UniProtKB - Q9JI66 (S4A4_RAT)
Electrogenic sodium bicarbonate cotransporter 1
Slc4a4
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 similarity3 PublicationsMay have a higher activity than isoform 1.
By similarityActivity regulationi
GO - Molecular functioni
- identical protein binding Source: RGD
- inorganic anion exchanger activity Source: InterPro
- sodium:bicarbonate symporter activity Source: UniProtKB
- symporter activity Source: RGD
- transmembrane transporter activity Source: GO_Central
GO - Biological processi
- bicarbonate transport Source: RGD
- ion homeostasis Source: GO_Central
- positive regulation of glycolytic process Source: RGD
- regulation of intracellular pH Source: RGD
- regulation of membrane potential Source: RGD
- regulation of pH Source: RGD
- sodium ion export across plasma membrane Source: RGD
- sodium ion transmembrane transport Source: RGD
- sodium ion transport Source: UniProtKB
- transmembrane transport Source: RGD
Keywordsi
Biological process | Ion transport, Sodium transport, Symport, Transport |
Ligand | Sodium |
Enzyme and pathway databases
Reactomei | R-RNO-425381, Bicarbonate transporters |
Protein family/group databases
TCDBi | 2.A.31.2.2, the anion exchanger (ae) family |
Names & Taxonomyi
Protein namesi | Recommended name: Electrogenic sodium bicarbonate cotransporter 1Short name: Sodium bicarbonate cotransporter Alternative name(s): NBC-like protein Na(+)/HCO3(-) cotransporter Solute carrier family 4 member 4 |
Gene namesi | Name:Slc4a4 Synonyms:Nbc, Nbc1, Nbce1, Rnbc1 |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 68936, Slc4a4 |
Subcellular locationi
Plasma membrane
- Basolateral cell membrane 1 Publication; Multi-pass membrane protein 1 Publication
Plasma Membrane
- basolateral plasma membrane Source: UniProtKB
- integral component of plasma membrane Source: RGD
- plasma membrane Source: RGD
Other locations
- cell surface Source: RGD
- membrane Source: ARUK-UCL
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 466 | CytoplasmicBy similarityAdd BLAST | 466 | |
Transmembranei | 467 – 491 | Helical; Name=1By similarityAdd BLAST | 25 | |
Topological domaini | 492 – 501 | ExtracellularBy similarity | 10 | |
Transmembranei | 502 – 520 | Helical; Name=2By similarityAdd BLAST | 19 | |
Topological domaini | 521 | CytoplasmicBy similarity | 1 | |
Transmembranei | 522 – 542 | Discontinuously helical; Name=3By similarityAdd BLAST | 21 | |
Topological domaini | 543 – 550 | ExtracellularBy similarity | 8 | |
Transmembranei | 551 – 571 | Helical; Name=4By similarityAdd BLAST | 21 | |
Topological domaini | 572 – 585 | CytoplasmicBy similarityAdd BLAST | 14 | |
Transmembranei | 586 – 609 | Helical; Name=5By similarityAdd BLAST | 24 | |
Topological domaini | 610 – 692 | ExtracellularBy similarityAdd BLAST | 83 | |
Transmembranei | 693 – 710 | Helical; Name=6By similarityAdd BLAST | 18 | |
Topological domaini | 711 – 725 | CytoplasmicBy similarityAdd BLAST | 15 | |
Transmembranei | 726 – 745 | Helical; Name=7By similarityAdd BLAST | 20 | |
Topological domaini | 746 – 779 | ExtracellularBy similarityAdd BLAST | 34 | |
Transmembranei | 780 – 807 | Helical; Name=8By similarityAdd BLAST | 28 | |
Topological domaini | 808 – 819 | CytoplasmicBy similarityAdd BLAST | 12 | |
Transmembranei | 820 – 836 | Helical; Name=9By similarityAdd BLAST | 17 | |
Topological domaini | 837 | ExtracellularBy similarity | 1 | |
Transmembranei | 838 – 855 | Discontinuously helical; Name=10By similarityAdd BLAST | 18 | |
Topological domaini | 856 – 877 | CytoplasmicBy similarityAdd BLAST | 22 | |
Transmembranei | 878 – 894 | Helical; Name=11By similarityAdd BLAST | 17 | |
Topological domaini | 895 – 901 | ExtracellularBy similarity | 7 | |
