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O54784

- DAPK3_MOUSE

UniProt

O54784 - DAPK3_MOUSE

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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

Functioni

Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation and actin cytoskeleton reorganization. Regulates both type I (caspase-dependent) apoptotic and type II (caspase-independent) autophagic cell deaths signal, depending on the cellular setting. Involved in formation of promyelocytic leukemia protein nuclear body (PML-NB). Involved in apoptosis involving PAWR which mediates cytoplasmic relocation; in vitro phosphorylates PAWR (By similarity). Phosphorylates MYL12B in non-muscle cells leading to reorganization of actin cytoskeleton such as in regulation of cell polarity and cell migration. Positively regulates canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2; disrupts the NLK-TCF7L2 complex thereby influencing the phosphorylation of TCF7L2 by NLK. Phosphorylates STAT3 and enhances its transcriptional activity. Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Phosphorylates histone H3 on 'Thr-11' at centromeres during mitosis (By similarity). Phosphorylates RPL13A on 'Ser-77' upon interferon-gamma activation which is causing RPL13A release from the ribosome, RPL13A association with the GAIT complex and its subsequent involvement in transcript-selective translation inhibition.By similarity6 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.4 Publications

Cofactori

Mg2+1 Publication

Enzyme regulationi

A sequential activation is proposed: autophosphorylation at consensus sites is leading to dimerization of the catalytic domain and activation segment exchange (producing an active confirmation of both kinase modules in trans) followed by phosphorylation at Thr-180 in the activation segment and at other regulatory sites (Probable). Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity. Inhibited by pyridone 6 (K00225), a potent, ATP-competitive inhibitor. Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity.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 homodimerization activity Source: UniProtKB
  5. 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 cell migration Source: UniProtKB
  9. positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
  10. protein autophosphorylation Source: UniProtKB
  11. protein phosphorylation Source: UniProtKB
  12. regulation of apoptotic process Source: RefGenome
  13. regulation of cell shape Source: UniProtKB
  14. regulation of myosin II filament organization Source: UniProtKB
  15. regulation of transcription, DNA-templated Source: UniProtKB-KW
  16. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

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

Enzyme and pathway databases

ReactomeiREACT_252543. Role of DCC in regulating apoptosis.

Names & Taxonomyi

Protein namesi
Recommended name:
Death-associated protein kinase 3 (EC:2.7.11.14 Publications)
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 3 Publications. NucleusPML body 1 Publication. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity. Chromosomecentromere By similarity. Cytoplasm By similarity
Note: Predominantly localized to the nucleus. Relocates to the cytoplasm on binding PAWR where the complex appears to interact with actin filaments. 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-KW
  2. cytoplasm Source: UniProtKB-KW
  3. cytoskeleton Source: UniProtKB-KW
  4. nucleus Source: UniProtKB
  5. PML body Source: MGI
Complete GO annotation...

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
Mutagenesisi289 – 2902RR → AA: Nuclear localization. 1 Publication
Mutagenesisi294 – 2941A → D: Nuclear colocalization. 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; alternate1 Publication
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.1 Publication
The phosphorylation status is critical for kinase activity, oligomerization and intracellular localization. Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity. The phosphorylated form is localized in the cytoplasm and nuclear translocation or retention is maximal when it is not phosphorylated. Phosphorylation increases the trimeric form, and its dephosphorylation favors a kinase-inactive monomeric form.By similarity

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

BgeeiO54784.
CleanExiMM_DAPK3.
ExpressionAtlasiO54784. baseline and differential.
GenevestigatoriO54784.

Interactioni

Subunit structurei

Homooligomer in its kinase-active form (homotrimers and homodimers are reported); monomeric in its kinase-inactive form. Homodimerization is required for activation segment autophosphorylation (By similarity). Interacts with DAXX, PAWR, ATF4, NLK, TCF7L2, UBE2D1, UBE2D2, UBE2D3, and CDC5L. Interacts with AR; enhanced by AATF.By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ATF4P188482EBI-77359,EBI-492498From a different organism.
Atf4Q065073EBI-77359,EBI-77383
DaxxO356132EBI-77359,EBI-77304
PawrQ925B02EBI-77359,EBI-77397
Stat3P422278EBI-77359,EBI-602878
UBE2D3P610772EBI-77359,EBI-348268From a different organism.

