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Protein

Electrogenic sodium bicarbonate cotransporter 1

Gene

SLC4A4

Organism
Homo sapiens (Human)
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.7 Publications
Isoform 2: May have a higher activity than isoform 1.1 Publication

Enzyme regulationi

Inhibited by stilbene derivatives and regulated by cyclic AMP.

GO - Molecular functioni

  • inorganic anion exchanger activity Source: InterPro
  • sodium:bicarbonate symporter activity Source: UniProtKB

GO - Biological processi

  • bicarbonate transport Source: Reactome
  • regulation of intracellular pH Source: GO_Central
  • sodium ion transport Source: UniProtKB
  • transport Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Ion transport, Sodium transport, Symport, Transport

Keywords - Ligandi

Sodium

Enzyme and pathway databases

ReactomeiR-HSA-425381. Bicarbonate transporters.

Protein family/group databases

TCDBi2.A.31.2.12. the anion exchanger (ae) family.

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
kNBC1
Gene namesi
Name:SLC4A4
Synonyms:NBC, NBC1, NBCE1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:11030. SLC4A4.

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

  • basolateral plasma membrane Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Renal tubular acidosis, proximal, with ocular abnormalities and mental retardation (pRTA-OA)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn extremely rare autosomal recessive syndrome characterized by short stature, profound proximal renal tubular acidosis, mental retardation, bilateral glaucoma, cataracts and bandkeratopathy. pRTA is due to a failure of the proximal tubular cells to reabsorb filtered bicarbonate from the urine, leading to urinary bicarbonate wasting and subsequent acidemia.
See also OMIM:604278
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_024751342R → S in pRTA-OA; decreased localization to the basolateral membrane; mistargeting to the apical membrane probably explains the loss of the cotransporter activity. 1 Publication3 PublicationsCorresponds to variant rs121908856dbSNPEnsembl.1
Natural variantiVAR_024752471S → L in pRTA-OA; mistargeting to the apical membrane and altered function. 2 Publications1
Natural variantiVAR_024753529T → S in pRTA-OA; decreased cotransporter activity. 1 Publication1 Publication1
Natural variantiVAR_071661530G → R in pRTA-OA; decreased cotransporter activity; no effect on localization to the basolateral membrane. 1 Publication1
Natural variantiVAR_024754554R → H in pRTA-OA; mistargeting and altered function. 3 PublicationsCorresponds to variant rs121908857dbSNPEnsembl.1
Natural variantiVAR_071662566L → P in pRTA-OA; loss of localization to the plasma membrane; the retention in the cytoplasm probably explains the loss of the cotransporter activity. 1 Publication1 Publication1
Natural variantiVAR_024755843A → V in pRTA-OA; altered function. 1 Publication1
Natural variantiVAR_024756925R → C in pRTA-OA; altered function. 1 Publication1

Loss of interaction with and stimulation by CA4 is the cause of retinitis pigmentosa type 17 (RP17).

