ID S52A3_HUMAN Reviewed; 469 AA. AC Q9NQ40; A0A2I6BQ49; A8K6P1; K0A6P4; Q5W1A0; Q5W1A1; Q8NCL7; Q96GD5; DT 10-JAN-2003, integrated into UniProtKB/Swiss-Prot. DT 22-NOV-2005, sequence version 4. DT 24-JAN-2024, entry version 171. DE RecName: Full=Solute carrier family 52, riboflavin transporter, member 3; DE AltName: Full=Riboflavin transporter 2; DE Short=hRFT2; GN Name=SLC52A3; Synonyms=C20orf54, RFT2, RFVT3; 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] {ECO:0000312|EMBL:AUI80409.1} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND SUBCELLULAR LOCATION RP (ISOFORMS 1 AND 2). RX PubMed=29428966; DOI=10.1007/s00018-018-2757-4; RA Long L., Pang X.X., Lei F., Zhang J.S., Wang W., Liao L.D., Xu X.E., RA He J.Z., Wu J.Y., Wu Z.Y., Wang L.D., Lin D.C., Li E.M., Xu L.Y.; RT "SLC52A3 expression is activated by NF-kappaB p65/Rel-B and serves as a RT prognostic biomarker in esophageal cancer."; RL Cell. Mol. Life Sci. 75:2643-2661(2018). RN [2] {ECO:0000312|EMBL:AFS68799.1} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Huang Z.G., Hong Q.N., Lun J.X., Lin W., Yang W., Deng Q.L., He Z., RA Lai Y.X., Xing J.M., Liu Y.Q.; RT "Clone and bioinformatics analysis on the coding region of c20orf54 gene."; RL Submitted (AUG-2012) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Mammary gland, 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [5] {ECO:0000312|EMBL:EAX10658.1} 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS LEU-267; RP MET-278 AND VAL-303. RC TISSUE=Pancreas; 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 [7] RP IDENTIFICATION. RX PubMed=19122205; DOI=10.1093/jb/mvn181; RA Yamamoto S., Inoue K., Ohta K.Y., Fukatsu R., Maeda J.Y., Yoshida Y., RA Yuasa H.; RT "Identification and functional characterization of rat riboflavin RT transporter 2."; RL J. Biochem. 145:437-443(2009). RN [8] RP FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL RP PROPERTIES, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=20463145; DOI=10.3945/jn.110.122911; RA Yao Y., Yonezawa A., Yoshimatsu H., Masuda S., Katsura T., Inui K.; RT "Identification and comparative functional characterization of a new human RT riboflavin transporter hRFT3 expressed in the brain."; RL J. Nutr. 140:1220-1226(2010). RN [9] RP SUBCELLULAR LOCATION, TOPOLOGY, DISULFIDE BOND, AND MUTAGENESIS OF CYS-326; RP CYS-386; ARG-455; CYS-463 AND CYS-467. RX PubMed=21512156; DOI=10.1152/ajpgi.00120.2011; RA Subramanian V.S., Rapp L., Marchant J.S., Said H.M.; RT "Role of cysteine residues in cell surface expression of the human RT riboflavin transporter-2 (hRFT2) in intestinal epithelial cells."; RL Am. J. Physiol. 301:G100-G109(2011). RN [10] RP INVOLVEMENT IN FALOND, INVOLVEMENT IN BVVLS1, AND VARIANT BVVLS1 ARG-17. RX PubMed=21110228; DOI=10.1007/s10545-010-9242-z; RA Bosch A.M., Abeling N.G., Ijlst L., Knoester H., van der Pol W.L., RA Stroomer A.E., Wanders R.J., Visser G., Wijburg F.A., Duran M., RA Waterham H.R.; RT "Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a RT riboflavin transporter defect mimicking mild MADD: a new inborn error of RT metabolism with potential treatment."; RL J. Inherit. Metab. Dis. 34:159-164(2011). RN [11] RP FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY REGULATION, AND SUBCELLULAR RP LOCATION. RX PubMed=24264046; DOI=10.1152/ajpgi.00349.2013; RA Yoshimatsu H., Yonezawa A., Yao Y., Sugano K., Nakagawa S., Omura T., RA Matsubara K.; RT "Functional involvement of RFVT3/SLC52A3 in intestinal riboflavin RT absorption."; RL Am. J. Physiol. 