P40417
SS
Gene name |
rl (ERKa, MAPK, CG12559) |
Protein name |
Mitogen-activated protein kinase ERK-A |
Names |
EC 2.7.11.24 , Extracellular-regulated kinase A , Protein rolled |
Species |
Drosophila melanogaster (Fruit fly) |
KEGG Pathway |
dme:Dmel_CG12559 |
EC number |
2.7.11.24: Protein-serine/threonine kinases |
Protein Class |
|
Descriptions
MAPK1 encodes Mitogen-activated protein kinase 1, and is involved in diverse cellular responses by phosphorylating cytoplasmic and nuclear proteins. Unlike other MAP kinases, MAPK1 activates via dual phosphorylation of Thr-186 and Tyr-193 within the activation lip, and mutations at Q105 alone were sufficient for autoactivation. Additionally, in the inactive form, L76, Q10 and I87 form a structural unit that restrains intramolecular autophosphorylation by preventing interactions between activation lip residues and the catalytic base (D149) needed for phosphoryl transfer. Mutations at L76, I87 and additionally S153 increased basal specific activity via autophosphorylation of Thr-186 and Tyr-193.
Autoinhibitory domains (AIDs)
Target domain |
38-326 (Protein kinase domain) |
Relief mechanism |
PTM |
Assay |
|
Accessory elements
179-205 (Activation loop from InterPro)
Target domain |
38-326 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
References
- Emrick MA et al. (2006) "The gatekeeper residue controls autoactivation of ERK2 via a pathway of intramolecular connectivity", Proceedings of the National Academy of Sciences of the United States of America, 103, 18101-6
- Emrick MA et al. (2001) "Constitutive activation of extracellular signal-regulated kinase 2 by synergistic point mutations", The Journal of biological chemistry, 276, 46469-79
Autoinhibited structure
Activated structure
1 structures for P40417
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P40417-F1 | Predicted | AlphaFoldDB |
No variants for P40417
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for P40417 | |||||
No associated diseases with P40417
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.11.24 | Protein-serine/threonine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
4 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| neuromuscular junction | The junction between the axon of a motor neuron and a muscle fiber. In response to the arrival of action potentials, the presynaptic button releases molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane of the muscle fiber, leading to a change in post-synaptic potential. |
| 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. |
6 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| DNA-binding transcription factor binding | Binding to a DNA-binding transcription factor, a protein that interacts with a specific DNA sequence (sometimes referred to as a motif) within the regulatory region of a gene to modulate transcription. |
| MAP kinase activity | Catalysis of the reaction |
| protein kinase binding | Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate. |
| protein serine kinase activity | Catalysis of the reactions |
| protein serine/threonine kinase activity | Catalysis of the reactions |
39 GO annotations of biological process
| Name | Definition |
|---|---|
| behavioral response to ethanol | Any process that results in a change in the behavior of an organism as a result of an ethanol stimulus. |
| branching involved in open tracheal system development | The process in which the anatomical structures of branches in the open tracheal system are generated and organized. |
| cell surface receptor signaling pathway | The series of molecular signals initiated by activation of a receptor on the surface of a cell. The pathway begins with binding of an extracellular ligand to a cell surface receptor, or for receptors that signal in the absence of a ligand, by ligand-withdrawal or the activity of a constitutively active receptor. The pathway ends with regulation of a downstream cellular process, e.g. transcription. |
