NPT2A_RAT
ID NPT2A_RAT Reviewed; 637 AA.
AC Q06496;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 145.
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=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|RGD:3708};
GN Name=Slc34a1 {ECO:0000312|RGD:3708};
GN Synonyms=Slc17a2 {ECO:0000312|RGD:3708};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=8327470; DOI=10.1073/pnas.90.13.5979;
RA Magagnin S., Werner A., Markovich D., Sorribas V., Stange G., Biber J.,
RA Murer H.;
RT "Expression cloning of human and rat renal cortex Na/Pi cotransport.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:5979-5983(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=8691716; DOI=10.1038/ki.1996.145;
RA Lotscher M., Kaissling B., Biber J., Murer H., Kempson S.A., Levi M.;
RT "Regulation of rat renal Na/Pi-cotransporter by parathyroid hormone:
RT immunohistochemistry.";
RL Kidney Int. 49:1010-1011(1996).
RN [4]
RP FUNCTION, TRANSPORTER ACTIVITY, TISSUE SPECIFICITY, ACTIVITY REGULATION,
RP INDUCTION, AND SUBCELLULAR LOCATION.
RX PubMed=9058191; DOI=10.1093/oxfordjournals.jbchem.a021569;
RA Katai K., Segawa H., Haga H., Morita K., Arai H., Tatsumi S., Taketani Y.,
RA Miyamoto K., Hisano S., Fukui Y., Takeda E.;
RT "Acute regulation by dietary phosphate of the sodium-dependent phosphate
RT transporter (NaP(i)-2) in rat kidney.";
RL J. Biochem. 121:50-55(1997).
RN [5]
RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP STOICHIOMETRY.
RX PubMed=10198426; DOI=10.1152/ajprenal.1999.276.4.f644;
RA Forster I.C., Loo D.D., Eskandari S.;
RT "Stoichiometry and Na+ binding cooperativity of rat and flounder renal type
RT II Na+-Pi cotransporters.";
RL Am. J. Physiol. 276:F644-F649(1999).
RN [6]
RP FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=10370077; DOI=10.1007/s004240050869;
RA Lambert G., Traebert M., Hernando N., Biber J., Murer H.;
RT "Studies on the topology of the renal type II NaPi-cotransporter.";
RL Pflugers Arch. 437:972-978(1999).
RN [7]
RP FUNCTION, TRANSPORTER ACTIVITY, DISULFIDE BONDS, REVISED TOPOLOGY, AND
RP MUTAGENESIS OF CYS-62; CYS-70; CYS-116; CYS-225; CYS-306; CYS-334; CYS-361;
RP CYS-363; CYS-474; CYS-491; CYS-520 AND CYS-597.
RX PubMed=10926678; DOI=10.1007/s00232001082;
RA Lambert G., Forster I.C., Biber J., Murer H.;
RT "Cysteine residues and the structure of the rat renal proximal tubular type
RT II sodium phosphate cotransporter (rat NaPi IIa).";
RL J. Membr. Biol. 176:133-141(2000).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-605; THR-621 AND
RP SER-623, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Involved in actively transporting phosphate into cells via
CC Na(+) cotransport in the renal brush border membrane (PubMed:8327470,
CC PubMed:9058191, PubMed:10198426, PubMed:10370077, PubMed:10926678). The
CC cotransport has a Na(+):Pi stoichiometry of 3:1 and is electrogenic
CC (PubMed:10198426). {ECO:0000269|PubMed:10198426,
CC ECO:0000269|PubMed:10370077, ECO:0000269|PubMed:10926678,
CC ECO:0000269|PubMed:8327470, ECO:0000269|PubMed:9058191}.
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:10198426, ECO:0000269|PubMed:10370077,
CC ECO:0000269|PubMed:10926678, ECO:0000269|PubMed:8327470,
CC ECO:0000269|PubMed:9058191};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71256;
CC Evidence={ECO:0000305|PubMed:8327470};
CC -!- ACTIVITY REGULATION: Transport activity is significantly increased in
CC response to dietary phosphate deprivation.
CC {ECO:0000269|PubMed:9058191}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.13 mM for phosphate {ECO:0000269|PubMed:8327470};
CC KM=0.03 mM for phosphate {ECO:0000269|PubMed:10198426};
CC KM=59 mM for sodium {ECO:0000269|PubMed:10198426};
CC pH dependence:
CC Optimum pH is 8.0. {ECO:0000269|PubMed:8327470};
CC -!- SUBUNIT: Interacts via its C-terminal region with PDZK2. Interacts with
CC SLC9A3R1. {ECO:0000250|UniProtKB:Q06495, ECO:0000250|UniProtKB:Q60825}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000250|UniProtKB:Q06495}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:10370077,
CC ECO:0000269|PubMed:8691716, ECO:0000269|PubMed:9058191}; Multi-pass
CC membrane protein {ECO:0000255}. Note==Localized at the brush border
CC membranes of the proximal tubules. {ECO:0000269|PubMed:8691716,
CC ECO:0000269|PubMed:9058191}.
