S20A1_HUMAN
ID S20A1_HUMAN Reviewed; 679 AA.
AC Q8WUM9; Q08344; Q6DHX8; Q9UQ82;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Sodium-dependent phosphate transporter 1;
DE AltName: Full=Gibbon ape leukemia virus receptor 1;
DE Short=GLVR-1;
DE AltName: Full=Leukemia virus receptor 1 homolog;
DE AltName: Full=Phosphate transporter 1;
DE Short=PiT-1;
DE AltName: Full=Solute carrier family 20 member 1;
GN Name=SLC20A1; Synonyms=GLVR1, PIT1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION (MICROBIAL INFECTION), AND TISSUE
RP SPECIFICITY.
RX PubMed=2078500;
RA O'Hara B., Johann S.V., Klinger H.P., Blair D.G., Rubinson H., Dunn K.J.,
RA Sass P., Vitek S.M., Robins T.;
RT "Characterization of a human gene conferring sensitivity to infection by
RT gibbon ape leukemia virus.";
RL Cell Growth Differ. 1:119-127(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney, and Skin;
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-646.
RX PubMed=9889306; DOI=10.1016/s0378-1119(98)00572-1;
RA Palmer G., Manen D., Bonjour J.-P., Caverzasio J.;
RT "Characterization of the human Glvr-1 phosphate transporter/retrovirus
RT receptor gene and promoter region.";
RL Gene 226:25-33(1999).
RN [5]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=1309898; DOI=10.1128/jvi.66.2.1219-1222.1992;
RA Takeuchi Y., Vile R.G., Simpson G., O'Hara B., Collins M.K., Weiss R.A.;
RT "Feline leukemia virus subgroup B uses the same cell surface receptor as
RT gibbon ape leukemia virus.";
RL J. Virol. 66:1219-1222(1992).
RN [6]
RP IDENTIFICATION.
RX PubMed=1531369; DOI=10.1128/jvi.66.3.1635-1640.1992;
RA Johann S.V., Gibbons J.J., O'Hara B.;
RT "GLVR1, a receptor for gibbon ape leukemia virus, is homologous to a
RT phosphate permease of Neurospora crassa and is expressed at high levels in
RT the brain and thymus.";
RL J. Virol. 66:1635-1640(1992).
RN [7]
RP MUTAGENESIS OF 550-ASP--VAL-558 AND ASP-550, AND REGION.
RX PubMed=8411375; DOI=10.1128/jvi.67.11.6733-6736.1993;
RA Johann S.V., van Zeijl M., Cekleniak J., O'Hara B.;
RT "Definition of a domain of GLVR1 which is necessary for infection by gibbon
RT ape leukemia virus and which is highly polymorphic between species.";
RL J. Virol. 67:6733-6736(1993).
RN [8]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=7929240; DOI=10.1016/s0021-9258(18)47267-5;
RA Olah Z., Lehel C., Anderson W.B., Eiden M.V., Wilson C.A.;
RT "The cellular receptor for gibbon ape leukemia virus is a novel high
RT affinity sodium-dependent phosphate transporter.";
RL J. Biol. Chem. 269:25426-25431(1994).
RN [9]
RP FUNCTION.
RX PubMed=7966619; DOI=10.1128/jvi.68.12.8270-8276.1994;
RA Miller D.G., Miller A.D.;
RT "A family of retroviruses that utilize related phosphate transporters for
RT cell entry.";
RL J. Virol. 68:8270-8276(1994).
RN [10]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND INDUCTION.
RX PubMed=8041748; DOI=10.1073/pnas.91.15.7071;
RA Kavanaugh M.P., Miller D.G., Zhang W., Law W., Kozak S.L., Kabat D.,
RA Miller A.D.;
RT "Cell-surface receptors for gibbon ape leukemia virus and amphotropic
RT murine retrovirus are inducible sodium-dependent phosphate symporters.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:7071-7075(1994).
RN [11]
RP FUNCTION.
