Q8BTY2 (S4A7_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium bicarbonate cotransporter 3

Alternative name(s):
Solute carrier family 4 member 7

Gene names

Name:	Slc4a7
Synonyms:	Nbc3

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1034 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Electroneutral sodium- and bicarbonate-dependent cotransporter with a Na+:HCO3- 1:1 stoichiometry. Regulates intracellular pH and may play a role in bicarbonate salvage in secretory epithelia. May also have an associated sodium channel activity. Ref.4
Enzyme regulation	Transporter activity is regulated by CA2/carbonic anhydrase 2, cAMP and PKA. Insensitive to stilbene derivatives. May be inhibited by 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) By similarity.
Subunit structure	Forms a complex with ATP6V1B1 and SLC9A3R1/EBP50. Interacts in a pH dependent-manner with CA2/carbonic anhydrase 2 By similarity. Interacts with CFTR through SLC9A3R1/EBP50. Interacts with USH1C. Ref.3 Ref.5
Subcellular location	Basolateral cell membrane; Multi-pass membrane protein. Apical cell membrane; Multi-pass membrane protein By similarity. Cell projection › stereocilium By similarity. Note: Also described at the apical cell membrane. Localizes to the stereocilia of cochlear outer hair cells and to the lateral membrane of cochlear inner hair cells By similarity.
Tissue specificity	Expressed in the spiral ligament throughout the cochlea and in photoreceptors of the outer plexiform layer of the retina (at protein level). Ref.4 Ref.5
Domain	The PDZ-binding motif mediates interaction with the CFTR, SLC9A3R1/EBP50 complex and probably with USH1C By similarity.
Disruption phenotype	Deafness and blindness due to degeneration of sensory receptors in internal ear and retina. Ref.4
Sequence similarities	Belongs to the anion exchanger (TC 2.A.31) family. [View classification]

Ontologies

Keywords
Biological process	Ion transport Sodium transport Symport Transport
Cellular component	Cell membrane Cell projection Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Ligand	Sodium
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	auditory receptor cell development Inferred from mutant phenotype Ref.4. Source: MGI cochlear nucleus development Inferred from mutant phenotype Ref.4. Source: MGI retina vasculature morphogenesis in camera-type eye Inferred from mutant phenotype Ref.4. Source: MGI retinal cell programmed cell death Inferred from mutant phenotype Ref.4. Source: MGI sodium ion transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	apical plasma membrane Inferred from direct assay PubMed 16144965. Source: UniProtKB basolateral plasma membrane Inferred from direct assay PubMed 16144965. Source: UniProtKB cytoplasm Inferred from direct assay PubMed 16144965. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW stereocilium Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	inorganic anion exchanger activity Inferred from electronic annotation. Source: InterPro symporter activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q8BTY2-1)

