Q06495 (NPT2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium-dependent phosphate transport protein 2A
Short name=Sodium-phosphate transport protein 2A

Alternative name(s):
Na(+)-dependent phosphate cotransporter 2A
NaPi-3
Sodium/phosphate cotransporter 2A
Short name=Na(+)/Pi cotransporter 2A
Short name=NaPi-2a
Solute carrier family 34 member 1

Gene names

Name:	SLC34A1
Synonyms:	NPT2, SLC17A2

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	639 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May be involved in actively transporting phosphate into cells via Na+ cotransport in the renal brush border membrane. Probably mediates 70-80% of the apical influx.
Subunit structure	Interacts via its C-terminal region with PDZK2 By similarity. Interacts with SLC9A3R1. Ref.4
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Kidney and lung.
Involvement in disease	Nephrolithiasis/osteoporosis, hypophosphatemic, 1 (NPHLOP1) [MIM:612286]: A disease characterized by decreased renal phosphate absorption, renal phosphate wasting, hypophosphatemia, hyperphosphaturia, hypercalciuria, nephrolithiasis and osteoporosis. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Fanconi renotubular syndrome 2 (FRTS2) [MIM:613388]: A disease due to a generalized dysfunction of the proximal kidney tubule resulting in decreased solute and water reabsorption. Patients have polydipsia and polyuria with phosphaturia, glycosuria and aminoaciduria. They may develop hypophosphatemic rickets or osteomalacia, acidosis and a tendency toward dehydration. Some eventually develop renal insufficiency. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6
Sequence similarities	Belongs to the SLC34A transporter family.

Ontologies

Keywords
Biological process	Ion transport Sodium transport Symport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Ligand	Sodium
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bone remodeling Inferred from electronic annotation. Source: Compara phosphate ion homeostasis Inferred from direct assay Ref.1PubMed 8898024PubMed 9530108. Source: UniProtKB response to cadmium ion Inferred from direct assay PubMed 8898024. Source: UniProtKB response to lead ion Inferred from direct assay PubMed 8898024. Source: UniProtKB response to magnesium ion Inferred from electronic annotation. Source: Compara response to mercury ion Inferred from direct assay PubMed 8898024. Source: UniProtKB sodium ion transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	basolateral plasma membrane Inferred from electronic annotation. Source: Compara brush border membrane Inferred from sequence or structural similarity. Source: UniProtKB integral to plasma membrane Non-traceable author statement Ref.1. Source: UniProtKB
Molecular_function	sodium-dependent phosphate transmembrane transporter activity Inferred from direct assay Ref.1PubMed 8898024PubMed 9530108. Source: UniProtKB symporter activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q06495-1)

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: Q06495-2)

The sequence of this isoform differs from the canonical sequence as follows:
     313-639: APTSMSRAEA...LPAHHNATRL → QNLEGREITHFDLRKKQAMEDSSVPHCP

