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Q8VDF3

- DAPK2_MOUSE

UniProt

Q8VDF3 - DAPK2_MOUSE

Protein

Death-associated protein kinase 2

Gene

Dapk2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 115 (01 Oct 2014)
      Sequence version 1 (01 Mar 2002)
      Previous versions | rss
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    Functioni

    Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Capable of regulating both type I apoptotic and type II autophagic cell deaths signal. The former involves caspase activation, chromatin and mitochondrial condensation while the latter involves caspase-independent cell death in conjunction with accumulation of mature autophagic vesicles, plasma membrane blebs, and nuclear condensation without DNA degradation. Mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation By similarity.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Cofactori

    Magnesium.By similarity

    Enzyme regulationi

    Activated by Ca2+/calmodulin. Regulated by a double locking mechanism, involving autophosphorylation at Ser-318, calmodulin binding, and dimerization. In the inactive state, Ser-318 is phosphorylated, and the kinase is dimeric. Activation involves: dephosphorylation at Ser-318, release-of-autoinhibition mechanism where calmodulin binding induces a conformational change that relieves the steric block of the active site by the autoinhibitory domain, and generation of the monomeric active form of the kinase.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei52 – 521ATP1 PublicationPROSITE-ProRule annotation
    Active sitei149 – 1491Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi29 – 379ATP1 PublicationPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB
    2. calmodulin binding Source: UniProtKB
    3. calmodulin-dependent protein kinase activity Source: RefGenome

    GO - Biological processi

    1. anoikis Source: Ensembl
    2. intracellular signal transduction Source: UniProtKB
    3. positive regulation of execution phase of apoptosis Source: Ensembl
    4. protein phosphorylation Source: UniProtKB
    5. regulation of apoptotic process Source: RefGenome
    6. regulation of intrinsic apoptotic signaling pathway Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Apoptosis

    Keywords - Ligandi

    ATP-binding, Calmodulin-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Death-associated protein kinase 2 (EC:2.7.11.1)
    Short name:
    DAP kinase 2
    Alternative name(s):
    DAP-kinase-related protein 1
    Short name:
    DRP-1
    Gene namesi
    Name:Dapk2
    OrganismiMus musculus (Mouse)Imported
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 9

    Organism-specific databases

    MGIiMGI:1341297. Dapk2.

    Subcellular locationi

    Cytoplasm By similarity. Cytoplasmic vesicleautophagosome lumen By similarity

    GO - Cellular componenti

    1. autophagic vacuole lumen Source: UniProtKB-SubCell
    2. cytoplasm Source: UniProtKB
    3. cytoplasmic vesicle Source: UniProtKB-KW

    Keywords - Cellular componenti

    Cytoplasm, Cytoplasmic vesicle

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 370370Death-associated protein kinase 2PRO_0000085913Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei299 – 2991Phosphoserine1 Publication
    Modified residuei318 – 3181Phosphoserine; by autocatalysisBy similarity
    Modified residuei349 – 3491Phosphoserine1 Publication

    Post-translational modificationi

    Autophosphorylation at Ser-318 inhibits its catalytic activity. Dephosphorylated at Ser-318 in response to activated Fas and TNF-alpha receptors.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ8VDF3.
    PaxDbiQ8VDF3.
    PRIDEiQ8VDF3.

    PTM databases

    PhosphoSiteiQ8VDF3.

    Expressioni

    Tissue specificityi

    Isoform 1 is found in the adult brain while isoform 2 is expressed in brains of embryos and young mice (at protein level).1 Publication

    Gene expression databases

    BgeeiQ8VDF3.
    CleanExiMM_DAPK2.
    GenevestigatoriQ8VDF3.

    Interactioni

    Subunit structurei

    Homodimer in its autoinhibited state. Active as monomer.1 Publication

    Protein-protein interaction databases

    BioGridi199051. 1 interaction.
    STRINGi10090.ENSMUSP00000034944.

