UniProtKB - Q2Y0W8 (S4A8_HUMAN)
Electroneutral sodium bicarbonate exchanger 1
SLC4A8
Functioni
Mediates electroneutral sodium- and carbonate-dependent chloride-HCO3- exchange with a Na+:HCO3- stoichiometry of 2:1. Plays a major role in pH regulation in neurons. May be involved in cell pH regulation by transporting HCO3- from blood to cell. Enhanced expression in severe acid stress could be important for cell survival by mediating the influx of HCO3- into the cells. Also mediates lithium-dependent HCO3- cotransport. May be regulated by osmolarity.
2 PublicationsActivity regulationi
GO - Molecular functioni
- anion:anion antiporter activity Source: UniProtKB-KW
- bicarbonate transmembrane transporter activity Source: ARUK-UCL
- chloride transmembrane transporter activity Source: ARUK-UCL
- inorganic anion exchanger activity Source: Reactome
- sodium:bicarbonate symporter activity Source: ARUK-UCL
- sodium ion transmembrane transporter activity Source: ARUK-UCL
- transmembrane transporter activity Source: GO_Central
GO - Biological processi
- bicarbonate transport Source: ARUK-UCL
- chloride transmembrane transport Source: ARUK-UCL
- ion homeostasis Source: GO_Central
- modulation of chemical synaptic transmission Source: ARUK-UCL
- positive regulation of synaptic vesicle exocytosis Source: ARUK-UCL
- regulation of intracellular pH Source: ARUK-UCL
- regulation of membrane potential Source: ARUK-UCL
- sodium ion transmembrane transport Source: ARUK-UCL
- transmembrane transport Source: GO_Central
- transport across blood-brain barrier Source: ARUK-UCL
Keywordsi
Biological process | Anion exchange, Antiport, Ion transport, Sodium transport, Transport |
Ligand | Sodium |
Enzyme and pathway databases
PathwayCommonsi | Q2Y0W8 |
Reactomei | R-HSA-425381, Bicarbonate transporters |
SignaLinki | Q2Y0W8 |
SIGNORi | Q2Y0W8 |
Protein family/group databases
TCDBi | 2.A.31.2.4, the anion exchanger (ae) family |
Names & Taxonomyi
Protein namesi | Recommended name: Electroneutral sodium bicarbonate exchanger 1Alternative name(s): Electroneutral Na(+)-driven Cl-HCO3 exchanger Solute carrier family 4 member 8 k-NBC3 |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:11034, SLC4A8 |
MIMi | 605024, gene |
neXtProti | NX_Q2Y0W8 |
VEuPathDBi | HostDB:ENSG00000050438 |
Subcellular locationi
Other locations
- Membrane 1 Publication; Multi-pass membrane protein 1 Publication
Plasma Membrane
- neuronal cell body membrane Source: ARUK-UCL
- plasma membrane Source: ARUK-UCL
- presynaptic membrane Source: ARUK-UCL
Other locations
- asymmetric synapse Source: ARUK-UCL
- axon terminus Source: ARUK-UCL
- dendrite Source: ARUK-UCL
- glial cell projection Source: ARUK-UCL
- glutamatergic synapse Source: ARUK-UCL
- hippocampal mossy fiber Source: ARUK-UCL
- integral component of membrane Source: UniProtKB-KW
- membrane Source: ARUK-UCL
- neuron projection Source: ARUK-UCL
- presynapse Source: ARUK-UCL
- symmetric synapse Source: ARUK-UCL
- synaptic vesicle Source: ARUK-UCL
- terminal bouton Source: ARUK-UCL
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 478 | ExtracellularSequence analysisAdd BLAST | 478 | |
Transmembranei | 479 – 499 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 500 – 523 | CytoplasmicSequence analysisAdd BLAST | 24 | |
Transmembranei | 524 – 544 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 545 – 565 | ExtracellularSequence analysisAdd BLAST | 21 | |
Transmembranei | 566 – 586 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 587 – 595 | CytoplasmicSequence analysis | 9 | |
Transmembranei | 596 – 616 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 617 – 687 | ExtracellularSequence analysisAdd BLAST | 71 | |