CC -!- TISSUE SPECIFICITY: Kidney. {ECO:0000269|PubMed:8327470,
CC ECO:0000269|PubMed:9058191}.
CC -!- INDUCTION: Up-regulated by a low-phosphate diet (PubMed:9058191). Down-
CC regulated by PTH at brush border membrane of proximal tubules
CC (PubMed:8691716). {ECO:0000269|PubMed:8691716,
CC ECO:0000269|PubMed:9058191}.
CC -!- SIMILARITY: Belongs to the SLC34A transporter family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L13257; AAC37608.1; -; mRNA.
DR EMBL; BC078876; AAH78876.1; -; mRNA.
DR PIR; A48189; A48189.
DR RefSeq; NP_037162.1; NM_013030.1.
DR AlphaFoldDB; Q06496; -.
DR STRING; 10116.ENSRNOP00000031764; -.
DR BindingDB; Q06496; -.
DR ChEMBL; CHEMBL4296024; -.
DR TCDB; 2.A.58.1.1; the phosphate:na(+) symporter (pnas) family.
DR GlyGen; Q06496; 2 sites.
DR iPTMnet; Q06496; -.
DR PhosphoSitePlus; Q06496; -.
DR PaxDb; Q06496; -.
DR Ensembl; ENSRNOT00000033749; ENSRNOP00000031764; ENSRNOG00000015262.
DR GeneID; 25548; -.
DR KEGG; rno:25548; -.
DR UCSC; RGD:3708; rat.
DR CTD; 6569; -.
DR RGD; 3708; Slc34a1.
DR eggNOG; ENOG502QQ3I; Eukaryota.
DR GeneTree; ENSGT00950000183177; -.
DR HOGENOM; CLU_025063_0_0_1; -.
DR InParanoid; Q06496; -.
DR OMA; TWDFLPA; -.
DR OrthoDB; 976094at2759; -.
DR PhylomeDB; Q06496; -.
DR TreeFam; TF313981; -.
DR Reactome; R-RNO-427589; Type II Na+/Pi cotransporters.
DR Reactome; R-RNO-5683826; Surfactant metabolism.
DR PRO; PR:Q06496; -.
DR Proteomes; UP000002494; Chromosome 17.
DR Bgee; ENSRNOG00000015262; Expressed in adult mammalian kidney and 12 other tissues.
DR Genevisible; Q06496; RN.
DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:RGD.
DR GO; GO:0005903; C:brush border; IBA:GO_Central.
DR GO; GO:0031526; C:brush border membrane; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005768; C:endosome; IDA:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; IDA:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0072686; C:mitotic spindle; IEA:Ensembl.
DR GO; GO:0016607; C:nuclear speck; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0031982; C:vesicle; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0030165; F:PDZ domain binding; IPI:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0005436; F:sodium:phosphate symporter activity; IDA:UniProtKB.
DR GO; GO:1901684; P:arsenate ion transmembrane transport; IDA:RGD.
DR GO; GO:0046849; P:bone remodeling; ISO:RGD.
DR GO; GO:0055074; P:calcium ion homeostasis; ISO:RGD.
DR GO; GO:0030643; P:cellular phosphate ion homeostasis; IBA:GO_Central.
DR GO; GO:0071248; P:cellular response to metal ion; IEP:RGD.
DR GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; IEP:RGD.
DR GO; GO:0016036; P:cellular response to phosphate starvation; IDA:UniProtKB.
DR GO; GO:0072734; P:cellular response to staurosporine; IEP:RGD.
DR GO; GO:0097187; P:dentinogenesis; IEP:RGD.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:1901128; P:gentamycin metabolic process; IEP:RGD.
DR GO; GO:0009100; P:glycoprotein metabolic process; IEP:RGD.
DR GO; GO:0042431; P:indole metabolic process; IEP:RGD.
DR GO; GO:0030505; P:inorganic diphosphate transport; ISO:RGD.
DR GO; GO:0001822; P:kidney development; IEP:RGD.
DR GO; GO:0001503; P:ossification; IEP:RGD.
DR GO; GO:0055062; P:phosphate ion homeostasis; ISO:RGD.
DR GO; GO:0035435; P:phosphate ion transmembrane transport; IMP:RGD.
DR GO; GO:0006817; P:phosphate ion transport; ISO:RGD.
DR GO; GO:0045838; P:positive regulation of membrane potential; IDA:RGD.
DR GO; GO:2000187; P:positive regulation of phosphate transmembrane transport; IDA:RGD.
DR GO; GO:2000120; P:positive regulation of sodium-dependent phosphate transport; IDA:RGD.
DR GO; GO:0046686; P:response to cadmium ion; ISO:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0060416; P:response to growth hormone; IEP:RGD.
DR GO; GO:0010288; P:response to lead ion; ISO:RGD.
DR GO; GO:0032026; P:response to magnesium ion; IEP:RGD.
DR GO; GO:0046689; P:response to mercury ion; ISO:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0071107; P:response to parathyroid hormone; IEP:RGD.
DR GO; GO:1901652; P:response to peptide; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:0035864; P:response to potassium ion; IEP:RGD.
