O44997
SS
Gene name |
dapk-1 (mor-3, tag-119, K12C11.4) |
Protein name |
Death-associated protein kinase dapk-1 |
Names |
EC 2.7.11.1 |
Species |
Caenorhabditis elegans |
KEGG Pathway |
cel:CELE_K12C11.4 |
EC number |
2.7.11.1: Protein-serine/threonine kinases |
Protein Class |
|
Descriptions
DAPK1, Death-associated protein kinase 1, is a Ca2+/calmodulin (CaM)-regulated Ser/Thr kinase that functions as a positive mediator of programmed cell death. It associates with actin microfilament and has a unique multidomain structure. The structure/function analysis of the protein revealed two modules that regulate the pro-apoptotic effect of DAPK1. One comprises the CaM-regulatory segment, which possesses an autoinhibitory effect on the catalytic activity, relieved by binding to Ca2+-activated CaM. The deletion of this segment from DAPK1 generated a constitutively active kinase, which displayed CaM-independent substrate phosphorylation, and enhanced the apoptotic activity in vivo. Second is the autophosphorylation site (Ser308) which resides within the CaM regulatory segment. The autophosphorylation of Ser308 strengthens a locking device, generated by the interaction of the CaM-autoinhibitory domain with the catalytic cleft. Conversely, absence of the phosphate group weakens the lock and therefore partially relieves the autoinhibition, resulting in Ca2+/CaM-independent activity.
Autoinhibitory domains (AIDs)
Target domain |
28-289 (Protein kinase domain) |
Relief mechanism |
Partner binding, PTM |
Assay |
|
Accessory elements
No accessory elements
References
- Shohat G et al. (2002) "The DAP-kinase family of proteins: study of a novel group of calcium-regulated death-promoting kinases", Biochimica et biophysica acta, 1600, 45-50
- Cohen O et al. (1997) "DAP-kinase is a Ca2+/calmodulin-dependent, cytoskeletal-associated protein kinase, with cell death-inducing functions that depend on its catalytic activity", The EMBO journal, 16, 998-1008
- Shohat G et al. (2001) "The pro-apoptotic function of death-associated protein kinase is controlled by a unique inhibitory autophosphorylation-based mechanism", The Journal of biological chemistry, 276, 47460-7
- Temmerman K et al. (2014) "A PEF/Y substrate recognition and signature motif plays a critical role in DAPK-related kinase activity", Chemistry & biology, 21, 264-73
Autoinhibited structure
Activated structure
1 structures for O44997
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-O44997-F1 | Predicted | AlphaFoldDB |
No variants for O44997
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for O44997 | |||||
No associated diseases with O44997
11 regional properties for O44997
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Death domain | 1295 - 1389 | IPR000488 |
| domain | Protein kinase domain | 28 - 289 | IPR000719 |
| repeat | Ankyrin repeat | 369 - 457 | IPR002110-1 |
| repeat | Ankyrin repeat | 458 - 490 | IPR002110-2 |
| repeat | Ankyrin repeat | 491 - 589 | IPR002110-3 |
| repeat | Ankyrin repeat | 590 - 622 | IPR002110-4 |
| repeat | Ankyrin repeat | 623 - 655 | IPR002110-5 |
| repeat | Ankyrin repeat | 810 - 841 | IPR002110-6 |
| active_site | Serine/threonine-protein kinase, active site | 151 - 163 | IPR008271 |
| binding_site | Protein kinase, ATP binding site | 34 - 61 | IPR017441 |
| domain | Roc domain | 695 - 950 | IPR020859 |
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.11.1 | Protein-serine/threonine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
