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Protein

Death-associated protein kinase 3

Gene

Dapk3

Organism
Rattus norvegicus (Rat)
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. 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 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 similarity). Phosphorylates STAT3 and enhances its transcriptional activity (By similarity). Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Phosphorylates histone H3 on 'Thr-11' at centromeres during mitosis.By similarity6 Publications

Catalytic activityi

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

Cofactori

Mg2+2 Publications

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).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: RGD
  • protein C-terminus binding Source: RGD
  • protein homodimerization activity Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

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

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
OrganismiRattus norvegicus (Rat)Imported
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 7

Organism-specific databases

RGDi621766. Dapk3.

Subcellular locationi

GO - Cellular componenti

  • actin filament Source: RGD
  • chromosome, centromeric region Source: UniProtKB-SubCell
  • cytoplasm Source: RGD
  • membrane raft Source: UniProtKB
  • nucleus Source: UniProtKB
  • PML body Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Centromere, Chromosome, Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi42K → A: Loss of kinase activity, loss of PAWR-linked translocation into the cytoplasm; maintains nuclear localization but loss of localization to PML-NB. 2 Publications1
Mutagenesisi294A → T: Causes dissociation from promyelocytic leukemia oncogenic bodies and increased blebbing-inducing potency; when associated with T-300. 1 Publication1
Mutagenesisi295A → T: Causes dissociation from promyelocytic leukemia oncogenic bodies and increased blebbing-inducing potency; when associated with T-299. 1 Publication1
Mutagenesisi406 – 407RR → AL: Cytoplasmic localization. 1 Publication2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000859161 – 448Death-associated protein kinase 3Add BLAST448

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei180PhosphothreonineBy similarity1
Modified residuei225PhosphothreonineBy similarity1
Modified residuei265Phosphothreonine; by autocatalysisBy similarity1
Modified residuei265Phosphothreonine; by ROCK1; alteranteBy 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 (By similarity).By similarity
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

PaxDbiO88764.
PRIDEiO88764.

PTM databases

iPTMnetiO88764.

Expressioni

Tissue specificityi

Ubiquitously expressed in all tissue types examined. High levels in brain, heart, lung and spleen, lower expression in kidney, liver, skeletal muscle and testis. Isoform 2 is expressed in the smooth muscle.1 Publication

Gene expression databases

BgeeiENSRNOG00000020383.
ExpressionAtlasiO88764. baseline and differential.
GenevisibleiO88764. RN.

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, ATF4, NLK, TCF7L2, UBE2D1, UBE2D2, UBE2D3 and CDC5L. Interacts with PAWR; also demonstrated in aorta smooth muscle cells indicative for the cytoskeletal targeting function of PAWR. Interacts with AR; enhanced by AATF.By similarity6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PawrQ626275EBI-4404236,EBI-1187240

GO - Molecular functioni

  • protein C-terminus binding Source: RGD
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi249061. 6 interactors.
IntActiO88764. 5 interactors.
STRINGi10116.ENSRNOP00000027634.

Structurei

3D structure databases

ProteinModelPortaliO88764.
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 CDC5L1 PublicationAdd BLAST59
Regioni418 – 448Required for interaction with ATF4 but not with PAWR1 PublicationAdd BLAST31
Regioni422 – 436Leucine-zipperBy similarityAdd BLAST15

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0032. Eukaryota.
ENOG410XRMJ. LUCA.
GeneTreeiENSGT00760000118877.
HOGENOMiHOG000233016.
HOVERGENiHBG101549.
InParanoidiO88764.
KOiK08803.
OMAiFRIVALC.
OrthoDBiEOG091G0J2O.
PhylomeDBiO88764.
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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O88764-1) [UniParc]FASTAAdd to basket

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

        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
LRVAAEQREA RCRDGSAGLG RDLRRLRTEL GRTEALRTRA QEEARAALLG
410 420 430 440
AGGLKRRLCR LENRYDALAA QVAAEVQFVR DLVRALEQER LQAECGVR
Length:448
Mass (Da):51,450
Last modified:November 1, 1998 - v1
Checksum:i843C0FD0BF0C1EEA
GO
Isoform 2 (identifier: O88764-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MIDSSCVPRILQKDSAMM

Show »
Length:465
Mass (Da):53,326
Checksum:i1AC035BCAB567234
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0420611M → MIDSSCVPRILQKDSAMM in isoform 2. Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ006971 mRNA. Translation: CAA07360.1.
BC062076 mRNA. Translation: AAH62076.1.
RefSeqiNP_071991.1. NM_022546.1. [O88764-1]
XP_006241055.1. XM_006240993.2. [O88764-1]
XP_017450587.1. XM_017595098.1. [O88764-1]
XP_017450588.1. XM_017595099.1. [O88764-1]
UniGeneiRn.60353.

Genome annotation databases

EnsembliENSRNOT00000027634; ENSRNOP00000027634; ENSRNOG00000020383. [O88764-1]
GeneIDi64391.
KEGGirno:64391.
UCSCiRGD:621766. rat. [O88764-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ006971 mRNA. Translation: CAA07360.1.
BC062076 mRNA. Translation: AAH62076.1.
RefSeqiNP_071991.1. NM_022546.1. [O88764-1]
XP_006241055.1. XM_006240993.2. [O88764-1]
XP_017450587.1. XM_017595098.1. [O88764-1]
XP_017450588.1. XM_017595099.1. [O88764-1]
UniGeneiRn.60353.

3D structure databases

ProteinModelPortaliO88764.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249061. 6 interactors.
IntActiO88764. 5 interactors.
STRINGi10116.ENSRNOP00000027634.

PTM databases

iPTMnetiO88764.

Proteomic databases

PaxDbiO88764.
PRIDEiO88764.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000027634; ENSRNOP00000027634; ENSRNOG00000020383. [O88764-1]
GeneIDi64391.
KEGGirno:64391.
UCSCiRGD:621766. rat. [O88764-1]

Organism-specific databases

CTDi1613.
RGDi621766. Dapk3.

Phylogenomic databases

eggNOGiKOG0032. Eukaryota.
ENOG410XRMJ. LUCA.
GeneTreeiENSGT00760000118877.
HOGENOMiHOG000233016.
HOVERGENiHBG101549.
InParanoidiO88764.
KOiK08803.
OMAiFRIVALC.
OrthoDBiEOG091G0J2O.
PhylomeDBiO88764.
TreeFamiTF314166.

Miscellaneous databases

PROiO88764.

Gene expression databases

BgeeiENSRNOG00000020383.
ExpressionAtlasiO88764. baseline and differential.
GenevisibleiO88764. RN.

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_RAT
AccessioniPrimary (citable) accession number: O88764
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2003
Last sequence update: November 1, 1998
Last modified: November 30, 2016
This is version 135 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.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.