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi49T → A: Loss of conductance regulation by cAMP; isoform 1. 1 Publication1
Mutagenesisi49T → D: Loss of conductance regulation by cAMP; isoform 1. 1 Publication1
Mutagenesisi135E → R: Mistargeting and altered function. 1 Publication1
Mutagenesisi477Y → F: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi493D → N: Prevents membrane targeting. 1 Publication1
Mutagenesisi494A → K: Prevents membrane targeting. 1 Publication1
Mutagenesisi503E → Q: Strong reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi504S → L: Prevents membrane targeting. 1 Publication1
Mutagenesisi536E → Q: Prevents membrane targeting. 1 Publication1
Mutagenesisi552E → N: Prevents membrane targeting. 1 Publication1
Mutagenesisi554R → D: Prevents membrane targeting. 1 Publication1
Mutagenesisi582R → N: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi582R → Q: Strong reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi586E → Q: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi599D → N: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi600A → T: Strong reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi602K → Q: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi603K → Q: Strong reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi691D → R: Strong reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi700F → M: Strong reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi711K → E, N or Q: Strong reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi711K → R: No effect on the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi712K → N: Strong reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi714K → Q: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi715T → N: Strong reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi721T → G: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi724R → E: Strong reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi725K → N: Strong reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi728S → G: Strong reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi729D → N or R: Strong reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi743D → K or N: Prevents membrane targeting. 1 Publication1
Mutagenesisi749D → N: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi752K → Q: Prevents membrane targeting. 1 Publication1
Mutagenesisi766R → Q: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi767G → T: Alters interaction with CA4. 1 Publication1
Mutagenesisi775E → N: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi798D → E, N or R: Strong reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi808 – 809RK → NN: Strong reduction of the sodium-dependent ion transport activity. 1 Publication2
Mutagenesisi814 – 815KK → NN: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication2
Mutagenesisi820H → D, N, S or R: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi822D → N: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi851H → N: Prevents membrane targeting. 1 Publication1
Mutagenesisi853D → N: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi858 – 860ETE → MSK: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication3
Mutagenesisi875 – 877EQR → QQQ: Prevents membrane targeting. 1 Publication3
Mutagenesisi875E → Q: Strong reduction of the sodium-dependent ion transport activity. 1
Mutagenesisi898K → E: Strong reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi925 – 927RLK → NLN: Prevents membrane targeting. 1 Publication3
Mutagenesisi948R → E: Strong reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi949R → E: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi951H → D: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi951H → N or R: Prevents membrane targeting. 1 Publication1
Mutagenesisi968K → Q: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi987R → E or N: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication1
Mutagenesisi1002L → N: Partial loss of interaction with CA2. 1 Publication1
Mutagenesisi1003D → N: Abolishes interaction with CA2. 1 Publication1
Mutagenesisi1004D → N: Partial loss of interaction with CA2. 1 Publication1
Mutagenesisi1026S → A: Prevents phosphorylation by PKA. Loss of regulation by cAMP of the transporter stoichiometry. 2 Publications1
Mutagenesisi1026S → D: Loss of regulation by cAMP of the transporter stoichiometry. Shifts transporter stoichiometry from 3:1 to 2:1. 2 Publications1
Mutagenesisi1030 – 1033DNDD → NNNN: Abolishes interaction with CA2. 1 Publication4
Mutagenesisi1030D → N: Loss of regulation by cAMP of the transporter stoichiometry. Abolishes interaction with CA2. 1 Publication1
Mutagenesisi1032D → N: Loss of regulation by cAMP of the transporter stoichiometry. Partial loss of interaction with CA2. 1 Publication1
Mutagenesisi1033D → N: No effect on regulation by cAMP of the transporter stoichiometry. Partial loss of interaction with CA2. 1 Publication1
Mutagenesisi1057F → A: Targeting to apical membrane. 1 Publication1

Keywords - Diseasei

Disease mutation, Retinitis pigmentosa

Organism-specific databases

DisGeNETi8671.
MalaCardsiSLC4A4.
MIMi604278. phenotype.
OpenTargetsiENSG00000080493.
Orphaneti93607. Autosomal recessive proximal renal tubular acidosis.
PharmGKBiPA35898.

Chemistry databases

DrugBankiDB01390. Sodium bicarbonate.

Polymorphism and mutation databases

BioMutaiSLC4A4.
DMDMi74721543.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000792271 – 1079Electrogenic sodium bicarbonate cotransporter 1Add BLAST1079

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei30PhosphotyrosineBy similarity1
Modified residuei49Phosphothreonine; by PKA1 Publication1
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 residuei254PhosphothreonineCombined sources1
Modified residuei256PhosphoserineBy similarity1
Modified residuei257PhosphoserineCombined sources1
Modified residuei262PhosphoserineBy similarity1
Disulfide bondi627 ↔ 6291 Publication
Glycosylationi641N-linked (GlcNAc...)1 Publication1
Glycosylationi661N-linked (GlcNAc...)1 Publication1
Disulfide bondi674 ↔ 6861 Publication
Modified residuei1026Phosphoserine; by PKA1 Publication1
Modified residuei1029PhosphoserineBy similarity1
Modified residuei1034PhosphoserineCombined sources1
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 similarity2 Publications
N-glycosylation is not necessary for the transporter basic functions.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ9Y6R1.
PeptideAtlasiQ9Y6R1.
PRIDEiQ9Y6R1.

PTM databases

iPTMnetiQ9Y6R1.
PhosphoSitePlusiQ9Y6R1.
SwissPalmiQ9Y6R1.

Expressioni

Tissue specificityi

Isoform 1 is expressed in pancreas and to a lower extent in heart, skeletal muscle, liver, parotid salivary glands, prostate, colon, stomach, thyroid, brain and spinal chord. Corneal endothelium cells express only isoform 1 (at protein level). Isoform 2 is specifically expressed in kidney at the level of proximal tubules.7 Publications

Gene expression databases

BgeeiENSG00000080493.
CleanExiHS_SLC4A4.
ExpressionAtlasiQ9Y6R1. baseline and differential.
GenevisibleiQ9Y6R1. HS.

Organism-specific databases

HPAiCAB022493.
HPA035628.
HPA035629.

