Q08357 (S20A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium-dependent phosphate transporter 2

Alternative name(s):
Gibbon ape leukemia virus receptor 2
Short name=GLVR-2
Phosphate transporter 2
Short name=PiT-2
Short name=Pit2
Short name=hPit2
Solute carrier family 20 member 2

Gene names

Name:	SLC20A2
Synonyms:	GLVR2, PIT2

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

General annotation (Comments)

Function	Sodium-phosphate symporter which seems to play a fundamental housekeeping role in phosphate transport by absorbing phosphate from interstitial fluid for normal cellular functions such as cellular metabolism, signal transduction, and nucleic acid and lipid synthesis. In vitro, sodium-dependent phosphate uptake is not siginificantly affected by acidic and alkaline conditions, however sodium-independent phosphate uptake occurs at acidic conditions. May play a role in extracellular matrix, cartilage and vascular calcification. Functions as a retroviral receptor and confers human cells susceptibility to infection to amphotropic murine leukemia virus (A-MuLV), 10A1 murine leukemia virus (10A1 MLV) and some feline leukemia virus subgroup B (FeLV-B) variants. Ref.1 Ref.6 Ref.7 Ref.8 Ref.9
Subunit structure	Homodimer. Ref.7 Ref.8
Subcellular location	Cell membrane; Multi-pass membrane protein Ref.5.
Tissue specificity	Ubiquitously expressed.
Induction	Increased by phosphate depletion in osteosarcoma cell lines. Ref.5
Involvement in disease	Basal ganglia calcification, idiopathic, 3 (IBGC3) [MIM:614540]: An autosomal dominant condition characterized by symmetric calcification in the basal ganglia and other brain regions. Affected individuals can either be asymptomatic or show a wide spectrum of neuropsychiatric symptoms, including parkinsonism, dystonia, tremor, ataxia, dementia, psychosis, seizures, and chronic headache. Serum levels of calcium, phosphate, alkaline phosphatase and parathyroid hormone are normal. The neuropathological hallmark of the disease is vascular and pericapillary calcification, mainly of calcium phosphate, in the affected brain areas. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11
Sequence similarities	Belongs to the inorganic phosphate transporter (PiT) (TC 2.A.20) family. [View classification]

Ontologies

Keywords
Biological process	Host-virus interaction Ion transport Phosphate transport Sodium transport Symport Transport
Cellular component	Cell membrane Membrane
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Ligand	Sodium
Molecular function	Host cell receptor for virus entry Receptor
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	inorganic phosphate transmembrane transporter activity Inferred from electronic annotation. Source: InterPro receptor activity Traceable author statement Ref.1. Source: ProtInc sodium:phosphate symporter activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 652	652	Sodium-dependent phosphate transporter 2		PRO_0000341268
Regions
	Topological domain	1 – 5	5	Extracellular Potential
	Transmembrane	6 – 26	21	Helical; Potential
	Topological domain	27 – 46	20	Cytoplasmic Potential
	Transmembrane	47 – 67	21	Helical; Potential
	Topological domain	68 – 86	19	Extracellular Potential
	Transmembrane	87 – 107	21	Helical; Potential
	Topological domain	108 – 109	2	Cytoplasmic Potential
	Transmembrane	110 – 130	21	Helical; Potential
	Topological domain	131 – 142	12	Extracellular Potential
	Transmembrane	143 – 163	21	Helical; Potential
	Topological domain	164 – 190	27	Cytoplasmic Potential
	Transmembrane	191 – 211	21	Helical; Potential
	Topological domain	212 – 213	2	Extracellular Potential
	Transmembrane	214 – 234	21	Helical; Potential
	Topological domain	235 – 482	248	Cytoplasmic Potential
	Transmembrane	483 – 503	21	Helical; Potential
	Topological domain	504 – 530	27	Extracellular Potential
	Transmembrane	531 – 551	21	Helical; Potential
	Topological domain	552 – 571	20	Cytoplasmic Potential
	Transmembrane	572 – 586	15	Helical; Potential
	Topological domain	587 – 593	7	Extracellular Potential
	Transmembrane	594 – 609	16	Helical; Potential
	Topological domain	610 – 621	12	Cytoplasmic Potential
	Transmembrane	622 – 642	21	Helical; Potential
	Topological domain	643 – 652	10	Extracellular Potential
Amino acid modifications
	Modified residue	268	1	Phosphoserine Ref.10
	Glycosylation	81	1	N-linked (GlcNAc...) Ref.4
Natural variations
	Natural variant	42	1	Missing in IBGC3; substantially impaired phosphate transport. Ref.11		VAR_067545
	Natural variant	498	1	G → R in IBGC3; substantially impaired phosphate transport. Ref.11		VAR_067546
	Natural variant	575	1	E → K in IBGC3; substantially impaired phosphate transport. Ref.11		VAR_067547
	Natural variant	595	1	T → M in IBGC3; substantially impaired phosphate transport. Ref.11		VAR_067548
	Natural variant	601	1	S → L in IBGC3; substantially impaired phosphate transport. Ref.11		VAR_067549
	Natural variant	601	1	S → W in IBGC3; substantially impaired phosphate transport. Ref.11		VAR_067550
Experimental info
	Mutagenesis	28	1	D → N: Impairs phosphate transport; no effect on retroviral receptor function. Ref.8
	Mutagenesis	55	1	E → D or K: Abolishes sodium-dependent phosphate transport; no effect on retroviral receptor function. Ref.7 Ref.9
	Mutagenesis	55	1	E → Q: Abolishes phosphate but not sodium uptake; when associated with Q-91 and Q-575. Ref.7 Ref.9
	Mutagenesis	81	1	N → V: Abolishes N-glycosylation. Ref.4
	Mutagenesis	91	1	E → Q: Abolishes phosphate but not sodium uptake; when associated with Q-55 and Q-575. Ref.9
	Mutagenesis	506	1	D → N: Impairs phosphate transport; no effect on retroviral receptor function. Ref.8
	Mutagenesis	575	1	E → D or K: Abolishes sodium-dependent phosphate transport; no effect on retroviral receptor function. Ref.7 Ref.9
	Mutagenesis	575	1	E → Q: Abolishes phosphate but not sodium uptake; when associated with Q-55 and Q-91. Ref.7 Ref.9

