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Q8N568

- DCLK2_HUMAN

UniProt

Q8N568 - DCLK2_HUMAN

Protein

Serine/threonine-protein kinase DCLK2

Gene

DCLK2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 112 (01 Oct 2014)
      Sequence version 4 (18 May 2010)
      Previous versions | rss
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    Functioni

    Protein kinase with a significantly reduced C(a2+)/CAM affinity and dependence compared to other members of the CaMK family. May play a role in the down-regulation of CRE-dependent gene activation probably by phosphorylation of the CREB coactivator CRTC2/TORC2 and the resulting retention of TORC2 in the cytoplasm By similarity.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei423 – 4231ATPPROSITE-ProRule annotation
    Active sitei515 – 5151Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi400 – 4089ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. protein serine/threonine kinase activity Source: UniProtKB-KW

    GO - Biological processi

    1. intracellular signal transduction Source: InterPro

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    SignaLinkiQ8N568.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Serine/threonine-protein kinase DCLK2 (EC:2.7.11.1)
    Alternative name(s):
    CaMK-like CREB regulatory kinase 2
    Short name:
    CL2
    Short name:
    CLICK-II
    Short name:
    CLICK2
    Doublecortin domain-containing protein 3B
    Doublecortin-like and CAM kinase-like 2
    Doublecortin-like kinase 2
    Gene namesi
    Name:DCLK2
    Synonyms:DCAMKL2, DCDC3B, DCK2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:19002. DCLK2.

    Subcellular locationi

    Cytoplasmcytoskeleton
    Note: Colocalizes with microtubules.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-KW
    2. cytoskeleton Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Cytoskeleton

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA162383366.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 766766Serine/threonine-protein kinase DCLK2PRO_0000085922Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei647 – 6471PhosphoserineBy similarity
    Modified residuei666 – 6661PhosphothreonineBy similarity

    Post-translational modificationi

    Autophosphorylated.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ8N568.
    PaxDbiQ8N568.
    PRIDEiQ8N568.

    PTM databases

    PhosphoSiteiQ8N568.

    Expressioni

    Tissue specificityi

    Expressed in the brain, heart and eyes.1 Publication

    Developmental stagei

    Expressed in fetal brain, and, to a lower extent, in fetal kidney.1 Publication

    Gene expression databases

    ArrayExpressiQ8N568.
    BgeeiQ8N568.
    CleanExiHS_DCLK2.
    GenevestigatoriQ8N568.

    Organism-specific databases

    HPAiHPA015770.

    Interactioni

    Subunit structurei

    Binds to and stabilizes microtubules. Interacts with MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK9/JNK2, PPP1R9B/NEURABIN-2 and actin.By similarity

    Protein-protein interaction databases

    BioGridi127929. 2 interactions.
    IntActiQ8N568. 3 interactions.
    STRINGi9606.ENSP00000296550.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8N568.
    SMRiQ8N568. Positions 64-169, 352-694.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini72 – 15887Doublecortin 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini197 – 28084Doublecortin 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini394 – 651258Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi293 – 36270Ser-richAdd
    BLAST
    Compositional biasi713 – 75341Pro-richAdd
    BLAST

    Domaini

    The doublecortin domains are involved in the colocalization with microtubules.By similarity

    Sequence similaritiesi

    Contains 2 doublecortin domains.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000230855.
    HOVERGENiHBG003790.
    KOiK08805.
    OMAiTWRRHRD.
    OrthoDBiEOG7M98FQ.
    PhylomeDBiQ8N568.
    TreeFamiTF318770.

