Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Electrogenic sodium bicarbonate cotransporter 1

Gene

SLC4A4

Organism
Oryctolagus cuniculus (Rabbit)
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 similarity
Isoform 2: May have a higher activity than isoform 1.By similarity

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):
Na(+)/HCO3(-) cotransporter
Solute carrier family 4 member 4
Gene namesi
Name:SLC4A4
Synonyms:NBC1, NBCE1
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 Componenti: Unplaced

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

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_0000079230Add
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

Expressioni

Tissue specificityi

Expressed in colonic mucosa, kidney cortex and to gastric mucosa.1 Publication

Interactioni

Subunit structurei

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 similarity

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000002024.

Structurei

3D structure databases

ProteinModelPortaliQ9XSZ4.
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.
HOGENOMiHOG000280684.
HOVERGENiHBG004326.
InParanoidiQ9XSZ4.
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.

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9XSZ4-1) [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
MEDEAVLDRG ASFLKHVCDE EEVEGHHTIY IGVHVPKSYR RRRRHKRKTG
60 70 80 90 100
HKEKREKERI SENYSDKSDV ENADESSSSI LKPLISPAAE RIRFILGEED
110 120 130 140 150
DSPAPPQLFT ELDELLAVDG QEMEWKETAR WIKFEEKVEQ GGERWSKPHV
160 170 180 190 200
ATLSLHSLFE LRTCMEKGSI MLDREATSLP QLVEMIVDHQ IETGLLKPDL
210 220 230 240 250
KDKVTYTLLR KHRHQTKKSN LRSLADIGKT VSSASRMFTS 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 ADCEELQRTG RFCGGLIKDL
460 470 480 490 500
KRKAPFFASD FYDALNIQSL 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 YPINSDFKVG YNTFFSCACV PPDPVNISIA NDTTPAPQEL
660 670 680 690 700
SAVSSTDMHQ NATFDWAFLS KKECLRYGGK LVGNNCNFVP DVTLMSFILF
710 720 730 740 750
LGTYTSSMAL KKFKTSRYFP TTARKLISDF AIILSILIFC VIDALVGVDT
760 770 780 790 800
PKLIVPSEFK PTSPNRGWFV PPFGGNPWWV 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 KKKKGSLDSD NDDSDCPYSE KVPSIKIPMD
1060 1070
IMEQQPFLSE SKPSDREKSS TFLERHTSC
Length:1,079
Mass (Da):121,427
Last modified:November 1, 1999 - v1
Checksum:iB3353A66282C532E
GO
Isoform 2 (identifier: Q9XSZ4-2) [UniParc]FASTAAdd to basket

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

Show »
Length:1,035
Mass (Da):116,044
Checksum:i50EBE6177FB21C2E
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4444Missing in isoform 2. 1 PublicationVSP_016715Add
BLAST
Alternative sequencei45 – 8541HKRKT…LKPLI → MSTENVEGKPSNLGERGRAR SYTFLRVVQPMFNLSIFTSA V in isoform 2. 1 PublicationVSP_016716Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF149418 mRNA. Translation: AAD38154.1.
AF119816 mRNA. Translation: AAD18037.1.
RefSeqiNP_001075529.1. NM_001082060.1. [Q9XSZ4-1]
UniGeneiOcu.2331.

Genome annotation databases

GeneIDi100008727.
KEGGiocu:100008727.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF149418 mRNA. Translation: AAD38154.1.
AF119816 mRNA. Translation: AAD18037.1.
RefSeqiNP_001075529.1. NM_001082060.1. [Q9XSZ4-1]
UniGeneiOcu.2331.

3D structure databases

ProteinModelPortaliQ9XSZ4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000002024.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100008727.
KEGGiocu:100008727.

Organism-specific databases

CTDi8671.

Phylogenomic databases

eggNOGiKOG1172. Eukaryota.
ENOG410XPHD. LUCA.
HOGENOMiHOG000280684.
HOVERGENiHBG004326.
InParanoidiQ9XSZ4.
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...

Entry informationi

Entry nameiS4A4_RABIT
AccessioniPrimary (citable) accession number: Q9XSZ4
Secondary accession number(s): O97915
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: November 1, 1999
Last modified: July 6, 2016
This is version 86 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.