ID BROWN_DROME Reviewed; 675 AA. AC P12428; Q24264; Q7KVI1; Q7KVI2; Q8MRN9; Q9W1N7; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1989, sequence version 1. DT 27-MAR-2024, entry version 182. DE RecName: Full=Protein brown; DE EC=7.6.2.- {ECO:0000305|PubMed:33820991}; DE EC=7.6.2.6 {ECO:0000305|PubMed:117796}; DE AltName: Full=ATP-binding cassette transporter sub-family G member brown {ECO:0000305}; DE AltName: Full=Broad substrate specificity ATP-binding cassette transporter brown {ECO:0000305}; GN Name=bw {ECO:0000312|FlyBase:FBgn0000241}; GN ORFNames=CG17632 {ECO:0000312|FlyBase:FBgn0000241}; 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]. RX PubMed=3149712; DOI=10.1128/mcb.8.12.5206-5215.1988; RA Dreesen T.D., Johnson D.H., Henikoff S.; RT "The brown protein of Drosophila melanogaster is similar to the white RT protein and to components of active transport complexes."; RL Mol. Cell. Biol. 8:5206-5215(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=7956072; DOI=10.1101/sqb.1993.058.01.064; RA Martin-Morris L.E., Loughney K., Kershisnik E.O., Poortinga G., RA Henikoff S.; RT "Characterization of sequences responsible for trans-inactivation of the RT Drosophila brown gene."; RL Cold Spring Harb. Symp. Quant. Biol. 58:577-584(1993). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=IG281; RX PubMed=7753025; DOI=10.1007/bf00705646; RA Nitasaka E., Yamazaki T., Green M.M.; RT "The molecular analysis of brown eye color mutations isolated from RT geographically discrete populations of Drosophila melanogaster."; RL Mol. Gen. Genet. 247:164-168(1995). RN [4] 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 [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-316. RC STRAIN=Berkeley; TISSUE=Head; 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 [7] RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE. RX PubMed=117796; DOI=10.1007/bf00498891; RA Sullivan D.T., Bell L.A., Paton D.R., Sullivan M.C.; RT "Purine transport by malpighian tubules of pteridine-deficient eye color RT mutants of Drosophila melanogaster."; RL Biochem. Genet. 17:565-573(1979). RN [8] RP FUNCTION, SUBUNIT, AND MUTAGENESIS OF GLY-578 AND ASN-638. RX PubMed=8144619; DOI=10.1016/s0021-9258(17)34070-x; RA Ewart G.D., Cannell D., Cox G.B., Howells A.J.; RT "Mutational analysis of the traffic ATPase (ABC) transporters involved in RT uptake of eye pigment precursors in Drosophila melanogaster. Implications RT for structure-function relationships."; RL J. Biol. Chem. 269:10370-10377(1994). RN [9] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=10407069; DOI=10.1016/s0005-2736(99)00064-4; RA Mackenzie S.M., Brooker M.R., Gill T.R., Cox G.B., Howells A.J., RA Ewart G.D.; RT "Mutations in the white gene of Drosophila melanogaster affecting ABC RT transporters that determine eye colouration."; RL Biochim. Biophys. Acta 1419:173-185(1999). RN [10] RP FUNCTION, SUBUNIT, AND DISRUPTION PHENOTYPE. RX PubMed=18931318; DOI=10.1242/jeb.021162; RA Borycz J., Borycz J.A., Kubow A., Lloyd V., Meinertzhagen I.A.; RT "Drosophila ABC transporter mutants white, brown and scarlet have altered RT contents and distribution of biogenic amines in the brain."; RL J. Exp. Biol. 211:3454-3466(2008). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, INDUCTION, AND DISRUPTION PHENOTYPE. RX PubMed=33820991; DOI=10.1038/s42255-021-00375-x; RA Sasaki A., Nishimura T., Takano T., Naito S., Yoo S.K.; RT "white regulates proliferative homeostasis of intestinal stem cells during RT ageing in Drosophila."; RL Nat. Metab. 3:546-557(2021). CC -!- FUNCTION: ATP-dependent transporter of the ATP-binding cassette (ABC) CC family which transports various molecules including bioamines, CC neurotransmitters and metabolic intermediates (PubMed:117796, CC PubMed:8144619, PubMed:10407069, PubMed:18931318, PubMed:33820991). In CC the eye and probably in association with w/white, required for the CC transport of the eye red pigment precursor, guanine, into pigment cell CC granules (PubMed:8144619, PubMed:117796). In Malpighian tubules, CC involved in guanine uptake (PubMed:117796). Probably in association CC with w/white, involved in aging-induced intestinal stem cell CC proliferation in the midgut by regulating tetrahydrofolate transport CC (PubMed:33820991). {ECO:0000269|PubMed:10407069, CC ECO:0000269|PubMed:117796, ECO:0000269|PubMed:18931318, CC