Q9NQ40 (S52A3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Solute carrier family 52, riboflavin transporter, member 3

Alternative name(s):
Riboflavin transporter 2
Short name=hRFT2

Gene names

Name:	SLC52A3
Synonyms:	C20orf54, RFT2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	469 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Riboflavin transporter. Riboflavin transport is Na+-independent but moderately pH-sensitive. Activity is strongly inhibited by riboflavin analogs, such as lumiflavin, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), and to a lesser extent by amiloride. Ref.5
Subcellular location	Cell membrane; Multi-pass membrane protein Ref.5.
Tissue specificity	Predominantly expressed in testis. Highly expressed in small intestine and prostate. Ref.5
Involvement in disease	Brown-Vialetto-Van Laere syndrome 1 (BVVLS1) [MIM:211530]: A 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Fazio-Londe disease (FALOND) [MIM:211500]: A 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6
Sequence similarities	Belongs to the riboflavin transporter family.
Caution	It is uncertain whether Met-1 or Met-5 is the initiator.
Biophysicochemical properties	Kinetic parameters: KM=0.98 µM for riboflavin Ref.5

Ontologies

Keywords
Biological process	Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Deafness Disease mutation
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to heat Inferred from electronic annotation. Source: Compara sensory perception of sound Inferred from mutant phenotype Ref.7. Source: UniProtKB
Cellular_component	integral to plasma membrane Inferred from direct assay Ref.5. Source: UniProtKB
Molecular_function	riboflavin transporter activity Inferred from direct assay Ref.5. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NQ40-1)

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.

