S4A8_MOUSE
ID S4A8_MOUSE Reviewed; 1089 AA.
AC Q8JZR6; Q3TAV7; Q6A004; Q8BYI7; Q9JKV6;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Electroneutral sodium bicarbonate exchanger 1;
DE AltName: Full=Electroneutral Na+-driven Cl-HCO3 exchanger;
DE AltName: Full=Solute carrier family 4 member 8;
DE AltName: Full=k-NBC3;
GN Name=Slc4a8 {ECO:0000312|EMBL:AAH30388.1, ECO:0000312|MGI:MGI:1928745};
GN Synonyms=Kiaa0739;
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] {ECO:0000305, ECO:0000312|EMBL:AAF61705.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND
RP INHIBITION.
RC TISSUE=Kidney inner medulla {ECO:0000312|EMBL:AAF61705.1};
RX PubMed=11260402; DOI=10.1046/j.1523-1755.2001.0590041405.x;
RA Wang Z., Conforti L., Petrovic S., Amlal H., Burnham C.E., Soleimani M.;
RT "Mouse Na+: HCO3- cotransporter isoform NBC-3 (kNBC-3): cloning,
RT expression, and renal distribution.";
RL Kidney Int. 59:1405-1414(2001).
RN [2] {ECO:0000305, ECO:0000312|EMBL:BAC30341.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC30341.1};
RC TISSUE=Dendritic cell {ECO:0000269|PubMed:16141072}, and
RC Spinal cord {ECO:0000312|EMBL:BAC30341.1};
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 [3] {ECO:0000305, ECO:0000312|EMBL:BAD32292.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain {ECO:0000312|EMBL:BAD32292.1};
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [4] {ECO:0000305, ECO:0000312|EMBL:AAH30388.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J {ECO:0000269|PubMed:15489334};
RC TISSUE=Retina {ECO:0000312|EMBL:AAH30388.1};
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).
CC -!- FUNCTION: Mediates electroneutral sodium- and carbonate-dependent
CC chloride-HCO3(-) exchange with a Na(+):HCO3(-) stoichiometry of 2:1.
CC Plays a major role in pH regulation in neurons. May be involved in cell
CC pH regulation by transporting HCO3(-) from blood to cell. Enhanced
CC expression in severe acid stress could be important for cell survival
CC by mediating the influx of HCO3(-) into the cells. Also mediates
CC lithium-dependent HCO3(-) cotransport. May be regulated by osmolarity.
CC {ECO:0000269|PubMed:11260402}.
CC -!- ACTIVITY REGULATION: Activity is inhibited by 4,4'-Di-
CC isothiocyanatostilbene-2,2'-disulfonic acid (DIDS - an inhibitor of
CC several anion channels and transporters).
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:11260402}; Multi-
CC pass membrane protein {ECO:0000269|PubMed:11260402}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:11260402, ECO:0000269|PubMed:15489334,
CC ECO:0000269|PubMed:16141072};
CC IsoId=Q8JZR6-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:16141072};
CC IsoId=Q8JZR6-2; Sequence=VSP_052769;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain with lower levels in
CC lung, kidney and heart. In the kidney, there is high expression in the
CC inner medulla, localized to the inner medullary collecting duct. In the
CC brain, there seems to be three transcripts each having a different
CC expression pattern. The smaller 3kb transcript has highest expression
CC levels in the thalamus and the largest 9.5kb transcript has highest
CC levels in the substantia nigra. The middle transcript of 4.4kb, which
CC is also the main transcript in kidney, is highly expressed in thalamus.
CC Hence, the highest levels are observed in the thalamus, amygdala and
CC caudate nucleus and very low expression was seen in the corpus
CC callosum. {ECO:0000269|PubMed:11260402}.
CC -!- SIMILARITY: Belongs to the anion exchanger (TC 2.A.31) family.
CC {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD32292.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF224508; AAF61705.1; -; mRNA.
DR EMBL; AK039404; BAC30341.1; -; mRNA.
DR EMBL; AK171610; BAE42561.1; -; mRNA.
DR EMBL; AK173014; BAD32292.1; ALT_INIT; mRNA.
DR EMBL; BC030388; AAH30388.1; -; mRNA.
DR CCDS; CCDS37214.1; -. [Q8JZR6-1]
DR CCDS; CCDS84193.1; -. [Q8JZR6-2]
DR RefSeq; NP_001334031.1; NM_001347102.1. [Q8JZR6-2]
DR RefSeq; NP_067505.2; NM_021530.2. [Q8JZR6-1]
DR RefSeq; XP_017172207.1; XM_017316718.1. [Q8JZR6-2]
DR AlphaFoldDB; Q8JZR6; -.