Interactioni

Subunit structurei

Interacts with CA2/carbonic anhydrase 2 and CA4/carbonic anhydrase 4 which may regulate transporter activity (PubMed:12411514, PubMed:14567693, PubMed:15218065, PubMed:15563508). Isoform 1 but not isoform 2 interacts with AHCYL1 (via PEST domain when phosphorylated); the interaction increases SLC4A4 isoform 1 activity (PubMed:16769890). Interacts with AHCYL2 (By similarity).By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CA4P482832EBI-6859278,EBI-6859264From a different organism.

Protein-protein interaction databases

BioGridi114219. 1 interactor.
DIPiDIP-59373N.
IntActiQ9Y6R1. 4 interactors.
STRINGi9606.ENSP00000393557.

Structurei

3D structure databases

ProteinModelPortaliQ9Y6R1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 62Required for interaction with AHCYL11 PublicationAdd BLAST62
Regioni748 – 779Interaction with CA4Add BLAST32
Regioni1002 – 1004CA2-binding3
Regioni1030 – 1033CA2-binding4
Regioni1057 – 1059Required for basolateral targeting3

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.
GeneTreeiENSGT00760000119021.
HOVERGENiHBG004326.
InParanoidiQ9Y6R1.
KOiK13575.
OMAiVCSFMAL.
PhylomeDBiQ9Y6R1.
TreeFamiTF313630.

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 (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y6R1-1) [UniParc]FASTAAdd to basket
Also known as: hcNBC, hhNBC, hNBC1, pNBC, pNCB1, pNBC-1, NBC1b

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
HKEKKEKERI SENYSDKSDI ENADESSSSI LKPLISPAAE RIRFILGEED
110 120 130 140 150
DSPAPPQLFT ELDELLAVDG QEMEWKETAR WIKFEEKVEQ GGERWSKPHV
160 170 180 190 200
ATLSLHSLFE LRTCMEKGSI MLDREASSLP QLVEMIVDHQ IETGLLKPEL
210 220 230 240 250
KDKVTYTLLR KHRHQTKKSN LRSLADIGKT VSSASRMFTN 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 NFSKDNNFDY
560 570 580 590 600
LEFRLWIGLW SAFLCLILVA TDASFLVQYF TRFTEEGFSS LISFIFIYDA
610 620 630 640 650
FKKMIKLADY YPINSNFKVG YNTLFSCTCV PPDPANISIS NDTTLAPEYL
660 670 680 690 700
PTMSSTDMYH NTTFDWAFLS KKECSKYGGN LVGNNCNFVP DITLMSFILF
710 720 730 740 750
LGTYTSSMAL KKFKTSPYFP TTARKLISDF AIILSILIFC VIDALVGVDT
760 770 780 790 800
PKLIVPSEFK PTSPNRGWFV PPFGENPWWV CLAAAIPALL VTILIFMDQQ
810 820 830 840 850
ITAVIVNRKE HKLKKGAGYH LDLFWVAILM VICSLMALPW 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 SKPSDRERSP TFLERHTSC
Length:1,079
Mass (Da):121,461
Last modified:November 1, 1999 - v1
Checksum:i14B981A94DD64293
GO
Isoform 2 (identifier: Q9Y6R1-2) [UniParc]FASTAAdd to basket
Also known as: hkNBC, hkNBCe1, kNBC, kNBC1, kNBC-1, NBC1a

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

Show »
Length:1,035
Mass (Da):116,040
Checksum:i122096381B33D776
GO
Isoform 3 (identifier: Q9Y6R1-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-44: Missing.
     45-85: HKRKTGHKEK...SSSSILKPLI → MSTENVEGKP...FNHSIFTSAV
     635-690: ANISISNDTT...LVGNNCNFVP → GEGITLCVYA...EFDVSLPEVF
     691-1079: Missing.

Show »
Length:646
Mass (Da):72,049
Checksum:i285D5E23C540A516
GO
Isoform 4 (identifier: Q9Y6R1-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     813-896: Missing.

Show »
Length:995
Mass (Da):112,272
Checksum:i38B4A37EA047E9AC
GO
Isoform 5 (identifier: Q9Y6R1-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1034-1079: SDCPYSEKVP...PTFLERHTSC → EKDHQHSLNA...WRSKGTETTL