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 639	639	Sodium-dependent phosphate transport protein 2A		PRO_0000068607
Regions
	Topological domain	1 – 103	103	Cytoplasmic Potential
	Transmembrane	104 – 125	22	Helical; Name=M1; Potential
	Topological domain	126 – 145	20	Extracellular Potential
	Transmembrane	146 – 163	18	Helical; Name=M2; Potential
	Topological domain	164 – 165	2	Cytoplasmic Potential
	Transmembrane	166 – 185	20	Helical; Name=M3; Potential
	Topological domain	186 – 347	162	Extracellular Potential
	Transmembrane	348 – 370	23	Helical; Name=M4; Potential
	Topological domain	371 – 412	42	Cytoplasmic Potential
	Transmembrane	413 – 436	24	Helical; Name=M5; Potential
	Topological domain	437 – 466	30	Extracellular Potential
	Transmembrane	467 – 487	21	Helical; Name=M6; Potential
	Topological domain	488 – 513	26	Cytoplasmic Potential
	Transmembrane	514 – 534	21	Helical; Name=M7; Potential
	Topological domain	535 – 539	5	Extracellular Potential
	Transmembrane	540 – 561	22	Helical; Name=M8; Potential
	Topological domain	562 – 639	78	Cytoplasmic Potential
Amino acid modifications
	Modified residue	508	1	Phosphothreonine; by PKC Potential
	Glycosylation	298	1	N-linked (GlcNAc...) Potential
	Glycosylation	323	1	N-linked (GlcNAc...) Potential
	Glycosylation	330	1	N-linked (GlcNAc...) Potential
	Disulfide bond	225 ↔ 522		By similarity
	Disulfide bond	306 ↔ 336		By similarity
Natural variations
	Alternative sequence	313 – 639	327	APTSM…NATRL → QNLEGREITHFDLRKKQAME DSSVPHCP in isoform 2.		VSP_042311
	Natural variant	48	1	A → F in NPHLOP1; causes hypophosphatemic urolithiasis; results in lower phosphate current, decreases affinity for phosphate and decreases phosphate uptake compared to wild-type; shows a dominant-negative effect; requires 2 nucleotide substitutions. Ref.5		VAR_024765
	Natural variant	147	1	V → M in NPHLOP1; causes hypophosphatemic osteoporosis; results in lower phosphate current, decreases affinity for phosphate and decreases phosphate uptake compared to wild-type; shows a dominant-negative effect. Ref.5		VAR_024766
	Natural variant	160	1	V → VILVTVLV in FRTS2; loss of function in the homozygous state.		VAR_063812

