MELT_DROME
ID MELT_DROME Reviewed; 994 AA.
AC Q9VS24; Q058T9; Q59E21; Q9U422;
DT 21-AUG-2007, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 2.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Protein melted;
GN Name=melt; ORFNames=CG8624;
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 [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 [2]
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING (ISOFORM B).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C).
RC STRAIN=Berkeley;
RA Stapleton M., Carlson J.W., Frise E., Kapadia B., Park S., Wan K.H., Yu C.,
RA Celniker S.E.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-717 (ISOFORM C), AND FUNCTION.
RX PubMed=11102367; DOI=10.1093/genetics/156.4.1691;
RA Prokopenko S.N., He Y., Lu Y., Bellen H.J.;
RT "Mutations affecting the development of the peripheral nervous system in
RT Drosophila: a molecular screen for novel proteins.";
RL Genetics 156:1691-1715(2000).
RN [5]
RP FUNCTION.
RX PubMed=16143107; DOI=10.1016/j.cell.2005.07.026;
RA Mikeladze-Dvali T., Wernet M.F., Pistillo D., Mazzoni E.O., Teleman A.A.,
RA Chen Y.-W., Cohen S., Desplan C.;
RT "The growth regulators warts/lats and melted interact in a bistable loop to
RT specify opposite fates in Drosophila R8 photoreceptors.";
RL Cell 122:775-787(2005).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TSC1 AND FOXO.
RX PubMed=16054033; DOI=10.1016/j.devcel.2005.07.004;
RA Teleman A.A., Chen Y.-W., Cohen S.M.;
RT "Drosophila Melted modulates FOXO and TOR activity.";
RL Dev. Cell 9:271-281(2005).
CC -!- FUNCTION: Participates in fat metabolism regulation by recruiting FOXO
CC and the TSC1-TSC2 complex to the cell membrane, which positively
CC regulates TOR activity and negatively regulates the expression of FOXO
CC target genes. Involved in R8 photoreceptor subtype specification.
CC During early embryonic development, may be required for ectodermal
CC patterning. {ECO:0000269|PubMed:11102367, ECO:0000269|PubMed:16054033,
CC ECO:0000269|PubMed:16143107}.
CC -!- SUBUNIT: Interacts with TSC1 and FOXO. {ECO:0000269|PubMed:16054033}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16054033};
CC Peripheral membrane protein {ECO:0000269|PubMed:16054033}; Cytoplasmic
CC side {ECO:0000269|PubMed:16054033}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=C;
CC IsoId=Q9VS24-3; Sequence=Displayed;
CC Name=B;
CC IsoId=Q9VS24-2; Sequence=VSP_027438;
CC -!- DOMAIN: The PH domain is required for membrane targeting.
CC -!- SIMILARITY: Belongs to the MELT/VEPH family. {ECO:0000305}.
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DR EMBL; AE014296; AAF50606.2; -; Genomic_DNA.
DR EMBL; AE014296; AAX52758.1; -; Genomic_DNA.
DR EMBL; BT029129; ABJ17062.1; -; mRNA.
DR EMBL; AF205831; AAF14808.1; -; mRNA.
DR RefSeq; NP_001014572.1; NM_001014572.4. [Q9VS24-2]
DR RefSeq; NP_523953.2; NM_079229.4. [Q9VS24-3]
DR AlphaFoldDB; Q9VS24; -.
DR BioGRID; 64230; 13.
DR STRING; 7227.FBpp0291254; -.
DR PaxDb; Q9VS24; -.
DR DNASU; 38785; -.
DR EnsemblMetazoa; FBtr0100141; FBpp0099491; FBgn0023001. [Q9VS24-2]
DR EnsemblMetazoa; FBtr0302044; FBpp0291254; FBgn0023001. [Q9VS24-3]
DR GeneID; 38785; -.
DR KEGG; dme:Dmel_CG8624; -.
DR UCSC; CG8624-RA; d. melanogaster. [Q9VS24-3]
DR CTD; 38785; -.
DR FlyBase; FBgn0023001; melt.
DR VEuPathDB; VectorBase:FBgn0023001; -.
DR eggNOG; KOG3723; Eukaryota.
DR GeneTree; ENSGT00390000018660; -.