306:G102-G110(2014). RN [12] RP VARIANTS BVVLS1 LYS-36; TRP-132; LEU-224; ALA-413 AND LEU-457, AND VARIANT RP MET-350. RX PubMed=20206331; DOI=10.1016/j.ajhg.2010.02.006; RA Green P., Wiseman M., Crow Y.J., Houlden H., Riphagen S., Lin J.P., RA Raymond F.L., Childs A.M., Sheridan E., Edwards S., Josifova D.J.; RT "Brown-Vialetto-Van Laere syndrome, a ponto-bulbar palsy with deafness, is RT caused by mutations in c20orf54."; RL Am. J. Hum. Genet. 86:485-489(2010). RN [13] RP VARIANTS BVVLS1 THR-28 AND LYS-71. RX PubMed=20920669; DOI=10.1016/j.ajhg.2010.05.021; RA Johnson J.O., Gibbs J.R., Van Maldergem L., Houlden H., Singleton A.B.; RT "Exome sequencing in Brown-Vialetto-van Laere syndrome."; RL Am. J. Hum. Genet. 87:567-569(2010). RN [14] RP VARIANTS BVVLS1 SER-21; HIS-220; VAL-312 AND ASP-375. RX PubMed=22718020; DOI=10.1038/jhg.2012.70; RA Dezfouli M.A., Yadegari S., Nafissi S., Elahi E.; RT "Four novel C20orf54 mutations identified in Brown-Vialetto-Van Laere RT syndrome patients."; RL J. Hum. Genet. 57:613-617(2012). RN [15] RP CHARACTERIZATION OF VARIANTS BVVLS1 ARG-17; THR-28; LYS-36; LYS-71 AND RP TRP-132, CHARACTERIZATION OF VARIANT MET-350, FUNCTION, TRANSPORTER RP ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=22273710; DOI=10.1016/j.ymgme.2011.12.021; RA Nabokina S.M., Subramanian V.S., Said H.M.; RT "Effect of clinical mutations on functionality of the human riboflavin RT transporter-2 (hRFT-2)."; RL Mol. Genet. Metab. 105:652-657(2012). RN [16] RP VARIANTS BVVLS1 ASP-58; TRP-266; SER-319 AND ALA-413, AND VARIANT VAL-303. RX PubMed=22824638; DOI=10.1016/j.nmd.2012.05.007; RA Ciccolella M., Catteruccia M., Benedetti S., Moroni I., Uziel G., RA Pantaleoni C., Chiapparini L., Bizzi A., D'Amico A., Fattori F., RA Salsano M.L., Pastore A., Tozzi G., Piemonte F., Bertini E.; RT "Brown-Vialetto-van Laere and Fazio-Londe overlap syndromes: a clinical, RT biochemical and genetic study."; RL Neuromuscul. Disord. 22:1075-1082(2012). RN [17] RP VARIANT BVVLS1 VAL-330. RX PubMed=22633641; DOI=10.1016/j.pediatrneurol.2012.03.008; RA Koy A., Pillekamp F., Hoehn T., Waterham H., Klee D., Mayatepek E., RA Assmann B.; RT "Brown-Vialetto-Van Laere syndrome: a riboflavin-unresponsive patient with RT a novel mutation in the C20orf54 gene."; RL Pediatr. Neurol. 46:407-409(2012). RN [18] RP VARIANT BVVLS1 SER-21, CHARACTERIZATION OF VARIANT BVVLS1 SER-21, FUNCTION, RP TRANSPORTER ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=27702554; DOI=10.1016/j.cca.2016.09.022; RA Udhayabanu T., Subramanian V.S., Teafatiller T., Gowda V.K., Raghavan V.S., RA Varalakshmi P., Said H.M., Ashokkumar B.; RT "SLC52A2 [p.P141T] and SLC52A3 [p.N21S] causing Brown-Vialetto-Van Laere RT syndrome in an Indian patient: First genetically proven case with mutations RT in two riboflavin transporters."; RL Clin. Chim. Acta 462:210-214(2016). CC -!