Transmembranei | 902 – 918 | Helical; Name=12By similarityAdd BLAST | 17 | |
Topological domaini | 919 – 960 | CytoplasmicBy similarityAdd BLAST | 42 | |
Intramembranei | 961 – 986 | Discontinuously helicalBy similarityAdd BLAST | 26 | |
Topological domaini | 987 – 1079 | CytoplasmicBy similarityAdd BLAST | 93 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 243 | N → Q: No effect on N-glycosylation. 1 Publication | 1 | |
Mutagenesisi | 252 | N → Q: No effect on N-glycosylation. 1 Publication | 1 | |
Mutagenesisi | 541 | N → Q: No effect on N-glycosylation. 1 Publication | 1 | |
Mutagenesisi | 636 | N → Q: No effect on N-glycosylation. Complete loss of N-glycosylation without effect on transporter basic function; when associated with Q-641 and Q-661. 1 Publication | 1 | |
Mutagenesisi | 641 | N → Q: Reduces the extent of N-glycosylation. Complete loss of N-glycosylation without effect on transporter basic function; when associated with Q-636 and Q-661. 1 Publication | 1 | |
Mutagenesisi | 661 | N → Q: Reduces the extent of N-glycosylation. Complete loss of N-glycosylation without effect on transporter basic function; when associated with Q-636 and Q-641. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000079231 | 1 – 1079 | Electrogenic sodium bicarbonate cotransporter 1Add BLAST | 1079 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
---|---|---|---|---|---|
Modified residuei | 30 | PhosphotyrosineBy similarity | 1 | ||
Modified residuei | 61 | PhosphoserineBy similarity | 1 | ||
Modified residuei | 65 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 68 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 223 | PhosphoserineBy similarity | 1 | ||
Modified residuei | 232 | PhosphoserineBy similarity | 1 | ||
Modified residuei | 233 | PhosphoserineBy similarity | 1 | ||
Modified residuei | 245 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 249 | PhosphothreonineCombined sources | 1 | ||
Modified residuei | 254 | PhosphothreonineCombined sources | 1 | ||
Modified residuei | 256 | PhosphoserineBy similarity | 1 | ||
Modified residuei | 257 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 262 | PhosphoserineCombined sources | 1 | ||
Disulfide bondi | 627 ↔ 629 | By similarity | |||
Glycosylationi | 641 | N-linked (GlcNAc...) asparagine1 Publication | 1 | ||
Glycosylationi | 661 | N-linked (GlcNAc...) asparagine1 Publication | 1 | ||
Disulfide bondi | 674 ↔ 686 | By similarity | |||
Modified residuei | 1026 | Phosphoserine; by PKABy similarity | 1 | ||
Modified residuei | 1029 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 1034 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 1044 | PhosphoserineBy similarity | 1 | ||
Modified residuei | 1069 | PhosphoserineCombined sources | 1 | ||
Isoform 2 (identifier: Q9JI66-2) | |||||
Modified residuei | 2 | PhosphoserineCombined sources | 1 | ||
Isoform 3 (identifier: Q9JI66-3) | |||||
Modified residuei | 1026 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 1029 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 1060 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 1064 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 1078 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 636 | Not glycosylated | 1 |
Keywords - PTMi
Disulfide bond, Glycoprotein, PhosphoproteinProteomic databases
PaxDbi | Q9JI66 |
PRIDEi | Q9JI66 |
PTM databases
GlyGeni | Q9JI66, 2 sites |
iPTMneti | Q9JI66 |
PhosphoSitePlusi | Q9JI66 |
SwissPalmi | Q9JI66 |
Expressioni
Tissue specificityi
Developmental stagei
Inductioni
Gene expression databases
Bgeei | ENSRNOG00000003134, Expressed in adult mammalian kidney and 20 other tissues |
ExpressionAtlasi | Q9JI66, baseline and differential |
Genevisiblei | Q9JI66, RN |
Interactioni
Subunit structurei
Homodimer.
