DAPK1
entrez
1612
canonical
uniprot
P53355
canonical
ensembl
ENSG00000196730
resolver
ensp
ENSP00000350785
resolver
ensp
ENSP00000386135
resolver
ensp
ENSP00000417076
resolver
ensp
ENSP00000484267
resolver
ensp
ENSP00000586449
resolver
ensp
ENSP00000586457
resolver
ensp
ENSP00000747187
resolver
ensp
ENSP00000747188
resolver
genesymbol
DAPK1
resolver
genesymbol_syn
DAPK
resolver
hgnc
HGNC:2674
resolver
uniprot
B4DHI4
resolver
uniprot
B7ZLD2
resolver
uniprot
B7ZLE7
resolver
uniprot
Q14CQ7
resolver
uniprot
Q1W5W0
resolver
uniprot
Q59H88
resolver
uniprot
Q68CP8
resolver
uniprot
Q6ZRZ3
resolver
uniprot
Q9BTL8
resolver
uniprot_entry
B4DHI4_HUMAN
resolver
uniprot_entry
DAPK1_HUMAN
resolver
uniprot_entry
Q59H88_HUMAN
resolver
uniprot_sec
B7ZLD2
resolver
uniprot_sec
B7ZLE7
resolver
uniprot_sec
Q14CQ7
resolver
uniprot_sec
Q1W5W0
resolver
uniprot_sec
Q68CP8
resolver
uniprot_sec
Q6ZRZ3
resolver
uniprot_sec
Q9BTL8
resolver
activity_regulation
ACTIVITY 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. {ECO:0000269|PubMed:11579085, ECO:0000269|PubMed:15729359, ECO:0000269|PubMed:17056602}.
uniprot
proteins
amino_acid_sequence
MTVFRQENVDDYYDTGEELGSGQFAVVKKCREKSTGLQYAAKFIKKRRTKSSRRGVSREDIEREVSILKEIQHPNVITLHEVYENKTDVILILELVAGGELFDFLAEKESLTEEEATEFLKQILNGVYYLHSLQIAHFDLKPENIMLLDRNVPKPRIKIIDFGLAHKIDFGNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANVSAVNYEFEDEYFSNTSALAKDFIRRLLVKDPKKRMTIQDSLQHPWIKPKDTQQALSRKASAVNMEKFKKFAARKKWKQSVRLISLCQRLSRSFLSRSNMSVARSDDTLDEEDSFVMKAIIHAINDDNVPGLQHLLGSLSNYDVNQPNKHGTPPLLIAAGCGNIQILQLLIKRGSRIDVQDKGGSNAVYWAARHGHVDTLKFLSENKCPLDVKDKSGEMALHVAARYGHADVAQLLCSFGSNPNIQDKEEETPLHCAAWHGYYSVAKALCEAGCNVNIKNREGETPLLTASARGYHDIVECLAEHGADLNACDKDGHIALHLAVRRCQMEVIKTLLSQGCFVDYQDRHGNTPLHVACKDGNMPIVVALCEANCNLDISNKYGRTPLHLAANNGILDVVRYLCLMGASVEALTTDGKTAEDLARSEQHEHVAGLLARLRKDTHRGLFIQQLRPTQNLQPRIKLKLFGHSGSGKTTLVESLKCGLLRSFFRRRRPRLSSTNSSRFPPSPLASKPTVSVSINNLYPGCENVSVRSRSMMFEPGLTKGMLEVFVAPTHHPHCSADDQSTKAIDIQNAYLNGVGDFSVWEFSGNPVYFCCYDYFAANDPTSIHVVVFSLEEPYEIQLNQVIFWLSFLKSLVPVEEPIAFGGKLKNPLQVVLVATHADIMNVPRPAGGEFGYDKDTSLLKEIRNRFGNDLHISNKLFVLDAGASGSKDMKVLRNHLQEIRSQIVSVCPPMTHLCEKIISTLPSWRKLNGPNQLMSLQQFVYDVQDQLNPLASEEDLRRIAQQLHSTGEINIMQSETVQDVLLLDPRWLCTNVLGKLLSVETPRALHHYRGRYTVEDIQRLVPDSDVEELLQILDAMDICARDLSSGTMVDVPALIKTDNLHRSWADEEDEVMVYGGVRIVPVEHLTPFPCGIFHKVQVNLCRWIHQQSTEGDADIRLWVNGCKLANRGAELLVLLVNHGQGIEVQVRGLETEKIKCCLLLDSVCSTIENVMATTLPGLLTVKHYLSPQQLREHHEPVMIYQPRDFFRAQTLKETSLTNTMGGYKESFSSIMCFGCHDVYSQASLGMDIHASDLNLLTRRKLSRLLDPPDPLGKDWCLLAMNLGLPDLVAKYNTSNGAPKDFLPSPLHALLREWTTYPESTVGTLMSKLRELGRRDAADFLLKASSVFKINLDGNGQEAYASSCNSGTSYNSISSVVSR
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
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.; FUNCTION: Isoform 2 cannot induce apoptosis but can induce membrane blebbing.