- FUNCTION: Plasma membrane transporter mediating the uptake by cells of CC the water soluble vitamin B2/riboflavin that plays a key role in CC biochemical oxidation-reduction reactions of the carbohydrate, lipid, CC and amino acid metabolism (PubMed:20463145, PubMed:22273710, CC PubMed:24264046, PubMed:27702554). Humans are unable to synthesize CC vitamin B2/riboflavin and must obtain it via intestinal absorption CC (PubMed:20463145). {ECO:0000269|PubMed:20463145, CC ECO:0000269|PubMed:22273710, ECO:0000269|PubMed:24264046, CC ECO:0000269|PubMed:27702554, ECO:0000303|PubMed:20463145}. CC -!- CATALYTIC ACTIVITY: CC Reaction=riboflavin(in) = riboflavin(out); Xref=Rhea:RHEA:35015, CC ChEBI:CHEBI:57986; Evidence={ECO:0000269|PubMed:20463145, CC ECO:0000269|PubMed:22273710, ECO:0000269|PubMed:24264046, CC ECO:0000269|PubMed:27702554}; CC -!- ACTIVITY REGULATION: Activity is strongly inhibited by riboflavin CC analogs, such as lumiflavin, flavin mononucleotide (FMN), flavin CC adenine dinucleotide (FAD), by methylene blue, and to a lesser extent CC by amiloride. Riboflavin transport is Na(+)-independent at low pH but CC significantly reduced by Na(+) depletion under neutral pH conditions. CC {ECO:0000269|PubMed:20463145, ECO:0000269|PubMed:24264046}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.98 uM for riboflavin {ECO:0000269|PubMed:20463145}; CC -!- INTERACTION: CC Q9NQ40; P54252: ATXN3; NbExp=3; IntAct=EBI-25845274, EBI-946046; CC Q9NQ40; P50570-2: DNM2; NbExp=3; IntAct=EBI-25845274, EBI-10968534; CC Q9NQ40; O14656-2: TOR1A; NbExp=3; IntAct=EBI-25845274, EBI-25847109; CC -!- SUBCELLULAR LOCATION: Apical cell membrane CC {ECO:0000269|PubMed:20463145, ECO:0000269|PubMed:21512156, CC ECO:0000269|PubMed:24264046}; Multi-pass membrane protein CC {ECO:0000269|PubMed:20463145}. Cell membrane CC {ECO:0000269|PubMed:22273710, ECO:0000269|PubMed:27702554}. CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane CC {ECO:0000269|PubMed:29428966}; Multi-pass membrane protein CC {ECO:0000255}. Nucleus membrane {ECO:0000269|PubMed:29428966}; Multi- CC pass membrane protein. Cytoplasm {ECO:0000269|PubMed:29428966}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm CC {ECO:0000269|PubMed:29428966}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=SLC52A3a {ECO:0000303|PubMed:29428966}; CC IsoId=Q9NQ40-1; Sequence=Displayed; CC Name=2; Synonyms=SLC52A3b {ECO:0000303|PubMed:29428966}; CC IsoId=Q9NQ40-2; Sequence=VSP_003814, VSP_003815; CC -!- TISSUE SPECIFICITY: Predominantly expressed in testis. Highly expressed CC in small intestine and prostate. {ECO:0000269|PubMed:20463145}. CC -!