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O88764

- DAPK3_RAT

UniProt

O88764 - DAPK3_RAT

Protein

Death-associated protein kinase 3

Gene

Dapk3

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 117 (01 Oct 2014)
      Sequence version 1 (01 Nov 1998)
      Previous versions | rss
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    Functioni

    Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation, actin cytoskeleton reorganization, cell motility, smooth muscle contraction, and mitosis, particularly cytokinesis. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Regulates myosin phosphorylation in both smooth muscle and non-muscle cells. In smooth muscle, regulates myosin either directly by phosphorylating MYL12B and MYL9 or through inhibition of smooth muscle myosin phosphatase (SMPP1M) via phosphorylation of PPP1R12A, and the inhibition of SMPP1M functions to enhance muscle responsiveness to Ca2+ and promote a contractile state. Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Phosphorylates STAT3 and enhances its transcriptional activity. Positively regulates the canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2. Can disrupt the NLK-TCF7L2 complex thereby influencing the phosphorylation of TCF7L2 by NLK. Phosphorylates histone H3 on 'Thr-11' at centromeres during mitosis. Involved in the formation of promyelocytic leukemia protein nuclear body (PML-NB), one of many subnuclear domains in the eukaryotic cell nucleus, and which is involved in oncogenesis and viral infection. Phosphorylates RPL13A on 'Ser-77' upon interferon-gamma activation which is causing RPL13A release from the ribosome, its association with the GAIT complex and its subsequent involvement in transcript-selective translation inhibition By similarity.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.2 Publications

    Cofactori

    Magnesium.2 Publications

    Enzyme regulationi

    Inhibited by pyridone 6 (K00225), a potent, ATP-competitive inhibitor. Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity. Oligomerization is required for full enzymatic activity By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei42 – 421ATPCurated
    Binding sitei94 – 941InhibitorBy similarity
    Binding sitei96 – 961InhibitorBy similarity
    Active sitei139 – 1391Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi19 – 279ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB
    2. calmodulin-dependent protein kinase activity Source: RefGenome
    3. protein homodimerization activity Source: UniProtKB
    4. protein serine/threonine kinase activity Source: UniProtKB

    GO - Biological processi

    1. apoptotic process Source: UniProtKB
    2. apoptotic signaling pathway Source: Ensembl
    3. cellular response to interferon-gamma Source: Ensembl
    4. chromatin modification Source: UniProtKB-KW
    5. intracellular signal transduction Source: UniProtKB
    6. negative regulation of translation Source: Ensembl
    7. neuron differentiation Source: RGD
    8. positive regulation of canonical Wnt signaling pathway Source: Ensembl
    9. positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
    10. protein autophosphorylation Source: UniProtKB
    11. regulation of transcription, DNA-templated Source: UniProtKB-KW
    12. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Activator, Chromatin regulator, Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Apoptosis, Transcription, Transcription regulation

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Death-associated protein kinase 3 (EC:2.7.11.1)
    Short name:
    DAP kinase 3
    Alternative name(s):
    DAP-like kinase
    Short name:
    Dlk
    MYPT1 kinase
    ZIP-kinase
    Gene namesi
    Name:Dapk3
    Synonyms:Zipk
    OrganismiRattus norvegicus (Rat)Imported
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi621766. Dapk3.

    Subcellular locationi

    Nucleus. Cytoplasm. NucleusPML body By similarity. Chromosomecentromere. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity
    Note: Relocates to the cytoplasm on binding PAWR where the complex appears to interact with actin filaments. Localizes to promyelocytic leukemia protein nuclear bodies (PML-NBs). Associated: with the centrosomes throughout the mitotic cell cycle, with the centromeres from prophase to anaphase and with the contractile ring during cytokinesis By similarity.By similarity

    GO - Cellular componenti

    1. chromosome, centromeric region Source: UniProtKB-SubCell
    2. cytoplasm Source: UniProtKB-SubCell
    3. membrane raft Source: UniProtKB
    4. microtubule organizing center Source: UniProtKB-SubCell
    5. nucleus Source: UniProtKB
    6. PML body Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Centromere, Chromosome, Cytoplasm, Cytoskeleton, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi42 – 421K → A: Loss of kinase activity and of translocation into the cytoplasm. 1 Publication
    Mutagenesisi294 – 2941A → T: Causes dissociation from promyelocytic leukemia oncogenic bodies and increased blebbing-inducing potency; when associated with T-300. 1 Publication
    Mutagenesisi295 – 2951A → T: Causes dissociation from promyelocytic leukemia oncogenic bodies and increased blebbing-inducing potency; when associated with T-299. 1 Publication
    Mutagenesisi418 – 44831Missing: Prevents binding to ATF4 but not PAWR. Add
    BLAST