Interacts with CA2/carbonic anhydrase 2 and CA4/carbonic anhydrase 4 which may regulate transporter activity. Isoform 1 but not isoform 2 interacts with AHCYL1 (via PEST domain when phosphorylated); the interaction increases SLC4A4 isoform 1 activity.
Interacts with AHCYL2.
By similarityGO - Molecular functioni
- identical protein binding Source: RGD
Protein-protein interaction databases
BioGRIDi | 249983, 4 interactors |
IntActi | Q9JI66, 2 interactors |
MINTi | Q9JI66 |
STRINGi | 10116.ENSRNOP00000004391 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 62 | Required for interaction with AHCYL1By similarityAdd BLAST | 62 | |
Regioni | 39 – 78 | DisorderedSequence analysisAdd BLAST | 40 | |
Regioni | 235 – 266 | DisorderedSequence analysisAdd BLAST | 32 | |
Regioni | 748 – 779 | Interaction with CA4By similarityAdd BLAST | 32 | |
Regioni | 1002 – 1004 | CA2-bindingBy similarity | 3 | |
Regioni | 1012 – 1079 | DisorderedSequence analysisAdd BLAST | 68 | |
Regioni | 1030 – 1033 | CA2-bindingBy similarity | 4 | |
Regioni | 1057 – 1059 | Required for basolateral targetingBy similarity | 3 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 39 – 53 | Basic residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 54 – 73 | Basic and acidic residuesSequence analysisAdd BLAST | 20 | |
Compositional biasi | 235 – 260 | Polar residuesSequence analysisAdd BLAST | 26 | |
Compositional biasi | 1012 – 1039 | Basic and acidic residuesSequence analysisAdd BLAST | 28 | |
Compositional biasi | 1060 – 1079 | Basic and acidic residuesSequence analysisAdd BLAST | 20 |
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1172, Eukaryota |
GeneTreei | ENSGT00940000156290 |
HOGENOMi | CLU_002289_5_0_1 |
InParanoidi | Q9JI66 |
OrthoDBi | 265068at2759 |
PhylomeDBi | Q9JI66 |
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 (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
This 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
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 PPGEWDPAIR 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 NFSKDHSFDY
560 570 580 590 600
LEFRLWIGLW SAFMCLILVA TDASFLVQYF TRFTEEGFSS LISFIFIYDA
610 620 630 640 650
FKKMIKLADY YPINSDFRVG YNTHFSCACL PPDPVNLSVS NDTTLAPEDL
660 670 680 690 700
PTVSSTDMYH NATFDWAYLS KKECVKFGGK LVGNNCDFVP DITLMSFILF
710 720 730 740 750
LGTYTSSMAM KKFKTSRYFP TTARKLISDF AIILSILIFC VIDALVGVDT
760 770 780 790 800
PKLIVPSEFK PTSPHRGWFV 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
HLFTSLQVLC LALLWILKST VAAIIFPVMI LALVAVRKGM DYLFSQHDLS
1010 1020 1030 1040 1050
FLDDVIPEKD KKKKEDEKKK KKKKGSLDSD NDDSDCPYSE KVPSIKIPMD
1060 1070
ITEQQPFLSD NKPLDRERSS TFLERHTSC
The sequence of this isoform differs from the canonical sequence as follows:
1-44: Missing.
