INDY1_DROME
ID INDY1_DROME Reviewed; 590 AA.
AC Q9VVT2; A4V236; Q7KUS6; Q9NHY9;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Protein I'm not dead yet;
DE AltName: Full=INDY transporter protein;
DE AltName: Full=drIndy;
GN Name=Indy; ORFNames=CG3979;
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 {ECO:0000312|EMBL:AAM27515.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), AND FUNCTION.
RX PubMed=12186628; DOI=10.1042/bj20021132;
RA Inoue K., Fei Y.-J., Huang W., Zhuang L., Chen Z., Ganapathy V.;
RT "Functional identity of Drosophila melanogaster Indy as a cation-
RT independent, electroneutral transporter for tricarboxylic acid-cycle
RT intermediates.";
RL Biochem. J. 367:313-319(2002).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132};
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, AND ALTERNATIVE SPLICING.
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] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=Berkeley {ECO:0000269|PubMed:12537569};
RC TISSUE=Embryo {ECO:0000269|PubMed:12537569};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 366-572.
RC STRAIN=Canton-S {ECO:0000312|EMBL:AAF73384.1}; TISSUE=Embryo;
RX PubMed=10581279; DOI=10.1093/genetics/153.4.1717;
RA Schmid K.J., Nigro L., Aquadro C.F., Tautz D.;
RT "Large number of replacement polymorphisms in rapidly evolving genes of
RT Drosophila. Implications for genome-wide surveys of DNA polymorphism.";
RL Genetics 153:1717-1729(1999).
RN [6] {ECO:0000305}
RP IDENTIFICATION, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11118146; DOI=10.1126/science.290.5499.2137;
RA Rogina B., Reenan R.A., Nilsen S.P., Helfand S.L.;
RT "Extended life-span conferred by cotransporter gene mutations in
RT Drosophila.";
RL Science 290:2137-2140(2000).
RN [7] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=12391301; DOI=10.1073/pnas.222531899;
RA Knauf F., Rogina B., Jiang Z., Aronson P.S., Helfand S.L.;
RT "Functional characterization and immunolocalization of the transporter
RT encoded by the life-extending gene Indy.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:14315-14319(2002).
CC -!- FUNCTION: Cation-independent electroneutral transporter (not associated
CC with membrane depolarization) of a variety of tricarboxylic and
CC dicarboxylic acid-cycle intermediates. There is also small, but
CC detectable, transport of monocarboxylics. Transport is through the
CC epithelium of the gut and across the plasma membranes of organs
CC involved in intermediary metabolism and storage. Affinity for
CC substrates is citrate > succinate > pyruvate. Fumarate, a-
CC ketoglutarate, and glutarate are also transported, but not lactate.
CC Transport mechanism that is not coupled to Na(+), K(+), or Cl(-).
CC Function is shown in Xenopus oocytes and human retinal pigment
CC epithelial (HRPE) cell lines. {ECO:0000269|PubMed:11118146,
CC ECO:0000269|PubMed:12186628, ECO:0000269|PubMed:12391301}.
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC {ECO:0000269|PubMed:12391301}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:12391301}. Note=Basolateral membrane of cells in
CC the midgut.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A; Synonyms=C;
CC IsoId=Q9VVT2-1; Sequence=Displayed;
CC Name=B;
CC IsoId=Q9VVT2-2; Sequence=VSP_029170;
CC -!- TISSUE SPECIFICITY: In adults, abundantly expressed in the fat body,
CC basolateral region of midgut cells and oenocytes. Low level expression
CC is seen in the halteres, procardia, restricted regions of the esophagus
CC and hindgut, base of the legs and in a subset of cells in the third
CC segment of the antennae. {ECO:0000269|PubMed:11118146,
CC ECO:0000269|PubMed:12391301}.
CC -!- INDUCTION: Completely inhibited by DIDS. Modest but significant
CC inhibition by phloretin or furosemide. {ECO:0000269|PubMed:12391301}.
CC -!- MISCELLANEOUS: The life-extending effect of mutations is likely caused
CC by an alteration in energy balance caused by a decrease in transport
CC function. {ECO:0000269|PubMed:11118146, ECO:0000269|PubMed:12391301}.
CC -!- SIMILARITY: Belongs to the SLC13A/DASS transporter (TC 2.A.47) family.
CC NADC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF73384.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF509505; AAN86815.1; -; mRNA.
DR EMBL; AE014296; AAF49226.1; -; Genomic_DNA.
DR EMBL; AE014296; AAF49227.2; -; Genomic_DNA.
DR EMBL; AE014296; AAN11670.1; -; Genomic_DNA.
DR EMBL; AY102686; AAM27515.1; -; mRNA.
DR EMBL; AF217399; AAF73384.1; ALT_INIT; mRNA.
