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Q9Y6R1

- S4A4_HUMAN

UniProt

Q9Y6R1 - S4A4_HUMAN

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Protein
Electrogenic sodium bicarbonate cotransporter 1
Gene
SLC4A4, NBC, NBC1, NBCE1
Organism
Homo sapiens (Human)
Status
Reviewed - 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.4 Publications

Enzyme regulationi

Inhibited by stilbene derivatives and regulated by cyclic AMP.

GO - Molecular functioni

  1. inorganic anion exchanger activity Source: InterPro
  2. protein binding Source: DFLAT
  3. sodium:bicarbonate symporter activity Source: ProtInc

GO - Biological processi

  1. bicarbonate transport Source: Reactome
  2. ion transport Source: Reactome
  3. sodium ion transmembrane transport Source: GOC
  4. transmembrane transport Source: Reactome
  5. transport Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Ion transport, Sodium transport, Symport, Transport

Keywords - Ligandi

Sodium

Enzyme and pathway databases

ReactomeiREACT_19298. 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
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:11030. SLC4A4.

Subcellular locationi

Basolateral cell membrane; Multi-pass membrane protein 2 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 468468Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei469 – 48820Helical; Reviewed prediction
Add
BLAST
Topological domaini489 – 50416Extracellular Reviewed prediction
Add
BLAST
Transmembranei505 – 52622Helical; Reviewed prediction
Add
BLAST
Topological domaini527 – 55428Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei555 – 58026Helical; Reviewed prediction
Add
BLAST
Topological domaini581 – 691111Extracellular Reviewed prediction
Add
BLAST
Transmembranei692 – 71019Helical; Reviewed prediction
Add
BLAST
Topological domaini711 – 72515Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei726 – 74823Helical; Reviewed prediction
Add
BLAST
Topological domaini749 – 77729Extracellular Reviewed prediction
Add
BLAST
Transmembranei778 – 79720Helical; Reviewed prediction
Add
BLAST
Topological domaini798 – 82225Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei823 – 84725Helical; Reviewed prediction
Add
BLAST
Topological domaini848 – 88134Extracellular Reviewed prediction
Add
BLAST
Transmembranei882 – 90120Helical; Reviewed prediction
Add
BLAST
Topological domaini902 – 94948Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei950 – 96718Helical; Reviewed prediction
Add
BLAST
Topological domaini968 – 9703Extracellular Reviewed prediction
Transmembranei971 – 98616Helical; Reviewed prediction
Add
BLAST
Topological domaini987 – 107993Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. basolateral plasma membrane Source: UniProtKB-SubCell
  2. extracellular vesicular exosome Source: UniProt
  3. integral component of plasma membrane Source: ProtInc
  4. 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) [MIM:604278]: An 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti342 – 3421R → S in pRTA-OA; mistargeting and altered function. 3 Publications
VAR_024751
Natural varianti471 – 4711S → L in pRTA-OA; mistargeting to the apical membrane and altered function. 2 Publications
VAR_024752
Natural varianti529 – 5291T → S in pRTA-OA; mistargeting and altered function. 1 Publication
VAR_024753
Natural varianti554 – 5541R → H in pRTA-OA; mistargeting and altered function. 3 Publications
VAR_024754
Natural varianti843 – 8431A → V in pRTA-OA; altered function. 1 Publication
VAR_024755
Natural varianti925 – 9251R → C in pRTA-OA; altered function. 1 Publication
VAR_024756
Loss of interaction with and stimulation by CA4 is the cause of retinitis pigmentosa type 17 (RP17).

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi49 – 491T → A: Loss of conductance regulation by cAMP; isoform 1. 1 Publication
Mutagenesisi49 – 491T → D: Loss of conductance regulation by cAMP; isoform 1. 1 Publication
Mutagenesisi135 – 1351E → R: Mistargeting and altered function. 1 Publication
Mutagenesisi477 – 4771Y → F: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi493 – 4931D → N: Prevents membrane targeting. 1 Publication
Mutagenesisi494 – 4941A → K: Prevents membrane targeting. 1 Publication
Mutagenesisi503 – 5031E → Q: Strong reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi504 – 5041S → L: Prevents membrane targeting. 1 Publication
Mutagenesisi536 – 5361E → Q: Prevents membrane targeting. 1 Publication
Mutagenesisi552 – 5521E → N: Prevents membrane targeting. 1 Publication
Mutagenesisi554 – 5541R → D: Prevents membrane targeting. 1 Publication
Mutagenesisi582 – 5821R → N: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi582 – 5821R → Q: Strong reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi586 – 5861E → Q: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi599 – 5991D → N: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi600 – 6001A → T: Strong reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi602 – 6021K → Q: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi603 – 6031K → Q: Strong reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi691 – 6911D → R: Strong reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi700 – 7001F → M: Strong reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi711 – 7111K → E, N or Q: Strong reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi711 – 7111K → R: No effect on the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi712 – 7121K → N: Strong reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi714 – 7141K → Q: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi715 – 7151T → N: Strong reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi721 – 7211T → G: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi724 – 7241R → E: Strong reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi725 – 7251K → N: Strong reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi728 – 7281S → G: Strong reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi729 – 7291D → N or R: Strong reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi743 – 7431D → K or N: Prevents membrane targeting. 1 Publication
Mutagenesisi749 – 7491D → N: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi752 – 7521K → Q: Prevents membrane targeting. 1 Publication
Mutagenesisi766 – 7661R → Q: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi767 – 7671G → T: Alters interaction with CA4. 1 Publication
Mutagenesisi775 – 7751E → N: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi798 – 7981D → E, N or R: Strong reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi808 – 8092RK → NN: Strong reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi814 – 8152KK → NN: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi820 – 8201H → D, N, S or R: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi822 – 8221D → N: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi851 – 8511H → N: Prevents membrane targeting. 1 Publication
Mutagenesisi853 – 8531D → N: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi858 – 8603ETE → MSK: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi875 – 8773EQR → QQQ: Prevents membrane targeting. 1 Publication
Mutagenesisi875 – 8751E → Q: Strong reduction of the sodium-dependent ion transport activity.
Mutagenesisi898 – 8981K → E: Strong reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi925 – 9273RLK → NLN: Prevents membrane targeting. 1 Publication
Mutagenesisi948 – 9481R → E: Strong reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi949 – 9491R → E: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi951 – 9511H → D: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi951 – 9511H → N or R: Prevents membrane targeting. 1 Publication
Mutagenesisi968 – 9681K → Q: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi987 – 9871R → E or N: Moderate reduction of the sodium-dependent ion transport activity. 1 Publication
Mutagenesisi1002 – 10021L → N: Partial loss of interaction with CA2.
Mutagenesisi1003 – 10031D → N: Abolishes interaction with CA2.
Mutagenesisi1004 – 10041D → N: Partial loss of interaction with CA2.
Mutagenesisi1026 – 10261S → A: Prevents phosphorylation by PKA. Loss of regulation by cAMP of the transporter stoichiometry. 2 Publications
Mutagenesisi1026 – 10261S → D: Loss of regulation by cAMP of the transporter stoichiometry. Shifts transporter stoichiometry from 3:1 to 2:1. 2 Publications
Mutagenesisi1030 – 10334DNDD → NNNN: Abolishes interaction with CA2. 2 Publications
Mutagenesisi1030 – 10301D → N: Loss of regulation by cAMP of the transporter stoichiometry. Abolishes interaction with CA2. 1 Publication
Mutagenesisi1032 – 10321D → N: Loss of regulation by cAMP of the transporter stoichiometry. Partial loss of interaction with CA2. 1 Publication
Mutagenesisi1033 – 10331D → N: No effect on regulation by cAMP of the transporter stoichiometry. Partial loss of interaction with CA2. 1 Publication
Mutagenesisi1057 – 10571F → A: Targeting to apical membrane. 1 Publication