3 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoskeleton | A cellular structure that forms the internal framework of eukaryotic and prokaryotic cells. The cytoskeleton includes intermediate filaments, microfilaments, microtubules, the microtrabecular lattice, and other structures characterized by a polymeric filamentous nature and long-range order within the cell. The various elements of the cytoskeleton not only serve in the maintenance of cellular shape but also have roles in other cellular functions, including cellular movement, cell division, endocytosis, and movement of organelles. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
5 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| GTP binding | Binding to GTP, guanosine triphosphate. |
| metal ion binding | Binding to a metal ion. |
| protein serine kinase activity | Catalysis of the reactions |
| protein serine/threonine kinase activity | Catalysis of the reactions |
5 GO annotations of biological process
| Name | Definition |
|---|---|
| innate immune response | Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens. |
| intracellular signal transduction | The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell. |
| phosphorylation | The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide. |
| positive regulation of apoptotic process | Any process that activates or increases the frequency, rate or extent of cell death by apoptotic process. |
| regulation of response to stimulus | Any process that modulates the frequency, rate or extent of a response to a stimulus. Response to stimulus is a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus. |
99 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| A4IFM7 | MYLK2 | Myosin light chain kinase 2, skeletal/cardiac muscle | Bos taurus (Bovine) | SS |
| Q0V7M1 | PSKH1 | Serine/threonine-protein kinase H1 | Bos taurus (Bovine) | SS |
| Q0VD22 | STK33 | Serine/threonine-protein kinase 33 | Bos taurus (Bovine) | PR |
| Q96NX5 | CAMK1G | Calcium/calmodulin-dependent protein kinase type 1G | Homo sapiens (Human) | SS |
| O15075 | DCLK1 | Serine/threonine-protein kinase DCLK1 | Homo sapiens (Human) | EV |
| Q14012 | CAMK1 | Calcium/calmodulin-dependent protein kinase type 1 | Homo sapiens (Human) | EV |
| O94768 | STK17B | Serine/threonine-protein kinase 17B | Homo sapiens (Human) | PR |
| Q86YV6 | MYLK4 | Myosin light chain kinase family member 4 | Homo sapiens (Human) | SS |
| Q16566 | CAMK4 | Calcium/calmodulin-dependent protein kinase type IV | Homo sapiens (Human) | SS |
| P11801 | PSKH1 | Serine/threonine-protein kinase H1 | Homo sapiens (Human) | SS |
| Q8N568 | DCLK2 | Serine/threonine-protein kinase DCLK2 | Homo sapiens (Human) | PR |
| Q9UEE5 | STK17A | Serine/threonine-protein kinase 17A | Homo sapiens (Human) | SS |
| O75962 | TRIO | Triple functional domain protein | Homo sapiens (Human) | EV |
| Q9H1R3 | MYLK2 | Myosin light chain kinase 2, skeletal/cardiac muscle | Homo sapiens (Human) | EV |
| Q32MK0 | MYLK3 | Myosin light chain kinase 3 | Homo sapiens (Human) | SS |
| Q8WWF8 | CAPSL | Calcyphosin-like protein | Homo sapiens (Human) | PR |
| Q6P2M8 | PNCK | Calcium/calmodulin-dependent protein kinase type 1B | Homo sapiens (Human) | SS |
| Q9BYT3 | STK33 | Serine/threonine-protein kinase 33 | Homo sapiens (Human) | PR |
| Q8NCB2 | CAMKV | CaM kinase-like vesicle-associated protein | Homo sapiens (Human) | SS |
| Q8IU85 | CAMK1D | Calcium/calmodulin-dependent protein kinase type 1D | Homo sapiens (Human) | SS |
