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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, 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 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

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-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
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

BgeeiO54784.
CleanExiMM_DAPK3.
ExpressionAtlasiO54784. baseline and differential.
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
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 2-297.
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.
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:
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 2-297.
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.

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], 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 29, 2014
This is version 125 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