Protein: Death-associated protein kinase 1 (DAP kinase 1) (EC 2.7.11.1) (Q80YE7)
Organism: Mus musculus (Mouse)
Function: 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 (By similarity). 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.
Sequence: MTVFRQENVDDYYDTGEELGSGQFAVVKKCREKSTGLQYAAKFIKKRRTKSSRRGVSREDIEREVSILKEIRHPNVITLHEVYENKTDVILILELVAGGELFDFLAEKESLTEEEATEFLKQILSGVYYLHSLQIAHFDLKPENIMLLDRNVPKPRIKIIDFGLAHKIDFGNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANVSAVNYDFEEEFFRNTSTLAKDFIRRLLVKDPKKRMTIQDSLQHPWIKPKDTQQALSRKASAVNMEKFKKFAARKKWKQSVRLISLCQRLSRSFLSRSNMSVARSDDTLDEEDSFVMKAIIHAINDDNVPGLQHLLGSLSSYDVNQPNKHGTPPLLIAAGCGNIQMLQLLIKRGSRIDVQDKGGSNAIYWASRHGHVDTLKFLNENKCPLDVKDKSGETALHVAARYGHADVVQLLCSFGSNPDFQDKEEETPLHCAAWHGYYSVAKALCEVGCNVNIKNREGETPLLTASARGYHDIVECLAEHGADLNASDKDGHIALHLAVRRCQMEVIKTLLGHGSFVDFQDRHGNTPLHVACKDGSAPIVVALCEASCNLDISNKYGRTPLHLAANNGILDVVRYLCLMGANVEALTSDGKTAEDLAKAEQHEHVAGLLARLRKDTHRGLFIQQLRPTQNLQPRIKLKLFGHSGSGKSTLVESLKCGLLRSFFRRRRPRLSSTNSTRFPPSPLAAKPTVSVSINNLYPGCENVSVRSRSMMFEPGLTKGMLEVFVAPSHHLHCSTDDQSTKAIDIQNAYLNGVGDFSVWEFSGNPVYFCCYDYFAANDPTSIHIIVFSLEEPYEIQLNQVIFWLSFLKSLVPVEEPIAFGGKLKNPLRVVLVATHADIMNIPRPAGGEFGYDKDTSLLKEIRNRFGNDLHVSNKLFVLDAGASGSKDIKVLRNHLQEIRSQIVSGCSPMTHLCEKIISTLPSWRKLNGPNQLMSLQQFVYDVQDQLNPLASEDDLRRIAQQLHSTGEINIMQSETVQDVLLLDPRWLCTNVLGKLLSVETPRALHHYRGRYTMEDIQRLVPDSDVEELLQILDAMDICARDLSSGTMVDIPALIKTDSLQRSWADEEDEVMVYGGVRIVPVEHLTPFPCGIFHKVQVNLCRWIHQQSAEGDADIRLWVSGCRIANRGAELLVLLVNHGQGIEVQVRGLETEKIKCCLLLDSVCSTIETVMATTLPGLLTVKHYLSPQQLREHHEPVMVYQPRDFFRAQTLKESSLTNTMGGYKESFSSITCFGCHDVYSQASLGMDIHASDLSLLTRRKLSRLLDPPDPMGKDWCLLAMNLGLPDMVAKHNVNNRASRDFLPSPVHALLQEWTSYPESTVGILISKLRELGRRDAADFLLKASSVFKINLDGNGQEAYASSCNSGTSYNSISSVVSRRDSHAWTPLYDL
InterPro domains: - IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [6-291]
- IPR020676: Death-associated protein kinase 1, catalytic domain (domain) [7-275]
- IPR011029: Death-like domain superfamily (homologous_superfamily) [1295-1398]
- IPR036770: Ankyrin repeat-containing domain superfamily (homologous_superfamily) [324-677]
- IPR020859: Roc domain (domain) [681-955]
- IPR008271: Serine/threonine-protein kinase, active site (active_site) [135-147]
- IPR002110: Ankyrin repeat (repeat) [378-671]
- IPR027417: P-loop containing nucleoside triphosphate hydrolase (homologous_superfamily) [673-893]
- IPR017441: Protein kinase, ATP binding site (binding_site) [19-46]
- IPR000719: Protein kinase domain (domain) [13-275]
- IPR000488: Death domain (domain) [1299-1396]
Interaction partners: - Beclin-1
- Mitogen-activated protein kinase 1
- Mitogen-activated protein kinase 3
- Death-associated protein kinase 2
- Death-associated protein kinase 3
- Glutamate receptor ionotropic, NMDA 2B
- Netrin receptor UNC5B
- Cellular tumor antigen p53
- Kelch-like protein 20
- E3 ubiquitin-protein ligase MIB1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016740 (transferase activity), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0004672 (protein kinase activity), GO:0016772 (transferase activity, transferring phosphorus-containing groups), GO:0016773 (phosphotransferase activity, alcohol group as acceptor), GO:0004674 (protein serine/threonine kinase activity), GO:0016301 (kinase activity), GO:0004683 (calmodulin-dependent protein kinase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0002376 (immune system process), GO:0023052 (signaling), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0009605 (response to external stimulus), GO:0048869 (cellular developmental process), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0009653 (anatomical structure morphogenesis), GO:0042221 (response to chemical), GO:0019222 (regulation of metabolic process), GO:0006955 (immune response), GO:0006807 (nitrogen compound metabolic process), GO:0071704 (organic substance metabolic process), GO:0048646 (anatomical structure formation involved in morphogenesis), GO:0009892 (negative regulation of metabolic process), GO:0044237 (cellular metabolic process), GO:0044281 (small molecule metabolic process), GO:0008219 (cell death), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0065009 (regulation of molecular function), GO:0006950 (response to stress), GO:0048523 (negative regulation of cellular process), GO:0051707 (response to other organism), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0044238 (primary metabolic process), GO:0050790 (regulation of catalytic activity), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0012501 (programmed cell death), GO:1901564 (organonitrogen compound metabolic process), GO:0048729 (tissue morphogenesis), GO:0043207 (response to external biotic stimulus), GO:0035556 (intracellular signal transduction), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0080134 (regulation of response to stress), GO:0044092 (negative regulation of molecular function), GO:0048731 (system development), GO:0019538 (protein metabolic process), GO:0080135 (regulation of cellular response to stress), GO:0006952 (defense response), GO:0060255 (regulation of macromolecule metabolic process), GO:1901700 (response to oxygen-containing compound), GO:0002347 (response to tumor cell), GO:0031324 (negative regulation of cellular metabolic process), GO:0043170 (macromolecule metabolic process), GO:0010033 (response to organic substance), GO:0045087 (innate immune response), GO:0098542 (defense response to other organism), GO:0006793 (phosphorus metabolic process), GO:0009894 (regulation of catabolic process), GO:0048598 (embryonic morphogenesis), GO:0010941 (regulation of cell death), GO:0009888 (tissue development), GO:0070887 (cellular response to chemical stimulus), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0033554 (cellular response to stress), GO:0097190 (apoptotic signaling pathway), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0009790 (embryo development), GO:0080090 (regulation of primary metabolic process), GO:0034097 (response to cytokine), GO:0043086 (negative regulation of catalytic activity), GO:0034097 (response to cytokine), GO:0021915 (neural tube development), GO:0051246 (regulation of protein metabolic process), GO:0071310 (cellular response to organic substance), GO:0043067 (regulation of programmed cell death), GO:0051248 (negative regulation of protein metabolic process), GO:0010506 (regulation of autophagy), GO:0033194 (response to hydroperoxide), GO:0006796 (phosphate-containing compound metabolic process), GO:0002009 (morphogenesis of an epithelium), GO:0072331 (signal transduction by p53 class mediator), GO:0016331 (morphogenesis of embryonic epithelium), GO:0010468 (regulation of gene expression), GO:0072175 (epithelial tube formation), GO:0036211 (protein modification process), GO:0006631 (fatty acid metabolic process), GO:0043412 (macromolecule modification), GO:0006954 (inflammatory response), GO:0007399 (nervous system development), GO:0060606 (tube closure), GO:0010563 (negative regulation of phosphorus metabolic process), GO:0097193 (intrinsic apoptotic signaling pathway), GO:0034341 (response to type II interferon), GO:0060429 (epithelium development), GO:0031329 (regulation of cellular catabolic process), GO:1901701 (cellular response to oxygen-containing compound), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0051174 (regulation of phosphorus metabolic process), GO:0009792 (embryo development ending in birth or egg hatching), GO:0001838 (embryonic epithelial tube formation), GO:0043009 (chordate embryonic development), GO:0042981 (regulation of apoptotic process), GO:0031399 (regulation of protein modification process), GO:0031400 (negative regulation of protein modification process), GO:0006468 (protein phosphorylation), GO:0018193 (peptidyl-amino acid modification), GO:0071345 (cellular response to cytokine stimulus), GO:0019220 (regulation of phosphate metabolic process), GO:0016310 (phosphorylation), GO:0043549 (regulation of kinase activity), GO:0051348 (negative regulation of transferase activity), GO:0034612 (response to tumor necrosis factor), GO:0001841 (neural tube formation), GO:0045936 (negative regulation of phosphate metabolic process), GO:0042325 (regulation of phosphorylation), GO:0001933 (negative regulation of protein phosphorylation), GO:0001932 (regulation of protein phosphorylation), GO:0018108 (peptidyl-tyrosine phosphorylation), GO:0033673 (negative regulation of kinase activity), GO:0042326 (negative regulation of phosphorylation), GO:0045859 (regulation of protein kinase activity), GO:0071347 (cellular response to interleukin-1), GO:0018210 (peptidyl-threonine modification), GO:0018105 (peptidyl-serine phosphorylation), GO:0018107 (peptidyl-threonine phosphorylation), GO:0018209 (peptidyl-serine modification), GO:0071900 (regulation of protein serine/threonine kinase activity), GO:0006469 (negative regulation of protein kinase activity), GO:0071901 (negative regulation of protein serine/threonine kinase activity)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0005737 (cytoplasm), GO:0071944 (cell periphery), GO:0005739 (mitochondrion), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)