| cellular response to arsenic-containing substance | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an arsenic stimulus from compounds containing arsenic, including arsenates, arsenites, and arsenides. |
| cellular response to cadmium ion | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cadmium (Cd) ion stimulus. |
| cellular response to reactive oxygen species | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a reactive oxygen species stimulus. Reactive oxygen species include singlet oxygen, superoxide, and oxygen free radicals. |
| cellular response to starvation | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of deprivation of nourishment. |
| defense response to virus | Reactions triggered in response to the presence of a virus that act to protect the cell or organism. |
| determination of adult lifespan | The pathways that regulate the duration of the adult phase of the life-cycle of an animal. |
| dorsal appendage formation | Establishment of the dorsal filaments, elaborate specializations of the chorion that protrude from the anterior end of the egg and facilitate embryonic respiration. |
| epidermal growth factor receptor signaling pathway | The series of molecular signals initiated by binding of a ligand to the tyrosine kinase receptor EGFR (ERBB1) on the surface of a cell. The pathway ends with regulation of a downstream cellular process, e.g. transcription. |
| ERK1 and ERK2 cascade | An intracellular protein kinase cascade containing at least ERK1 or ERK2 (MAPKs), a MEK (a MAPKK) and a MAP3K. The cascade may involve 4 different kinases, as it can also contain an additional tier |
| fibroblast growth factor receptor signaling pathway | The series of molecular signals generated as a consequence of a fibroblast growth factor receptor binding to one of its physiological ligands. |
| imaginal disc-derived wing morphogenesis | The process in which the anatomical structures of the imaginal disc-derived wing are generated and organized. The wing is an appendage modified for flying. |
| imaginal disc-derived wing vein specification | The regionalization process in which the area of a imaginal disc-derived wing that will form a wing vein is specified. |
| insulin receptor signaling pathway | The series of molecular signals generated as a consequence of the insulin receptor binding to insulin. |
| 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. |
| leg disc proximal/distal pattern formation | The establishment, maintenance and elaboration of the proximal/distal axis of the leg imaginal disc, a precursor to the adult leg. |
| lymph gland crystal cell differentiation | The process in which a relatively unspecialized larval lymph gland-derived hemocyte precursor cell acquires the specialized features of a crystal cell. Crystal cells are a class of cells that contain crystalline inclusions and are involved in the melanization of pathogenic material in the hemolymph. |
| lymph gland plasmatocyte differentiation | The process in which a relatively unspecialized larval lymph gland-derived hemocyte precursor cell acquires the specialized features of the phagocytic blood-cell type, the plasmatocyte. |
| MAPK cascade | An intracellular protein kinase cascade containing at least a MAPK, a MAPKK and a MAP3K. The cascade can also contain an additional tiers |
| metamorphosis | A biological process in which an animal physically develops after birth or hatching, involving a conspicuous and relatively abrupt change in the animal's form or structure. Examples include the change from tadpole to frog, and the change from larva to adult. An example of this is found in Drosophila melanogaster. |
| mitotic cell cycle | Progression through the phases of the mitotic cell cycle, the most common eukaryotic cell cycle, which canonically comprises four successive phases called G1, S, G2, and M and includes replication of the genome and the subsequent segregation of chromosomes into daughter cells. In some variant cell cycles nuclear replication or nuclear division may not be followed by cell division, or G1 and G2 phases may be absent. |
