Names & Taxonomy
- Uniprot ID:
- P53355
- Entry Name:
- DAPK1_HUMAN
- Status:
- reviewed
- Protein Names:
- Death-associated protein kinase 1 (DAP kinase 1) (EC 2.7.11.1)
- Gene Names:
- DAPK1 DAPK
- Gene Names Primary:
- DAPK1
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 1430
- Sequence:
- MTVFRQENVDDYYDTGEELGSGQFAVVKKCREKSTGLQYAAKFIKKRRTKSSRRGVSREDIEREVSILKEIQHPNVITLHEVYENKTDVILILELVAGGELFDFLAEKESLTEEEATEFLKQILNGVYYLHSLQIAHFDLKPENIMLLDRNVPKPRIKIIDFGLAHKIDFGNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANVSAVNYEFEDEYFSNTSALAKDFIRRLLVKDPKKRMTIQDSLQHPWIKPKDTQQALSRKASAVNMEKFKKFAARKKWKQSVRLISLCQRLSRSFLSRSNMSVARSDDTLDEEDSFVMKAIIHAINDDNVPGLQHLLGSLSNYDVNQPNKHGTPPLLIAAGCGNIQILQLLIKRGSRIDVQDKGGSNAVYWAARHGHVDTLKFLSENKCPLDVKDKSGEMALHVAARYGHADVAQLLCSFGSNPNIQDKEEETPLHCAAWHGYYSVAKALCEAGCNVNIKNREGETPLLTASARGYHDIVECLAEHGADLNACDKDGHIALHLAVRRCQMEVIKTLLSQGCFVDYQDRHGNTPLHVACKDGNMPIVVALCEANCNLDISNKYGRTPLHLAANNGILDVVRYLCLMGASVEALTTDGKTAEDLARSEQHEHVAGLLARLRKDTHRGLFIQQLRPTQNLQPRIKLKLFGHSGSGKTTLVESLKCGLLRSFFRRRRPRLSSTNSSRFPPSPLASKPTVSVSINNLYPGCENVSVRSRSMMFEPGLTKGMLEVFVAPTHHPHCSADDQSTKAIDIQNAYLNGVGDFSVWEFSGNPVYFCCYDYFAANDPTSIHVVVFSLEEPYEIQLNQVIFWLSFLKSLVPVEEPIAFGGKLKNPLQVVLVATHADIMNVPRPAGGEFGYDKDTSLLKEIRNRFGNDLHISNKLFVLDAGASGSKDMKVLRNHLQEIRSQIVSVCPPMTHLCEKIISTLPSWRKLNGPNQLMSLQQFVYDVQDQLNPLASEEDLRRIAQQLHSTGEINIMQSETVQDVLLLDPRWLCTNVLGKLLSVETPRALHHYRGRYTVEDIQRLVPDSDVEELLQILDAMDICARDLSSGTMVDVPALIKTDNLHRSWADEEDEVMVYGGVRIVPVEHLTPFPCGIFHKVQVNLCRWIHQQSTEGDADIRLWVNGCKLANRGAELLVLLVNHGQGIEVQVRGLETEKIKCCLLLDSVCSTIENVMATTLPGLLTVKHYLSPQQLREHHEPVMIYQPRDFFRAQTLKETSLTNTMGGYKESFSSIMCFGCHDVYSQASLGMDIHASDLNLLTRRKLSRLLDPPDPLGKDWCLLAMNLGLPDLVAKYNTSNGAPKDFLPSPLHALLREWTTYPESTVGTLMSKLRELGRRDAADFLLKASSVFKINLDGNGQEAYASSCNSGTSYNSISSVVSR
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Isoform 1: Cytoplasm. Cytoplasm, cytoskeleton. Note=Colocalizes with MAP1B in the microtubules and cortical actin fibers.; Isoform 2: Cytoplasm. Cytoplasm, cytoskeleton.
Function
- 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. 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.; Isoform 2 cannot induce apoptosis but can induce membrane blebbing.
- Catalytic Activity:
- ATP + a protein = ADP + a phosphoprotein.
- Cofactor:
- COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
- Enzyme Regulation:
- 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.
- Active Site:
- ACT_SITE 139 139 Proton acceptor.
- Gene Ontology Go:
- actin cytoskeleton
cytoplasm
plasma membrane
ATP binding
calmodulin binding
calmodulin-dependent protein kinase activity
GTP binding
identical protein binding
protein kinase activity
protein serine/threonine kinase activity
syntaxin-1 binding
apoptotic process
apoptotic signaling pathway
cellular response to interferon-gamma
extrinsic apoptotic signaling pathway
extrinsic apoptotic signaling pathway in absence of ligand
extrinsic apoptotic signaling pathway via death domain receptors
intracellular signal transduction
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
negative regulation of translation
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
programmed cell death
protein autophosphorylation
protein phosphorylation
regulation of apoptotic process
regulation of autophagy
regulation of N-methyl-D-aspartate selective glutamate receptor activity - Gene Ontology Biological Process:
- apoptotic process
apoptotic signaling pathway
cellular response to interferon-gamma
extrinsic apoptotic signaling pathway
extrinsic apoptotic signaling pathway in absence of ligand
extrinsic apoptotic signaling pathway via death domain receptors
intracellular signal transduction
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
negative regulation of translation
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
programmed cell death
protein autophosphorylation
protein phosphorylation
regulation of apoptotic process
regulation of autophagy
regulation of N-methyl-D-aspartate selective glutamate receptor activity - Gene Ontology Molecular Function:
- ATP binding
calmodulin binding
calmodulin-dependent protein kinase activity
GTP binding
identical protein binding
protein kinase activity
protein serine/threonine kinase activity
syntaxin-1 binding - Gene Ontology Cellular Component:
- actin cytoskeleton
cytoplasm
plasma membrane - Keywords:
- 3D-structure
ANK repeat
ATP-binding
Alternative splicing
Apoptosis
Calmodulin-binding
Complete proteome
Cytoplasm
Cytoskeleton
GTP-binding
Kinase
Nucleotide-binding
Phosphoprotein
Polymorphism
Reference proteome
Repeat
Serine/threonine-protein kinase
Transferase
Translation regulation
Ubl conjugation - Interacts With:
- Itself; Q14457; P62158; Q9Y2M5; Q38SD2; Q5S007; P27361; O75340; P14618; P14618-1