O54784 · DAPK3_MOUSE
- ProteinDeath-associated protein kinase 3
- GeneDapk3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids448 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation and actin cytoskeleton reorganization. Regulates both type I (caspase-dependent) apoptotic and type II (caspase-independent) autophagic cell deaths signal, depending on the cellular setting. Involved in formation of promyelocytic leukemia protein nuclear body (PML-NB). Involved in apoptosis involving PAWR which mediates cytoplasmic relocation; in vitro phosphorylates PAWR (By similarity).
Phosphorylates MYL12B in non-muscle cells leading to reorganization of actin cytoskeleton such as in regulation of cell polarity and cell migration. Positively regulates canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2; disrupts the NLK-TCF7L2 complex thereby influencing the phosphorylation of TCF7L2 by NLK. Phosphorylates STAT3 and enhances its transcriptional activity. Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Phosphorylates histone H3 on 'Thr-11' at centromeres during mitosis (By similarity).
Phosphorylates RPL13A on 'Ser-77' upon interferon-gamma activation which is causing RPL13A release from the ribosome, RPL13A association with the GAIT complex and its subsequent involvement in transcript-selective translation inhibition
Phosphorylates MYL12B in non-muscle cells leading to reorganization of actin cytoskeleton such as in regulation of cell polarity and cell migration. Positively regulates canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2; disrupts the NLK-TCF7L2 complex thereby influencing the phosphorylation of TCF7L2 by NLK. Phosphorylates STAT3 and enhances its transcriptional activity. Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Phosphorylates histone H3 on 'Thr-11' at centromeres during mitosis (By similarity).
Phosphorylates RPL13A on 'Ser-77' upon interferon-gamma activation which is causing RPL13A release from the ribosome, RPL13A association with the GAIT complex and its subsequent involvement in transcript-selective translation inhibition
Miscellaneous
A species-specific loss of a key phosphorylation site in murine DAPK3 seems to direct it mainly to the nucleus which is proposed to be compensated by the interaction with PAWR to maintain at least the cytoplasmic basic membrane blebbing function in the apoptosis pathway.
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Cofactor
Activity regulation
A sequential activation is proposed: autophosphorylation at consensus sites is leading to dimerization of the catalytic domain and activation segment exchange (producing an active confirmation of both kinase modules in trans) followed by phosphorylation at Thr-180 in the activation segment and at other regulatory sites (Probable). Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity. Inhibited by pyridone 6 (K00225), a potent, ATP-competitive inhibitor. Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity.
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDeath-associated protein kinase 3
- EC number
- Short namesDAP kinase 3
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionO54784
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Predominantly localized to the nucleus. Relocates to the cytoplasm on binding PAWR where the complex appears to interact with actin filaments. Associated with the centrosomes throughout the mitotic cell cycle, with the centromeres from prophase to anaphase and with the contractile ring during cytokinesis (By similarity).
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 42 | Loss of activity. | ||||
Sequence: K → A | ||||||
Mutagenesis | 289-290 | Nuclear localization. | ||||
Sequence: RR → AA | ||||||
Mutagenesis | 294 | Nuclear colocalization. | ||||
Sequence: A → D | ||||||
Mutagenesis | 422 | Decreased activity; when associated with A-429 and A-436. | ||||
Sequence: V → A | ||||||
Mutagenesis | 429 | Decreased activity; when associated with A-422 and A-436. | ||||
Sequence: V → A | ||||||
Mutagenesis | 436 | Decreased activity; when associated with A-422 and A-429. | ||||
Sequence: L → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 4 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000085915 | 1-448 | Death-associated protein kinase 3 | |||
Sequence: MSTFRQEDVEDHYEMGEELGSGQFAIVRKCQQKGTGMEYAAKFIKKRRLPSSRRGVSREEIEREVSILREIRHPNIITLHDVFENKTDVVLILELVSGGELFDFLAEKESLTEDEATQFLKQILDGVHYLHSKRIAHFDLKPENIMLLDKHAASPRIKLIDFGIAHRIEAGSEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGETKQETLTNISAVNYDFDEEYFSSTSELAKDFIRRLLVKDPKRRMTIAQSLEHSWIKVRRREDGARKPERRRLRAARLREYSLKSHSSMPRNTSYASFERFSRVLEDVAAAEQGLRELQRGRRQCRERVCALRAAAEQREARCRDGSAGLGRDLRRLRTELGRTEALRTRAQEEARAALLGAGGLKRRLCRLENRYDALAAQVAAEVQFVRDLVRALEQERLQAECGVR | ||||||
Modified residue | 180 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 225 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 265 | Phosphothreonine; by autocatalysis | ||||
Sequence: T | ||||||
Modified residue | 265 | Phosphothreonine; by ROCK1 | ||||
Sequence: T | ||||||
Modified residue | 304 | Phosphoserine; by DAPK1 | ||||
Sequence: S | ||||||
Modified residue | 306 | Phosphoserine; by autocatalysis and DAPK1 | ||||
Sequence: S | ||||||
Modified residue | 307 | Phosphoserine; by DAPK1 | ||||
Sequence: S | ||||||
Modified residue | 313 | Phosphoserine; by DAPK1 | ||||
Sequence: S | ||||||
Modified residue | 321 | Phosphoserine; by DAPK1 | ||||
Sequence: S |
Post-translational modification
Ubiquitinated. Ubiquitination mediated by the UBE2D3 E3 ligase does not lead to proteasomal degradation, but influences promyelocytic leukemia protein nuclear bodies (PML-NBs) formation in the nucleus.