Sequences

	Sequence		Length	Mass (Da)
	Q08357 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: A0A870C7927DE39C	FASTA	652	70,392
	10 20 30 40 50 60 MAMDEYLWMV ILGFIIAFIL AFSVGANDVA NSFGTAVGSG VVTLRQACIL ASIFETTGSV 70 80 90 100 110 120 LLGAKVGETI RKGIIDVNLY NETVETLMAG EVSAMVGSAV WQLIASFLRL PISGTHCIVG 130 140 150 160 170 180 STIGFSLVAI GTKGVQWMEL VKIVASWFIS PLLSGFMSGL LFVLIRIFIL KKEDPVPNGL 190 200 210 220 230 240 RALPVFYAAT IAINVFSIMY TGAPVLGLVL PMWAIALISF GVALLFAFFV WLFVCPWMRR 250 260 270 280 290 300 KITGKLQKEG ALSRVSDESL SKVQEAESPV FKELPGAKAN DDSTIPLTGA AGETLGTSEG 310 320 330 340 350 360 TSAGSHPRAA YGRALSMTHG SVKSPISNGT FGFDGHTRSD GHVYHTVHKD SGLYKDLLHK 370 380 390 400 410 420 IHIDRGPEEK PAQESNYRLL RRNNSYTCYT AAICGLPVHA TFRAADSSAP EDSEKLVGDT 430 440 450 460 470 480 VSYSKKRLRY DSYSSYCNAV AEAEIEAEEG GVEMKLASEL ADPDQPREDP AEEEKEEKDA 490 500 510 520 530 540 PEVHLLFHFL QVLTACFGSF AHGGNDVSNA IGPLVALWLI YKQGGVTQEA ATPVWLLFYG 550 560 570 580 590 600 GVGICTGLWV WGRRVIQTMG KDLTPITPSS GFTIELASAF TVVIASNIGL PVSTTHCKVG 610 620 630 640 650 SVVAVGWIRS RKAVDWRLFR NIFVAWFVTV PVAGLFSAAV MALLMYGILP YV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A human amphotropic retrovirus receptor is a second member of the gibbon ape leukemia virus receptor family." van Zeijl M., Johann S.V., Closs E., Cunningham J., Eddy R., Shows T.B., O'Hara B. Proc. Natl. Acad. Sci. U.S.A. 91:1168-1172(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION AS RETROVIRAL RECEPTOR. Tissue: Placenta.
[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].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"Transmembrane topology of PiT-2, a phosphate transporter-retrovirus receptor." Salauen C., Rodrigues P., Heard J.M. J. Virol. 75:5584-5592(2001) [PubMed] [Europe PMC] [Abstract] Cited for: TOPOLOGY, GLYCOSYLATION AT ASN-81, MUTAGENESIS OF ASN-81.
[5]	"The amphotropic murine leukemia virus receptor gene encodes a 71-kilodalton protein that is induced by phosphate depletion." Chien M.L., Foster J.L., Douglas J.L., Garcia J.V. J. Virol. 71:4564-4570(1997) [PubMed] [Europe PMC] [Abstract] Cited for: TOPOLOGY, SUBCELLULAR LOCATION, INDUCTION.
[6]	"Identification of envelope determinants of feline leukemia virus subgroup B that permit infection and gene transfer to cells expressing human Pit1 or Pit2." Sugai J., Eiden M., Anderson M.M., Van Hoeven N., Meiering C.D., Overbaugh J. J. Virol. 75:6841-6849(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS RETROVIRAL RECEPTOR.
[7]	"Two highly conserved glutamate residues critical for type III sodium-dependent phosphate transport revealed by uncoupling transport function from retroviral receptor function." Boettger P., Pedersen L. J. Biol. Chem. 277:42741-42747(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS SODIUM-PHOSPHATE SYMPORTER, SUBUNIT, MUTAGENESIS OF GLU-55 AND GLU-575.
[8]	"Evolutionary and experimental analyses of inorganic phosphate transporter PiT family reveals two related signature sequences harboring highly conserved aspartic acids critical for sodium-dependent phosphate transport function of human PiT2." Boettger P., Pedersen L. FEBS J. 272:3060-3074(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS SODIUM-PHOSPHATE SYMPORTER, SUBUNIT, MUTAGENESIS OF ASP-28 AND ASP-506.
