PATH_DROME
ID PATH_DROME Reviewed; 471 AA.
AC Q9VT04;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Proton-coupled amino acid transporter-like protein pathetic {ECO:0000305};
GN Name=path {ECO:0000312|FlyBase:FBgn0036007};
GN ORFNames=CG3424 {ECO:0000312|FlyBase:FBgn0036007};
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:AAL48140.1, ECO:0000312|EMBL:AAL48159.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL48140.1, ECO:0000312|EMBL:AAL48159.1};
RC TISSUE=Head {ECO:0000312|EMBL:AAL48140.1, ECO:0000312|EMBL:AAL48159.1};
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 [4] {ECO:0000312|EMBL:ACS54291.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:ACS54291.1};
RA Carlson J., Booth B., Frise E., Sandler J., Wan K., Yu C., Celniker S.;
RL Submitted (JUN-2009) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15843412; DOI=10.1242/dev.01821;
RA Goberdhan D.C., Meredith D., Boyd C.A., Wilson C.;
RT "PAT-related amino acid transporters regulate growth via a novel mechanism
RT that does not require bulk transport of amino acids.";
RL Development 132:2365-2375(2005).
RN [6] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22574197; DOI=10.1371/journal.pone.0036616;
RA Oegmundsdottir M.H., Heublein S., Kazi S., Reynolds B., Visvalingam S.M.,
RA Shaw M.K., Goberdhan D.C.;
RT "Proton-assisted amino acid transporter PAT1 complexes with Rag GTPases and
RT activates TORC1 on late endosomal and lysosomal membranes.";
RL PLoS ONE 7:E36616-E36616(2012).
RN [7] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=26735916; DOI=10.1080/19336934.2015.1129089;
RA Lin W.Y., Williams C.R., Yan C., Parrish J.Z.;
RT "Functions of the SLC36 transporter Pathetic in growth control.";
RL Fly 9:99-106(2015).
RN [8] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=26063572; DOI=10.1101/gad.259119.115;
RA Lin W.Y., Williams C., Yan C., Koledachkina T., Luedke K., Dalton J.,
RA Bloomsburg S., Morrison N., Duncan K.E., Kim C.C., Parrish J.Z.;
RT "The SLC36 transporter Pathetic is required for extreme dendrite growth in
RT Drosophila sensory neurons.";
RL Genes Dev. 29:1120-1135(2015).
CC -!- FUNCTION: Amino acid transporter which has pH-dependent electrogenic
CC transport activity for alanine and glycine but not for proline
CC (PubMed:15843412). Plays a role in positive regulation of growth by
CC directly or indirectly modulating the effects of the TOR signaling
CC pathway (PubMed:15843412, PubMed:22574197). Required in a cell-
CC autonomous manner for dendrite growth in neurons with large dendrite
CC arbors (PubMed:26735916, PubMed:26063572).
CC {ECO:0000269|PubMed:15843412, ECO:0000269|PubMed:22574197,
CC ECO:0000269|PubMed:26063572, ECO:0000269|PubMed:26735916}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22574197,
CC ECO:0000269|PubMed:26063572}; Multi-pass membrane protein
CC {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:22574197}; Multi-
CC pass membrane protein {ECO:0000255}. Late endosome membrane
CC {ECO:0000269|PubMed:22574197}; Multi-pass membrane protein
CC {ECO:0000255}. Cell projection, axon {ECO:0000269|PubMed:26063572}.
CC Cell projection, dendrite {ECO:0000269|PubMed:26063572}. Perikaryon
CC {ECO:0000269|PubMed:26063572}. Cytoplasm {ECO:0000269|PubMed:22574197}.
CC Note=Localizes to endolysosomes in class IV da neurons.
CC {ECO:0000269|PubMed:26063572}.
CC -!- TISSUE SPECIFICITY: In third instar larvae, expressed at highest levels
CC in the brain and digestive system with particularly high levels in
CC surface glia of the brain (at protein level) (PubMed:26735916). In
CC third instar larvae, expressed in all cells of the body wall (at
CC protein level) (PubMed:26063572). Within the body wall of third instar
CC larvae, most highly expressed in epithelial cells and sensory neurons
CC (PubMed:26735916). Expressed at a similar level in all da neurons (at
CC protein level). Widely expressed during embryonic and late larval
CC stages. Levels are highly dynamic in embryogenesis with surges of
CC expression in many structures, including muscle primordia, salivary
CC glands, proventriculus, trachea and gonads. Expressed in all or most
CC cells of larval imaginal disks. Expression is also particularly strong
CC in the pouch and hinge regions of the wing disk and in the
CC morphogenetic furrow of the eye disk (PubMed:15843412).
CC {ECO:0000269|PubMed:15843412, ECO:0000269|PubMed:26063572,
CC ECO:0000269|PubMed:26735916}.
CC -!- DISRUPTION PHENOTYPE: Severe dendrite growth defects in class IV da
CC neurons which normally have large dendrite arbors, moderate defects in
CC class III neurons which normally have medium-sized dendrite arbors and
CC no effect in class I or III neurons which normally have small dendrite
CC arbors (PubMed:26063572). Induction of starvation response and altered
CC protein homeostasis in class III and IV neurons (PubMed:26063572).