Show »
Length:1,094
Mass (Da):123,181
Checksum:iB02FF2193A5F95C9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6V → A in AAG47773 (PubMed:12907161).Curated1
Sequence conflicti49T → A in BAH58226 (Ref. 6) Curated1
Sequence conflicti78S → G in AAF21718 (PubMed:10069984).Curated1
Sequence conflicti256S → F in AAD42020 (PubMed:10069984).Curated1
Sequence conflicti263D → E in AAF21718 (PubMed:10069984).Curated1
Sequence conflicti298P → H in BAH58226 (Ref. 6) Curated1
Sequence conflicti364H → R in AAF21719 (PubMed:10069984).Curated1
Sequence conflicti605I → V in AAF21718 (PubMed:10069984).Curated1
Sequence conflicti654S → P in AAF21718 (PubMed:10069984).Curated1
Sequence conflicti749D → G in AAF21719 (PubMed:10069984).Curated1
Sequence conflicti799Q → R in AAG47773 (PubMed:12907161).Curated1
Sequence conflicti856K → R in AAG47773 (PubMed:12907161).Curated1
Sequence conflicti912M → R in AAF21718 (PubMed:10069984).Curated1
Sequence conflicti913G → R in AAF21719 (PubMed:10069984).Curated1
Sequence conflicti940I → V in AAF21718 (PubMed:10069984).Curated1
Sequence conflicti1007P → S in AAF21719 (PubMed:10069984).Curated1
Sequence conflicti1069S → P in AAF21719 (PubMed:10069984).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_024751342R → S in pRTA-OA; decreased localization to the basolateral membrane; mistargeting to the apical membrane probably explains the loss of the cotransporter activity. 1 Publication3 PublicationsCorresponds to variant rs121908856dbSNPEnsembl.1
Natural variantiVAR_024752471S → L in pRTA-OA; mistargeting to the apical membrane and altered function. 2 Publications1
Natural variantiVAR_024753529T → S in pRTA-OA; decreased cotransporter activity. 1 Publication1 Publication1
Natural variantiVAR_071661530G → R in pRTA-OA; decreased cotransporter activity; no effect on localization to the basolateral membrane. 1 Publication1
Natural variantiVAR_024754554R → H in pRTA-OA; mistargeting and altered function. 3 PublicationsCorresponds to variant rs121908857dbSNPEnsembl.1
Natural variantiVAR_071662566L → P in pRTA-OA; loss of localization to the plasma membrane; the retention in the cytoplasm probably explains the loss of the cotransporter activity. 1 Publication1 Publication1
Natural variantiVAR_024755843A → V in pRTA-OA; altered function. 1 Publication1
Natural variantiVAR_024756925R → C in pRTA-OA; altered function. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0167041 – 44Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST44
Alternative sequenceiVSP_01670545 – 85HKRKT…LKPLI → MSTENVEGKPSNLGERGRAR SSTFLRVVQPMFNHSIFTSA V in isoform 2 and isoform 3. 2 PublicationsAdd BLAST41
Alternative sequenceiVSP_016706635 – 690ANISI…CNFVP → GEGITLCVYARFVFGGRCRL HACKFSTCCHGPQELVLFFS LKNSATEFDVSLPEVF in isoform 3. 1 PublicationAdd BLAST56
Alternative sequenceiVSP_016707691 – 1079Missing in isoform 3. 1 PublicationAdd BLAST389
Alternative sequenceiVSP_016708813 – 896Missing in isoform 4. 1 PublicationAdd BLAST84
Alternative sequenceiVSP_0410031034 – 1079SDCPY…RHTSC → EKDHQHSLNATHHADKIPFL QSLGMPSPPRTPVKVVPQIR IELEPEDNDYFWRSKGTETT L in isoform 5. 1 PublicationAdd BLAST46

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF007216 mRNA. Translation: AAC51645.1.
AF011390 mRNA. Translation: AAC39840.1.
AF053753 mRNA. Translation: AAF21718.1.
AF053754 mRNA. Translation: AAF21719.1.
AF069510 mRNA. Translation: AAD42020.1.
AF310248 mRNA. Translation: AAG47773.1.
AF157492 mRNA. Translation: AAF80343.1.
AB470072 mRNA. Translation: BAH58226.1.
AC019089 Genomic DNA. No translation available.
AC079230 Genomic DNA. No translation available.
AC096713 Genomic DNA. No translation available.
AC110783 Genomic DNA. No translation available.
AC112226 Genomic DNA. No translation available.
BC030977 mRNA. Translation: AAH30977.1.
CCDSiCCDS3549.1. [Q9Y6R1-2]
CCDS43236.1. [Q9Y6R1-1]
CCDS47071.1. [Q9Y6R1-5]
RefSeqiNP_001091954.1. NM_001098484.2. [Q9Y6R1-1]
NP_003750.1. NM_003759.3. [Q9Y6R1-2]
UniGeneiHs.5462.