[9]	"Characterization of transport mechanisms and determinants critical for Na+-dependent Pi symport of the PiT family paralogs human PiT1 and PiT2." Boettger P., Hede S.E., Grunnet M., Hoyer B., Klaerke D.A., Pedersen L. Am. J. Physiol. 291:C1377-C1387(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS SODIUM-PHOSPHATE SYMPORTER, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF GLU-55; GLU-91 AND GLU-575.
[10]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis." Wang C., Li Y., Shi L., Ren J., Patti M., Wang T., de Oliveira J.R., Sobrido M.J., Quintans B., Baquero M., Cui X., Zhang X.Y., Wang L., Xu H., Wang J., Yao J., Dai X., Liu J. , Zhang L., Ma H., Gao Y., Ma X., Feng S., Liu M., Wang Q.K., Forster I.C., Zhang X., Liu J.Y. Nat. Genet. 44:254-256(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS IBGC3 VAL-42 DEL; ARG-498; LYS-575; MET-595; TRP-601 AND LEU-601, CHARACTERIZATION OF VARIANTS IBGC3 VAL-42 DEL; ARG-498; LYS-575; MET-595; TRP-601 AND LEU-601.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L20852 mRNA. Translation: AAA18018.1. AK291202 mRNA. Translation: BAF83891.1. BC028600 mRNA. Translation: AAH28600.1.
IPI	IPI00009504.
PIR	A37000.
RefSeq	NP_001244109.1. NM_001257180.1. NP_001244110.1. NM_001257181.1. NP_006740.1. NM_006749.4.
UniGene	Hs.653173. Hs.654763.
3D structure databases
ProteinModelPortal	Q08357.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000340465.
Protein family/group databases
TCDB	2.A.20.2.3. inorganic phosphate transporter (PiT) family.
PTM databases
PhosphoSite	Q08357.
Polymorphism databases
DMDM	74735615.
Proteomic databases
PaxDb	Q08357.
PRIDE	Q08357.
Protocols and materials databases
DNASU	6575.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000342228; ENSP00000340465; ENSG00000168575. ENST00000520179; ENSP00000429712; ENSG00000168575. ENST00000520262; ENSP00000429754; ENSG00000168575.
GeneID	6575.
KEGG	hsa:6575.
UCSC	uc003xpe.3. human.
Organism-specific databases
CTD	6575.
GeneCards	GC08M042291.
HGNC	HGNC:10947. SLC20A2.
HPA	HPA026540.
MIM	158378. gene. 614540. phenotype.
neXtProt	NX_Q08357.
Orphanet	1980. Bilateral striopallidodentate calcinosis.
PharmGKB	PA35834.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0306.
HOGENOM	HOG000231892.
HOVERGEN	HBG053358.
InParanoid	Q08357.
KO	K14640.
OMA	HPRVPYG.
OrthoDB	EOG40S0F7.
PhylomeDB	Q08357.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q08357.
Bgee	Q08357.
CleanEx	HS_SLC20A2.
Genevestigator	Q08357.
Family and domain databases
InterPro	IPR001204. Phos_transporter. [Graphical view]
PANTHER	PTHR11101. PTHR11101. 1 hit.
Pfam	PF01384. PHO4. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SLC20A2. human.
GenomeRNAi	6575.
NextBio	25583.
SOURCE	Search...

Entry information

Entry name

S20A2_HUMAN

Accession

Primary (citable) accession number: Q08357

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 10, 2008
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 98 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.