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Protein

Solute carrier family 52, riboflavin transporter, member 3

Gene

SLC52A3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Transporter for riboflavin, which must be obtained as a nutrient via intestinal absorption. Riboflavin transport is Na+-independent at low pH but significantly reduced by Na+ depletion under neutral pH conditions. Activity is strongly inhibited by riboflavin analogs, such as lumiflavin, flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), by methylene blue, and to a lesser extent by amiloride.4 Publications

Caution

It is uncertain whether Met-1 or Met-5 is the initiator.Curated

Kineticsi

  1. KM=0.98 µM for riboflavin1 Publication

    GO - Molecular functioni

    • riboflavin transmembrane transporter activity Source: UniProtKB

    GO - Biological processi

    • riboflavin metabolic process Source: Reactome
    • riboflavin transport Source: UniProtKB
    • sensory perception of sound Source: UniProtKB

    Keywordsi

    Biological processTransport

    Enzyme and pathway databases

    ReactomeiR-HSA-196843 Vitamin B2 (riboflavin) metabolism

    Protein family/group databases

    TCDBi2.A.125.1.2 the eukaryotic riboflavin transporter (e-rft) family

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Solute carrier family 52, riboflavin transporter, member 3
    Alternative name(s):
    Riboflavin transporter 2
    Short name:
    hRFT2
    Gene namesi
    Name:SLC52A3
    Synonyms:C20orf54, RFT2, RFVT3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 20

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000101276.14
    HGNCiHGNC:16187 SLC52A3
    MIMi613350 gene
    neXtProtiNX_Q9NQ40

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 2CytoplasmicSequence analysis2
    Transmembranei3 – 23HelicalSequence analysisAdd BLAST21
    Topological domaini24 – 43ExtracellularSequence analysisAdd BLAST20
    Transmembranei44 – 64HelicalSequence analysisAdd BLAST21
    Topological domaini65 – 71CytoplasmicSequence analysis7
    Transmembranei72 – 92HelicalSequence analysisAdd BLAST21
    Topological domaini93 – 97ExtracellularSequence analysis5
    Transmembranei98 – 118HelicalSequence analysisAdd BLAST21
    Topological domaini119 – 137CytoplasmicSequence analysisAdd BLAST19
    Transmembranei138 – 158HelicalSequence analysisAdd BLAST21
    Topological domaini159 – 220ExtracellularSequence analysisAdd BLAST62
    Transmembranei221 – 241HelicalSequence analysisAdd BLAST21
    Topological domaini242 – 292CytoplasmicSequence analysisAdd BLAST51
    Transmembranei293 – 313HelicalSequence analysisAdd BLAST21
    Topological domaini314 – 335ExtracellularSequence analysisAdd BLAST22
    Transmembranei336 – 356HelicalSequence analysisAdd BLAST21
    Topological domaini357 – 359CytoplasmicSequence analysis3
    Transmembranei360 – 380HelicalSequence analysisAdd BLAST21
    Topological domaini381 – 396ExtracellularSequence analysisAdd BLAST16
    Transmembranei397 – 417HelicalSequence analysisAdd BLAST21
    Topological domaini418 – 427CytoplasmicSequence analysis10
    Transmembranei428 – 448HelicalSequence analysisAdd BLAST21
    Topological domaini449 – 469ExtracellularSequence analysisAdd BLAST21

