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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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 468468CytoplasmicSequence analysisAdd
BLAST
Transmembranei469 – 48820HelicalSequence analysisAdd
BLAST
Topological domaini489 – 50416ExtracellularSequence analysisAdd
BLAST
Transmembranei505 – 52622HelicalSequence analysisAdd
BLAST
Topological domaini527 – 55428CytoplasmicSequence analysisAdd
BLAST
Transmembranei555 – 58026HelicalSequence analysisAdd
BLAST
Topological domaini581 – 691111ExtracellularSequence analysisAdd
BLAST
Transmembranei692 – 71019HelicalSequence analysisAdd
BLAST
Topological domaini711 – 72515CytoplasmicSequence analysisAdd
BLAST
Transmembranei726 – 74823HelicalSequence analysisAdd
BLAST
Topological domaini749 – 77729ExtracellularSequence analysisAdd
BLAST
Transmembranei778 – 79720HelicalSequence analysisAdd
BLAST
Topological domaini798 – 82225CytoplasmicSequence analysisAdd
BLAST
Transmembranei823 – 84725HelicalSequence analysisAdd
BLAST
Topological domaini848 – 88134ExtracellularSequence analysisAdd
BLAST
Transmembranei882 – 90120HelicalSequence analysisAdd
BLAST
Topological domaini902 – 94948CytoplasmicSequence analysisAdd
BLAST
Transmembranei950 – 96718HelicalSequence analysisAdd
BLAST
Topological domaini968 – 9703ExtracellularSequence analysis
Transmembranei971 – 98616HelicalSequence analysisAdd
BLAST
Topological domaini987 – 107993CytoplasmicSequence analysisAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10791079Electrogenic sodium bicarbonate cotransporter 1PRO_0000079228Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei30 – 301PhosphotyrosineCombined sources
Modified residuei61 – 611PhosphoserineCombined sources
Modified residuei65 – 651PhosphoserineCombined sources
Modified residuei68 – 681PhosphoserineCombined sources
Modified residuei223 – 2231PhosphoserineCombined sources
Modified residuei232 – 2321PhosphoserineCombined sources
Modified residuei233 – 2331PhosphoserineCombined sources
Modified residuei245 – 2451PhosphoserineCombined sources
Modified residuei249 – 2491PhosphothreonineBy similarity
Modified residuei254 – 2541PhosphothreonineCombined sources
Modified residuei256 – 2561PhosphoserineCombined sources
Modified residuei257 – 2571PhosphoserineCombined sources
Modified residuei262 – 2621PhosphoserineCombined sources
Disulfide bondi627 ↔ 629By similarity
Glycosylationi641 – 6411N-linked (GlcNAc...)By similarity
Glycosylationi661 – 6611N-linked (GlcNAc...)By similarity
Disulfide bondi674 ↔ 686By similarity
Modified residuei1026 – 10261PhosphoserineCombined sources
Modified residuei1029 – 10291PhosphoserineCombined sources
Modified residuei1034 – 10341PhosphoserineCombined sources
Modified residuei1044 – 10441PhosphoserineCombined sources
Modified residuei1069 – 10691PhosphoserineBy similarity
Isoform 2 (identifier: O88343-2)
Modified residuei21 – 211PhosphoserineCombined sources
Isoform 3 (identifier: O88343-3)
Modified residuei21 – 211PhosphoserineCombined sources

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.
PhosphoSiteiO88343.
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 interactions.
MINTiMINT-4130871.
STRINGi10090.ENSMUSP00000121744.

Structurei

3D structure databases

ProteinModelPortaliO88343.
SMRiO88343. Positions 107-382, 453-493.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 6262Required for interaction with AHCYL1By similarityAdd
BLAST
Regioni748 – 77932Interaction with CA4By similarityAdd
BLAST
Regioni1002 – 10043CA2-bindingBy similarity
Regioni1030 – 10334CA2-bindingBy similarity
Regioni1057 – 10593Required for basolateral targetingBy similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi1009 – 102416Lys-richAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti388 – 3881T → A in AAC40160 (PubMed:9651366).Curated
Sequence conflicti546 – 5461H → N in AAC40160 (PubMed:9651366).Curated
Sequence conflicti560 – 5601W → R in AAC40160 (PubMed:9651366).Curated
Sequence conflicti564 – 5641M → L in AAC40160 (PubMed:9651366).Curated
Sequence conflicti567 – 5671V → I in AAC40160 (PubMed:9651366).Curated
Sequence conflicti589 – 5891S → P in AAC40160 (PubMed:9651366).Curated
Sequence conflicti740 – 7401C → G in AAC40160 (PubMed:9651366).Curated
Sequence conflicti775 – 7751G → E in AAC40160 (PubMed:9651366).Curated
Sequence conflicti814 – 8141K → Q in AAC40160 (PubMed:9651366).Curated
Sequence conflicti832 – 8321V → I in AAC40160 (PubMed:9651366).Curated
Sequence conflicti835 – 8351F → L in AAC40160 (PubMed:9651366).Curated
Sequence conflicti848 – 8481S → F in AAD31036 (PubMed:11171615).Curated
Sequence conflicti876 – 8761Q → P in AAD31036 (PubMed:11171615).Curated
Sequence conflicti884 – 8841F → L in AAC40160 (PubMed:9651366).Curated
Sequence conflicti901 – 9011P → R in AAD31036 (PubMed:11171615).Curated
Sequence conflicti909 – 9102FL → SW in AAD31036 (PubMed:11171615).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4444Missing in isoform 2 and isoform 3. 2 PublicationsVSP_016709Add
BLAST
Alternative sequencei45 – 8541HKRKA…LKPLI → MSTENVEGKPNNLGERGRAR SSTFLRVFQPMFNHSIFTSA V in isoform 2 and isoform 3. 2 PublicationsVSP_016710Add
BLAST
Alternative sequencei185 – 20117MIADH…KPDLK → LLGESRKVIRPAGFIRP in isoform 3. 1 PublicationVSP_016711Add
BLAST
Alternative sequencei202 – 1079878Missing in isoform 3. 1 PublicationVSP_016712Add
BLAST

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]
XP_006535201.2. XM_006535138.2. [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]
XP_006535201.2. XM_006535138.2. [O88343-1]
UniGeneiMm.41044.

3D structure databases

ProteinModelPortaliO88343.
SMRiO88343. Positions 107-382, 453-493.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

iPTMnetiO88343.
PhosphoSiteiO88343.
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: September 7, 2016
This is version 128 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.