MDR65_DROME
ID MDR65_DROME Reviewed; 1302 AA.
AC Q00748; Q9VRW3;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2001, sequence version 2.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Multidrug resistance protein homolog 65;
DE EC=7.6.2.2;
DE AltName: Full=P-glycoprotein 65;
GN Name=Mdr65; ORFNames=CG10181;
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].
RC TISSUE=Head;
RX PubMed=2072901; DOI=10.1128/mcb.11.8.3940-3948.1991;
RA Wu C.-T., Budding M., Griffin M.S., Croop J.M.;
RT "Isolation and characterization of Drosophila multidrug resistance gene
RT homologs.";
RL Mol. Cell. Biol. 11:3940-3948(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=WSIII25, and WSIII27;
RX PubMed=11012721; DOI=10.1046/j.1365-2540.2000.00729.x;
RA Begun D.J., Whitley P.;
RT "Genetics of alpha-amanitin resistance in a natural population of
RT Drosophila melanogaster.";
RL Heredity 85:184-190(2000).
RN [3]
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 [4]
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 [5]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-103, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Oregon-R; TISSUE=Head;
RX PubMed=17893096; DOI=10.1093/glycob/cwm097;
RA Koles K., Lim J.-M., Aoki K., Porterfield M., Tiemeyer M., Wells L.,
RA Panin V.;
RT "Identification of N-glycosylated proteins from the central nervous system
RT of Drosophila melanogaster.";
RL Glycobiology 17:1388-1403(2007).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + xenobioticSide 1 = ADP + phosphate +
CC xenobioticSide 2.; EC=7.6.2.2;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCB family.
CC Multidrug resistance exporter (TC 3.A.1.201) subfamily. {ECO:0000305}.
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DR EMBL; M59077; AAA28680.1; -; mRNA.
DR EMBL; AF251287; AAF69147.1; -; Genomic_DNA.
DR EMBL; AF251286; AAF69146.1; -; Genomic_DNA.
DR EMBL; AE014296; AAF50669.1; -; Genomic_DNA.
DR PIR; B41249; B41249.
DR RefSeq; NP_476831.1; NM_057483.4.
DR AlphaFoldDB; Q00748; -.
DR SMR; Q00748; -.
DR BioGRID; 64179; 11.
DR DIP; DIP-17575N; -.
DR IntAct; Q00748; 2.
DR STRING; 7227.FBpp0076719; -.
DR TCDB; 3.A.1.201.31; the atp-binding cassette (abc) superfamily.
DR GlyGen; Q00748; 1 site.
DR iPTMnet; Q00748; -.
DR PaxDb; Q00748; -.
DR PRIDE; Q00748; -.
DR EnsemblMetazoa; FBtr0077011; FBpp0076719; FBgn0004513.
DR GeneID; 38726; -.
DR KEGG; dme:Dmel_CG10181; -.
DR CTD; 38726; -.
DR FlyBase; FBgn0004513; Mdr65.
DR VEuPathDB; VectorBase:FBgn0004513; -.
DR eggNOG; KOG0055; Eukaryota.
DR HOGENOM; CLU_000604_17_2_1; -.
DR InParanoid; Q00748; -.
DR OMA; ENIKQSW; -.
DR OrthoDB; 186078at2759; -.
DR PhylomeDB; Q00748; -.
DR Reactome; R-DME-1369007; Mitochondrial ABC transporters.
DR BioGRID-ORCS; 38726; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 38726; -.
DR PRO; PR:Q00748; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0004513; Expressed in oviduct (Drosophila) and 22 other tissues.
DR ExpressionAtlas; Q00748; baseline and differential.
DR Genevisible; Q00748; DM.
DR GO; GO:0043190; C:ATP-binding cassette (ABC) transporter complex; IDA:FlyBase.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005919; C:pleated septate junction; IDA:FlyBase.
DR GO; GO:0008559; F:ABC-type xenobiotic transporter activity; IDA:FlyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015562; F:efflux transmembrane transporter activity; IDA:FlyBase.
DR GO; GO:0060857; P:establishment of glial blood-brain barrier; IDA:FlyBase.
DR GO; GO:0097254; P:renal tubular secretion; IEP:FlyBase.
DR GO; GO:0017085; P:response to insecticide; IMP:FlyBase.
DR GO; GO:0009636; P:response to toxic substance; IEP:FlyBase.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR GO; GO:0042908; P:xenobiotic transport; IDA:FlyBase.
DR Gene3D; 1.20.1560.10; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR036640; ABC1_TM_sf.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR039421; Type_1_exporter.
