DCLK2_RAT
ID DCLK2_RAT Reviewed; 767 AA.
AC Q5MPA9; Q5MPA7; Q5MPA8; Q5MPB0;
DT 23-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 23-MAR-2010, sequence version 2.
DT 03-AUG-2022, entry version 139.
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-like and CAM kinase-like 2;
DE AltName: Full=Doublecortin-like kinase 2;
GN Name=Dclk2; Synonyms=Dcamkl2, Dck2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), NUCLEOTIDE SEQUENCE [MRNA]
RP OF 269-386 (ISOFORM 3), INTERACTION WITH MICROTUBULES, SUBCELLULAR
RP LOCATION, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF LYS-438.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=15611072; DOI=10.1074/jbc.m411027200;
RA Edelman A.M., Kim W.Y., Higgins D., Goldstein E.G., Oberdoerster M.,
RA Sigurdson W.;
RT "Doublecortin kinase-2, a novel doublecortin-related protein kinase
RT associated with terminal segments of axons and dendrites.";
RL J. Biol. Chem. 280:8531-8543(2005).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-662 AND THR-681, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
CC -!- FUNCTION: Protein kinase with a significantly reduced Ca(2+)+/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: Interacts with MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK9/JNK2,
CC PPP1R9B/NEURABIN-2 and actin (By similarity). Binds to and stabilizes
CC microtubules; binding affinity is strongly reduced by
CC autophosphorylation. {ECO:0000250, ECO:0000269|PubMed:15611072}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:15611072}. Note=Colocalizes with microtubules. When
CC overexpressed in sympathetic neurons, localizes to cell body and to the
CC terminal segments of axons and dendrites.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q5MPA9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5MPA9-2; Sequence=VSP_038898, VSP_038899;
CC Name=3;
CC IsoId=Q5MPA9-3; Sequence=VSP_038897;
CC -!- DOMAIN: The doublecortin domains are involved in the binding to
CC microtubules.
CC -!- PTM: Autophosphorylated.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. CaMK subfamily. {ECO:0000305}.
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DR EMBL; AY673997; AAV85461.1; -; mRNA.
DR EMBL; AY673998; AAV85462.1; -; mRNA.
DR EMBL; AY673999; AAV85463.1; -; mRNA.
DR EMBL; AY674000; AAV85464.1; -; mRNA.
DR RefSeq; NP_001009691.3; NM_001009691.3. [Q5MPA9-1]
DR RefSeq; NP_001182761.1; NM_001195832.1. [Q5MPA9-2]
DR RefSeq; XP_006232741.1; XM_006232679.3. [Q5MPA9-1]
DR RefSeq; XP_006232743.1; XM_006232681.3. [Q5MPA9-3]
DR RefSeq; XP_017446402.1; XM_017590913.1. [Q5MPA9-2]
DR AlphaFoldDB; Q5MPA9; -.
DR SMR; Q5MPA9; -.
DR BioGRID; 259725; 2.
DR STRING; 10116.ENSRNOP00000053894; -.
DR iPTMnet; Q5MPA9; -.
DR PhosphoSitePlus; Q5MPA9; -.
DR PaxDb; Q5MPA9; -.
DR PRIDE; Q5MPA9; -.
DR GeneID; 310698; -.
DR KEGG; rno:310698; -.
DR UCSC; RGD:1308384; rat. [Q5MPA9-1]
DR CTD; 166614; -.
DR RGD; 1308384; Dclk2.
DR VEuPathDB; HostDB:ENSRNOG00000016550; -.
DR eggNOG; KOG0032; Eukaryota.
DR InParanoid; Q5MPA9; -.
DR OMA; LMTECKV; -.
DR OrthoDB; 330091at2759; -.
DR PhylomeDB; Q5MPA9; -.
DR TreeFam; TF318770; -.
DR PRO; PR:Q5MPA9; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000016550; Expressed in cerebellum and 19 other tissues.
DR ExpressionAtlas; Q5MPA9; baseline and differential.
DR Genevisible; Q5MPA9; RN.
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; ISO:RGD.
DR GO; GO:0004672; F:protein kinase activity; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; ISO:RGD.
DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; ISO:RGD.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0034504; P:protein localization to nucleus; IEA:Ensembl.
DR GO; GO:0021860; P:pyramidal neuron development; ISO:RGD.
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..767
FT /note="Serine/threonine-protein kinase DCLK2"
FT /id="PRO_0000393224"
FT DOMAIN 72..158
FT /note="Doublecortin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00072"
FT DOMAIN 196..279
FT /note="Doublecortin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00072"
FT DOMAIN 409..666
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 301..391
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 721..767
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..41
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 301..383
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 738..754
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 530
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 415..423
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 438
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:0000250|UniProtKB:Q8N568"
FT MOD_RES 377
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N568"
FT MOD_RES 662
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 681
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT VAR_SEQ 320..335
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15611072"
FT /id="VSP_038897"
FT VAR_SEQ 707..715
FT /note="NTALDKEGQ -> VQGHEHGSR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15611072"
FT /id="VSP_038898"
FT VAR_SEQ 716..767
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15611072"
FT /id="VSP_038899"
FT MUTAGEN 438
FT /note="K->A: Loss of autophosphorylation."
FT /evidence="ECO:0000269|PubMed:15611072"
FT CONFLICT 126
FT /note="V -> I (in Ref. 1; AAV85464)"
FT /evidence="ECO:0000305"
FT CONFLICT 308
FT /note="P -> L (in Ref. 1; AAV85464)"
FT /evidence="ECO:0000305"
FT CONFLICT 387
FT /note="R -> C (in Ref. 1; AAV85461/AAV85462)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 767 AA; 84016 MW; 2348331B01FF5B79 CRC64;
MASTRSIELE HFEERDKRPR PGSRRGAPSS SGGSSISGPK GNGLIPSPAH SAHCSFYRTR
TLQALSSEKK AKKARFYRNG DRYFKGLVFA ISSDRFRSFD ALLIELTRSL SDNVNLPQGV
RTIYTVDGSR KVTSLDELLE GESYVCASNE PFRKVDYTKN VNPNWSVNIK GGTTRTLAVA
SAKSEVKESK DFIKPKLVTV IRSGVKPRKA VRILLNKKTA HSFEQVLTDI TEAIKLDSGV
VKRLCTLDGK QVTCLQDFFG DDDVFIACGP EKYRYAQDDF VLDHSECRVL KSSYSRASAA
KYSGSRSPGL SRRSKSPASV KRAGHSSAYS TAKSPVNGTP SSQLSTPKST KSSSSSPTSP
GSFRGLKQIS AQGRSSSNVN GGPELDRCMS PEGVNGNRCS ESFTLLEKYR IGKVIGDGNF
AVVKECMDRS TGKEFALKII DKAKCCGKEH LIENEVSILR RVKHPNIIML VEEMETTTEL
FLVMELVKGG DLFDAITSST KYTERDGSAM VYNLASALRY LHGLSIVHRD IKPENLLVCE
YPDGTKSLKL GDFGLATVVE GPLYTVCGTP TYVAPEIIAE TGYGLKVDVW AAGVITYILL
CGFPPFRSEN NLQEDLFDQI LAGKLEFPAP YWDNITDSAK ELISQMLQVN VEARCTAGEI
LSHPWVSDDA SQENNMQAEV TGKLKQHFNN ALPKQNSTTT GVSVIMNTAL DKEGQVFCSK
HCRDSSKSSR EQTSAREAPP PPESPRPPGP PATSGCDPAG TWRRHRD
