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Protein

Electrogenic sodium bicarbonate cotransporter 1

Gene

Slc4a4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Electrogenic sodium/bicarbonate cotransporter with a Na+:HCO3- stoichiometry varying from 1:2 to 1:3. May regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intracellular pH.By similarity1 Publication
Isoform 2: May have a higher activity than isoform 1.By similarity

Enzyme regulationi

Inhibited by stilbene derivatives and regulated by cyclic AMP.

GO - Molecular functioni

GO - Biological processi

  • anion transmembrane transport Source: GO_Central
  • bicarbonate transport Source: MGI
  • regulation of intracellular pH Source: GO_Central
  • regulation of pH Source: MGI
  • sodium ion transport Source: MGI
Complete GO annotation...

Keywords - Biological processi

Ion transport, Sodium transport, Symport, Transport

Keywords - Ligandi

Sodium

Enzyme and pathway databases

ReactomeiR-MMU-425381. Bicarbonate transporters.

Names & Taxonomyi

Protein namesi
Recommended name:
Electrogenic sodium bicarbonate cotransporter 1
Short name:
Sodium bicarbonate cotransporter
Alternative name(s):
Na(+)/HCO3(-) cotransporter
Solute carrier family 4 member 4
Gene namesi
Name:Slc4a4
Synonyms:Nbc1, Nbce1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1927555. Slc4a4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 468CytoplasmicSequence analysisAdd BLAST468
Transmembranei469 – 488HelicalSequence analysisAdd BLAST20
Topological domaini489 – 504ExtracellularSequence analysisAdd BLAST16
Transmembranei505 – 526HelicalSequence analysisAdd BLAST22
Topological domaini527 – 554CytoplasmicSequence analysisAdd BLAST28
Transmembranei555 – 580HelicalSequence analysisAdd BLAST26
Topological domaini581 – 691ExtracellularSequence analysisAdd BLAST111
Transmembranei692 – 710HelicalSequence analysisAdd BLAST19
Topological domaini711 – 725CytoplasmicSequence analysisAdd BLAST15
Transmembranei726 – 748HelicalSequence analysisAdd BLAST23
Topological domaini749 – 777ExtracellularSequence analysisAdd BLAST29
Transmembranei778 – 797HelicalSequence analysisAdd BLAST20
Topological domaini798 – 822CytoplasmicSequence analysisAdd BLAST25
Transmembranei823 – 847HelicalSequence analysisAdd BLAST25
Topological domaini848 – 881ExtracellularSequence analysisAdd BLAST34
Transmembranei882 – 901HelicalSequence analysisAdd BLAST20
Topological domaini902 – 949CytoplasmicSequence analysisAdd BLAST48
Transmembranei950 – 967HelicalSequence analysisAdd BLAST18
Topological domaini968 – 970ExtracellularSequence analysis3
Transmembranei971 – 986HelicalSequence analysisAdd BLAST16
Topological domaini987 – 1079CytoplasmicSequence analysisAdd BLAST93

GO - Cellular componenti

  • basolateral plasma membrane Source: UniProtKB
  • extracellular exosome Source: MGI
  • integral component of plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000792281 – 1079Electrogenic sodium bicarbonate cotransporter 1Add BLAST1079

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei30PhosphotyrosineCombined sources1
Modified residuei61PhosphoserineCombined sources1
Modified residuei65PhosphoserineCombined sources1
Modified residuei68PhosphoserineCombined sources1
Modified residuei223PhosphoserineCombined sources1
Modified residuei232PhosphoserineCombined sources1
Modified residuei233PhosphoserineCombined sources1
Modified residuei245PhosphoserineCombined sources1
Modified residuei249PhosphothreonineBy similarity1
Modified residuei254PhosphothreonineCombined sources1
Modified residuei256PhosphoserineCombined sources1
Modified residuei257PhosphoserineCombined sources1
Modified residuei262PhosphoserineCombined sources1
Disulfide bondi627 ↔ 629By similarity
Glycosylationi641N-linked (GlcNAc...)By similarity1
Glycosylationi661N-linked (GlcNAc...)By similarity1
Disulfide bondi674 ↔ 686By similarity
Modified residuei1026PhosphoserineCombined sources1
Modified residuei1029PhosphoserineCombined sources1
Modified residuei1034PhosphoserineCombined sources1
Modified residuei1044PhosphoserineCombined sources1
Modified residuei1069PhosphoserineBy similarity1
Isoform 2 (identifier: O88343-2)
Modified residuei21PhosphoserineCombined sources1
Isoform 3 (identifier: O88343-3)
Modified residuei21PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation of Ser-1026 by PKA increases the binding of CA2 and changes the Na+:HCO3- stoichiometry of the transporter from 3:1 to 2:1. Phosphorylated in presence of STK39 and dephosphorylated in presence of PP1 phosphatase; phosphorylation seems to inhibit SLC4A4 activity (PubMed:21317537).By similarity1 Publication
N-glycosylated. May not be necessary for the transporter basic functions.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiO88343.
PaxDbiO88343.
PeptideAtlasiO88343.
PRIDEiO88343.