| P53355 | DAPK1 | Death-associated protein kinase 1 | Homo sapiens (Human) | EV |
| O43293 | DAPK3 | Death-associated protein kinase 3 | Homo sapiens (Human) | PR |
| Q9UIK4 | DAPK2 | Death-associated protein kinase 2 | Homo sapiens (Human) | EV |
| Q9QYK9 | Pnck | Calcium/calmodulin-dependent protein kinase type 1B | Mus musculus (Mouse) | PR |
| Q91VB2 | Camk1g | Calcium/calmodulin-dependent protein kinase type 1G | Mus musculus (Mouse) | SS |
| Q8BG48 | Stk17b | Serine/threonine-protein kinase 17B | Mus musculus (Mouse) | PR |
| Q8VCR8 | Mylk2 | Myosin light chain kinase 2, skeletal/cardiac muscle | Mus musculus (Mouse) | SS |
| Q6PGN3 | Dclk2 | Serine/threonine-protein kinase DCLK2 | Mus musculus (Mouse) | PR |
| Q91YS8 | Camk1 | Calcium/calmodulin-dependent protein kinase type 1 | Mus musculus (Mouse) | SS |
| Q3UIZ8 | Mylk3 | Myosin light chain kinase 3 | Mus musculus (Mouse) | SS |
| Q6P8Y1 | Capsl | Calcyphosin-like protein | Mus musculus (Mouse) | PR |
| Q8BW96 | Camk1d | Calcium/calmodulin-dependent protein kinase type 1D | Mus musculus (Mouse) | SS |
| Q3UHL1 | Camkv | CaM kinase-like vesicle-associated protein | Mus musculus (Mouse) | SS |
| P08414 | Camk4 | Calcium/calmodulin-dependent protein kinase type IV | Mus musculus (Mouse) | SS |
| Q9JLM8 | Dclk1 | Serine/threonine-protein kinase DCLK1 | Mus musculus (Mouse) | SS |
| Q91YA2 | Pskh1 | Serine/threonine-protein kinase H1 | Mus musculus (Mouse) | SS |
| Q62407 | Speg | Striated muscle-specific serine/threonine-protein kinase | Mus musculus (Mouse) | SS |
| Q0KL02 | Trio | Triple functional domain protein | Mus musculus (Mouse) | SS |
| Q924X7 | Stk33 | Serine/threonine-protein kinase 33 | Mus musculus (Mouse) | PR |
| O54784 | Dapk3 | Death-associated protein kinase 3 | Mus musculus (Mouse) | PR |
| Q80YE7 | Dapk1 | Death-associated protein kinase 1 | Mus musculus (Mouse) | SS |
| Q8VDF3 | Dapk2 | Death-associated protein kinase 2 | Mus musculus (Mouse) | EV |
| Q7TNJ7 | Camk1g | Calcium/calmodulin-dependent protein kinase type 1G | Rattus norvegicus (Rat) | SS |
| P20689 | Mylk2 | Myosin light chain kinase 2, skeletal/cardiac muscle | Rattus norvegicus (Rat) | SS |
| F1M0Z1 | Trio | Triple functional domain protein | Rattus norvegicus (Rat) | SS |
| Q91XS8 | Stk17b | Serine/threonine-protein kinase 17B | Rattus norvegicus (Rat) | PR |
| O08875 | Dclk1 | Serine/threonine-protein kinase DCLK1 | Rattus norvegicus (Rat) | PR |
| E9PT87 | Mylk3 | Myosin light chain kinase 3 | Rattus norvegicus (Rat) | SS |
| O70150 | Pnck | Calcium/calmodulin-dependent protein kinase type 1B | Rattus norvegicus (Rat) | PR |
| Q63092 | Camkv | CaM kinase-like vesicle-associated protein | Rattus norvegicus (Rat) | SS |
| Q63638 | Speg | Striated muscle-specific serine/threonine-protein kinase | Rattus norvegicus (Rat) | SS |
| P13234 | Camk4 | Calcium/calmodulin-dependent protein kinase type IV | Rattus norvegicus (Rat) | SS |
| Q63450 | Camk1 | Calcium/calmodulin-dependent protein kinase type 1 | Rattus norvegicus (Rat) | EV |
| P97924 | Kalrn | Kalirin | Rattus norvegicus (Rat) | SS |
| Q5MPA9 | Dclk2 | Serine/threonine-protein kinase DCLK2 | Rattus norvegicus (Rat) | PR |
| O88764 | Dapk3 | Death-associated protein kinase 3 | Rattus norvegicus (Rat) | PR |
| Q5VQQ5 | CPK2 | Calcium-dependent protein kinase 2 | Oryza sativa subsp. japonica (Rice) | SS |
| Q8LPZ7 | CPK3 | Calcium-dependent protein kinase 3 | Oryza sativa subsp. japonica (Rice) | SS |
