S4A11_MOUSE
ID S4A11_MOUSE Reviewed; 862 AA.
AC A2AJN7; Q0VG86; Q3URQ1;
DT 14-OCT-2008, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Solute carrier family 4 member 11;
DE AltName: Full=Sodium borate cotransporter 1;
DE Short=NaBC1;
GN Name=Slc4a11; Synonyms=BTR1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 486-862.
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=20185830; DOI=10.1074/jbc.m109.094680;
RA Groger N., Frohlich H., Maier H., Olbrich A., Kostin S., Braun T.,
RA Boettger T.;
RT "SLC4A11 prevents osmotic imbalance leading to corneal endothelial
RT dystrophy, deafness, and polyuria.";
RL J. Biol. Chem. 285:14467-14474(2010).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=23813972; DOI=10.1093/hmg/ddt307;
RA Vilas G.L., Loganathan S.K., Liu J., Riau A.K., Young J.D., Mehta J.S.,
RA Vithana E.N., Casey J.R.;
RT "Transmembrane water-flux through SLC4A11: a route defective in genetic
RT corneal diseases.";
RL Hum. Mol. Genet. 22:4579-4590(2013).
RN [6]
RP FUNCTION.
RX PubMed=33247189; DOI=10.1038/s42003-020-01449-4;
RA Rico P., Rodrigo-Navarro A., Sanchez Perez L., Salmeron-Sanchez M.;
RT "Borax induces osteogenesis by stimulating NaBC1 transporter via activation
RT of BMP pathway.";
RL Commun. Biol. 3:717-717(2020).
CC -!- FUNCTION: Multifunctional transporter with an impact in cell morphology
CC and differentiation (PubMed:20185830). In the presence of borate
CC B(OH)4(-), acts as a voltage-dependent electrogenic Na(+)-coupled
CC B(OH)4(-) cotransporter controlling boron homeostasis (By similarity).
CC At early stages of stem cell differentiation, participates in synergy
CC with ITGA5-ITGB1 and ITGAV-ITGB3 integrins and BMPR1A to promote cell
CC adhesion and contractility that drives differentiation toward
CC osteogenic commitment while inhibiting adipogenesis (PubMed:33247189).
CC In the absence of B(OH)4(-), acts as a Na(+)-coupled OH(-) or H(+)
CC permeable channel with implications in cellular redox balance.
CC Regulates the oxidative stress response in corneal endothelium by
CC enhancing antioxidant defenses and protecting cells from reactive
CC oxygen species. In response to hypo-osmotic challenge, also acts as
CC water permeable channel at the basolateral cell membrane of corneal
CC endothelial cells and facilitates transendothelial fluid reabsorption
CC in the aqueous humor. In the presence of ammonia, acts as an
CC electrogenic NH3/H(+) cotransporter and may play a role in ammonia
CC transport and reabsorption in renal Henle's loop epithelium (By
CC similarity). {ECO:0000250|UniProtKB:Q8NBS3,
CC ECO:0000269|PubMed:20185830, ECO:0000269|PubMed:33247189}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 Na(+)(in) + tetrahydroxoborate(in) = 2 Na(+)(out) +
CC tetrahydroxoborate(out); Xref=Rhea:RHEA:66816, ChEBI:CHEBI:29101,
CC ChEBI:CHEBI:41132; Evidence={ECO:0000250|UniProtKB:Q8NBS3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66817;
CC Evidence={ECO:0000250|UniProtKB:Q8NBS3};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q8NBS3}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8NBS3};
CC Multi-pass membrane protein {ECO:0000255}. Basolateral cell membrane
CC {ECO:0000250|UniProtKB:Q8NBS3}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in the endothelial cells of the cornea.
CC In the inner ear, is located in fibrocytes underlying the stria
CC vascularis. In the kidney, is expressed in the thin descending limb of
CC Henle loop. {ECO:0000269|PubMed:20185830}.
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:Q8NBS3}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice show corneal defects characterized by
CC progressive thickening of the stroma and descement membrane concomitant
CC with increased sodium chloride concentration in the stroma
CC (PubMed:20185830, PubMed:23813972). They show impaired urinary
CC concentration, increased urinary volume, and increased urinary sodium
CC loss in the kidney. They also show stress-induced morphological changes
CC of fibrocytes of the inner ear resulting in deafness.
