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P40417 (ERKA_DROME) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mitogen-activated protein kinase ERK-A

EC=2.7.11.24
Alternative name(s):
Extracellular-regulated kinase A
Protein rolled
Gene names
Name:rl
Synonyms:ERKa
ORF Names:CG12559
OrganismDrosophila melanogaster (Fruit fly) [Reference proteome]
Taxonomic identifier7227 [NCBI]
Taxonomic lineageEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora

Protein attributes

Sequence length376 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Required downstream of Raf in the sevenless (sev), torso (tor), and Drosophila EGF receptor homolog (DER) signal transduction pathways. Required for embryonic epithelial tissue repair. Ref.6 Ref.8

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

Enzyme regulation

Activated by tyrosine and threonine phosphorylation By similarity.

Subcellular location

Cytoplasm. Nucleus Ref.1.

Tissue specificity

In third instar larvae, expressed in eye imaginal disks. In adults, expressed in head and body. Ref.1

Developmental stage

Embryos, larvae and adults. Ref.1

Domain

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

Post-translational modification

Dually phosphorylated on Thr-198 and Tyr-200, which activates the enzyme By similarity. Phosphorylated on tyrosine residue(s) in response to insulin. Ref.1

Disruption phenotype

Embryonic wound healing defects. Ref.8

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processCell cycle
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processJUN phosphorylation

Inferred from direct assay PubMed 8946916. Source: GOC

MAPK cascade

Non-traceable author statement PubMed 10878576. Source: FlyBase

R7 cell development

Traceable author statement PubMed 10929403. Source: FlyBase

adherens junction maintenance

Inferred from mutant phenotype PubMed 17438281. Source: FlyBase

anterior/posterior axis specification, embryo

Traceable author statement PubMed 10494038. Source: FlyBase

behavioral response to ethanol

Inferred from mutant phenotype PubMed 19464045. Source: FlyBase

cellular response to DNA damage stimulus

Inferred from mutant phenotype PubMed 19543366. Source: FlyBase

cellular response to arsenic-containing substance

Inferred from direct assay PubMed 16451733. Source: FlyBase

cellular response to cadmium ion

Inferred from direct assay PubMed 16451733. Source: FlyBase

cellular response to reactive oxygen species

Inferred from direct assay PubMed 16451733. Source: FlyBase

cellular response to starvation

Inferred from mutant phenotype PubMed 18794330. Source: FlyBase

gastrulation

Non-traceable author statement PubMed 10369659. Source: FlyBase

heart development

Non-traceable author statement PubMed 12027431. Source: FlyBase

imaginal disc-derived wing morphogenesis

Inferred from mutant phenotype PubMed 16308331. Source: FlyBase

imaginal disc-derived wing vein morphogenesis

Inferred from mutant phenotype PubMed 23549788. Source: FlyBase

imaginal disc-derived wing vein specification

Inferred from mutant phenotype PubMed 15704110. Source: FlyBase

metamorphosis

Inferred from mutant phenotype PubMed 19965758. Source: FlyBase

mitosis

Inferred from mutant phenotype PubMed 16308331. Source: FlyBase

negative regulation of apoptotic process

Non-traceable author statement PubMed 11832236. Source: FlyBase

negative regulation of macroautophagy

Inferred from mutant phenotype PubMed 18794330. Source: FlyBase

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 19141677. Source: FlyBase

positive regulation of photoreceptor cell differentiation

Inferred from mutant phenotype PubMed 16763554. Source: FlyBase

positive regulation of wound healing

Inferred from mutant phenotype Ref.8. Source: FlyBase

protein phosphorylation

Non-traceable author statement PubMed 10908587. Source: FlyBase

regulation of response to drug

Inferred from mutant phenotype PubMed 22678283. Source: FlyBase

regulation of synapse structure and activity

Traceable author statement PubMed 14630214. Source: FlyBase

regulation of synaptic transmission

Inferred from mutant phenotype PubMed 19144852. Source: FlyBase

regulation of transcription, DNA-templated

Traceable author statement PubMed 10929403. Source: FlyBase

torso signaling pathway

Non-traceable author statement PubMed 10494038. Source: FlyBase

transmembrane receptor protein tyrosine kinase signaling pathway

Inferred from mutant phenotype PubMed 8124723. Source: FlyBase

   Cellular_componentcell junction

Inferred from direct assay PubMed 17438281. Source: FlyBase

cytoplasm

Inferred from direct assay PubMed 11782402Ref.1PubMed 16763554PubMed 17438281PubMed 23827710. Source: FlyBase

nucleus

Inferred from direct assay PubMed 11782402Ref.1PubMed 16763554PubMed 23827710. Source: FlyBase

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

JUN kinase activity

Inferred from direct assay PubMed 8946916. Source: FlyBase

MAP kinase activity

Inferred from sequence or structural similarity Ref.1. Source: FlyBase

protein kinase binding

Inferred from physical interaction PubMed 15487973PubMed 16763554. Source: FlyBase

protein serine/threonine kinase activity

Non-traceable author statement PubMed 10908587. Source: FlyBase

transcription factor binding

Inferred from physical interaction PubMed 17255944. Source: FlyBase

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform C (identifier: P40417-3)

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.
Isoform H (identifier: P40417-1)

