NPT2A_MOUSE
ID NPT2A_MOUSE Reviewed; 637 AA.
AC Q60825; E9QKA0; Q62110; Q62111; Q62112; Q62113; Q62114; Q62115; Q62116;
AC Q62564;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Sodium-dependent phosphate transport protein 2A;
DE Short=Sodium-phosphate transport protein 2A;
DE AltName: Full=Na(+)-dependent phosphate cotransporter 2A;
DE AltName: Full=NaPi-7 {ECO:0000303|PubMed:7478940};
DE AltName: Full=Sodium/phosphate cotransporter 2A;
DE Short=Na(+)/Pi cotransporter 2A;
DE Short=NaPi-2a;
DE AltName: Full=Solute carrier family 34 member 1 {ECO:0000312|MGI:MGI:1345284};
GN Name=Slc34a1 {ECO:0000312|MGI:MGI:1345284};
GN Synonyms=Npt2 {ECO:0000303|PubMed:7478940},
GN Slc17a2 {ECO:0000312|MGI:MGI:1345284};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY, AND TISSUE
RP SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Kidney cortex;
RX PubMed=8070635; DOI=10.1096/fasebj.8.11.8070635;
RA Collins J.F., Ghishan F.K.;
RT "Molecular cloning, functional expression, tissue distribution, and in situ
RT hybridization of the renal sodium phosphate (Na+/P(i)) transporter in the
RT control and hypophosphatemic mouse.";
RL FASEB J. 8:862-869(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=BALB/cJ; TISSUE=Kidney cortex;
RX PubMed=7478940; DOI=10.1007/bf00386183;
RA Hartmann C.M., Wagner C.A., Busch A.E., Markovich D., Biber J., Lang F.,
RA Murer H.;
RT "Transport characteristics of a murine renal Na/Pi-cotransporter.";
RL Pflugers Arch. 430:830-836(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-94; 110-177; 179-242; 254-312;
RP 313-318; 332-333; 335-337 AND 349-485.
RC STRAIN=129/Sv;
RX PubMed=8693007; DOI=10.1073/pnas.93.14.7409;
RA Hartmann C.M., Hewson A.S., Kos C.H., Hilfiker H., Soumounou Y., Murer H.,
RA Tenenhouse H.S.;
RT "Structure of murine and human renal type II Na+-phosphate cotransporter
RT genes (Npt2 and NPT2).";
RL Proc. Natl. Acad. Sci. U.S.A. 93:7409-7414(1996).
RN [5]
RP INDUCTION.
RC STRAIN=ICR;
RX PubMed=10497181; DOI=10.1074/jbc.274.40.28256;
RA Kido S., Miyamoto K., Mizobuchi H., Taketani Y., Ohkido I., Ogawa N.,
RA Kaneko Y., Harashima S., Takeda E.;
RT "Identification of regulatory sequences and binding proteins in the type II
RT sodium/phosphate cotransporter NPT2 gene responsive to dietary phosphate.";
RL J. Biol. Chem. 274:28256-28263(1999).
RN [6]
RP INTERACTION WITH PDZK2.
RX PubMed=11950846; DOI=10.1074/jbc.m202434200;
RA Scott R.O., Thelin W.R., Milgram S.L.;
RT "A novel PDZ protein regulates the activity of guanylyl cyclase C, the
RT heat-stable enterotoxin receptor.";
RL J. Biol. Chem. 277:22934-22941(2002).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-34; THR-621 AND SER-623, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Involved in actively transporting phosphate into cells via
CC Na(+) cotransport in the renal brush border membrane (PubMed:8070635,
CC PubMed:7478940). The cotransport has a Na(+):Pi stoichiometry of 3:1
CC and is electrogenic (By similarity). {ECO:0000250|UniProtKB:Q06496,
CC ECO:0000269|PubMed:7478940, ECO:0000269|PubMed:8070635}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 Na(+)(out) + phosphate(out) = 3 Na(+)(in) + phosphate(in);
CC Xref=Rhea:RHEA:71255, ChEBI:CHEBI:29101, ChEBI:CHEBI:43474;
CC Evidence={ECO:0000269|PubMed:7478940, ECO:0000269|PubMed:8070635};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71256;
CC Evidence={ECO:0000305|PubMed:8070635};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=79.6 mM for sodium (at pH 6.3 and a phosphate concentration of 1
CC mM) {ECO:0000269|PubMed:7478940};
CC KM=37.5 mM for sodium (at pH 7.4 and a phosphate concentration of 1
CC mM) {ECO:0000269|PubMed:7478940};
CC KM=41.7 mM for sodium (at pH 7.4 and a phosphate concentration of 0.3
CC mM) {ECO:0000269|PubMed:7478940};
CC KM=48.7 mM for sodium (at pH 7.8 and a phosphate concentration of 1
CC mM) {ECO:0000269|PubMed:7478940};
CC KM=0.07 mM for phosphate (at a sodium concentration of 100 mM)
CC {ECO:0000269|PubMed:7478940};
CC KM=0.47 mM for phosphate (at a sodium concentration of 50 mM)
CC {ECO:0000269|PubMed:7478940};
CC -!- SUBUNIT: Interacts via its C-terminal region with PDZK2
CC (PubMed:11950846). Interacts with SLC9A3R1 (By similarity).