    Structurei

    Secondary structure

    1
    370
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi19 – 213
    Beta strandi23 – 3210
    Beta strandi35 – 428
    Turni43 – 453
    Beta strandi48 – 569
    Beta strandi59 – 613
    Beta strandi63 – 664
    Helixi68 – 7811
    Beta strandi89 – 946
    Beta strandi96 – 1049
    Helixi111 – 1155
    Helixi123 – 14220
    Helixi152 – 1543
    Beta strandi155 – 1584
    Beta strandi162 – 1643
    Beta strandi167 – 1693
    Helixi191 – 1933
    Helixi196 – 1994
    Helixi207 – 22216
    Helixi232 – 2409
    Helixi248 – 2514
    Helixi256 – 26510
    Turni270 – 2723
    Helixi276 – 2805
    Turni283 – 2853
    Helixi290 – 2978
    Helixi303 – 3097

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2YA9X-ray2.30A/B11-370[»]
    2YAAX-ray2.30A/B11-370[»]
    2YABX-ray1.90A/B11-370[»]
    ProteinModelPortaliQ8VDF3.
    SMRiQ8VDF3. Positions 13-311.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ8VDF3.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini23 – 285263Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni287 – 35468Calmodulin-bindingBy similarityAdd
    BLAST
    Regioni292 – 30110Autoinhibitory domain

    Domaini

    The autoinhibitory domain sterically blocks the substrate peptide-binding site by making both hydrophobic and electrostatic contacts with the kinase core.

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00740000114993.
    HOGENOMiHOG000233016.
    HOVERGENiHBG100551.
    InParanoidiQ8VDF3.
    KOiK08803.
    OMAiCNHLSRS.
    OrthoDBiEOG7QZGBH.
    PhylomeDBiQ8VDF3.
    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: Q8VDF3-1) [UniParc]FASTAAdd to Basket

    Also known as: Alpha

    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

    MVQASMRSPN METFKQQKVE DFYDIGEELG SGQFAIVKKC REKSTGLEYA    50
    AKFIKKRQSR ASRRGVCREE IEREVSILRQ VLHPNIITLH DVYENRTDVV 100
    LILELVSGGE LFDFLAQKES LSEEEATSFI KQILDGVNYL HTKKIAHFDL 150
    KPENIMLLDK NIPIPHIKLI DFGLAHEIED GVEFKNIFGT PEFVAPEIVN 200
    YEPLGLEADM WSIGVITYIL LSGASPFLGD TKQETLANIT AVSYDFDEEF 250
    FSQTSELAKD FIRKLLVKET RKRLTIQEAL RHPWITPVDT QQAMVRRESV 300
    VNLENFKKQY VRRRWKLSFS IVSLCNHLTR SLMKKVHLRT SEDLRNCESD 350
    TEENIARRKA LHPRRRSSTS 370
    Length:370
    Mass (Da):42,778
    Last modified:March 1, 2002 - v1
    Checksum:i7BF8577140B5F883
    GO
    Isoform 2 (identifier: Q8VDF3-2) [UniParc]FASTAAdd to Basket

    Also known as: Beta

    The sequence of this isoform differs from the canonical sequence as follows:
         286-370: TPVDTQQAMV...LHPRRRSSTS → SKGEARAPEQ...AEEVLAGLSL

    Show »
    Length:489
    Mass (Da):56,035
    Checksum:iDB08AE634C47ABFC
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti89 – 891L → R in AAC35002. (PubMed:10629061)Curated
    Sequence conflicti90 – 901H → Q in BAA88064. (PubMed:10376525)Curated
    Sequence conflicti270 – 2701T → P in AAC35002. (PubMed:10629061)Curated
    Sequence conflicti341 – 3411S → I in AAC35002. (PubMed:10629061)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei286 – 37085TPVDT…RSSTS → SKGEARAPEQWKAQPAQLKT KRLREYTLKCHSSMPPNNTY VNFERFAHVVEDVARVDKGC RALAGAHDTLQDDVESLVSI YNEKEAWYREENENARHNLS QLKYEYRKVESLKKLLREDI QATGASLGGVARKLDHLQAQ FETLRQQLSADIQWMQELVG IFQLESENTDSHSLGFMFHR DPSESLSELLNRSHAEEVLA GLSL in isoform 2. CuratedVSP_042058Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB018002 mRNA. Translation: BAA88064.1.
    BC022165 mRNA. Translation: AAH22165.1.
    AF052942 mRNA. Translation: AAC35002.1.
    CCDSiCCDS23303.1. [Q8VDF3-1]
    RefSeqiNP_034149.2. NM_010019.3. [Q8VDF3-1]
    UniGeneiMm.304472.
    Mm.335252.

