Protein: 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) (O43293)
Organism: Homo sapiens (Human)
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.
Subcellular location: Nucleus {ECO:0000269|PubMed:15367680, ECO:0000269|PubMed:15910542, ECO:0000269|PubMed:20854903}. Nucleus, PML body {ECO:0000250|UniProtKB:O54784}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250|UniProtKB:O54784}. Chromosome, centromere {ECO:0000269|PubMed:38009294}. Cytoplasm {ECO:0000269|PubMed:15367680, ECO:0000269|PubMed:15611134, ECO:0000269|PubMed:17953487, ECO:0000269|PubMed:20854903}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:38009294}. Midbody {ECO:0000269|PubMed:38009294}. Note=Predominantly localizes to the cytoplasm but can shuttle between the nucleus and cytoplasm; cytoplasmic localization is promoted by phosphorylation at Thr-299 and involves Rho/Rock signaling. {ECO:0000269|PubMed:17953487, ECO:0000269|PubMed:20854903}.; SUBCELLULAR LOCATION: [Isoform 1]: Nucleus {ECO:0000269|PubMed:17126281}. Cytoplasm {ECO:0000269|PubMed:17126281}.; SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000269|PubMed:17126281}. Cytoplasm {ECO:0000269|PubMed:17126281}.
Interaction partners:
- Leucine zipper protein 1
- Beclin-1
- PRKC apoptosis WT1 regulator protein
- Death-associated protein kinase 1
- Mitogen-activated protein kinase 3
- Mitogen-activated protein kinase 1
- Beclin-2
- Death-associated protein kinase 2
- Calmodulin-like protein 3
- Calmodulin-like protein 5
Sequence:
MSTFRQEDVEDHYEMGEELGSGQFAIVRKCRQKGTGKEYAAKFIKKRRLSSSRRGVSREEIEREVNILREIRHPNIITLHDIFENKTDVVLILELVSGGELFDFLAEKESLTEDEATQFLKQILDGVHYLHSKRIAHFDLKPENIMLLDKNVPNPRIKLIDFGIAHKIEAGNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGETKQETLTNISAVNYDFDEEYFSNTSELAKDFIRRLLVKDPKRRMTIAQSLEHSWIKAIRRRNVRGEDSGRKPERRRLKTTRLKEYTIKSHSSLPPNNSYADFERFSKVLEEAAAAEEGLRELQRSRRLCHEDVEALAAIYEEKEAWYREESDSLGQDLRRLRQELLKTEALKRQAQEEAKGALLGTSGLKRRFSRLENRYEALAKQVASEMRFVQDLVRALEQEKLQGVECGLR