DAPK1 - Death-associated protein kinase 1 - human protein (Function)
 
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DAPK1 »  Death-associated protein kinase 1   [ EC 2.7.11.1 ]  (DAP kinase 1)
 
Gene name:  DAPK1
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. 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. Phosphorylates PIN1 resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors at extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca(2+) influx through NMDA receptor channels, resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon interferon-gamma activation which is causing RPL13A involvement in transcript-selective translation inhibition.  
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  • UniProtKB
Isoform  Iso 2   Cannot induce apoptosis but can induce membrane blebbing.  
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  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
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  • UniProtKB
Calmodulin bindingdefinition[GO:0005516]  
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  • UniProtKB
Calmodulin-dependent protein kinase activitydefinition[GO:0004683]  
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  • UniProtKB
Identical protein bindingdefinition[GO:0042802]  
3
  • IntAct
Protein bindingdefinition[GO:0005515]  
8
  • IntAct
Protein kinase activitydefinition[GO:0004672]  
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  • UniProtKB
  • MGI
Protein serine/threonine kinase activitydefinition[GO:0004674]  
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  • UniProtKB
Syntaxin-1 bindingdefinition[GO:0017075]  
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  • UniProtKB
GO biological process 
Apoptotic processdefinition[GO:0006915]  
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  • UniProtKB
  • MGI
Apoptotic signaling pathwaydefinition[GO:0097190]  
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  • UniProtKB
Cellular response to interferon-gammadefinition[GO:0071346]  
1
  • UniProtKB
Extrinsic apoptotic signaling pathway via death domain receptorsdefinition[GO:0008625] silver  
1
  • Ortholog Compara
Intracellular signal transductiondefinition[GO:0035556]  
1
  • UniProtKB
Negative regulation of extrinsic apoptotic signaling pathway via death domain receptorsdefinition[GO:1902042] silver  
1
  • Ortholog Compara
Negative regulation of translationdefinition[GO:0017148]  
1
  • UniProtKB
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic processdefinition[GO:0043280]  
1
  • UniProtKB
Protein autophosphorylationdefinition[GO:0046777]  
3
  • UniProtKB
Protein phosphorylationdefinition[GO:0006468]  
2
  • UniProtKB
Regulation of apoptotic processdefinition[GO:0042981]  
2
  • UniProtKB
  • RefGenome
Regulation of autophagydefinition[GO:0010506]  
1
  • UniProtKB
Regulation of N-methyl-D-aspartate selective glutamate receptor activitydefinition[GO:2000310]  
1
  • Ortholog Curator
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.  
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  • UniProtKB
It requires the following cofactor
 Mg(2+)  
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  • UniProtKB
It is regulated in the following manner
Activated by Ca(2+)/calmodulin. Regulated by a locking mechanism, involving autophosphorylation at Ser-308 and calmodulin binding. In the inactive state, Ser-308 is phosphorylated. Activation involves its dephosphorylation and a release-of-autoinhibition mechanism where binding of calmodulin induces a conformational change that relieves the steric block of the active site by the autoinhibitory domain. Activity is modulated by UNC5B and NTN1. UNC5B activates it by inhibiting the phosphorylation at Ser-308, whereas NTN1 inhibits UNC5B-mediated activation of DAPK1. Endoplasmic-stress activates by causing Ser-308 dephosphorylation.  
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  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Bladder cancer  hsa05219+1612  
Pathways in cancer  hsa05200+1612  
According to Reactome, this protein belongs to the following pathway:
Role of DCC in regulating apoptosis  REACT_22128  
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Translation regulation  definition   [KW-0810]
Molecular function 
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: DAPK1
GenomeRNAi: 1612
PRO: PR:P53355
Chemistry
GuidetoPHARMACOLOGY: 2002