| Q6K968 | CPK6 | Calcium-dependent protein kinase 6 | Oryza sativa subsp. japonica (Rice) | SS |
| P53684 | CPK7 | Calcium-dependent protein kinase 7 | Oryza sativa subsp japonica (Rice) | PR |
| Q75GE8 | CPK8 | Calcium-dependent protein kinase 8 | Oryza sativa subsp. japonica (Rice) | SS |
| Q6I5I8 | CPK16 | Calcium-dependent protein kinase 16 | Oryza sativa subsp. japonica (Rice) | SS |
| Q6AVM3 | CCAMK | Calcium and calcium/calmodulin-dependent serine/threonine-protein kinase | Oryza sativa subsp japonica (Rice) | PR |
| Q84SL0 | CPK20 | Calcium-dependent protein kinase 20 | Oryza sativa subsp. japonica (Rice) | SS |
| P53682 | CPK23 | Calcium-dependent protein kinase 23 | Oryza sativa subsp japonica (Rice) | PR |
| Q9TXJ0 | cmk-1 | Calcium/calmodulin-dependent protein kinase type 1 | Caenorhabditis elegans | PR |
| Q95QC4 | zyg-8 | Serine/threonine-protein kinase zyg-8 | Caenorhabditis elegans | PR |
| P28583 | Calcium-dependent protein kinase SK5 | Glycine max (Soybean) (Glycine hispida) | PR | |
| Q9M9V8 | CPK10 | Calcium-dependent protein kinase 10 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q39016 | CPK11 | Calcium-dependent protein kinase 11 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q9FX86 | CRK8 | CDPK-related kinase 8 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9SSF8 | CPK30 | Calcium-dependent protein kinase 30 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q38872 | CPK6 | Calcium-dependent protein kinase 6 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q7XJR9 | CPK16 | Calcium-dependent protein kinase 16 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9SIQ7 | CPK24 | Calcium-dependent protein kinase 24 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9SJ61 | CPK25 | Calcium-dependent protein kinase 25 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9ZV15 | CPK20 | Calcium-dependent protein kinase 20 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| P93759 | GK-1 | Calcium-dependent protein kinase 14 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q8S8S2 | LPEAT2 | Lysophospholipid acyltransferase LPEAT2 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q38870 | CPK2 | Calcium-dependent protein kinase 2 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9LJL9 | CRK2 | CDPK-related kinase 2 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9SG12 | CRK6 | CDPK-related kinase 6 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9SCS2 | CRK5 | CDPK-related kinase 5 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q8W4I7 | CPK13 | Calcium-dependent protein kinase 13 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q6NLQ6 | CPK32 | Calcium-dependent protein kinase 32 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9ZSA4 | CPK27 | Calcium-dependent protein kinase 27 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q38869 | CPK4 | Calcium-dependent protein kinase 4 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q42479 | CPK3 | Calcium-dependent protein kinase 3 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q1PE17 | CPK18 | Calcium-dependent protein kinase 18 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q06850 | CPK1 | Calcium-dependent protein kinase 1 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9FMP5 | CPK17 | Calcium-dependent protein kinase 17 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q38873 | CPK7 | Calcium-dependent protein kinase 7 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q3E9C0 | CPK34 | Calcium-dependent protein kinase 34 