ID MFSD8_HUMAN Reviewed; 518 AA.
AC Q8NHS3; B2RDM1; B7Z205; Q8N2P3;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 24-JAN-2024, entry version 167.
DE RecName: Full=Major facilitator superfamily domain-containing protein 8;
DE AltName: Full=Ceroid-lipofuscinosis neuronal protein 7;
GN Name=MFSD8 {ECO:0000303|PubMed:17564970, ECO:0000312|HGNC:HGNC:28486};
GN Synonyms=CLN7 {ECO:0000303|PubMed:34910516};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP VAL-423.
RC TISSUE=Amygdala, Embryo, and Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [5]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Placenta;
RX PubMed=17897319; DOI=10.1111/j.1600-0854.2007.00643.x;
RA Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H.,
RA Elsaesser H.-P., Mann M., Hasilik A.;
RT "Integral and associated lysosomal membrane proteins.";
RL Traffic 8:1676-1686(2007).
RN [6]
RP GLYCOSYLATION AT ASN-371 AND ASN-376, DILEUCINE MOTIF, AND SUBCELLULAR
RP LOCATION.
RX PubMed=20406422; DOI=10.1111/j.1600-0854.2010.01073.x;
RA Steenhuis P., Herder S., Gelis S., Braulke T., Storch S.;
RT "Lysosomal targeting of the CLN7 membrane glycoprotein and transport via
RT the plasma membrane require a dileucine motif.";
RL Traffic 11:987-1000(2010).
RN [7]
RP FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP TOPOLOGY, DILEUCINE MOTIF, MUTAGENESIS OF LEU-13; LEU-14; ARG-153; GLU-287
RP AND TYR-438, AND CHARACTERIZATION OF VARIANTS CLN7 PRO-157; LYS-294;
RP GLN-336; GLN-465 AND TRP-465.
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).
RN [8]
RP VARIANTS CLN7 ASP-310 AND ASP-429, CHARACTERIZATION OF VARIANTS CLN7
RP ASP-310 AND ASP-429, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17564970; DOI=10.1086/518902;
RA Siintola E., Topcu M., Aula N., Lohi H., Minassian B.A., Paterson A.D.,
RA Liu X.-Q., Wilson C., Lahtinen U., Anttonen A.-K., Lehesjoki A.-E.;
RT "The novel neuronal ceroid lipofuscinosis gene MFSD8 encodes a putative
RT lysosomal transporter.";
RL Am. J. Hum. Genet. 81:136-146(2007).
RN [9]
RP VARIANTS CLN7 HIS-139; PRO-157; LYS-294; ASP-310 AND TRP-465.
RX PubMed=19201763; DOI=10.1093/brain/awn366;
RA Kousi M., Siintola E., Dvorakova L., Vlaskova H., Turnbull J., Topcu M.,
RA Yuksel D., Gokben S., Minassian B.A., Elleder M., Mole S.E.,
RA Lehesjoki A.-E.;
RT "Mutations in CLN7/MFSD8 are a common cause of variant late-infantile
RT neuronal ceroid lipofuscinosis.";
RL Brain 132:810-819(2009).
RN [10]
RP VARIANTS CLN7 ARG-52; LYS-294; ASP-310 AND LEU-447.
RX PubMed=19177532; DOI=10.1002/humu.20975;
RA Aiello C., Terracciano A., Simonati A., Discepoli G., Cannelli N.,
RA Claps D., Crow Y.J., Bianchi M., Kitzmuller C., Longo D., Tavoni A.,
RA Franzoni E., Tessa A., Veneselli E., Boldrini R., Filocamo M.,
RA Williams R.E., Bertini E.S., Biancheri R., Carrozzo R., Mole S.E.,
RA Santorelli F.M.;
RT "Mutations in MFSD8/CLN7 are a frequent cause of variant-late infantile
RT neuronal ceroid lipofuscinosis.";
RL Hum. Mutat. 30:E530-E540(2009).
