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Protein

Death-associated protein kinase 3

Gene

Dapk3

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

  • ATP binding Source: UniProtKB
  • kinase activity Source: MGI
  • leucine zipper domain binding Source: MGI
  • protein homodimerization activity Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB
  • Rho GTPase binding Source: MGI

GO - Biological processi

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

ReactomeiR-MMU-418889. Ligand-independent caspase activation via DCC.

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
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1203520. Dapk3.

Subcellular locationi

GO - Cellular componenti

  • actin filament Source: Ensembl
  • chromosome, centromeric region Source: UniProtKB-SubCell
  • cytoplasm Source: UniProtKB-SubCell
  • membrane raft Source: Ensembl
  • microtubule organizing center Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
  • PML body Source: MGI
Complete GO annotation...

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.
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

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.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199052. 5 interactors.
IntActiO54784. 10 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

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

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

Family and domain databases

InterProiIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24347. PTHR24347. 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_006513195.2.
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.
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. 5 interactors.
IntActiO54784. 10 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.
GeneIDi13144.
KEGGimmu:13144.
UCSCiuc007ggg.2. mouse.

Organism-specific databases

CTDi1613.
MGIiMGI:1203520. Dapk3.

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-MMU-418889. Ligand-independent caspase activation via DCC.

Miscellaneous databases

PROiO54784.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000034974.
CleanExiMM_DAPK3.
ExpressionAtlasiO54784. baseline and differential.
GenevisibleiO54784. MM.

Family and domain databases

InterProiIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24347. PTHR24347. 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]
ProtoNetiSearch...

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 30, 2016
This is version 145 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.