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O54784 (DAPK3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Death-associated protein kinase 3

Short name=DAP kinase 3
EC=2.7.11.1
Alternative name(s):
DAP-like kinase
Short name=Dlk
MYPT1 kinase
ZIP-kinase
Gene names
Name:Dapk3
Synonyms:Zipk
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length448 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.5

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.1

Cofactor

Magnesium. Ref.1

Enzyme regulation

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.

Subunit structure

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. Ref.1 Ref.2 Ref.3

Subcellular location

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. Ref.1 Ref.2 Ref.4

Tissue specificity

Highly expressed in heart, brain, lung, skeletal muscle, kidney and testis. Lower levels in liver and spleen. Ref.1

Post-translational modification

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.

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.

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.

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processApoptosis
Transcription
Transcription regulation
   Cellular componentCentromere
Chromosome
Cytoplasm
Cytoskeleton
Nucleus
   LigandATP-binding
Nucleotide-binding
   Molecular functionActivator
Chromatin regulator
Kinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic signaling pathway

Inferred from direct assay Ref.1. Source: MGI

cellular response to interferon-gamma

Inferred from mutant phenotype Ref.5. Source: UniProtKB

chromatin modification

Inferred from electronic annotation. Source: UniProtKB-KW

intracellular signal transduction

Inferred from direct assay Ref.1. Source: UniProtKB

negative regulation of translation

Inferred from electronic annotation. Source: Ensembl

neuron differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of canonical Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of extrinsic apoptotic signaling pathway in absence of ligand

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.1. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentPML body

Inferred from direct assay Ref.2. Source: MGI

chromosome, centromeric region

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

microtubule organizing center

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay Ref.1. Source: UniProtKB

   Molecular_functionATP binding

Inferred from direct assay Ref.1. Source: UniProtKB

kinase activity

Inferred from sequence orthology PubMed 18310078. Source: MGI

protein homodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.1. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

DaxxO356132EBI-77359,EBI-77304
PawrQ925B02EBI-77359,EBI-77397

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 448448Death-associated protein kinase 3
PRO_0000085915

Regions

Domain13 – 275263Protein kinase
Nucleotide binding19 – 279ATP By similarity UniProtKB P53355
Region161 – 20444Activation segment By similarity
Region276 – 32853Interaction with AR By similarity
Region277 – 30630Interaction with MYPT1 By similarity
Region390 – 44859Interaction with CDC5L By similarity
Region422 – 43615Leucine-zipper By similarity

Sites

Active site1391Proton acceptor By similarity UniProtKB P53355
Binding site421ATP Probable Ref.1
Binding site941Inhibitor By similarity
Binding site961Inhibitor By similarity

Amino acid modifications

Modified residue1801Phosphothreonine By similarity
Modified residue2251Phosphothreonine By similarity
Modified residue2651Phosphothreonine; by autocatalysis; alternate By similarity
Modified residue2651Phosphothreonine; by ROCK1; alternate By similarity
Modified residue3041Phosphoserine; by DAPK1 By similarity
Modified residue3061Phosphoserine; by autocatalysis and DAPK1 By similarity
Modified residue3071Phosphoserine; by DAPK1 By similarity
Modified residue3131Phosphoserine; by DAPK1 By similarity
Modified residue3211Phosphoserine; by DAPK1 By similarity

Experimental info

Mutagenesis421K → A: Loss of activity. Ref.1
Mutagenesis4221V → A: Decreased activity; when associated with A-429 and A-436. Ref.1
Mutagenesis4291V → A: Decreased activity; when associated with A-422 and A-436. Ref.1
Mutagenesis4361L → A: Decreased activity; when associated with A-422 and A-429. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O54784 [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: DA32EF3EB1F20EFC

FASTA44851,422
        10         20         30         40         50         60 
MSTFRQEDVE DHYEMGEELG SGQFAIVRKC QQKGTGMEYA AKFIKKRRLP SSRRGVSREE 

        70         80         90        100        110        120 
IEREVSILRE IRHPNIITLH DVFENKTDVV LILELVSGGE LFDFLAEKES LTEDEATQFL 

       130        140        150        160        170        180 
KQILDGVHYL HSKRIAHFDL KPENIMLLDK HAASPRIKLI DFGIAHRIEA GSEFKNIFGT 

       190        200        210        220        230        240 
PEFVAPEIVN YEPLGLEADM WSIGVITYIL LSGASPFLGE TKQETLTNIS AVNYDFDEEY 

       250        260        270        280        290        300 
FSSTSELAKD FIRRLLVKDP KRRMTIAQSL EHSWIKVRRR EDGARKPERR RLRAARLREY 

       310        320        330        340        350        360 
SLKSHSSMPR NTSYASFERF SRVLEDVAAA EQGLRELQRG RRQCRERVCA LRAAAEQREA 

       370        380        390        400        410        420 
RCRDGSAGLG RDLRRLRTEL GRTEALRTRA QEEARAALLG AGGLKRRLCR LENRYDALAA 

       430        440 
QVAAEVQFVR DLVRALEQER LQAECGVR 

« Hide

References

[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]"Physical and functional interactions between ZIP kinase and UbcH5."
Ohbayashi N., Okada K., Kawakami S., Togi S., Sato N., Ikeda O., Kamitani S., Muromoto R., Sekine Y., Kawai T., Akira S., Matsuda T.
Biochem. Biophys. Res. Commun. 372:708-712(2008) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB007143 mRNA. Translation: BAA24954.1.
RefSeqNP_001177402.1. NM_001190473.1.
NP_031854.1. NM_007828.2.
XP_006513258.1. XM_006513195.1.
UniGeneMm.10294.

3D structure databases

ProteinModelPortalO54784.
SMRO54784. Positions 2-296.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199052. 5 interactions.
IntActO54784. 4 interactions.
STRING10090.ENSMUSP00000035962.

PTM databases

PhosphoSiteO54784.

Proteomic databases

PaxDbO54784.
PRIDEO54784.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000047665; ENSMUSP00000035962; ENSMUSG00000034974.
ENSMUST00000178422; ENSMUSP00000137333; ENSMUSG00000034974.
GeneID13144.
KEGGmmu:13144.
UCSCuc007ggg.2. mouse.

Organism-specific databases

CTD1613.
MGIMGI:1203520. Dapk3.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233016.
HOVERGENHBG101549.
InParanoidO54784.
KOK08803.
OMADYSAREI.
OrthoDBEOG7QZGBH.
PhylomeDBO54784.
TreeFamTF314166.

Enzyme and pathway databases

ReactomeREACT_100962. Apoptosis.

Gene expression databases

ArrayExpressO54784.
BgeeO54784.
CleanExMM_DAPK3.
GenevestigatorO54784.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR020675. Myosin_light_ch_kinase-rel.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERPTHR22964. PTHR22964. 1 hit.
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio283230.
PROO54784.
SOURCESearch...

Entry information

Entry nameDAPK3_MOUSE
AccessionPrimary (citable) accession number: O54784
Entry history
Integrated into UniProtKB/Swiss-Prot: November 28, 2003
Last sequence update: June 1, 1998
Last modified: April 16, 2014
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot