DAPK3 - Death-associated protein kinase 3 - human protein (Function)
 
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DAPK3 »  Death-associated protein kinase 3   [ EC 2.7.11.1 ]  (DAP kinase 3)
 
Protein also known as:  Zipper-interacting protein kinase (ZIP-kinase).
Gene name:  DAPK3
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 43 2
GENE REF ISO

Function

 show evidences
Overview 
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 Ca(2+) 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. 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.  
12
  • CuratedUniProtKB
Isoform  Iso 2   Can phosphorylate myosin, PPP1R12A and MYL12B.  
12
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • IDAUniProtKB
Identical protein bindingdefinition[GO:0042802]  
1
  • IPIIntAct
Leucine zipper domain bindingdefinition[GO:0043522]  
1
  • IPIUniProtKB
Protein homodimerization activitydefinition[GO:0042803]  
1
  • IDAUniProtKB
Protein serine/threonine kinase activitydefinition[GO:0004674]  
3
  • IDAUniProtKB
GO biological process 
Apoptotic processdefinition[GO:0006915]  
2
  • IMPUniProtKB
Apoptotic signaling pathwaydefinition[GO:0097190] silver  
  • IEAOrtholog Compara
Cellular response to interferon-gammadefinition[GO:0071346]  
1
  • IDAUniProtKB
Chromatin modificationdefinition[GO:0016568]  
  • IEAUniProtKB KW
Intracellular signal transductiondefinition[GO:0035556]  
1
  • IDAUniProtKB
Negative regulation of translationdefinition[GO:0017148]  
1
  • IDAUniProtKB
Neuron differentiationdefinition[GO:0030182] silver  
  • IEAOrtholog Compara
Positive regulation of canonical Wnt signaling pathwaydefinition[GO:0090263]  
1
  • IMPUniProtKB
Positive regulation of extrinsic apoptotic signaling pathway in absence of liganddefinition[GO:2001241] silver  
  • IEAOrtholog Compara
Protein autophosphorylationdefinition[GO:0046777]  
2
  • IDAUniProtKB
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDAUniProtKB
Regulation of apoptotic processdefinition[GO:0042981]  
1
  • TASUniProtKB
Regulation of autophagydefinition[GO:0010506]  
1
  • TASUniProtKB
Transcription, DNA-templateddefinition[GO:0006351]  
  • IEAUniProtKB KW
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
1
  • CuratedUniProtKB
It requires the following cofactor
Magnesium.  
1
  • CuratedUniProtKB
It is regulated in the following manner
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.  
3
  • CuratedUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
Bladder cancer  hsa05219+1613  
Pathways in cancer  hsa05200+1613  
According to Reactome, this protein belongs to the following pathway:
Apoptosis  REACT_578  
Note 
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.  
  • CuratedUniProtKB
 

Biophysicochemical properties

Kinetic parameters
KM 12 uM for myosin (isoform 2)
KM 10.4 uM for MYL12B (isoform 1)
KM 73 uM for MYL12B (isoform 2)
KM 6.2 uM for myosin (isoform 1)
Vmax 248 nmol/min/mg enzyme toward myosin (isoform 2)
Vmax 271 nmol/min/mg enzyme toward MYL12B (isoform 1)
Vmax 1.3 umol/min/mg enzyme toward MYL12B (isoform 2)
Vmax 120 nmol/min/mg enzyme toward myosin (isoform 1)

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Translation regulation  definition   [KW-0810]
Molecular function 
Activator  definition   [KW-0010]
Chromatin regulator  definition   [KW-0156]
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: DAPK3
GenomeRNAi: 1613
PRO: PR:O43293
Chemistry
GuidetoPHARMACOLOGY: 2004