| modulation of chemical synaptic transmission | Any process that modulates the frequency or amplitude of synaptic transmission, the process of communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. Amplitude, in this case, refers to the change in postsynaptic membrane potential due to a single instance of synaptic transmission. |
| negative regulation of macroautophagy | Any process that stops, prevents, or reduces the frequency, rate or extent of macroautophagy. |
| 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 cell population proliferation | Any process that activates or increases the rate or extent of cell proliferation. |
| positive regulation of cell size | Any process that increases cell size. |
| positive regulation of photoreceptor cell differentiation | Any process that activates or increases the frequency, rate or extent of photoreceptor cell differentiation. An example of this process is found in Drosophila melanogaster. |
| positive regulation of wound healing | Any process that increases the rate, frequency, or extent of the series of events that restore integrity to a damaged tissue, following an injury. |
| R7 cell fate commitment | The process in which the R7 photoreceptor commits to its cell fate. The R7 receptor contributes the central part of the rhabdomere in the apical parts of the ommatidium. |
| regulation of heart morphogenesis | Any process that modulates the frequency, rate or extent of heart morphogenesis. |
| regulation of response to drug | Any process that modulates the frequency, rate or extent of response to drug. |
| sevenless signaling pathway | The series of molecular signals initiated by an extracellular ligand binding to sevenless (sev; a receptor tyrosine kinase) on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. |
| terminal branching, open tracheal system | Formation of terminal branches in the open tracheal system. These are long cytoplasmic extensions that form fine tubules that transport oxygen directly to the tissues. An example of the process is found in Drosophila melanogaster. |
| terminal region determination | Specification of the terminal regions (the two non-segmented ends) of the embryo by the gap genes; exemplified in insects by the actions of huckebein and tailless gene products. |
| torso signaling pathway | The series of molecular signals initiated by an extracellular ligand binding to torso (a receptor tyrosine kinase) on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. |
| tracheal pit formation in open tracheal system | Formation of the tracheal pits, the first tube-like structures to form in the open tracheal system. Once cells are determined to their tracheal cell fate, the tracheal pits arise by invagination of each ectodermal cluster of tracheal placode cells, between 5 and 7 hours after egg laying. An example of this is found in Drosophila melanogaster. |
| vascular endothelial growth factor receptor signaling pathway | The series of molecular signals initiated by a ligand binding to a vascular endothelial growth factor receptor (VEGFR) on the surface of the target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. |
86 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P16892 | FUS3 | Mitogen-activated protein kinase FUS3 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) | SS |
| P14681 | KSS1 | Mitogen-activated protein kinase KSS1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) | SS |
| A5PKJ4 | MAPK7 | Mitogen-activated protein kinase 7 | Bos taurus (Bovine) | SS |
| Q3T0N5 | MAPK13 | Mitogen-activated protein kinase 13 | Bos taurus (Bovine) | SS |
| P46196 | MAPK1 | Mitogen-activated protein kinase 1 | Bos taurus (Bovine) | SS |
| Q5F3W3 | MAPK6 | Mitogen-activated protein kinase 6 | Gallus gallus (Chicken) | SS |
| Q95NE7 | MAPK14 | Mitogen-activated protein kinase 14 | Pan troglodytes (Chimpanzee) | SS |
| Q9N272 | MAPK13 | Mitogen-activated protein kinase 13 | Pan troglodytes (Chimpanzee) | SS |
| O61443 | p38b | Mitogen-activated protein kinase p38b | Drosophila melanogaster (Fruit fly) | SS |
