Reviewed, UniProtKB/Swiss-Prot Q8T4F7 (ENA_DROME)

Names and origin

Protein names

Recommended name:
    Protein enabled

Gene names

Name:	ena
Synonyms:	enb
ORF Names:	CG15112

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	829 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Functions, together with Abl, Trio and Fra, in a complex signaling network that regulates axon guidance at the CNS midline. Required in part for Robo-mediated repulsive axon guidance. May be involved in lamellipodial dynamics.
Subunit structure	Interacts with Abl and Src SH3 domains. Binds, in vitro and in vivo, the cytoplasmic domain of Robo. Interacts with Zyx102 and Chic.
Subcellular location	Cell projection › lamellipodium. Cytoplasm › cytoskeleton. Note= Expressed at the leading edge of lamellipodia. Co-localizes with Chic at the periphery of cells.
Tissue specificity	Expressed in axons of the embryonic nervous system.
Domain	The EVH2 domain is comprised of 3 regions. Block A is a thymosin-like domain required for G-actin binding. The KLKR motif within this block is essential for the G-actin binding and for actin polymerization. Block B is required for F-actin binding and subcellular location, and Block C for tetramerization.
Post-translational modification	Tyrosine phosphorylated on multiple sites by Abl kinase. In vitro, phosphorylation on specific tyrosine residues inhibits interaction with Abl and Src SH3 domains.
Sequence similarities	Belongs to the Ena/VASP family. Contains 1 WH1 domain.

Ontologies

Keywords
Cellular component	Cell projection Cytoplasm Cytoskeleton
Coding sequence diversity	Alternative splicing
Domain	SH3-binding
Ligand	Actin-binding
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	actin filament organization Inferred from mutant phenotype. Source: FlyBase axon guidance Ref.9 Inferred from mutant phenotype. Source: FlyBase dendrite morphogenesis Inferred from mutant phenotype. Source: FlyBase dorsal closure Traceable author statement. Source: FlyBase regulation of actin polymerization and/or depolymerization Traceable author statement. Source: FlyBase regulation of cell shape Inferred from mutant phenotype. Source: FlyBase
Cellular component	lamellipodium Ref.11 Inferred from direct assay. Source: UniProtKB
Molecular function	SH3 domain binding Ref.1 Ref.8 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
	Q9VHK9	1	EBI-466810,EBI-135037
	Q9VVC2	1	EBI-466810,EBI-141024
	Q9W242	1	EBI-466810,EBI-191849
Abl	P00522	2	EBI-466810,EBI-534090
chic	P25843	3	EBI-466810,EBI-156199
Dlc90F	Q94524	1	EBI-466810,EBI-158251
drk	Q08012	1	EBI-466810,EBI-161391
Lar	P16621	2	EBI-466810,EBI-668630
larp	Q9VAW5	1	EBI-466810,EBI-123668
Ptp10D	P35992	1	EBI-466810,EBI-675831
Ptp69D	P16620	1	EBI-466810,EBI-676392
Src	P05480	2	EBI-466810,EBI-298680	From a different organism.

Alternative products

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

Isoform 1 (identifier: Q8T4F7-1)

Also known as: B;

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 2 (identifier: Q8T4F7-2)

Also known as: A; C;

The sequence of this isoform differs from the canonical sequence as follows:
     2-146: Missing.
     147-147: F → T

Notes: No experimental confirmation available.

Isoform 3 (identifier: Q8T4F7-3)

Also known as: D;

The sequence of this isoform differs from the canonical sequence as follows:
     2-146: Missing.
     147-147: F → T
     331-331: S → SRNSL
     413-413: Missing.

