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Protein

Electroneutral sodium bicarbonate exchanger 1

Gene

Slc4a8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

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.1 Publication

Enzyme regulationi

Activity is inhibited by 4,4'-Di-isothiocyanatostilbene-2,2'-disulfonic acid (DIDS - an inhibitor of several anion channels and transporters).

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processAnion exchange, Antiport, Ion transport, Sodium transport, Transport
LigandSodium

Enzyme and pathway databases

ReactomeiR-MMU-425381 Bicarbonate transporters

Names & Taxonomyi

Protein namesi
Recommended name:
Electroneutral sodium bicarbonate exchanger 1
Alternative name(s):
Electroneutral Na+-driven Cl-HCO3 exchanger
Solute carrier family 4 member 8
k-NBC3
Gene namesi
Name:Slc4a8Imported
Synonyms:Kiaa0739
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:1928745 Slc4a8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 476ExtracellularSequence analysisAdd BLAST476
Transmembranei477 – 497HelicalSequence analysisAdd BLAST21
Topological domaini498 – 505CytoplasmicSequence analysis8
Transmembranei506 – 526HelicalSequence analysisAdd BLAST21
Topological domaini527 – 563ExtracellularSequence analysisAdd BLAST37
Transmembranei564 – 584HelicalSequence analysisAdd BLAST21
Topological domaini585 – 593CytoplasmicSequence analysis9
Transmembranei594 – 614HelicalSequence analysisAdd BLAST21
Topological domaini615 – 685ExtracellularSequence analysisAdd BLAST71
Transmembranei686 – 706HelicalSequence analysisAdd BLAST21
Topological domaini707 – 729CytoplasmicSequence analysisAdd BLAST23
Transmembranei730 – 750HelicalSequence analysisAdd BLAST21
Topological domaini751 – 776ExtracellularSequence analysisAdd BLAST26
Transmembranei777 – 797HelicalSequence analysisAdd BLAST21
Topological domaini798 – 822CytoplasmicSequence analysisAdd BLAST25
Transmembranei823 – 843HelicalSequence analysisAdd BLAST21
Topological domaini844 – 879ExtracellularSequence analysisAdd BLAST36
Transmembranei880 – 900HelicalSequence analysisAdd BLAST21
Topological domaini901 – 902CytoplasmicSequence analysis2
Transmembranei903 – 923HelicalSequence analysisAdd BLAST21
Topological domaini924 – 960ExtracellularSequence analysisAdd BLAST37
Transmembranei961 – 981HelicalSequence analysisAdd BLAST21
Topological domaini982 – 1089CytoplasmicSequence analysisAdd BLAST108

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003289231 – 1089Electroneutral sodium bicarbonate exchanger 1Add BLAST1089

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi634 ↔ 636By similarity
Disulfide bondi670 ↔ 682By similarity

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiQ8JZR6
PeptideAtlasiQ8JZR6
PRIDEiQ8JZR6

PTM databases

iPTMnetiQ8JZR6
PhosphoSitePlusiQ8JZR6

Expressioni

Tissue specificityi

Highly expressed in brain with lower levels in lung, kidney and heart. In the kidney, there is high expression in the inner medulla, localized to the inner medullary collecting duct. In the brain, there seems to be three transcripts each having a different expression pattern. The smaller 3kb transcript has highest expression levels in the thalamus and the largest 9.5kb transcript has highest levels in the substantia nigra. The middle transcript of 4.4kb, which is also the main transcript in kidney, is highly expressed in thalamus. Hence, the highest levels are observed in the thalamus, amygdala and caudate nucleus and very low expression was seen in the corpus callosum.1 Publication

Gene expression databases

BgeeiENSMUSG00000023032
ExpressionAtlasiQ8JZR6 baseline and differential
GenevisibleiQ8JZR6 MM

Interactioni

Protein-protein interaction databases

BioGridi208500, 1 interactor
IntActiQ8JZR6, 1 interactor
STRINGi10090.ENSMUSP00000023776

Structurei

3D structure databases

ProteinModelPortaliQ8JZR6
SMRiQ8JZR6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1021 – 1026Poly-GluSequence analysis6

Sequence similaritiesi

Belongs to the anion exchanger (TC 2.A.31) family. [View classification]Sequence analysis

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1172 Eukaryota
ENOG410XPHD LUCA
GeneTreeiENSGT00760000119021
HOGENOMiHOG000280684
HOVERGENiHBG004326
InParanoidiQ8JZR6
KOiK13859
OMAiTEVHWAN
OrthoDBiEOG091G01FT
PhylomeDBiQ8JZR6
TreeFamiTF313630