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 448448Death-associated protein kinase 3PRO_0000085916Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei180 – 1801PhosphothreonineBy similarity
    Modified residuei225 – 2251PhosphothreonineBy similarity
    Modified residuei265 – 2651Phosphothreonine; by autocatalysis and ROCK1By similarity
    Modified residuei304 – 3041Phosphoserine; by DAPK1By similarity
    Modified residuei306 – 3061Phosphoserine; by autocatalysis and DAPK1By similarity
    Modified residuei307 – 3071Phosphoserine; by DAPK1By similarity
    Modified residuei313 – 3131Phosphoserine; by DAPK1By similarity
    Modified residuei321 – 3211Phosphoserine; by DAPK1By similarity

    Post-translational modificationi

    Ubiquitinated. Ubiquitination mediated by the UBE2D3 E3 ligase does not lead to proteasomal degradation, but influences promyelocytic leukemia protein nuclear bodies (PML-NBs) formation in the nucleus By similarity.By similarity
    The phosphorylation status is critical for its activity and its ability to oligomerize. Phosphorylation increases the trimeric form, and its dephosphorylation shifts the equilibrium towards the monomeric form. Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity. A species-specific loss of a key phosphorylation site in murine DAPK3 seems to direct it to the nucleus, while the presence of the 'Thr-299' site in human DAPK3 correlates with cytoplasmic localization.

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiO88764.

    Expressioni

    Tissue specificityi

    Ubiquitously expressed in all tissue types examined. High levels in brain, heart, lung and spleen, lower expression in kidney, liver, skeletal muscle and testis. Isoform 2 is expressed in the smooth muscle.1 Publication

    Gene expression databases

    GenevestigatoriO88764.

    Interactioni

    Subunit structurei

    Monomer and homotrimer. Can also exist as homodimer or form heterodimers with ATF4. Homodimerization is required for activation segment autophosphorylation. Both interactions require an intact leucine zipper domain and oligomerization is required for full enzymatic activity. Interacts with UBE2D1, UBE2D2 AND UBE2D3. Interacts with AR and this interaction is enhanced by AATF. Interacts (via leucine zipper) with TCP10L (via leucine zipper). Interacts (via kinase domain) with DAPK1 (via kinase domain). Interacts with STAT3, NLK and TCF7L2 By similarity. Also binds to DAXX and PAWR, possibly in a ternary complex which plays a role in caspase activation. Interacts with AATF and CDC5L.By similarity4 Publications

    Protein-protein interaction databases

    BioGridi249061. 5 interactions.
    IntActiO88764. 2 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliO88764.
    SMRiO88764. Positions 2-276.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini13 – 275263Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni161 – 20444Activation segmentBy similarityAdd
    BLAST
    Regioni276 – 32853Interaction with ARBy similarityAdd
    BLAST
    Regioni277 – 30630Interaction with MYPT1By similarityAdd
    BLAST
    Regioni390 – 44859Interaction with CDC5LAdd
    BLAST
    Regioni422 – 43615Leucine-zipperBy similarityAdd
    BLAST

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000233016.
    HOVERGENiHBG101549.
    InParanoidiO88764.
    KOiK08803.
    PhylomeDBiO88764.
    TreeFamiTF314166.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR020675. Myosin_light_ch_kinase-rel.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PANTHERiPTHR22964. PTHR22964. 1 hit.
    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]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O88764-1) [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

    MSTFRQEDVE DHYEMGEELG SGQFAIVRKC QQKGTGMEYA AKFIKKRRLP    50
    SSRRGVSREE IEREVSILRE IRHPNIITLH DVFENKTDVV LILELVSGGE 100
    LFDFLAEKES LTEDEATQFL KQILDGVHYL HSKRIAHFDL KPENIMLLDK 150
    HAASPRIKLI DFGIAHRIEA GSEFKNIFGT PEFVAPEIVN YEPLGLEADM 200
    WSIGVITYIL LSGASPFLGE TKQETLTNIS AVNYDFDEEY FSSTSELAKD 250
    FIRRLLVKDP KRRMTIAQSL EHSWIKVRRR EDGARKPERR RLRAARLREY 300
    SLKSHSSMPR NTSYASFERF SRVLEDVAAA EQGLRELQRG RRQCRERVCA 350
    LRVAAEQREA RCRDGSAGLG RDLRRLRTEL GRTEALRTRA QEEARAALLG 400
    AGGLKRRLCR LENRYDALAA QVAAEVQFVR DLVRALEQER LQAECGVR 448
    Length:448
    Mass (Da):51,450
    Last modified:November 1, 1998 - v1
    Checksum:i843C0FD0BF0C1EEA
    GO
    Isoform 2 (identifier: O88764-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MIDSSCVPRILQKDSAMM

    Show »
    Length:465
    Mass (Da):53,326
    Checksum:i1AC035BCAB567234
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 11M → MIDSSCVPRILQKDSAMM in isoform 2. CuratedVSP_042061

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ006971 mRNA. Translation: CAA07360.1.
    BC062076 mRNA. Translation: AAH62076.1.
    RefSeqiNP_071991.1. NM_022546.1. [O88764-1]
    XP_006241054.1. XM_006240992.1. [O88764-1]
    XP_006241055.1. XM_006240993.1. [O88764-1]
    XP_006241056.1. XM_006240994.1. [O88764-1]
    UniGeneiRn.60353.

