UniProtKB - P40417 (ERKA_DROME)
Protein
Mitogen-activated protein kinase ERK-A
Gene
rl
Organism
Drosophila melanogaster (Fruit fly)
Status
Functioni
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway to regulate poliferation, differentiation and effect cell fate decisions in various tissues (PubMed:8157002, PubMed:19965758, PubMed:22140578, PubMed:27552662). Required downstream of phl/Raf in the sev/sevenless, tor/torso, and EGF receptor homolog Egfr signal transduction pathways (PubMed:8157002). Required for embryonic epithelial tissue repair (PubMed:22140578). During larval development, mediates Ptth/tor signaling leading to the production of ecdysone, a hormone required for the initiation of metamorphosis (PubMed:19965758).4 Publications
Catalytic activityi
Cofactori
Mg2+By similarity
Activity regulationi
Activated by tyrosine and threonine phosphorylation.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 67 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 162 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 44 – 52 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- MAP kinase activity Source: FlyBase
- protein kinase binding Source: FlyBase
- protein serine/threonine kinase activity Source: FlyBase
- transcription factor binding Source: FlyBase
GO - Biological processi
- behavioral response to ethanol Source: FlyBase
- branching involved in open tracheal system development Source: FlyBase
- cell surface receptor signaling pathway Source: GO_Central
- cellular response to arsenic-containing substance Source: FlyBase
- cellular response to cadmium ion Source: FlyBase
- cellular response to reactive oxygen species Source: FlyBase
- cellular response to starvation Source: FlyBase
- defense response to virus Source: FlyBase
- determination of adult lifespan Source: FlyBase
- dorsal appendage formation Source: FlyBase
- epidermal growth factor receptor signaling pathway Source: FlyBase
- ERK1 and ERK2 cascade Source: FlyBase
- fibroblast growth factor receptor signaling pathway Source: FlyBase
- imaginal disc-derived wing morphogenesis Source: FlyBase
- imaginal disc-derived wing vein specification Source: FlyBase
- insulin receptor signaling pathway Source: FlyBase
- intracellular signal transduction Source: GO_Central
- leg disc proximal/distal pattern formation Source: FlyBase
- lymph gland crystal cell differentiation Source: FlyBase
- lymph gland plasmatocyte differentiation Source: FlyBase
- MAPK cascade Source: UniProtKB
- metamorphosis Source: FlyBase
- mitotic cell cycle Source: FlyBase
- modulation of chemical synaptic transmission Source: FlyBase
- negative regulation of macroautophagy Source: FlyBase
- positive regulation of cell population proliferation Source: FlyBase
- positive regulation of cell size Source: FlyBase
- positive regulation of DNA-binding transcription factor activity Source: FlyBase
- positive regulation of photoreceptor cell differentiation Source: FlyBase
- positive regulation of wound healing Source: FlyBase
- R7 cell fate commitment Source: FlyBase
- regulation of gene expression Source: GO_Central
- regulation of heart morphogenesis Source: FlyBase
- regulation of response to drug Source: FlyBase
- sevenless signaling pathway Source: FlyBase
- terminal branching, open tracheal system Source: FlyBase
- terminal region determination Source: FlyBase
- torso signaling pathway Source: FlyBase
- tracheal pit formation in open tracheal system Source: FlyBase
- vascular endothelial growth factor receptor signaling pathway Source: FlyBase
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Cell cycle |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.11.24, 1994 |