ECO:0000269|PubMed:33820991, ECO:0000269|PubMed:8144619}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + guanine(out) + H2O = ADP + guanine(in) + H(+) + CC phosphate; Xref=Rhea:RHEA:20832, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16235, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=7.6.2.6; CC Evidence={ECO:0000305|PubMed:117796}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O + riboflavin(in) = ADP + H(+) + phosphate + CC riboflavin(out); Xref=Rhea:RHEA:61352, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:57986, ChEBI:CHEBI:456216; CC Evidence={ECO:0000305|PubMed:33820991}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(6S)-5,6,7,8-tetrahydrofolate(out) + ATP + H2O = (6S)-5,6,7,8- CC tetrahydrofolate(in) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:68592, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57453, ChEBI:CHEBI:456216; CC Evidence={ECO:0000305|PubMed:33820991}; CC -!- SUBUNIT: May form a heterodimer with w/white. CC {ECO:0000305|PubMed:18931318, ECO:0000305|PubMed:8144619}. CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane CC protein {ECO:0000255}. CC -!- INDUCTION: Up-regulated during aging in intestinal stem cells. CC {ECO:0000269|PubMed:33820991}. CC -!- DISRUPTION PHENOTYPE: Eyes are brown due to a defect in red pigment CC production (PubMed:10407069). In Malpighian tubules, guanine uptake is CC impaired (PubMed:117796). Reduces the levels of several metabolites, CC including kynurenine, kynurenic acid, 3-hydroxykynurenine, guanosine, CC xanthine, urate, riboflavin, and tetrahydrofolate, and increases the CC levels of guanine (PubMed:33820991). In the head, levels of CC neurotransmitters histamine, dopamine and serotonin are reduced; CC specifically, histamine is reduced in the retina (PubMed:18931318). CC Severe loss of white protein in the retina lamina and photoreceptors CC (PubMed:18931318). In addition, in lamina photoreceptor terminals R1- CC R6, number of synaptic vesicles is reduced (PubMed:18931318). Inhibits CC aging-induced intestinal stem cell proliferation (PubMed:33820991). CC {ECO:0000269|PubMed:10407069, ECO:0000269|PubMed:117796, CC ECO:0000269|PubMed:18931318, ECO:0000269|PubMed:33820991}. CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCG family. CC Eye pigment precursor importer (TC 3.A.1.204) subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAM50157.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M20630; AAA28397.1; -; mRNA. DR EMBL; L23543; AAC37214.1; -; Genomic_DNA. DR EMBL; L05635; AAA28398.1; -; Genomic_DNA. DR EMBL; AE013599; AAF47020.3; -; Genomic_DNA. DR EMBL; AY119503; AAM50157.1; ALT_SEQ; mRNA. DR PIR; A31399; FYFFB. DR RefSeq; NP_001286769.1; NM_001299840.1. DR RefSeq; NP_523824.1; NM_079100.3. DR AlphaFoldDB; P12428; -. DR SMR; P12428; -. DR BioGRID; 63324; 38. DR DIP; DIP-387N; -. DR IntAct; P12428; 1. DR STRING; 7227.FBpp0072026; -. DR TCDB; 3.A.1.204.18; the atp-binding cassette (abc) superfamily. DR PaxDb; 7227-FBpp0072026; -. DR DNASU; 37724; -. DR EnsemblMetazoa; FBtr0072117; FBpp0072026; FBgn0000241. DR EnsemblMetazoa; FBtr0346612; FBpp0312192; FBgn0000241. DR GeneID; 37724; -. DR KEGG; dme:Dmel_CG17632; -. DR AGR; FB:FBgn0000241; -. DR CTD; 37724; -. DR FlyBase; FBgn0000241; bw. DR VEuPathDB; VectorBase:FBgn0000241; -. DR eggNOG; KOG0061; Eukaryota. DR HOGENOM; CLU_406887_0_0_1; -. DR InParanoid; P12428; -. DR OMA; HPCVKSG; -. DR OrthoDB; 5354772at2759; -. DR PhylomeDB; P12428; -. DR Reactome; R-DME-1369062; ABC transporters in lipid homeostasis. DR Reactome; R-DME-189451; Heme biosynthesis. DR Reactome; R-DME-189483; Heme degradation. DR Reactome; R-DME-917937; Iron uptake and transport. DR Reactome; R-DME-9753281; Paracetamol ADME. DR Reactome; R-DME-9793528; Ciprofloxacin ADME. DR BioGRID-ORCS; 37724; 0 hits in 1 CRISPR screen. DR GenomeRNAi; 37724; -. DR PRO; PR:P12428; -. DR Proteomes; UP000000803; Chromosome 2R. DR Bgee; FBgn0000241; Expressed in seminal fluid secreting gland and 18 other cell types or tissues. DR ExpressionAtlas; P12428; baseline and differential. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0098793; C:presynapse; IEA:GOC. DR GO; GO:0140359; F:ABC-type transporter activity; IEA:InterPro. DR GO; GO:0005275; F:amine transmembrane transporter activity; IMP:FlyBase. