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Protein

Mitogen-activated protein kinase ERK-A

Gene

rl

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

Activated by tyrosine and threonine phosphorylation.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei67ATPPROSITE-ProRule annotation1
Active sitei162Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi44 – 52ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • MAP kinase activity Source: FlyBase
  • protein kinase activity Source: FlyBase
  • protein kinase binding Source: FlyBase
  • protein serine/threonine kinase activity Source: FlyBase
  • transcription factor binding Source: FlyBase

GO - Biological processi

  • adherens junction maintenance Source: FlyBase
  • behavioral response to ethanol Source: FlyBase
  • cellular response to arsenic-containing substance Source: FlyBase
  • cellular response to cadmium ion Source: FlyBase
  • cellular response to organic substance Source: GO_Central
  • 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
  • epidermal growth factor receptor signaling pathway Source: FlyBase
  • ERK1 and ERK2 cascade Source: FlyBase
  • imaginal disc-derived wing morphogenesis Source: FlyBase
  • imaginal disc-derived wing vein morphogenesis Source: FlyBase
  • imaginal disc-derived wing vein specification Source: FlyBase
  • insulin receptor signaling pathway 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 proliferation Source: FlyBase
  • positive regulation of photoreceptor cell differentiation Source: FlyBase
  • positive regulation of wound healing Source: FlyBase
  • protein phosphorylation Source: FlyBase
  • regulation of heart morphogenesis Source: FlyBase
  • regulation of response to drug Source: FlyBase
  • sevenless signaling pathway Source: FlyBase
  • torso signaling pathway Source: FlyBase

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.24 1994
ReactomeiR-DME-110056 MAPK3 (ERK1) activation
R-DME-112409 RAF-independent MAPK1/3 activation
R-DME-112411 MAPK1 (ERK2) activation
R-DME-1295596 Spry regulation of FGF signaling
R-DME-162658 Golgi Cisternae Pericentriolar Stack Reorganization
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-442742 CREB phosphorylation through the activation of Ras
R-DME-444257 RSK activation
R-DME-445144 Signal transduction by L1
R-DME-450341 Activation of the AP-1 family of transcription factors
R-DME-456926 Thrombin signalling through proteinase activated receptors (PARs)
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
SignaLinkiP40417

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
Name:rl1 PublicationImported
Synonyms:ERKa1 Publication, MAPK1 Publication
ORF Names:CG12559Imported
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraHolometabolaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome 2R

Organism-specific databases

FlyBaseiFBgn0003256 rl

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Embryonic wound healing defects (PubMed:22140578). RNAi-mediated knockdown in the prothoracic gland (PG) delays the onset of pupariation by prolonging the L3 larval stage and increases adult weight (PubMed:19965758).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001863091 – 376Mitogen-activated protein kinase ERK-AAdd BLAST376

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei198Phosphothreonine1 Publication1
Modified residuei200Phosphotyrosine1 Publication1

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

Phosphoprotein

Proteomic databases

PaxDbiP40417
PRIDEiP40417

PTM databases

iPTMnetiP40417

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

BgeeiFBgn0003256
ExpressionAtlasiP40417 baseline
GenevisibleiP40417 DM

Interactioni

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein kinase binding Source: FlyBase
  • transcription factor binding Source: FlyBase

Protein-protein interaction databases

BioGridi78013, 79 interactors
DIPiDIP-17266N
IntActiP40417, 13 interactors
MINTiP40417
STRINGi7227.FBpp0112426

Structurei

3D structure databases

ProteinModelPortaliP40417
SMRiP40417
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini38 – 326Protein kinasePROSITE-ProRule annotationAdd BLAST289

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi198 – 200TXY3

Domaini

The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0660 Eukaryota
ENOG410XNY0 LUCA
GeneTreeiENSGT00910000144035
InParanoidiP40417
KOiK04371
OMAiMEKCLTF
OrthoDBiEOG091G08QL

Family and domain databases

InterProiView 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
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PRINTSiPR01770 ERK1ERK2MAPK
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView 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

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform C (identifier: P40417-3) [UniParc]FASTAAdd to basket
Also known as: D, E

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:376
Mass (Da):43,151
Last modified:September 18, 2013 - v3
Checksum:i2642B3CBB0F234D2
GO
Isoform H (identifier: P40417-1) [UniParc]FASTAAdd to basket
Also known as: F

The sequence of this isoform differs from the canonical sequence as follows:
     1-110: Missing.

Note: No experimental confirmation available.
Show »
Length:266
Mass (Da):30,778
Checksum:iFF3E31EA7A9EDC24
GO
Isoform G (identifier: P40417-2) [UniParc]FASTAAdd to basket
Also known as: B

The sequence of this isoform differs from the canonical sequence as follows:
     1-45: Missing.
     46-53: EGAYGMVV → MESALVIR

Note: No experimental confirmation available.
Show »
Length:331
Mass (Da):38,430
Checksum:iB4BC3B8FE279331A
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0477921 – 110Missing in isoform H. CuratedAdd BLAST110
Alternative sequenceiVSP_0477931 – 45Missing in isoform G. CuratedAdd BLAST45
Alternative sequenceiVSP_04779446 – 53EGAYGMVV → MESALVIR in isoform G. Curated8

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
PIRiA46036
B46036
RefSeqiNP_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]
UniGeneiDm.20303

Genome annotation databases

EnsemblMetazoaiFBtr0113700; 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]
GeneIDi3354888
KEGGidme:Dmel_CG12559

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiERKA_DROME
AccessioniPrimary (citable) accession number: P40417
Secondary accession number(s): A0A021WW06
, A8Y4W1, A8Y4W2, Q7PL59, Q9W5M2, Q9W5M3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: September 18, 2013
Last modified: May 23, 2018
This is version 185 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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