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POLYP_DROME
ID   POLYP_DROME             Reviewed;         460 AA.
AC   Q4V5R4; A0A0B4LG39;
DT   12-APR-2017, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2006, sequence version 1.
DT   03-AUG-2022, entry version 122.
DE   RecName: Full=Glutamate transporter polyphemus {ECO:0000303|PubMed:24210616};
GN   Name=polyph {ECO:0000303|PubMed:24210616, ECO:0000312|FlyBase:FBgn0033572};
GN   ORFNames=CG12943 {ECO:0000312|FlyBase:FBgn0033572};
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|Proteomes:UP000000803};
RN   [1] {ECO:0000312|Proteomes:UP000000803}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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] {ECO:0000312|Proteomes:UP000000803}
RP   GENOME REANNOTATION.
RC   STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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] {ECO:0000312|EMBL:AAY55008.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley {ECO:0000312|EMBL:AAY55008.1};
RA   Stapleton M., Carlson J., Chavez C., Frise E., George R., Pacleb J.,
RA   Park S., Wan K., Yu C., Celniker S.;
RL   Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4] {ECO:0000305}
RP   FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=24210616; DOI=10.1016/j.cub.2013.09.061;
RA   Gonzalez E.A., Garg A., Tang J., Nazario-Toole A.E., Wu L.P.;
RT   "A glutamate-dependent redox system in blood cells is integral for
RT   phagocytosis in Drosophila melanogaster.";
RL   Curr. Biol. 23:2319-2324(2013).
CC   -!- FUNCTION: Probable glutamate transporter which transports extracellular
CC       glutamate into the cells. Regulates the production of intracellular
CC       reactive oxygen species (ROS) probably by controlling the synthesis of
CC       antioxidant glutathione. By regulating ROS production in blood cells,
CC       required for maintaining bacteria phagocytosis following infection with
CC       S.aureus and possibly E.coli. {ECO:0000269|PubMed:24210616}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24210616};
CC       Multi-pass membrane protein {ECO:0000255}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=A {ECO:0000312|FlyBase:FBgn0033572};
CC         IsoId=Q4V5R4-1; Sequence=Displayed;
CC       Name=C {ECO:0000312|FlyBase:FBgn0033572};
CC         IsoId=Q4V5R4-2; Sequence=VSP_058852, VSP_058853;
CC   -!- DEVELOPMENTAL STAGE: Expressed in the hemolymph of larvae and adults.
CC       {ECO:0000269|PubMed:24210616}.
CC   -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in adult blood cells
CC       results in decreased survival following infection with S.aureus. Adults
CC       infected with S.aureus display decreased phagocytosis, increased
CC       bacterial load and increased production of reactive oxygen species
CC       (ROS) in the hemolymph. Phagocytosis of latex beads is normal, however
CC       flies pre-injected with S.aureus display a significant decrease in
CC       subsequent bead phagocytosis. Increased survival following infection
CC       with L.monocytogenes. Increased extracellular glutamate in the
CC       hemolymph. No effect on motor functions, adult weight and no increase
CC       in susceptibility to wounding. Induction of the antimicrobial peptides
CC       Drs and DptA in response to S.aureus or E.coli infection is not
CC       affected. {ECO:0000269|PubMed:24210616}.
CC   -!- MISCELLANEOUS: The name 'polyphemus' derives from the Cyclops in Greek
CC       mythology that failed to guard against Odysseus as mutants are unable
CC       to defend against microbial infection. {ECO:0000303|PubMed:24210616}.
CC   -!- SIMILARITY: Belongs to the amino acid/polyamine transporter 2 family.
CC       {ECO:0000305}.
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DR   EMBL; AE013599; AAF58727.1; -; Genomic_DNA.
DR   EMBL; AE013599; AHN56099.1; -; Genomic_DNA.
DR   EMBL; BT022592; AAY55008.1; -; mRNA.
DR   RefSeq; NP_001286301.1; NM_001299372.1. [Q4V5R4-2]
DR   RefSeq; NP_610631.1; NM_136787.2. [Q4V5R4-1]
DR   AlphaFoldDB; Q4V5R4; -.
DR   SMR; Q4V5R4; -.
DR   STRING; 7227.FBpp0087294; -.
DR   PaxDb; Q4V5R4; -.