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro. DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; ISS:FlyBase. DR GO; GO:0015208; F:guanine transmembrane transporter activity; IMP:UniProtKB. DR GO; GO:0031409; F:pigment binding; IEA:UniProtKB-KW. DR GO; GO:0015842; P:aminergic neurotransmitter loading into synaptic vesicle; IMP:FlyBase. DR GO; GO:0006856; P:eye pigment precursor transport; TAS:FlyBase. DR GO; GO:0015854; P:guanine transport; IMP:UniProtKB. DR GO; GO:0007605; P:sensory perception of sound; IMP:FlyBase. DR GO; GO:0055085; P:transmembrane transport; IMP:UniProtKB. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR013525; ABC2_TM. DR InterPro; IPR003439; ABC_transporter-like_ATP-bd. DR InterPro; IPR017871; ABC_transporter-like_CS. DR InterPro; IPR043926; ABCG_dom. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR005284; Pigment_permease/Abcg. DR NCBIfam; TIGR00955; 3a01204; 1. DR PANTHER; PTHR48041; ABC TRANSPORTER G FAMILY MEMBER 28; 1. DR PANTHER; PTHR48041:SF116; PROTEIN BROWN; 1. DR Pfam; PF01061; ABC2_membrane; 1. DR Pfam; PF19055; ABC2_membrane_7; 1. DR Pfam; PF00005; ABC_tran; 1. DR SMART; SM00382; AAA; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1. DR PROSITE; PS50893; ABC_TRANSPORTER_2; 1. DR Genevisible; P12428; DM. PE 1: Evidence at protein level; KW ATP-binding; Membrane; Nucleotide-binding; Pigment; Reference proteome; KW Translocase; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..675 FT /note="Protein brown" FT /id="PRO_0000093375" FT TOPO_DOM 1..419 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 420..440 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 441..460 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 461..481 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 482..497 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 498..518 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 519..531 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 532..552 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 553..568 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 569..589 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 590..644 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 645..665 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 666..675 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT DOMAIN 34..261 FT /note="ABC transporter" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434" FT REGION 229..249 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 229..247 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 66..73 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434" FT MUTAGEN 578 FT /note="G->D: In T50; normal eye color. Eyes are brown due FT to a reduction in red pigment production in a w/white co2 FT mutant background." FT /evidence="ECO:0000269|PubMed:8144619" FT MUTAGEN 638 FT /note="N->T: In 6; normal eye color. Eyes are brown due to FT a reduction in red pigment production in a w/white co2 FT mutant background." FT /evidence="ECO:0000269|PubMed:8144619" FT CONFLICT 28 FT /note="D -> A (in Ref. 2; AAC37214, 3; AAA28398 and 6; FT AAM50157)" FT /evidence="ECO:0000305" FT CONFLICT 44 FT /note="R -> P (in Ref. 3; AAA28398)" FT /evidence="ECO:0000305" FT CONFLICT 274 FT /note="L -> I (in Ref. 2; AAC37214 and 3; AAA28398)" FT /evidence="ECO:0000305" FT CONFLICT 331 FT /note="E -> Q (in Ref. 2; AAC37214)" FT /evidence="ECO:0000305" FT CONFLICT 407 FT /note="R -> P (in Ref. 2; AAC37214)" FT /evidence="ECO:0000305" FT CONFLICT 638 FT /note="N -> T (in Ref. 2; AAC37214 and 3; AAA28398)" FT /evidence="ECO:0000305" SQ SEQUENCE 675 AA; 75943 MW; 81DEBDF856F4F174 CRC64; MQESGGSSGQ GGPSLCLEWK QLNYYVPDQE QSNYSFWNEC RKKRELRILQ DASGHMKTGD LIAILGGSGA GKTTLLAAIS QRLRGNLTGD VVLNGMAMER HQMTRISSFL PQFEINVKTF TAYEHLYFMS HFKMHRRTTK AEKRQRVADL LLAVGLRDAA HTRIQQLSGG ERKRLSLAEE LITDPIFLFC DEPTTGLDSF SAYSVIKTLR HLCTRRRIAK HSLNQVYGED SFETPSGESS ASGSGSKSIE MEVVAESHES LLQTMRELPA LGVLSNSPNG THKKAAICSI HQPTSDIFEL FTHIILMDGG RIVYQGRTEQ AAKFFTDLGY ELPLNCNPAD FYLKTLADKE GKENAGAVLR AKYEHETDGL YSGSWLLARS YSGDYLKHVQ NFKKIRWIYQ VYLLMVRFMT EDLRNIRSGL IAFGFFMITA VTLSLMYSGI GGLTQRTVQD VGGSIFMLSN EMIFTFSYGV TYIFPAALPI IRREVGEGTY SLSAYYVALV LSFVPVAFFK GYVFLSVIYA SIYYTRGFLL YLSMGFLMSL SAVAAVGYGV FLSSLFESDK MASECAAPFD LIFLIFGGTY MNVDTVPGLK YLSLFFYSNE ALMYKFWIDI DNIDCPVNED HPCIKTGVEV LQQGSYRNAD YTYWLDCFSL VVVAVIFHIV SFGLVRRYIH RSGYY //