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: Q8BTY2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     243-243: G → GKKHSDPHLLERNG
     815-815: F → KGAGYHLDLL...FILSCKEIKH
     816-1034: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1034	1034	Sodium bicarbonate cotransporter 3		PRO_0000079234
Regions
	Topological domain	1 – 476	476	Extracellular Potential
	Transmembrane	477 – 497	21	Helical; Potential
	Topological domain	498 – 505	8	Cytoplasmic Potential
	Transmembrane	506 – 526	21	Helical; Potential
	Topological domain	527 – 563	37	Extracellular Potential
	Transmembrane	564 – 584	21	Helical; Potential
	Topological domain	585 – 593	9	Cytoplasmic Potential
	Transmembrane	594 – 614	21	Helical; Potential
	Topological domain	615 – 685	71	Extracellular Potential
	Transmembrane	686 – 706	21	Helical; Potential
	Topological domain	707 – 729	23	Cytoplasmic Potential
	Transmembrane	730 – 750	21	Helical; Potential
	Topological domain	751 – 776	26	Extracellular Potential
	Transmembrane	777 – 797	21	Helical; Potential
	Topological domain	798 – 812	15	Cytoplasmic Potential
	Transmembrane	813 – 833	21	Helical; Potential
	Topological domain	834 – 876	43	Extracellular Potential
	Transmembrane	877 – 897	21	Helical; Potential
	Topological domain	898 – 1034	137	Cytoplasmic Potential
	Region	918 – 920	3	CA2-binding By similarity
	Motif	1031 – 1034	4	PDZ-binding By similarity
Amino acid modifications
	Modified residue	238	1	Phosphoserine Ref.7
	Modified residue	247	1	Phosphoserine Ref.7
	Modified residue	271	1	Phosphoserine By similarity
	Modified residue	275	1	Phosphoserine Ref.6
	Modified residue	951	1	Phosphothreonine Ref.7
	Modified residue	960	1	Phosphoserine Ref.7 Ref.8
	Modified residue	1033	1	Phosphoserine Ref.7
	Glycosylation	176	1	N-linked (GlcNAc...) Potential
	Glycosylation	274	1	N-linked (GlcNAc...) Potential
	Glycosylation	644	1	N-linked (GlcNAc...) Potential
	Glycosylation	654	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	664	1	N-linked (GlcNAc...) Ref.9
Natural variations
	Alternative sequence	243	1	G → GKKHSDPHLLERNG in isoform 2.		VSP_017166
	Alternative sequence	815	1	F → KGAGYHLDLLMVGVMLGVCS IMGLPWFVAATVLSISHVNS LKVESECSAPGEQPKFLGIR EQRVTGLMIFILMGLSVFMT SVLKVKPLWQCSTILFTLTF ILSCKEIKH in isoform 2.		VSP_017167
	Alternative sequence	816 – 1034	219	Missing in isoform 2.		VSP_017168
Experimental info
	Sequence conflict	430	1	G → D in BAC40330. Ref.1
	Sequence conflict	717	1	G → R in BAC40330. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 7, 2006. Version 2. Checksum: 92B080274D206097	FASTA	1,034	116,514
	10 20 30 40 50 60 MEADGAGEQM RPLLTRGPDE EAVVDLGKTS STVNTKFEKE ELESHRAVYV GVHVPFSKES 70 80 90 100 110 120 RRRHKHRGHK HHHRRRKDKD SDKEDGRESP SYDTPSQRVQ FILGTEDDDE EHIPHDLFTE 130 140 150 160 170 180 MDELCYRDGE EYEWKETARW LKFEEDVEDG GDRWSKPYVA TLSLHSLFEL RSCILNGTVM 190 200 210 220 230 240 LDMRASTLDE IADMVLDNMI ASGQLDDSIR ENVREALLKR HHHQNEKRFT SRIPLVRSFA 250 260 270 280 290 300 DIGILASPQS APGNLDNSKS GEMKGNGSGG SRENSTVDFS KVDMNFMRKI PTGAEASNVL 310 320 330 340 350 360 VGEVDFLERP IIAFVRLAPA VLLSGLTEVP VPTRFLFLLL GPAGKAPQYH EIGRSIATLM 370 380 390 