PTM databases

iPTMnetiO88343.
PhosphoSitePlusiO88343.
SwissPalmiO88343.

Expressioni

Tissue specificityi

Isoform 1 is specifically expressed in pancreatic ducts and acini (PubMed:19033647). Also expressed in parotid acinar cells and in the colonic crypts.5 Publications

Gene expression databases

BgeeiENSMUSG00000060961.
ExpressionAtlasiO88343. baseline and differential.
GenevisibleiO88343. MM.

Interactioni

Subunit structurei

Interacts with CA2/carbonic anhydrase 2 and CA4/carbonic anhydrase 4 which may regulate transporter activity (PubMed:14567693, PubMed:15218065). Isoform 1 but not isoform 2 interacts with AHCYL1 (via PEST domain when phosphorylated); the interaction increases SLC4A4 isoform 1 activity (PubMed:16769890, PubMed:19033647, PubMed:21317537). Interacts with AHCYL2 (By similarity).By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Ca4Q644442EBI-771342,EBI-6859308

Protein-protein interaction databases

IntActiO88343. 7 interactors.
MINTiMINT-4130871.
STRINGi10090.ENSMUSP00000121744.

Structurei

3D structure databases

ProteinModelPortaliO88343.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 62Required for interaction with AHCYL1By similarityAdd BLAST62
Regioni748 – 779Interaction with CA4By similarityAdd BLAST32
Regioni1002 – 1004CA2-bindingBy similarity3
Regioni1030 – 1033CA2-bindingBy similarity4
Regioni1057 – 1059Required for basolateral targetingBy similarity3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1009 – 1024Lys-richAdd BLAST16

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1172. Eukaryota.
ENOG410XPHD. LUCA.
GeneTreeiENSGT00760000119021.
HOGENOMiHOG000280684.
HOVERGENiHBG004326.
InParanoidiO88343.
KOiK13575.
PhylomeDBiO88343.

Family and domain databases

Gene3Di3.40.1100.10. 1 hit.
InterProiIPR013769. Band3_cytoplasmic_dom.
IPR011531. HCO3_transpt_C.
IPR003020. HCO3_transpt_euk.
IPR003024. Na/HCO3_transpt.
IPR016152. PTrfase/Anion_transptr.
[Graphical view]
PANTHERiPTHR11453. PTHR11453. 2 hits.
PfamiPF07565. Band_3_cyto. 1 hit.
PF00955. HCO3_cotransp. 1 hit.
[Graphical view]
PRINTSiPR01231. HCO3TRNSPORT.
PR01232. NAHCO3TRSPRT.
SUPFAMiSSF55804. SSF55804. 1 hit.
TIGRFAMsiTIGR00834. ae. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O88343-1) [UniParc]FASTAAdd to basket
Also known as: pNBC