Notes: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 829	829	Protein enabled
Regions
	Domain	146 – 256	111	WH1
	Region	640 – 829	190	EVH2
	Region	640 – 659	20	EVH2 block A
	Region	686 – 703	18	EVH2 block B
	Region	796 – 829	34	EVH2 block C
	Motif	649 – 652	4	KLKR
	Compositional bias	306 – 534	229	Gln-rich
	Compositional bias	482 – 633	152	Pro-rich
Amino acid modifications
	Modified residue	274	1	Phosphotyrosine
	Modified residue	456	1	Phosphotyrosine
	Modified residue	474	1	Phosphotyrosine
	Modified residue	499	1	Phosphotyrosine
	Modified residue	515	1	Phosphotyrosine
	Modified residue	675	1	Phosphotyrosine
	Modified residue	754	1	Phosphoserine
	Modified residue	763	1	Phosphoserine
	Modified residue	773	1	Phosphoserine
Natural variations
	Alternative sequence	2 – 146	145	Missing in isoform 2 and isoform 3.
	Alternative sequence	147	1	F → T in isoform 2 and isoform 3.
	Alternative sequence	331	1	S → SRNSL in isoform 3.
	Alternative sequence	413	1	Missing in isoform 3.
Experimental info
	Sequence conflict	120	1	Q → H in AAL89948. Ref.4
	Sequence conflict	340 – 342	3	Missing in AAL89948. Ref.4
	Sequence conflict	461	1	G → S in AAA85120. Ref.1
	Sequence conflict	648	1	I → F Ref.1 Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (B) [UniParc]. Last modified July 25, 2006. Version 3. Checksum: D0106BB286C7E756	FASTA	829	88,682
	10 20 30 40 50 60 MAMKKLYAKT SFTSKKPSSA ANSTPILAYH QQQHQQPGNG ICEFQVVAPG HSGELMIRRS 70 80 90 100 110 120 QSMHHKMSPP VGGLGSKSEY YSIEELQELD LLDYRHPMYH HYQQQELRQR YHEHEQLVLQ 130 140 150 160 170 180 LPKATSPKAG PIYEAPQRSQ QQQDQMFEQS IIGARASVMV YDDNQKKWVP SGSSSGLSKV 190 200 210 220 230 240 QIYHHQQNNT FRVVGRKLQD HEVVINCSIL KGLKYNQATA TFHQWRDSKF VYGLNFSSQN 250 260 270 280 290 300 DAENFARAMM HALEVLSGRV ANNPGGPPTN GNGYEEDMGY RTMTSEDAAI LRQNNSIGGH 310 320 330 340 350 360 VTPSAQTPTS QTNQNNIPQS PPTPQGHHRT SSAPPAPQPQ QQQQQQQAQQ MGQPGSHYGP 370 380 390 400 410 420 TGNGPTSNGL PQQVNSQIPP APQQQPQQQQ FQQQQQQQQY QQMVQAGYAP SQQYQQPHYV 430 440 450 460 470 480 LSNSNPNLTV HQYPTQQAQQ QPPQAPQPPL QNGGMYMVGH GHLPSSASAN SVVYASQQQM 490 500 510 520 530 540 LPQAHPQAPQ APTMPGPGYG GPPVPPPQQQ AENPYGQVPM PPPMNPSQQQ QPGQVPLNRM 550 560 570 580 590 600 SSQGGPGGPP APAPPPPPPS FGGAAGGGPP PPAPPQMFNG APPPPAMGGG PPPAPPAPPA 610 620 630 640 650 660 MGGGPPPAPG GPGAPPPPPP PPGLGGAPKK EDPQADLMGS LASQLQQIKL KKNKVTTSAP 670 680 690 700 710 720 ENSGSSTSSG GSGNYGTIGR SSNGMASMMD EMAKTLARRR AQAEKKDPDP EAEVKKRPWE 730 740 750 760 770 780 KSNTLPHKLS GGAGSGSAGS GHEGANGNSG GAGSNTTNSG GESPRPMRKR FGSASEETIL 790 800 810 820 KVNGDGLSLA LSNGDLDTLK AEIVREMRLE IQKVKNEIID AIKSEFNRR
	Isoform 2 (A) (C) [UniParc]. Checksum: E1FFB5A8091FA77E		684	71,985
