ID   MFSD8_MOUSE             Reviewed;         519 AA.
AC   Q8BH31; Q91VS1; Q9CZ06;
DT   13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   24-JAN-2024, entry version 136.
DE   RecName: Full=Major facilitator superfamily domain-containing protein 8;
GN   Name=Mfsd8 {ECO:0000250|UniProtKB:Q8NHS3,
GN   ECO:0000312|MGI:MGI:1919425};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Medulla oblongata, and Testis;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-519.
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   FUNCTION, TRANSPORTER ACTIVITY, AND DISRUPTION PHENOTYPE.
RX   PubMed=34910516; DOI=10.1126/sciadv.abj9608;
RA   Wang Y., Zeng W., Lin B., Yao Y., Li C., Hu W., Wu H., Huang J., Zhang M.,
RA   Xue T., Ren D., Qu L., Cang C.;
RT   "CLN7 is an organellar chloride channel regulating lysosomal function.";
RL   Sci. Adv. 7:eabj9608-eabj9608(2021).
CC   -!- FUNCTION: Outward-rectifying chloride channel involved in endolysosomal
CC       chloride homeostasis, membrane fusion and function. Conducts chloride
CC       currents up to hundreds of picoamperes. Regulates lysosomal calcium
CC       content by reducing the lysosomal membrane potential, thereby
CC       activating TRPML1 channel and further release of lysosomal calcium
CC       ions. Regulates the pH in endolysosomal compartments and may contribute
CC       to progressive acidification from endosome to lysosome. Permeable to
CC       other halides such as iodide and fluoride ions.
CC       {ECO:0000250|UniProtKB:Q8NHS3, ECO:0000269|PubMed:34910516}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=chloride(in) = chloride(out); Xref=Rhea:RHEA:29823,
CC         ChEBI:CHEBI:17996; Evidence={ECO:0000269|PubMed:34910516};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:29825;
CC         Evidence={ECO:0000305|PubMed:34910516};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=iodide(out) = iodide(in); Xref=Rhea:RHEA:66324,
CC         ChEBI:CHEBI:16382; Evidence={ECO:0000250|UniProtKB:Q8NHS3};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66325;
CC         Evidence={ECO:0000250|UniProtKB:Q8NHS3};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=fluoride(in) = fluoride(out); Xref=Rhea:RHEA:76159,
CC         ChEBI:CHEBI:17051; Evidence={ECO:0000250|UniProtKB:Q8NHS3};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:76161;
CC         Evidence={ECO:0000250|UniProtKB:Q8NHS3};
CC   -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000250|UniProtKB:Q8NHS3};
CC       Multi-pass membrane protein {ECO:0000255}. Lysosome membrane
CC       {ECO:0000250|UniProtKB:Q8NHS3}; Multi-pass membrane protein
CC       {ECO:0000255}. Note=Sorting to lysosomes involves dileucine-based
CC       motif. {ECO:0000250|UniProtKB:Q8NHS3}.
CC   -!- DISRUPTION PHENOTYPE: Retinal degeneration associated with blindness.
CC       {ECO:0000269|PubMed:34910516}.
CC   -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC       {ECO:0000305}.
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DR   EMBL; AK013144; BAB28676.1; -; mRNA.
DR   EMBL; AK032080; BAC27687.1; -; mRNA.
DR   EMBL; AK077957; BAC37083.1; -; mRNA.
DR   EMBL; BC010483; AAH10483.1; -; mRNA.
DR   EMBL; BC113183; AAI13184.1; -; mRNA.
DR   EMBL; BC113790; AAI13791.1; -; mRNA.
DR   CCDS; CCDS17329.1; -.
DR   RefSeq; NP_082416.2; NM_028140.4.
DR   AlphaFoldDB; Q8BH31; -.
DR   SMR; Q8BH31; -.
DR   STRING; 10090.ENSMUSP00000026859; -.
DR   GlyCosmos; Q8BH31; 2 sites, No reported glycans.
DR   GlyGen; Q8BH31; 2 sites.
DR   iPTMnet; Q8BH31; -.
DR   PhosphoSitePlus; Q8BH31; -.
DR   EPD; Q8BH31; -.
DR   MaxQB; Q8BH31; -.
DR   PaxDb; 10090-ENSMUSP00000026859; -.
DR   ProteomicsDB; 292315; -.
DR   Antibodypedia; 45354; 79 antibodies from 21 providers.
DR   DNASU; 72175; -.
DR   Ensembl; ENSMUST00000026859.11; ENSMUSP00000026859.6; ENSMUSG00000025759.12.
DR   GeneID; 72175; -.
DR   KEGG; mmu:72175; -.
DR   UCSC; uc008pbp.1; mouse.
DR   AGR; MGI:1919425; -.
DR   CTD; 256471; -.
DR   MGI; MGI:1919425; Mfsd8.
DR   VEuPathDB; HostDB:ENSMUSG00000025759; -.
DR   eggNOG; KOG2325; Eukaryota.
DR   GeneTree; ENSGT00530000063854; -.
DR   HOGENOM; CLU_027024_2_0_1; -.
DR   InParanoid; Q8BH31; -.
DR   OMA; DQFAWSK; -.
DR   OrthoDB; 6977at2759; -.
DR   PhylomeDB; Q8BH31; -.
