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Q06495 (NPT2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 129. 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 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length639 AA.
Sequence statusComplete.
Protein existenceEvidence 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 processIon transport
Sodium transport
Symport
Transport
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   DomainTransmembrane
Transmembrane helix
   LigandSodium
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processarsenate ion transmembrane transport

Inferred from electronic annotation. Source: Ensembl

bone remodeling

Inferred from electronic annotation. Source: Ensembl

cellular response to metal ion

Inferred from electronic annotation. Source: Ensembl

cellular response to parathyroid hormone stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to staurosporine

Inferred from electronic annotation. Source: Ensembl

dentinogenesis

Inferred from electronic annotation. Source: Ensembl

gentamycin metabolic process

Inferred from electronic annotation. Source: Ensembl

glycoprotein metabolic process

Inferred from electronic annotation. Source: Ensembl

indole metabolic process

Inferred from electronic annotation. Source: Ensembl

ion transport

Traceable author statement. Source: Reactome

kidney development

Inferred from electronic annotation. Source: Ensembl

ossification

Inferred from electronic annotation. Source: Ensembl

phosphate ion homeostasis

Inferred from direct assay Ref.1PubMed 8898024PubMed 9530108. Source: UniProtKB

phosphate ion transport

Inferred from direct assay Ref.1PubMed 8898024PubMed 9530108. Source: UniProtKB

positive regulation of membrane potential

Inferred from electronic annotation. Source: Ensembl

positive regulation of phosphate transmembrane transport

Inferred from electronic annotation. Source: Ensembl

positive regulation of sodium-dependent phosphate transport

Inferred from electronic annotation. Source: Ensembl

protein homooligomerization

Inferred from electronic annotation. Source: Ensembl

response to cadmium ion

Inferred from direct assay PubMed 8898024. Source: UniProtKB

response to drug

Inferred from electronic annotation. Source: Ensembl

response to estradiol

Inferred from electronic annotation. Source: Ensembl

response to growth hormone

Inferred from electronic annotation. Source: Ensembl

response to lead ion

Inferred from direct assay PubMed 8898024. Source: UniProtKB

response to magnesium ion

Inferred from electronic annotation. Source: Ensembl

response to mercury ion

Inferred from direct assay PubMed 8898024. Source: UniProtKB

response to potassium ion

Inferred from electronic annotation. Source: Ensembl

response to thyroid hormone

Inferred from electronic annotation. Source: Ensembl

response to vitamin A

Inferred from electronic annotation. Source: Ensembl

sodium ion transport

Inferred from electronic annotation. Source: UniProtKB-KW

transmembrane transport

Traceable author statement. Source: Reactome

tricarboxylic acid metabolic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentapical plasma membrane

Inferred from electronic annotation. Source: Ensembl

basolateral plasma membrane

Inferred from electronic annotation. Source: Ensembl

brush border membrane

Inferred from sequence or structural similarity. Source: UniProtKB

cell surface

Inferred from electronic annotation. Source: Ensembl

endosome

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Non-traceable author statement Ref.1. Source: UniProtKB

membrane raft

Inferred from electronic annotation. Source: Ensembl

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionprotein binding

Inferred from physical interaction PubMed 17895247Ref.4. Source: UniProtKB

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 639639Sodium-dependent phosphate transport protein 2A
PRO_0000068607

Regions

Topological domain1 – 103103Cytoplasmic Potential
Transmembrane104 – 12522Helical; Name=M1; Potential
Topological domain126 – 14520Extracellular Potential
Transmembrane146 – 16318Helical; Name=M2; Potential
Topological domain164 – 1652Cytoplasmic Potential
Transmembrane166 – 18520Helical; Name=M3; Potential
Topological domain186 – 347162Extracellular Potential
Transmembrane348 – 37023Helical; Name=M4; Potential
Topological domain371 – 41242Cytoplasmic Potential
Transmembrane413 – 43624Helical; Name=M5; Potential
Topological domain437 – 46630Extracellular Potential
Transmembrane467 – 48721Helical; Name=M6; Potential
Topological domain488 – 51326Cytoplasmic Potential
Transmembrane514 – 53421Helical; Name=M7; Potential
Topological domain535 – 5395Extracellular Potential
Transmembrane540 – 56122Helical; Name=M8; Potential
Topological domain562 – 63978Cytoplasmic Potential