400 410 420 TDEIFHDVAY KAKDRNDLLS GIDEFLDQVT VLPPGEWDPS IRIEPPKSVP SQEKRKIPVF 430 440 450 460 470 480 PNGSAAMSVG PPKEDDHHAG PELQRTGRLF GGLILDIKRK APFFLSDFKD ALSLQCLASI 490 500 510 520 530 540 LFLYCACMSP VITFGGLLGE ATEGRISAIE SLFGASLTGI AYSLFAGQPL TILGSTGPVL 550 560 570 580 590 600 VFEKILFKFC RDYHLSYLSL RTSIGLWTSF LCIVLVATDA SSLVCYITRF TEEAFAALIC 610 620 630 640 650 660 IIFIYEALEK LFHLGEIYAF NMHNNLDELT SYTCVCAEPS NPSNETLELW KRKNITAYSV 670 680 690 700 710 720 SWGNLTVSEC KTFHGMFVGS ACGPHGPYVP DVLFWCVVLF FTTFFLSSFL KQFKTKGYFP 730 740 750 760 770 780 TKVRSTISDF AVFLTIVIMV AIDYLVGIPS PKLHVPEKFE PTDPSRGWII SPLGDNPWWT 790 800 810 820 830 840 LLIAAVPALL CTILIFMDQQ ITAVIINRKE HKLKFIPMPV LYGVFLYMGV SSLKGIQFFD 850 860 870 880 890 900 RIKLFGMPAK HQPDLIYLRY VPLWKVHVFT VVQLTCLVLL WVIKASAAAV VFPMMVLALV 910 920 930 940 950 960 FVRKLMDLCF TKRELSWLDD LMPESKKKKE DDKKKKEKEE AERMLQDDED TVHLPFERGS 970 980 990 1000 1010 1020 LLQIPVKTLK YSIDPSVVNI SDEMAKTAQW KALSMNTENA KVTRPNTSPE KPVSVTINFE 1030 DEPSKKYMDA ETSL
	Isoform 2 [UniParc]. Checksum: 03664D0534FD2EBC	FASTA	936	104,678
	10 20 30 40 50 60 MEADGAGEQM RPLLTRGPDE EAVVDLGKTS STVNTKFEKE ELESHRAVYV GVHVPFSKES 70 80 90 100 110 120 RRRHKHRGHK HHHRRRKDKD SDKEDGRESP SYDTPSQRVQ FILGTEDDDE EHIPHDLFTE 130 140 150 160 170 180 MDELCYRDGE EYEWKETARW LKFEEDVEDG GDRWSKPYVA TLSLHSLFEL RSCILNGTVM 190 200 210 220 230 240 LDMRASTLDE IADMVLDNMI ASGQLDDSIR ENVREALLKR HHHQNEKRFT SRIPLVRSFA 250 260 270 280 290 300 DIGKKHSDPH LLERNGILAS PQSAPGNLDN SKSGEMKGNG SGGSRENSTV DFSKVDMNFM 310 320 330 340 350 360 RKIPTGAEAS NVLVGEVDFL ERPIIAFVRL APAVLLSGLT EVPVPTRFLF LLLGPAGKAP 370 380 390 400 410 420 QYHEIGRSIA TLMTDEIFHD VAYKAKDRND LLSGIDEFLD QVTVLPPGEW DPSIRIEPPK 430 440 450 460 470 480 SVPSQEKRKI PVFPNGSAAM SVGPPKEDDH HAGPELQRTG RLFGGLILDI KRKAPFFLSD 490 500 510 520 530 540 FKDALSLQCL ASILFLYCAC MSPVITFGGL LGEATEGRIS AIESLFGASL TGIAYSLFAG 550 560 570 580 590 600 QPLTILGSTG PVLVFEKILF KFCRDYHLSY LSLRTSIGLW TSFLCIVLVA TDASSLVCYI 610 620 630 640 650 660 TRFTEEAFAA LICIIFIYEA LEKLFHLGEI YAFNMHNNLD ELTSYTCVCA EPSNPSNETL 670 680 690 700 710 720 ELWKRKNITA YSVSWGNLTV SECKTFHGMF VGSACGPHGP YVPDVLFWCV VLFFTTFFLS 730 740 750 760 770 780 SFLKQFKTKG YFPTKVRSTI SDFAVFLTIV IMVAIDYLVG IPSPKLHVPE KFEPTDPSRG 790 800 810 820 830 840 WIISPLGDNP WWTLLIAAVP ALLCTILIFM DQQITAVIIN RKEHKLKKGA GYHLDLLMVG 850 860 870 880 890 900 VMLGVCSIMG LPWFVAATVL SISHVNSLKV ESECSAPGEQ PKFLGIREQR VTGLMIFILM 910 920 930 GLSVFMTSVL KVKPLWQCST ILFTLTFILS CKEIKH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-932 (ISOFORM 1). Strain: C57BL/6J and NOD. Tissue: Bone marrow and Thymus.
[2]	"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] OF 826-1034 (ISOFORM 1). Strain: C57BL/6. Tissue: Brain.
[3]	"The cystic fibrosis transmembrane conductance regulator interacts with and regulates the activity of the HCO3- salvage transporter human Na+-HCO3-cotransport isoform 3." Park M., Ko S.B.H., Choi J.Y., Muallem G., Thomas P.J., Pushkin A., Lee M.-S., Kim J.Y., Lee M.G., Muallem S., Kurtz I. J. Biol. Chem. 277:50503-50509(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CFTR AND SLC9A3R1.