| O62618 | p38a | Mitogen-activated protein kinase p38a | Drosophila melanogaster (Fruit fly) | SS |
| P83100 | p38c | Putative mitogen-activated protein kinase 14C | Drosophila melanogaster (Fruit fly) | SS |
| Q9W354 | Erk7 | Extracellular signal-regulated kinase 7 | Drosophila melanogaster (Fruit fly) | SS |
| O15264 | MAPK13 | Mitogen-activated protein kinase 13 | Homo sapiens (Human) | SS |
| P53778 | MAPK12 | Mitogen-activated protein kinase 12 | Homo sapiens (Human) | SS |
| Q16539 | MAPK14 | Mitogen-activated protein kinase 14 | Homo sapiens (Human) | SS |
| Q13164 | MAPK7 | Mitogen-activated protein kinase 7 | Homo sapiens (Human) | SS |
| Q15759 | MAPK11 | Mitogen-activated protein kinase 11 | Homo sapiens (Human) | SS |
| Q8TD08 | MAPK15 | Mitogen-activated protein kinase 15 | Homo sapiens (Human) | SS |
| P28482 | MAPK1 | Mitogen-activated protein kinase 1 | Homo sapiens (Human) | EV |
| P27361 | MAPK3 | Mitogen-activated protein kinase 3 | Homo sapiens (Human) | SS |
| P31152 | MAPK4 | Mitogen-activated protein kinase 4 | Homo sapiens (Human) | SS |
| Q16659 | MAPK6 | Mitogen-activated protein kinase 6 | Homo sapiens (Human) | SS |
| Q9Z1B7 | Mapk13 | Mitogen-activated protein kinase 13 | Mus musculus (Mouse) | SS |
| P47811 | Mapk14 | Mitogen-activated protein kinase 14 | Mus musculus (Mouse) | SS |
| Q9WVS8 | Mapk7 | Mitogen-activated protein kinase 7 | Mus musculus (Mouse) | SS |
| Q9WUI1 | Mapk11 | Mitogen-activated protein kinase 11 | Mus musculus (Mouse) | SS |
| O08911 | Mapk12 | Mitogen-activated protein kinase 12 | Mus musculus (Mouse) | SS |
| Q80Y86 | Mapk15 | Mitogen-activated protein kinase 15 | Mus musculus (Mouse) | SS |
| Q63844 | Mapk3 | Mitogen-activated protein kinase 3 | Mus musculus (Mouse) | SS |
| P63085 | Mapk1 | Mitogen-activated protein kinase 1 | Mus musculus (Mouse) | SS |
| Q61532 | Mapk6 | Mitogen-activated protein kinase 6 | Mus musculus (Mouse) | SS |
| Q6P5G0 | Mapk4 | Mitogen-activated protein kinase 4 | Mus musculus (Mouse) | SS |
| P70618 | Mapk14 | Mitogen-activated protein kinase 14 | Rattus norvegicus (Rat) | SS |
| Q9WTY9 | Mapk13 | Mitogen-activated protein kinase 13 | Rattus norvegicus (Rat) | SS |
| Q9Z2A6 | Mapk15 | Mitogen-activated protein kinase 15 | Rattus norvegicus (Rat) | SS |
| Q63538 | Mapk12 | Mitogen-activated protein kinase 12 | Rattus norvegicus (Rat) | SS |
| P0C865 | Mapk7 | Mitogen-activated protein kinase 7 | Rattus norvegicus (Rat) | SS |
| P21708 | Mapk3 | Mitogen-activated protein kinase 3 | Rattus norvegicus (Rat) | SS |
| P63086 | Mapk1 | Mitogen-activated protein kinase 1 | Rattus norvegicus (Rat) | SS |
| P27704 | Mapk6 | Mitogen-activated protein kinase 6 | Rattus norvegicus (Rat) | SS |
| Q63454 | Mapk4 | Mitogen-activated protein kinase 4 | Rattus norvegicus (Rat) | SS |
| Q5ZCI1 | MPK10 | Mitogen-activated protein kinase 10 | Oryza sativa subsp. japonica (Rice) | SS |
| Q5VP69 | MPK16 | Mitogen-activated protein kinase 16 | Oryza sativa subsp. japonica (Rice) | SS |
| Q5SN53 | MPK8 | Mitogen-activated protein kinase 8 | Oryza sativa subsp. japonica (Rice) | SS |
| Q0E459 | MPK13 | Mitogen-activated protein kinase 13 | Oryza sativa subsp. japonica (Rice) | SS |
| Q75KK8 | MPK14 | Mitogen-activated protein kinase 14 | Oryza sativa subsp. japonica (Rice) | SS |
| Q67C40 | MPK7 | Mitogen-activated protein kinase 7 | Oryza sativa subsp. japonica (Rice) | SS |
| Q6L5F7 | MPK17 | Mitogen-activated protein kinase 17 | Oryza sativa subsp. japonica (Rice) | SS |
| Q5VN19 | MPK11 | Mitogen-activated protein kinase 11 | Oryza sativa subsp. japonica (Rice) | SS |
| Q5Z9J0 | MPK12 | Mitogen-activated protein kinase 12 | Oryza sativa subsp. japonica (Rice) | SS |
| Q53N72 | MPK15 | Mitogen-activated protein kinase 15 | Oryza sativa subsp. japonica (Rice) | SS |
| Q5Z859 | MPK4 | Mitogen-activated protein kinase 4 | Oryza sativa subsp. japonica (Rice) | SS |
| Q6Z437 | MPK3 | Mitogen-activated protein kinase 3 | Oryza sativa subsp. japonica (Rice) | SS |