RN [11]
RP VARIANT CLN7 CYS-121.
RX PubMed=18850119; DOI=10.1007/s10048-008-0153-1;
RA Stogmann E., El Tawil S., Wagenstaller J., Gaber A., Edris S.,
RA Abdelhady A., Assem-Hilger E., Leutmezer F., Bonelli S., Baumgartner C.,
RA Zimprich F., Strom T.M., Zimprich A.;
RT "A novel mutation in the MFSD8 gene in late infantile neuronal ceroid
RT lipofuscinosis.";
RL Neurogenetics 10:73-77(2009).
RN [12]
RP VARIANT CLN7 LEU-412.
RX PubMed=19277732; DOI=10.1007/s10048-009-0185-1;
RA Aldahmesh M.A., Al-Hassnan Z.N., Aldosari M., Alkuraya F.S.;
RT "Neuronal ceroid lipofuscinosis caused by MFSD8 mutations: a common theme
RT emerging.";
RL Neurogenetics 10:307-311(2009).
RN [13]
RP VARIANT CLN7 LYS-294.
RX PubMed=22612257; DOI=10.1111/j.1528-1167.2012.03516.x;
RA Lemke J.R., Riesch E., Scheurenbrand T., Schubach M., Wilhelm C.,
RA Steiner I., Hansen J., Courage C., Gallati S., Buerki S., Strozzi S.,
RA Simonetti B.G., Grunt S., Steinlin M., Alber M., Wolff M., Klopstock T.,
RA Prott E.C., Lorenz R., Spaich C., Rona S., Lakshminarasimhan M., Kroell J.,
RA Dorn T., Kraemer G., Synofzik M., Becker F., Weber Y.G., Lerche H.,
RA Boehm D., Biskup S.;
RT "Targeted next generation sequencing as a diagnostic tool in epileptic
RT disorders.";
RL Epilepsia 53:1387-1398(2012).
RN [14]
RP VARIANTS CLN7 PRO-157; ASN-160; ILE-160; LYS-458; GLN-465 AND VAL-470.
RX PubMed=21990111; DOI=10.1002/humu.21624;
RA Kousi M., Lehesjoki A.E., Mole S.E.;
RT "Update of the mutation spectrum and clinical correlations of over 360
RT mutations in eight genes that underlie the neuronal ceroid
RT lipofuscinoses.";
RL Hum. Mutat. 33:42-63(2012).
RN [15]
RP INVOLVEMENT IN CCMD, AND VARIANT CCMD GLN-336.
RX PubMed=25227500; DOI=10.1016/j.ophtha.2014.07.040;
RA Roosing S., van den Born L.I., Sangermano R., Banfi S., Koenekoop R.K.,
RA Zonneveld-Vrieling M.N., Klaver C.C., van Lith-Verhoeven J.J.,
RA Cremers F.P., den Hollander A.I., Hoyng C.B.;
RT "Mutations in MFSD8, encoding a lysosomal membrane protein, are associated
RT with nonsyndromic autosomal recessive macular dystrophy.";
RL Ophthalmology 122:170-179(2015).
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: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:0000269|PubMed:34910516};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66325;
CC Evidence={ECO:0000305|PubMed:34910516};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=fluoride(in) = fluoride(out); Xref=Rhea:RHEA:76159,
CC ChEBI:CHEBI:17051; Evidence={ECO:0000269|PubMed:34910516};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:76161;
CC Evidence={ECO:0000305|PubMed:34910516};
CC -!- ACTIVITY REGULATION: Inhibited by chloride channel blockers 4,4'-
CC diisothiocyano-2,2'-stilbenedisulfonate (DIDS), niflumic acid (NFA),
CC and 5-Nitro-2-(3-phenylpropylamino) benzoic acid (NPPB).
CC {ECO:0000269|PubMed:34910516}.