CC {ECO:0000269|PubMed:20185830, ECO:0000269|PubMed:23813972}.
CC -!- SIMILARITY: Belongs to the anion exchanger (TC 2.A.31) family.
CC {ECO:0000305}.
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DR EMBL; AL772162; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC111884; AAI11885.1; -; mRNA.
DR EMBL; AK141286; BAE24637.1; -; mRNA.
DR CCDS; CCDS38244.1; -.
DR RefSeq; NP_001074631.1; NM_001081162.1.
DR AlphaFoldDB; A2AJN7; -.
DR SMR; A2AJN7; -.
DR STRING; 10090.ENSMUSP00000096963; -.
DR GlyGen; A2AJN7; 2 sites.
DR iPTMnet; A2AJN7; -.
DR PhosphoSitePlus; A2AJN7; -.
DR EPD; A2AJN7; -.
DR PaxDb; A2AJN7; -.
DR PeptideAtlas; A2AJN7; -.
DR PRIDE; A2AJN7; -.
DR ProteomicsDB; 256825; -.
DR Antibodypedia; 7351; 111 antibodies from 27 providers.
DR Ensembl; ENSMUST00000099362; ENSMUSP00000096963; ENSMUSG00000074796.
DR GeneID; 269356; -.
DR KEGG; mmu:269356; -.
DR UCSC; uc008mjv.1; mouse.
DR CTD; 83959; -.
DR MGI; MGI:2138987; Slc4a11.
DR VEuPathDB; HostDB:ENSMUSG00000074796; -.
DR eggNOG; KOG1172; Eukaryota.
DR GeneTree; ENSGT00940000154894; -.
DR HOGENOM; CLU_002289_6_0_1; -.
DR InParanoid; A2AJN7; -.
DR OMA; YDHNVSS; -.
DR OrthoDB; 265068at2759; -.
DR PhylomeDB; A2AJN7; -.
DR TreeFam; TF313630; -.
DR BioGRID-ORCS; 269356; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Slc4a11; mouse.
DR PRO; PR:A2AJN7; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; A2AJN7; protein.
DR Bgee; ENSMUSG00000074796; Expressed in vestibular membrane of cochlear duct and 82 other tissues.
DR ExpressionAtlas; A2AJN7; baseline and differential.
DR Genevisible; A2AJN7; MM.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0012506; C:vesicle membrane; ISO:MGI.
DR GO; GO:0046715; F:active borate transmembrane transporter activity; ISO:MGI.
DR GO; GO:0015301; F:anion:anion antiporter activity; IEA:UniProtKB-KW.
DR GO; GO:0015106; F:bicarbonate transmembrane transporter activity; ISO:MGI.
DR GO; GO:0005452; F:inorganic anion exchanger activity; IEA:InterPro.
DR GO; GO:0046983; F:protein dimerization activity; ISS:UniProtKB.
DR GO; GO:0015252; F:proton channel activity; ISO:MGI.
DR GO; GO:0015078; F:proton transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0005272; F:sodium channel activity; ISO:MGI.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0005372; F:water transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015701; P:bicarbonate transport; ISO:MGI.
DR GO; GO:0046713; P:borate transport; ISO:MGI.
DR GO; GO:0030003; P:cellular cation homeostasis; ISO:MGI.
DR GO; GO:0071476; P:cellular hypotonic response; ISS:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0042044; P:fluid transport; IMP:UniProtKB.
DR GO; GO:0050801; P:ion homeostasis; IMP:UniProtKB.
DR GO; GO:1902600; P:proton transmembrane transport; ISO:MGI.
DR GO; GO:2000739; P:regulation of mesenchymal stem cell differentiation; IMP:UniProtKB.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; ISS:UniProtKB.
DR GO; GO:0006814; P:sodium ion transport; ISO:MGI.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR Gene3D; 3.40.930.10; -; 1.
DR InterPro; IPR011531; HCO3_transpt-like_TM_dom.