- DISEASE: Brown-Vialetto-Van Laere syndrome 1 (BVVLS1) [MIM:211530]: A CC rare neurologic disorder characterized by sensorineural hearing loss CC and a variety of cranial nerve palsies, which develop over a relatively CC short period of time in a previously healthy individual. Sensorineural CC hearing loss may precede the neurological signs. The course is CC invariably progressive, but the rate of decline is variable within and CC between families. With disease evolution, long tract signs, lower motor CC neuron signs, cerebellar ataxia and lower cranial nerve (III-VI) CC palsies develop, giving rise to a complex picture resembling CC amyotrophic lateral sclerosis. Diaphragmatic weakness and respiratory CC compromise are some of the most distressing features, leading to CC recurrent chest infections and respiratory failure, which are often the CC cause of patients' demise. {ECO:0000269|PubMed:20206331, CC ECO:0000269|PubMed:20920669, ECO:0000269|PubMed:21110228, CC ECO:0000269|PubMed:22273710, ECO:0000269|PubMed:22633641, CC ECO:0000269|PubMed:22718020, ECO:0000269|PubMed:22824638, CC ECO:0000269|PubMed:27702554}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Fazio-Londe disease (FALOND) [MIM:211500]: A rare neurological CC disease characterized by progressive weakness of the muscles innervated CC by cranial nerves of the lower brain stem. It may present in childhood CC with severe neurological deterioration with hypotonia, respiratory CC insufficiency leading to premature death, or later in life with bulbar CC weakness which progresses to involve motor neurons throughout the CC neuroaxis. Clinical manifestations include dysarthria, dysphagia, CC facial weakness, tongue weakness, and fasciculations of the tongue and CC facial muscles. {ECO:0000269|PubMed:21110228}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the riboflavin transporter family. CC {ECO:0000305}. CC -!- CAUTION: It is uncertain whether Met-1 or Met-5 is the initiator. CC {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; KY978478; AUI80409.1; -; mRNA. DR EMBL; KY978479; AUI80410.1; -; mRNA. DR EMBL; JX478249; AFS68799.1; -; mRNA. DR EMBL; AK074650; BAC11113.1; -; mRNA. DR EMBL; AK291706; BAF84395.1; -; mRNA. DR EMBL; AL118502; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471133; EAX10658.1; -; Genomic_DNA. DR EMBL; CH471133; EAX10659.1; -; Genomic_DNA. DR EMBL; BC009750; AAH09750.2; -; mRNA. DR CCDS; CCDS13007.1; -. [Q9NQ40-1] DR RefSeq; NP_212134.3; NM_033409.3. [Q9NQ40-1] DR RefSeq; XP_005260712.1; XM_005260655.3. DR RefSeq; XP_011527450.1; XM_011529148.1. DR AlphaFoldDB; Q9NQ40; -. DR BioGRID; 125241; 2. DR IntAct; Q9NQ40; 3. DR STRING; 9606.ENSP00000494009; -. DR TCDB; 2.A.125.1.2; the eukaryotic riboflavin transporter (e-rft) family. DR GlyCosmos; Q9NQ40; 3 sites, 1 glycan. DR GlyGen; Q9NQ40; 4 sites, 2 O-linked glycans (2 sites). DR iPTMnet; Q9NQ40; -. DR PhosphoSitePlus; Q9NQ40; -. DR BioMuta; SLC52A3; -. DR DMDM; 82654931; -. DR MassIVE; Q9NQ40; -. DR PaxDb; 9606-ENSP00000217254; -. DR PeptideAtlas; Q9NQ40; -. DR ProteomicsDB; 82078; -. [Q9NQ40-1] DR ProteomicsDB; 82079; -. [Q9NQ40-2] DR Antibodypedia; 54121; 104 antibodies from 15 providers. DR DNASU; 113278; -. DR Ensembl; ENST00000217254.11; ENSP00000217254.7; ENSG00000101276.18. [Q9NQ40-1] DR Ensembl; ENST00000381944.5; ENSP00000371370.3; ENSG00000101276.18. [Q9NQ40-2] DR Ensembl; ENST00000488495.3; ENSP00000494009.1; ENSG00000101276.18. [Q9NQ40-1] DR Ensembl; ENST00000645534.1; ENSP00000494193.1; ENSG00000101276.18. [Q9NQ40-1] DR GeneID; 113278; -. DR KEGG; hsa:113278; -. DR MANE-Select; ENST00000645534.1; ENSP00000494193.1; NM_033409.4; NP_212134.3. DR