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000269|PubMed:34910516};
CC Multi-pass membrane protein {ECO:0000255}. Lysosome membrane
CC {ECO:0000269|PubMed:17564970, ECO:0000269|PubMed:17897319,
CC ECO:0000269|PubMed:20406422, ECO:0000269|PubMed:34910516}; Multi-pass
CC membrane protein {ECO:0000255}. Note=Sorting to lysosomes involves
CC dileucine-based motif.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8NHS3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NHS3-2; Sequence=VSP_057054, VSP_057055, VSP_057056,
CC VSP_057057;
CC -!- TISSUE SPECIFICITY: Expressed at very low levels in all tissues tested.
CC {ECO:0000269|PubMed:17564970}.
CC -!- DISEASE: Ceroid lipofuscinosis, neuronal, 7 (CLN7) [MIM:610951]: A form
CC of neuronal ceroid lipofuscinosis with onset in early childhood.
CC Neuronal ceroid lipofuscinoses are progressive neurodegenerative,
CC lysosomal storage diseases characterized by intracellular accumulation
CC of autofluorescent liposomal material, and clinically by seizures,
CC dementia, visual loss, and/or cerebral atrophy. The lipopigment
CC patterns observed most often in neuronal ceroid lipofuscinosis type 7
CC comprise mixed combinations of granular, curvilinear, fingerprint, and
CC rectilinear profiles. {ECO:0000269|PubMed:17564970,
CC ECO:0000269|PubMed:18850119, ECO:0000269|PubMed:19177532,
CC ECO:0000269|PubMed:19201763, ECO:0000269|PubMed:19277732,
CC ECO:0000269|PubMed:21990111, ECO:0000269|PubMed:22612257,
CC ECO:0000269|PubMed:34910516}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Macular dystrophy with central cone involvement (CCMD)
CC [MIM:616170]: An ocular disease characterized by decreased visual
CC acuity, slight pigmentary changes and color vision abnormalities,
CC becoming apparent in the third to sixth decade of life. Fundus
CC anomalies are variable and include bull's eye maculopathy, severe
CC atrophy of central fovea, relatively spared fovea with surrounding
CC atrophic ring, central retinal pigment epithelium and/or choroid
CC changes, pale or atrophic peripapillary area, pale optic disk,
CC relatively spared periphery, and slightly or moderately attenuated
CC vessels. {ECO:0000269|PubMed:25227500}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NCL CLN7/MFSD8; Note=Neural Ceroid Lipofuscinoses
CC mutation db;
CC URL="https://www.ucl.ac.uk/ncl/cln7.shtml";
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DR EMBL; AK074564; BAC11062.1; -; mRNA.
DR EMBL; AK294184; BAH11691.1; -; mRNA.
DR EMBL; AK315596; BAG37968.1; -; mRNA.
DR EMBL; AC099340; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471056; EAX05195.1; -; Genomic_DNA.
DR EMBL; BC029503; AAH29503.1; -; mRNA.
DR CCDS; CCDS3736.1; -. [Q8NHS3-1]
DR RefSeq; NP_689991.1; NM_152778.2. [Q8NHS3-1]
DR RefSeq; XP_005262950.1; XM_005262893.1.
DR AlphaFoldDB; Q8NHS3; -.
DR SMR; Q8NHS3; -.
DR BioGRID; 129168; 67.
DR IntAct; Q8NHS3; 25.
DR STRING; 9606.ENSP00000493218; -.
DR TCDB; 2.A.1.2.56; the major facilitator superfamily (mfs).
DR GlyCosmos; Q8NHS3; 2 sites, No reported glycans.
DR GlyGen; Q8NHS3; 2 sites.
DR iPTMnet; Q8NHS3; -.
DR PhosphoSitePlus; Q8NHS3; -.
DR BioMuta; MFSD8; -.
DR DMDM; 74730313; -.
DR EPD; Q8NHS3; -.
DR jPOST; Q8NHS3; -.
DR MassIVE; Q8NHS3; -.
DR MaxQB; Q8NHS3; -.