DR   DNASU; 36161; -.
DR   EnsemblMetazoa; FBtr0088198; FBpp0087294; FBgn0033572. [Q4V5R4-1]
DR   EnsemblMetazoa; FBtr0339474; FBpp0308557; FBgn0033572. [Q4V5R4-2]
DR   GeneID; 36161; -.
DR   KEGG; dme:Dmel_CG12943; -.
DR   UCSC; CG12943-RA; d. melanogaster. [Q4V5R4-1]
DR   CTD; 36161; -.
DR   FlyBase; FBgn0033572; polyph.
DR   VEuPathDB; VectorBase:FBgn0033572; -.
DR   eggNOG; KOG1304; Eukaryota.
DR   GeneTree; ENSGT00940000167965; -.
DR   HOGENOM; CLU_009646_0_1_1; -.
DR   InParanoid; Q4V5R4; -.
DR   OMA; YIYNPYE; -.
DR   PhylomeDB; Q4V5R4; -.
DR   Reactome; R-DME-352230; Amino acid transport across the plasma membrane.
DR   Reactome; R-DME-428559; Proton-coupled neutral amino acid transporters.
DR   Reactome; R-DME-71240; Tryptophan catabolism.
DR   BioGRID-ORCS; 36161; 0 hits in 3 CRISPR screens.
DR   GenomeRNAi; 36161; -.
DR   PRO; PR:Q4V5R4; -.
DR   Proteomes; UP000000803; Chromosome 2R.
DR   Bgee; FBgn0033572; Expressed in testis and 7 other tissues.
DR   ExpressionAtlas; Q4V5R4; baseline and differential.
DR   GO; GO:0005615; C:extracellular space; HDA:FlyBase.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0015171; F:amino acid transmembrane transporter activity; ISS:FlyBase.
DR   GO; GO:0015179; F:L-amino acid transmembrane transporter activity; IBA:GO_Central.
DR   GO; GO:0003333; P:amino acid transmembrane transport; ISS:FlyBase.
DR   GO; GO:0042742; P:defense response to bacterium; IMP:FlyBase.
DR   GO; GO:0006909; P:phagocytosis; IMP:FlyBase.
DR   GO; GO:0019953; P:sexual reproduction; HEP:FlyBase.
DR   InterPro; IPR013057; AA_transpt_TM.
DR   Pfam; PF01490; Aa_trans; 1.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Amino-acid transport; Cell membrane; Membrane;
KW   Phagocytosis; Reference proteome; Transmembrane; Transmembrane helix;
KW   Transport.
FT   CHAIN           1..460
FT                   /note="Glutamate transporter polyphemus"
FT                   /id="PRO_0000439490"
FT   TRANSMEM        51..71
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        78..98
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        139..159
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        181..201
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        203..223
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        241..261
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        275..295
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        324..344
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        368..388
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        390..410
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        428..448
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         98..100
FT                   /note="IAD -> VYS (in isoform C)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_058852"
FT   VAR_SEQ         101..460
FT                   /note="Missing (in isoform C)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_058853"
SQ   SEQUENCE   460 AA;  52035 MW;  0B088DD47C0F4A97 CRC64;
     MEPKSQDQAP NRDDPDLQTE PLTIAQSITS FYMYNPYEKR SVEVPLTNCD AFISLLKCVI
     GTGILAMPLA FRCSGFVMGT VMSILLMILL TYSIHLLIAD MTECCRRRRV PQVSMPEAVR
     IAYEEGPKWI NCFGRAAGFM TTCVLVFGQF LLCTVYLVFV SKNFKEIGDH YIERYNERYY
     VLVACLLLLP LFMIRRLKYL VPLNLISNFL LYAGFALIMY YLFNGLPNIN DREMVTPPVE
     WIEFIAIAAF SLTAVGSMLV VEAHMAHPQS YLGLFGVLNL AVLFILLSNM FFGIIGYWRF
     GDNVHASITL NIPQDEILSQ FIKVFIASGI FLSYPLNGFV VITVMFSDYE NSEPRGRYRT
     LIEYVVRLLF LFLTGAVAIG VPNLAALTEL EGAFSLSNLN LLCPALIDVF LNYNVGYGRL
     MWKLIRDILL ILIGLIFGIV GCTVALMQLI RDFQLTLNSM
 
 
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