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Brown-Vialetto-Van Laere syndrome 1 (BVVLS1)8 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA rare neurologic disorder characterized by sensorineural hearing loss and a variety of cranial nerve palsies, which develop over a relatively short period of time in a previously healthy individual. Sensorineural hearing loss may precede the neurological signs. The course is invariably progressive, but the rate of decline is variable within and between families. With disease evolution, long tract signs, lower motor neuron signs, cerebellar ataxia and lower cranial nerve (III-VI) palsies develop, giving rise to a complex picture resembling amyotrophic lateral sclerosis. Diaphragmatic weakness and respiratory compromise are some of the most distressing features, leading to recurrent chest infections and respiratory failure, which are often the cause of patients' demise.
    See also OMIM:211530
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_07742217W → R in BVVLS1; loss of riboflavin transport; no effect on localization to cell membrane; does not affect protein abundance. 2 PublicationsCorresponds to variant dbSNP:rs797045190EnsemblClinVar.1
    Natural variantiVAR_07742321N → S in BVVLS1; loss of localization to cell membrane; loss of riboflavin transport. 2 PublicationsCorresponds to variant dbSNP:rs199588390EnsemblClinVar.1
    Natural variantiVAR_07742428P → T in BVVLS1; loss of localization to cell membrane; loss of riboflavin transport; does not affect protein abundance. 2 PublicationsCorresponds to variant dbSNP:rs267606688EnsemblClinVar.1
    Natural variantiVAR_06369436E → K in BVVLS1; loss of localization to cell membrane; loss of riboflavin transport; does not affect protein abundance. 2 PublicationsCorresponds to variant dbSNP:rs267606686EnsemblClinVar.1
    Natural variantiVAR_07742558V → D in BVVLS1. 1 PublicationCorresponds to variant dbSNP:rs797045192EnsemblClinVar.1
    Natural variantiVAR_07742671E → K in BVVLS1; loss of localization to cell membrane; loss of riboflavin transport; does not affect protein abundance. 2 PublicationsCorresponds to variant dbSNP:rs267606683EnsemblClinVar.1
    Natural variantiVAR_063695132R → W in BVVLS1; loss of localization to cell membrane; loss of riboflavin transport; does not affect protein abundance. 2 PublicationsCorresponds to variant dbSNP:rs267606684EnsemblClinVar.1
    Natural variantiVAR_077427220P → H in BVVLS1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs797045194EnsemblClinVar.1
    Natural variantiVAR_063696224F → L in BVVLS1. 1 PublicationCorresponds to variant dbSNP:rs267606685EnsemblClinVar.1
    Natural variantiVAR_077428266R → W in BVVLS1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs370499474EnsemblClinVar.1
    Natural variantiVAR_077429312A → V in BVVLS1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs752218005EnsemblClinVar.1
    Natural variantiVAR_077430319P → S in BVVLS1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs797045195EnsemblClinVar.1
    Natural variantiVAR_077431330G → V in BVVLS1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs797045196EnsemblClinVar.1
    Natural variantiVAR_077432375G → D in BVVLS1; unknown pathological significance. 1 Publication1
    Natural variantiVAR_063700413V → A in BVVLS1. 2 PublicationsCorresponds to variant dbSNP:rs267606687EnsemblClinVar.1
    Natural variantiVAR_063701457F → L in BVVLS1. 1 PublicationCorresponds to variant dbSNP:rs779750163Ensembl.1
    Fazio-Londe disease (FALOND)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA rare neurological disease characterized by progressive weakness of the muscles innervated by cranial nerves of the lower brain stem. It may present in childhood with severe neurological deterioration with hypotonia, respiratory insufficiency leading to premature death, or later in life with bulbar weakness which progresses to involve motor neurons throughout the neuroaxis. Clinical manifestations include dysarthria, dysphagia, facial weakness, tongue weakness, and fasciculations of the tongue and facial muscles.
    See also OMIM:211500

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi326C → A: No effect on cell surface localization. 1 Publication1
    Mutagenesisi386C → A: Abolishes cell surface localization. 1 Publication1
    Mutagenesisi455R → A: No effect on cell surface localization. 1 Publication1
    Mutagenesisi463C → A: Abolishes cell surface localization. 1 Publication1
    Mutagenesisi467C → A: Abolishes cell surface localization. 1 Publication1

    Keywords - Diseasei

    Deafness, Disease mutation

    Organism-specific databases

    DisGeNETi113278
    MalaCardsiSLC52A3
    MIMi211500 phenotype
    211530 phenotype
    OpenTargetsiENSG00000101276
    Orphaneti97229 Riboflavin transporter deficiency
    PharmGKBiPA25764

    Polymorphism and mutation databases

    BioMutaiSLC52A3
    DMDMi82654931

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000426361 – 469Solute carrier family 52, riboflavin transporter, member 3Add BLAST469

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Glycosylationi94N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi168N-linked (GlcNAc...) asparagineSequence analysis1
    Modified residuei251PhosphoserineBy similarity1
    Disulfide bondi386 ↔ 4631 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiQ9NQ40
    PeptideAtlasiQ9NQ40
    PRIDEiQ9NQ40