Transmembranei | 688 – 708 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 709 – 731 | CytoplasmicSequence analysisAdd BLAST | 23 | |
Transmembranei | 732 – 752 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 753 – 778 | ExtracellularSequence analysisAdd BLAST | 26 | |
Transmembranei | 779 – 799 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 800 – 824 | CytoplasmicSequence analysisAdd BLAST | 25 | |
Transmembranei | 825 – 845 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 846 – 881 | ExtracellularSequence analysisAdd BLAST | 36 | |
Transmembranei | 882 – 902 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 903 – 904 | CytoplasmicSequence analysis | 2 | |
Transmembranei | 905 – 925 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 926 – 962 | ExtracellularSequence analysisAdd BLAST | 37 | |
Transmembranei | 963 – 983 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 984 – 1093 | CytoplasmicSequence analysisAdd BLAST | 110 |
Keywords - Cellular componenti
MembranePathology & Biotechi
Organism-specific databases
DisGeNETi | 9498 |
OpenTargetsi | ENSG00000050438 |
PharmGKBi | PA35900 |
Miscellaneous databases
Pharosi | Q2Y0W8, Tbio |
Chemistry databases
DrugBanki | DB01390, Sodium bicarbonate |
Genetic variation databases
BioMutai | SLC4A8 |
DMDMi | 121942008 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000328922 | 1 – 1093 | Electroneutral sodium bicarbonate exchanger 1Add BLAST | 1093 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 636 ↔ 638 | By similarity | ||
Disulfide bondi | 672 ↔ 684 | By similarity |
Keywords - PTMi
Disulfide bondProteomic databases
EPDi | Q2Y0W8 |
jPOSTi | Q2Y0W8 |
MassIVEi | Q2Y0W8 |
MaxQBi | Q2Y0W8 |
PaxDbi | Q2Y0W8 |
PeptideAtlasi | Q2Y0W8 |
PRIDEi | Q2Y0W8 |
ProteomicsDBi | 16963 24921 61540 [Q2Y0W8-1] 61541 [Q2Y0W8-2] 61542 [Q2Y0W8-3] 61543 [Q2Y0W8-4] 61544 [Q2Y0W8-5] 61545 [Q2Y0W8-6] 61546 [Q2Y0W8-7] |
PTM databases
iPTMneti | Q2Y0W8 |
PhosphoSitePlusi | Q2Y0W8 |
SwissPalmi | Q2Y0W8 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000050438, Expressed in corpus callosum and 201 other tissues |
Genevisiblei | Q2Y0W8, HS |
Organism-specific databases
HPAi | ENSG00000050438, Group enriched (brain, pituitary gland, retina, testis) |
Interactioni
Protein-protein interaction databases
BioGRIDi | 114877, 34 interactors |
IntActi | Q2Y0W8, 30 interactors |
STRINGi | 9606.ENSP00000405812 |
Miscellaneous databases
RNActi | Q2Y0W8, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q2Y0W8 |
SMRi | Q2Y0W8 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 25 | DisorderedSequence analysisAdd BLAST | 25 | |
Regioni | 55 – 95 | DisorderedSequence analysisAdd BLAST | 41 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 1010 – 1036 | Sequence analysisAdd BLAST | 27 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 57 – 77 | Basic residuesSequence analysisAdd BLAST | 21 |
Sequence similaritiesi
Keywords - Domaini
Coiled coil, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1172, Eukaryota |
GeneTreei | ENSGT00940000157422 |
HOGENOMi | CLU_002289_5_3_1 |
InParanoidi | Q2Y0W8 |
OMAi | VCHIEAE |
OrthoDBi | 265068at2759 |
PhylomeDBi | Q2Y0W8 |
TreeFami | TF313630 |
Family and domain databases
Gene3Di | 3.40.930.10, 1 hit |
InterProi | View protein in InterPro IPR013769, Band3_cytoplasmic_dom IPR011531, HCO3_transpt-like_TM_dom IPR003020, HCO3_transpt_euk IPR003024, Na/HCO3_transpt IPR016152, PTrfase/Anion_transptr |
PANTHERi | PTHR11453, PTHR11453, 1 hit |
Pfami | View protein in Pfam PF07565, Band_3_cyto, 1 hit PF00955, HCO3_cotransp, 1 hit |
PRINTSi | PR01231, HCO3TRNSPORT PR01232, NAHCO3TRSPRT |
SUPFAMi | SSF55804, SSF55804, 1 hit |
TIGRFAMsi | TIGR00834, ae, 1 hit |
s (8)i Sequence
Sequence statusi: Complete.
