O95436 (NPT2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium-dependent phosphate transport protein 2B
Short name=Sodium-phosphate transport protein 2B

Alternative name(s):
Na(+)-dependent phosphate cotransporter 2B
NaPi3b
Sodium/phosphate cotransporter 2B
Short name=Na(+)/Pi cotransporter 2B
Short name=NaPi-2b
Solute carrier family 34 member 2

Gene names

Name:

SLC34A2

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

General annotation (Comments)

Function	May be involved in actively transporting phosphate into cells via Na+ cotransport. It may be the main phosphate transport protein in the intestinal brush border membrane. May have a role in the synthesis of surfactant in lungs' alveoli.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Highly expressed in lung. Also detected in pancreas, kidney, small intestine, ovary, testis, prostate and mammary gland. In lung, it is found in alveolar type II cells but not in bronchiolar epithelium. Ref.1 Ref.2
Induction	Down-regulated by EGF. Ref.5
Involvement in disease	Pulmonary alveolar microlithiasis (PALM) [MIM:265100]: Rare disease characterized by the deposition of calcium phosphate microliths throughout the lungs. Most patients are asymptomatic for several years or even for decades and generally, the diagnosis is incidental to clinical investigations unrelated to the disease. Cases with early-onset or rapid progression are rare. A 'sandstorm-appearing' chest roentgenogram is a typical diagnostic finding. The onset of this potentially lethal disease varies from the neonatal period to old age and the disease follows a long-term, progressive course, resulting in a slow deterioration of lung functions. Pulmonary alveolar microlithiasis is a recessive monogenic disease with full penetrance. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8 A chromosomal aberration involving SLC34A2 is found in a glioblastoma multiforme cell line U-118MG. Results in the formation of a SLC34A2-ROS1 chimeric protein that retains a constitutive kinase activity. Ref.7
Sequence similarities	Belongs to the SLC34A transporter family.
Biophysicochemical properties	pH dependence: Optimum pH is 6.6. Ref.1
Sequence caution	The sequence BAC11354.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Ion transport Sodium transport Symport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Ligand	Sodium
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	aging Inferred from electronic annotation. Source: Compara cellular phosphate ion homeostasis Inferred from direct assay Ref.2. Source: UniProtKB in utero embryonic development Inferred from electronic annotation. Source: Compara response to estradiol stimulus Inferred from electronic annotation. Source: Compara response to estrogen stimulus Inferred from expression pattern PubMed 12893629. Source: UniProtKB response to fructose stimulus Inferred from electronic annotation. Source: Compara
Cellular_component	apical plasma membrane Inferred from direct assay PubMed 15970207. Source: UniProtKB brush border membrane Inferred from sequence or structural similarity. Source: UniProtKB integral to plasma membrane Non-traceable author statement Ref.1. Source: UniProtKB
Molecular_function	phosphate ion binding Inferred from direct assay PubMed 12488042. Source: UniProtKB sodium ion binding Inferred from direct assay PubMed 12488042. Source: UniProtKB sodium-dependent phosphate transmembrane transporter activity Inferred from direct assay Ref.1Ref.2PubMed 12488042. Source: UniProtKB sodium:phosphate symporter activity Inferred from direct assay Ref.1Ref.2PubMed 12488042. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O95436-1)

Also known as: NaPi-3b;

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: O95436-2)

Also known as: NaPi-2b; NaPi-IIb;

The sequence of this isoform differs from the canonical sequence as follows:
     38-39: TD → N