DR PaxDb; 9606-ENSP00000296468; -.
DR PeptideAtlas; Q8NHS3; -.
DR ProteomicsDB; 73747; -. [Q8NHS3-1]
DR Pumba; Q8NHS3; -.
DR Antibodypedia; 45354; 79 antibodies from 21 providers.
DR DNASU; 256471; -.
DR Ensembl; ENST00000296468.8; ENSP00000296468.3; ENSG00000164073.11. [Q8NHS3-1]
DR Ensembl; ENST00000641434.1; ENSP00000493279.1; ENSG00000164073.11. [Q8NHS3-1]
DR Ensembl; ENST00000641464.1; ENSP00000493438.1; ENSG00000164073.11. [Q8NHS3-2]
DR Ensembl; ENST00000641686.2; ENSP00000493218.2; ENSG00000164073.11. [Q8NHS3-1]
DR Ensembl; ENST00000641748.1; ENSP00000493330.1; ENSG00000164073.11. [Q8NHS3-1]
DR Ensembl; ENST00000641928.1; ENSP00000493418.1; ENSG00000164073.11. [Q8NHS3-2]
DR GeneID; 256471; -.
DR KEGG; hsa:256471; -.
DR MANE-Select; ENST00000641686.2; ENSP00000493218.2; NM_001371596.2; NP_001358525.1.
DR UCSC; uc003ifp.4; human. [Q8NHS3-1]
DR AGR; HGNC:28486; -.
DR CTD; 256471; -.
DR DisGeNET; 256471; -.
DR GeneCards; MFSD8; -.
DR HGNC; HGNC:28486; MFSD8.
DR HPA; ENSG00000164073; Low tissue specificity.
DR MalaCards; MFSD8; -.
DR MIM; 610951; phenotype.
DR MIM; 611124; gene.
DR MIM; 616170; phenotype.
DR neXtProt; NX_Q8NHS3; -.
DR OpenTargets; ENSG00000164073; -.
DR Orphanet; 79264; Juvenile neuronal ceroid lipofuscinosis.
DR Orphanet; 168491; Late infantile neuronal ceroid lipofuscinosis.
DR PharmGKB; PA162395842; -.
DR VEuPathDB; HostDB:ENSG00000164073; -.
DR eggNOG; KOG2325; Eukaryota.
DR GeneTree; ENSGT00530000063854; -.
DR HOGENOM; CLU_1712618_0_0_1; -.
DR InParanoid; Q8NHS3; -.
DR OMA; DQFAWSK; -.
DR OrthoDB; 6977at2759; -.
DR PhylomeDB; Q8NHS3; -.
DR TreeFam; TF316590; -.
DR PathwayCommons; Q8NHS3; -.
DR SignaLink; Q8NHS3; -.
DR BioGRID-ORCS; 256471; 14 hits in 1164 CRISPR screens.
DR ChiTaRS; MFSD8; human.
DR GeneWiki; MFSD8; -.
DR GenomeRNAi; 256471; -.
DR Pharos; Q8NHS3; Tbio.
DR PRO; PR:Q8NHS3; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q8NHS3; Protein.
DR Bgee; ENSG00000164073; Expressed in oviduct epithelium and 176 other cell types or tissues.
DR ExpressionAtlas; Q8NHS3; baseline and differential.
DR Genevisible; Q8NHS3; HS.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005254; F:chloride channel activity; IDA:UniProtKB.
DR GO; GO:0062054; F:fluoride channel activity; IDA:UniProtKB.
DR GO; GO:0015111; F:iodide transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0097352; P:autophagosome maturation; IEA:Ensembl.
DR GO; GO:0007040; P:lysosome organization; IEA:Ensembl.
DR GO; GO:0048666; P:neuron development; IEA:Ensembl.
DR GO; GO:0010506; P:regulation of autophagy; IEA:Ensembl.
DR GO; GO:1905165; P:regulation of lysosomal protein catabolic process; IEA:Ensembl.