RX PubMed=11009570; DOI=10.1161/01.res.87.7.e10;
RA Jono S., McKee M.D., Murry C.E., Shioi A., Nishizawa Y., Mori K., Morii H.,
RA Giachelli C.M.;
RT "Phosphate regulation of vascular smooth muscle cell calcification.";
RL Circ. Res. 87:E10-E17(2000).
RN [12]
RP FUNCTION (MICROBIAL INFECTION), MUTAGENESIS OF ASP-550, AND REGION.
RX PubMed=12097582; DOI=10.1128/jvi.76.15.7683-7693.2002;
RA Farrell K.B., Russ J.L., Murthy R.K., Eiden M.V.;
RT "Reassessing the role of region A in Pit1-mediated viral entry.";
RL J. Virol. 76:7683-7693(2002).
RN [13]
RP INDUCTION.
RX PubMed=15641067; DOI=10.1002/art.20748;
RA Cecil D.L., Rose D.M., Terkeltaub R., Liu-Bryan R.;
RT "Role of interleukin-8 in PiT-1 expression and CXCR1-mediated inorganic
RT phosphate uptake in chondrocytes.";
RL Arthritis Rheum. 52:144-154(2005).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-269, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-265 AND SER-269, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: Sodium-phosphate symporter which plays a fundamental
CC housekeeping role in phosphate transport, such as absorbing phosphate
CC from interstitial fluid for normal cellular functions such as cellular
CC metabolism, signal transduction, and nucleic acid and lipid synthesis.
CC May play a role in extracellular matrix and cartilage calcification as
CC well as in vascular calcification. {ECO:0000269|PubMed:11009570,
CC ECO:0000269|PubMed:7929240, ECO:0000269|PubMed:7966619,
CC ECO:0000269|PubMed:8041748}.
CC -!- FUNCTION: (Microbial infection) May function as a retroviral receptor
CC as it confers human cells susceptibility to infection to Gibbon Ape
CC Leukemia Virus (GaLV), Simian sarcoma-associated virus (SSAV) and
CC Feline leukemia virus subgroup B (FeLV-B) as well as 10A1 murine
CC leukemia virus (10A1 MLV). {ECO:0000269|PubMed:12097582,
CC ECO:0000269|PubMed:1309898, ECO:0000269|PubMed:2078500}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=24.1 uM for phosphate {ECO:0000269|PubMed:7929240,
CC ECO:0000269|PubMed:8041748};
CC Vmax=1.9 nmol/min/mg enzyme (in the presence of 0.05-2 mM phosphate)
CC {ECO:0000269|PubMed:7929240, ECO:0000269|PubMed:8041748};
CC Note=With an increase in pH, a decrease in phosphate uptake is
CC observed.;
CC pH dependence:
CC Optimum pH is 6.5 and 7.5. {ECO:0000269|PubMed:7929240,
CC ECO:0000269|PubMed:8041748};
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:2078500}.
CC -!- INDUCTION: By phosphate deprivation as well as by IL8/interleukin-8 in
CC hypertrophic chondrocytes. {ECO:0000269|PubMed:15641067,
CC ECO:0000269|PubMed:8041748}.
CC -!- DOMAIN: Region A confers human cells susceptibility to infection by
CC Gibbon Ape Leukemia Virus (GaLV) and Feline leukemia virus subgroup B
CC (FeLV-B). Substitution of Human SLC20A1 region A by region A of murine
CC SLC20A1 prevents viral infection.
CC -!- SIMILARITY: Belongs to the inorganic phosphate transporter (PiT) (TC
CC 2.A.20) family. {ECO:0000305}.
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DR EMBL; L20859; AAA52572.1; -; mRNA.
DR EMBL; AC079922; AAY14922.1; -; Genomic_DNA.
DR EMBL; BC019944; AAH19944.1; -; mRNA.
DR EMBL; BC075818; AAH75818.1; -; mRNA.
DR EMBL; AH007490; AAD20286.1; -; Genomic_DNA.