Protein-protein interaction databases

BioGridi199052. 5 interactions.
IntActiO54784. 10 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
Regioni390 – 44859Interaction with CDC5LBy similarityAdd
BLAST
Regioni422 – 43615Leucine-zipper1 PublicationAdd
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.
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

        10         20         30         40         50
MSTFRQEDVE DHYEMGEELG SGQFAIVRKC QQKGTGMEYA AKFIKKRRLP
60 70 80 90 100
SSRRGVSREE IEREVSILRE IRHPNIITLH DVFENKTDVV LILELVSGGE
110 120 130 140 150
LFDFLAEKES LTEDEATQFL KQILDGVHYL HSKRIAHFDL KPENIMLLDK
160 170 180 190 200
HAASPRIKLI DFGIAHRIEA GSEFKNIFGT PEFVAPEIVN YEPLGLEADM
210 220 230 240 250
WSIGVITYIL LSGASPFLGE TKQETLTNIS AVNYDFDEEY FSSTSELAKD
260 270 280 290 300
FIRRLLVKDP KRRMTIAQSL EHSWIKVRRR EDGARKPERR RLRAARLREY
310 320 330 340 350
SLKSHSSMPR NTSYASFERF SRVLEDVAAA EQGLRELQRG RRQCRERVCA
360 370 380 390 400
LRAAAEQREA RCRDGSAGLG RDLRRLRTEL GRTEALRTRA QEEARAALLG
410 420 430 440
AGGLKRRLCR LENRYDALAA QVAAEVQFVR DLVRALEQER LQAECGVR
Length:448
Mass (Da):51,422
Last modified:June 1, 1998 - v1
Checksum:iDA32EF3EB1F20EFC
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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. 10 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.

Enzyme and pathway databases

Reactomei REACT_252543. Role of DCC in regulating apoptosis.

Miscellaneous databases

NextBioi 283230.
PROi O54784.
SOURCEi Search...

Gene expression databases

Bgeei O54784.
CleanExi MM_DAPK3.
ExpressionAtlasi O54784. baseline and differential.
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.
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], CATALYTIC ACTIVITY, COFACTOR, FUNCTION IN APOPTOSIS, 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: FUNCTION IN APOPTOSIS, SUBCELLULAR LOCATION, INTERACTION WITH DAXX AND PAWR.
  3. "ZIP kinase is responsible for the phosphorylation of myosin II and necessary for cell motility in mammalian fibroblasts."
    Komatsu S., Ikebe M.
    J. Cell Biol. 165:243-254(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF MYL12B, CATALYTIC ACTIVITY, FUNCTION IN CYTOSKELETON REORGANIZATION.
  4. "Physical and functional interactions between STAT3 and ZIP kinase."
    Sato N., Kawai T., Sugiyama K., Muromoto R., Imoto S., Sekine Y., Ishida M., Akira S., Matsuda T.
    Int. Immunol. 17:1543-1552(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF STAT3, CATALYTIC ACTIVITY, INTERACTION WITH STAT3.
  5. "Phosphorylation of threonine-265 in zipper-interacting protein kinase plays an important role in its activity and is induced by IL-6 family cytokines."
    Sato N., Kamada N., Muromoto R., Kawai T., Sugiyama K., Watanabe T., Imoto S., Sekine Y., Ohbayashi N., Ishida M., Akira S., Matsuda T.
    Immunol. Lett. 103:127-134(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: AUTOPHOSPHORYLATION AT THR-265.
  6. Cited for: INTERACTION WITH UBE2D1; UBE2D2 AND UBE2D3, UBIQUITINATION, SUBCELLULAR LOCATION.
  7. "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, MUTAGENESIS OF 289-ARG-ARG-290 AND ALA-294.
  8. "Zipper-interacting protein kinase (ZIPK) modulates canonical Wnt/beta-catenin signaling through interaction with Nemo-like kinase and T-cell factor 4 (NLK/TCF4)."
    Togi S., Ikeda O., Kamitani S., Nakasuji M., Sekine Y., Muromoto R., Nanbo A., Oritani K., Kawai T., Akira S., Matsuda T.
    J. Biol. Chem. 286:19170-19177(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH NLK AND TCF7L2.
  9. "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 IN PHOSPHORYLATION OF RPL13A, CATALYTIC ACTIVITY.

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: November 26, 2014
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

A species-specific loss of a key phosphorylation site in murine DAPK3 seems to direct it mainly to the nucleus which is proposed to be compensated by the interaction with PAWR to maintain at least the cytoplasmic basic membrane blebbing function in the apoptosis pathway.By similarity

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