Reactomei | R-DME-110056, MAPK3 (ERK1) activation R-DME-112409, RAF-independent MAPK1/3 activation R-DME-112411, MAPK1 (ERK2) activation R-DME-1169408, ISG15 antiviral mechanism R-DME-162658, Golgi Cisternae Pericentriolar Stack Reorganization R-DME-170968, Frs2-mediated activation R-DME-198753, ERK/MAPK targets R-DME-202670, ERKs are inactivated R-DME-2029482, Regulation of actin dynamics for phagocytic cup formation R-DME-2559580, Oxidative Stress Induced Senescence R-DME-2559582, Senescence-Associated Secretory Phenotype (SASP) R-DME-2559585, Oncogene Induced Senescence R-DME-2871796, FCERI mediated MAPK activation R-DME-3371453, Regulation of HSF1-mediated heat shock response R-DME-375165, NCAM signaling for neurite out-growth R-DME-437239, Recycling pathway of L1 R-DME-445144, Signal transduction by L1 R-DME-450341, Activation of the AP-1 family of transcription factors R-DME-5654726, Negative regulation of FGFR1 signaling R-DME-5654727, Negative regulation of FGFR2 signaling R-DME-5654732, Negative regulation of FGFR3 signaling R-DME-5654733, Negative regulation of FGFR4 signaling R-DME-5663213, RHO GTPases Activate WASPs and WAVEs R-DME-5673001, RAF/MAP kinase cascade R-DME-5674135, MAP2K and MAPK activation R-DME-5674499, Negative feedback regulation of MAPK pathway R-DME-5675221, Negative regulation of MAPK pathway R-DME-6798695, Neutrophil degranulation R-DME-74749, Signal attenuation R-DME-881907, Gastrin-CREB signalling pathway via PKC and MAPK R-DME-9627069, Regulation of the apoptosome activity R-DME-9634635, Estrogen-stimulated signaling through PRKCZ R-DME-9634638, Estrogen-dependent nuclear events downstream of ESR-membrane signaling |
SignaLinki | P40417 |
Names & Taxonomyi
Protein namesi | Recommended name: Mitogen-activated protein kinase ERK-A (EC:2.7.11.24)Alternative name(s): Extracellular-regulated kinase A Protein rolled |
Gene namesi | ORF Names:CG12559Imported |
Organismi | Drosophila melanogaster (Fruit fly) |
Taxonomic identifieri | 7227 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Ecdysozoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Holometabola › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora › |
Proteomesi |
|
Organism-specific databases
FlyBasei | FBgn0003256, rl |
Subcellular locationi
Cytosol
- cytosol Source: FlyBase
Nucleus
- nucleus Source: FlyBase
Other locations
- cytoplasm Source: GO_Central
- neuromuscular junction Source: FlyBase
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Disruption phenotypei
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000186309 | 1 – 376 | Mitogen-activated protein kinase ERK-AAdd BLAST | 376 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 198 | Phosphothreonine1 Publication | 1 | |
Modified residuei | 200 | Phosphotyrosine1 Publication | 1 |
Post-translational modificationi
Dually phosphorylated on Thr-198 and Tyr-200, which activates the enzyme (By similarity). Phosphorylated on tyrosine residue(s) in response to insulin.By similarity2 Publications
Keywords - PTMi
PhosphoproteinProteomic databases
PaxDbi | P40417 |
PRIDEi | P40417 |
PTM databases
iPTMneti | P40417 |
Expressioni
Tissue specificityi
In third instar larvae, expressed in eye imaginal disks. In adults, expressed in head and body.1 Publication
Developmental stagei
Embryos, larvae and adults.1 Publication
Gene expression databases
Bgeei | FBgn0003256, Expressed in embryo and 26 other tissues |
ExpressionAtlasi | P40417, baseline and differential |
Genevisiblei | P40417, DM |
Interactioni
Binary interactionsi
Hide detailsP40417
GO - Molecular functioni
- protein kinase binding Source: FlyBase
- transcription factor binding Source: FlyBase
Protein-protein interaction databases
BioGRIDi | 78013, 85 interactors |
DIPi | DIP-17266N |
IntActi | P40417, 13 interactors |
MINTi | P40417 |