DR SMR; Q8JZR6; -.
DR BioGRID; 208500; 2.
DR IntAct; Q8JZR6; 1.
DR STRING; 10090.ENSMUSP00000023776; -.
DR iPTMnet; Q8JZR6; -.
DR PhosphoSitePlus; Q8JZR6; -.
DR EPD; Q8JZR6; -.
DR jPOST; Q8JZR6; -.
DR MaxQB; Q8JZR6; -.
DR PaxDb; Q8JZR6; -.
DR PeptideAtlas; Q8JZR6; -.
DR PRIDE; Q8JZR6; -.
DR ProteomicsDB; 256826; -. [Q8JZR6-1]
DR ProteomicsDB; 256827; -. [Q8JZR6-2]
DR Antibodypedia; 26410; 177 antibodies from 25 providers.
DR DNASU; 59033; -.
DR Ensembl; ENSMUST00000023776; ENSMUSP00000023776; ENSMUSG00000023032. [Q8JZR6-1]
DR Ensembl; ENSMUST00000162049; ENSMUSP00000125090; ENSMUSG00000023032. [Q8JZR6-2]
DR GeneID; 59033; -.
DR KEGG; mmu:59033; -.
DR UCSC; uc007xse.1; mouse. [Q8JZR6-1]
DR CTD; 9498; -.
DR MGI; MGI:1928745; Slc4a8.
DR VEuPathDB; HostDB:ENSMUSG00000023032; -.
DR eggNOG; KOG1172; Eukaryota.
DR GeneTree; ENSGT00940000157422; -.
DR HOGENOM; CLU_002289_5_2_1; -.
DR InParanoid; Q8JZR6; -.
DR OMA; VCHIEAE; -.
DR OrthoDB; 265068at2759; -.
DR PhylomeDB; Q8JZR6; -.
DR TreeFam; TF313630; -.
DR Reactome; R-MMU-425381; Bicarbonate transporters.
DR BioGRID-ORCS; 59033; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Slc4a8; mouse.
DR PRO; PR:Q8JZR6; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q8JZR6; protein.
DR Bgee; ENSMUSG00000023032; Expressed in spermatocyte and 132 other tissues.
DR ExpressionAtlas; Q8JZR6; baseline and differential.
DR Genevisible; Q8JZR6; MM.
DR GO; GO:0032279; C:asymmetric synapse; ISO:MGI.
DR GO; GO:0043679; C:axon terminus; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0097386; C:glial cell projection; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:ARUK-UCL.
DR GO; GO:0097457; C:hippocampal mossy fiber; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0043005; C:neuron projection; IDA:MGI.
DR GO; GO:0032809; C:neuronal cell body membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0098793; C:presynapse; IDA:ARUK-UCL.
DR GO; GO:0042734; C:presynaptic membrane; IDA:ARUK-UCL.
DR GO; GO:0032280; C:symmetric synapse; ISO:MGI.
DR GO; GO:0008021; C:synaptic vesicle; ISO:MGI.
DR GO; GO:0043195; C:terminal bouton; 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:0015108; F:chloride transmembrane transporter activity; ISO:MGI.
DR GO; GO:0005452; F:inorganic anion exchanger activity; IEA:InterPro.
DR GO; GO:0015081; F:sodium ion transmembrane transporter activity; ISO:MGI.
DR GO; GO:0008510; F:sodium:bicarbonate symporter activity; ISO:MGI.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015701; P:bicarbonate transport; ISO:MGI.
DR GO; GO:1902476; P:chloride transmembrane transport; ISO:MGI.
DR GO; GO:0050801; P:ion homeostasis; IBA:GO_Central.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IMP:ARUK-UCL.
DR GO; GO:2000302; P:positive regulation of synaptic vesicle exocytosis; IMP:ARUK-UCL.
DR GO; GO:0051453; P:regulation of intracellular pH; IMP:ARUK-UCL.
DR GO; GO:0042391; P:regulation of membrane potential; ISO:MGI.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISO:MGI.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR Gene3D; 3.40.930.10; -; 1.
DR InterPro; IPR013769; Band3_cytoplasmic_dom.
DR InterPro; IPR011531; HCO3_transpt-like_TM_dom.
DR InterPro; IPR003020; HCO3_transpt_euk.
DR InterPro; IPR003024; Na/HCO3_transpt.
DR InterPro; IPR016152; PTrfase/Anion_transptr.
DR PANTHER; PTHR11453; PTHR11453; 1.
DR Pfam; PF07565; Band_3_cyto; 1.
DR Pfam; PF00955; HCO3_cotransp; 1.