CC {ECO:0000250|UniProtKB:Q06495, ECO:0000269|PubMed:11950846}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000250|UniProtKB:Q06495}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:Q06496}; Multi-pass
CC membrane protein {ECO:0000255}. Note=Localized at the brush border
CC membranes of the proximal tubules. {ECO:0000250|UniProtKB:Q06496}.
CC -!- TISSUE SPECIFICITY: Kidney. {ECO:0000269|PubMed:8070635}.
CC -!- INDUCTION: Up-regulated by low-phosphate diet.
CC {ECO:0000269|PubMed:10497181}.
CC -!- SIMILARITY: Belongs to the SLC34A transporter family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC52684.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; L33878; AAC42026.1; -; mRNA.
DR EMBL; U22465; AAC52361.1; -; mRNA.
DR EMBL; CT009762; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U56664; AAC52684.1; ALT_INIT; Genomic_DNA.
DR EMBL; U56665; AAC52685.1; -; Genomic_DNA.
DR EMBL; U56666; AAC52686.1; -; Genomic_DNA.
DR EMBL; U56667; AAC52687.1; -; Genomic_DNA.
DR EMBL; U56668; AAC52688.1; -; Genomic_DNA.
DR EMBL; U56669; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U56670; AAC52689.1; -; Genomic_DNA.
DR EMBL; U56671; AAC52690.1; -; Genomic_DNA.
DR EMBL; U56672; AAC52691.1; -; Genomic_DNA.
DR EMBL; U56673; AAC52692.1; -; Genomic_DNA.
DR CCDS; CCDS49271.1; -.
DR AlphaFoldDB; Q60825; -.
DR CORUM; Q60825; -.
DR IntAct; Q60825; 11.
DR MINT; Q60825; -.
DR STRING; 10090.ENSMUSP00000059138; -.
DR BindingDB; Q60825; -.
DR ChEMBL; CHEMBL4295855; -.
DR GlyGen; Q60825; 2 sites.
DR iPTMnet; Q60825; -.
DR PhosphoSitePlus; Q60825; -.
DR jPOST; Q60825; -.
DR MaxQB; Q60825; -.
DR PaxDb; Q60825; -.
DR PeptideAtlas; Q60825; -.
DR PRIDE; Q60825; -.
DR ProteomicsDB; 293956; -.
DR MGI; MGI:1345284; Slc34a1.
DR eggNOG; ENOG502QQ3I; Eukaryota.
DR InParanoid; Q60825; -.
DR Reactome; R-MMU-427589; Type II Na+/Pi cotransporters.
DR Reactome; R-MMU-5683826; Surfactant metabolism.
DR ChiTaRS; Slc34a1; mouse.
DR PRO; PR:Q60825; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q60825; protein.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:MGI.
DR GO; GO:0005903; C:brush border; IBA:GO_Central.
DR GO; GO:0031526; C:brush border membrane; ISO:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISO:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0072686; C:mitotic spindle; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0031982; C:vesicle; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0030165; F:PDZ domain binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0005436; F:sodium:phosphate symporter activity; IDA:UniProtKB.
DR GO; GO:1901684; P:arsenate ion transmembrane transport; ISO:MGI.
DR GO; GO:0046849; P:bone remodeling; IMP:MGI.
DR GO; GO:0055074; P:calcium ion homeostasis; IMP:MGI.
DR GO; GO:0030643; P:cellular phosphate ion homeostasis; IBA:GO_Central.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0030505; P:inorganic diphosphate transport; IMP:MGI.
DR GO; GO:0055062; P:phosphate ion homeostasis; ISO:MGI.
DR GO; GO:0035435; P:phosphate ion transmembrane transport; ISO:MGI.
DR GO; GO:0006817; P:phosphate ion transport; ISO:MGI.
DR GO; GO:0045838; P:positive regulation of membrane potential; ISO:MGI.
DR GO; GO:2000187; P:positive regulation of phosphate transmembrane transport; ISO:MGI.
DR GO; GO:2000120; P:positive regulation of sodium-dependent phosphate transport; ISO:MGI.
DR GO; GO:0046686; P:response to cadmium ion; ISO:MGI.
DR GO; GO:0010288; P:response to lead ion; ISO:MGI.
DR GO; GO:0046689; P:response to mercury ion; ISO:MGI.
