DIP2_DROME
ID DIP2_DROME Reviewed; 1773 AA.
AC Q9W0S9; Q9NGP2;
DT 11-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Disco-interacting protein 2;
GN Name=DIP2; ORFNames=CG7020;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Decroos F.C., Voas M.G., Rebay I.;
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP TISSUE SPECIFICITY, AND INTERACTION WITH DISCO.
RX PubMed=12137943; DOI=10.1016/s0378-1119(02)00694-7;
RA Mukhopadhyay M., Pelka P., DeSousa D., Kablar B., Schindler A.,
RA Rudnicki M.A., Campos A.R.;
RT "Cloning, genomic organization and expression pattern of a novel Drosophila
RT gene, the disco-interacting protein 2 (dip2), and its murine homolog.";
RL Gene 293:59-65(2002).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-60 AND TYR-61, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=28396149; DOI=10.1016/j.bbrc.2017.04.028;
RA Nitta Y., Sugie A.;
RT "DISCO interacting protein 2 determines direction of axon projection under
RT the regulation of c-Jun N-terminal kinase in the Drosophila mushroom
RT body.";
RL Biochem. Biophys. Res. Commun. 487:116-121(2017).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=27908785; DOI=10.1016/j.ydbio.2016.11.015;
RA Nitta Y., Yamazaki D., Sugie A., Hiroi M., Tabata T.;
RT "DISCO Interacting Protein 2 regulates axonal bifurcation and guidance of
RT Drosophila mushroom body neurons.";
RL Dev. Biol. 421:233-244(2017).
CC -!- FUNCTION: Required for precise axonal bifurcation in mushroom body
CC neurons by suppressing ectopic bifurcation and regulating the guidance
CC of sister axons (PubMed:28396149, PubMed:27908785). Acts downstream of
CC the serine/threonine-protein kinase Bsk to modulate the direction of
CC axon projection (PubMed:28396149). May play a role in fatty acid
CC metabolism (PubMed:27908785). {ECO:0000269|PubMed:27908785,
CC ECO:0000269|PubMed:28396149}.
CC -!- SUBUNIT: Interacts with Disco. {ECO:0000269|PubMed:12137943}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:27908785,
CC ECO:0000269|PubMed:28396149}; Peripheral membrane protein
CC {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in the developing nervous system
CC (PubMed:12137943). Ubiquitously expressed in the developing brain
CC (PubMed:27908785). Within the mushroom body, a higher level is detected
CC in the core of lobes and peduncle in the late third instar larva
CC (PubMed:12137943). Detected in whole mushroom body neuron structures at
CC 48 hours after puparium formation and during later stages
CC (PubMed:27908785). {ECO:0000269|PubMed:12137943,
CC ECO:0000269|PubMed:27908785}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in the central nervous system
CC (CNS) in both the brain lobes and the ventral cord throughout
CC embryogenesis, from early stages of neurogenesis. Expressed in both
CC neuroblasts and neurons. Expressed at lower level in the visceral
CC mesoderm during stage 12. Expression of DIP2 overlaps with that of
CC Disco in the visceral mesoderm and CNS.
CC -!- DISRUPTION PHENOTYPE: Mushroom body lobe defects including ectopic axon
CC bifurcations and/or axon guidance defects (PubMed:27908785). RNAi-
CC mediated knockdown results in an increase in the number of mushroom
CC body lobes as well as ectopic lobes and guidance defects
CC (PubMed:28396149, PubMed:27908785). {ECO:0000269|PubMed:27908785,
CC ECO:0000269|PubMed:28396149}.
CC -!- SIMILARITY: Belongs to the DIP2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF64300.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF246991; AAF64300.1; ALT_FRAME; mRNA.
DR EMBL; AE014296; AAF47364.2; -; Genomic_DNA.
DR RefSeq; NP_612019.2; NM_138175.4.
DR AlphaFoldDB; Q9W0S9; -.
DR SMR; Q9W0S9; -.
DR BioGRID; 76010; 1.
DR IntAct; Q9W0S9; 3.
DR STRING; 7227.FBpp0072420; -.
DR iPTMnet; Q9W0S9; -.
DR PaxDb; Q9W0S9; -.
DR PRIDE; Q9W0S9; -.
DR EnsemblMetazoa; FBtr0072520; FBpp0072420; FBgn0024806.
DR GeneID; 252479; -.
DR KEGG; dme:Dmel_CG7020; -.
DR CTD; 252479; -.
DR FlyBase; FBgn0024806; DIP2.
DR VEuPathDB; VectorBase:FBgn0024806; -.
DR eggNOG; KOG3628; Eukaryota.
DR GeneTree; ENSGT00950000182997; -.
DR InParanoid; Q9W0S9; -.
DR OrthoDB; 539697at2759; -.
DR PhylomeDB; Q9W0S9; -.
DR SignaLink; Q9W0S9; -.
DR BioGRID-ORCS; 252479; 1 hit in 3 CRISPR screens.
DR ChiTaRS; norpA; fly.
DR GenomeRNAi; 252479; -.
DR PRO; PR:Q9W0S9; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0024806; Expressed in eye disc (Drosophila) and 28 other tissues.
DR ExpressionAtlas; Q9W0S9; baseline and differential.
DR Genevisible; Q9W0S9; DM.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0003987; F:acetate-CoA ligase activity; ISS:FlyBase.
DR GO; GO:0006085; P:acetyl-CoA biosynthetic process; ISS:FlyBase.