Keywords - Diseasei

Disease mutation, Retinitis pigmentosa

Organism-specific databases

MIMi604278. phenotype.
Orphaneti93607. Autosomal recessive proximal renal tubular acidosis.
PharmGKBiPA35898.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10791079Electrogenic sodium bicarbonate cotransporter 1
PRO_0000079227Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei30 – 301Phosphotyrosine By similarity
Modified residuei49 – 491Phosphothreonine; by PKA1 Publication
Modified residuei254 – 2541Phosphothreonine By similarity
Modified residuei257 – 2571Phosphoserine By similarity
Modified residuei262 – 2621Phosphoserine By similarity
Glycosylationi641 – 6411N-linked (GlcNAc...) By similarity
Glycosylationi661 – 6611N-linked (GlcNAc...) By similarity
Modified residuei1026 – 10261Phosphoserine; by PKA1 Publication
Modified residuei1029 – 10291Phosphoserine By similarity
Modified residuei1034 – 10341Phosphoserine By 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. Phosphorylation of Thr-49 regulates isoform 1 conductance.
N-glycosylation is not necessary for the transporter basic functions.

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ9Y6R1.
PaxDbiQ9Y6R1.
PRIDEiQ9Y6R1.

PTM databases

PhosphoSiteiQ9Y6R1.

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

ArrayExpressiQ9Y6R1.
BgeeiQ9Y6R1.
CleanExiHS_SLC4A4.
GenevestigatoriQ9Y6R1.

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.4 Publications

Binary interactionsi

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

Protein-protein interaction databases

BioGridi114219. 1 interaction.
DIPiDIP-59373N.
IntActiQ9Y6R1. 4 interactions.
STRINGi9606.ENSP00000393557.

Structurei

3D structure databases

ProteinModelPortaliQ9Y6R1.
SMRiQ9Y6R1. Positions 107-382, 453-493.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni748 – 77932Interaction with CA4
Add
BLAST
Regioni1002 – 10043CA2-binding
Regioni1030 – 10334CA2-binding
Regioni1057 – 10593Required for basolateral targeting

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi1009 – 102416Lys-rich
Add
BLAST

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG251607.
HOVERGENiHBG004326.
InParanoidiQ9Y6R1.
KOiK13575.
OMAiVCSFMAL.
OrthoDBiEOG7TMZR0.
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. 1 hit.
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. Align

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

MEDEAVLDRG ASFLKHVCDE EEVEGHHTIY IGVHVPKSYR RRRRHKRKTG     50
HKEKKEKERI SENYSDKSDI ENADESSSSI LKPLISPAAE RIRFILGEED 100
DSPAPPQLFT ELDELLAVDG QEMEWKETAR WIKFEEKVEQ GGERWSKPHV 150
ATLSLHSLFE LRTCMEKGSI MLDREASSLP QLVEMIVDHQ IETGLLKPEL 200
KDKVTYTLLR KHRHQTKKSN LRSLADIGKT VSSASRMFTN PDNGSPAMTH 250
RNLTSSSLND ISDKPEKDQL KNKFMKKLPR DAEASNVLVG EVDFLDTPFI 300
AFVRLQQAVM LGALTEVPVP TRFLFILLGP KGKAKSYHEI GRAIATLMSD 350
EVFHDIAYKA KDRHDLIAGI DEFLDEVIVL PPGEWDPAIR IEPPKSLPSS 400
DKRKNMYSGG ENVQMNGDTP HDGGHGGGGH GDCEELQRTG RFCGGLIKDI 450
KRKAPFFASD FYDALNIQAL SAILFIYLAT VTNAITFGGL LGDATDNMQG 500
VLESFLGTAV SGAIFCLFAG QPLTILSSTG PVLVFERLLF NFSKDNNFDY 550
LEFRLWIGLW SAFLCLILVA TDASFLVQYF TRFTEEGFSS LISFIFIYDA 600
FKKMIKLADY YPINSNFKVG YNTLFSCTCV PPDPANISIS NDTTLAPEYL 650
PTMSSTDMYH NTTFDWAFLS KKECSKYGGN LVGNNCNFVP DITLMSFILF 700
LGTYTSSMAL KKFKTSPYFP TTARKLISDF AIILSILIFC VIDALVGVDT 750
PKLIVPSEFK PTSPNRGWFV PPFGENPWWV CLAAAIPALL VTILIFMDQQ 800
ITAVIVNRKE HKLKKGAGYH LDLFWVAILM VICSLMALPW YVAATVISIA 850
HIDSLKMETE TSAPGEQPKF LGVREQRVTG TLVFILTGLS VFMAPILKFI 900
PMPVLYGVFL YMGVASLNGV QFMDRLKLLL MPLKHQPDFI YLRHVPLRRV 950
HLFTFLQVLC LALLWILKST VAAIIFPVMI LALVAVRKGM DYLFSQHDLS 1000
FLDDVIPEKD KKKKEDEKKK KKKKGSLDSD NDDSDCPYSE KVPSIKIPMD 1050
IMEQQPFLSD SKPSDRERSP TFLERHTSC 1079
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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti342 – 3421R → S in pRTA-OA; mistargeting and altered function. 3 Publications
VAR_024751
Natural varianti471 – 4711S → L in pRTA-OA; mistargeting to the apical membrane and altered function. 2 Publications
VAR_024752
Natural varianti529 – 5291T → S in pRTA-OA; mistargeting and altered function. 1 Publication
VAR_024753
Natural varianti554 – 5541R → H in pRTA-OA; mistargeting and altered function. 3 Publications
VAR_024754
Natural varianti843 – 8431A → V in pRTA-OA; altered function. 1 Publication
VAR_024755
Natural varianti925 – 9251R → C in pRTA-OA; altered function. 1 Publication
VAR_024756