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
MEDEAVLDRG ASFLKHVCDE EEVEGHHTIY IGVHVPKSYR RRRRHKRKAG
60 70 80 90 100
HKEKKEKERI SENYSDKSDV ENADESSSSI LKPLISPAAE RIRFILGEED
110 120 130 140 150
DSPAPPQLFT ELDELLAVDG QEMEWKETAR WIKFEEKVEQ GGERWSKPHV
160 170 180 190 200
ATLSLHSLFE LRTCMEKGSI MLDREASSLP QLVEMIADHQ IETGLLKPDL
210 220 230 240 250
KDKVTYTLLR KHRHQTKKSN LRSLADIGKT VSSASRMFSN PDNGSPAMTH
260 270 280 290 300
RNLTSSSLND ISDKPEKDQL KNKFMKKLPR DAEASNVLVG EVDFLDTPFI
310 320 330 340 350
AFVRLQQAVM LGALTEVPVP TRFLFILLGP KGKAKSYHEI GRAIATLMSD
360 370 380 390 400
EVFHDIAYKA KDRHDLIAGI DEFLDEVIVL PPGEWDPTIR IEPPKSLPSS
410 420 430 440 450
DKRKNMYSGG ENVQMNGDTP HDGGHGGGGH GDCEELQRTG RFCGGLIKDI
460 470 480 490 500
KRKAPFFASD FYDALNIQAL SAILFIYLAT VTNAITFGGL LGDATDNMQG
510 520 530 540 550
VLESFLGTAV SGAIFCLFAG QPLTILSSTG PVLVFERLLF NFSKDHNFDY
560 570 580 590 600
LEFRLWIGLW SAFMCLVLVA TDASFLVQYF TRFTEEGFSS LISFIFIYDA
610 620 630 640 650
FKKMIKLADY YPINSDFKVG YNTHFSCACL PPDPVNLSVS NDTTLAPEDL
660 670 680 690 700
PTISSTDMYH NVTFDWAYLS KKECVKYGGK LVGNNCDFVP DITLMSFILF
710 720 730 740 750
LGTYTSSMAM KKFKTSRYFP TTARKLISDF AIILSILIFC VIDALVGVDT
760 770 780 790 800
PKLIVPSEFK PTSPNRGWFV PPFGGNPWWV CLAAAIPALL VTILIFMDQQ
810 820 830 840 850
ITAVIVNRKE HKLKKGAGYH LDLFWVAILM VVCSFMALPW YVAATVISIA
860 870 880 890 900
HIDSLKMETE TSAPGEQPKF LGVREQRVTG TLVFILTGLS VFMAPILKFI
910 920 930 940 950
PMPVLYGVFL YMGVASLNGV QFMDRLKLLL MPLKHQPDFI YLRHVPLRRV
960 970 980 990 1000
HLFTFLQVLC LALLWILKST VAAIIFPVMI LALVAVRKGM DYLFSQHDLS
1010 1020 1030 1040 1050
FLDDVIPEKD KKKKEDEKKK KKKKGSLDSD NDDSDCPYSE KVPSIKIPMD
1060 1070
IMEQQPFLSD NKPLDRERSS TFLERHTSC
Length:1,079
Mass (Da):121,484
Last modified:December 20, 2005 - v2
Checksum:iDBC7C3DEBE10BE97
GO
Isoform 2 (identifier: O88343-2) [UniParc]FASTAAdd to basket
Also known as: kNBC

The sequence of this isoform differs from the canonical sequence as follows:
     1-44: Missing.
     45-85: HKRKAGHKEK...SSSSILKPLI → MSTENVEGKP...FNHSIFTSAV

Show »
Length:1,035
Mass (Da):116,182
Checksum:i75CD2F7008D52ADE
GO
Isoform 3 (identifier: O88343-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-44: Missing.
     45-85: HKRKAGHKEK...SSSSILKPLI → MSTENVEGKP...FNHSIFTSAV
     185-201: MIADHQIETGLLKPDLK → LLGESRKVIRPAGFIRP
     202-1079: Missing.

Note: No experimental confirmation available.Combined sources
Show »
Length:157
Mass (Da):17,829
Checksum:i95E7EA3165687E5D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti388T → A in AAC40160 (PubMed:9651366).Curated1
Sequence conflicti546H → N in AAC40160 (PubMed:9651366).Curated1
Sequence conflicti560W → R in AAC40160 (PubMed:9651366).Curated1
Sequence conflicti564M → L in AAC40160 (PubMed:9651366).Curated1
Sequence conflicti567V → I in AAC40160 (PubMed:9651366).Curated1
Sequence conflicti589S → P in AAC40160 (PubMed:9651366).Curated1
Sequence conflicti740C → G in AAC40160 (PubMed:9651366).Curated1
Sequence conflicti775G → E in AAC40160 (PubMed:9651366).Curated1
Sequence conflicti814K → Q in AAC40160 (PubMed:9651366).Curated1
Sequence conflicti832V → I in AAC40160 (PubMed:9651366).Curated1
Sequence conflicti835F → L in AAC40160 (PubMed:9651366).Curated1
Sequence conflicti848S → F in AAD31036 (PubMed:11171615).Curated1
Sequence conflicti876Q → P in AAD31036 (PubMed:11171615).Curated1
Sequence conflicti884F → L in AAC40160 (PubMed:9651366).Curated1
Sequence conflicti901P → R in AAD31036 (PubMed:11171615).Curated1
Sequence conflicti909 – 910FL → SW in AAD31036 (PubMed:11171615).Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0167091 – 44Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST44
Alternative sequenceiVSP_01671045 – 85HKRKA…LKPLI → MSTENVEGKPNNLGERGRAR SSTFLRVFQPMFNHSIFTSA V in isoform 2 and isoform 3. 2 PublicationsAdd BLAST41
Alternative sequenceiVSP_016711185 – 201MIADH…KPDLK → LLGESRKVIRPAGFIRP in isoform 3. 1 PublicationAdd BLAST17
Alternative sequenceiVSP_016712202 – 1079Missing in isoform 3. 1 PublicationAdd BLAST878

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF020195 mRNA. Translation: AAC40160.1.
AF141934 mRNA. Translation: AAD31036.3.
AK085387 mRNA. Translation: BAC39437.1.
AK140443 mRNA. Translation: BAE24389.1.
BC026592 mRNA. Translation: AAH26592.1.
CCDSiCCDS19406.1. [O88343-1]
PIRiT14031.
RefSeqiNP_001129732.1. NM_001136260.1.
NP_061230.2. NM_018760.2. [O88343-1]
UniGeneiMm.41044.

Genome annotation databases

EnsembliENSMUST00000113216; ENSMUSP00000108842; ENSMUSG00000060961. [O88343-3]
ENSMUST00000130041; ENSMUSP00000118413; ENSMUSG00000060961. [O88343-2]
ENSMUST00000148750; ENSMUSP00000119325; ENSMUSG00000060961. [O88343-1]
GeneIDi54403.
KEGGimmu:54403.
UCSCiuc008yak.1. mouse. [O88343-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF020195 mRNA. Translation: AAC40160.1.
AF141934 mRNA. Translation: AAD31036.3.
AK085387 mRNA. Translation: BAC39437.1.
AK140443 mRNA. Translation: BAE24389.1.
BC026592 mRNA. Translation: AAH26592.1.
CCDSiCCDS19406.1. [O88343-1]
PIRiT14031.
RefSeqiNP_001129732.1. NM_001136260.1.
NP_061230.2. NM_018760.2. [O88343-1]
UniGeneiMm.41044.

3D structure databases

ProteinModelPortaliO88343.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO88343. 7 interactors.
MINTiMINT-4130871.
STRINGi10090.ENSMUSP00000121744.

PTM databases

iPTMnetiO88343.
PhosphoSitePlusiO88343.
SwissPalmiO88343.

Proteomic databases

MaxQBiO88343.
PaxDbiO88343.
PeptideAtlasiO88343.
PRIDEiO88343.

Protocols and materials databases

DNASUi54403.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000113216; ENSMUSP00000108842; ENSMUSG00000060961. [O88343-3]
ENSMUST00000130041; ENSMUSP00000118413; ENSMUSG00000060961. [O88343-2]
ENSMUST00000148750; ENSMUSP00000119325; ENSMUSG00000060961. [O88343-1]
GeneIDi54403.
KEGGimmu:54403.
UCSCiuc008yak.1. mouse. [O88343-1]

Organism-specific databases

CTDi8671.
MGIiMGI:1927555. Slc4a4.

Phylogenomic databases

eggNOGiKOG1172. Eukaryota.
ENOG410XPHD. LUCA.
GeneTreeiENSGT00760000119021.
HOGENOMiHOG000280684.
HOVERGENiHBG004326.
InParanoidiO88343.
KOiK13575.
PhylomeDBiO88343.

Enzyme and pathway databases

ReactomeiR-MMU-425381. Bicarbonate transporters.

Miscellaneous databases

ChiTaRSiSlc4a4. mouse.
PROiO88343.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000060961.
ExpressionAtlasiO88343. baseline and differential.
GenevisibleiO88343. MM.

Family and domain databases

Gene3Di3.40.1100.10. 1 hit.
InterProiIPR013769. Band3_cytoplasmic_dom.
IPR011531. HCO3_transpt_C.
IPR003020. HCO3_transpt_euk.
IPR003024. Na/HCO3_transpt.
IPR016152. PTrfase/Anion_transptr.
[Graphical view]
PANTHERiPTHR11453. PTHR11453. 2 hits.
PfamiPF07565. Band_3_cyto. 1 hit.
PF00955. HCO3_cotransp. 1 hit.
[Graphical view]
PRINTSiPR01231. HCO3TRNSPORT.
PR01232. NAHCO3TRSPRT.
SUPFAMiSSF55804. SSF55804. 1 hit.
TIGRFAMsiTIGR00834. ae. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiS4A4_MOUSE
AccessioniPrimary (citable) accession number: O88343
Secondary accession number(s): Q3USE4
, Q8BUG0, Q8QZR9, Q9R1C4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: December 20, 2005
Last modified: November 2, 2016
This is version 130 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.