[4]	"Blindness and auditory impairment caused by loss of the sodium bicarbonate cotransporter NBC3." Bok D., Galbraith G., Lopez I., Woodruff M., Nusinowitz S., BeltrandelRio H., Huang W., Zhao S., Geske R., Montgomery C., van Sligtenhorst I., Friddle C., Platt K., Sparks M.J., Pushkin A., Abuladze N., Ishiyama A., Dukkipati R., Liu W., Kurtz I. Nat. Genet. 34:313-319(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[5]	"Scaffold protein harmonin (USH1C) provides molecular links between Usher syndrome type 1 and type 2." Reiners J., van Wijk E., Maerker T., Zimmermann U., Juergens K., te Brinke H., Overlack N., Roepman R., Knipper M., Kremer H., Wolfrum U. Hum. Mol. Genet. 14:3933-3943(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH USH1C, TISSUE SPECIFICITY.
[6]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275, MASS SPECTROMETRY. Tissue: Liver.
[7]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-238; SER-247; THR-951; SER-960 AND SER-1033, MASS SPECTROMETRY. Tissue: Macrophage.
[8]	"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry." Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J. Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-960, MASS SPECTROMETRY. Tissue: Embryonic fibroblast.
[9]	"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins." Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D. Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-654 AND ASN-664, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK088400 mRNA. Translation: BAC40330.1. AK152233 mRNA. Translation: BAE31059.1. AK153567 mRNA. Translation: BAE32101.1. CN532915 mRNA. No translation available.
IPI	IPI00225306. IPI00986787.
UniGene	Mm.258893.
3D structure databases
ProteinModelPortal	Q8BTY2.
SMR	Q8BTY2. Positions 115-394, 460-500.
ModBase	Search...
PTM databases
PhosphoSite	Q8BTY2.
Proteomic databases
PaxDb	Q8BTY2.
PRIDE	Q8BTY2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Organism-specific databases
MGI	MGI:2443878. Slc4a7.
Phylogenomic databases
eggNOG	NOG268067.
HOGENOM	HOG000280684.
HOVERGEN	HBG004326.
OrthoDB	EOG40GCQ3.
Gene expression databases
Genevestigator	Q8BTY2.
Family and domain databases
Gene3D	3.40.1100.10. 1 hit.
InterPro	IPR013769. Band3_cytoplasmic_dom. IPR011531. HCO3_transpt_C. IPR003020. HCO3_transpt_euk. IPR003024. Na/HCO3_transpt. IPR016152. PTrfase/Anion_transptr. [Graphical view]
PANTHER	PTHR11453. PTHR11453. 1 hit.
Pfam	PF07565. Band_3_cyto. 1 hit. PF00955. HCO3_cotransp. 1 hit. [Graphical view]
PRINTS	PR01231. HCO3TRNSPORT. PR01232. NAHCO3TRSPRT.
SUPFAM	SSF55804. PTrfase/Anion_transptr. 1 hit.
TIGRFAMs	TIGR00834. ae. 1 hit.
PROSITE	PS00219. ANION_EXCHANGER_1. False negative. PS00220. ANION_EXCHANGER_2. False negative. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SLC4A7. mouse.
SOURCE	Search...

Entry information

Entry name

S4A7_MOUSE

Accession

Primary (citable) accession number: Q8BTY2
Secondary accession number(s): Q3U5H7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 7, 2006
Last sequence update:	February 7, 2006
Last modified:	May 1, 2013
This is version 81 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program