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
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GENE REF ISO

Function

 show evidences
Overview 
Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation and actin cytoskeleton reorganization. Involved in the regulation of smooth muscle contraction. Regulates both type I (caspase-dependent) apoptotic and type II (caspase-independent) autophagic cell deaths signal, depending on the cellular setting. Involved in regulation of starvation-induced autophagy. 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; the inhibition of SMPP1M functions to enhance muscle responsiveness to Ca(2+) and promote a contractile state. Phosphorylates MYL12B in non-muscle cells leading to reorganization of actin cytoskeleton.  
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  • UniProtKB
Isoform  Iso 2   Can phosphorylate myosin, PPP1R12A and MYL12B. Overexpression leads to condensation of actin stress fibers into thick bundles. Involved in actin filament focal adhesion dynamics. The function in both reorganization of actin cytoskeleton and focal adhesion dissolution is modulated by RhoD. Positively regulates canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2. 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. Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Involved in regulation of cell cycle progression and cell proliferation. May be a tumor suppressor.  
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  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB
Calmodulin-dependent protein kinase activitydefinition[GO:0004683]  
1
  • RefGenome
cAMP response element binding protein bindingdefinition[GO:0008140]  
1
  • ParkinsonsUK-UCL
Identical protein bindingdefinition[GO:0042802]  
2
  • IntAct
Leucine zipper domain bindingdefinition[GO:0043522]  
1
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
4
  • IntAct
Protein homodimerization activitydefinition[GO:0042803]  
1
  • UniProtKB
Protein serine/threonine kinase activitydefinition[GO:0004674]  
3
  • UniProtKB
Rho GTPase bindingdefinition[GO:0017048]  
1
  • UniProtKB
GO biological process 
Apoptotic processdefinition[GO:0006915]  
2
  • UniProtKB
Apoptotic signaling pathwaydefinition[GO:0097190] silver  
1
  • Ortholog Compara
Cellular response to interferon-gammadefinition[GO:0071346]  
1
  • UniProtKB
Chromatin modificationdefinition[GO:0016568]  
1
  • UniProtKB KW
Intracellular signal transductiondefinition[GO:0035556]  
1
  • UniProtKB
Negative regulation of translationdefinition[GO:0017148]  
1
  • UniProtKB
Neuron differentiationdefinition[GO:0030182] silver  
1
  • Ortholog Compara
Positive regulation of apoptotic processdefinition[GO:0043065]  
1
  • UniProtKB
Positive regulation of canonical Wnt signaling pathwaydefinition[GO:0090263]  
1
  • UniProtKB
Positive regulation of cell migrationdefinition[GO:0030335] silver  
1
  • Ortholog Compara
Positive regulation of extrinsic apoptotic signaling pathway in absence of liganddefinition[GO:2001241] silver  
1
  • Ortholog Compara
Protein autophosphorylationdefinition[GO:0046777]  
2
  • UniProtKB
Protein phosphorylationdefinition[GO:0006468]  
1
  • UniProtKB
Regulation of actin cytoskeleton reorganizationdefinition[GO:2000249]  
1
  • UniProtKB
Regulation of apoptotic processdefinition[GO:0042981]  
2
  • UniProtKB
  • RefGenome
Regulation of autophagydefinition[GO:0010506]  
1
  • UniProtKB
Regulation of cell shapedefinition[GO:0008360] silver  
1
  • Ortholog Compara
Regulation of focal adhesion assemblydefinition[GO:0051893]  
1
  • UniProtKB
Regulation of mitotic cell cycledefinition[GO:0007346]  
1
  • UniProtKB
Regulation of myosin II filament organizationdefinition[GO:0043519] silver  
1
  • Ortholog Compara
Transcription, DNA-templateddefinition[GO:0006351]  
1
  • UniProtKB 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.  
7
  • UniProtKB
It requires the following cofactor
 Mg(2+)  
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  • UniProtKB
It is regulated in the following manner
A sequential activation is proposed: autophosphorylation at consensus sites is leading to dimerization of the catalytic domain stabilized by phosphorylation at Ser-50 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. Oligomerization is required for full enzymatic activity. Inhibited by pyridone 6 (K00225), a potent, ATP-competitive inhibitor.  
5
  • UniProtKB
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:
Role of DCC in regulating apoptosis  REACT_22128  
 

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