	10 20 30 40 50 60 MTEQSIIGAR ASVMVYDDNQ KKWVPSGSSS GLSKVQIYHH QQNNTFRVVG RKLQDHEVVI 70 80 90 100 110 120 NCSILKGLKY NQATATFHQW RDSKFVYGLN FSSQNDAENF ARAMMHALEV LSGRVANNPG 130 140 150 160 170 180 GPPTNGNGYE EDMGYRTMTS EDAAILRQNN SIGGHVTPSA QTPTSQTNQN NIPQSPPTPQ 190 200 210 220 230 240 GHHRTSSAPP APQPQQQQQQ QQAQQMGQPG SHYGPTGNGP TSNGLPQQVN SQIPPAPQQQ 250 260 270 280 290 300 PQQQQFQQQQ QQQQYQQMVQ AGYAPSQQYQ QPHYVLSNSN PNLTVHQYPT QQAQQQPPQA 310 320 330 340 350 360 PQPPLQNGGM YMVGHGHLPS SASANSVVYA SQQQMLPQAH PQAPQAPTMP GPGYGGPPVP 370 380 390 400 410 420 PPQQQAENPY GQVPMPPPMN PSQQQQPGQV PLNRMSSQGG PGGPPAPAPP PPPPSFGGAA 430 440 450 460 470 480 GGGPPPPAPP QMFNGAPPPP AMGGGPPPAP PAPPAMGGGP PPAPGGPGAP PPPPPPPGLG 490 500 510 520 530 540 GAPKKEDPQA DLMGSLASQL QQIKLKKNKV TTSAPENSGS STSSGGSGNY GTIGRSSNGM 550 560 570 580 590 600 ASMMDEMAKT LARRRAQAEK KDPDPEAEVK KRPWEKSNTL PHKLSGGAGS GSAGSGHEGA 610 620 630 640 650 660 NGNSGGAGSN TTNSGGESPR PMRKRFGSAS EETILKVNGD GLSLALSNGD LDTLKAEIVR 670 680 EMRLEIQKVK NEIIDAIKSE FNRR
	Isoform 3 (D) [UniParc]. Checksum: F480275EB4CC79A8		687	72,327
	10 20 30 40 50 60 MTEQSIIGAR ASVMVYDDNQ KKWVPSGSSS GLSKVQIYHH QQNNTFRVVG RKLQDHEVVI 70 80 90 100 110 120 NCSILKGLKY NQATATFHQW RDSKFVYGLN FSSQNDAENF ARAMMHALEV LSGRVANNPG 130 140 150 160 170 180 GPPTNGNGYE EDMGYRTMTS EDAAILRQNN SIGGHVTPSA QTPTSQTNQN NIPQSPPTPQ 190 200 210 220 230 240 GHHRTSRNSL SAPPAPQPQQ QQQQQQAQQM GQPGSHYGPT GNGPTSNGLP QQVNSQIPPA 250 260 270 280 290 300 PQQQPQQQQF QQQQQQQQYQ QMVQAGYAPS QYQQPHYVLS NSNPNLTVHQ YPTQQAQQQP 310 320 330 340 350 360 PQAPQPPLQN GGMYMVGHGH LPSSASANSV VYASQQQMLP QAHPQAPQAP TMPGPGYGGP 370 380 390 400 410 420 PVPPPQQQAE NPYGQVPMPP PMNPSQQQQP GQVPLNRMSS QGGPGGPPAP APPPPPPSFG 430 440 450 460 470 480 GAAGGGPPPP APPQMFNGAP PPPAMGGGPP PAPPAPPAMG GGPPPAPGGP GAPPPPPPPP 490 500 510 520 530 540 GLGGAPKKED PQADLMGSLA SQLQQIKLKK NKVTTSAPEN SGSSTSSGGS GNYGTIGRSS 550 560 570 580 590 600 NGMASMMDEM AKTLARRRAQ AEKKDPDPEA EVKKRPWEKS NTLPHKLSGG AGSGSAGSGH 610 620 630 640 650 660 EGANGNSGGA GSNTTNSGGE SPRPMRKRFG SASEETILKV NGDGLSLALS NGDLDTLKAE 670 680 IVREMRLEIQ KVKNEIIDAI KSEFNRR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Enabled, a dosage-sensitive suppressor of mutations in the Drosophila Abl tyrosine kinase, encodes an Abl substrate with SH3 domain-binding properties." Gertler F.B., Comer A.R., Juang J.-L., Ahern S.M., Clark M.J., Liebl E.C., Hoffmann F.M. Genes Dev. 9:521-533(1995) [PubMed: 7535279] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 2), INTERACTION WITH ABL AND SRC, PHOSPHORYLATION, TISSUE SPECIFICITY. Tissue: Embryo.
[2]	"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.
[3]	"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.
[4]	"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 1). Strain: Berkeley. Tissue: Embryo.
[5]	Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Champe M., Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.A., Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., Miranda A. , Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., Patel S., Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., Celniker S.E. Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Strain: Berkeley. Tissue: Embryo.
[6]	"The Abelson tyrosine kinase, the Trio GEF and Enabled interact with the Netrin receptor Frazzled in Drosophila." Forsthoefel D.J., Liebl E.C., Kolodziej P.A., Seeger M.A. Development 132:1983-1994(2005) [PubMed: 15790972] [Abstract] Cited for: FUNCTION.
