O00476 (NPT4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	420 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Ion transport Sodium transport Symport Transport
Cellular component	Cell membrane Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Sodium
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	glucose-6-phosphate transport Traceable author statement Ref.6. Source: UniProtKB urate metabolic process Inferred from mutant phenotype PubMed 18834626PubMed 20053405PubMed 20162743. Source: UniProtKB urate transport Inferred from direct assay Ref.7. Source: UniProtKB
Cellular_component	apical plasma membrane Inferred from direct assay Ref.7. Source: UniProtKB brush border membrane Inferred from sequence or structural similarity. Source: UniProtKB endoplasmic reticulum membrane Inferred from direct assay Ref.6. Source: UniProtKB integral to plasma membrane Inferred from direct assay Ref.7. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay Ref.6. Source: UniProtKB
Molecular_function	drug 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 420	420	Sodium-dependent phosphate transport protein 4		PRO_0000351138
Regions
	Transmembrane	126 – 146	21	Helical; Potential
	Transmembrane	154 – 174	21	Helical; Potential
	Transmembrane	218 – 238	21	Helical; Potential
	Transmembrane	256 – 276	21	Helical; Potential
	Transmembrane	292 – 314	23	Helical; Potential
	Transmembrane	319 – 341	23	Helical; Potential
	Transmembrane	357 – 377	21	Helical; Potential
	Transmembrane	385 – 405	21	Helical; Potential
Amino acid modifications
	Glycosylation	49	1	N-linked (GlcNAc...) Potential
	Glycosylation	60	1	N-linked (GlcNAc...) Potential
	Glycosylation	68	1	N-linked (GlcNAc...) Potential
	Glycosylation	77	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	101	1	K → KAPVYDWSPQIQGIIFGAVG YGGILTMAPSGYLAGRVGTK RVVGISLFATSFLTLCIPLA TDFGIVLLIVTRIVQGLSQ in isoform 2.		VSP_042888
	Natural variant	68	1	N → 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 variant	100	1	A → T. Ref.5 Corresponds to variant rs1165165 [ dbSNP | Ensembl ].		VAR_024533
	Natural variant	201	1	G → R. Ref.6 Corresponds to variant rs56027330 [ dbSNP | Ensembl ].		VAR_034700
	Natural variant	226	1	F → 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 variant	300	1	P → L. Corresponds to variant rs11966370 [ dbSNP | Ensembl ].		VAR_046633
Experimental info
	Sequence conflict	31	1	V → G in AAB53423. Ref.1
	Sequence conflict	179	1	V → F in AAB53423. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 23, 2008. Version 2. Checksum: BFDFCC7F4345F573	FASTA	420	46,106
	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
	Isoform 2 [UniParc]. Checksum: 28523A1A29FD2562	FASTA	498	54,259
	10 20 30 40 50 60 MATKTELSPT ARESKNAQDM QVDETLIPRK VPSLCSARYG IALVLHFCNF TTIAQNVIMN 70 80 90 100 110 120 ITMVAMVNST SPQSQLNDSS EVLPVDSFGG LSKAPKSLPA KAPVYDWSPQ IQGIIFGAVG 130 140 150 160 170 180 YGGILTMAPS GYLAGRVGTK RVVGISLFAT SFLTLCIPLA TDFGIVLLIV TRIVQGLSQS 190 200 210 220 230 240 SILGGQFAIW EKWGPPQERS RLCSIALSGM LLGCFTAILI GGFISETLGW PFVFYIFGGV 250 260 270 280 290 300 GCVCCLLWFV VIYDDPVSYP WISTSEKEYI ISSLKQQVGS SKQPLPIKAM LRSLPIWSIC 310 320 330 340 350 360 LGCFSHQWLV STMVVYIPTY ISSVYHVNIR DNGLLSALPF IVAWVIGMVG GYLADFLLTK 370 380 390 400 410 420 KFRLITVRKI ATILGSLPSS ALIVSLPYLN SGYITATALL TLSCGLSTLC QSGIYINVLD 430 440 450 460 470 480 IAPRYSSFLM GASRGFSSIA PVIVPTVSGF LLSQDPEFGW RNVFFLLFAV NLLGLLFYLI 490 FGEADVQEWA KERKLTRL

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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. , 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.
IPI	IPI00014076. IPI00465027.
RefSeq	NP_001091956.1. NM_001098486.1. NP_006623.2. NM_006632.3.
UniGene	Hs.327179.
3D structure databases
ProteinModelPortal	O00476.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000380250.
Proteomic databases
PaxDb	O00476.
PRIDE	O00476.
Protocols and materials databases
DNASU	10786.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000360657; ENSP00000353873; ENSG00000124564. ENST00000361703; ENSP00000355307; ENSG00000124564. ENST00000397060; ENSP00000380250; ENSG00000124564.
GeneID	10786.
KEGG	hsa:10786.
UCSC	uc003nfi.4. human.
Organism-specific databases
CTD	10786.
GeneCards	GC06M025833.
H-InvDB	HIX0005635.
HGNC	HGNC:10931. SLC17A3.
HPA	HPA016569.
MIM	611034. gene. 612671. phenotype.
neXtProt	NX_O00476.
PharmGKB	PA35822.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0477.
HOGENOM	HOG000230813.
HOVERGEN	HBG008834.
InParanoid	O00476.
KO	K12300.
OMA	GQFALWE.
PhylomeDB	O00476.
Gene expression databases
ArrayExpress	O00476.
Bgee	O00476.
CleanEx	HS_SLC17A3.
Genevestigator	O00476.
GermOnline	ENSG00000124564. Homo sapiens.
Family and domain databases
InterPro	IPR011701. MFS. IPR020846. MFS_dom. IPR016196. MFS_dom_general_subst_transpt. IPR017373. Na-dep_P-transpt_4_prd. [Graphical view]
Pfam	PF07690. MFS_1. 1 hit. [Graphical view]
PIRSF	PIRSF038072. Na(+)/PI_cotransporter4_prd. 1 hit.
SUPFAM	SSF103473. MFS_gen_substrate_transporter. 1 hit.
PROSITE	PS50850. MFS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	10786.
NextBio	40966.
SOURCE	Search...

Entry information

Entry name

NPT4_HUMAN

Accession

Primary (citable) accession number: O00476
Secondary accession number(s): B7WNJ5 , B7Z511, Q8WWC7, Q9H533

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	September 23, 2008
Last modified:	April 3, 2013
This is version 101 of the entry and version 2 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.