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Protein

Death-associated protein kinase 3

Gene

Dapk3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

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

Catalytic activityi

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

Cofactori

Mg2+1 Publication

Activity 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)DescriptionActionsGraphical viewLength
Binding sitei42ATPCurated1
Binding sitei94InhibitorBy similarity1
Binding sitei96InhibitorBy similarity1
Active sitei139Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi19 – 27ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, Chromatin regulator, Kinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Transcription, Transcription regulation
LigandATP-binding, Nucleotide-binding

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1203520 Dapk3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Centromere, Chromosome, Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi42K → A: Loss of activity. 1 Publication1
Mutagenesisi289 – 290RR → AA: Nuclear localization. 1 Publication2
Mutagenesisi294A → D: Nuclear colocalization. 1 Publication1
Mutagenesisi422V → A: Decreased activity; when associated with A-429 and A-436. 1 Publication1
Mutagenesisi429V → A: Decreased activity; when associated with A-422 and A-436. 1 Publication1
Mutagenesisi436L → A: Decreased activity; when associated with A-422 and A-429. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000859151 – 448Death-associated protein kinase 3Add BLAST448

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei180PhosphothreonineBy similarity1
Modified residuei225PhosphothreonineBy similarity1
Modified residuei265Phosphothreonine; by autocatalysis1 Publication1
Modified residuei265Phosphothreonine; by ROCK1By similarity1
Modified residuei304Phosphoserine; by DAPK1By similarity1
Modified residuei306Phosphoserine; by autocatalysis and DAPK1By similarity1
Modified residuei307Phosphoserine; by DAPK1By similarity1
Modified residuei313Phosphoserine; by DAPK1By similarity1
Modified residuei321Phosphoserine; by DAPK1By similarity1

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

EPDiO54784
PaxDbiO54784
PeptideAtlasiO54784
PRIDEiO54784

PTM databases

iPTMnetiO54784
PhosphoSitePlusiO54784

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

BgeeiENSMUSG00000034974 Expressed in 227 organ(s), highest expression level in cerebellum
CleanExiMM_DAPK3
ExpressionAtlasiO54784 baseline and differential
GenevisibleiO54784 MM

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199052, 6 interactors
IntActiO54784, 11 interactors
STRINGi10090.ENSMUSP00000035962

Structurei

3D structure databases

ProteinModelPortaliO54784
SMRiO54784
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini13 – 275Protein kinasePROSITE-ProRule annotationAdd BLAST263

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni161 – 204Activation segmentBy similarityAdd BLAST44
Regioni390 – 448Interaction with CDC5LBy similarityAdd BLAST59
Regioni422 – 436Leucine-zipper1 PublicationAdd BLAST15

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0032 Eukaryota
ENOG410XRMJ LUCA
GeneTreeiENSGT00760000118877
HOGENOMiHOG000233016
HOVERGENiHBG101549
InParanoidiO54784
KOiK08803
OrthoDBiEOG091G0J2O
PhylomeDBiO54784
TreeFamiTF314166

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A1W2P6J6A0A1W2P6J6_MOUSE
Death-associated protein kinase 3
Dapk3
256Annotation score:
A0A1W2P6K3A0A1W2P6K3_MOUSE
Death-associated protein kinase 3
Dapk3
205Annotation score:
A0A1W2P730A0A1W2P730_MOUSE
Death-associated protein kinase 3
Dapk3
135Annotation score:

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_006513195.2
UniGeneiMm.10294

Genome annotation databases

EnsembliENSMUST00000047665; ENSMUSP00000035962; ENSMUSG00000034974
ENSMUST00000178422; ENSMUSP00000137333; ENSMUSG00000034974
ENSMUST00000219850; ENSMUSP00000151577; ENSMUSG00000034974
GeneIDi13144
KEGGimmu:13144
UCSCiuc007ggg.2 mouse

Similar proteinsi

Cross-referencesi

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_006513195.2
UniGeneiMm.10294

3D structure databases

ProteinModelPortaliO54784
SMRiO54784
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199052, 6 interactors
IntActiO54784, 11 interactors
STRINGi10090.ENSMUSP00000035962

PTM databases

iPTMnetiO54784
PhosphoSitePlusiO54784

Proteomic databases

EPDiO54784
PaxDbiO54784
PeptideAtlasiO54784
PRIDEiO54784

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000047665; ENSMUSP00000035962; ENSMUSG00000034974
ENSMUST00000178422; ENSMUSP00000137333; ENSMUSG00000034974
ENSMUST00000219850; ENSMUSP00000151577; ENSMUSG00000034974
GeneIDi13144
KEGGimmu:13144
UCSCiuc007ggg.2 mouse

Organism-specific databases

CTDi1613
MGIiMGI:1203520 Dapk3

Phylogenomic databases

eggNOGiKOG0032 Eukaryota
ENOG410XRMJ LUCA
GeneTreeiENSGT00760000118877
HOGENOMiHOG000233016
HOVERGENiHBG101549
InParanoidiO54784
KOiK08803
OrthoDBiEOG091G0J2O
PhylomeDBiO54784
TreeFamiTF314166

Miscellaneous databases

PROiPR:O54784
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000034974 Expressed in 227 organ(s), highest expression level in cerebellum
CleanExiMM_DAPK3
ExpressionAtlasiO54784 baseline and differential
GenevisibleiO54784 MM

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDAPK3_MOUSE
AccessioniPrimary (citable) accession number: O54784
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2003
Last sequence update: June 1, 1998
Last modified: November 7, 2018
This is version 160 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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