    PTM databases

    iPTMnetiQ9NQ40
    PhosphoSitePlusiQ9NQ40

    Expressioni

    Tissue specificityi

    Predominantly expressed in testis. Highly expressed in small intestine and prostate.1 Publication

    Gene expression databases

    BgeeiENSG00000101276
    CleanExiHS_C20orf54
    ExpressionAtlasiQ9NQ40 baseline and differential
    GenevisibleiQ9NQ40 HS

    Organism-specific databases

    HPAiHPA049391

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000217254

    Structurei

    3D structure databases

    ProteinModelPortaliQ9NQ40
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the riboflavin transporter family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG4255 Eukaryota
    ENOG410YE1U LUCA
    GeneTreeiENSGT00390000003774
    HOGENOMiHOG000247012
    HOVERGENiHBG051170
    InParanoidiQ9NQ40
    KOiK14620
    OMAiAMFLHFT
    OrthoDBiEOG091G0BZA
    PhylomeDBiQ9NQ40
    TreeFamiTF314820

    Family and domain databases

    InterProiView protein in InterPro
    IPR009357 Riboflavin_transptr
    PANTHERiPTHR12929 PTHR12929, 1 hit
    PfamiView protein in Pfam
    PF06237 DUF1011, 1 hit

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q9NQ40-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MAFLMHLLVC VFGMGSWVTI NGLWVELPLL VMELPEGWYL PSYLTVVIQL
    60 70 80 90 100
    ANIGPLLVTL LHHFRPSCLS EVPIIFTLLG VGTVTCIIFA FLWNMTSWVL
    110 120 130 140 150
    DGHHSIAFLV LTFFLALVDC TSSVTFLPFM SRLPTYYLTT FFVGEGLSGL
    160 170 180 190 200
    LPALVALAQG SGLTTCVNVT EISDSVPSPV PTRETDIAQG VPRALVSALP
    210 220 230 240 250
    GMEAPLSHLE SRYLPAHFSP LVFFLLLSIM MACCLVAFFV LQRQPRCWEA
    260 270 280 290 300
    SVEDLLNDQV TLHSIRPREE NDLGPAGTVD SSQGQGYLEE KAAPCCPAHL
    310 320 330 340 350
    AFIYTLVAFV NALTNGMLPS VQTYSCLSYG PVAYHLAATL SIVANPLASL
    360 370 380 390 400
    VSMFLPNRSL LFLGVLSVLG TCFGGYNMAM AVMSPCPLLQ GHWGGEVLIV
    410 420 430 440 450
    ASWVLFSGCL SYVKVMLGVV LRDLSRSALL WCGAAVQLGS LLGALLMFPL
    460
    VNVLRLFSSA DFCNLHCPA
    Length:469
    Mass (Da):50,805
    Last modified:November 22, 2005 - v4
    Checksum:i239ED67348C93739
    GO
    Isoform 2 (identifier: Q9NQ40-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         401-415: ASWVLFSGCLSYVKV → SIRPVGLLPLRTPHP
         416-469: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:415
    Mass (Da):45,043
    Checksum:i8E072208A8998A56
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti11V → D in BAF84395 (PubMed:14702039).Curated1
    Sequence conflicti199L → P in BAC11113 (PubMed:14702039).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_07742217W → R in BVVLS1; loss of riboflavin transport; no effect on localization to cell membrane; does not affect protein abundance. 2 PublicationsCorresponds to variant dbSNP:rs797045190EnsemblClinVar.1
    Natural variantiVAR_07742321N → S in BVVLS1; loss of localization to cell membrane; loss of riboflavin transport. 2 PublicationsCorresponds to variant dbSNP:rs199588390EnsemblClinVar.1
    Natural variantiVAR_07742428P → T in BVVLS1; loss of localization to cell membrane; loss of riboflavin transport; does not affect protein abundance. 2 PublicationsCorresponds to variant dbSNP:rs267606688EnsemblClinVar.1
    Natural variantiVAR_06369436E → K in BVVLS1; loss of localization to cell membrane; loss of riboflavin transport; does not affect protein abundance. 2 PublicationsCorresponds to variant dbSNP:rs267606686EnsemblClinVar.1
    Natural variantiVAR_07742558V → D in BVVLS1. 1 PublicationCorresponds to variant dbSNP:rs797045192EnsemblClinVar.1
    Natural variantiVAR_07742671E → K in BVVLS1; loss of localization to cell membrane; loss of riboflavin transport; does not affect protein abundance. 2 PublicationsCorresponds to variant dbSNP:rs267606683EnsemblClinVar.1
    Natural variantiVAR_05356574I → M. Corresponds to variant dbSNP:rs35655964EnsemblClinVar.1
    Natural variantiVAR_063695132R → W in BVVLS1; loss of localization to cell membrane; loss of riboflavin transport; does not affect protein abundance. 2 PublicationsCorresponds to variant dbSNP:rs267606684EnsemblClinVar.1
    Natural variantiVAR_053566174D → G. Corresponds to variant dbSNP:rs6054614EnsemblClinVar.1
    Natural variantiVAR_077427220P → H in BVVLS1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs797045194EnsemblClinVar.1
    Natural variantiVAR_063696224F → L in BVVLS1. 1 PublicationCorresponds to variant dbSNP:rs267606685EnsemblClinVar.1
    Natural variantiVAR_077428266R → W in BVVLS1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs370499474EnsemblClinVar.1
    Natural variantiVAR_053567267P → L1 PublicationCorresponds to variant dbSNP:rs3746804EnsemblClinVar.1
    Natural variantiVAR_053568278T → M1 PublicationCorresponds to variant dbSNP:rs3746803EnsemblClinVar.1
    Natural variantiVAR_053569303I → V2 PublicationsCorresponds to variant dbSNP:rs3746802EnsemblClinVar.1
    Natural variantiVAR_077429312A → V in BVVLS1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs752218005EnsemblClinVar.1
    Natural variantiVAR_077430319P → S in BVVLS1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs797045195EnsemblClinVar.1
    Natural variantiVAR_077431330G → V in BVVLS1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs797045196EnsemblClinVar.1
    Natural variantiVAR_063698350L → M Polymorphism; no effect on riboflavin transport; no effect on localization to cell membrane. 2 PublicationsCorresponds to variant dbSNP:rs76947760EnsemblClinVar.1
    Natural variantiVAR_077432375G → D in BVVLS1; unknown pathological significance. 1 Publication1
    Natural variantiVAR_063699411S → R. Corresponds to variant dbSNP:rs910857Ensembl.1
    Natural variantiVAR_063700413V → A in BVVLS1. 2 PublicationsCorresponds to variant dbSNP:rs267606687EnsemblClinVar.1
    Natural variantiVAR_063701457F → L in BVVLS1. 1 PublicationCorresponds to variant dbSNP:rs779750163Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_003814401 – 415ASWVL…SYVKV → SIRPVGLLPLRTPHP in isoform 2. 1 PublicationAdd BLAST15
    Alternative sequenceiVSP_003815416 – 469Missing in isoform 2. 1 PublicationAdd BLAST54

