Tchem DAPK1 Death-associated protein kinase 1

Protein Summary

Description

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. Death-associated protein kinase 1 is a positive mediator of gamma-interferon induced programmed cell death. DAPK1 encodes a structurally unique 160-kD calmodulin dependent serine-threonine kinase that carries 8 ankyrin repeats and 2 putative P-loop consensus sites. It is a tumor suppressor candidate. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

Uniprot Accession IDs

• P53355
• B7ZLD2
• B7ZLE7
• Q14CQ7
• Q1W5W0
• Q68CP8
• Q6ZRZ3
• Q9BTL8
• DAP kinase 1

Gene Name

• DAPK1

Ensembl ID

• ENST00000358077
• ENSP00000350785
• ENSG00000196730
• ENST00000408954
• ENSP00000386135
• ENST00000469640
• ENSP00000418885
• ENST00000472284
• ENSP00000417076
• ENST00000491893
• ENSP00000419026
• ENST00000622514
• ENSP00000484267

Symbol

• DAPK
• DAPK
• ROCO3

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	1
molecular function	0.97
biological term	0.87
biological process	0.85
hub protein	0.85

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Death-associated Protein Kinase 1

DTO Classes

Protein / Kinase / Protein Kinase / Camk Group / Dapk Family / Death-associated Protein Kinase 1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 384.23   (req: < 5)

Gene RIFs: 230   (req: <= 3)

Antibodies: 362   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 384.23   (req: >= 5)

Gene RIFs: 230   (req: > 3)

Antibodies: 362   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 23

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 5

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 1