Also known as: F;

The sequence of this isoform differs from the canonical sequence as follows:
     1-110: Missing.
Note: No experimental confirmation available.
Isoform G (identifier: P40417-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 376376Mitogen-activated protein kinase ERK-A
PRO_0000186309

Regions

Domain38 – 326289Protein kinase
Nucleotide binding44 – 529ATP By similarity
Motif198 – 2003TXY

Sites

Active site1621Proton acceptor By similarity
Binding site671ATP By similarity

Amino acid modifications

Modified residue1981Phosphothreonine Ref.7
Modified residue2001Phosphotyrosine Ref.7

Natural variations

Alternative sequence1 – 110110Missing in isoform H.
VSP_047792
Alternative sequence1 – 4545Missing in isoform G.
VSP_047793
Alternative sequence46 – 538EGAYGMVV → MESALVIR in isoform G.
VSP_047794

Sequences

Sequence LengthMass (Da)Tools
Isoform C (D) (E) [UniParc].

Last modified September 18, 2013. Version 3.
Checksum: 2642B3CBB0F234D2

FASTA37643,151
        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 

« Hide

Isoform H (F) [UniParc].

Checksum: FF3E31EA7A9EDC24
Show »

FASTA26630,778
Isoform G (B) [UniParc].

Checksum: B4BC3B8FE279331A
Show »

FASTA33138,430

References

« Hide 'large scale' references
[1]"Primary structure, expression, and signal-dependent tyrosine phosphorylation of a Drosophila homolog of extracellular signal-regulated kinase."
Biggs W.H. III, Zipursky S.L.
Proc. Natl. Acad. Sci. U.S.A. 89:6295-6299(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, PHOSPHORYLATION.
Strain: Oregon-R.
Tissue: Embryo and Imaginal disk.
[2]Erratum
Biggs W.H. III, Zipursky S.L.
Proc. Natl. Acad. Sci. U.S.A. 90:6377-6377(1993)
[3]"The genome sequence of Drosophila melanogaster."
Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. expand/collapse author list , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.
Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Berkeley.
[4]"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review."
Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. expand/collapse author list , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.
Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: GENOME REANNOTATION.
Strain: Berkeley.
[5]"A Drosophila full-length cDNA resource."
Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E.
Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C).
Strain: Berkeley.
Tissue: Embryo.
[6]"The Drosophila rolled locus encodes a MAP kinase required in the sevenless signal transduction pathway."
Biggs W.H. III, Zavitz K.H., Dickson B., van der Straten A., Brunner D., Hafen E., Zipursky S.L.
EMBO J. 13:1628-1635(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
Strain: Oregon-R.
[7]"Phosphoproteome analysis of Drosophila melanogaster embryos."
Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.
J. Proteome Res. 7:1675-1682(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-198 AND TYR-200, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Embryo.
[8]"Hole-in-one mutant phenotypes link EGFR/ERK signaling to epithelial tissue repair in Drosophila."
Geiger J.A., Carvalho L., Campos I., Santos A.C., Jacinto A.
PLoS ONE 6:E28349-E28349(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M95124 mRNA. Translation: AAA28677.1.
CM000457 Genomic DNA. Translation: EAA46310.2.
CM000457 Genomic DNA. Translation: EAA46311.2.
CM000457 Genomic DNA. Translation: EAA46312.4.
CM000457 Genomic DNA. Translation: EDP28106.2.
CM000457 Genomic DNA. Translation: EDP28107.1.
AY070996 mRNA. Translation: AAL48618.1.
PIRA46036.
B46036.
RefSeqNP_001015121.3. NM_001015121.3.
NP_001015122.1. NM_001015122.3.
NP_001015123.1. NM_001015123.3.
NP_001104348.2. NM_001110878.2.
NP_001104349.1. NM_001110879.2.
UniGeneDm.20303.

3D structure databases

ProteinModelPortalP40417.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid78013. 47 interactions.
DIPDIP-17266N.
IntActP40417. 11 interactions.
MINTMINT-312120.

Proteomic databases

PaxDbP40417.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID3354888.
KEGGdme:Dmel_CG12559.

Organism-specific databases

CTD3354888.
FlyBaseFBgn0003256. rl.

Phylogenomic databases

eggNOGCOG0515.
InParanoidP40417.
KOK04371.
OMAVCSAYDR.
OrthoDBEOG7M3J0K.

Enzyme and pathway databases

BRENDA2.7.11.24. 1994.
SignaLinkP40417.

Gene expression databases

BgeeP40417.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008349. MAPK_ERK1/2.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERPTHR24055:SF111. PTHR24055:SF111. 1 hit.
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSPR01770. ERK1ERK2MAPK.
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSrl. drosophila.
GenomeRNAi3354888.
NextBio849506.

Entry information

Entry nameERKA_DROME
AccessionPrimary (citable) accession number: P40417
Secondary accession number(s): A8Y4W1 expand/collapse secondary AC list , A8Y4W2, Q7PL59, Q9W5M2, Q9W5M3
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: September 18, 2013
Last modified: April 16, 2014
This is version 140 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Relevant documents

SIMILARITY comments

Index of protein domains and families

Drosophila

Drosophila: entries, gene names and cross-references to FlyBase