DR GO; GO:0007411; P:axon guidance; IMP:UniProtKB.
DR CDD; cd05905; Dip2; 2.
DR Gene3D; 3.30.300.30; -; 2.
DR Gene3D; 3.40.50.12780; -; 2.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR037337; Dip2-like_dom.
DR InterPro; IPR010506; DMAP1-bd.
DR Pfam; PF00501; AMP-binding; 2.
DR Pfam; PF06464; DMAP_binding; 1.
DR SMART; SM01137; DMAP_binding; 1.
DR PROSITE; PS51912; DMAP1_BIND; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Developmental protein; Membrane; Neurogenesis;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..1773
FT /note="Disco-interacting protein 2"
FT /id="PRO_0000079905"
FT DOMAIN 3..110
FT /note="DMAP1-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01260"
FT REGION 112..185
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 198..319
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 112..126
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 149..166
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 210..224
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 270..301
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 302..317
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 60
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 61
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT CONFLICT 1038..1048
FT /note="PLGGIHLCEAR -> LLGAYIYAKHG (in Ref. 1; AAF64300)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1773 AA; 194154 MW; 2A05C475B47DCF9A CRC64;
MEHTASLPGY VREKLAELDL ELSEGDITQK GYEKKRAKLL QPFLKKPEGD KVKSTPPPPY
YNVKNANNST NHGNINNDGV IVSSEGYSYV TEVPSLSSSQ QRHSKKIDFH QQAAMSLSSA
PQSGNAGAPG YENMRPQGGA VGDPGYQNTR EPSAFQNQQS TNNSQHRQRR TQRKVTHNEK
RYHSEVRQEA VQQALAALKG RPKPSLPMPS KRTSVLNRSP GCNDELDSST DDESIPEETI
SPDKEYNYPR DHISNSILPP EPIIKPPIRE SSMGSQQHAR TDVKQNQITN QKYTAPNSAP
ERRPPQNLPP LPTSEPLSSD YPPIAYKREN DFSDKAFKQK QYNAPDITQF NNAHRAADRV
TRYVNVSQNE LNETDANGKW KVSAKIQQLL NTLKRPKRRP LPEFYEDNDI ELEIAANTKD
PNAPKPEGST MTPVQGEQLS IPAGLPRTLE CALQRYGTNS FKSPMATVLD PNGKVTTTLT
YGKLLSRAQK IAHALSTKIF SKGPEQVTLK PGDRVALVYP NNDPLSFITA WYGCMFRGLV
PLPIELPLSS SDTPPQQVGF LLSSCGITVA LTSEACLKGL PKSTTTGEIA KLKGWPRLQW
FVTEHLPKPP KEFNVGNLRA DDSAAAYIEY TTDKEGSVMG VTVTRAAMIN HCRALTMACH
YTEGETIVCV LDFKREVGLW HSVLTSVLNG MHVIFIPYAL MKLRPSSWMQ LITKHRASCC
LVKSRDLHWG LLATKDHKDI SLSSLRMLLV ADGANPWSLS SCDQFLSVFQ AKGLRSDAIC
PCASSSEVFT VSLRRPGRGS CGFSPSATGR GVLSMAALSH GVVRVDSEDS LTSLTLQDCG
QVMPAAQMVV VRSEGPPVLC KTDQVGEICV TSGSTSASYF GLDGMTNSTF KVQPLLEELE
QPKDGNGTVN IISKPIGEDF YVRSGLLGFL GPGGLVFVCG SRDGLMTVTG RKHNADDIIA
TVLAVEPMRF IYRGRIAVFS IKVLRDERVC VIAEQRPDCS EEESFQWMSR VLQAVDSIHQ
VGIYCLALVP PNHLPKTPLG GIHLCEARRR FLEGSLHPAN VLMCPHTCVT NLPKPRELHQ
GVQTAAKLSS SSGCGITDTG VGPASVMVGN LVQGNRLAEA HGRDVGLAED CERKPQLITG
VLRWRANTSP DHIIFTLLNS KGAIAKTLTC SELHKRAEKI AALLQERGRI EPGDHVALIF
PPGLDLLCAF YGCLYLGAIP ITIRPPHPQN LNTTLPTVRM IVDVSKSGIV LSIQPIIKLL
KSREAATSID PKTWPPILDI DDNPKRKYAG IATVSFDSSA YLDFSVSTCG RLSGVNITHR
SLSSLCASLK LACELYPSRH VALCLDPYCG LGFVMWTLIG VYSGHHSILI APYEVEANPS
LWLSTLSQHR VRDTFCSYGV IELCTKALSN SIPSLKQRNI DLRCVRTCVV VAEERPRVQL
TQQFCKLFQA LGLNTRCVST SFGCRVNPAI CVQGASSAES AQVYVDMRAL RNNRVALVER
GAPNSLCVIE SGKLLPGVKV IIANPETKGH CGDSHLGEIW VQAPHNANGY FTIYGDETDY
NDHFNAKLVT GATSELYART GYLGFLRRTE CSQSASLLDE TTPSVASRDS DTESLNSISQ
LQLNFSNVSL GGNSEHSLVG GASNANDQEL HDAVYVVGAV DEVISLRGMN YHPIDIENSV
MRCHKKIAEC AVFTWTNLLV VVVELDGNES EALDLVPLVT NTVLEDHQLI VGVVVVVDPG
VVPINSRGEK QRMHLRDGFL ADQLDPIYVA YNM