Reviewed, UniProtKB/Swiss-Prot P40417 (ERKA_DROME)

Names and origin

Protein names

Recommended 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

Organism

Drosophila melanogaster (Fruit fly) [Complete proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	426 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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. Ref.7
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.
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-248 and Tyr-250, which activates the enzyme By similarity. Phosphorylated on tyrosine residue(s) in response to insulin.
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 process	Cell cycle
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	MAPKKK cascade Non-traceable author statement. Source: FlyBase R7 cell development Traceable author statement. Source: FlyBase adherens junction maintenance Inferred from mutant phenotype. Source: FlyBase anti-apoptosis Non-traceable author statement. Source: FlyBase behavioral response to ethanol Inferred from mutant phenotype. Source: FlyBase cellular response to DNA damage stimulus Inferred from mutant phenotype. Source: FlyBase determination of anterior/posterior axis, embryo Traceable author statement. Source: FlyBase gastrulation Non-traceable author statement. Source: FlyBase heart development Non-traceable author statement. Source: FlyBase imaginal disc-derived wing vein specification Inferred from mutant phenotype. Source: FlyBase mitosis Inferred from mutant phenotype. Source: FlyBase positive regulation of photoreceptor cell differentiation Inferred from mutant phenotype. Source: FlyBase protein amino acid phosphorylation Traceable author statement. Source: FlyBase regulation of synapse structure and activity Traceable author statement. Source: FlyBase regulation of synaptic transmission Inferred from mutant phenotype. Source: FlyBase regulation of transcription, DNA-dependent Traceable author statement. Source: FlyBase torso signaling pathway Non-traceable author statement. Source: FlyBase
Cellular component	cell junction Inferred from direct assay. Source: FlyBase cytoplasm Ref.1 Inferred from direct assay. Source: FlyBase nucleus Ref.1 Inferred from direct assay. Source: FlyBase
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW JUN kinase activity Inferred from direct assay. Source: FlyBase identical protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-867790,EBI-867790
Ccp84Ad	O97061	1	EBI-867790,EBI-188987
mael	Q9VNS0	1	EBI-867790,EBI-140243
Mekk1	Q9VE37	1	EBI-867790,EBI-108552
Sas-4	Q9VI72	1	EBI-867790,EBI-131879

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform F (identifier: P40417-1)

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.

Note: No experimental confirmation available.

Isoform B (identifier: P40417-2)

The sequence of this isoform differs from the canonical sequence as follows:
     21-39: Missing.

Note: No experimental confirmation available.

Isoform C (identifier: P40417-3)

Also known as: D; E;

The sequence of this isoform differs from the canonical sequence as follows:
     1-50: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 426	426	Mitogen-activated protein kinase ERK-A		PRO_0000186309
Regions
	Domain	88 – 376	289	Protein kinase
	Nucleotide binding	94 – 102	9	ATP By similarity
	Motif	248 – 250	3	TXY
Sites
	Active site	212	1	Proton acceptor By similarity
	Binding site	117	1	ATP By similarity
Amino acid modifications
	Modified residue	248	1	Phosphothreonine Ref.8
	Modified residue	250	1	Phosphotyrosine Ref.8
Natural variations
	Alternative sequence	1 – 50	50	Missing in isoform C.		VSP_032691
	Alternative sequence	21 – 39	19	Missing in isoform B.		VSP_032692