    Family and domain databases

    Gene3Di3.10.20.230. 2 hits.
    InterProiIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
    IPR003533. Doublecortin_dom.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PANTHERiPTHR24347. PTHR24347. 1 hit.
    PfamiPF03607. DCX. 2 hits.
    PF00069. Pkinase. 1 hit.
    [Graphical view]
    SMARTiSM00537. DCX. 2 hits.
    SM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS50309. DC. 2 hits.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q8N568-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MASTRSIELE HFEERDKRPR PGSRRGAPSS SGGSSSSGPK GNGLIPSPAH    50
    SAHCSFYRTR TLQALSSEKK AKKARFYRNG DRYFKGLVFA ISSDRFRSFD 100
    ALLIELTRSL SDNVNLPQGV RTIYTIDGSR KVTSLDELLE GESYVCASNE 150
    PFRKVDYTKN INPNWSVNIK GGTSRALAAA SSVKSEVKES KDFIKPKLVT 200
    VIRSGVKPRK AVRILLNKKT AHSFEQVLTD ITEAIKLDSG VVKRLCTLDG 250
    KQVTCLQDFF GDDDVFIACG PEKFRYAQDD FVLDHSECRV LKSSYSRSSA 300
    VKYSGSKSPG PSRRSKSPAS VNGTPSSQLS TPKSTKSSSS SPTSPGSFRG 350
    LKQISAHGRS SSNVNGGPEL DRCISPEGVN GNRCSESSTL LEKYKIGKVI 400
    GDGNFAVVKE CIDRSTGKEF ALKIIDKAKC CGKEHLIENE VSILRRVKHP 450
    NIIMLVEEME TATELFLVME LVKGGDLFDA ITSSTKYTER DGSAMVYNLA 500
    NALRYLHGLS IVHRDIKPEN LLVCEYPDGT KSLKLGDFGL ATVVEGPLYT 550
    VCGTPTYVAP EIIAETGYGL KVDIWAAGVI TYILLCGFPP FRSENNLQED 600
    LFDQILAGKL EFPAPYWDNI TDSAKELISQ MLQVNVEARC TAGQILSHPW 650
    VSDDASQENN MQAEVTGKLK QHFNNALPKQ NSTTTGVSVI MNTALDKEGQ 700
    IFCSKHCQDS GRPGMEPISP VPPSVEEIPV PGEAVPAPTP PESPTPHPPP 750
    AAPGGERAGT WRRHRD 766
    Length:766
    Mass (Da):83,606
    Last modified:May 18, 2010 - v4
    Checksum:i024F3223874AE83C
    GO
    Isoform 2 (identifier: Q8N568-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         353-353: Missing.

    Note: By homology to mouse isoform 2.

    Show »
    Length:765
    Mass (Da):83,478
    Checksum:i48EE55037EFF8AD8
    GO
    Isoform 3 (identifier: Q8N568-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         321-321: V → VKRGGHYSSAYSTAKSPV

    Show »
    Length:783
    Mass (Da):85,384
    Checksum:iD69154961F0CFF77
    GO

    Sequence cautioni

    The sequence BAD92418.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti694 – 6941A → V in CAD39156. (PubMed:17974005)Curated
    Sequence conflicti748 – 7481P → C in BAD92418. 1 PublicationCurated
    Sequence conflicti748 – 7481P → C in CAD39156. (PubMed:17974005)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti119 – 1191G → C.1 Publication
    Corresponds to variant rs56327537 [ dbSNP | Ensembl ].
    VAR_040441
    Natural varianti372 – 3721R → H.1 Publication
    Corresponds to variant rs34386880 [ dbSNP | Ensembl ].
    VAR_040442
    Natural varianti583 – 5831I → V.1 Publication
    Corresponds to variant rs35745104 [ dbSNP | Ensembl ].
    VAR_040443

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei321 – 3211V → VKRGGHYSSAYSTAKSPV in isoform 3. 1 PublicationVSP_012793
    Alternative sequencei353 – 3531Missing in isoform 2. CuratedVSP_012794

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB209181 mRNA. Translation: BAD92418.1. Different initiation.
    AC093748 Genomic DNA. No translation available.
    AC105343 Genomic DNA. No translation available.
    AC108934 Genomic DNA. No translation available.
    AC118064 Genomic DNA. No translation available.
    AL834498 mRNA. Translation: CAD39156.1.
    CCDSiCCDS34076.1. [Q8N568-1]
    CCDS47142.2. [Q8N568-3]
    RefSeqiNP_001035350.2. NM_001040260.3. [Q8N568-1]
    NP_001035351.4. NM_001040261.4. [Q8N568-3]
    XP_005262843.1. XM_005262786.1. [Q8N568-2]
    UniGeneiHs.591683.

