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Protein

Mitogen-activated protein kinase ERK-A

Gene

rl

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).3 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
  • JUN kinase activity Source: FlyBase
  • 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

  • adherens junction maintenance Source: FlyBase
  • anterior/posterior axis specification, embryo 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 DNA damage stimulus Source: FlyBase
  • cellular response to reactive oxygen species Source: FlyBase
  • cellular response to starvation Source: FlyBase
  • determination of adult lifespan Source: FlyBase
  • gastrulation Source: FlyBase
  • heart development 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
  • MAPK cascade Source: FlyBase
  • metamorphosis Source: FlyBase
  • mitotic nuclear division Source: FlyBase
  • modulation of synaptic transmission Source: FlyBase
  • negative regulation of apoptotic process Source: FlyBase
  • negative regulation of macroautophagy Source: FlyBase
  • positive regulation of cell proliferation Source: FlyBase
  • positive regulation of ERK1 and ERK2 cascade Source: FlyBase
  • positive regulation of photoreceptor cell differentiation Source: FlyBase
  • positive regulation of Ras protein signal transduction Source: FlyBase
  • positive regulation of wound healing Source: FlyBase
  • protein phosphorylation Source: FlyBase
  • R7 cell development Source: FlyBase
  • regulation of heart morphogenesis Source: FlyBase
  • regulation of response to drug Source: FlyBase
  • regulation of synapse structure or activity Source: FlyBase
  • regulation of transcription, DNA-templated Source: FlyBase
  • torso signaling pathway Source: FlyBase
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: FlyBase
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle

Keywords - Ligandi

ATP-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-1169408. ISG15 antiviral mechanism.
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-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:rl
Synonyms:ERKa
ORF Names:CG12559
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome 2R

Organism-specific databases

FlyBaseiFBgn0003256. rl.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus 1 Publication

GO - Cellular componenti

  • cell junction Source: FlyBase
  • cytoplasm Source: FlyBase
  • neuromuscular junction Source: FlyBase
  • nucleus Source: FlyBase
Complete GO annotation...

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.
GenevisibleiP40417. DM.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
ARRB2P321214EBI-867790,EBI-714559From a different organism.
cicQ9U1H03EBI-867790,EBI-98330
Dsor1Q243242EBI-867790,EBI-671282
krzQ9V39312EBI-867790,EBI-100228
S6kIIQ244962EBI-867790,EBI-870498

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi78013. 47 interactors.
DIPiDIP-17266N.
IntActiP40417. 11 interactors.
MINTiMINT-312120.
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

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0660. Eukaryota.
ENOG410XNY0. LUCA.
GeneTreeiENSGT00550000074298.
InParanoidiP40417.
KOiK04371.
OMAiEEAESHH.
OrthoDBiEOG091G08QL.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008349. MAPK_ERK1/2.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01770. ERK1ERK2MAPK.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

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]
FBtr0345337; FBpp0311493; FBgn0003256. [P40417-3]
GeneIDi3354888.
KEGGidme:Dmel_CG12559.

Keywords - Coding sequence diversityi

Alternative splicing

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.
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.

3D structure databases

ProteinModelPortaliP40417.
SMRiP40417.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi78013. 47 interactors.
DIPiDIP-17266N.
IntActiP40417. 11 interactors.
MINTiMINT-312120.
STRINGi7227.FBpp0112426.

PTM databases

iPTMnetiP40417.

Proteomic databases

PaxDbiP40417.
PRIDEiP40417.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiFBtr0113700; FBpp0112423; FBgn0003256. [P40417-3]
FBtr0113702; FBpp0112425; FBgn0003256. [P40417-3]
FBtr0113703; FBpp0112426; FBgn0003256. [P40417-3]
FBtr0345337; FBpp0311493; FBgn0003256. [P40417-3]
GeneIDi3354888.
KEGGidme:Dmel_CG12559.

Organism-specific databases

CTDi3354888.
FlyBaseiFBgn0003256. rl.

Phylogenomic databases

eggNOGiKOG0660. Eukaryota.
ENOG410XNY0. LUCA.
GeneTreeiENSGT00550000074298.
InParanoidiP40417.
KOiK04371.
OMAiEEAESHH.
OrthoDBiEOG091G08QL.

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-1169408. ISG15 antiviral mechanism.
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-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.

Miscellaneous databases

ChiTaRSirl. fly.
GenomeRNAii3354888.
PROiP40417.

Gene expression databases

BgeeiFBgn0003256.
GenevisibleiP40417. DM.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008349. MAPK_ERK1/2.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01770. ERK1ERK2MAPK.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiERKA_DROME
AccessioniPrimary (citable) accession number: P40417
Secondary accession number(s): A0A021WW06
, A8Y4W1, A8Y4W2, Q7PL59, Q9W5M2, Q9W5M3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: September 18, 2013
Last modified: November 30, 2016
This is version 169 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Drosophila
    Drosophila: entries, gene names and cross-references to FlyBase
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.