Isoform 2 (identifier: Q9NQ40-2)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 469	469	Solute carrier family 52, riboflavin transporter, member 3		PRO_0000042636
Regions
	Transmembrane	3 – 23	21	Helical; Potential
	Transmembrane	44 – 64	21	Helical; Potential
	Transmembrane	72 – 92	21	Helical; Potential
	Transmembrane	98 – 118	21	Helical; Potential
	Transmembrane	138 – 158	21	Helical; Potential
	Transmembrane	221 – 241	21	Helical; Potential
	Transmembrane	293 – 313	21	Helical; Potential
	Transmembrane	336 – 356	21	Helical; Potential
	Transmembrane	360 – 380	21	Helical; Potential
	Transmembrane	382 – 402	21	Helical; Potential
	Transmembrane	405 – 425	21	Helical; Potential
	Transmembrane	433 – 453	21	Helical; Potential
Amino acid modifications
	Glycosylation	94	1	N-linked (GlcNAc...) Potential
	Glycosylation	168	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	401 – 415	15	ASWVL…SYVKV → SIRPVGLLPLRTPHP in isoform 2.		VSP_003814
	Alternative sequence	416 – 469	54	Missing in isoform 2.		VSP_003815
	Natural variant	36	1	E → K in BVVLS1. Ref.7		VAR_063694
	Natural variant	74	1	I → M. Corresponds to variant rs35655964 [ dbSNP | Ensembl ].		VAR_053565
	Natural variant	132	1	R → W in BVVLS1. Ref.7		VAR_063695
	Natural variant	174	1	D → G. Corresponds to variant rs6054614 [ dbSNP | Ensembl ].		VAR_053566
	Natural variant	224	1	F → L in BVVLS1. Ref.7		VAR_063696
	Natural variant	267	1	P → L. Ref.3 Corresponds to variant rs3746804 [ dbSNP | Ensembl ].		VAR_053567
	Natural variant	278	1	T → M. Ref.3 Corresponds to variant rs3746803 [ dbSNP | Ensembl ].		VAR_053568
	Natural variant	303	1	I → V. Ref.3 Corresponds to variant rs3746802 [ dbSNP | Ensembl ].		VAR_053569
	Natural variant	350	1	L → M May be a common polymorphism. Ref.7		VAR_063698
	Natural variant	411	1	S → R. Corresponds to variant rs910857 [ dbSNP | Ensembl ].		VAR_063699
	Natural variant	413	1	V → A in BVVLS1; may cause a mild form of the disease. Ref.7		VAR_063700
	Natural variant	457	1	F → L in BVVLS1. Ref.7		VAR_063701
Experimental info
	Sequence conflict	11	1	V → D in BAF84395. Ref.1
	Sequence conflict	199	1	L → P in BAC11113. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 22, 2005. Version 4. Checksum: 239ED67348C93739	FASTA	469	50,805
	10 20 30 40 50 60 MAFLMHLLVC VFGMGSWVTI NGLWVELPLL VMELPEGWYL PSYLTVVIQL ANIGPLLVTL 70 80 90 100 110 120 LHHFRPSCLS EVPIIFTLLG VGTVTCIIFA FLWNMTSWVL DGHHSIAFLV LTFFLALVDC 130 140 150 160 170 180 TSSVTFLPFM SRLPTYYLTT FFVGEGLSGL LPALVALAQG SGLTTCVNVT EISDSVPSPV 190 200 210 220 230 240 PTRETDIAQG VPRALVSALP GMEAPLSHLE SRYLPAHFSP LVFFLLLSIM MACCLVAFFV 250 260 270 280 290 300 LQRQPRCWEA SVEDLLNDQV TLHSIRPREE NDLGPAGTVD SSQGQGYLEE KAAPCCPAHL 310 320 330 340 350 360 AFIYTLVAFV NALTNGMLPS VQTYSCLSYG PVAYHLAATL SIVANPLASL VSMFLPNRSL 370 380 390 400 410 420 LFLGVLSVLG TCFGGYNMAM AVMSPCPLLQ GHWGGEVLIV ASWVLFSGCL SYVKVMLGVV 430 440 450 460 LRDLSRSALL WCGAAVQLGS LLGALLMFPL VNVLRLFSSA DFCNLHCPA
	Isoform 2 [UniParc]. Checksum: 8E072208A8998A56	FASTA	415	45,043
	10 20 30 40 50 60 MAFLMHLLVC VFGMGSWVTI NGLWVELPLL VMELPEGWYL PSYLTVVIQL ANIGPLLVTL 70 80 90 100 110 120 LHHFRPSCLS EVPIIFTLLG VGTVTCIIFA FLWNMTSWVL DGHHSIAFLV LTFFLALVDC 130 140 150 160 170 180 TSSVTFLPFM SRLPTYYLTT FFVGEGLSGL LPALVALAQG SGLTTCVNVT EISDSVPSPV 190 200 210 220 230 240 PTRETDIAQG VPRALVSALP GMEAPLSHLE SRYLPAHFSP LVFFLLLSIM MACCLVAFFV 250 260 270 280 290 300 LQRQPRCWEA SVEDLLNDQV TLHSIRPREE NDLGPAGTVD SSQGQGYLEE KAAPCCPAHL 310 320 330 340 350 360 AFIYTLVAFV NALTNGMLPS VQTYSCLSYG PVAYHLAATL SIVANPLASL VSMFLPNRSL 370 380 390 400 410 LFLGVLSVLG TCFGGYNMAM AVMSPCPLLQ GHWGGEVLIV SIRPVGLLPL RTPHP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Mammary gland and Placenta.
[2]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS LEU-267; MET-278 AND VAL-303. Tissue: Pancreas.
[4]	"Identification and functional characterization of rat riboflavin transporter 2." Yamamoto S., Inoue K., Ohta K.Y., Fukatsu R., Maeda J.Y., Yoshida Y., Yuasa H. J. Biochem. 145:437-443(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION.
[5]	"Identification and comparative functional characterization of a new human riboflavin transporter hRFT3 expressed in the brain." Yao Y., Yonezawa A., Yoshimatsu H., Masuda S., Katsura T., Inui K. J. Nutr. 140:1220-1226(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES.
[6]	"Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment." Bosch A.M., Abeling N.G., Ijlst L., Knoester H., van der Pol W.L., Stroomer A.E., Wanders R.J., Visser G., Wijburg F.A., Duran M., Waterham H.R. J. Inherit. Metab. Dis. 34:159-164(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN FALOND.
[7]	"Brown-Vialetto-Van Laere syndrome, a ponto-bulbar palsy with deafness, is caused by mutations in c20orf54." Green P., Wiseman M., Crow Y.J., Houlden H., Riphagen S., Lin J.P., Raymond F.L., Childs A.M., Sheridan E., Edwards S., Josifova D.J. Am. J. Hum. Genet. 86:485-489(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BVVLS1 LYS-36; TRP-132; LEU-224; ALA-413 AND LEU-457, VARIANT MET-350.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK074650 mRNA. Translation: BAC11113.1. AK291706 mRNA. Translation: BAF84395.1. AL118502 Genomic DNA. Translation: CAH73077.2. AL118502 Genomic DNA. Translation: CAH73078.2. BC009750 mRNA. Translation: AAH09750.2.
IPI	IPI00012749. IPI00215738.
RefSeq	NP_212134.3. NM_033409.3.
UniGene	Hs.283865.
3D structure databases
ProteinModelPortal	Q9NQ40.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000217254.
PTM databases
PhosphoSite	Q9NQ40.
Polymorphism databases
DMDM	82654931.
Proteomic databases
PRIDE	Q9NQ40.
Protocols and materials databases
DNASU	113278.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000217254; ENSP00000217254; ENSG00000101276. ENST00000381944; ENSP00000371370; ENSG00000101276.
GeneID	113278.
KEGG	hsa:113278.
UCSC	uc002wed.4. human. uc002wee.2. human.
Organism-specific databases
CTD	113278.
GeneCards	GC20M000741.
H-InvDB	HIX0015557.
HGNC	HGNC:16187. SLC52A3.
HPA	HPA049391.
MIM	211500. phenotype. 211530. phenotype. 613350. gene.
neXtProt	NX_Q9NQ40.
Orphanet	97229. Brown-Vialetto-van Laere syndrome. 56965. Progressive bulbar paralysis of childhood.
PharmGKB	PA25764.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG326568.
HOGENOM	HOG000247012.
HOVERGEN	HBG051170.
InParanoid	Q9NQ40.
KO	K14620.
OMA	LACFLSM.
OrthoDB	EOG4XWFZ3.
PhylomeDB	Q9NQ40.
Gene expression databases
Bgee	Q9NQ40.
CleanEx	HS_C20orf54.
Genevestigator	Q9NQ40.
GermOnline	ENSG00000101276. Homo sapiens.
Family and domain databases
InterPro	IPR009357. Endogenous_retrovirus_rcpt. [Graphical view]
PANTHER	PTHR12929. PTHR12929. 1 hit.
Pfam	PF06237. DUF1011. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	113278.
NextBio	78824.
SOURCE	Search...

Entry information

Entry name

S52A3_HUMAN

Accession

Primary (citable) accession number: Q9NQ40
Secondary accession number(s): A8K6P1 , Q5W1A0, Q5W1A1, Q8NCL7, Q96GD5

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 10, 2003
Last sequence update:	November 22, 2005
Last modified:	May 1, 2013
This is version 98 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.