DAPK3
entrez
1613
canonical
uniprot
O43293
canonical
ensembl
ENSG00000167657
resolver
ensp
ENSP00000442973
resolver
ensp
ENSP00000545627
resolver
genesymbol
DAPK3
resolver
genesymbol_syn
ZIPK
resolver
hgnc
HGNC:2676
resolver
uniprot
A0AVN4
resolver
uniprot
B3KNJ3
resolver
uniprot
B3KQE2
resolver
uniprot
Q05JY4
resolver
uniprot_entry
B3KNJ3_HUMAN
resolver
uniprot_entry
DAPK3_HUMAN
resolver
uniprot_sec
A0AVN4
resolver
uniprot_sec
B3KQE2
resolver
uniprot_sec
Q05JY4
resolver
activity_regulation
ACTIVITY 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. {ECO:0000269|PubMed:15611134, ECO:0000269|PubMed:17158456, ECO:0000269|PubMed:18239682, ECO:0000303|PubMed:18239682}.
uniprot
proteins
amino_acid_sequence
MSTFRQEDVEDHYEMGEELGSGQFAIVRKCRQKGTGKEYAAKFIKKRRLSSSRRGVSREEIEREVNILREIRHPNIITLHDIFENKTDVVLILELVSGGELFDFLAEKESLTEDEATQFLKQILDGVHYLHSKRIAHFDLKPENIMLLDKNVPNPRIKLIDFGIAHKIEAGNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGETKQETLTNISAVNYDFDEEYFSNTSELAKDFIRRLLVKDPKRRMTIAQSLEHSWIKAIRRRNVRGEDSGRKPERRRLKTTRLKEYTIKSHSSLPPNNSYADFERFSKVLEEAAAAEEGLRELQRSRRLCHEDVEALAAIYEEKEAWYREESDSLGQDLRRLRQELLKTEALKRQAQEEAKGALLGTSGLKRRFSRLENRYEALAKQVASEMRFVQDLVRALEQEKLQGVECGLR
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
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. {ECO:0000269|PubMed:10356987, ECO:0000269|PubMed:11384979, ECO:0000269|PubMed:11781833, ECO:0000269|PubMed:12917339, ECO:0000269|PubMed:15096528, ECO:0000269|PubMed:15367680, ECO:0000269|PubMed:16219639, ECO:0000269|PubMed:17126281, ECO:0000269|PubMed:17158456, ECO:0000269|PubMed:18084323, ECO:0000269|PubMed:18995835, ECO:0000269|PubMed:21169990, ECO:0000269|PubMed:21408167, ECO:0000269|PubMed:21454679, ECO:0000269|PubMed:21487036, ECO:0000269|PubMed:23454120, ECO:0000269|PubMed:38009294}.
uniprot
proteins
mass_dalton
52536
uniprot
proteins
mutagenesis
MUTAGEN 42; /note="K->A: Loss of kinase activity at low concentrations of ATP."; /evidence="ECO:0000269|PubMed:17158456"; MUTAGEN 161; /note="D->A: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:17158456"; MUTAGEN 180; /note="T->A: Greatly reduced kinase activity."; /evidence="ECO:0000269|PubMed:21487036"; MUTAGEN 225; /note="T->A: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:17158456"; MUTAGEN 265; /note="T->A: Loss of phosphorylation by ROCK1, catalytically inactive."; /evidence="ECO:0000269|PubMed:17158456"; MUTAGEN 294..295; /note="RR->AA: Cytoplasmic localization."; /evidence="ECO:0000269|PubMed:20854903"; MUTAGEN 299..300; /note="TT->AA: Predominantly nuclear localization."; /evidence="ECO:0000269|PubMed:15611134"; MUTAGEN 299; /note="T->A: Loss of phosphorylation by ROCK1."; /evidence="ECO:0000269|PubMed:17158456"; MUTAGEN 299; /note="T->D: Predominantly cytoplasmic localization; phosphomimetic."; /evidence="ECO:0000269|PubMed:15611134"; MUTAGEN 427; /note="V->A: Predominantly nuclear localization; when associated with A-434 and A-441."; /evidence="ECO:0000269|PubMed:15611134"; MUTAGEN 434; /note="V->A: Predominantly nuclear localization; when associated with A-427 and A-441."; /evidence="ECO:0000269|PubMed:15611134"; MUTAGEN 441; /note="L->A: Predominantly nuclear localization; when associated with A-427 and A-434."; /evidence="ECO:0000269|PubMed:15611134
uniprot
proteins
post_translational_modification
PTM: 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 promoted by phosphorylation at Thr-299; 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. Both isoform 1 and isoform 2 can undergo autophosphorylation. {ECO:0000269|PubMed:15367680, ECO:0000269|PubMed:15611134, ECO:0000269|PubMed:17158456, ECO:0000269|PubMed:20854903}.
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
10356987
uniprot
proteins
pubmed
11384979
uniprot
proteins
pubmed
11781833
uniprot
proteins
pubmed
12917339
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15096528
uniprot
proteins
pubmed
15292222
uniprot
proteins
pubmed
15367680
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15611134
uniprot
proteins
pubmed
15910542
uniprot
proteins
pubmed
16219639
uniprot
proteins
pubmed
16756490
uniprot
proteins
pubmed
17126281
uniprot
proteins
pubmed
17158456
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17953487
uniprot
proteins
pubmed
18084323
uniprot
proteins
pubmed
18239682
uniprot
proteins
pubmed
18995835
uniprot
proteins
pubmed
20854903
uniprot
proteins
pubmed
21169990
uniprot
proteins
pubmed
21408167
uniprot
proteins
pubmed
21454679
uniprot
proteins
pubmed
21487036
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23454120
uniprot
proteins
pubmed
38009294
uniprot
proteins
pubmed
9488481
uniprot
proteins
sequence_length
454
uniprot
proteins
subcellular_location
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}.
uniprot
proteins