CC Severe defects in axon growth with mutants showing no defects 48 hours
CC after egg laying (AEL) but severe defects apparent by 120 hours AEL
CC (PubMed:26735916). {ECO:0000269|PubMed:26063572,
CC ECO:0000269|PubMed:26735916}.
CC -!- SIMILARITY: Belongs to the amino acid/polyamine transporter 2 family.
CC {ECO:0000305}.
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DR EMBL; AE014296; AAF50252.1; -; Genomic_DNA.
DR EMBL; AE014296; AGB94329.1; -; Genomic_DNA.
DR EMBL; AY070669; AAL48140.1; -; mRNA.
DR EMBL; AY070688; AAL48159.1; -; mRNA.
DR EMBL; BT088839; ACS54291.1; -; mRNA.
DR RefSeq; NP_001261634.1; NM_001274705.1.
DR RefSeq; NP_648327.1; NM_140070.3.
DR AlphaFoldDB; Q9VT04; -.
DR IntAct; Q9VT04; 54.
DR STRING; 7227.FBpp0076156; -.
DR TCDB; 2.A.18.8.3; the amino acid/auxin permease (aaap) family.
DR GlyGen; Q9VT04; 1 site.
DR PaxDb; Q9VT04; -.
DR PRIDE; Q9VT04; -.
DR DNASU; 39106; -.
DR EnsemblMetazoa; FBtr0076427; FBpp0076156; FBgn0036007.
DR EnsemblMetazoa; FBtr0333864; FBpp0305997; FBgn0036007.
DR GeneID; 39106; -.
DR KEGG; dme:Dmel_CG3424; -.
DR UCSC; CG3424-RA; d. melanogaster.
DR CTD; 39106; -.
DR FlyBase; FBgn0036007; path.
DR VEuPathDB; VectorBase:FBgn0036007; -.
DR eggNOG; KOG1304; Eukaryota.
DR OrthoDB; 464614at2759; -.
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; 39106; 1 hit in 3 CRISPR screens.
DR ChiTaRS; path; fly.
DR GenomeRNAi; 39106; -.
DR PRO; PR:Q9VT04; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0036007; Expressed in adult Malpighian tubule (Drosophila) and 72 other tissues.
DR ExpressionAtlas; Q9VT04; baseline and differential.
DR GO; GO:0030424; C:axon; IDA:FlyBase.
DR GO; GO:0030425; C:dendrite; IDA:FlyBase.
DR GO; GO:0036019; C:endolysosome; IDA:FlyBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; IDA:FlyBase.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:FlyBase.
DR GO; GO:0015171; F:amino acid transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015179; F:L-amino acid transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0003333; P:amino acid transmembrane transport; IDA:UniProtKB.
DR GO; GO:0097484; P:dendrite extension; IMP:FlyBase.
DR GO; GO:0048813; P:dendrite morphogenesis; IMP:FlyBase.
DR GO; GO:0032536; P:regulation of cell projection size; IMP:UniProtKB.
DR GO; GO:0040008; P:regulation of growth; IMP:FlyBase.
DR InterPro; IPR013057; AA_transpt_TM.
DR Pfam; PF01490; Aa_trans; 1.
PE 1: Evidence at protein level;
KW Amino-acid transport; Cell membrane; Cell projection; Cytoplasm; Endosome;
KW Glycoprotein; Growth regulation; Lysosome; Membrane; Neurogenesis;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..471
FT /note="Proton-coupled amino acid transporter-like protein
FT pathetic"
FT /id="PRO_0000436782"
FT TRANSMEM 81..101
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 153..173
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 187..207
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 216..236
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 253..273
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 283..303
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 337..357
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 375..395
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 397..417
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 432..452
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 61
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 471 AA; 52056 MW; 223214E48077DFE3 CRC64;
MVNIVDSGSK HAPQEMEQFL PGEGKVMYKI QPRKSDTEQA LAGNDFDPFA LRDNPHPTTD
NETLTHLLKA SLGTGILGMP FAFMCSGLIM GIFSTIFTAF ICTHCSYVLV KCGHKLYYRT
RRTKMTFAEI AEAAFQKGPK WCRGFAPVAK FSILFGLFLT YFGTCSVYTV IVASNFEQLI
SYWTGTAVSL RMLICIMLVP LILIAWVPNL KYLAPVSMVA NVFMGLGLGI TFYYLVQDLP
PVEERESVVW STLPQFFSIT IFAMEAIGVV MPLENNMKTP QSFLGICGVL SQGMSGVTLI
YMLLGFLGYL RYGSATGESI TLNLPIEEWP AQTVKVLISL AVYCTFGLQF FVCLEIIWDG
IKEKCKKRPT LVNYVLRTVL VTAAVVLAVA VPTIGPFMGL IGAFCFSILG LIFPVVIELI
VHWESGFGKY NWILWKNAII TLCGIGALVF GTQAAIKDIV KAYSNNENVG E