| Q336X9 | MPK6 | Mitogen-activated protein kinase 6 | Oryza sativa subsp. japonica (Rice) | SS |
| Q5J4W4 | MPK2 | Mitogen-activated protein kinase 2 | Oryza sativa subsp. japonica (Rice) | SS |
| Q84UI5 | MPK1 | Mitogen-activated protein kinase 1 | Oryza sativa subsp. japonica (Rice) | SS |
| Q10N20 | MPK5 | Mitogen-activated protein kinase 5 | Oryza sativa subsp. japonica (Rice) | SS |
| Q17446 | pmk-1 | Mitogen-activated protein kinase pmk-1 | Caenorhabditis elegans | SS |
| Q11179 | mapk-15 | Mitogen-activated protein kinase 15 | Caenorhabditis elegans | SS |
| Q8MXI4 | pmk-2 | Mitogen-activated protein kinase pmk-2 | Caenorhabditis elegans | SS |
| O44514 | pmk-3 | Mitogen-activated protein kinase pmk-3 | Caenorhabditis elegans | PR |
| G5EBT1 | sma-5 | Mitogen-activated protein kinase sma-5 | Caenorhabditis elegans | SS |
| P39745 | mpk-1 | Mitogen-activated protein kinase mpk-1 | Caenorhabditis elegans | SS |
| Q9C9U4 | MPK15 | Mitogen-activated protein kinase 15 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q9LV37 | MPK9 | Mitogen-activated protein kinase 9 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| O23236 | MPK14 | Mitogen-activated protein kinase 14 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q39021 | MPK1 | Mitogen-activated protein kinase 1 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q39022 | MPK2 | Mitogen-activated protein kinase 2 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q39027 | MPK7 | Mitogen-activated protein kinase 7 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q84M93 | MPK17 | Mitogen-activated protein kinase 17 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q8W4J2 | MPK16 | Mitogen-activated protein kinase 16 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q9C5C0 | MPK18 | Mitogen-activated protein kinase 18 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q9LM33 | MPK8 | Mitogen-activated protein kinase 8 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q9LUC3 | MPK19 | Mitogen-activated protein kinase 19 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q9SJG9 | MPK20 | Mitogen-activated protein kinase 20 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q39023 | MPK3 | Mitogen-activated protein kinase 3 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q39026 | MPK6 | Mitogen-activated protein kinase 6 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q39025 | MPK5 | Mitogen-activated protein kinase 5 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q39024 | MPK4 | Mitogen-activated protein kinase 4 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q9M1Z5 | MPK10 | Mitogen-activated protein kinase 10 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q8GYQ5 | MPK12 | Mitogen-activated protein kinase 12 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q9LMM5 | MPK11 | Mitogen-activated protein kinase 11 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q9LQQ9 | MPK13 | Mitogen-activated protein kinase 13 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| O42376 | mapk12 | Mitogen-activated protein kinase 12 | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q9DGE1 | mapk14b | Mitogen-activated protein kinase 14B | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q9DGE2 | mapk14a | Mitogen-activated protein kinase 14A | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MEEFNSSGSV | VNGTGSTEVP | QSNAEVIRGQ | IFEVGPRYIK | LAYIGEGAYG | MVVSADDTLT |
| 70 | 80 | 90 | 100 | 110 | 120 |
| NQRVAIKKIS | PFEHQTYCQR | TLREITILTR | FKHENIIDIR | DILRVDSIDQ | MRDVYIVQCL |
| 130 | 140 | 150 | 160 | 170 | 180 |
| METDLYKLLK | TQRLSNDHIC | YFLYQILRGL | KYIHSANVLH | RDLKPSNLLL | NKTCDLKICD |
| 190 | 200 | 210 | 220 | 230 | 240 |
| FGLARIADPE | HDHTGFLTEY | VATRWYRAPE | IMLNSKGYTK | SIDIWSVGCI | LAEMLSNRPI |
| 250 | 260 | 270 | 280 | 290 | 300 |
| FPGKHYLDQL | NHILGVLGSP | SRDDLECIIN | EKARNYLESL | PFKPNVPWAK | LFPNADALAL |
| 310 | 320 | 330 | 340 | 350 | 360 |
| DLLGKMLTFN | PHKRIPVEEA | LAHPYLEQYY | DPGDEPVAEV | PFRINMENDD | ISRDALKSLI |
| 370 | |||||
| FEETLKFKER | QPDNAP |