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 690	690	Sodium-dependent phosphate transport protein 2B		PRO_0000068613
Regions
	Topological domain	1 – 100	100	Cytoplasmic Potential
	Transmembrane	101 – 121	21	Helical; Name=M1; Potential
	Topological domain	122 – 135	14	Extracellular Potential
	Transmembrane	136 – 156	21	Helical; Name=M2; Potential
	Topological domain	157 – 212	56	Cytoplasmic Potential
	Transmembrane	213 – 233	21	Helical; Name=M3; Potential
	Topological domain	234 – 362	129	Extracellular Potential
	Transmembrane	363 – 383	21	Helical; Name=M4; Potential
	Topological domain	384 – 407	24	Cytoplasmic Potential
	Transmembrane	408 – 428	21	Helical; Name=M5; Potential
	Topological domain	429 – 485	57	Extracellular Potential
	Transmembrane	486 – 506	21	Helical; Name=M6; Potential
	Topological domain	507 – 525	19	Cytoplasmic Potential
	Transmembrane	526 – 546	21	Helical; Name=M7; Potential
	Topological domain	547 – 552	6	Extracellular Potential
	Transmembrane	553 – 573	21	Helical; Name=M8; Potential
	Topological domain	574 – 689	116	Cytoplasmic Potential
	Compositional bias	464 – 467	4	Poly-Thr
	Compositional bias	612 – 644	33	Cys-rich
Sites
	Site	126 – 127	2	Breakpoint for translocation to form a SLC34A2-ROS1 fusion protein
Amino acid modifications
	Glycosylation	295	1	N-linked (GlcNAc...) Potential
	Glycosylation	308	1	N-linked (GlcNAc...) Potential
	Glycosylation	313	1	N-linked (GlcNAc...) Potential
	Glycosylation	321	1	N-linked (GlcNAc...) Potential
	Glycosylation	340	1	N-linked (GlcNAc...) Potential
	Disulfide bond	303 ↔ 350		By similarity
Natural variations
	Alternative sequence	38 – 39	2	TD → N in isoform 2.		VSP_016755
	Natural variant	45	1	V → A. Corresponds to variant rs35426730 [ dbSNP | Ensembl ].		VAR_034156
	Natural variant	106	1	G → R in PALM. Ref.8		VAR_030677
	Natural variant	634	1	D → G. Ref.1 Ref.2 Ref.4 Ref.6 Corresponds to variant rs6448389 [ dbSNP | Ensembl ].		VAR_030678
Experimental info
	Sequence conflict	228	1	V → L in AAF31328. Ref.2
	Sequence conflict	228	1	V → L in AAL55657. Ref.5
	Sequence conflict	330	1	T → V in BAC11354. Ref.6
	Sequence conflict	590 – 595	6	Missing in BAC11354. Ref.6
	Sequence conflict	620	1	C → Y in AAC98695. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (NaPi-3b) [UniParc]. Last modified November 30, 2010. Version 3. Checksum: 3BDB1920CA92C035	FASTA	690	75,759
	10 20 30 40 50 60 MAPWPELGDA QPNPDKYLEG AAGQQPTAPD KSKETNKTDN TEAPVTKIEL LPSYSTATLI 70 80 90 100 110 120 DEPTEVDDPW NLPTLQDSGI KWSERDTKGK ILCFFQGIGR LILLLGFLYF FVCSLDILSS 130 140 150 160 170 180 AFQLVGGKMA GQFFSNSSIM SNPLLGLVIG VLVTVLVQSS STSTSIVVSM VSSSLLTVRA 190 200 210 220 230 240 AIPIIMGANI GTSITNTIVA LMQVGDRSEF RRAFAGATVH DFFNWLSVLV LLPVEVATHY 250 260 270 280 290 300 LEIITQLIVE SFHFKNGEDA PDLLKVITKP FTKLIVQLDK KVISQIAMND EKAKNKSLVK 310 320 330 340 350 360 IWCKTFTNKT QINVTVPSTA NCTSPSLCWT DGIQNWTMKN VTYKENIAKC QHIFVNFHLP 370 380 390 400 410 420 DLAVGTILLI LSLLVLCGCL IMIVKILGSV LKGQVATVIK KTINTDFPFP FAWLTGYLAI 430 440 450 460 470 480 LVGAGMTFIV QSSSVFTSAL TPLIGIGVIT IERAYPLTLG SNIGTTTTAI LAALASPGNA 490 500 510 520 530 540 LRSSLQIALC HFFFNISGIL LWYPIPFTRL PIRMAKGLGN ISAKYRWFAV FYLIIFFFLI 550 560 570 580 590 600 PLTVFGLSLA GWRVLVGVGV PVVFIIILVL CLRLLQSRCP RVLPKKLQNW NFLPLWMRSL 610 620 630 640 650 660 KPWDAVVSKF TGCFQMRCCC CCRVCCRACC LLCDCPKCCR CSKCCEDLEE AQEGQDVPVK 670 680 690 APETFDNITI SREAQGEVPA SDSKTECTAL
	Isoform 2 (NaPi-2b) (NaPi-IIb) [UniParc]. Checksum: B8D40075B1266490	FASTA	689	75,657
	10 20 30 40 50 60 MAPWPELGDA QPNPDKYLEG AAGQQPTAPD KSKETNKNNT EAPVTKIELL PSYSTATLID 70 80 90 100 110 120 EPTEVDDPWN LPTLQDSGIK WSERDTKGKI LCFFQGIGRL ILLLGFLYFF VCSLDILSSA 130 140 150 160 170 180 FQLVGGKMAG QFFSNSSIMS NPLLGLVIGV LVTVLVQSSS TSTSIVVSMV SSSLLTVRAA 190 200 210 220 230 240 IPIIMGANIG TSITNTIVAL MQVGDRSEFR RAFAGATVHD FFNWLSVLVL LPVEVATHYL 250 260 270 280 290 300 EIITQLIVES FHFKNGEDAP DLLKVITKPF TKLIVQLDKK VISQIAMNDE KAKNKSLVKI 310 320 330 340 350 360 WCKTFTNKTQ INVTVPSTAN CTSPSLCWTD GIQNWTMKNV TYKENIAKCQ HIFVNFHLPD 370 380 390 400 410 420 LAVGTILLIL SLLVLCGCLI MIVKILGSVL KGQVATVIKK TINTDFPFPF AWLTGYLAIL 430 440 450 460 470 480 VGAGMTFIVQ SSSVFTSALT PLIGIGVITI ERAYPLTLGS NIGTTTTAIL AALASPGNAL 490 500 510 520 530 540 RSSLQIALCH FFFNISGILL WYPIPFTRLP IRMAKGLGNI SAKYRWFAVF YLIIFFFLIP 550 560 570 580 590 600 LTVFGLSLAG WRVLVGVGVP VVFIIILVLC LRLLQSRCPR VLPKKLQNWN FLPLWMRSLK 610 620 630 640 650 660 PWDAVVSKFT GCFQMRCCCC CRVCCRACCL LCDCPKCCRC SKCCEDLEEA QEGQDVPVKA 670 680 PETFDNITIS REAQGEVPAS DSKTECTAL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and functional characterization of a sodium-dependent phosphate transporter expressed in human lung and small intestine." Feild J.A., Zhang L., Brun K.A., Brooks D.P., Edwards R.M. Biochem. Biophys. Res. Commun. 258:578-582(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, VARIANT GLY-634. Tissue: Lung and Small intestine.