STRINGi | 7227.FBpp0112426 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 38 – 326 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 289 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 198 – 200 | TXY | 3 |
Domaini
The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Sequence similaritiesi
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.Curated
Phylogenomic databases
eggNOGi | KOG0660, Eukaryota |
GeneTreei | ENSGT00940000156771 |
InParanoidi | P40417 |
OMAi | DIYIVQC |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR003527, MAP_kinase_CS IPR008349, MAPK_ERK1/2 IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
PRINTSi | PR01770, ERK1ERK2MAPK |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS01351, MAPK, 1 hit PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
Isoform C (identifier: P40417-3) [UniParc]FASTAAdd to basket
Also known as: D, E
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MEEFNSSGSV VNGTGSTEVP QSNAEVIRGQ IFEVGPRYIK LAYIGEGAYG
60 70 80 90 100
MVVSADDTLT NQRVAIKKIS PFEHQTYCQR TLREITILTR FKHENIIDIR
110 120 130 140 150
DILRVDSIDQ MRDVYIVQCL METDLYKLLK TQRLSNDHIC YFLYQILRGL
160 170 180 190 200
KYIHSANVLH RDLKPSNLLL NKTCDLKICD FGLARIADPE HDHTGFLTEY
210 220 230 240 250
VATRWYRAPE IMLNSKGYTK SIDIWSVGCI LAEMLSNRPI FPGKHYLDQL
260 270 280 290 300
NHILGVLGSP SRDDLECIIN EKARNYLESL PFKPNVPWAK LFPNADALAL
310 320 330 340 350
DLLGKMLTFN PHKRIPVEEA LAHPYLEQYY DPGDEPVAEV PFRINMENDD
360 370
ISRDALKSLI FEETLKFKER QPDNAP
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA8Y4W5 | A8Y4W5_DROME | RE73195p | rl 12559, 2, BcDNA:RE08694, CG18732, CT34260 | 190 | Annotation score: |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_047792 | 1 – 110 | Missing in isoform H. CuratedAdd BLAST | 110 | |
Alternative sequenceiVSP_047793 | 1 – 45 | Missing in isoform G. CuratedAdd BLAST | 45 | |
Alternative sequenceiVSP_047794 | 46 – 53 | EGAYGMVV → MESALVIR in isoform G. Curated | 8 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M95124 mRNA Translation: AAA28677.1 AE013599 Genomic DNA Translation: EAA46310.2 AE013599 Genomic DNA Translation: EAA46311.2 AE013599 Genomic DNA Translation: EAA46312.4 AE013599 Genomic DNA Translation: EDP28106.2 AE013599 Genomic DNA Translation: EDP28107.1 AE013599 Genomic DNA Translation: EYR77323.1 AY070996 mRNA Translation: AAL48618.1 |
PIRi | A46036 B46036 |
RefSeqi | NP_001015121.3, NM_001015121.3 [P40417-2] NP_001015122.1, NM_001015122.3 [P40417-3] NP_001015123.1, NM_001015123.3 [P40417-3] NP_001104348.2, NM_001110878.4 [P40417-1] NP_001104349.1, NM_001110879.2 [P40417-3] NP_001287635.1, NM_001300706.2 [P40417-3] |
Genome annotation databases
EnsemblMetazoai | FBtr0113700; FBpp0112423; FBgn0003256 [P40417-3] FBtr0113702; FBpp0112425; FBgn0003256 [P40417-3] FBtr0113703; FBpp0112426; FBgn0003256 [P40417-3] FBtr0329919; FBpp0302952; FBgn0003256 [P40417-2] FBtr0329920; FBpp0302953; FBgn0003256 [P40417-1] FBtr0345337; FBpp0311493; FBgn0003256 [P40417-3] |
GeneIDi | 3354888 |
KEGGi | dme:Dmel_CG12559 |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M95124 mRNA Translation: AAA28677.1 AE013599 Genomic DNA Translation: EAA46310.2 AE013599 Genomic DNA Translation: EAA46311.2 AE013599 Genomic DNA Translation: EAA46312.4 AE013599 Genomic DNA Translation: EDP28106.2 AE013599 Genomic DNA Translation: EDP28107.1 AE013599 Genomic DNA Translation: EYR77323.1 AY070996 mRNA Translation: AAL48618.1 |
PIRi | A46036 B46036 |
RefSeqi | NP_001015121.3, NM_001015121.3 [P40417-2] NP_001015122.1, NM_001015122.3 [P40417-3] NP_001015123.1, NM_001015123.3 [P40417-3] NP_001104348.2, NM_001110878.4 [P40417-1] NP_001104349.1, NM_001110879.2 [P40417-3] NP_001287635.1, NM_001300706.2 [P40417-3] |
3D structure databases
SMRi | P40417 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 78013, 85 interactors |