The phosphorylation status is critical for kinase activity, oligomerization and intracellular localization. Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity. The phosphorylated form is localized in the cytoplasm and nuclear translocation or retention is maximal when it is not phosphorylated. Phosphorylation increases the trimeric form, and its dephosphorylation favors a kinase-inactive monomeric form.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in heart, brain, lung, skeletal muscle, kidney and testis. Lower levels in liver and spleen.
Gene expression databases
Interaction
Subunit
Homooligomer in its kinase-active form (homotrimers and homodimers are reported); monomeric in its kinase-inactive form. Homodimerization is required for activation segment autophosphorylation (By similarity).
Interacts with DAXX, PAWR, ATF4, NLK, TCF7L2, UBE2D1, UBE2D2, UBE2D3, and CDC5L. Interacts with AR; enhanced by AATF
Interacts with DAXX, PAWR, ATF4, NLK, TCF7L2, UBE2D1, UBE2D2, UBE2D3, and CDC5L. Interacts with AR; enhanced by AATF
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O54784 | Atf4 Q06507 | 3 | EBI-77359, EBI-77383 | |
XENO | O54784 | ATF4 P18848 | 2 | EBI-77359, EBI-492498 | |
BINARY | O54784 | Daxx O35613 | 2 | EBI-77359, EBI-77304 | |
BINARY | O54784 | Pawr Q925B0 | 2 | EBI-77359, EBI-77397 | |
BINARY | O54784 | Stat3 P42227 | 8 | EBI-77359, EBI-602878 | |
XENO | O54784 | UBE2D3 P61077 | 2 | EBI-77359, EBI-348268 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 13-275 | Protein kinase | ||||
Sequence: YEMGEELGSGQFAIVRKCQQKGTGMEYAAKFIKKRRLPSSRRGVSREEIEREVSILREIRHPNIITLHDVFENKTDVVLILELVSGGELFDFLAEKESLTEDEATQFLKQILDGVHYLHSKRIAHFDLKPENIMLLDKHAASPRIKLIDFGIAHRIEAGSEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGETKQETLTNISAVNYDFDEEYFSSTSELAKDFIRRLLVKDPKRRMTIAQSLEHSWI | ||||||
Region | 161-204 | Activation segment | ||||
Sequence: DFGIAHRIEAGSEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIG | ||||||
Region | 390-448 | Interaction with CDC5L | ||||
Sequence: AQEEARAALLGAGGLKRRLCRLENRYDALAAQVAAEVQFVRDLVRALEQERLQAECGVR | ||||||
Region | 422-436 | Leucine-zipper | ||||
Sequence: VAAEVQFVRDLVRAL |
Sequence similarities
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length448
- Mass (Da)51,422
- Last updated1998-06-01 v1
- ChecksumDA32EF3EB1F20EFC
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A1W2P6J6 | A0A1W2P6J6_MOUSE | Dapk3 | 256 | ||
A0A1W2P6K3 | A0A1W2P6K3_MOUSE | Dapk3 | 205 | ||
A0A1W2P730 | A0A1W2P730_MOUSE | Dapk3 | 135 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB007143 EMBL· GenBank· DDBJ | BAA24954.1 EMBL· GenBank· DDBJ | mRNA |