; -.
DR SignaLink; Q8N568; -.
DR BioGRID-ORCS; 166614; 13 hits in 1104 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 120 other tissues.
DR ExpressionAtlas; Q8N568; baseline and differential.
DR Genevisible; Q8N568; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
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:0018105; P:peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0034504; P:protein localization to nucleus; IEA:Ensembl.
DR GO; GO:0021860; P:pyramidal neuron development; IEA:Ensembl.
DR Gene3D; 3.10.20.230; -; 2.
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 Pfam; PF03607; DCX; 2.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00537; DCX; 2.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF89837; SSF89837; 2.
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; unknown pathological 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