This entry describes 8 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MPAAGSNEPD GVLSYQRPDE EAVVDQGGTS TILNIHYEKE ELEGHRTLYV
60 70 80 90 100
GVRMPLGRQS HRHHRTHGQK HRRRGRGKGA SQGEEGLEAL AHDTPSQRVQ
110 120 130 140 150
FILGTEEDEE HVPHELFTEL DEICMKEGED AEWKETARWL KFEEDVEDGG
160 170 180 190 200
ERWSKPYVAT LSLHSLFELR SCLINGTVLL DMHANSIEEI SDLILDQQEL
210 220 230 240 250
SSDLNDSMRV KVREALLKKH HHQNEKKRNN LIPIVRSFAE VGKKQSDPHL
260 270 280 290 300
MDKHGQTVSP QSVPTTNLEV KNGVNCEHSP VDLSKVDLHF MKKIPTGAEA
310 320 330 340 350
SNVLVGEVDI LDRPIVAFVR LSPAVLLSGL TEVPIPTRFL FILLGPVGKG
360 370 380 390 400
QQYHEIGRSM ATIMTDEIFH DVAYKAKERD DLLAGIDEFL DQVTVLPPGE
410 420 430 440 450
WDPSIRIEPP KNVPSQEKRK MPGVPNGNVC HIEQEPHGGH SGPELQRTGR
460 470 480 490 500
LFGGLVLDIK RKAPWYWSDY RDALSLQCLA SFLFLYCACM SPVITFGGLL
510 520 530 540 550
GEATEGRISA IESLFGASMT GIAYSLFAGQ ALTILGSTGP VLVFEKILFK
560 570 580 590 600
FCKDYALSYL SLRACIGLWT AFLCIVLVAT DASSLVCYIT RFTEEAFASL
610 620 630 640 650
ICIIFIYEAI EKLIHLAETY PIHMHSQLDH LSLYYCRCTL PENPNNHTLQ
660 670 680 690 700
YWKDHNIVTA EVHWANLTVS ECQEMHGEFM GSACGHHGPY TPDVLFWSCI
710 720 730 740 750
LFFTTFILSS TLKTFKTSRY FPTRVRSMVS DFAVFLTIFT MVIIDFLIGV
760 770 780 790 800
PSPKLQVPSV FKPTRDDRGW IINPIGPNPW WTVIAAIIPA LLCTILIFMD
810 820 830 840 850
QQITAVIINR KEHKLKKGCG YHLDLLMVAI MLGVCSIMGL PWFVAATVLS
860 870 880 890 900
ITHVNSLKLE SECSAPGEQP KFLGIREQRV TGLMIFVLMG CSVFMTAILK
910 920 930 940 950
FIPMPVLYGV FLYMGVSSLQ GIQFFDRLKL FGMPAKHQPD FIYLRHVPLR
960 970 980 990 1000
KVHLFTLIQL TCLVLLWVIK ASPAAIVFPM MVLALVFVRK VMDLCFSKRE
1010 1020 1030 1040 1050
LSWLDDLMPE SKKKKLDDAK KKAKEEEEAE KMLEIGGDKF PLESRKLLSS
1060 1070 1080 1090
PGKNISCRCD PSEINISDEM PKTTVWKALS MNSGNAKEKS LFN
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
---|---|---|---|---|---|
Sequence conflicti | 482 | F → L in BAG58292 (PubMed:14702039).Curated | 1 | ||
Sequence conflicti | 1008 | M → T in AAC82380 (PubMed:11133997).Curated | 1 | ||
Isoform 7 (identifier: Q2Y0W8-7) | |||||
Sequence conflicti | 707 | Q → R in CAD38576 (PubMed:17974005).Curated | 1 | ||
Sequence conflicti | 716 | R → G in CAD38576 (PubMed:17974005).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_048351 | 312 | D → A. Corresponds to variant dbSNP:rs35966334Ensembl. | 1 | |
Natural variantiVAR_048352 | 898 | I → V. Corresponds to variant dbSNP:rs12318785Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_052759 | 1 – 53 | Missing in isoform 4, isoform 5, isoform 7 and isoform 8. 3 PublicationsAdd BLAST | 53 | |