DR InterPro; IPR003020; HCO3_transpt_euk.
DR InterPro; IPR016152; PTrfase/Anion_transptr.
DR PANTHER; PTHR11453; PTHR11453; 1.
DR Pfam; PF00955; HCO3_cotransp; 1.
DR PRINTS; PR01231; HCO3TRNSPORT.
DR SUPFAM; SSF55804; SSF55804; 1.
PE 2: Evidence at transcript level;
KW Anion exchange; Cell membrane; Glycoprotein; Ion transport; Membrane;
KW Reference proteome; Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..862
FT /note="Solute carrier family 4 member 11"
FT /id="PRO_0000352350"
FT TOPO_DOM 1..343
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8NBS3"
FT TRANSMEM 344..366
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 367..379
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8NBS3"
FT TRANSMEM 380..393
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 394..398
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8NBS3"
FT TRANSMEM 399..415
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 416..428
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8NBS3"
FT TRANSMEM 429..452
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 453..460
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8NBS3"
FT TRANSMEM 461..481
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 482..542
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8NBS3"
FT TRANSMEM 543..564
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 565..577
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8NBS3"
FT TRANSMEM 578..599
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 600..627
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8NBS3"
FT TRANSMEM 628..645
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 646..670
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8NBS3"
FT TRANSMEM 671..691
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 692..721
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8NBS3"
FT TRANSMEM 722..746
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 747..752
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8NBS3"
FT TRANSMEM 753..770
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 771..774
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8NBS3"
FT TRANSMEM 775..797
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 798..802
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8NBS3"
FT TRANSMEM 803..819
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 820..823
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8NBS3"
FT TRANSMEM 824..844
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 845..862
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8NBS3"
FT CARBOHYD 511
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 519
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 151
FT /note="A -> T (in Ref. 2; AAI11885)"
FT /evidence="ECO:0000305"
FT CONFLICT 850
FT /note="A -> S (in Ref. 2; AAI11885)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 862 AA; 96751 MW; D8118D841B1B8D6A CRC64;
MSQNEHCQDS GEYFSAGTQG YFKNNMEDNL EVREDSLGDE VFDTVNSSIV SGESIRFFVN
VNLEVQPSKS DLEAATGGCV LLHTSRKYLK LKNFEEEVRA HRDLDGFLAQ ASIILNETAT
SLDDVLRTML NRFALDPNHA EPDCDLDLLM AKLFTDAGAP MESKVHLLSD TIQGVTATVR
GVQYEQSWLC IICTMKTLQK RHVCISRLVR PQNWGENSCE VRFVILVLAP PKMKSTKTAM
EVARTFATMF SDITFRQKLL KTRTEEEFKE ALVHQRQLLT MMMPRAAGHS MSSLHTHRHP
QPPKCKDFFP FGKGIWMDIM RRFPVYPMDF TDGIIGKSKS VGKYVTTTLF LYFACLLPTI
AFGSLNDENT NGAIDVQKTI AGQSIGGLLY ALFSGQPLVI LLTTAPLAIY TQVIRVICDD
YNLDFNAFYA WTGLWNSFFL ALYAFLNLSL LMNLFKRSTE EIIALFISIT FVLDAVKGMV
KIFGKYYYGH HYHTKRTSSL VSLLGIGRSP NSSLHTALNA SLLASPVEMA TTSSPGSTHS
GQATAVLSLL IMLGTLWLGY TLYQFKKSPY LHPCVRETLS DCALPIAVLS FSLIGSYGFQ
EIEMSKFRYN PSESLFEVAQ IHSLSFKAIG SAMGLGFLLS LLFFIEQNLV AALVNAPENR
LVKGTAYHWD LLLLAIINTG LSLFGLPWIH AAYPHSPLHV RALALVEERV ENGHIYETIV
DVKETRLTAL GASVLVGLSL LLLPFPLQWI PKPVLYGLFL YIALTSLDGN QLFSRVALLL
KEQTSYPPTH YIRRVPQRKI HYFTGLQILQ LLLLCAFGMS SLPYMKMVFP LIMIAMIPIR
YNLLPRIIEA KYLDVMDAEH RP