[2]	"Molecular cloning, functional characterization, tissue distribution, and chromosomal localization of a human, small intestinal sodium-phosphate (Na+-Pi) transporter (SLC34A2)." Xu H., Bai L., Collins J.F., Ghishan F.K. Genomics 62:281-284(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, VARIANT GLY-634. Tissue: Small intestine.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] (ISOFORM 2), VARIANT GLY-634.
[5]	"Regulation of the human sodium-phosphate cotransporter NaPi-IIb gene promoter by epidermal growth factor." Xu H., Collins J.F., Bai L., Kiela P.R., Ghishan F.K. Am. J. Physiol. 280:C628-C636(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-592 (ISOFORM 2), INDUCTION. Tissue: Intestine.
[6]	"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] OF 266-690, VARIANT GLY-634. Tissue: Ovarian carcinoma.
[7]	"Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with an interstitial del(6)(q21q21)." Charest A., Lane K., McMahon K., Park J., Preisinger E., Conroy H., Housman D. Genes Chromosomes Cancer 37:58-71(2003) [PubMed] [Europe PMC] [Abstract] Cited for: DISEASE, CHROMOSOMAL TRANSLOCATION WITH ROS1.
[8]	"Mutations in SLC34A2 cause pulmonary alveolar microlithiasis and are possibly associated with testicular microlithiasis." Corut A., Senyigit A., Ugur S.A., Altin S., Ozcelik U., Calisir H., Yildirim Z., Gocmen A., Tolun A. Am. J. Hum. Genet. 79:650-656(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PALM ARG-106.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF111856 mRNA. Translation: AAC98695.1. AF146796 mRNA. Translation: AAF31328.1. AC092436 Genomic DNA. No translation available. BC142704 mRNA. Translation: AAI42705.1. BC146666 mRNA. Translation: AAI46667.1. AH011306 Genomic DNA. Translation: AAL55657.1. AK075015 mRNA. Translation: BAC11354.1. Different initiation.
IPI	IPI00007910. IPI00657725.
RefSeq	NP_001171469.1. NM_001177998.1. NP_001171470.1. NM_001177999.1. NP_006415.2. NM_006424.2.
UniGene	Hs.479372.
3D structure databases
ProteinModelPortal	O95436.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000371483.
PTM databases
PhosphoSite	O95436.
Proteomic databases
PaxDb	O95436.
PRIDE	O95436.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000382051; ENSP00000371483; ENSG00000157765. ENST00000503434; ENSP00000423021; ENSG00000157765. ENST00000504570; ENSP00000425501; ENSG00000157765.
GeneID	10568.
KEGG	hsa:10568.
UCSC	uc003grr.3. human.
Organism-specific databases
CTD	10568.
GeneCards	GC04P025657.
HGNC	HGNC:11020. SLC34A2.
HPA	HPA037989.
MIM	265100. phenotype. 604217. gene.
neXtProt	NX_O95436.
Orphanet	60025. Pulmonary alveolar microlithiasis.
PharmGKB	PA35888.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1283.
HOGENOM	HOG000006550.
HOVERGEN	HBG006527.
InParanoid	O95436.
KO	K14683.
OMA	KCCEDLE.
PhylomeDB	O95436.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	O95436.
Bgee	O95436.
CleanEx	HS_SLC34A2.
Genevestigator	O95436.
GermOnline	ENSG00000157765. Homo sapiens.
Family and domain databases
InterPro	IPR003841. Na/Pi_transpt. [Graphical view]
Pfam	PF02690. Na_Pi_cotrans. 2 hits. [Graphical view]
TIGRFAMs	TIGR01013. 2a58. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	SLC34A2. human.
GenomeRNAi	10568.
NextBio	40109.
SOURCE	Search...

Entry information

Entry name

NPT2B_HUMAN

Accession

Primary (citable) accession number: O95436
Secondary accession number(s): A5PL17 , Q8N2K2, Q8WYA9, Q9P0V7

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 20, 2005
Last sequence update:	November 30, 2010
Last modified:	May 1, 2013
This is version 93 of the entry and version 3 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.