Alternative sequenceiVSP_052760 | 1 – 16 | MPAAG…VLSYQ → MFNKNNSNKLRSTPRYRRGD PGYLNFTELGPLKPEQKDQW SQH in isoform 2. 1 PublicationAdd BLAST | 16 | |
Alternative sequenceiVSP_052761 | 671 – 691 | ECQEM…HGPYT → VSLGAARCPSIVTTGLGGTS K in isoform 6 and isoform 8. 2 PublicationsAdd BLAST | 21 | |
Alternative sequenceiVSP_052762 | 692 – 1093 | Missing in isoform 6 and isoform 8. 2 PublicationsAdd BLAST | 402 | |
Alternative sequenceiVSP_052763 | 725 – 800 | VRSMV…LIFMD → MESCSVAWLECGGVILAHCN LRLLPSSWDYRHAPPQPANF CIFSRDGVSPCWPGWSQSLD LVICLPRPPKMLGLQA in isoform 7. 1 PublicationAdd BLAST | 76 | |
Alternative sequenceiVSP_052764 | 801 – 1093 | Missing in isoform 7. 1 PublicationAdd BLAST | 293 | |
Alternative sequenceiVSP_052765 | 1028 – 1093 | EAEKM…KSLFN → VIVLAPTVYLGASNYRT in isoform 2, isoform 3 and isoform 4. 3 PublicationsAdd BLAST | 66 |
Sequence databases
Genome annotation databases
Ensembli | ENST00000358657.7; ENSP00000351483.4; ENSG00000050438.17 [Q2Y0W8-5] ENST00000453097.7; ENSP00000405812.2; ENSG00000050438.17 ENST00000514353.7; ENSP00000442561.2; ENSG00000050438.17 [Q2Y0W8-7] ENST00000535225.6; ENSP00000441520.1; ENSG00000050438.17 [Q2Y0W8-8] |
GeneIDi | 9498 |
KEGGi | hsa:9498 |
MANE-Selecti | ENST00000453097.7; ENSP00000405812.2; NM_001039960.3; NP_001035049.1 |
UCSCi | uc001rys.3, human [Q2Y0W8-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5JHO | X-ray | 2.80 | A/B | 54-397 | [»] | |
AlphaFoldDBi | Q2Y0W8 | |||||
SMRi | Q2Y0W8 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114877, 34 interactors |
IntActi | Q2Y0W8, 30 interactors |
STRINGi | 9606.ENSP00000405812 |
Chemistry databases
DrugBanki | DB01390, Sodium bicarbonate |
Protein family/group databases
TCDBi | 2.A.31.2.4, the anion exchanger (ae) family |
PTM databases
iPTMneti | Q2Y0W8 |
PhosphoSitePlusi | Q2Y0W8 |
SwissPalmi | Q2Y0W8 |
Genetic variation databases
BioMutai | SLC4A8 |
DMDMi | 121942008 |
Proteomic databases
EPDi | Q2Y0W8 |
jPOSTi | Q2Y0W8 |
MassIVEi | Q2Y0W8 |
MaxQBi | Q2Y0W8 |
PaxDbi | Q2Y0W8 |
PeptideAtlasi | Q2Y0W8 |
PRIDEi | Q2Y0W8 |
ProteomicsDBi | 16963 24921 61540 [Q2Y0W8-1] 61541 [Q2Y0W8-2] 61542 [Q2Y0W8-3] 61543 [Q2Y0W8-4] 61544 [Q2Y0W8-5] 61545 [Q2Y0W8-6] 61546 [Q2Y0W8-7] |
Protocols and materials databases
Antibodypediai | 26410, 176 antibodies from 25 providers |
DNASUi | 9498 |
Genome annotation databases