    Genome annotation databases

    GeneIDi64391.
    KEGGirno:64391.
    UCSCiRGD:621766. rat. [O88764-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ006971 mRNA. Translation: CAA07360.1 .
    BC062076 mRNA. Translation: AAH62076.1 .
    RefSeqi NP_071991.1. NM_022546.1. [O88764-1 ]
    XP_006241054.1. XM_006240992.1. [O88764-1 ]
    XP_006241055.1. XM_006240993.1. [O88764-1 ]
    XP_006241056.1. XM_006240994.1. [O88764-1 ]
    UniGenei Rn.60353.

    3D structure databases

    ProteinModelPortali O88764.
    SMRi O88764. Positions 2-276.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 249061. 5 interactions.
    IntActi O88764. 2 interactions.

    Proteomic databases

    PaxDbi O88764.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 64391.
    KEGGi rno:64391.
    UCSCi RGD:621766. rat. [O88764-1 ]

    Organism-specific databases

    CTDi 1613.
    RGDi 621766. Dapk3.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233016.
    HOVERGENi HBG101549.
    InParanoidi O88764.
    KOi K08803.
    PhylomeDBi O88764.
    TreeFami TF314166.

    Miscellaneous databases

    NextBioi 613146.
    PROi O88764.

    Gene expression databases

    Genevestigatori O88764.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR020675. Myosin_light_ch_kinase-rel.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    PANTHERi PTHR22964. PTHR22964. 1 hit.
    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. "Cloning and characterization of Dlk, a novel serine/threonine kinase that is tightly associated with chromatin and phosphorylates core histones."
      Koegel D., Ploettner O., Landsberg G., Christian S., Scheidtmann K.H.
      Oncogene 17:2645-2654(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Prostate.
    3. "AATF -- a novel transcription factor that interacts with Dlk/ZIP kinase and interferes with apoptosis."
      Page G., Loedige I., Kogel D., Scheidtmann K.H.
      FEBS Lett. 462:187-191(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AATF.
    4. "Interaction partners of Dlk/ZIP kinase: co-expression of Dlk/ZIP kinase and Par-4 results in cytoplasmic retention and apoptosis."
      Page G., Kogel D., Rangnekar V., Scheidtmann K.H.
      Oncogene 18:7265-7273(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH ATF4 AND PAWR, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-42.
    5. "Zipper-interacting protein kinase induces Ca(2+)-free smooth muscle contraction via myosin light chain phosphorylation."
      Niiro N., Ikebe M.
      J. Biol. Chem. 276:29567-29574(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: ALTERNATIVE SPLICING (ISOFORM 2), FUNCTION IN PHOSPHORYLATION OF MYL12B AND PPP1R12A.
    6. "DAP-like kinase interacts with the rat homolog of Schizosaccharomyces pombe CDC5 protein, a factor involved in pre-mRNA splicing and required for G2/M phase transition."
      Engemann H., Heinzel V., Page G., Preuss U., Scheidtmann K.H.
      Nucleic Acids Res. 30:1408-1417(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CDC5L.
    7. "ZIPK: a unique case of murine-specific divergence of a conserved vertebrate gene."
      Shoval Y., Pietrokovski S., Kimchi A.
      PLoS Genet. 3:1884-1893(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PAWR, MUTAGENESIS OF ALA-294 AND ALA-295.
    8. "Phosphorylation-dependent control of ZIPK nuclear import is species specific."
      Weitzel D.H., Chambers J., Haystead T.A.
      Cell. Signal. 23:297-303(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.

    Entry informationi

    Entry nameiDAPK3_RAT
    AccessioniPrimary (citable) accession number: O88764
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 28, 2003
    Last sequence update: November 1, 1998
    Last modified: October 1, 2014
    This is version 117 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    The murine DAPK3 protein differs from the human ortholog, losing an important phosphorylation site and displaying distinct altered cellular localization. The murine protein localizes only to the nucleus while the human protein shows both nuclear and cytoplasmic localization. A different protein interaction capacity, with an important protein partner in the apoptosis pathway (PAWR), evolved in the murine system to maintain the basic membrane blebbing function in the apoptosis pathway.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3