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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)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

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000792301 – 1079Electrogenic sodium bicarbonate cotransporter 1Add BLAST1079

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei30PhosphotyrosineBy similarity1
Modified residuei49Phosphothreonine; by PKABy similarity1
Modified residuei61PhosphoserineBy similarity1
Modified residuei65PhosphoserineBy similarity1
Modified residuei68PhosphoserineBy similarity1
Modified residuei223PhosphoserineBy similarity1
Modified residuei232PhosphoserineBy similarity1
Modified residuei233PhosphoserineBy similarity1
Modified residuei245PhosphoserineBy similarity1
Modified residuei249PhosphothreonineBy similarity1
Modified residuei254PhosphothreonineBy similarity1
Modified residuei256PhosphoserineBy similarity1
Modified residuei257PhosphoserineBy similarity1
Modified residuei262PhosphoserineBy similarity1
Disulfide bondi627 ↔ 629By similarity
Glycosylationi641N-linked (GlcNAc...)By similarity1
Glycosylationi661N-linked (GlcNAc...)By similarity1
Disulfide bondi674 ↔ 686By similarity
Modified residuei1026Phosphoserine; by PKABy similarity1
Modified residuei1029PhosphoserineBy similarity1
Modified residuei1034PhosphoserineBy similarity1
Modified residuei1044PhosphoserineBy similarity1
Modified residuei1069PhosphoserineBy similarity1

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)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.
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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0167151 – 44Missing in isoform 2. 1 PublicationAdd BLAST44
Alternative sequenceiVSP_01671645 – 85HKRKT…LKPLI → MSTENVEGKPSNLGERGRAR SYTFLRVVQPMFNLSIFTSA V in isoform 2. 1 PublicationAdd BLAST41

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.