UCSC; uc002wed.5; human. [Q9NQ40-1] DR AGR; HGNC:16187; -. DR CTD; 113278; -. DR DisGeNET; 113278; -. DR GeneCards; SLC52A3; -. DR GeneReviews; SLC52A3; -. DR HGNC; HGNC:16187; SLC52A3. DR HPA; ENSG00000101276; Tissue enhanced (intestine, testis). DR MalaCards; SLC52A3; -. DR MIM; 211500; phenotype. DR MIM; 211530; phenotype. DR MIM; 613350; gene. DR neXtProt; NX_Q9NQ40; -. DR OpenTargets; ENSG00000101276; -. DR Orphanet; 572550; RFVT3-related riboflavin transporter deficiency. DR PharmGKB; PA25764; -. DR VEuPathDB; HostDB:ENSG00000101276; -. DR eggNOG; KOG4255; Eukaryota. DR GeneTree; ENSGT00390000003774; -. DR HOGENOM; CLU_034789_1_0_1; -. DR InParanoid; Q9NQ40; -. DR OMA; CGAAAQM; -. DR OrthoDB; 5477759at2759; -. DR PhylomeDB; Q9NQ40; -. DR TreeFam; TF314820; -. DR PathwayCommons; Q9NQ40; -. DR Reactome; R-HSA-196843; Vitamin B2 (riboflavin) metabolism. DR SignaLink; Q9NQ40; -. DR BioGRID-ORCS; 113278; 13 hits in 1149 CRISPR screens. DR ChiTaRS; SLC52A3; human. DR GeneWiki; C20orf54; -. DR GenomeRNAi; 113278; -. DR Pharos; Q9NQ40; Tbio. DR PRO; PR:Q9NQ40; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; Q9NQ40; Protein. DR Bgee; ENSG00000101276; Expressed in right testis and 119 other cell types or tissues. DR ExpressionAtlas; Q9NQ40; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0032217; F:riboflavin transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0034605; P:cellular response to heat; IEA:Ensembl. DR GO; GO:0072388; P:flavin adenine dinucleotide biosynthetic process; IEA:Ensembl. DR GO; GO:0006771; P:riboflavin metabolic process; TAS:Reactome. DR GO; GO:0032218; P:riboflavin transport; IDA:UniProtKB. DR GO; GO:0007605; P:sensory perception of sound; IMP:UniProtKB. DR InterPro; IPR009357; Riboflavin_transptr. DR PANTHER; PTHR12929; SOLUTE CARRIER FAMILY 52; 1. DR PANTHER; PTHR12929:SF4; SOLUTE CARRIER FAMILY 52, RIBOFLAVIN TRANSPORTER, MEMBER 3; 1. DR Pfam; PF06237; SLC52_ribofla_tr; 1. DR Genevisible; Q9NQ40; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Cytoplasm; Deafness; Disease variant; KW Disulfide bond; Glycoprotein; Membrane; Nucleus; Phosphoprotein; KW Reference proteome; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..469 FT /note="Solute carrier family 52, riboflavin transporter, FT member 3" FT /id="PRO_0000042636" FT TOPO_DOM 1..2 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 3..23 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 24..43 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 44..64 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 65..71 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 72..92 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 93..97 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 98..118 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 119..137 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 138..158 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 159..220 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 221..241 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 242..292 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 293..313 