Names & Taxonomy
- Uniprot ID:
- O43293
- Entry Name:
- DAPK3_HUMAN
- Status:
- reviewed
- Protein Names:
- Death-associated protein kinase 3 (DAP kinase 3) (EC 2.7.11.1) (DAP-like kinase) (Dlk) (MYPT1 kinase) (Zipper-interacting protein kinase) (ZIP-kinase)
- Gene Names:
- DAPK3 ZIPK
- Gene Names Primary:
- DAPK3
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 454
- Sequence:
- MSTFRQEDVEDHYEMGEELGSGQFAIVRKCRQKGTGKEYAAKFIKKRRLSSSRRGVSREEIEREVNILREIRHPNIITLHDIFENKTDVVLILELVSGGELFDFLAEKESLTEDEATQFLKQILDGVHYLHSKRIAHFDLKPENIMLLDKNVPNPRIKLIDFGIAHKIEAGNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGETKQETLTNISAVNYDFDEEYFSNTSELAKDFIRRLLVKDPKRRMTIAQSLEHSWIKAIRRRNVRGEDSGRKPERRRLKTTRLKEYTIKSHSSLPPNNSYADFERFSKVLEEAAAAEEGLRELQRSRRLCHEDVEALAAIYEEKEAWYREESDSLGQDLRRLRQELLKTEALKRQAQEEAKGALLGTSGLKRRFSRLENRYEALAKQVASEMRFVQDLVRALEQEKLQGVECGLR
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Nucleus
Function
- Function:
- Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation and actin cytoskeleton reorganization. Involved in the regulation of smooth muscle contraction. Regulates both type I (caspase-dependent) apoptotic and type II (caspase-independent) autophagic cell deaths signal, depending on the cellular setting. Involved in regulation of starvation-induced autophagy. Regulates myosin phosphorylation in both smooth muscle and non-muscle cells. In smooth muscle, regulates myosin either directly by phosphorylating MYL12B and MYL9 or through inhibition of smooth muscle myosin phosphatase (SMPP1M) via phosphorylation of PPP1R12A; the inhibition of SMPP1M functions to enhance muscle responsiveness to Ca(2+) and promote a contractile state. Phosphorylates MYL12B in non-muscle cells leading to reorganization of actin cytoskeleton. Isoform 2 can phosphorylate myosin, PPP1R12A and MYL12B. Overexpression leads to condensation of actin stress fibers into thick bundles. Involved in actin filament focal adhesion dynamics. The function in both reorganization of actin cytoskeleton and focal adhesion dissolution is modulated by RhoD. Positively regulates canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2. 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. Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Involved in regulation of cell cycle progression and cell proliferation. May be a tumor suppressor.
- Catalytic Activity:
- ATP + a protein = ADP + a phosphoprotein.
- Cofactor:
- COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
- Kinetics:
- BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=12 uM for myosin (isoform 2)
- Enzyme Regulation:
- ENZYME REGULATION: A sequential activation is proposed: autophosphorylation at consensus sites is leading to dimerization of the catalytic domain stabilized by phosphorylation at Ser-50 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. Oligomerization is required for full enzymatic activity. Inhibited by pyridone 6 (K00225), a potent, ATP-competitive inhibitor.
- Active Site:
- ACT_SITE 139 139 Proton acceptor.
- Gene Ontology Go:
- actin filament
cytoplasm
membrane raft
nucleus
PML body
ATP binding
cAMP response element binding protein binding
identical protein binding
leucine zipper domain binding
protein homodimerization activity
protein serine/threonine kinase activity
Rho GTPase binding
apoptotic process
apoptotic signaling pathway
cellular response to interferon-gamma
chromatin modification
cytokinesis
intracellular signal transduction
negative regulation of translation
neuron differentiation
positive regulation of apoptotic process
positive regulation of canonical Wnt signaling pathway
positive regulation of cell migration
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand
protein autophosphorylation
protein phosphorylation
regulation of actin cytoskeleton reorganization
regulation of apoptotic process
regulation of autophagy
regulation of cell motility
regulation of cell shape
regulation of focal adhesion assembly
regulation of mitotic cell cycle
regulation of mitotic nuclear division
regulation of myosin II filament organization
regulation of smooth muscle contraction
regulation of transcription, DNA-templated
transcription, DNA-templated - Gene Ontology Biological Process:
- apoptotic process
apoptotic signaling pathway
cellular response to interferon-gamma
chromatin modification
cytokinesis
intracellular signal transduction
negative regulation of translation
neuron differentiation
positive regulation of apoptotic process
positive regulation of canonical Wnt signaling pathway
positive regulation of cell migration
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand
protein autophosphorylation
protein phosphorylation
regulation of actin cytoskeleton reorganization
regulation of apoptotic process
regulation of autophagy
regulation of cell motility
regulation of cell shape
regulation of focal adhesion assembly
regulation of mitotic cell cycle
regulation of mitotic nuclear division
regulation of myosin II filament organization
regulation of smooth muscle contraction
regulation of transcription, DNA-templated
transcription, DNA-templated - Gene Ontology Molecular Function:
- ATP binding
cAMP response element binding protein binding
identical protein binding
leucine zipper domain binding
protein homodimerization activity
protein serine/threonine kinase activity
Rho GTPase binding - Gene Ontology Cellular Component:
- actin filament
cytoplasm
membrane raft
nucleus
PML body - Keywords:
- 3D-structure
ATP-binding
Activator
Alternative splicing
Apoptosis
Chromatin regulator
Complete proteome
Cytoplasm
Kinase
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Serine/threonine-protein kinase
Transcription
Transcription regulation
Transferase
Translation regulation
Tumor suppressor - Interacts With:
- Itself; O14974; Q10728; Q8TDR4