DR   TreeFam; TF316590; -.
DR   BioGRID-ORCS; 72175; 3 hits in 78 CRISPR screens.
DR   ChiTaRS; Mfsd8; mouse.
DR   PRO; PR:Q8BH31; -.
DR   Proteomes; UP000000589; Chromosome 3.
DR   RNAct; Q8BH31; Protein.
DR   Bgee; ENSMUSG00000025759; Expressed in white adipose tissue and 66 other cell types or tissues.
DR   ExpressionAtlas; Q8BH31; baseline and differential.
DR   GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR   GO; GO:0010008; C:endosome membrane; ISS:UniProtKB.
DR   GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR   GO; GO:0005764; C:lysosome; IDA:MGI.
DR   GO; GO:0016020; C:membrane; IDA:MGI.
DR   GO; GO:0005254; F:chloride channel activity; IMP:UniProtKB.
DR   GO; GO:0062054; F:fluoride channel activity; ISS:UniProtKB.
DR   GO; GO:0015111; F:iodide transmembrane transporter activity; ISO:MGI.
DR   GO; GO:0097352; P:autophagosome maturation; IMP:MGI.
DR   GO; GO:0007040; P:lysosome organization; IMP:MGI.
DR   GO; GO:0048666; P:neuron development; IMP:MGI.
DR   GO; GO:0010506; P:regulation of autophagy; IMP:MGI.
DR   GO; GO:1905165; P:regulation of lysosomal protein catabolic process; IMP:MGI.
DR   GO; GO:0038202; P:TORC1 signaling; IMP:MGI.
DR   CDD; cd17326; MFS_MFSD8; 1.
DR   Gene3D; 1.20.1250.20; MFS general substrate transporter like domains; 1.
DR   InterPro; IPR011701; MFS.
DR   InterPro; IPR020846; MFS_dom.
DR   InterPro; IPR036259; MFS_trans_sf.
DR   PANTHER; PTHR23510; INNER MEMBRANE TRANSPORT PROTEIN YAJR; 1.
DR   PANTHER; PTHR23510:SF3; MAJOR FACILITATOR SUPERFAMILY DOMAIN-CONTAINING PROTEIN 8; 1.
DR   Pfam; PF07690; MFS_1; 1.
DR   SUPFAM; SSF103473; MFS general substrate transporter; 1.
DR   PROSITE; PS50850; MFS; 1.
DR   Genevisible; Q8BH31; MM.
PE   2: Evidence at transcript level;
KW   Chloride; Chloride channel; Endosome; Glycoprotein; Ion channel;
KW   Ion transport; Lysosome; Membrane; Reference proteome; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..519
FT                   /note="Major facilitator superfamily domain-containing
FT                   protein 8"
FT                   /id="PRO_0000311233"
FT   TOPO_DOM        1..41
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        42..62
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        63..75
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        76..96
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        97..106
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        107..127
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        128..140
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        141..161
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        162..174
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        175..195
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        196..212
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        213..233
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        234..267
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        268..288
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        289..310
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        311..331
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        332..338
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        339..359
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        360..416
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        417..439
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        440..452
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        453..473
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        474..483
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        484..504
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        505..519
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          1..25
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           13..14
FT                   /note="Dileucine internalization motif"
FT                   /evidence="ECO:0000250|UniProtKB:Q8NHS3"
FT   CARBOHYD        372
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        377
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        25
FT                   /note="S -> G (in Ref. 2; AAH10483)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        39
FT                   /note="S -> F (in Ref. 1; BAB28676)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        50
FT                   /note="S -> N (in Ref. 1; BAB28676)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        116
FT                   /note="V -> G (in Ref. 1; BAB28676)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        129
FT                   /note="A -> T (in Ref. 1; BAB28676)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        313
FT                   /note="L -> F (in Ref. 2; AAH10483)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        391
FT                   /note="S -> P (in Ref. 2; AAH10483)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   519 AA;  57569 MW;  552FF574371BE4FE CRC64;
     MANLGSEAER EPLLGPGSPG SREWSEIETQ EHYKSRWKSV RILYLTMFLS SVGFSIVIMS
     IWPYLQKIDQ TADASFLGWV IASYSLGQMV ASPLFGLWSN YRPRKEPLIV SISISVAANC
     LYAYVHVPAA HNKYYMLIAR GLVGFGAGNV AVVRSYIAGA TSLQERTNAM ANTSTCQALG
     FILGPVFQTC FALIGEKGVT WDIIKLQVNM YTAPVLLAAF LGILNIILIL FILREHRVDD
     LGRQCKSVNF QEENTDEPQI PEGSIDQVAV VATNIVFFVV LFIFAVYETI LTPLTLDMYA
     WTQEQAVLYD GILLVAFGVE AVLVFMGVKL LSKKIGERAI LLGGFVVVWV GFFILLPWGN
     QFPKIQWEDL HNSSTPNTTF GEIIIGLWNS SREDHSEQPT GCPIEQTWCL YTPVIHLAQF
     LTAAVLIGTG YPACSVMSYT LYSKVLGPKP QGIYMGWLTT SGSAARILGP VFISHVYTYL
     GPRWAFSLVC GIVVLTILLI GAVYKRLVAF SVRYMRIQE
//