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O54784

- DAPK3_MOUSE

UniProt

O54784 - DAPK3_MOUSE

Protein

Death-associated protein kinase 3

Gene

Dapk3

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 1 (01 Jun 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 By similarity. 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 similarity2 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.1 Publication

    Cofactori

    Magnesium.1 Publication

    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. kinase activity Source: MGI
    4. protein binding Source: IntAct
    5. protein homodimerization activity Source: UniProtKB
    6. protein serine/threonine kinase activity Source: UniProtKB

    GO - Biological processi

    1. apoptotic signaling pathway Source: MGI
    2. cellular response to interferon-gamma Source: UniProtKB
    3. chromatin modification Source: UniProtKB-KW
    4. intracellular signal transduction Source: UniProtKB
    5. negative regulation of translation Source: Ensembl
    6. neuron differentiation Source: Ensembl
    7. positive regulation of canonical Wnt signaling pathway Source: Ensembl
    8. positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
    9. protein autophosphorylation Source: UniProtKB
    10. protein phosphorylation Source: UniProtKB
    11. regulation of apoptotic process Source: RefGenome
    12. regulation of transcription, DNA-templated Source: UniProtKB-KW
    13. 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
    OrganismiMus musculus (Mouse)Imported
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 10

    Organism-specific databases

    MGIiMGI:1203520. 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. microtubule organizing center Source: UniProtKB-SubCell
    4. nucleus Source: UniProtKB
    5. PML body Source: MGI

    Keywords - Cellular componenti

    Centromere, Chromosome, Cytoplasm, Cytoskeleton, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi42 – 421K → A: Loss of activity. 1 Publication
    Mutagenesisi422 – 4221V → A: Decreased activity; when associated with A-429 and A-436. 1 Publication
    Mutagenesisi429 – 4291V → A: Decreased activity; when associated with A-422 and A-436. 1 Publication
    Mutagenesisi436 – 4361L → A: Decreased activity; when associated with A-422 and A-429. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 448448Death-associated protein kinase 3PRO_0000085915Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei180 – 1801PhosphothreonineBy similarity
    Modified residuei225 – 2251PhosphothreonineBy similarity
    Modified residuei265 – 2651Phosphothreonine; by autocatalysis; alternateBy similarity
    Modified residuei265 – 2651Phosphothreonine; by ROCK1; alternateBy 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

    MaxQBiO54784.
    PaxDbiO54784.
    PRIDEiO54784.

    PTM databases

    PhosphoSiteiO54784.

    Expressioni

    Tissue specificityi

    Highly expressed in heart, brain, lung, skeletal muscle, kidney and testis. Lower levels in liver and spleen.1 Publication

    Gene expression databases

    ArrayExpressiO54784.
    BgeeiO54784.
    CleanExiMM_DAPK3.
    GenevestigatoriO54784.

    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 similarity3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    DaxxO356132EBI-77359,EBI-77304
    PawrQ925B02EBI-77359,EBI-77397

    Protein-protein interaction databases

    BioGridi199052. 5 interactions.
    IntActiO54784. 4 interactions.
    STRINGi10090.ENSMUSP00000035962.

    Structurei

    3D structure databases

    ProteinModelPortaliO54784.
    SMRiO54784. Positions 2-296.
    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 CDC5LBy similarityAdd
    BLAST
    Regioni422 – 43615Leucine-zipperBy similarityAdd
    BLAST

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000233016.
    HOVERGENiHBG101549.
    InParanoidiO54784.
    KOiK08803.
    OMAiDYSAREI.
    OrthoDBiEOG7QZGBH.
    PhylomeDBiO54784.
    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]

    Sequencei

    Sequence statusi: Complete.

    O54784-1 [UniParc]FASTAAdd to Basket

    « 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
    LRAAAEQREA RCRDGSAGLG RDLRRLRTEL GRTEALRTRA QEEARAALLG 400
    AGGLKRRLCR LENRYDALAA QVAAEVQFVR DLVRALEQER LQAECGVR 448
    Length:448
    Mass (Da):51,422
    Last modified:June 1, 1998 - v1
    Checksum:iDA32EF3EB1F20EFC
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB007143 mRNA. Translation: BAA24954.1.
    CCDSiCCDS24045.1.
    RefSeqiNP_001177402.1. NM_001190473.1.
    NP_031854.1. NM_007828.2.
    XP_006513258.1. XM_006513195.1.
    UniGeneiMm.10294.

    Genome annotation databases

    EnsembliENSMUST00000047665; ENSMUSP00000035962; ENSMUSG00000034974.
    ENSMUST00000178422; ENSMUSP00000137333; ENSMUSG00000034974.
    GeneIDi13144.
    KEGGimmu:13144.
    UCSCiuc007ggg.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB007143 mRNA. Translation: BAA24954.1 .
    CCDSi CCDS24045.1.
    RefSeqi NP_001177402.1. NM_001190473.1.
    NP_031854.1. NM_007828.2.
    XP_006513258.1. XM_006513195.1.
    UniGenei Mm.10294.

    3D structure databases

    ProteinModelPortali O54784.
    SMRi O54784. Positions 2-296.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 199052. 5 interactions.
    IntActi O54784. 4 interactions.
    STRINGi 10090.ENSMUSP00000035962.

    PTM databases

    PhosphoSitei O54784.

    Proteomic databases

    MaxQBi O54784.
    PaxDbi O54784.
    PRIDEi O54784.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000047665 ; ENSMUSP00000035962 ; ENSMUSG00000034974 .
    ENSMUST00000178422 ; ENSMUSP00000137333 ; ENSMUSG00000034974 .
    GeneIDi 13144.
    KEGGi mmu:13144.
    UCSCi uc007ggg.2. mouse.

    Organism-specific databases

    CTDi 1613.
    MGIi MGI:1203520. Dapk3.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233016.
    HOVERGENi HBG101549.
    InParanoidi O54784.
    KOi K08803.
    OMAi DYSAREI.
    OrthoDBi EOG7QZGBH.
    PhylomeDBi O54784.
    TreeFami TF314166.

    Miscellaneous databases

    NextBioi 283230.
    PROi O54784.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O54784.
    Bgeei O54784.
    CleanExi MM_DAPK3.
    Genevestigatori O54784.

    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. "ZIP kinase, a novel serine/threonine kinase which mediates apoptosis."
      Kawai T., Matsumoto M., Takeda K., Sanjo H., Akira S.
      Mol. Cell. Biol. 18:1642-1651(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH ATF4, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-42; VAL-422; VAL-429 AND LEU-436.
    2. "ZIP kinase triggers apoptosis from nuclear PML oncogenic domains."
      Kawai T., Akira S., Reed J.C.
      Mol. Cell. Biol. 23:6174-6186(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, INTERACTION WITH DAXX AND PAWR.
    3. Cited for: INTERACTION WITH UBE2D3.
    4. "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.
    5. "Heterotrimeric GAIT complex drives transcript-selective translation inhibition in murine macrophages."
      Arif A., Chatterjee P., Moodt R.A., Fox P.L.
      Mol. Cell. Biol. 32:5046-5055(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry nameiDAPK3_MOUSE
    AccessioniPrimary (citable) accession number: O54784
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 28, 2003
    Last sequence update: June 1, 1998
    Last modified: October 1, 2014
    This is version 124 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. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3