DR PRINTS; PR01231; HCO3TRNSPORT.
DR PRINTS; PR01232; NAHCO3TRSPRT.
DR SUPFAM; SSF55804; SSF55804; 1.
DR TIGRFAMs; TIGR00834; ae; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Anion exchange; Antiport; Disulfide bond;
KW Ion transport; Membrane; Reference proteome; Sodium; Sodium transport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1089
FT /note="Electroneutral sodium bicarbonate exchanger 1"
FT /id="PRO_0000328923"
FT TOPO_DOM 1..476
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 477..497
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 498..505
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 506..526
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 527..563
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 564..584
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 585..593
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 594..614
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 615..685
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 686..706
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 707..729
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 730..750
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 751..776
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 777..797
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 798..822
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 823..843
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 844..879
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 880..900
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 901..902
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 903..923
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 924..960
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 961..981
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 982..1089
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 55..90
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 56..76
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 634..636
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT DISULFID 670..682
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT VAR_SEQ 1..52
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_052769"
FT CONFLICT 219
FT /note="K -> E (in Ref. 2; BAE42561)"
FT /evidence="ECO:0000305"
FT CONFLICT 258
FT /note="V -> M (in Ref. 1; AAF61705)"
FT /evidence="ECO:0000305"
FT CONFLICT 291
FT /note="K -> R (in Ref. 2; BAE42561)"
FT /evidence="ECO:0000305"
FT CONFLICT 644
FT /note="N -> S (in Ref. 2; BAC30341)"
FT /evidence="ECO:0000305"
FT CONFLICT 707
FT /note="S -> P (in Ref. 1; AAF61705)"
FT /evidence="ECO:0000305"
FT CONFLICT 949
FT /note="K -> E (in Ref. 2; BAE42561)"
FT /evidence="ECO:0000305"
FT CONFLICT 1015
FT /note="D -> G (in Ref. 2; BAC30341)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1089 AA; 122421 MW; CFAE127D3853DDD8 CRC64;
MPAGSNEPDG VLSYQRPDEE AVVDQGGTST ILNIHYEKEE LEGHRTLYVG VRMPLGRQSH
RHHRTHGQKH RRRGGRGKGA SQGEEGLEAL AHDTPSQRVQ FILGTEEDEE HVPHELFTEL
DEICMKEGED AEWKETARWL KFEEDVEDGG ERWSKPYVAT LSLHSLFELR SCLINGSVLL
DMRASSIEEI SDLILDQQEL LRDLSDSVRV KVREALLKKH HHQNERRRNN LIPIVRSFAE
VGKKQSDPHS MDRDGQTVSP QSATNLEVKN GVNCEHSPVD LSKVDLHFMK KIPTGAEASN
VLVGEVDTLD RPIVAFVRLS PAVLLSGLTE VPIPTRFLFI LLGPVGKGQQ YHEIGRSMAT
IMTDEIFHDV AYKAKERDDL LAGIDEFLDQ VTVLPPGEWD PSIRIEPPKN VPSQEKRKMP
GVPNGNVCHI EPEPHGGHSG PELERTGRLF GGLVLDVKRK APWYWSDYRD ALSLQCLASF
LFLYCACMSP VITFGGLLGE ATEGRISAIE SLFGASMTGI AYSLFAGQPL TILGSTGPVL
VFEKILFKFC KDYALSYLSL RALIGLWTAF LCIVLVATDA SSLVCYITRF TEEAFASLIC
IIFIYEAIEK LIHLAETYPI HMHSQLDHLS LYYCRCVLPE NPNNHTLQYW KDHNILAAEV
NWANLTVSEC QEMHGEFMGS ACGHHGPYTP DVLFWSCILF FATFIVSSTL KTFKTSRYFP
TRVRSMVSDF AVFLTIFTMV VLDFLIGVPS PKLQVPNVFK PTRDDRGWFI NPIGPNPWWT
VIAAIIPALL CTILIFMDQQ ITAVIINRKE HKLKKGCGYH LDLLMVAVML GVCSIMGLPW
FVAATVLSIT HVNSLKLESE CSAPGEQPKF LGIREQRVTG LMIFVLMGCS VFMTAVLKFI
PMPVLYGVFL YMGVSSLQGI QFFDRLKLFG MPAKHQPDFI YLRHVPLRKV HLFTLVQLTC
LVLLWVIKAS PAAIVFPMMV LALVFVRKVM DLCFSKRELS WLDDLMPESK KKKLDDAKKK
EEEEAEKMLD IGGDKFPLES RKLLSSPGKS SSFRCDPSEI NISDEMPKTT VWKALSINSG
NTKEKSPFN