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: 65D21D968C35D61B	FASTA	639	68,937
	10 20 30 40 50 60 MLSYGERLGS PAVSPLPVRG GHVMRGTAFA YVPSPQVLHR IPGTSAYAFP SLGPVALAEH 70 80 90 100 110 120 TCPCGEVLER HEPLPAKLAL EEEQKPESRL VPKLRQAGAM LLKVPLMLTF LYLFVCSLDM 130 140 150 160 170 180 LSSAFQLAGG KVAGDIFKDN AILSNPVAGL VVGILVTVLV QSSSTSTSII VSMVSSGLLE 190 200 210 220 230 240 VSSAIPIIMG SNIGTSVTNT IVALMQAGDR TDFRRAFAGA TVHDCFNWLS VLVLLPLEAA 250 260 270 280 290 300 TGYLHHITRL VVASFNIHGG RDAPDLLKII TEPFTKLIIQ LDESVITSIA TGDESLRNHS 310 320 330 340 350 360 LIQIWCHPDS LQAPTSMSRA EANSSQTLGN ATMEKCNHIF VDTGLPDLAV GLILLAGSLV 370 380 390 400 410 420 LLCTCLILLV KMLNSLLKGQ VAKVIQKVIN TDFPAPFTWV TGYFAMVVGA SMTFVVQSSS 430 440 450 460 470 480 VFTSAITPLI GLGVISIERA YPLTLGSNIG TTTTAILAAL ASPREKLSSA FQIALCHFFF 490 500 510 520 530 540 NISGILLWYP VPCTRLPIRM AKALGKRTAK YRWFAVLYLL VCFLLLPSLV FGISMAGWQV 550 560 570 580 590 600 MVGVGTPFGA LLAFVVLINV LQSRSPGHLP KWLQTWDFLP RWMHSLKPLD HLITRATLCC 610 620 630 ARPEPRSPPL PPRVFLEELP PATPSPRLAL PAHHNATRL
	Isoform 2 [UniParc]. Checksum: 829AAD6A913307A4	FASTA	340	36,603
	10 20 30 40 50 60 MLSYGERLGS PAVSPLPVRG GHVMRGTAFA YVPSPQVLHR IPGTSAYAFP SLGPVALAEH 70 80 90 100 110 120 TCPCGEVLER HEPLPAKLAL EEEQKPESRL VPKLRQAGAM LLKVPLMLTF LYLFVCSLDM 130 140 150 160 170 180 LSSAFQLAGG KVAGDIFKDN AILSNPVAGL VVGILVTVLV QSSSTSTSII VSMVSSGLLE 190 200 210 220 230 240 VSSAIPIIMG SNIGTSVTNT IVALMQAGDR TDFRRAFAGA TVHDCFNWLS VLVLLPLEAA 250 260 270 280 290 300 TGYLHHITRL VVASFNIHGG RDAPDLLKII TEPFTKLIIQ LDESVITSIA TGDESLRNHS 310 320 330 340 LIQIWCHPDS LQQNLEGREI THFDLRKKQA MEDSSVPHCP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Expression cloning of human and rat renal cortex Na/Pi cotransport." Magagnin S., Werner A., Markovich D., Sorribas V., Stange G., Biber J., Murer H. Proc. Natl. Acad. Sci. U.S.A. 90:5979-5983(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Kidney.
[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 comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"A new human NHERF1 mutation decreases renal phosphate transporter NPT2a expression by a PTH-independent mechanism." Courbebaisse M., Leroy C., Bakouh N., Salaun C., Beck L., Grandchamp B., Planelles G., Hall R.A., Friedlander G., Prie D. PLoS ONE 7:E34764-E34764(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SLC9A3R1.
[5]	"Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter." Prie D., Huart V., Bakouh N., Planelles G., Dellis O., Gerard B., Hulin P., Benque-Blanchet F., Silve C., Grandchamp B., Friedlander G. N. Engl. J. Med. 347:983-991(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS NPHLOP1 PHE-48 AND MET-147, CHARACTERIZATION OF VARIANTS NPHLOP1 PHE-48 AND MET-147.
[6]	"A loss-of-function mutation in NaPi-IIa and renal Fanconi's syndrome." Magen D., Berger L., Coady M.J., Ilivitzki A., Militianu D., Tieder M., Selig S., Lapointe J.Y., Zelikovic I., Skorecki K. N. Engl. J. Med. 362:1102-1109(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FRTS2 ILE-LEU-VAL-THR-VAL-LEU-VAL-160 INS, CHARACTERIZATION OF VARIANT FRTS2 ILE-LEU-VAL-THR-VAL-LEU-VAL-160 INS.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L13258 mRNA. Translation: AAA36354.1. AK298299 mRNA. Translation: BAG60555.1. AC145098 Genomic DNA. No translation available.
IPI	IPI00031050.
PIR	B48189.
RefSeq	NP_001161051.1. NM_001167579.1. NP_003043.3. NM_003052.4.
UniGene	Hs.936.
3D structure databases
ProteinModelPortal	Q06495.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000321424.
PTM databases
PhosphoSite	Q06495.
Polymorphism databases
DMDM	730113.
Proteomic databases
PaxDb	Q06495.
PRIDE	Q06495.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000324417; ENSP00000321424; ENSG00000131183. ENST00000512593; ENSP00000423022; ENSG00000131183.
GeneID	6569.
KEGG	hsa:6569.
UCSC	uc003mgk.4. human.
Organism-specific databases
CTD	6569.
GeneCards	GC05P176812.
HGNC	HGNC:11019. SLC34A1.
HPA	HPA051255.
MIM	182309. gene. 612286. phenotype. 613388. phenotype.
neXtProt	NX_Q06495.
Orphanet	244305. Dominant hypophosphatemia with nephrolithiasis or osteoporosis. 3337. Primary Fanconi syndrome.
PharmGKB	PA35887.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1283.
HOGENOM	HOG000070039.
HOVERGEN	HBG079110.
InParanoid	Q06495.
KO	K14683.
OMA	LPKWLQT.
OrthoDB	EOG4FTW0B.
PhylomeDB	Q06495.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q06495.
Bgee	Q06495.
CleanEx	HS_SLC17A2. HS_SLC34A1.
Genevestigator	Q06495.
GermOnline	ENSG00000131183. Homo sapiens.
Family and domain databases
InterPro	IPR003841. Na/Pi_transpt. [Graphical view]
Pfam	PF02690. Na_Pi_cotrans. 2 hits. [Graphical view]
TIGRFAMs	TIGR01013. 2a58. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	6569.
NextBio	25559.
SOURCE	Search...

Entry information

Entry name

NPT2A_HUMAN

Accession

Primary (citable) accession number: Q06495
Secondary accession number(s): B4DPE3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	May 1, 2013
This is version 116 of the entry and version 1 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.