DR GO; GO:0038202; P:TORC1 signaling; IEA:Ensembl.
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.
PE 1: Evidence at protein level;
KW Alternative splicing; Chloride; Chloride channel; Disease variant;
KW Endosome; Glycoprotein; Ion channel; Ion transport; Lysosome; Membrane;
KW Neurodegeneration; Neuronal ceroid lipofuscinosis; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..518
FT /note="Major facilitator superfamily domain-containing
FT protein 8"
FT /id="PRO_0000311232"
FT TOPO_DOM 1..40
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:34910516"
FT TRANSMEM 41..61
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 62..74
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 75..95
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 96..105
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 106..126
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 127..131
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 132..152
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 153..173
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 174..194
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 195..211
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 212..232
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 233..266
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 267..287
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 288..304
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 305..325
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 326..337
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 338..358
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 359..412
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 413..433
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 434..451
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 452..472
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 473..482
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 483..503
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 504..518
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:34910516"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 13..14
FT /note="Dileucine internalization motif"
FT /evidence="ECO:0000269|PubMed:34910516"
FT CARBOHYD 371
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:20406422"
FT CARBOHYD 376
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:20406422"
FT VAR_SEQ 1..45
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057054"
FT VAR_SEQ 147..184
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057055"
FT VAR_SEQ 233..236
FT /note="REHR -> SKYR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057056"
FT VAR_SEQ 237..518
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057057"
FT VARIANT 52
FT /note="G -> R (in CLN7; dbSNP:rs779838200)"
FT /evidence="ECO:0000269|PubMed:19177532"
FT /id="VAR_058427"
FT VARIANT 109
FT /note="V -> G (in dbSNP:rs11732377)"
FT /id="VAR_037176"
FT VARIANT 121
FT /note="Y -> C (in CLN7; dbSNP:rs118203978)"
FT /evidence="ECO:0000269|PubMed:18850119"
FT /id="VAR_058428"
FT VARIANT 139
FT /note="R -> H (in CLN7; dbSNP:rs749704755)"
FT /evidence="ECO:0000269|PubMed:19201763"
FT /id="VAR_058429"
FT VARIANT 157
FT /note="A -> P (in CLN7; due to a deletion-insertion
FT mutation at nucleotide level; endolysosomal localization;
FT decreased chloride channel activity)"
FT /evidence="ECO:0000269|PubMed:19201763,
FT ECO:0000269|PubMed:21990111, ECO:0000269|PubMed:34910516"