DR GO; GO:1904383; P:response to sodium phosphate; IMP:MGI.
DR GO; GO:0098719; P:sodium ion import across plasma membrane; ISO:MGI.
DR GO; GO:0044341; P:sodium-dependent phosphate transport; IBA:GO_Central.
DR InterPro; IPR003841; Na/Pi_transpt.
DR InterPro; IPR029848; Na/Pi_transpt_2A.
DR PANTHER; PTHR10010; PTHR10010; 1.
DR PANTHER; PTHR10010:SF21; PTHR10010:SF21; 1.
DR Pfam; PF02690; Na_Pi_cotrans; 2.
DR TIGRFAMs; TIGR01013; 2a58; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Glycoprotein; Ion transport; Membrane;
KW Phosphoprotein; Reference proteome; Sodium; Sodium transport; Symport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..637
FT /note="Sodium-dependent phosphate transport protein 2A"
FT /id="PRO_0000068608"
FT TOPO_DOM 1..103
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q06496"
FT TRANSMEM 104..125
FT /note="Helical; Name=M1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 126..145
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q06496"
FT TRANSMEM 146..163
FT /note="Helical; Name=M2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 164..165
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q06496"
FT TRANSMEM 166..185
FT /note="Helical; Name=M3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 186..345
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q06496"
FT TRANSMEM 346..368
FT /note="Helical; Name=M4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 369..410
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q06496"
FT TRANSMEM 411..434
FT /note="Helical; Name=M5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 435..464
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q06496"
FT TRANSMEM 465..485
FT /note="Helical; Name=M6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 486..511
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q06496"
FT TRANSMEM 512..532
FT /note="Helical; Name=M7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 533..537
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q06496"
FT TRANSMEM 538..559
FT /note="Helical; Name=M8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 560..637
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q06496"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06496"
FT MOD_RES 34
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 506
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000255"
FT MOD_RES 605
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06496"
FT MOD_RES 621
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 623
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 298
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 328
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 225..520
FT /evidence="ECO:0000250|UniProtKB:Q06496"
FT DISULFID 306..334
FT /evidence="ECO:0000250|UniProtKB:Q06496"
FT CONFLICT 324
FT /note="G -> A (in Ref. 1; AAC42026)"
FT /evidence="ECO:0000305"
FT CONFLICT 345
FT /note="D -> A (in Ref. 2; AAC52361)"
FT /evidence="ECO:0000305"
FT CONFLICT 379
FT /note="V -> VA (in Ref. 1; AAC42026, 2; AAC52361 and 4;
FT AAC52690)"
FT /evidence="ECO:0000305"
FT CONFLICT 380..389
FT /note="MSSRRSSTQT -> NVIQKVINTD (in Ref. 1; AAC42026)"
FT /evidence="ECO:0000305"
FT CONFLICT 390
FT /note="Missing (in Ref. 2; AAC52361 and 4; AAC52690)"
FT /evidence="ECO:0000305"
FT CONFLICT 444
FT /note="G -> D (in Ref. 1; AAC42026)"
FT /evidence="ECO:0000305"
FT CONFLICT 458
FT /note="L -> V (in Ref. 1; AAC42026 and 2; AAC52361)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 637 AA; 68774 MW; EF6F68AB1EDC6557 CRC64;
MMSYSERLGG PAVSPLPVRG RHMVHGATFA YVPSPQVLHR IPGTSTYAIS SLSPVTLTEH
SCPCGEVLEC HDPLPTKLAQ EEEQKPEPRL SQKLAQVGTK LLKVPLMLAF LYLFVCSLDV
LSSAFQLAGG KVAGDIFKDN AILSNPVAGL VVGILVTVLV QSSSTSTSII VSMVSSGLLE
VSSAIPIIMG SNIGTSVTNT IVALMQAGDR TDFRRAFAGA TVHDCFNWLS VLVLLPLEAA
TGYLHHVTGL VVASFNIRGG RDAPDLLKVI TEPFTRLIIQ LDKSVITSIA VGDESLRNHS
LIRIWCHPDT TEASTSMSRV EAIGSLANTT MEKCNHIFVD TGLPDLAVGL ILLAGSLVVL
CTCLILLVKM LNSLLKGQVM SSRRSSTQTD FPAPFTWVTG YFAMVVGASM TFVVQSSSVF
TSAITPLIGL GVISIERAYP LTLGSNIGTT TTAILAALAS PREKLSSSFQ IALCHFFFNI
SGILLWYPLP CTRLPIRMAK ALGKRTAKYR WFAVLYLLVC FLLLPSLVFG ISMAGWQAMV
GVGTPFGALL AFVVLVNVLQ SRSPGHLPKW LQTWDFLPRW MHSLQPLDGL ITRATLCYAR
PEPRSPQLPP RVFLEELPPA TPSPRLALPA HHNATRL