DR RefSeq; NP_001163465.1; NM_001169994.2. [Q9VVT2-2]
DR RefSeq; NP_524150.1; NM_079426.4. [Q9VVT2-2]
DR RefSeq; NP_730363.2; NM_168778.2. [Q9VVT2-1]
DR RefSeq; NP_730364.1; NM_168779.2. [Q9VVT2-2]
DR AlphaFoldDB; Q9VVT2; -.
DR SMR; Q9VVT2; -.
DR BioGRID; 65330; 4.
DR DIP; DIP-18443N; -.
DR IntAct; Q9VVT2; 3.
DR STRING; 7227.FBpp0074848; -.
DR TCDB; 2.A.47.1.10; the divalent anion:na(+) symporter (dass) family.
DR SwissPalm; Q9VVT2; -.
DR PaxDb; Q9VVT2; -.
DR PRIDE; Q9VVT2; -.
DR DNASU; 40049; -.
DR EnsemblMetazoa; FBtr0075081; FBpp0074848; FBgn0036816. [Q9VVT2-1]
DR EnsemblMetazoa; FBtr0075082; FBpp0074849; FBgn0036816. [Q9VVT2-2]
DR EnsemblMetazoa; FBtr0075083; FBpp0074850; FBgn0036816. [Q9VVT2-2]
DR EnsemblMetazoa; FBtr0301857; FBpp0291071; FBgn0036816. [Q9VVT2-2]
DR GeneID; 40049; -.
DR KEGG; dme:Dmel_CG3979; -.
DR CTD; 40049; -.
DR FlyBase; FBgn0036816; Indy.
DR VEuPathDB; VectorBase:FBgn0036816; -.
DR eggNOG; KOG1281; Eukaryota.
DR GeneTree; ENSGT01030000234550; -.
DR InParanoid; Q9VVT2; -.
DR PhylomeDB; Q9VVT2; -.
DR Reactome; R-DME-433137; Sodium-coupled sulphate, di- and tri-carboxylate transporters.
DR SignaLink; Q9VVT2; -.
DR BioGRID-ORCS; 40049; 0 hits in 3 CRISPR screens.
DR ChiTaRS; Indy; fly.
DR GenomeRNAi; 40049; -.
DR PRO; PR:Q9VVT2; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0036816; Expressed in crop (Drosophila) and 34 other tissues.
DR ExpressionAtlas; Q9VVT2; baseline and differential.
DR Genevisible; Q9VVT2; DM.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:FlyBase.
DR GO; GO:0015137; F:citrate transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0050833; F:pyruvate transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015141; F:succinate transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0098656; P:anion transmembrane transport; IBA:GO_Central.
DR GO; GO:0015746; P:citrate transport; IDA:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IDA:FlyBase.
DR GO; GO:0006848; P:pyruvate transport; IDA:UniProtKB.
DR GO; GO:0010889; P:regulation of sequestering of triglyceride; IDA:FlyBase.
DR GO; GO:0015744; P:succinate transport; IDA:UniProtKB.
DR InterPro; IPR031312; Na/sul_symport_CS.
DR InterPro; IPR001898; SLC13A/DASS.
DR Pfam; PF00939; Na_sulph_symp; 1.
DR PROSITE; PS01271; NA_SULFATE; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..590
FT /note="Protein I'm not dead yet"
FT /id="PRO_0000172499"
FT TRANSMEM 43..63
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 82..102
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 115..135
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 153..173
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 224..244
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 270..290
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 329..349
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 373..393
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 457..477
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 509..529
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 540..560
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..18
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000305"
FT /id="VSP_029170"
SQ SEQUENCE 590 AA; 65585 MW; ECA7857BB6B34414 CRC64;
MATETTKMIY TPPPLDIKME IEIGEQPQPP VKCSNFFANH WKGLVVFLVP LLCLPVMLLN
EGAEFRCMYL LLVMAIFWVT EALPLYVTSM IPIVAFPIMG IMSSDQTCRL YFKDTLVMFM
GGIMVALAVE YCNLHKRLAL RVIQIVGCSP RRLHFGLIMV TMFLSMWISN AACTAMMCPI
IQAVLEELQA QGVCKINHEP QYQIVGGNKK NNEDEPPYPT KITLCYYLGI AYASSLGGCG
TIIGTATNLT FKGIYEARFK NSTEQMDFPT FMFYSVPSML VYTLLTFVFL QWHFMGLWRP
KSKEAQEVQR GREGADVAKK VIDQRYKDLG PMSIHEIQVM ILFIFMVVMY FTRKPGIFLG
WADLLNSKDI RNSMPTIFVV VMCFMLPANY AFLRYCTRRG GPVPTGPTPS LITWKFIQTK
VPWGLVFLLG GGFALAEGSK QSGMAKLIGN ALIGLKVLPN SVLLLVVILV AVFLTAFSSN
VAIANIIIPV LAEMSLAIEI HPLYLILPAG LACSMAFHLP VSTPPNALVA GYANIRTKDM
AIAGIGPTII TIITLFVFCQ TWGLVVYPNL NSFPEWAQIY AAAALGNKTH
