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O00476 (NPT4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium-dependent phosphate transport protein 4
Alternative name(s):
Na(+)/PI cotransporter 4
Sodium/phosphate cotransporter 4
Solute carrier family 17 member 3
Gene names
Name:SLC17A3
Synonyms:NPT4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length420 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Isoform 2:voltage-driven, multispecific, organic anion transporter able to transport para-aminohippurate (PAH), estrone sulfate, estradiol-17-beta-glucuronide, bumetanide, and ochratoxin A. Isoform 2 functions as urate efflux transporter on the apical side of renal proximal tubule and is likely to act as an exit path for organic anionic drugs as well as urate in vivo. May be involved in actively transporting phosphate into cells via Na+ cotransport. Ref.7

Subcellular location

Isoform 1: Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.6 Ref.7.

Isoform 2: Cell membrane; Multi-pass membrane protein Ref.6 Ref.7.

Tissue specificity

Expressed in the liver and kidney. It is detected in proximal tubules in renal cortex as well as some tubules and glomeruli, with highest expression at the apical side of proximal tubules (at protein level). Ref.1 Ref.7

Polymorphism

Genetic variations in SLC17A3 influence the variance in serum uric acid concentrations and define the serum uric acid concentration quantitative trait locus 4 (UAQTL4) [MIM:612671]. Excess serum accumulation of uric acid can lead to the development of gout, a common disorder characterized by tissue deposition of monosodium urate crystals as a consequence of hyperuricemia.

Sequence similarities

Belongs to the major facilitator superfamily. Sodium/anion cotransporter family.

Sequence caution

The sequence AAB53423.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processIon transport
Sodium transport
Symport
Transport
   Cellular componentCell membrane
Endoplasmic reticulum
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   LigandSodium
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdrug transmembrane transport

Inferred from direct assay Ref.7. Source: GOC

drug transport

Inferred from direct assay Ref.7. Source: UniProtKB

glucose-6-phosphate transport

Traceable author statement Ref.6. Source: UniProtKB

ion transmembrane transport

Traceable author statement. Source: Reactome

organic acid transport

Inferred from direct assay Ref.7. Source: GOC

organic anion transport

Inferred from direct assay Ref.7. Source: UniProtKB

phosphate ion transmembrane transport

Inferred from sequence or structural similarity. Source: GOC

phosphate ion transport

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of anion transport

Inferred from direct assay Ref.7. Source: GOC

sodium ion transmembrane transport

Inferred from sequence or structural similarity. Source: GOC

sodium ion transport

Inferred from sequence or structural similarity. Source: UniProtKB

toxin transport

Inferred from direct assay Ref.7. Source: GOC

transmembrane transport

Traceable author statement. Source: Reactome

urate metabolic process

Inferred from mutant phenotype PubMed 18834626PubMed 20053405PubMed 20162743. Source: UniProtKB

urate transport

Inferred from direct assay Ref.7. Source: UniProtKB

   Cellular_componentapical plasma membrane

Inferred from direct assay Ref.7. Source: UniProtKB

brush border membrane

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.7. Source: UniProtKB

endoplasmic reticulum membrane

Inferred from direct assay Ref.6. Source: UniProtKB

integral component of plasma membrane

Inferred from direct assay Ref.7. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay Ref.6. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functiondrug transmembrane transporter activity

Inferred from direct assay Ref.7. Source: UniProtKB

efflux transmembrane transporter activity

Inferred from direct assay Ref.7. Source: UniProtKB

organic anion transmembrane transporter activity

Inferred from direct assay Ref.7. Source: UniProtKB

sodium:phosphate symporter activity

Inferred from sequence or structural similarity. Source: UniProtKB

toxin transporter activity

Inferred from direct assay Ref.7. Source: UniProtKB

urate transmembrane transporter activity

Inferred from direct assay Ref.7. Source: UniProtKB

voltage-gated anion channel activity

Inferred from direct assay Ref.7. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O00476-1)

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: O00476-2)

The sequence of this isoform differs from the canonical sequence as follows:
     101-101: K → KAPVYDWSPQ...VTRIVQGLSQ
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 420420Sodium-dependent phosphate transport protein 4
PRO_0000351138

Regions

Transmembrane126 – 14621Helical; Potential
Transmembrane154 – 17421Helical; Potential
Transmembrane218 – 23821Helical; Potential
Transmembrane256 – 27621Helical; Potential
Transmembrane292 – 31423Helical; Potential
Transmembrane319 – 34123Helical; Potential
Transmembrane357 – 37721Helical; Potential
Transmembrane385 – 40521Helical; Potential

Amino acid modifications

Glycosylation491N-linked (GlcNAc...) Potential
Glycosylation601N-linked (GlcNAc...) Potential
Glycosylation681N-linked (GlcNAc...) Potential
Glycosylation771N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1011K → KAPVYDWSPQIQGIIFGAVG YGGILTMAPSGYLAGRVGTK RVVGISLFATSFLTLCIPLA TDFGIVLLIVTRIVQGLSQ in isoform 2.
VSP_042888
Natural variant681N → H Found in a patient with gout; does not affect isoform 2 localization at the cell membrane; results in reduced urate efflux. Ref.7
VAR_068680
Natural variant1001A → T. Ref.5
Corresponds to variant rs1165165 [ dbSNP | Ensembl ].
VAR_024533
Natural variant2011G → R. Ref.6
Corresponds to variant rs56027330 [ dbSNP | Ensembl ].
VAR_034700
Natural variant2261F → S Found in a patient with hyperuricemia; decreased expression of isoform 2 at the cell membrane; results in highly reduced urate efflux. Ref.7
VAR_068681
Natural variant3001P → L.
Corresponds to variant rs11966370 [ dbSNP | Ensembl ].
VAR_046633

Experimental info

Sequence conflict311V → G in AAB53423. Ref.1
Sequence conflict1791V → F in AAB53423. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 23, 2008. Version 2.
Checksum: BFDFCC7F4345F573

FASTA42046,106
        10         20         30         40         50         60 
MATKTELSPT ARESKNAQDM QVDETLIPRK VPSLCSARYG IALVLHFCNF TTIAQNVIMN 

        70         80         90        100        110        120 
ITMVAMVNST SPQSQLNDSS EVLPVDSFGG LSKAPKSLPA KSSILGGQFA IWEKWGPPQE 

       130        140        150        160        170        180 
RSRLCSIALS GMLLGCFTAI LIGGFISETL GWPFVFYIFG GVGCVCCLLW FVVIYDDPVS 

       190        200        210        220        230        240 
YPWISTSEKE YIISSLKQQV GSSKQPLPIK AMLRSLPIWS ICLGCFSHQW LVSTMVVYIP 

       250        260        270        280        290        300 
TYISSVYHVN IRDNGLLSAL PFIVAWVIGM VGGYLADFLL TKKFRLITVR KIATILGSLP 

       310        320        330        340        350        360 
SSALIVSLPY LNSGYITATA LLTLSCGLST LCQSGIYINV LDIAPRYSSF LMGASRGFSS 

       370        380        390        400        410        420 
IAPVIVPTVS GFLLSQDPEF GWRNVFFLLF AVNLLGLLFY LIFGEADVQE WAKERKLTRL 

« Hide

Isoform 2 [UniParc].

Checksum: 28523A1A29FD2562
Show »

FASTA49854,259

References

« Hide 'large scale' references
[1]"A 1.1-Mb transcript map of the hereditary hemochromatosis locus."
Ruddy D.A., Kronmal G.S., Lee V.K., Mintier G.A., Quintana L., Domingo R. Jr., Meyer N.C., Irrinki A., McClelland E.E., Fullan A., Mapa F.A., Moore T., Thomas W., Loeb D.B., Harmon C., Tsuchihashi Z., Wolff R.K., Schatzman R.C., Feder J.N.
Genome Res. 7:441-456(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[2]"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. expand/collapse author list , 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: Kidney.
[3]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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), VARIANT THR-100.
Tissue: Kidney.
[6]"NPT4, a new microsomal phosphate transporter: mutation analysis in glycogen storage disease type Ic."
Melis D., Havelaar A.C., Verbeek E., Smit G.P.A., Benedetti A., Mancini G.M.S., Verheijen F.
J. Inherit. Metab. Dis. 27:725-733(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, VARIANT ARG-201.
[7]"Human sodium phosphate transporter 4 (hNPT4/SLC17A3) as a common renal secretory pathway for drugs and urate."
Jutabha P., Anzai N., Kitamura K., Taniguchi A., Kaneko S., Yan K., Yamada H., Shimada H., Kimura T., Katada T., Fukutomi T., Tomita K., Urano W., Yamanaka H., Seki G., Fujita T., Moriyama Y., Yamada A. expand/collapse author list , Uchida S., Wempe M.F., Endou H., Sakurai H.
J. Biol. Chem. 285:35123-35132(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS ORGANIC ANION TRANSPORTER (ISOFORM 2), TISSUE SPECIFICITY, SUBCELLULAR LOCATION (ISOFORM 2), INVOLVEMENT IN UAQTL4, VARIANTS HIS-68 AND SER-226, CHARACTERIZATION OF VARIANTS HIS-68 AND SER-226.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U90545 mRNA. Translation: AAB53423.1. Different initiation.
AK298271 mRNA. Translation: BAH12747.1.
AL138726 Genomic DNA. Translation: CAC16543.1.
CH471087 Genomic DNA. Translation: EAW55495.1.
BC017952 mRNA. Translation: AAH17952.1.
CCDSCCDS4566.2. [O00476-1]
CCDS47385.1. [O00476-2]
RefSeqNP_001091956.1. NM_001098486.1. [O00476-2]
NP_006623.2. NM_006632.3. [O00476-1]
UniGeneHs.327179.

3D structure databases

ProteinModelPortalO00476.
SMRO00476. Positions 135-165.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000380250.

Protein family/group databases

TCDB2.A.1.14.28. the major facilitator superfamily (mfs).

Proteomic databases

PaxDbO00476.
PRIDEO00476.

Protocols and materials databases

DNASU10786.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000360657; ENSP00000353873; ENSG00000124564. [O00476-1]
ENST00000361703; ENSP00000355307; ENSG00000124564. [O00476-1]
ENST00000397060; ENSP00000380250; ENSG00000124564. [O00476-2]
GeneID10786.
KEGGhsa:10786.
UCSCuc003nfi.4. human. [O00476-1]
uc003nfk.4. human. [O00476-2]

Organism-specific databases

CTD10786.
GeneCardsGC06M025833.
H-InvDBHIX0005635.
HGNCHGNC:10931. SLC17A3.
HPAHPA016569.
MIM611034. gene.
612671. phenotype.
neXtProtNX_O00476.
PharmGKBPA35822.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0477.
HOGENOMHOG000230813.
HOVERGENHBG008834.
InParanoidO00476.
KOK12300.
OMALNSGYIT.
PhylomeDBO00476.
TreeFamTF313535.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressO00476.
BgeeO00476.
CleanExHS_SLC17A3.
GenevestigatorO00476.

Family and domain databases

InterProIPR011701. MFS.
IPR020846. MFS_dom.
IPR016196. MFS_dom_general_subst_transpt.
IPR017373. Na-dep_P-transpt_4_prd.
[Graphical view]
PfamPF07690. MFS_1. 1 hit.
[Graphical view]
PIRSFPIRSF038072. Na(+)/PI_cotransporter4_prd. 1 hit.
SUPFAMSSF103473. SSF103473. 1 hit.
PROSITEPS50850. MFS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi10786.
NextBio40966.
PROO00476.
SOURCESearch...

Entry information

Entry nameNPT4_HUMAN
AccessionPrimary (citable) accession number: O00476
Secondary accession number(s): B7WNJ5 expand/collapse secondary AC list , B7Z511, Q8WWC7, Q9H533
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: September 23, 2008
Last modified: July 9, 2014
This is version 113 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM