ID   S4A4_AMBTI              Reviewed;        1035 AA.
AC   O13134;
DT   20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1997, sequence version 1.
DT   13-SEP-2023, entry version 86.
DE   RecName: Full=Electrogenic sodium bicarbonate cotransporter 1;
DE            Short=Sodium bicarbonate cotransporter;
DE   AltName: Full=Na(+)/HCO3(-) cotransporter;
DE   AltName: Full=Solute carrier family 4 member 4;
GN   Name=SLC4A4; Synonyms=NBC, NBCE1;
OS   Ambystoma tigrinum (Eastern tiger salamander).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Caudata; Salamandroidea; Ambystomatidae; Ambystoma.
OX   NCBI_TaxID=8305;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND TRANSPORTER
RP   ACTIVITY.
RC   TISSUE=Kidney;
RX   PubMed=9163427; DOI=10.1038/387409a0;
RA   Romero M.F., Hediger M.A., Boulpaep E.L., Boron W.F.;
RT   "Expression cloning and characterization of a renal electrogenic
RT   Na+/HCO3- cotransporter.";
RL   Nature 387:409-413(1997).
RN   [2]
RP   SUBCELLULAR LOCATION.
RX   PubMed=11095641; DOI=10.1681/asn.v11122179;
RA   Maunsbach A.B., Vorum H., Kwon T.-H., Nielsen S., Simonsen B., Choi I.,
RA   Schmitt B.M., Boron W.F., Aalkjaer C.;
RT   "Immunoelectron microscopic localization of the electrogenic Na/HCO(3)
RT   cotransporter in rat and ambystoma kidney.";
RL   J. Am. Soc. Nephrol. 11:2179-2189(2000).
CC   -!- FUNCTION: Electrogenic sodium/bicarbonate cotransporter with a
CC       Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3. May regulate
CC       bicarbonate influx/efflux at the basolateral membrane of cells and
CC       regulate intracellular pH. {ECO:0000269|PubMed:9163427}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 hydrogencarbonate(out) + Na(+)(out) = 2
CC         hydrogencarbonate(in) + Na(+)(in); Xref=Rhea:RHEA:72215,
CC         ChEBI:CHEBI:17544, ChEBI:CHEBI:29101;
CC         Evidence={ECO:0000269|PubMed:9163427};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3 hydrogencarbonate(out) + Na(+)(out) = 3
CC         hydrogencarbonate(in) + Na(+)(in); Xref=Rhea:RHEA:72219,
CC         ChEBI:CHEBI:17544, ChEBI:CHEBI:29101;
CC         Evidence={ECO:0000269|PubMed:9163427};
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q9Y6R1}.
CC   -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC       {ECO:0000269|PubMed:11095641}; Multi-pass membrane protein
CC       {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:Q9Y6R1}; Multi-pass
CC       membrane protein {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Expressed in kidney and to a lower extent in
CC       bladder, brain, intestine, large intestine and eye.
CC       {ECO:0000269|PubMed:9163427}.
CC   -!- SIMILARITY: Belongs to the anion exchanger (TC 2.A.31) family.
CC       {ECO:0000305}.
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DR   EMBL; AF001958; AAB61339.1; -; mRNA.
DR   PIR; T31336; T31336.
DR   AlphaFoldDB; O13134; -.
DR   SMR; O13134; -.
DR   GlyCosmos; O13134; 4 sites, No reported glycans.
DR   GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0008509; F:monoatomic anion transmembrane transporter activity; IEA:InterPro.
DR   GO; GO:0008510; F:sodium:bicarbonate symporter activity; IDA:UniProtKB.
DR   GO; GO:0005452; F:solute:inorganic anion antiporter activity; IEA:InterPro.
DR   Gene3D; 1.10.287.570; Helical hairpin bin; 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   NCBIfam; TIGR00834; ae; 1.
DR   PANTHER; PTHR11453; ANION EXCHANGE PROTEIN; 1.
DR   PANTHER; PTHR11453:SF10; ELECTROGENIC SODIUM BICARBONATE COTRANSPORTER 1; 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; Phoshotransferase/anion transport protein; 1.
PE   2: Evidence at transcript level;
KW   Cell membrane; Glycoprotein; Ion transport; Membrane; Sodium;
KW   Sodium transport; Symport; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..1035
FT                   /note="Electrogenic sodium bicarbonate cotransporter 1"
FT                   /id="PRO_0000079232"
FT   TOPO_DOM        1..421
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TRANSMEM        422..446
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TOPO_DOM        447..456
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TRANSMEM        457..475
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TOPO_DOM        476
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TRANSMEM        477..497
FT                   /note="Discontinuously helical; Name=3"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TOPO_DOM        498..505
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TRANSMEM        506..526
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TOPO_DOM        527..540
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TRANSMEM        541..564
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TOPO_DOM        565..648
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TRANSMEM        649..666
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TOPO_DOM        667..681
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TRANSMEM        682..701
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TOPO_DOM        702..735
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TRANSMEM        736..763
FT                   /note="Helical; Name=8"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TOPO_DOM        764..775
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TRANSMEM        776..792
FT                   /note="Helical; Name=9"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TOPO_DOM        793
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TRANSMEM        794..811
FT                   /note="Discontinuously helical; Name=10"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TOPO_DOM        812..833
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TRANSMEM        834..850
FT                   /note="Helical; Name=11"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TOPO_DOM        851..857
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TRANSMEM        858..874
FT                   /note="Helical; Name=12"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TOPO_DOM        875..916
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   INTRAMEM        917..942
FT                   /note="Discontinuously helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   TOPO_DOM        943..1035
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   REGION          192..222
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          348..389
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          968..1035
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        192..217
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        968..995
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1009..1035
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        591
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        596
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        609
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        617
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   1035 AA;  116108 MW;  3CF50B31275A81AF CRC64;
     MSSEKECLEN MLNGYAESGR VLSRTSLVIN QAVNRSIFTS TVSPAAERIR FILGEEDDSP
     APPQLFTELD ELLAVDGQEM EWKETARWIK FEEKVEQGGE RWSKPHVATL SLHSLFELRT
     CIEKGTILLD LEATSLPQIV EIVINNQIEL GLLKADMKEN VTRTLLRKHR HQTKKSNLRS
     LADIGKTVSS ASRLFSTPDN GSPTMTHRNL TSTSLNDVSD KPDKEQLKNK FMKKLPRDAE
     ASNVLVGEVD FLESPFIAFV RLQQAVMLGS LTEVPVPTRF LFILLGPKGK AKSYHEIGRS
     IATLMSDEVF HDIAYKAKNR EDLIAGIDEF LDEVIVLPLG EWDPTIRIEP PKSLPSSDKR
     KNMYSGGDNL QMNGDAPHDD GGGGHGDSEE LQRTGRFCGG LIKDIQRKAP FFASDFYDAL
     SIQSLSAILF IYLGTVTNAI TFGGLLGDAT ENMQGVLESF LGTAVSGAVF CLFGGQPLTI
     LSSTGPVLVF ERLLFNFSKD NDFDYLEFRL WIGLWSAFQC LILVATDASF LVKYFTRFTE
     EGFSSLISFI FIYDAFKKMI KLADYYPINS HFKVDYITQY SCACFPPEPA NSSWFNMTTA
     ATTTQFLTNA STDMAYNGTI DWSLLSKKEC LKYGGLLVGS NCKYVPDITL MSFILFLGTY
     TCSMALKKFK TSRYFPTTAR KLISDFAIIL SILIFCGLDA LLGVDTPKLI VPSEFKPTSP
     NRGWFVPPFG GNPWWVYLAA AIPALLVTIL IFMDQQITGV IVNRKEHKLK KGAGYHLDLF
     WVAILMVVCS FMALPWYVAA TVISIAHIDS LKMETETSAP GEQPKFLGVR EQRVTGTVVF
     LLTGLSVFMA PILKFIPMPV LYGVFLYMGV ASLNGVQFMD RLKLLLMPPK YQPDFIYLRH
     VPLRRVHLFT FLQVVCLAML WILKSTVAAI IFPVMILALV AVRKAMDYFF SQHDLSFLDD
     VIPEKDKKKK EDEKKKKKKK GSIDSDVEDS DCPYPEKVPS IKIPMDIMEK EPFLIDSKPS
     DRENSPTFLE RHTSC
//