    Genome annotation databases

    EnsembliENST00000296550; ENSP00000296550; ENSG00000170390. [Q8N568-1]
    ENST00000302176; ENSP00000303887; ENSG00000170390. [Q8N568-3]
    ENST00000506325; ENSP00000427235; ENSG00000170390. [Q8N568-2]
    GeneIDi166614.
    KEGGihsa:166614.
    UCSCiuc003ilm.4. human. [Q8N568-1]
    uc003ilo.4. human. [Q8N568-3]

    Polymorphism databases

    DMDMi296439470.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB209181 mRNA. Translation: BAD92418.1 . Different initiation.
    AC093748 Genomic DNA. No translation available.
    AC105343 Genomic DNA. No translation available.
    AC108934 Genomic DNA. No translation available.
    AC118064 Genomic DNA. No translation available.
    AL834498 mRNA. Translation: CAD39156.1 .
    CCDSi CCDS34076.1. [Q8N568-1 ]
    CCDS47142.2. [Q8N568-3 ]
    RefSeqi NP_001035350.2. NM_001040260.3. [Q8N568-1 ]
    NP_001035351.4. NM_001040261.4. [Q8N568-3 ]
    XP_005262843.1. XM_005262786.1. [Q8N568-2 ]
    UniGenei Hs.591683.

    3D structure databases

    ProteinModelPortali Q8N568.
    SMRi Q8N568. Positions 64-169, 352-694.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 127929. 2 interactions.
    IntActi Q8N568. 3 interactions.
    STRINGi 9606.ENSP00000296550.

    Chemistry

    ChEMBLi CHEMBL5519.
    GuidetoPHARMACOLOGYi 2006.

    PTM databases

    PhosphoSitei Q8N568.

    Polymorphism databases

    DMDMi 296439470.

    Proteomic databases

    MaxQBi Q8N568.
    PaxDbi Q8N568.
    PRIDEi Q8N568.

    Protocols and materials databases

    DNASUi 166614.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000296550 ; ENSP00000296550 ; ENSG00000170390 . [Q8N568-1 ]
    ENST00000302176 ; ENSP00000303887 ; ENSG00000170390 . [Q8N568-3 ]
    ENST00000506325 ; ENSP00000427235 ; ENSG00000170390 . [Q8N568-2 ]
    GeneIDi 166614.
    KEGGi hsa:166614.
    UCSCi uc003ilm.4. human. [Q8N568-1 ]
    uc003ilo.4. human. [Q8N568-3 ]

    Organism-specific databases

    CTDi 166614.
    GeneCardsi GC04P150999.
    HGNCi HGNC:19002. DCLK2.
    HPAi HPA015770.
    MIMi 613166. gene.
    neXtProti NX_Q8N568.
    PharmGKBi PA162383366.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000230855.
    HOVERGENi HBG003790.
    KOi K08805.
    OMAi TWRRHRD.
    OrthoDBi EOG7M98FQ.
    PhylomeDBi Q8N568.
    TreeFami TF318770.

    Enzyme and pathway databases

    SignaLinki Q8N568.

    Miscellaneous databases

    GenomeRNAii 166614.
    NextBioi 88597.
    PROi Q8N568.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8N568.
    Bgeei Q8N568.
    CleanExi HS_DCLK2.
    Genevestigatori Q8N568.

    Family and domain databases

    Gene3Di 3.10.20.230. 2 hits.
    InterProi IPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
    IPR003533. Doublecortin_dom.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    PANTHERi PTHR24347. PTHR24347. 1 hit.
    Pfami PF03607. DCX. 2 hits.
    PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00537. DCX. 2 hits.
    SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS50309. DC. 2 hits.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
      Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Brain.
    2. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 68-766 (ISOFORM 3).
      Tissue: Amygdala.
    4. Cited for: GENE FAMILY.
    5. "Alternative transcripts of Dclk1 and Dclk2 and their expression in doublecortin knockout mice."
      Tuy F.P.D., Saillour Y., Kappeler C., Chelly J., Francis F.
      Dev. Neurosci. 30:171-186(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    6. Cited for: REVIEW, GENE FAMILY.
    7. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS [LARGE SCALE ANALYSIS] CYS-119; HIS-372 AND VAL-583.

    Entry informationi

    Entry nameiDCLK2_HUMAN
    AccessioniPrimary (citable) accession number: Q8N568
    Secondary accession number(s): C9J5Q9, Q59GC8, Q8N399
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 15, 2005
    Last sequence update: May 18, 2010
    Last modified: October 1, 2014
    This is version 112 of the entry and version 4 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 4
      Human chromosome 4: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3