uniprot
proteins
mass_dalton
160046
uniprot
proteins
mutagenesis
MUTAGEN 42; /note="K->A: Loss of activity, apoptotic function and of autophosphorylation."; /evidence="ECO:0000269|PubMed:11579085, ECO:0000269|PubMed:7828849"; MUTAGEN 289; /note="S->A: Loss of phosphorylation and significant increase in proapoptotic activity."; MUTAGEN 289; /note="S->E: Reduction in proapoptotic activity."; MUTAGEN 308; /note="S->A: Elevated Ca(2+)-calmodulin binding and Ca(2+)-calmodulin-independent kinase activity. Increases apoptotic activity."; /evidence="ECO:0000269|PubMed:11579085"; MUTAGEN 308; /note="S->D: Reduced Ca(2+)-calmodulin binding and Ca(2+)-calmodulin-independent kinase activity. Decreases apoptotic activity."; /evidence="ECO:0000269|PubMed:11579085"; MUTAGEN 313; /note="S->A: Minimal effect on activity."; /evidence="ECO:0000269|PubMed:11579085
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated by the BCR(KLHL20) E3 ubiquitin ligase complex, leading to its degradation by the proteasome. {ECO:0000269|PubMed:20389280}.; PTM: Removal of the C-terminal tail of isoform 2 (corresponding to amino acids 296-337 of isoform 2) by proteolytic cleavage stimulates maximally its membrane-blebbing function. {ECO:0000269|PubMed:18422656}.; PTM: In response to mitogenic stimulation (PMA or EGF), phosphorylated at Ser-289; phosphorylation suppresses DAPK1 pro-apoptotic function. Autophosphorylation at Ser-308 inhibits its catalytic activity. Phosphorylation at Ser-734 by MAPK1 increases its catalytic activity and promotes cytoplasmic retention of MAPK1. Endoplasmic-stress can cause dephosphorylation at Ser-308. {ECO:0000269|PubMed:11579085, ECO:0000269|PubMed:15616583, ECO:0000269|PubMed:15729359, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:17056602}.
uniprot
proteins
protein_family
CAMK Ser/Thr protein kinase family
uniprot
proteins
protein_family
DAP kinase subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
10629061
uniprot
proteins
pubmed
11573098
uniprot
proteins
pubmed
11579085
uniprot
proteins
pubmed
11980920
uniprot
proteins
pubmed
12730201
uniprot
proteins
pubmed
14505650
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
15367680
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15616583
uniprot
proteins
pubmed
15729359
uniprot
proteins
pubmed
16132846
uniprot
proteins
pubmed
16213824
uniprot
proteins
pubmed
16756490
uniprot
proteins
pubmed
17056602
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17703233
uniprot
proteins
pubmed
17895359
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18195017
uniprot
proteins
pubmed
18422656
uniprot
proteins
pubmed
18974095
uniprot
proteins
pubmed
18995835
uniprot
proteins
pubmed
19180116
uniprot
proteins
pubmed
19878313
uniprot
proteins
pubmed
20389280
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21408167
uniprot
proteins
pubmed
21497122
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
27068745
uniprot
proteins
pubmed
7828849
uniprot
proteins
sequence_length
1430
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm. Cytoplasm, cytoskeleton. Note=Colocalizes with MAP1B in the microtubules and cortical actin fibers.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm. Cytoplasm, cytoskeleton.
uniprot
proteins