[7]	"Phosphorylation of Enabled by the Drosophila Abelson tyrosine kinase regulates the in vivo function and protein-protein interactions of Enabled." Comer A.R., Ahern-Djamali S.M., Juang J.-L., Jackson P.D., Hoffmann F.M. Mol. Cell. Biol. 18:152-160(1998) [PubMed: 9418863] [Abstract] Cited for: PHOSPHORYLATION AT TYR-274; TYR-456; TYR-474; TYR-499; TYR-515 AND TYR-675.
[8]	"Identification of profilin and src homology 3 domains as binding partners for Drosophila enabled." Ahern-Djamali S.M., Bachmann C., Hua P., Reddy S.K., Kastenmeier A.S., Walter U., Hoffmann F.M. Proc. Natl. Acad. Sci. U.S.A. 96:4977-4982(1999) [PubMed: 10220404] [Abstract] Cited for: INTERACTION WITH CHIC.
[9]	"Repulsive axon guidance: Abelson and Enabled play opposing roles downstream of the roundabout receptor." Bashaw G.J., Kidd T., Murray D., Pawson T., Goodman C.S. Cell 101:703-715(2000) [PubMed: 10892742] [Abstract] Cited for: INTERACTION WITH ROBO.
[10]	"Molecular and phylogenetic characterization of Zyx102, a Drosophila orthologue of the zyxin family that interacts with Drosophila Enabled." Renfranz P.J., Siegrist S.E., Stronach B.E., Macalma T., Beckerle M.C. Gene 305:13-26(2003) [PubMed: 12594038] [Abstract] Cited for: INTERACTION WITH ZYX102.
[11]	"Cascade pathway of filopodia formation downstream of SCAR." Biyasheva A., Svitkina T., Kunda P., Baum B., Borisy G. J. Cell Sci. 117:837-848(2004) [PubMed: 14762109] [Abstract] Cited for: SUBCELLULAR LOCATION.
[12]	"An integrated chemical, mass spectrometric and computational strategy for (quantitative) phosphoproteomics: application to Drosophila melanogaster Kc167 cells." Bodenmiller B., Mueller L.N., Pedrioli P.G.A., Pflieger D., Juenger M.A., Eng J.K., Aebersold R., Tao W.A. Mol. Biosyst. 3:275-286(2007) [PubMed: 17372656] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-773, MASS SPECTROMETRY.
[13]	"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 SER-754; SER-763 AND SER-773, MASS SPECTROMETRY. Tissue: Embryo.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U21123 Genomic DNA. Translation: AAA85120.1. AE013599 Genomic DNA. Translation: AAF57598.2. AE013599 Genomic DNA. Translation: AAM68439.1. AE013599 Genomic DNA. Translation: AAX52696.1. AY084210 mRNA. Translation: AAL89948.1. BT004488 mRNA. Translation: AAO42652.1.
PIR	A56154.
RefSeq	NP_001014537.1. NP_725857.1. NP_725859.1.
UniGene	Dm.14700
3D structure databases
HSSP	HSSP built from PDB template 1QC6 based on UniProtKB P70429.
SMR	Q8T4F7. Positions 148-257.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8T4F7.
Genome annotation databases
Ensembl	CG15112. Drosophila melanogaster. [Contig view]
GeneID	37201.
Organism-specific databases
FlyBase	FBgn0000578. ena.
Phylogenomic databases
HOGENOM	Q8T4F7.
Gene expression databases
ArrayExpress	Q8T4F7.
GermOnline	CG15112. Drosophila melanogaster.
Family and domain databases
InterPro	IPR000697. EVH1. IPR011993. PH_type. IPR000156. RanBP1. IPR014885. VASP_tetra. [Graphical view]
Gene3D	G3DSA:2.30.29.30. PH_type. 1 hit.
Pfam	PF08776. VASP_tetra. 1 hit. PF00568. WH1. 1 hit. [Graphical view]
SMART	SM00160. RanBD. 1 hit. SM00461. WH1. 1 hit. [Graphical view]