Q08012 (DRK_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein enhancer of sevenless 2B
Short name=Protein E(sev)2B

Alternative name(s):
Downstream of receptor kinase
SH2-SH3 adapter protein drk

Gene names

Name:	drk
Synonyms:	E(sev)2B
ORF Names:	CG6033

Organism

Drosophila melanogaster (Fruit fly) [Reference proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Mandibulata › Pancrustacea › Hexapoda › Insecta › Dicondylia › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Eremoneura › Cyclorrhapha › Schizophora › Acalyptratae › Ephydroidea › Drosophilidae › Drosophilinae › Drosophilini › Drosophilina › Drosophiliti › Drosophila › Sophophora › melanogaster group › melanogaster subgroup

Protein attributes

Sequence length	211 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required for proper signaling by sevenless. May act to stimulate the ability of Sos to catalyze Ras1 activation by linking sevenless and Sos in a signaling complex. Ref.1 Ref.2
Subunit structure	Interacts with autophosphorylated sev via SH2 domain and Sos, Dos and Dab via SH3 domains. Binds to tyrosine phosphorylated Dab via the SH2 domain. Ref.1 Ref.2 Ref.7 Ref.8
Subcellular location	Membrane; Peripheral membrane protein Ref.2.
Tissue specificity	Found mainly in the developing eye and in the antennal disk. Also observed in other imaginal disks tested and in the embryo.
Sequence similarities	Belongs to the GRB2/sem-5/DRK family. Contains 1 SH2 domain. Contains 2 SH3 domains.

Ontologies

Keywords
Cellular component	Membrane
Domain	Repeat SH2 domain SH3 domain
Molecular function	Transducer
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Ras protein signal transduction Inferred from physical interaction Ref.2. Source: FlyBase actin filament organization Inferred from mutant phenotype PubMed 14527345. Source: FlyBase activation of JNKK activity Non-traceable author statement Ref.1Ref.2. Source: UniProtKB anterior/posterior axis specification, embryo Traceable author statement PubMed 10494038. Source: FlyBase embryonic development via the syncytial blastoderm Inferred from mutant phenotype PubMed 8978055. Source: FlyBase imaginal disc-derived wing morphogenesis Inferred from mutant phenotype PubMed 16648592. Source: FlyBase negative regulation of epidermal growth factor-activated receptor activity Inferred from genetic interaction PubMed 21340027. Source: FlyBase olfactory learning Inferred from mutant phenotype PubMed 19244537. Source: FlyBase positive regulation of R7 cell differentiation Inferred from genetic interaction PubMed 20980384. Source: FlyBase regulation of cell shape Inferred from mutant phenotype PubMed 14527345. Source: FlyBase sevenless signaling pathway Inferred from genetic interaction Ref.2. Source: FlyBase short-term memory Inferred from mutant phenotype PubMed 19244537. Source: FlyBase torso signaling pathway Traceable author statement PubMed 10494038. Source: FlyBase
Cellular_component	plasma membrane Inferred from direct assay Ref.2. Source: UniProtKB
Molecular_function	SH3/SH2 adaptor activity Non-traceable author statement Ref.1Ref.2. Source: UniProtKB signal transducer activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 211

211

Protein enhancer of sevenless 2B

PRO_0000088210

Regions

Domain

1 – 58

58

SH3 1

Domain

60 – 151

92

SH2

Domain

152 – 211

60

SH3 2

Experimental info

Mutagenesis

49

1

P → L: Inactivates the SH3 domain. Abolishes binding to Dab; when associated with R-199. Ref.7

Mutagenesis

67

1

R → H in Su(sevs11)R1 mutant; ommatidial cell development obstruction. Ref.2

Mutagenesis

85

1

R → K: Disrupts the SH2 domain. Does not affect binding to Dab. Ref.7

Mutagenesis

106

1

H → Y in E(sev)2B mutant; ommatidial cell development obstruction. Ref.2

Mutagenesis

199

1

G → R: Disrupts the SH3 domain. Abolishes binding to Dab; when associated with L-49. Ref.7

Secondary structure

1

.

.

.

.

.

.

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.

.

.

.

.

.

.

.

211

Helix Strand Turn

Details...