45-85: HKRKAGHKEK...SSSSILKPLI → MSTENVEGKP...FNHSIFTSAV
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A0H2UHB7 | A0A0H2UHB7_RAT | Anion exchange protein | Slc4a4 | 1,104 | Annotation score: | ||
A0A8I6ABC3 | A0A8I6ABC3_RAT | Electrogenic sodium bicarbonate cot... | Slc4a4 | 1,084 | Annotation score: | ||
A0A8I6AFE1 | A0A8I6AFE1_RAT | Electrogenic sodium bicarbonate cot... | Slc4a4 | 1,099 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 284 – 285 | AS → VP in AAB83997 (PubMed:9841505).Curated | 2 | |
Sequence conflicti | 284 – 285 | AS → VP in AAF21040 (PubMed:10648705).Curated | 2 | |
Sequence conflicti | 479 | A → G in AAB83997 (PubMed:9841505).Curated | 1 | |
Sequence conflicti | 479 | A → G in AAF21040 (PubMed:10648705).Curated | 1 | |
Sequence conflicti | 640 | S → Y in AAB83997 (PubMed:9841505).Curated | 1 | |
Sequence conflicti | 655 | S → F in AAB83997 (PubMed:9841505).Curated | 1 | |
Sequence conflicti | 803 | A → P in AAB83997 (PubMed:9841505).Curated | 1 | |
Sequence conflicti | 803 | A → P in AAF21040 (PubMed:10648705).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_016717 | 1 – 44 | Missing in isoform 2. 2 PublicationsAdd BLAST | 44 | |
Alternative sequenceiVSP_016718 | 45 – 85 | HKRKA…LKPLI → MSTENVEGKPNNLGERGRAR SSTFLRVFQPMFNHSIFTSA V in isoform 2. 2 PublicationsAdd BLAST | 41 | |
Alternative sequenceiVSP_016719 | 1034 – 1079 | SDCPY…RHTSC → EKDPQHSLNATHHADKIPFL ESLGLPSPPRSPVKVVPQIR IELESEDNDYLWRNKGTETT L in isoform 3. 1 PublicationAdd BLAST | 46 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF004017 mRNA Translation: AAC40034.1 AF027362 mRNA Translation: AAB83997.1 AF124441 mRNA Translation: AAF87312.1 AF254802 mRNA Translation: AAF87553.1 AF210250 mRNA Translation: AAF21040.1 |
PIRi | T13962 T14110 |
RefSeqi | NP_445876.1, NM_053424.1 [Q9JI66-1] XP_006250853.1, XM_006250791.3 [Q9JI66-3] |
Genome annotation databases
GeneIDi | 84484 |
KEGGi | rno:84484 |
UCSCi | RGD:68936, rat [Q9JI66-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF004017 mRNA Translation: AAC40034.1 AF027362 mRNA Translation: AAB83997.1 AF124441 mRNA Translation: AAF87312.1 AF254802 mRNA Translation: AAF87553.1 AF210250 mRNA Translation: AAF21040.1 |
PIRi | T13962 T14110 |
RefSeqi | NP_445876.1, NM_053424.1 [Q9JI66-1] XP_006250853.1, XM_006250791.3 [Q9JI66-3] |
3D structure databases
AlphaFoldDBi | Q9JI66 |
SMRi | Q9JI66 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 249983, 4 interactors |
IntActi | Q9JI66, 2 interactors |
MINTi | Q9JI66 |
STRINGi | 10116.ENSRNOP00000004391 |
Protein family/group databases
TCDBi | 2.A.31.2.2, the anion exchanger (ae) family |
PTM databases
GlyGeni | Q9JI66, 2 sites |
iPTMneti | Q9JI66 |
PhosphoSitePlusi | Q9JI66 |
SwissPalmi | Q9JI66 |
Proteomic databases
PaxDbi | Q9JI66 |
PRIDEi | Q9JI66 |
Genome annotation databases
GeneIDi | 84484 |
KEGGi | rno:84484 |
UCSCi | RGD:68936, rat [Q9JI66-1] |
Organism-specific databases
CTDi | 8671 |
RGDi | 68936, Slc4a4 |
Phylogenomic databases
eggNOGi | KOG1172, Eukaryota |
GeneTreei | ENSGT00940000156290 |
HOGENOMi | CLU_002289_5_0_1 |
InParanoidi | Q9JI66 |
OrthoDBi | 265068at2759 |
PhylomeDBi | Q9JI66 |
TreeFami | TF313630 |
Enzyme and pathway databases
Reactomei | R-RNO-425381, Bicarbonate transporters |
Miscellaneous databases
PROi | PR:Q9JI66 |
Gene expression databases
Bgeei | ENSRNOG00000003134, Expressed in adult mammalian kidney and 20 other tissues |
ExpressionAtlasi | Q9JI66, baseline and differential |
Genevisiblei | Q9JI66, RN |
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 | S4A4_RAT | |
Accessioni | Q9JI66Primary (citable) accession number: Q9JI66 Secondary accession number(s): O35422 Q9QXH6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 20, 2005 |
Last sequence update: | October 1, 2000 | |
Last modified: | May 25, 2022 | |
This is version 139 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families