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Subunit: Interacts with KLHL20. Interacts (via death domain) with MAPK1 and MAPK3. Interacts with MAP1B (via N-terminus). Interacts (via death domain) with UNC5B (via death domain). Interacts with PRKD1 in an oxidative stress-regulated manner. Interacts with PIN1, PDCD6, BECN1, GRINB, TSC2 and STX1A. Interacts (via kinase domain) with DAPK3 (via kinase domain) Sequence caution: Sequence=AAP35581.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the C-terminal part; Sequence=CAA53712.1; Type=Frameshift; Positions=462, 464; Selected PDB 3D structures from [IMAGE] and Proteopedia [IMAGE] for DAPK1 (see all 33): 1IG1 (3D) [IMAGE] 1JKK (3D) [IMAGE] 1JKL (3D) [IMAGE] 1JKS (3D) [IMAGE] 1JKT (3D) [IMAGE] 1P4F (3D) [IMAGE]
Tissue specificity: Isoform 2 is expressed in normal intestinal tissue as well as in colorectal carcinomas [IMAGE] Pathway & Disease-focused RT2 Profiler PCR Arrays including DAPK1 (see all 7): Leukemia in human mouse rat p53 Signaling Pathway in human mouse rat Neurotoxicit
Function: Isoform 2 cannot induce apoptosis but can induce membrane blebbing 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 Function: Isoform 2 cannot induce apoptosis but can induce membrane blebbing Catalytic activity: ATP + a protein = ADP + a phosphoprotein Enzyme regulation: 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
Catalytic activity: ATP + a protein = ADP + a phosphoprotein Enzyme regulation: 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
Similarity: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily Contains 10 ANK repeats Contains 1 death domain Contains 1 protein kinase domain [IMAGE]
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