Sequences

	Sequence		Length	Mass (Da)
	Isoform F [UniParc]. Last modified April 8, 2008. Version 2. Checksum: 9E09BAE68790C14C	FASTA	426	49,122
	10 20 30 40 50 60 MFYAVDFDKS YLRICLKSKK KLSLYIHILS YRLLVKFIIN ISSFPEETLV MEEFNSSGSV 70 80 90 100 110 120 VNGTGSTEVP QSNAEVIRGQ IFEVGPRYIK LAYIGEGAYG MVVSADDTLT NQRVAIKKIS 130 140 150 160 170 180 PFEHQTYCQR TLREITILTR FKHENIIDIR DILRVDSIDQ MRDVYIVQCL METDLYKLLK 190 200 210 220 230 240 TQRLSNDHIC YFLYQILRGL KYIHSANVLH RDLKPSNLLL NKTCDLKICD FGLARIADPE 250 260 270 280 290 300 HDHTGFLTEY VATRWYRAPE IMLNSKGYTK SIDIWSVGCI LAEMLSNRPI FPGKHYLDQL 310 320 330 340 350 360 NHILGVLGSP SRDDLECIIN EKARNYLESL PFKPNVPWAK LFPNADALAL DLLGKMLTFN 370 380 390 400 410 420 PHKRIPVEEA LAHPYLEQYY DPGDEPVAEV PFRINMENDD ISRDALKSLI FEETLKFKER QPDNAP
	Isoform B. Checksum: 847EFA95D78F4942	FASTA	407	46,807
	10 20 30 40 50 60 MFYAVDFDKS YLRICLKSKK NISSFPEETL VMEEFNSSGS VVNGTGSTEV PQSNAEVIRG 70 80 90 100 110 120 QIFEVGPRYI KLAYIGEGAY GMVVSADDTL TNQRVAIKKI SPFEHQTYCQ RTLREITILT 130 140 150 160 170 180 RFKHENIIDI RDILRVDSID QMRDVYIVQC LMETDLYKLL KTQRLSNDHI CYFLYQILRG 190 200 210 220 230 240 LKYIHSANVL HRDLKPSNLL LNKTCDLKIC DFGLARIADP EHDHTGFLTE YVATRWYRAP 250 260 270 280 290 300 EIMLNSKGYT KSIDIWSVGC ILAEMLSNRP IFPGKHYLDQ LNHILGVLGS PSRDDLECII 310 320 330 340 350 360 NEKARNYLES LPFKPNVPWA KLFPNADALA LDLLGKMLTF NPHKRIPVEE ALAHPYLEQY 370 380 390 400 YDPGDEPVAE VPFRINMEND DISRDALKSL IFEETLKFKE RQPDNAP
	Isoform C (D) (E). Checksum: 2642B3CBB0F234D2	FASTA	376	43,151
	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

References

	« Hide 'large scale' referencesShow '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: 1378625] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C), DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, 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. , 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: 10731132] [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. , 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: 12537572] [Abstract] Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING.
[5]	"Heterochromatic sequences in a Drosophila whole-genome shotgun assembly." Hoskins R.A., Smith C.D., Carlson J.W., Carvalho A.B., Halpern A., Kaminker J.S., Kennedy C., Mungall C.J., Sullivan B.A., Sutton G.G., Yasuhara J.C., Wakimoto B.T., Myers E.W., Celniker S.E., Rubin G.M., Karpen G.H. Genome Biol. 3:RESEARCH0085.1-RESEARCH0085.16(2002) [PubMed: 12537574] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[6]	"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: 12537569] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C). Strain: Berkeley. Tissue: Embryo.
[7]	"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: 8157002] [Abstract] Cited for: FUNCTION. Strain: Oregon-R.
[8]	"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: 18327897] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-248 AND TYR-250, MASS SPECTROMETRY. Tissue: Embryo.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M95124 mRNA. Translation: AAA28677.1. CM000457 Genomic DNA. Translation: EAA46310.2. CM000457 Genomic DNA. Translation: EAA46311.2. CM000457 Genomic DNA. Translation: EAA46312.3. CM000457 Genomic DNA. Translation: EDP28106.1. CM000457 Genomic DNA. Translation: EDP28107.1. AY070996 mRNA. Translation: AAL48618.1.
PIR	A46036. B46036.
RefSeq	NP_001015121.2. NP_001104348.1. NP_001104349.1.
UniGene	Dm.20303
3D structure databases
HSSP	HSSP built from PDB template 1PME based on UniProtKB P28482.
SMR	P40417. Positions 25-368.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:17266N.
IntAct	P40417. 15 interactions.
STRING	P40417.
Genome annotation databases
Ensembl	FBtr0113699; FBpp0112422; FBgn0003256; Drosophila melanogaster. [Genome view]
GeneID	3354888.
KEGG	dme:Dmel_CG12559.
Organism-specific databases
CTD	3354888.
FlyBase	FBgn0003256. rl.
Phylogenomic databases
HOGENOM	P40417.
OMA	LAREDTA.
Enzyme and pathway databases
BRENDA	2.7.11.24. 48.
Gene expression databases
GermOnline	CG12559. Drosophila melanogaster.
Family and domain databases
InterPro	IPR008349. Erk_1_2_MAPK. IPR003527. MAP_kinase_CS. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PRINTS	PR01770. ERK1ERK2MAPK.
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS01351. MAPK. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	849506.

Entry information

Entry name

ERKA_DROME

Accession

Primary (citable) accession number: P40417
Secondary accession number(s): A8Y4W1 , A8Y4W2, Q7PL59, Q9W5M2, Q9W5M3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	April 8, 2008
Last modified:	November 3, 2009
This is version 98 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project