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Q9HAZ1

- CLK4_HUMAN

UniProt

Q9HAZ1 - CLK4_HUMAN

Protein

Dual specificity protein kinase CLK4

Gene

CLK4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 114 (01 Oct 2014)
      Sequence version 1 (01 Mar 2001)
      Previous versions | rss
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    Functioni

    Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates SRSF1 and SRSF3. Required for the regulation of alternative splicing of MAPT/TAU. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.2 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Enzyme regulationi

    TG003 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei189 – 1891ATPPROSITE-ProRule annotation
    Active sitei286 – 2861Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi165 – 1739ATPPROSITE-ProRule annotation

    GO - Molecular functioni

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

    GO - Biological processi

    1. protein autophosphorylation Source: Ensembl
    2. regulation of RNA splicing Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    SignaLinkiQ9HAZ1.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Dual specificity protein kinase CLK4 (EC:2.7.12.1)
    Alternative name(s):
    CDC-like kinase 4
    Gene namesi
    Name:CLK4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:13659. CLK4.

    Subcellular locationi

    Nucleus By similarity

    GO - Cellular componenti

    1. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi189 – 1891K → R: Loss of function. 1 Publication

    Organism-specific databases

    PharmGKBiPA26598.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 481481Dual specificity protein kinase CLK4PRO_0000085873Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei136 – 1361Phosphoserine1 Publication
    Modified residuei138 – 1381Phosphoserine4 Publications

    Post-translational modificationi

    Autophosphorylates on all three types of residues.4 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ9HAZ1.
    PaxDbiQ9HAZ1.
    PRIDEiQ9HAZ1.

    PTM databases

    PhosphoSiteiQ9HAZ1.

    Expressioni

    Tissue specificityi

    Expressed in liver, kidney, heart, muscle, brain and endothelial cells.2 Publications

    Gene expression databases

    ArrayExpressiQ9HAZ1.
    BgeeiQ9HAZ1.
    CleanExiHS_CLK4.
    GenevestigatoriQ9HAZ1.

    Organism-specific databases

    HPAiHPA043746.
    HPA048118.

    Interactioni

    Subunit structurei

    Interacts with UBL5.2 Publications

    Protein-protein interaction databases

    BioGridi121501. 9 interactions.
    IntActiQ9HAZ1. 5 interactions.
    STRINGi9606.ENSP00000316948.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9HAZ1.
    SMRiQ9HAZ1. Positions 146-480.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini159 – 475317Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000203417.
    HOVERGENiHBG107720.
    InParanoidiQ9HAZ1.
    KOiK08823.
    OMAiCERYVPR.
    OrthoDBiEOG7TBC1V.
    PhylomeDBiQ9HAZ1.
    TreeFamiTF101041.

    Family and domain databases

    InterProiIPR011009. 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]
    PfamiPF00069. Pkinase. 1 hit.
    [Graphical view]
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9HAZ1-1 [UniParc]FASTAAdd to Basket

    « Hide

    MRHSKRTHCP DWDSRESWGH ESYRGSHKRK RRSHSSTQEN RHCKPHHQFK    50
    ESDCHYLEAR SLNERDYRDR RYVDEYRNDY CEGYVPRHYH RDIESGYRIH 100
    CSKSSVRSRR SSPKRKRNRH CSSHQSRSKS HRRKRSRSIE DDEEGHLICQ 150
    SGDVLRARYE IVDTLGEGAF GKVVECIDHG MDGMHVAVKI VKNVGRYREA 200
    ARSEIQVLEH LNSTDPNSVF RCVQMLEWFD HHGHVCIVFE LLGLSTYDFI 250
    KENSFLPFQI DHIRQMAYQI CQSINFLHHN KLTHTDLKPE NILFVKSDYV 300
    VKYNSKMKRD ERTLKNTDIK VVDFGSATYD DEHHSTLVST RHYRAPEVIL 350
    ALGWSQPCDV WSIGCILIEY YLGFTVFQTH DSKEHLAMME RILGPIPQHM 400
    IQKTRKRKYF HHNQLDWDEH SSAGRYVRRR CKPLKEFMLC HDEEHEKLFD 450
    LVRRMLEYDP TQRITLDEAL QHPFFDLLKK K 481
    Length:481
    Mass (Da):57,492
    Last modified:March 1, 2001 - v1
    Checksum:iF402C36835CDA306
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti352 – 3521L → F.1 Publication
    Corresponds to variant rs35272416 [ dbSNP | Ensembl ].
    VAR_040414
    Natural varianti363 – 3631I → V.1 Publication
    Corresponds to variant rs55746655 [ dbSNP | Ensembl ].
    VAR_040415

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF294429 mRNA. Translation: AAG10074.1.
    CCDSiCCDS4437.1.
    RefSeqiNP_065717.1. NM_020666.2.
    UniGeneiHs.406557.