    Genome annotation databases

    EnsembliENSMUST00000034944; ENSMUSP00000034944; ENSMUSG00000032380. [Q8VDF3-1]
    GeneIDi13143.
    KEGGimmu:13143.
    UCSCiuc009qen.2. mouse. [Q8VDF3-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB018002 mRNA. Translation: BAA88064.1 .
    BC022165 mRNA. Translation: AAH22165.1 .
    AF052942 mRNA. Translation: AAC35002.1 .
    CCDSi CCDS23303.1. [Q8VDF3-1 ]
    RefSeqi NP_034149.2. NM_010019.3. [Q8VDF3-1 ]
    UniGenei Mm.304472.
    Mm.335252.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2YA9 X-ray 2.30 A/B 11-370 [» ]
    2YAA X-ray 2.30 A/B 11-370 [» ]
    2YAB X-ray 1.90 A/B 11-370 [» ]
    ProteinModelPortali Q8VDF3.
    SMRi Q8VDF3. Positions 13-311.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 199051. 1 interaction.
    STRINGi 10090.ENSMUSP00000034944.

    PTM databases

    PhosphoSitei Q8VDF3.

    Proteomic databases

    MaxQBi Q8VDF3.
    PaxDbi Q8VDF3.
    PRIDEi Q8VDF3.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000034944 ; ENSMUSP00000034944 ; ENSMUSG00000032380 . [Q8VDF3-1 ]
    GeneIDi 13143.
    KEGGi mmu:13143.
    UCSCi uc009qen.2. mouse. [Q8VDF3-1 ]

    Organism-specific databases

    CTDi 23604.
    MGIi MGI:1341297. Dapk2.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00740000114993.
    HOGENOMi HOG000233016.
    HOVERGENi HBG100551.
    InParanoidi Q8VDF3.
    KOi K08803.
    OMAi CNHLSRS.
    OrthoDBi EOG7QZGBH.
    PhylomeDBi Q8VDF3.
    TreeFami TF314166.

    Miscellaneous databases

    EvolutionaryTracei Q8VDF3.
    NextBioi 283226.
    PROi Q8VDF3.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q8VDF3.
    CleanExi MM_DAPK2.
    Genevestigatori Q8VDF3.

    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. "Death-associated protein kinase 2 is a new calcium/calmodulin-dependent protein kinase that signals apoptosis through its catalytic activity."
      Kawai T., Nomura F., Hoshino K., Copeland N.G., Gilbert D.J., Jenkins N.A., Akira S.
      Oncogene 18:3471-3480(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    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].
    3. "Death-associated protein kinase-related protein 1, a novel serine/threonine kinase involved in apoptosis."
      Inbal B., Shani G., Cohen O., Kissil J.L., Kimchi A.
      Mol. Cell. Biol. 20:1044-1054(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 68-370.
    4. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299 AND SER-349, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    5. "New modularity of DAP-kinases: alternative splicing of the DRP-1 gene produces a ZIPk-like isoform."
      Shoval Y., Berissi H., Kimchi A., Pietrokovski S.
      PLoS ONE 6:E17344-E17344(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: ALTERNATIVE SPLICING (ISOFORM 2), TISSUE SPECIFICITY.
    6. "Structure of the dimeric autoinhibited conformation of DAPK2, a pro-apoptotic protein kinase."
      Patel A.K., Yadav R.P., Majava V., Kursula I., Kursula P.
      J. Mol. Biol. 409:369-383(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 11-370 IN COMPLEX WITH AMP AND ATP, SUBUNIT, ENZYME REGULATION, AUTOINHIBITORY DOMAIN.

    Entry informationi

    Entry nameiDAPK2_MOUSE
    AccessioniPrimary (citable) accession number: Q8VDF3
    Secondary accession number(s): O88861, Q9QYM4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 28, 2003
    Last sequence update: March 1, 2002
    Last modified: October 1, 2014
    This is version 115 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3