Ensembli | ENST00000358657.7; ENSP00000351483.4; ENSG00000050438.17 [Q2Y0W8-5] ENST00000453097.7; ENSP00000405812.2; ENSG00000050438.17 ENST00000514353.7; ENSP00000442561.2; ENSG00000050438.17 [Q2Y0W8-7] ENST00000535225.6; ENSP00000441520.1; ENSG00000050438.17 [Q2Y0W8-8] |
GeneIDi | 9498 |
KEGGi | hsa:9498 |
MANE-Selecti | ENST00000453097.7; ENSP00000405812.2; NM_001039960.3; NP_001035049.1 |
UCSCi | uc001rys.3, human [Q2Y0W8-1] |
Organism-specific databases
CTDi | 9498 |
DisGeNETi | 9498 |
GeneCardsi | SLC4A8 |
HGNCi | HGNC:11034, SLC4A8 |
HPAi | ENSG00000050438, Group enriched (brain, pituitary gland, retina, testis) |
MIMi | 605024, gene |
neXtProti | NX_Q2Y0W8 |
OpenTargetsi | ENSG00000050438 |
PharmGKBi | PA35900 |
VEuPathDBi | HostDB:ENSG00000050438 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1172, Eukaryota |
GeneTreei | ENSGT00940000157422 |
HOGENOMi | CLU_002289_5_3_1 |
InParanoidi | Q2Y0W8 |
OMAi | VCHIEAE |
OrthoDBi | 265068at2759 |
PhylomeDBi | Q2Y0W8 |
TreeFami | TF313630 |
Enzyme and pathway databases
PathwayCommonsi | Q2Y0W8 |
Reactomei | R-HSA-425381, Bicarbonate transporters |
SignaLinki | Q2Y0W8 |
SIGNORi | Q2Y0W8 |
Miscellaneous databases
BioGRID-ORCSi | 9498, 17 hits in 1072 CRISPR screens |
ChiTaRSi | SLC4A8, human |
GeneWikii | SLC4A8 |
GenomeRNAii | 9498 |
Pharosi | Q2Y0W8, Tbio |
PROi | PR:Q2Y0W8 |
RNActi | Q2Y0W8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000050438, Expressed in corpus callosum and 201 other tissues |
Genevisiblei | Q2Y0W8, HS |
Family and domain databases
Gene3Di | 3.40.930.10, 1 hit |
InterProi | View protein in InterPro IPR013769, Band3_cytoplasmic_dom IPR011531, HCO3_transpt-like_TM_dom IPR003020, HCO3_transpt_euk IPR003024, Na/HCO3_transpt IPR016152, PTrfase/Anion_transptr |
PANTHERi | PTHR11453, PTHR11453, 1 hit |
Pfami | View protein in Pfam PF07565, Band_3_cyto, 1 hit PF00955, HCO3_cotransp, 1 hit |
PRINTSi | PR01231, HCO3TRNSPORT PR01232, NAHCO3TRSPRT |
SUPFAMi | SSF55804, SSF55804, 1 hit |
TIGRFAMsi | TIGR00834, ae, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | S4A8_HUMAN | |
Accessioni | Q2Y0W8Primary (citable) accession number: Q2Y0W8 Secondary accession number(s): A0MMZ1 Q9UKX8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 8, 2008 |
Last sequence update: | December 20, 2005 | |
Last modified: | May 25, 2022 | |
This is version 136 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families