DR CCDS; CCDS2099.1; -.
DR PIR; I52822; I52822.
DR RefSeq; NP_005406.3; NM_005415.4.
DR AlphaFoldDB; Q8WUM9; -.
DR SMR; Q8WUM9; -.
DR BioGRID; 112462; 125.
DR IntAct; Q8WUM9; 26.
DR MINT; Q8WUM9; -.
DR STRING; 9606.ENSP00000272542; -.
DR BindingDB; Q8WUM9; -.
DR ChEMBL; CHEMBL4295909; -.
DR DrugBank; DB11348; Calcium Phosphate.
DR DrugBank; DB14481; Calcium phosphate dihydrate.
DR DrugBank; DB14502; Sodium phosphate, dibasic.
DR DrugBank; DB09449; Sodium phosphate, monobasic.
DR DrugBank; DB14503; Sodium phosphate, monobasic, unspecified form.
DR TCDB; 2.A.20.2.7; the inorganic phosphate transporter (pit) family.
DR GlyConnect; 2080; 1 N-Linked glycan (1 site).
DR GlyGen; Q8WUM9; 1 site, 2 N-linked glycans (1 site).
DR iPTMnet; Q8WUM9; -.
DR PhosphoSitePlus; Q8WUM9; -.
DR BioMuta; SLC20A1; -.
DR DMDM; 74730735; -.
DR EPD; Q8WUM9; -.
DR jPOST; Q8WUM9; -.
DR MassIVE; Q8WUM9; -.
DR MaxQB; Q8WUM9; -.
DR PaxDb; Q8WUM9; -.
DR PeptideAtlas; Q8WUM9; -.
DR PRIDE; Q8WUM9; -.
DR ProteomicsDB; 74696; -.
DR Antibodypedia; 33281; 178 antibodies from 28 providers.
DR DNASU; 6574; -.
DR Ensembl; ENST00000272542.8; ENSP00000272542.3; ENSG00000144136.11.
DR GeneID; 6574; -.
DR KEGG; hsa:6574; -.
DR MANE-Select; ENST00000272542.8; ENSP00000272542.3; NM_005415.5; NP_005406.3.
DR UCSC; uc002tib.4; human.
DR CTD; 6574; -.
DR DisGeNET; 6574; -.
DR GeneCards; SLC20A1; -.
DR HGNC; HGNC:10946; SLC20A1.
DR HPA; ENSG00000144136; Low tissue specificity.
DR MIM; 137570; gene.
DR neXtProt; NX_Q8WUM9; -.
DR OpenTargets; ENSG00000144136; -.
DR PharmGKB; PA35833; -.
DR VEuPathDB; HostDB:ENSG00000144136; -.
DR eggNOG; KOG2493; Eukaryota.
DR GeneTree; ENSGT00390000014879; -.
DR HOGENOM; CLU_015355_3_1_1; -.
DR InParanoid; Q8WUM9; -.
DR OMA; MSHLIIS; -.
DR OrthoDB; 712010at2759; -.
DR PhylomeDB; Q8WUM9; -.
DR TreeFam; TF314426; -.
DR BioCyc; MetaCyc:ENSG00000144136-MON; -.
DR BRENDA; 7.3.2.1; 2681.
DR PathwayCommons; Q8WUM9; -.
DR Reactome; R-HSA-427652; Sodium-coupled phosphate cotransporters.
DR SignaLink; Q8WUM9; -.
DR SIGNOR; Q8WUM9; -.
DR BioGRID-ORCS; 6574; 100 hits in 1079 CRISPR screens.
DR ChiTaRS; SLC20A1; human.
DR GeneWiki; SLC20A1; -.
DR GenomeRNAi; 6574; -.
DR Pharos; Q8WUM9; Tbio.
DR PRO; PR:Q8WUM9; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q8WUM9; protein.
DR Bgee; ENSG00000144136; Expressed in mucosa of transverse colon and 200 other tissues.
