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Protein

Electrogenic sodium bicarbonate cotransporter 1

Gene

SLC4A4

Organism
Bos taurus (Bovine)
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

Enzyme regulationi

Inhibited by stilbene derivatives and regulated by cyclic AMP.By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Ion transport, Sodium transport, Symport, Transport

Keywords - Ligandi

Sodium

Names & Taxonomyi

Protein namesi
Recommended name:
Electrogenic sodium bicarbonate cotransporter 1
Short name:
Sodium bicarbonate cotransporter
Alternative name(s):
Solute carrier family 4 member 4
Gene namesi
Name:SLC4A4
Synonyms:NBC, NBCE1
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

  • Basolateral cell membrane 1 Publication; Multi-pass membrane protein 1 Publication

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

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_0000079226Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei30 – 301PhosphotyrosineBy similarity
Modified residuei49 – 491Phosphothreonine; by PKABy similarity
Modified residuei61 – 611PhosphoserineBy similarity
Modified residuei65 – 651PhosphoserineBy similarity
Modified residuei68 – 681PhosphoserineBy similarity
Modified residuei223 – 2231PhosphoserineBy similarity
Modified residuei232 – 2321PhosphoserineBy similarity
Modified residuei233 – 2331PhosphoserineBy similarity
Modified residuei245 – 2451PhosphoserineBy similarity
Modified residuei249 – 2491PhosphothreonineBy similarity
Modified residuei254 – 2541PhosphothreonineBy similarity
Modified residuei256 – 2561PhosphoserineBy similarity
Modified residuei257 – 2571PhosphoserineBy similarity
Modified residuei262 – 2621PhosphoserineBy similarity
Disulfide bondi627 ↔ 629By similarity
Glycosylationi641 – 6411N-linked (GlcNAc...)By similarity
Glycosylationi661 – 6611N-linked (GlcNAc...)By similarity
Disulfide bondi674 ↔ 686By similarity
Modified residuei1026 – 10261Phosphoserine; by PKABy similarity
Modified residuei1029 – 10291PhosphoserineBy similarity
Modified residuei1034 – 10341PhosphoserineBy similarity
Modified residuei1044 – 10441PhosphoserineBy similarity
Modified residuei1069 – 10691PhosphoserineBy similarity

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.By similarity
N-glycosylated. May not be necessary for the transporter basic functions.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ9GL77.
PRIDEiQ9GL77.

Expressioni

Tissue specificityi

Expressed in acinar cells (at protein level).1 Publication

Interactioni

Subunit structurei

Interacts with CA2/carbonic anhydrase 2 and CA4/carbonic anhydrase 4 which may regulate transporter activity. Interacts with AHCYL1 (via PEST domain when phosphorylated); the interaction increases SLC4A4 activity. Interacts with AHCYL2 (PubMed:24472682).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
AHCYL1F1MWH23EBI-9076174,EBI-9079878
AHCYL2A6QLP25EBI-9076174,EBI-9076161

Protein-protein interaction databases

IntActiQ9GL77. 2 interactions.
STRINGi9913.ENSBTAP00000003032.

Structurei

3D structure databases

ProteinModelPortaliQ9GL77.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 6262Required for interation 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.
HOGENOMiHOG000280684.
HOVERGENiHBG004326.
InParanoidiQ9GL77.
KOiK13575.

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.

Sequencei

Sequence statusi: Complete.

Q9GL77-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEDEAVLDRG ASFLKHVCDE EEVEGHHTIY IGVHVPKSYR RRRRHKRKTG
60 70 80 90 100
HREKKEKERI SENYSDKSDV ENADESSSSI LKPLISPAAE RIRFILGEED
110 120 130 140 150
DSPAPPQLFT ELDELLAVDG QEMEWKETAR WIKFEEKVEQ GGERWSKPHV
160 170 180 190 200
ATLSLHSLFE LRTCMEKGSI MLDREASSLP QLVEMIVDHQ IETGLLKPDL
210 220 230 240 250
KDKVTYTLLR KHRHQTKKSN LRSLADIGKT VSSASRMFTN PDNGSPAMTH
260 270 280 290 300
RNLTSSSLND ISDKPEKDQL KNKFMKKLPR DAEASNVLVG EVDFLDSPFI
310 320 330 340 350
AFVRLQQAVM LGALTEVPVP TRFLFILLGP KGKAKSYHEI GRAIATLMSD
360 370 380 390 400
EVFHDIAYKA KDRQDLIAGI DEFLDEVIVL PPGEWDPAIR IEPPKSLPSS
410 420 430 440 450
DKRKNMYSGG ENVQMNGDTP PDGGHGGGGH ADCEELQRTG 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 SAFLCLILVA TDASFLVQYF TRFTEEGFSS LISFIFIYDA
610 620 630 640 650
FKKMIKLADY YPINSNFKVG YNTQFSCVCM PPDPVNISVS NDTTLAPEDL
660 670 680 690 700
PTISSSNMYH NATFDWAFLT TKECLKYGGK LVGNNCGFVP DITLMSFILF
710 720 730 740 750
LGTYTSSMAL KKFKTSPYFP TTARKLISDF AIILPILIFC VIDALVGVDT
760 770 780 790 800
PKLIVPSEFK PTSPNRGWFV APFGGNPWWV YLAAAIPALL 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 KKKKGSVDSD NDDSDCPYSE KVPSIKIPMD
1060 1070
IMEQQPFLSD SKPSDRERSP TFLERHTSC
Length:1,079
Mass (Da):121,331
Last modified:March 1, 2001 - v1
Checksum:i114367FC093C7B67
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF308160 mRNA. Translation: AAG29539.1.
RefSeqiNP_777030.1. NM_174605.1.
UniGeneiBt.7156.

Genome annotation databases

GeneIDi282360.
KEGGibta:282360.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF308160 mRNA. Translation: AAG29539.1.
RefSeqiNP_777030.1. NM_174605.1.
UniGeneiBt.7156.

3D structure databases

ProteinModelPortaliQ9GL77.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9GL77. 2 interactions.
STRINGi9913.ENSBTAP00000003032.

Proteomic databases

PaxDbiQ9GL77.
PRIDEiQ9GL77.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi282360.
KEGGibta:282360.

Organism-specific databases

CTDi8671.

Phylogenomic databases

eggNOGiKOG1172. Eukaryota.
ENOG410XPHD. LUCA.
HOGENOMiHOG000280684.
HOVERGENiHBG004326.
InParanoidiQ9GL77.
KOiK13575.

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...

Publicationsi

  1. "Expression and localization of Na(+)-HCO(3)(-) cotransporter in bovine corneal endothelium."
    Sun X.C., Bonanno J.A., Jelamskii S., Xie Q.
    Am. J. Physiol. 279:C1648-C1655(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION.
    Tissue: Cornea.
  2. "Role of glycosylation in the renal electrogenic Na+-HCO3-cotransporter (NBCe1)."
    Choi I., Hu L., Rojas J.D., Schmitt B.M., Boron W.F.
    Am. J. Physiol. 284:F1199-F1206(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION.
  3. "AHCYL2 (long-IRBIT) as a potential regulator of the electrogenic Na(+)-HCO3(-) cotransporter NBCe1-B."
    Yamaguchi S., Ishikawa T.
    FEBS Lett. 588:672-677(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH AHCYL2, TISSUE SPECIFICITY.

Entry informationi

Entry nameiS4A4_BOVIN
AccessioniPrimary (citable) accession number: Q9GL77
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: March 1, 2001
Last modified: June 8, 2016
This is version 89 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.