FT /id="VAR_058430"
FT VARIANT 160
FT /note="T -> I (in CLN7; dbSNP:rs1162750836)"
FT /evidence="ECO:0000269|PubMed:21990111"
FT /id="VAR_066915"
FT VARIANT 160
FT /note="T -> N (in CLN7)"
FT /evidence="ECO:0000269|PubMed:21990111"
FT /id="VAR_066916"
FT VARIANT 294
FT /note="T -> K (in CLN7; endolysosomal localization;
FT decreased chloride channel activity; dbSNP:rs140948465)"
FT /evidence="ECO:0000269|PubMed:19177532,
FT ECO:0000269|PubMed:19201763, ECO:0000269|PubMed:22612257,
FT ECO:0000269|PubMed:34910516"
FT /id="VAR_058431"
FT VARIANT 310
FT /note="G -> D (in CLN7; lysosomal localization;
FT dbSNP:rs118203975)"
FT /evidence="ECO:0000269|PubMed:17564970,
FT ECO:0000269|PubMed:19177532, ECO:0000269|PubMed:19201763"
FT /id="VAR_037177"
FT VARIANT 336
FT /note="E -> Q (in CCMD and CLN7; endolysosomal
FT localization; decreased chloride channel activity;
FT dbSNP:rs150418024)"
FT /evidence="ECO:0000269|PubMed:25227500,
FT ECO:0000269|PubMed:34910516"
FT /id="VAR_072673"
FT VARIANT 385
FT /note="G -> R (in dbSNP:rs11098943)"
FT /id="VAR_037178"
FT VARIANT 412
FT /note="P -> L (in CLN7; dbSNP:rs267607235)"
FT /evidence="ECO:0000269|PubMed:19277732"
FT /id="VAR_072674"
FT VARIANT 423
FT /note="A -> V (in dbSNP:rs3733319)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_037179"
FT VARIANT 429
FT /note="G -> D (in CLN7; lysosomal localization;
FT dbSNP:rs118203976)"
FT /evidence="ECO:0000269|PubMed:17564970"
FT /id="VAR_037180"
FT VARIANT 447
FT /note="P -> L (in CLN7)"
FT /evidence="ECO:0000269|PubMed:19177532"
FT /id="VAR_058432"
FT VARIANT 458
FT /note="T -> K (in CLN7)"
FT /evidence="ECO:0000269|PubMed:21990111"
FT /id="VAR_066917"
FT VARIANT 465
FT /note="R -> Q (in CLN7; decreased chloride channel
FT activity; dbSNP:rs1275962600)"
FT /evidence="ECO:0000269|PubMed:21990111,
FT ECO:0000269|PubMed:34910516"
FT /id="VAR_066918"
FT VARIANT 465
FT /note="R -> W (in CLN7; decreased chloride channel
FT activity; dbSNP:rs1043984708)"
FT /evidence="ECO:0000269|PubMed:19201763,
FT ECO:0000269|PubMed:34910516"
FT /id="VAR_058433"
FT VARIANT 470
FT /note="M -> V (in CLN7; dbSNP:rs764549054)"
FT /evidence="ECO:0000269|PubMed:21990111"
FT /id="VAR_066919"
FT MUTAGEN 13..14
FT /note="LL->A: Mistargeted to the plasma membrane."
FT /evidence="ECO:0000269|PubMed:34910516"
FT MUTAGEN 153
FT /note="R->A: Decreased chloride channel activity."
FT /evidence="ECO:0000269|PubMed:34910516"
FT MUTAGEN 287
FT /note="E->A: Decreased chloride channel activity."
FT /evidence="ECO:0000269|PubMed:34910516"
FT MUTAGEN 438
FT /note="Y->A: Decreased chloride channel activity."
FT /evidence="ECO:0000269|PubMed:34910516"
FT CONFLICT 189
FT /note="C -> Y (in Ref. 1; BAC11062)"
FT /evidence="ECO:0000305"
FT CONFLICT 487
FT /note="L -> R (in Ref. 1; BAC11062)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 518 AA; 57628 MW; 105A5F6A35B2291F CRC64;
MAGLRNESEQ EPLLGDTPGS REWDILETEE HYKSRWRSIR ILYLTMFLSS VGFSVVMMSI
WPYLQKIDPT ADTSFLGWVI ASYSLGQMVA SPIFGLWSNY RPRKEPLIVS ILISVAANCL
YAYLHIPASH NKYYMLVARG LLGIGAGNVA VVRSYTAGAT SLQERTSSMA NISMCQALGF
ILGPVFQTCF TFLGEKGVTW DVIKLQINMY TTPVLLSAFL GILNIILILA ILREHRVDDS
GRQCKSINFE EASTDEAQVP QGNIDQVAVV AINVLFFVTL FIFALFETII TPLTMDMYAW
TQEQAVLYNG IILAALGVEA VVIFLGVKLL SKKIGERAIL LGGLIVVWVG FFILLPWGNQ
FPKIQWEDLH NNSIPNTTFG EIIIGLWKSP MEDDNERPTG CSIEQAWCLY TPVIHLAQFL
TSAVLIGLGY PVCNLMSYTL YSKILGPKPQ GVYMGWLTAS GSGARILGPM FISQVYAHWG
PRWAFSLVCG IIVLTITLLG VVYKRLIALS VRYGRIQE
//