    Genome annotation databases

    EnsembliENST00000316308; ENSP00000316948; ENSG00000113240.
    GeneIDi57396.
    KEGGihsa:57396.
    UCSCiuc003mjf.1. human.

    Polymorphism databases

    DMDMi34922132.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF294429 mRNA. Translation: AAG10074.1 .
    CCDSi CCDS4437.1.
    RefSeqi NP_065717.1. NM_020666.2.
    UniGenei Hs.406557.

    3D structure databases

    ProteinModelPortali Q9HAZ1.
    SMRi Q9HAZ1. Positions 146-480.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 121501. 9 interactions.
    IntActi Q9HAZ1. 5 interactions.
    STRINGi 9606.ENSP00000316948.

    Chemistry

    BindingDBi Q9HAZ1.
    ChEMBLi CHEMBL4203.
    GuidetoPHARMACOLOGYi 1993.

    PTM databases

    PhosphoSitei Q9HAZ1.

    Polymorphism databases

    DMDMi 34922132.

    Proteomic databases

    MaxQBi Q9HAZ1.
    PaxDbi Q9HAZ1.
    PRIDEi Q9HAZ1.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000316308 ; ENSP00000316948 ; ENSG00000113240 .
    GeneIDi 57396.
    KEGGi hsa:57396.
    UCSCi uc003mjf.1. human.

    Organism-specific databases

    CTDi 57396.
    GeneCardsi GC05M177962.
    HGNCi HGNC:13659. CLK4.
    HPAi HPA043746.
    HPA048118.
    MIMi 607969. gene.
    neXtProti NX_Q9HAZ1.
    PharmGKBi PA26598.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000203417.
    HOVERGENi HBG107720.
    InParanoidi Q9HAZ1.
    KOi K08823.
    OMAi CERYVPR.
    OrthoDBi EOG7TBC1V.
    PhylomeDBi Q9HAZ1.
    TreeFami TF101041.

    Enzyme and pathway databases

    SignaLinki Q9HAZ1.

    Miscellaneous databases

    GenomeRNAii 57396.
    NextBioi 63494.
    PROi Q9HAZ1.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9HAZ1.
    Bgeei Q9HAZ1.
    CleanExi HS_CLK4.
    Genevestigatori Q9HAZ1.

    Family and domain databases

    InterProi 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 ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular characterization of a cDNA encoding functional human CLK4 kinase and localization to chromosome 5q35."
      Schultz J., Jones T., Bork P., Sheer D., Blencke S., Steyrer S., Wellbrock U., Bevec D., Ullrich A., Wallasch C.
      Genomics 71:368-370(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-189.
      Tissue: Kidney.
    2. "Structural analysis of UBL5, a novel ubiquitin-like modifier."
      McNally T., Huang Q., Janis R.S., Liu Z., Olejniczak E.T., Reilly R.M.
      Protein Sci. 12:1562-1566(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH UBL5.
    3. Cited for: INTERACTION WITH UBL5.
    4. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
      Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
      Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    5. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
      Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
      Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-136 AND SER-138, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    7. "Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor in human endothelial cells."
      Eisenreich A., Bogdanov V.Y., Zakrzewicz A., Pries A., Antoniak S., Poller W., Schultheiss H.P., Rauch U.
      Circ. Res. 104:589-599(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
    8. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    9. "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] PHE-352 AND VAL-363.

    Entry informationi

    Entry nameiCLK4_HUMAN
    AccessioniPrimary (citable) accession number: Q9HAZ1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 19, 2003
    Last sequence update: March 1, 2001
    Last modified: October 1, 2014
    This is version 114 of the entry and version 1 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 5
      Human chromosome 5: 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