DR ExpressionAtlas; Q8WUM9; baseline and differential.
DR Genevisible; Q8WUM9; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005316; F:high-affinity inorganic phosphate:sodium symporter activity; IEA:Ensembl.
DR GO; GO:0005315; F:inorganic phosphate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc.
DR GO; GO:0005436; F:sodium:phosphate symporter activity; TAS:Reactome.
DR GO; GO:0031214; P:biomineral tissue development; IEA:Ensembl.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0035435; P:phosphate ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006796; P:phosphate-containing compound metabolic process; TAS:ProtInc.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; HMP:UniProtKB.
DR InterPro; IPR001204; Phos_transporter.
DR PANTHER; PTHR11101; PTHR11101; 1.
DR Pfam; PF01384; PHO4; 1.
PE 1: Evidence at protein level;
KW Host-virus interaction; Membrane; Phosphate transport; Phosphoprotein;
KW Receptor; Reference proteome; Symport; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..679
FT /note="Sodium-dependent phosphate transporter 1"
FT /id="PRO_0000080771"
FT TRANSMEM 21..41
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 62..82
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 100..120
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 158..178
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 203..223
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 230..250
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 511..531
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 558..578
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 600..620
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 650..670
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 550..558
FT /note="A"
FT MOD_RES 265
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MUTAGEN 550..558
FT /note="DTGDVSSKV->KQEASTKA: Loss of virus infectibility."
FT /evidence="ECO:0000269|PubMed:8411375"
FT MUTAGEN 550
FT /note="D->K: Drastic reduction of virus infectibility, but
FT conserved virus binding ability."
FT /evidence="ECO:0000269|PubMed:12097582,
FT ECO:0000269|PubMed:8411375"
FT MUTAGEN 550
FT /note="Missing: Loss of virus infectibility."
FT /evidence="ECO:0000269|PubMed:12097582,
FT ECO:0000269|PubMed:8411375"
FT CONFLICT 376
FT /note="Y -> S (in Ref. 1; AAA52572)"
FT /evidence="ECO:0000305"
FT CONFLICT 443
FT /note="E -> R (in Ref. 4; AAD20286)"
FT /evidence="ECO:0000305"
FT CONFLICT 487
FT /note="E -> A (in Ref. 1; AAA52572)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 679 AA; 73700 MW; 5545F6E6DC8F5EA8 CRC64;
MATLITSTTA ATAASGPLVD YLWMLILGFI IAFVLAFSVG ANDVANSFGT AVGSGVVTLK
QACILASIFE TVGSVLLGAK VSETIRKGLI DVEMYNSTQG LLMAGSVSAM FGSAVWQLVA
SFLKLPISGT HCIVGATIGF SLVAKGQEGV KWSELIKIVM SWFVSPLLSG IMSGILFFLV
RAFILHKADP VPNGLRALPV FYACTVGINL FSIMYTGAPL LGFDKLPLWG TILISVGCAV
FCALIVWFFV CPRMKRKIER EIKCSPSESP LMEKKNSLKE DHEETKLSVG DIENKHPVSE
VGPATVPLQA VVEERTVSFK LGDLEEAPER ERLPSVDLKE ETSIDSTVNG AVQLPNGNLV
QFSQAVSNQI NSSGHYQYHT VHKDSGLYKE LLHKLHLAKV GDCMGDSGDK PLRRNNSYTS
YTMAICGMPL DSFRAKEGEQ KGEEMEKLTW PNADSKKRIR MDSYTSYCNA VSDLHSASEI
DMSVKAEMGL GDRKGSNGSL EEWYDQDKPE VSLLFQFLQI LTACFGSFAH GGNDVSNAIG
PLVALYLVYD TGDVSSKVAT PIWLLLYGGV GICVGLWVWG RRVIQTMGKD LTPITPSSGF
SIELASALTV VIASNIGLPI STTHCKVGSV VSVGWLRSKK AVDWRLFRNI FMAWFVTVPI
SGVISAAIMA IFRYVILRM
