S4A8_RAT
ID S4A8_RAT Reviewed; 1067 AA.
AC Q6RVG2; Q6RVG1; Q6RVG3;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 108.
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|RGD:735164}; Synonyms=Ndcbe1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAR37054.1, ECO:0000312|RGD:735164}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
RC STRAIN=Sprague-Dawley; TISSUE=Kidney inner medulla;
RA Attmane-Elakeb A., Vernimmen C., Karim Z., Bichara M.M.;
RT "Rat sodium-driven Cl-HCO3 exchanger.";
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=17715183; DOI=10.1152/ajpregu.00356.2007;
RA Damkier H.H., Nielsen S., Praetorius J.;
RT "Molecular expression of SLC4-derived Na+-dependent anion transporters in
RT selected human tissues.";
RL Am. J. Physiol. 293:R2136-R2146(2007).
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 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q2Y0W8,
CC ECO:0000250|UniProtKB:Q8JZR6}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q2Y0W8, ECO:0000250|UniProtKB:Q8JZR6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=2; Synonyms=NDCBE1-B;
CC IsoId=Q6RVG2-1; Sequence=Displayed;
CC Name=1; Synonyms=NDCBE1-A;
CC IsoId=Q6RVG2-2; Sequence=VSP_052766, VSP_052767, VSP_052768;
CC Name=3; Synonyms=NDCBE1-C;
CC IsoId=Q6RVG2-3; Sequence=VSP_052767;
CC -!- TISSUE SPECIFICITY: Expressed in the Purkinje cells and dendrites in
CC the molecular layer of the cerebellum (at protein level). Strong
CC expression observed in testis and moderate expression in kidney inner
CC medulla, the submandibular gland, eye, cerebrum and cerebellum.
CC {ECO:0000269|PubMed:17715183}.
CC -!- SIMILARITY: Belongs to the anion exchanger (TC 2.A.31) family.
CC {ECO:0000255}.
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DR EMBL; AY489024; AAR37053.1; -; mRNA.
DR EMBL; AY489025; AAR37054.1; -; mRNA.
DR EMBL; AY489026; AAR37055.1; -; mRNA.
DR RefSeq; NP_001257723.1; NM_001270794.1. [Q6RVG2-2]
DR RefSeq; NP_001257724.1; NM_001270795.1. [Q6RVG2-3]
DR RefSeq; NP_955791.1; NM_199497.2. [Q6RVG2-1]
DR AlphaFoldDB; Q6RVG2; -.
DR SMR; Q6RVG2; -.
DR STRING; 10116.ENSRNOP00000043825; -.
DR iPTMnet; Q6RVG2; -.
DR PhosphoSitePlus; Q6RVG2; -.
DR jPOST; Q6RVG2; -.
DR PaxDb; Q6RVG2; -.
DR PRIDE; Q6RVG2; -.
DR GeneID; 315311; -.
DR KEGG; rno:315311; -.
DR UCSC; RGD:735164; rat. [Q6RVG2-1]
DR CTD; 9498; -.
DR RGD; 735164; Slc4a8.
DR VEuPathDB; HostDB:ENSRNOG00000028879; -.
DR eggNOG; KOG1172; Eukaryota.
DR InParanoid; Q6RVG2; -.
DR PhylomeDB; Q6RVG2; -.
DR Reactome; R-RNO-425381; Bicarbonate transporters.
DR PRO; PR:Q6RVG2; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000028879; Expressed in frontal cortex and 9 other tissues.
DR ExpressionAtlas; Q6RVG2; baseline and differential.
DR GO; GO:0032279; C:asymmetric synapse; IDA:ARUK-UCL.
DR GO; GO:0043679; C:axon terminus; IDA:ARUK-UCL.
DR GO; GO:0030425; C:dendrite; ISO:RGD.
DR GO; GO:0097386; C:glial cell projection; IDA:ARUK-UCL.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:ARUK-UCL.
DR GO; GO:0097457; C:hippocampal mossy fiber; IDA:ARUK-UCL.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:ARUK-UCL.
DR GO; GO:0032809; C:neuronal cell body membrane; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0098793; C:presynapse; IDA:ARUK-UCL.
DR GO; GO:0042734; C:presynaptic membrane; ISO:RGD.
DR GO; GO:0032280; C:symmetric synapse; IDA:ARUK-UCL.
DR GO; GO:0008021; C:synaptic vesicle; IDA:ARUK-UCL.
DR GO; GO:0043195; C:terminal bouton; IDA:ARUK-UCL.
DR GO; GO:0015301; F:anion:anion antiporter activity; IEA:UniProtKB-KW.
DR GO; GO:0015106; F:bicarbonate transmembrane transporter activity; ISO:RGD.
DR GO; GO:0015108; F:chloride transmembrane transporter activity; ISO:RGD.
DR GO; GO:0005452; F:inorganic anion exchanger activity; IEA:InterPro.
DR GO; GO:0015081; F:sodium ion transmembrane transporter activity; ISO:RGD.
DR GO; GO:0008510; F:sodium:bicarbonate symporter activity; ISO:RGD.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015701; P:bicarbonate transport; ISO:RGD.
DR GO; GO:1902476; P:chloride transmembrane transport; ISO:RGD.
DR GO; GO:0050801; P:ion homeostasis; IBA:GO_Central.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; ISO:RGD.
DR GO; GO:2000302; P:positive regulation of synaptic vesicle exocytosis; ISO:RGD.
DR GO; GO:0051453; P:regulation of intracellular pH; ISO:RGD.
DR GO; GO:0042391; P:regulation of membrane potential; ISO:RGD.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISO:RGD.
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; 2.
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 1: Evidence at protein 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..1067
FT /note="Electroneutral sodium bicarbonate exchanger 1"
FT /id="PRO_0000328924"
FT TOPO_DOM 1..453
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 454..474
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 475..482
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 483..503
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 504..540
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 541..561
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 562..570
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 571..591
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 592..662
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 663..683
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 684..706
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 707..727
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 728..753
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 754..774
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 775..799
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 800..820
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 821..856
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 857..877
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 878..879
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 880..900
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 901..937
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 938..958
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 959..1067
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 55..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 243..263
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 611..613
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT DISULFID 647..659
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT VAR_SEQ 451
FT /note="L -> LFGGLVLDVKRKAPWYWSDYRDALSL (in isoform 1)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_052766"
FT VAR_SEQ 646..699
FT /note="Missing (in isoform 1 and isoform 3)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_052767"
FT VAR_SEQ 1002
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_052768"
SQ SEQUENCE 1067 AA; 119550 MW; BA8E72445DDB7749 CRC64;
MPAGSNEPDG VLSYQRPDEE AVVDQGGTST ILNIHYEKEE LEGHRTLYVG VRMPLGRQSH
RHHRTHGQKH RRRGGRGKGA SQGEEGLEAS AHDTPSQRVQ FILGTEEDEE HVPHELFTEL
DEICMKEGEE AEWKETARWL KFEEDVEDGG ERWSKPYVAT LSLHSLFELR SCLINGSVLL
DMRASSIEEI SDLILDQQEL LRDLSDSVRV KVREALLKKH HHQNEKKRNN LIPIVRSFAE
VGKKQSDPHS MDRDGQTVSP QSAPATNLEV KNGVNCEHSP VDLSKADLHF MKKIPAGAEA
SNVLVGEVDT LDRPIVAFVR LSPAVLLSGL TEVPIPTRFL FILLGPVGKG QQYHEIGRSM
ATIMTDEIFH DVAYKAKERD DLLAGIDEFL DQVTVLPPGE WDPSIRIEPP KNVPSQEKRK
MPGVPNGNIC HVEPEPHGGH SGPELERTGR LQCLASFLFL YCACMSPVIT FGGLLGEATE
GRISAIESLF GASMTGIAYS LFAGQPLTIL GSTGPVLVFE KILFKFCKDY ALSYLSLRAC
IGLWTAFLCI VLVATDASSL VCYITRFTEE AFASLICIIF IYEAIEKLIH LAETYPIHMH
SQLDHLSLYY CRCALPENPN NHTLQYWKEH SIPTADVNWA NLTVSECQEM HGEFIGSACG
HHGPYTPDVL FWSCILFFAT FIVSSTLKTF KTSRYFPTRV RSTVSDFAVF LTIFTMVILD
FLIGVPSPKL QVPSVFKPTR DDRGWFISPI GPNPWWTVIA AIIPALLCTI LIFMDQQITA
VIINRKEHKL KKGCGYHLDL LVVAIMLGVC SLMGLPWFVA ATVLSITHVN SLKLESECSA
PGEQPKFLGI REQRVTGLMI FVLMGCSVFM TAVLKFIPMP VLYGVFLYMG VSSLQGIQFF
DRLKLFGMPA KHQPDFIYLR HVPLRKVHLF TLVQLTCLVL LWVIKASPAA IVFPMMVLAL
VFVRKVMDLC FSKRELSWLD DLMPESKKKK LDDAKKKEEE EEAEKMLDIG GDKFPLESRK
LLSSPGKNNS FRCDPSEINI SDEMPKTTVW KALSINSGNT KEKSPFN