Family and domain databases

Gene3Di3.40.930.10, 1 hit
InterProiView protein in InterPro
IPR013769 Band3_cytoplasmic_dom
IPR011531 HCO3_transpt_C
IPR003020 HCO3_transpt_euk
IPR003024 Na/HCO3_transpt
IPR016152 PTrfase/Anion_transptr
PANTHERiPTHR11453 PTHR11453, 1 hit
PfamiView protein in Pfam
PF07565 Band_3_cyto, 1 hit
PF00955 HCO3_cotransp, 1 hit
PRINTSiPR01231 HCO3TRNSPORT
PR01232 NAHCO3TRSPRT
SUPFAMiSSF55804 SSF55804, 1 hit
TIGRFAMsiTIGR00834 ae, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 13 Publications (identifier: Q8JZR6-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPAGSNEPDG VLSYQRPDEE AVVDQGGTST ILNIHYEKEE LEGHRTLYVG
60 70 80 90 100
VRMPLGRQSH RHHRTHGQKH RRRGGRGKGA SQGEEGLEAL AHDTPSQRVQ
110 120 130 140 150
FILGTEEDEE HVPHELFTEL DEICMKEGED AEWKETARWL KFEEDVEDGG
160 170 180 190 200
ERWSKPYVAT LSLHSLFELR SCLINGSVLL DMRASSIEEI SDLILDQQEL
210 220 230 240 250
LRDLSDSVRV KVREALLKKH HHQNERRRNN LIPIVRSFAE VGKKQSDPHS
260 270 280 290 300
MDRDGQTVSP QSATNLEVKN GVNCEHSPVD LSKVDLHFMK KIPTGAEASN
310 320 330 340 350
VLVGEVDTLD RPIVAFVRLS PAVLLSGLTE VPIPTRFLFI LLGPVGKGQQ
360 370 380 390 400
YHEIGRSMAT IMTDEIFHDV AYKAKERDDL LAGIDEFLDQ VTVLPPGEWD
410 420 430 440 450
PSIRIEPPKN VPSQEKRKMP GVPNGNVCHI EPEPHGGHSG PELERTGRLF
460 470 480 490 500
GGLVLDVKRK APWYWSDYRD ALSLQCLASF LFLYCACMSP VITFGGLLGE
510 520 530 540 550
ATEGRISAIE SLFGASMTGI AYSLFAGQPL TILGSTGPVL VFEKILFKFC
560 570 580 590 600
KDYALSYLSL RALIGLWTAF LCIVLVATDA SSLVCYITRF TEEAFASLIC
610 620 630 640 650
IIFIYEAIEK LIHLAETYPI HMHSQLDHLS LYYCRCVLPE NPNNHTLQYW
660 670 680 690 700
KDHNILAAEV NWANLTVSEC QEMHGEFMGS ACGHHGPYTP DVLFWSCILF
710 720 730 740 750
FATFIVSSTL KTFKTSRYFP TRVRSMVSDF AVFLTIFTMV VLDFLIGVPS
760 770 780 790 800
PKLQVPNVFK PTRDDRGWFI NPIGPNPWWT VIAAIIPALL CTILIFMDQQ
810 820 830 840 850
ITAVIINRKE HKLKKGCGYH LDLLMVAVML GVCSIMGLPW FVAATVLSIT
860 870 880 890 900
HVNSLKLESE CSAPGEQPKF LGIREQRVTG LMIFVLMGCS VFMTAVLKFI
910 920 930 940 950
PMPVLYGVFL YMGVSSLQGI QFFDRLKLFG MPAKHQPDFI YLRHVPLRKV
960 970 980 990 1000
HLFTLVQLTC LVLLWVIKAS PAAIVFPMMV LALVFVRKVM DLCFSKRELS
1010 1020 1030 1040 1050
WLDDLMPESK KKKLDDAKKK EEEEAEKMLD IGGDKFPLES RKLLSSPGKS
1060 1070 1080
SSFRCDPSEI NISDEMPKTT VWKALSINSG NTKEKSPFN
Length:1,089
Mass (Da):122,421
Last modified:October 1, 2002 - v1
Checksum:iCFAE127D3853DDD8
GO
Isoform 21 Publication (identifier: Q8JZR6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-52: Missing.

Show »
Length:1,037
Mass (Da):116,681
Checksum:i81818C80B335F19B
GO

Sequence cautioni

The sequence BAD32292 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti219K → E in BAE42561 (PubMed:16141072).Curated1
Sequence conflicti258V → M in AAF61705 (PubMed:11260402).Curated1
Sequence conflicti291K → R in BAE42561 (PubMed:16141072).Curated1
Sequence conflicti644N → S in BAC30341 (PubMed:16141072).Curated1
Sequence conflicti707S → P in AAF61705 (PubMed:11260402).Curated1
Sequence conflicti949K → E in BAE42561 (PubMed:16141072).Curated1
Sequence conflicti1015D → G in BAC30341 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0527691 – 52Missing in isoform 2. 1 PublicationAdd BLAST52

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF224508 mRNA Translation: AAF61705.1
AK039404 mRNA Translation: BAC30341.1
AK171610 mRNA Translation: BAE42561.1
AK173014 mRNA Translation: BAD32292.1 Different initiation.
BC030388 mRNA Translation: AAH30388.1
CCDSiCCDS37214.1 [Q8JZR6-1]
CCDS84193.1 [Q8JZR6-2]
RefSeqiNP_001334031.1, NM_001347102.1 [Q8JZR6-2]
NP_067505.2, NM_021530.2 [Q8JZR6-1]
XP_017172207.1, XM_017316718.1 [Q8JZR6-2]
UniGeneiMm.209856

Genome annotation databases

EnsembliENSMUST00000023776; ENSMUSP00000023776; ENSMUSG00000023032 [Q8JZR6-1]
ENSMUST00000162049; ENSMUSP00000125090; ENSMUSG00000023032 [Q8JZR6-2]
GeneIDi59033
KEGGimmu:59033
UCSCiuc007xse.1 mouse [Q8JZR6-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiS4A8_MOUSE
AccessioniPrimary (citable) accession number: Q8JZR6
Secondary accession number(s): Q3TAV7
, Q6A004, Q8BYI7, Q9JKV6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 8, 2008
Last sequence update: October 1, 2002
Last modified: March 28, 2018
This is version 113 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health