Genome annotation databases

EnsembliENST00000264485; ENSP00000264485; ENSG00000080493. [Q9Y6R1-1]
ENST00000340595; ENSP00000344272; ENSG00000080493. [Q9Y6R1-2]
ENST00000351898; ENSP00000307349; ENSG00000080493. [Q9Y6R1-4]
ENST00000425175; ENSP00000393557; ENSG00000080493. [Q9Y6R1-5]
ENST00000512686; ENSP00000422400; ENSG00000080493. [Q9Y6R1-3]
GeneIDi8671.
KEGGihsa:8671.
UCSCiuc003hfy.4. human. [Q9Y6R1-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF007216 mRNA. Translation: AAC51645.1.
AF011390 mRNA. Translation: AAC39840.1.
AF053753 mRNA. Translation: AAF21718.1.
AF053754 mRNA. Translation: AAF21719.1.
AF069510 mRNA. Translation: AAD42020.1.
AF310248 mRNA. Translation: AAG47773.1.
AF157492 mRNA. Translation: AAF80343.1.
AB470072 mRNA. Translation: BAH58226.1.
AC019089 Genomic DNA. No translation available.
AC079230 Genomic DNA. No translation available.
AC096713 Genomic DNA. No translation available.
AC110783 Genomic DNA. No translation available.
AC112226 Genomic DNA. No translation available.
BC030977 mRNA. Translation: AAH30977.1.
CCDSiCCDS3549.1. [Q9Y6R1-2]
CCDS43236.1. [Q9Y6R1-1]
CCDS47071.1. [Q9Y6R1-5]
RefSeqiNP_001091954.1. NM_001098484.2. [Q9Y6R1-1]
NP_003750.1. NM_003759.3. [Q9Y6R1-2]
UniGeneiHs.5462.

3D structure databases

ProteinModelPortaliQ9Y6R1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114219. 1 interactor.
DIPiDIP-59373N.
IntActiQ9Y6R1. 4 interactors.
STRINGi9606.ENSP00000393557.

Chemistry databases

DrugBankiDB01390. Sodium bicarbonate.

Protein family/group databases

TCDBi2.A.31.2.12. the anion exchanger (ae) family.

PTM databases

iPTMnetiQ9Y6R1.
PhosphoSitePlusiQ9Y6R1.
SwissPalmiQ9Y6R1.

Polymorphism and mutation databases

BioMutaiSLC4A4.
DMDMi74721543.

Proteomic databases

PaxDbiQ9Y6R1.
PeptideAtlasiQ9Y6R1.
PRIDEiQ9Y6R1.

Protocols and materials databases

DNASUi8671.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264485; ENSP00000264485; ENSG00000080493. [Q9Y6R1-1]
ENST00000340595; ENSP00000344272; ENSG00000080493. [Q9Y6R1-2]
ENST00000351898; ENSP00000307349; ENSG00000080493. [Q9Y6R1-4]
ENST00000425175; ENSP00000393557; ENSG00000080493. [Q9Y6R1-5]
ENST00000512686; ENSP00000422400; ENSG00000080493. [Q9Y6R1-3]
GeneIDi8671.
KEGGihsa:8671.
UCSCiuc003hfy.4. human. [Q9Y6R1-1]

Organism-specific databases

CTDi8671.
DisGeNETi8671.
GeneCardsiSLC4A4.
HGNCiHGNC:11030. SLC4A4.
HPAiCAB022493.
HPA035628.
HPA035629.
MalaCardsiSLC4A4.
MIMi603345. gene.
604278. phenotype.
neXtProtiNX_Q9Y6R1.
OpenTargetsiENSG00000080493.
Orphaneti93607. Autosomal recessive proximal renal tubular acidosis.
PharmGKBiPA35898.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1172. Eukaryota.
ENOG410XPHD. LUCA.
GeneTreeiENSGT00760000119021.
HOVERGENiHBG004326.
InParanoidiQ9Y6R1.
KOiK13575.
OMAiVCSFMAL.
PhylomeDBiQ9Y6R1.
TreeFamiTF313630.

Enzyme and pathway databases

ReactomeiR-HSA-425381. Bicarbonate transporters.

Miscellaneous databases

ChiTaRSiSLC4A4. human.
GeneWikiiSLC4A4.
GenomeRNAii8671.
PROiQ9Y6R1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000080493.
CleanExiHS_SLC4A4.
ExpressionAtlasiQ9Y6R1. baseline and differential.
GenevisibleiQ9Y6R1. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: Q9Y6R1
Secondary accession number(s): C4B714
, O15153, Q8NEJ2, Q9H262, Q9NRZ1, Q9UIC0, Q9UIC1, Q9UP50
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: November 1, 1999
Last modified: November 30, 2016
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.