DIPi | DIP-17266N |
IntActi | P40417, 13 interactors |
MINTi | P40417 |
STRINGi | 7227.FBpp0112426 |
PTM databases
iPTMneti | P40417 |
Proteomic databases
PaxDbi | P40417 |
PRIDEi | P40417 |
Genome annotation databases
EnsemblMetazoai | FBtr0113700; FBpp0112423; FBgn0003256 [P40417-3] FBtr0113702; FBpp0112425; FBgn0003256 [P40417-3] FBtr0113703; FBpp0112426; FBgn0003256 [P40417-3] FBtr0329919; FBpp0302952; FBgn0003256 [P40417-2] FBtr0329920; FBpp0302953; FBgn0003256 [P40417-1] FBtr0345337; FBpp0311493; FBgn0003256 [P40417-3] |
GeneIDi | 3354888 |
KEGGi | dme:Dmel_CG12559 |
Organism-specific databases
CTDi | 3354888 |
FlyBasei | FBgn0003256, rl |
Phylogenomic databases
eggNOGi | KOG0660, Eukaryota |
GeneTreei | ENSGT00940000156771 |
InParanoidi | P40417 |
OMAi | DIYIVQC |
Enzyme and pathway databases
BRENDAi | 2.7.11.24, 1994 |
Reactomei | R-DME-110056, MAPK3 (ERK1) activation R-DME-112409, RAF-independent MAPK1/3 activation R-DME-112411, MAPK1 (ERK2) activation R-DME-1169408, ISG15 antiviral mechanism R-DME-162658, Golgi Cisternae Pericentriolar Stack Reorganization R-DME-170968, Frs2-mediated activation R-DME-198753, ERK/MAPK targets R-DME-202670, ERKs are inactivated R-DME-2029482, Regulation of actin dynamics for phagocytic cup formation R-DME-2559580, Oxidative Stress Induced Senescence R-DME-2559582, Senescence-Associated Secretory Phenotype (SASP) R-DME-2559585, Oncogene Induced Senescence R-DME-2871796, FCERI mediated MAPK activation R-DME-3371453, Regulation of HSF1-mediated heat shock response R-DME-375165, NCAM signaling for neurite out-growth R-DME-437239, Recycling pathway of L1 R-DME-445144, Signal transduction by L1 R-DME-450341, Activation of the AP-1 family of transcription factors R-DME-5654726, Negative regulation of FGFR1 signaling R-DME-5654727, Negative regulation of FGFR2 signaling R-DME-5654732, Negative regulation of FGFR3 signaling R-DME-5654733, Negative regulation of FGFR4 signaling R-DME-5663213, RHO GTPases Activate WASPs and WAVEs R-DME-5673001, RAF/MAP kinase cascade R-DME-5674135, MAP2K and MAPK activation R-DME-5674499, Negative feedback regulation of MAPK pathway R-DME-5675221, Negative regulation of MAPK pathway R-DME-6798695, Neutrophil degranulation R-DME-74749, Signal attenuation R-DME-881907, Gastrin-CREB signalling pathway via PKC and MAPK R-DME-9627069, Regulation of the apoptosome activity R-DME-9634635, Estrogen-stimulated signaling through PRKCZ R-DME-9634638, Estrogen-dependent nuclear events downstream of ESR-membrane signaling |
SignaLinki | P40417 |
Miscellaneous databases
BioGRID-ORCSi | 3354888, 1 hit in 3 CRISPR screens |
ChiTaRSi | rl, fly |
GenomeRNAii | 3354888 |
PROi | PR:P40417 |
Gene expression databases
Bgeei | FBgn0003256, Expressed in embryo and 26 other tissues |
ExpressionAtlasi | P40417, baseline and differential |
Genevisiblei | P40417, DM |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR003527, MAP_kinase_CS IPR008349, MAPK_ERK1/2 IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
PRINTSi | PR01770, ERK1ERK2MAPK |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS01351, MAPK, 1 hit PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ERKA_DROME | |
Accessioni | P40417Primary (citable) accession number: P40417 Secondary accession number(s): A0A021WW06 Q9W5M3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1995 |
Last sequence update: | September 18, 2013 | |
Last modified: | February 10, 2021 | |
This is version 205 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Drosophila annotation project |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Drosophila
Drosophila: entries, gene names and cross-references to FlyBase - SIMILARITY comments
Index of protein domains and families