DR GO; GO:1904383; P:response to sodium phosphate; ISO:RGD.
DR GO; GO:0097066; P:response to thyroid hormone; IEP:RGD.
DR GO; GO:0033189; P:response to vitamin A; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0098719; P:sodium ion import across plasma membrane; IDA:RGD.
DR GO; GO:0044341; P:sodium-dependent phosphate transport; IEP:RGD.
DR GO; GO:0072350; P:tricarboxylic acid metabolic process; IEP:RGD.
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_0000068610"
FT TOPO_DOM 1..103
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:10926678"
FT TRANSMEM 104..125
FT /note="Helical; Name=M1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 126..145
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:10926678"
FT TRANSMEM 146..163
FT /note="Helical; Name=M2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 164..216
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:10926678"
FT TRANSMEM 217..236
FT /note="Helical; Name=M3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 237..345
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:10926678"
FT TRANSMEM 346..368
FT /note="Helical; Name=M4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 369..410
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:10926678"
FT TRANSMEM 411..434
FT /note="Helical; Name=M5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 435..464
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:10926678"
FT TRANSMEM 465..485
FT /note="Helical; Name=M6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 486..511
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:10926678"
FT TRANSMEM 512..532
FT /note="Helical; Name=M7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 533..537
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:10926678"
FT TRANSMEM 538..559
FT /note="Helical; Name=M8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 560..637
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:10926678"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 34
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60825"
FT MOD_RES 506
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000255"
FT MOD_RES 605
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 621
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 623
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
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:0000269|PubMed:10926678"
FT DISULFID 306..334
FT /evidence="ECO:0000269|PubMed:10926678"
FT MUTAGEN 62
FT /note="C->S: Reduced protein expression and transport
FT activity."
FT /evidence="ECO:0000269|PubMed:10926678"
FT MUTAGEN 70
FT /note="C->S: No effect on protein expression and transport
FT activity."
FT /evidence="ECO:0000269|PubMed:10926678"
FT MUTAGEN 116
FT /note="C->S: No effect on protein expression and transport
FT activity."
FT /evidence="ECO:0000269|PubMed:10926678"
FT MUTAGEN 225
FT /note="C->S: No effect on protein expression but reduced
FT transport activity. Reduced protein expression and loss of
FT transport activity; when associated with S-306 or S-334."
FT /evidence="ECO:0000269|PubMed:10926678"
FT MUTAGEN 306
FT /note="C->S: No effect on protein expression but reduced
FT transport activity. Reduced protein expression and loss of
FT transport activity; when associated with S-225 or S-520. No
FT effect on protein expression and reduced transport
FT activity; when associated with S-334."
FT /evidence="ECO:0000269|PubMed:10926678"
FT MUTAGEN 334
FT /note="C->S: No effect on protein expression but reduced
FT transport activity. Reduced protein expression and loss of
FT transport activity; when associated with S-225. No effect
FT on protein expression and reduced transport activity; when
FT associated with S-306."
FT /evidence="ECO:0000269|PubMed:10926678"
FT MUTAGEN 361
FT /note="C->S: No effect on protein expression and transport
FT activity."
FT /evidence="ECO:0000269|PubMed:10926678"
FT MUTAGEN 363
FT /note="C->S: No effect on protein expression but reduced
FT transport activity."
FT /evidence="ECO:0000269|PubMed:10926678"
FT MUTAGEN 474
FT /note="C->S: Reduced protein expression and transport
FT activity."
FT /evidence="ECO:0000269|PubMed:10926678"
FT MUTAGEN 491
FT /note="C->S: No effect on protein expression and transport
FT activity."
FT /evidence="ECO:0000269|PubMed:10926678"
FT MUTAGEN 520
FT /note="C->S: No effect on protein expression and transport
FT activity. Reduced protein expression and loss of transport
FT activity; when associated with S-306."
FT /evidence="ECO:0000269|PubMed:10926678"
FT MUTAGEN 597
FT /note="C->S: Reduced protein expression and transport
FT activity."
FT /evidence="ECO:0000269|PubMed:10926678"
SQ SEQUENCE 637 AA; 68707 MW; 34D02E7817683F42 CRC64;
MMSYSERLGG PAVSPLPVRG RHMVHGAAFA YVPSPQVLHR IPGTTTYAIS SLSPVALTEH
SCPYGEVLEC HDPLPAKLAQ EEEQKPEPRL SQKLAQVGTK LLKVPLMLGF LYLFVCSLDV
LSSAFQLAGG KVAGDIFKDN AILSNPVAGL VVGILVTVLV QSSSTSTSII VSMVSSGLLE
VSSAIPIIMG SNIGTSVTNT IVALMQAGDR TDFRRAFAGA TVHDCFNWLS VLVLLPLEAA
TGYLHHVTGL VVASFNIRGG RDAPDLLKVI TEPFTKLIIQ LDKSVITSIA VGDESLRNHS
LIRIWCQPET KEASTSMSRV EAIGSLANTT MEKCNHIFVD TGLPDLAVGL ILLAGSLVVL
CTCLILLVKM LNSLLKGQVA NVIQKVINTD 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