Amino acid modifications

Modified residue5081Phosphothreonine; by PKC Potential
Glycosylation2981N-linked (GlcNAc...) Potential
Glycosylation3231N-linked (GlcNAc...) Potential
Glycosylation3301N-linked (GlcNAc...) Potential
Disulfide bond225 ↔ 522 By similarity
Disulfide bond306 ↔ 336 By similarity

Natural variations

Alternative sequence313 – 639327APTSM…NATRL → QNLEGREITHFDLRKKQAME DSSVPHCP in isoform 2.
VSP_042311
Natural variant481A → 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 variant1471V → 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 variant1601V → VILVTVLV in FRTS2; loss of function in the homozygous state.
VAR_063812

Sequences

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

Last modified February 1, 1995. Version 1.
Checksum: 65D21D968C35D61B

FASTA63968,937
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 829AAD6A913307A4
Show »

FASTA34036,603

References

« Hide '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. 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 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. expand/collapse author list , 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.
CCDSCCDS4418.1. [Q06495-1]
CCDS54953.1. [Q06495-2]
PIRB48189.
RefSeqNP_001161051.1. NM_001167579.1. [Q06495-2]
NP_003043.3. NM_003052.4. [Q06495-1]
XP_005266031.1. XM_005265974.1. [Q06495-1]
UniGeneHs.936.

3D structure databases

ProteinModelPortalQ06495.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000321424.

Protein family/group databases

TCDB2.A.58.1.5. the phosphate:na(+) symporter (pnas) family.

PTM databases

PhosphoSiteQ06495.

Polymorphism databases

DMDM730113.

Proteomic databases

PaxDbQ06495.
PRIDEQ06495.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000324417; ENSP00000321424; ENSG00000131183. [Q06495-1]
ENST00000512593; ENSP00000423022; ENSG00000131183. [Q06495-2]
GeneID6569.
KEGGhsa:6569.
UCSCuc003mgk.4. human. [Q06495-1]
uc021yis.1. human. [Q06495-2]

Organism-specific databases

CTD6569.
GeneCardsGC05P176812.
HGNCHGNC:11019. SLC34A1.
HPAHPA051255.
MIM182309. gene.
612286. phenotype.
613388. phenotype.
neXtProtNX_Q06495.
Orphanet244305. Dominant hypophosphatemia with nephrolithiasis or osteoporosis.
3337. Primary Fanconi syndrome.
PharmGKBPA35887.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1283.
HOGENOMHOG000070039.
HOVERGENHBG079110.
InParanoidQ06495.
KOK14683.
OMAHDPLPAK.
OrthoDBEOG72ZCDP.
PhylomeDBQ06495.
TreeFamTF313981.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.
SignaLinkQ06495.

Gene expression databases

ArrayExpressQ06495.
BgeeQ06495.
CleanExHS_SLC17A2.
HS_SLC34A1.
GenevestigatorQ06495.

Family and domain databases

InterProIPR003841. Na/Pi_transpt.
[Graphical view]
PfamPF02690. Na_Pi_cotrans. 2 hits.
[Graphical view]
TIGRFAMsTIGR01013. 2a58. 1 hit.
ProtoNetSearch...

Other

GeneWikiSodium/phosphate_cotransporter.
GenomeRNAi6569.
NextBio25559.
PROQ06495.
SOURCESearch...

Entry information

Entry nameNPT2A_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 129 of the entry and version 1 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 5

Human chromosome 5: entries, gene names and cross-references to MIM