Beta strand

3 – 5

3

Beta strand

13 – 16

4

Beta strand

23 – 29

7

Turn

31 – 33

3

Beta strand

36 – 41

6

Beta strand

44 – 50

7

Beta strand

53 – 55

3

Sequences

	Sequence		Length	Mass (Da)
	Q08012 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: A1D0614AF358F3C0	FASTA	211	24,435
	10 20 30 40 50 60 MEAIAKHDFS ATADDELSFR KTQILKILNM EDDSNWYRAE LDGKEGLIPS NYIEMKNHDW 70 80 90 100 110 120 YYGRITRADA EKLLSNKHEG AFLIRISESS PGDFSLSVKC PDGVQHFKVL RDAQSKFFLW 130 140 150 160 170 180 VVKFNSLNEL VEYHRTASVS RSQDVKLRDM IPEEMLVQAL YDFVPQESGE LDFRRGDVIT 190 200 210 VTDRSDENWW NGEIGNRKGI FPATYVTPYH S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro." Simon M.A., Dodson G.S., Rubin G.M. Cell 73:169-177(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH SEV AND SOS. Tissue: Eye.
[2]	"A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos." Olivier J.P., Raabe T., Henkemeyer M., Dickson B., Mbamalu G., Margolis B., Schlessinger J., Hafen E., Pawson T. Cell 73:179-191(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SEV AND SOS, MUTAGENESIS OF ARG-67 AND HIS-106. Tissue: Embryo.
[3]	"Contrasting selection pressures on components of the Ras-mediated signal transduction pathway in Drosophila." Riley R.M., Jin W., Gibson G. Mol. Ecol. 12:1315-1323(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Ann Arbor1, Ann Arbor16, Ann Arbor18, Ann Arbor20, Ann Arbor3, CA2, CT1, Georgia-5b, Kakamega-2, Kakamega-b1, Kakamega-b2, Kenya-HLa3, Kenya-HLa4, Kenya-HLa6, Kenya-LGC, M2, Makindu-1, Makindu-b1, Makindu-b5, PYR2, Reids2 and Sapporo.
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[5]	"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] [Europe PMC] [Abstract] Cited for: GENOME REANNOTATION. 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Berkeley. Tissue: Embryo.
[7]	"Disabled is a putative adaptor protein that functions during signaling by the sevenless receptor tyrosine kinase." Le N., Simon M.A. Mol. Cell. Biol. 18:4844-4854(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DAB, MUTAGENESIS OF PRO-49; ARG-85 AND GLY-199.
[8]	"SH3 domain-mediated binding of the Drk protein to Dos is an important step in signaling of Drosophila receptor tyrosine kinases." Feller S.M., Wecklein H., Lewitzky M., Kibler E., Raabe T. Mech. Dev. 116:129-139(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DOS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L12446 mRNA. Translation: AAA28898.1.
L13173 mRNA. No translation available.
AY135053 Genomic DNA. Translation: AAN17564.1.
AY135054 Genomic DNA. Translation: AAN17565.1.
AY135055 Genomic DNA. Translation: AAN17566.1.
AY135056 Genomic DNA. Translation: AAN17567.1.
AY135057 Genomic DNA. Translation: AAN17568.1.
AY135058 Genomic DNA. Translation: AAN17569.1.
AY135059 Genomic DNA. Translation: AAN17570.1.
AY135060 Genomic DNA. Translation: AAN17571.1.
AY135061 Genomic DNA. Translation: AAN17572.1.
AY135062 Genomic DNA. Translation: AAN17573.1.
AY135063 Genomic DNA. Translation: AAN17574.1.
AY135064 Genomic DNA. Translation: AAN17575.1.
AY135065 Genomic DNA. Translation: AAN17576.1.
AY135066 Genomic DNA. Translation: AAN17577.1.
AY135067 Genomic DNA. Translation: AAN17578.1.
AY135068 Genomic DNA. Translation: AAN17579.1.
AY135069 Genomic DNA. Translation: AAN17580.1.
AY135070 Genomic DNA. Translation: AAN17581.1.
AY135071 Genomic DNA. Translation: AAN17582.1.
AY135072 Genomic DNA. Translation: AAN17583.1.
AY135073 Genomic DNA. Translation: AAN17584.1.
AY135074 Genomic DNA. Translation: AAN17585.1.
AE013599 Genomic DNA. Translation: AAF58368.1.
AE013599 Genomic DNA. Translation: AAM68582.1.
AE013599 Genomic DNA. Translation: AAM68583.1.
AE013599 Genomic DNA. Translation: AAM68584.1.
AE013599 Genomic DNA. Translation: AAM68585.1.
AY061142 mRNA. Translation: AAL28690.1.

PIR

A46444.

RefSeq

NP_476858.1. NM_057510.3.
NP_725302.1. NM_165994.1.
NP_725303.1. NM_165995.1.
NP_725304.1. NM_165996.1.
NP_725305.1. NM_165997.1.
NP_725306.1. NM_165998.1.

UniGene

Dm.3707.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2A36	NMR	-	A	1-59	[»]
2A37	NMR	-	A	1-59	[»]
2AZS	NMR	-	A	1-59	[»]
2AZV	NMR	-	A	1-59	[»]

ProteinModelPortal

Q08012.

SMR

Q08012. Positions 1-211.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-21223N.

IntAct

Q08012. 5 interactions.

MINT

MINT-242311.

Proteomic databases

PaxDb

Q08012.

PRIDE

Q08012.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblMetazoa

FBtr0087693; FBpp0086812; FBgn0004638.
FBtr0087694; FBpp0086813; FBgn0004638.
FBtr0087695; FBpp0086814; FBgn0004638.
FBtr0087696; FBpp0086815; FBgn0004638.
FBtr0087697; FBpp0086816; FBgn0004638.
FBtr0087698; FBpp0086817; FBgn0004638.

GeneID

36497.

KEGG

dme:Dmel_CG6033.

Organism-specific databases

CTD

36497.

FlyBase

FBgn0004638. drk.

Phylogenomic databases

eggNOG

NOG298780.

GeneTree

ENSGT00550000074482.

InParanoid

Q08012.

KO

K04364.

OMA

VETKFVQ.

OrthoDB

EOG4RBP1M.

PhylomeDB

Q08012.

Gene expression databases

Bgee

Q08012.

GermOnline

CG6033. Drosophila melanogaster.

Family and domain databases

Gene3D

3.30.505.10. 1 hit.

InterPro

IPR000108. p67phox.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]

Pfam

PF00017. SH2. 1 hit.
PF00018. SH3_1. 2 hits.
[Graphical view]

PRINTS

PR00499. P67PHOX.
PR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.

SMART

SM00252. SH2. 1 hit.
SM00326. SH3. 2 hits.
[Graphical view]

SUPFAM

SSF50044. SH3. 1 hit.

PROSITE

PS50001. SH2. 1 hit.
PS50002. SH3. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

drk. drosophila.

EvolutionaryTrace

Q08012.

GenomeRNAi

36497.

NextBio

798864.

Entry information

Entry name

DRK_DROME

Accession

Primary (citable) accession number: Q08012
Secondary accession number(s): A4UZF9, Q0E989, Q9V6Q5

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	April 3, 2013
This is version 124 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project