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AK074650 mRNA Translation: BAC11113.1
    AK291706 mRNA Translation: BAF84395.1
    AL118502 Genomic DNA No translation available.
    BC009750 mRNA Translation: AAH09750.2
    CCDSiCCDS13007.1 [Q9NQ40-1]
    RefSeqiNP_212134.3, NM_033409.3 [Q9NQ40-1]
    XP_005260712.1, XM_005260655.3 [Q9NQ40-1]
    XP_011527450.1, XM_011529148.1 [Q9NQ40-1]
    UniGeneiHs.283865

    Genome annotation databases

    EnsembliENST00000217254; ENSP00000217254; ENSG00000101276 [Q9NQ40-1]
    ENST00000381944; ENSP00000371370; ENSG00000101276 [Q9NQ40-2]
    ENST00000632431; ENSP00000488723; ENSG00000101276 [Q9NQ40-1]
    GeneIDi113278
    KEGGihsa:113278
    UCSCiuc002wed.5 human [Q9NQ40-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiS52A3_HUMAN
    AccessioniPrimary (citable) accession number: Q9NQ40
    Secondary accession number(s): A8K6P1
    , Q5W1A0, Q5W1A1, Q8NCL7, Q96GD5
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 10, 2003
    Last sequence update: November 22, 2005
    Last modified: April 25, 2018
    This is version 138 of the entry and version 4 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health