DR InParanoid; Q9VS24; -.
DR PhylomeDB; Q9VS24; -.
DR BioGRID-ORCS; 38785; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 38785; -.
DR PRO; PR:Q9VS24; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0023001; Expressed in adult Malpighian tubule (Drosophila) and 19 other tissues.
DR ExpressionAtlas; Q9VS24; baseline and differential.
DR Genevisible; Q9VS24; DM.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:FlyBase.
DR GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; IDA:FlyBase.
DR GO; GO:0001708; P:cell fate specification; IMP:FlyBase.
DR GO; GO:0009267; P:cellular response to starvation; IMP:FlyBase.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IMP:FlyBase.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IMP:FlyBase.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; IMP:FlyBase.
DR GO; GO:0045464; P:R8 cell fate specification; IMP:FlyBase.
DR GO; GO:0031323; P:regulation of cellular metabolic process; IMP:FlyBase.
DR GO; GO:0009966; P:regulation of signal transduction; IBA:GO_Central.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR039888; Melted-like.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR PANTHER; PTHR21630; PTHR21630; 1.
DR SMART; SM00233; PH; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Developmental protein;
KW Lipid metabolism; Membrane; Reference proteome.
FT CHAIN 1..994
FT /note="Protein melted"
FT /id="PRO_0000297961"
FT DOMAIN 872..967
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 404..461
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 486..521
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 536..565
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 973..994
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 419..434
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 486..513
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 542..565
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 716..721
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000305"
FT /id="VSP_027438"
FT CONFLICT 405
FT /note="V -> A (in Ref. 4; AAF14808)"
FT /evidence="ECO:0000305"
FT CONFLICT 414
FT /note="S -> A (in Ref. 4; AAF14808)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 994 AA; 108105 MW; BE3A08490E2855E9 CRC64;
MHELFNKVLA KRDLSRAGDL FSVPDADIVD DITEVLSEIS PIISHADYVK NNNDQSVVEI
CVTRVLSCIR ETKTAERYCA ALVDLLRTCL LWNLQPSGTT KEEPPHAKIA ADIISSIFLN
YDKKELMKIA LPVAVQFLPK GNRELSRNLA SYLSLAAIDH AGLLSPHTES VMESILSGNY
GLLRVLSQVY EVAPEAVTPH APLLMPLLPQ CDPQERMAVF QLYLLIVQKS PEVLESCVPQ
LCGSLLDSDT SSITMQILLK LSQHSPSLLV DHFEQLRLAA KTNPGTIPLC AQIMTTAGIG
SKETAQQALD FVLEHLPTQA LLQQEATRLC SAYPVLFTDK VLACVRQKNA ALSSQQDVGN
GLANKTSGGV TIVSLNSSSP SPPLKPVPVG APAINTTIVQ PASVVSATPT PPPSSASAPI
ASSTPVSAAT PTPQHAGYTR RVKLGDSRST GRLHPASNTH RSVTRLNVAS GSVGGLHKSM
TRLSNSQINQ QPGGSSNGNV VVQSGATPKT PTGLSNPPVT PVPPLSNNVV ITGHNRHGIP
VTSGGVTVTT SPSKVRPHSQ GPSTLLNSST VLMKYSTDAL NQSVGSISIP QSAAVATLPS
TQTQNAVSVH HASPALPQSA SNGHAKSVMK LPVNGNSEVI VSGPTTNVAP RRSDNTSRTL
LNANSVMDQR MSTFEPYQIM RDPVQQFCEK NFNSIKSYMD EVSQHLPPPT RCSIEVSNEF
AERRTKKVAK LHFACQIRGP HCLYSKTCFT MRTRNPKTWI HMMFLDFQVR HFVKEKCVLS
TRESGISNLK NIWQILKCEN RSFTELVTSQ FPQVKDREIL VNELRHSGFL DVFEVSKTDK
SNPNCNELEY QWGCFLCNHP DKAVGFLNGS NQPMIEGQLK EKKGKWRLFR RWRTRYFTLS
GAHLSCKGSS GGESIDVNQI RSVKVSRGAR NIPKAFEIFT ADQTLILKPK DGKNAEEWVQ
CLSIVVAHSQ ARDNPTAKTN SLPARSIGSS KPSF