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 314..335 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 336..356 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 357..359 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 360..380 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 381..396 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 397..417 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 418..427 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 428..448 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 449..469 FT /note="Extracellular" FT /evidence="ECO:0000255" FT MOD_RES 251 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q4FZU9" FT CARBOHYD 94 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 168 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 386..463 FT /evidence="ECO:0000305|PubMed:21512156" FT VAR_SEQ 401..415 FT /note="ASWVLFSGCLSYVKV -> SIRPVGLLPLRTPHP (in isoform 2)" FT /evidence="ECO:0000269|PubMed:29428966, FT ECO:0000303|PubMed:14702039" FT /id="VSP_003814" FT VAR_SEQ 416..469 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000269|PubMed:29428966, FT ECO:0000303|PubMed:14702039" FT /id="VSP_003815" FT VARIANT 17 FT /note="W -> R (in BVVLS1; loss of riboflavin transport; no FT effect on localization to cell membrane; does not affect FT protein abundance; dbSNP:rs797045190)" FT /evidence="ECO:0000269|PubMed:21110228, FT ECO:0000269|PubMed:22273710" FT /id="VAR_077422" FT VARIANT 21 FT /note="N -> S (in BVVLS1; loss of localization to cell FT membrane; loss of riboflavin transport; dbSNP:rs199588390)" FT /evidence="ECO:0000269|PubMed:22718020, FT ECO:0000269|PubMed:27702554" FT /id="VAR_077423" FT VARIANT 28 FT /note="P -> T (in BVVLS1; loss of localization to cell FT membrane; loss of riboflavin transport; does not affect FT protein abundance; dbSNP:rs267606688)" FT /evidence="ECO:0000269|PubMed:20920669, FT ECO:0000269|PubMed:22273710" FT /id="VAR_077424" FT VARIANT 36 FT /note="E -> K (in BVVLS1; loss of localization to cell FT membrane; loss of riboflavin transport; does not affect FT protein abundance; dbSNP:rs267606686)" FT /evidence="ECO:0000269|PubMed:20206331, FT ECO:0000269|PubMed:22273710" FT /id="VAR_063694" FT VARIANT 58 FT /note="V -> D (in BVVLS1; dbSNP:rs797045192)" FT /evidence="ECO:0000269|PubMed:22824638" FT /id="VAR_077425" FT VARIANT 71 FT /note="E -> K (in BVVLS1; loss of localization to cell FT membrane; loss of riboflavin transport; does not affect FT protein abundance; dbSNP:rs267606683)" FT /evidence="ECO:0000269|PubMed:20920669, FT ECO:0000269|PubMed:22273710" FT /id="VAR_077426" FT VARIANT 74 FT /note="I -> M (in dbSNP:rs35655964)" FT /id="VAR_053565" FT VARIANT 132 FT /note="R -> W (in BVVLS1; loss of localization to cell FT membrane; loss of riboflavin transport; does not affect FT protein abundance; dbSNP:rs267606684)" FT /evidence="ECO:0000269|PubMed:20206331, FT ECO:0000269|PubMed:22273710" FT /id="VAR_063695" FT VARIANT 174 FT /note="D -> G (in dbSNP:rs6054614)" FT /id="VAR_053566" FT VARIANT 220 FT /note="P -> H (in BVVLS1; uncertain significance; FT dbSNP:rs797045194)" FT /evidence="ECO:0000269|PubMed:22718020" FT /id="VAR_077427" FT VARIANT 224 FT /note="F -> L (in BVVLS1; dbSNP:rs267606685)" FT /evidence="ECO:0000269|PubMed:20206331" FT /id="VAR_063696" FT VARIANT 266 FT /note="R -> W (in BVVLS1; uncertain significance; FT dbSNP:rs370499474)" FT /evidence="ECO:0000269|PubMed:22824638" FT /id="VAR_077428" FT VARIANT 267 FT /note="P -> L (in dbSNP:rs3746804)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_053567" FT VARIANT 278 FT /note="T -> M (in dbSNP:rs3746803)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_053568" FT VARIANT 303 FT /note="I -> V (in dbSNP:rs3746802)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:22824638" FT /id="VAR_053569" FT VARIANT 312 FT /note="A -> V (in BVVLS1; uncertain significance; FT dbSNP:rs752218005)" FT /evidence="ECO:0000269|PubMed:22718020" FT /id="VAR_077429" FT VARIANT 319 FT /note="P -> S (in BVVLS1; uncertain significance; FT dbSNP:rs797045195)" FT /evidence="ECO:0000269|PubMed:22824638" FT /id="VAR_077430" FT VARIANT 330 FT /note="G -> V (in BVVLS1; uncertain significance; FT dbSNP:rs797045196)" FT /evidence="ECO:0000269|PubMed:22633641" FT /id="VAR_077431" FT VARIANT 350 FT /note="L -> M (no effect on riboflavin transport; no effect FT on localization to cell membrane; dbSNP:rs76947760)" FT /evidence="ECO:0000269|PubMed:20206331, FT ECO:0000269|PubMed:22273710" FT /id="VAR_063698" FT VARIANT 375 FT /note="G -> D (in BVVLS1; uncertain significance; FT dbSNP:rs1219868273)" FT /evidence="ECO:0000269|PubMed:22718020" FT /id="VAR_077432" FT VARIANT 411 FT /note="S -> R (in dbSNP:rs910857)" FT /id="VAR_063699" FT VARIANT 413 FT /note="V -> A (in BVVLS1; dbSNP:rs267606687)" FT /evidence="ECO:0000269|PubMed:20206331, FT ECO:0000269|PubMed:22824638" FT /id="VAR_063700" FT VARIANT 457 FT /note="F -> L (in BVVLS1; dbSNP:rs779750163)" FT /evidence="ECO:0000269|PubMed:20206331" FT /id="VAR_063701" FT MUTAGEN 326 FT /note="C->A: No effect on cell surface localization." FT /evidence="ECO:0000269|PubMed:21512156" FT MUTAGEN 386 FT /note="C->A: Abolishes cell surface localization." FT /evidence="ECO:0000269|PubMed:21512156" FT MUTAGEN 455 FT /note="R->A: No effect on cell surface localization." FT /evidence="ECO:0000269|PubMed:21512156" FT MUTAGEN 463 FT /note="C->A: Abolishes cell surface localization." FT /evidence="ECO:0000269|PubMed:21512156" FT MUTAGEN 467 FT /note="C->A: Abolishes cell surface localization." FT /evidence="ECO:0000269|PubMed:21512156" FT CONFLICT 11 FT /note="V -> D (in Ref. 3; BAF84395)" FT /evidence="ECO:0000305" FT CONFLICT 199 FT /note="L -> P (in Ref. 3; BAC11113)" FT /evidence="ECO:0000305" SQ SEQUENCE 469 AA; 50805 MW; 239ED67348C93739 CRC64; MAFLMHLLVC VFGMGSWVTI NGLWVELPLL VMELPEGWYL PSYLTVVIQL ANIGPLLVTL LHHFRPSCLS EVPIIFTLLG VGTVTCIIFA FLWNMTSWVL DGHHSIAFLV LTFFLALVDC TSSVTFLPFM SRLPTYYLTT FFVGEGLSGL LPALVALAQG SGLTTCVNVT EISDSVPSPV PTRETDIAQG VPRALVSALP GMEAPLSHLE SRYLPAHFSP LVFFLLLSIM MACCLVAFFV LQRQPRCWEA SVEDLLNDQV TLHSIRPREE NDLGPAGTVD SSQGQGYLEE KAAPCCPAHL AFIYTLVAFV NALTNGMLPS VQTYSCLSYG PVAYHLAATL SIVANPLASL VSMFLPNRSL LFLGVLSVLG TCFGGYNMAM AVMSPCPLLQ GHWGGEVLIV ASWVLFSGCL SYVKVMLGVV LRDLSRSALL WCGAAVQLGS LLGALLMFPL VNVLRLFSSA DFCNLHCPA //