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q42438 | CPK8 | Calcium-dependent protein kinase 8 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q42396 | CPK12 | Calcium-dependent protein kinase 12 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q9FKW4 | CPK28 | Calcium-dependent protein kinase 28 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q1LUA6 | trio | Triple functional domain protein | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| A8C984 | mylk3 | Myosin light chain kinase 3 | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q7SY49 | camkv | CaM kinase-like vesicle-associated protein | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MSDDVNSSAT | STSSSTVHFD | DTPFEDVYEI | ETELGSGQFA | VVRRVRDRKT | GEKYAAKFIK |
| 70 | 80 | 90 | 100 | 110 | 120 |
| KRRYATSRRG | VTRQNIEREV | RVLQKIRGNS | NVVELHAVYE | TASDVIIVLE | LVSGGELFDH |
| 130 | 140 | 150 | 160 | 170 | 180 |
| VCAKECLDEV | EAAAFIKQIL | LAVRHLHSLH | IVHLDIKPEN | VMLKQRGDSQ | IKIIDFGLSR |
| 190 | 200 | 210 | 220 | 230 | 240 |
| EIEPGAVVKD | MVGTPEFVAP | EVVNYEALSP | ATDMWAVGVV | TYILLSGGSP | FLGDNRDETF |
| 250 | 260 | 270 | 280 | 290 | 300 |
| SNITRVRYHF | SDRYFKNTSK | HAKDFIYRLF | VRDVDQRATV | EECLQHPWIR | GPEGNAIDIR |
| 310 | 320 | 330 | 340 | 350 | 360 |
| KASCITISHI | QSFKTRQRWK | RCVELVMVLL | KASKSSRRIG | DGRFDEEDMV | ASCTLICAEE |
| 370 | 380 | 390 | 400 | 410 | 420 |
| GNLRALHKLS | ALHKLLPNAT | RKSLKSSFSE | PNGATAMHCA | AKYGHAEVFN | YFHMKGGNIC |
| 430 | 440 | 450 | 460 | 470 | 480 |
| ARDDNGDTPL | HVACRFAQHT | VAGYVANEKI | DVDSINKTGE | TALHCAVESA | DTRVVRLLLQ |
| 490 | 500 | 510 | 520 | 530 | 540 |
| LRPRLDLPNA | SGDTVLHLAA | DSINPRIVPL | LVCLAPPLHL | RNIREETPLH | VAAARGHVDC |
| 550 | 560 | 570 | 580 | 590 | 600 |
| VQALLDANSP | IDAVEQDGKT | ALIIALENGN | VDIASILITN | GCDINHADHH | GDTALHIASK |
| 610 | 620 | 630 | 640 | 650 | 660 |
| HGLLQAVQTL | CHCAVTVDSV | NANKKTALHL | AAHYGHVDII | RVLLLARADV | TLRGDDGLTA |
| 670 | 680 | 690 | 700 | 710 | 720 |
| ELVAVAAERL | EAHSLLKMVK | SQEIREEYIS | QLYPLDTSLR | RIKLKLLGHS | QSGKTRLVQT |
| 730 | 740 | 750 | 760 | 770 | 780 |
| LHSSRGISSF | LESVTRRISD | HYSPSSSMKD | DGIHSTNGSF | VSESNNNSSF | DLAAAAGSKY |
| 790 | 800 | 810 | 820 | 830 | 840 |
| APPHSQYTRG | IDVQTVNING | CGEFSVWEFG | GYEPMHTCYD | HFVGNADCIH | LILYRTSDPT |
| 850 | 860 | 870 | 880 | 890 | 900 |
| EVQYKQILYW | MNFLKGRVTP | FEPIGHCGFS | SRRSKVIIVG | THATSSLFPQ | MNQEGEYVSS |
| 910 | 920 | 930 | 940 | 950 | 960 |
| DIEAMLNTVR | LRFETHFDMD | HRLILLDATN | PSCIGMKTLK | MELAKCRTNI | LAKLLKPLAI |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| LDTVVNHLNL | VRKKHANFPV | ITWPDFIQLV | RNEINPLTGD | AHCRQIVQQL | QLIGELVYLR |
| 1030 | 1040 | 1050 | 1060 | 1070 | 1080 |
| NDLCDADYVV | LNAEWFGTHI | LGQLLSAEFL | SKASPNGSYH | TSSLAKIFPE | IPEQSDLMTI |
| 1090 | 1100 | 1110 | 1120 | 1130 | 1140 |
| LEVLQLCAPD | ARTGAHEFPV | FIQTEAPDSI | WRPYSLKEKE | RDTVYGGVRI | LPMRGMERSL |
| 1150 | 1160 | 1170 | 1180 | 1190 | 1200 |
| HSTFPRIQVA | LRRSINDYQP | AKDTQLHQWS | ECSKLVSQDR | EAVIRMVGDA | VEIRARGPSE |
| 1210 | 1220 | 1230 | 1240 | 1250 | 1260 |
| SATSMFYFME | DLINLVEHAA | AEVGPGISLE | RHFISPKHLK | EHREHPALFP | PESMMEMQQR |
| 1270 | 1280 | 1290 | 1300 | 1310 | 1320 |
| ESLSVKGTQD | EEELFTDVVC | FGSRDVARHL | TLGIDVGVAD | LQMASRCELA | CLLDPPHAMG |
| 1330 | 1340 | 1350 | 1360 | 1370 | 1380 |
| RDWSILAVKL | QLTDQVPDVD | STGQSLSRTD | QLLNEWAIHH | PEQASVGNLC | RILVELGRCD |
| 1390 | 1400 | 1410 | 1420 | ||
| ARDALYRTVP | LYVFAPLEDQ | FLLETNDSGV | VSSCHSSSEH | NPINI |