DR PANTHER; PTHR24221; PTHR24221; 1.
DR Pfam; PF00664; ABC_membrane; 2.
DR Pfam; PF00005; ABC_tran; 2.
DR SMART; SM00382; AAA; 2.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF90123; SSF90123; 2.
DR PROSITE; PS50929; ABC_TM1F; 2.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 2.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
PE 1: Evidence at protein level;
KW ATP-binding; Glycoprotein; Membrane; Nucleotide-binding;
KW Reference proteome; Repeat; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1302
FT /note="Multidrug resistance protein homolog 65"
FT /id="PRO_0000093348"
FT TOPO_DOM 1..48
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 49..69
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 70..118
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 119..147
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 148..194
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 195..215
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 216..223
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 224..242
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 243..302
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 303..323
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 324..341
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 342..362
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 363..731
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 732..753
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 754..776
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 777..798
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 799..852
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 853..873
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 874
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 875..894
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 895..956
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 957..977
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 978..993
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 994..1014
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1015..1302
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 48..369
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 405..641
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 732..1020
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1059..1298
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 440..447
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 1094..1101
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17893096"
FT CONFLICT 369
FT /note="T -> S (in Ref. 1; AAA28680)"
FT /evidence="ECO:0000305"
FT CONFLICT 678
FT /note="F -> L (in Ref. 1; AAA28680)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1302 AA; 143784 MW; 39A7BCABFA31924A CRC64;
MERDEVSTSS SEGKSQEEAP MAEGLEPTEP IAFLKLFRFS TYGEIGWLFF GFIMCCIKAL
TLPAVVIIYS EFTSMLVDRA MQFGTSSNVH ALPLFGGGKT LTNASREENN EALYDDSISY
GILLTIASVV MFISGIFSVD VFNMVALRQV TRMRIKLFSS VIRQDIGWHD LASKQNFTQS
MVDDVEKIRD GISEKVGHFV YLVVGFIITV AISFSYGWKL TLAVSSYIPL VILLNYYVAK
FQGKLTAREQ ESYAGAGNLA EEILSSIRTV VSFGGEKSEV QRYENFLVPA RKASQWKGAF
SGLSDAVLKS MLYLSCAGAF WYGVNLIIDD RNVENKEYTP AILMIAFFGI IVGADNIART
APFLESFATA RGCATNLFKV IDLTSKIDPL STDGKLLNYG LRGDVEFQDV FFRYPSRPEV
IVHRGLNIRI RAGQTVALVG SSGCGKSTCV QLLQRFYDPV FGSVLLDDLD IRKYNIQWLR
SNIAVVGQEP VLFLGTIAQN ISYGKPGATQ KEIEAAATQA GAHEFITNLP ESYRSMIGER
GSQLSGGQKQ RIAIARALIQ NPKILLLDEA TSALDYQSEK QVQQALDLAS KGRTTIVVSH
RLSAIRGADK IVFIHDGKVL EEGSHDDLMA LEGAYYNMVR AGDINMPDEV EKEDSIEDTK
QKSLALFEKS FETSPLNFEK GQKNSVQFEE PIIKALIKDT NAQSAEAPPE KPNFFRTFSR
ILQLAKQEWC YLILGTISAV AVGFLYPAFA VIFGEFYAAL AEKDPEDALR RTAVLSWACL
GLAFLTGLVC FLQTYLFNYA GIWLTTRMRA MTFNAMVNQE VGWFDDENNS VGALSARLSG
EAVDIQGAIG YPLSGMIQAL SNFISSVSVA MYYNWKLALL CLANCPIIVG SVILEAKMMS
NAVVREKQVI EEACRIATES ITNIRTVAGL RREADVIREY TEEIQRVEVL IRQKLRWRGV
LNSTMQASAF FAYAVALCYG GVLVSEGQLP FQDIIKVSET LLYGSMMLAQ SLAFTPAFSA
ALIAGHRLFQ ILDRKPKIQS PMGTIKNTLA KQLNLFEGVR YRGIQFRYPT RPDAKILNGL
DLEVLKGQTV ALVGHSGCGK STCVQLLQRY YDPDEGTIHI DHDDIQHDLT LDGVRTKLGI
VSQEPTLFER SIAENIAYGD NRRSVSMVEI IAAAKSANAH SFIISLPNGY DTRMGARGTQ
LSGGQKQRIA IARALVRNPK ILLLDEATSA LDLQSEQLVQ QALDTACSGR TCIVIAHRLS
TVQNADVICV IQNGQVVEQG NHMQLISQGG IYAKLHKTQK DH