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4444Missing in isoform 2 and isoform 3.
VSP_016704Add
BLAST
Alternative sequencei45 – 8541HKRKT…LKPLI → MSTENVEGKPSNLGERGRAR SSTFLRVVQPMFNHSIFTSA V in isoform 2 and isoform 3.
VSP_016705Add
BLAST
Alternative sequencei635 – 69056ANISI…CNFVP → GEGITLCVYARFVFGGRCRL HACKFSTCCHGPQELVLFFS LKNSATEFDVSLPEVF in isoform 3.
VSP_016706Add
BLAST
Alternative sequencei691 – 1079389Missing in isoform 3.
VSP_016707Add
BLAST
Alternative sequencei813 – 89684Missing in isoform 4.
VSP_016708Add
BLAST
Alternative sequencei1034 – 107946SDCPY…RHTSC → EKDHQHSLNATHHADKIPFL QSLGMPSPPRTPVKVVPQIR IELEPEDNDYFWRSKGTETT L in isoform 5.
VSP_041003Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti6 – 61V → A in AAG47773. 1 Publication
Sequence conflicti49 – 491T → A in BAH58226. 1 Publication
Sequence conflicti78 – 781S → G in AAF21718. 1 Publication
Sequence conflicti256 – 2561S → F in AAD42020. 1 Publication
Sequence conflicti263 – 2631D → E in AAF21718. 1 Publication
Sequence conflicti298 – 2981P → H in BAH58226. 1 Publication
Sequence conflicti364 – 3641H → R in AAF21719. 1 Publication
Sequence conflicti605 – 6051I → V in AAF21718. 1 Publication
Sequence conflicti654 – 6541S → P in AAF21718. 1 Publication
Sequence conflicti749 – 7491D → G in AAF21719. 1 Publication
Sequence conflicti799 – 7991Q → R in AAG47773. 1 Publication
Sequence conflicti856 – 8561K → R in AAG47773. 1 Publication
Sequence conflicti912 – 9121M → R in AAF21718. 1 Publication
Sequence conflicti913 – 9131G → R in AAF21719. 1 Publication
Sequence conflicti940 – 9401I → V in AAF21718. 1 Publication
Sequence conflicti1007 – 10071P → S in AAF21719. 1 Publication
Sequence conflicti1069 – 10691S → P in AAF21719. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.3. human. [Q9Y6R1-1]
uc003hga.2. human. [Q9Y6R1-3]
uc003hgc.4. human. [Q9Y6R1-2]
uc010iib.3. human. [Q9Y6R1-4]

Polymorphism databases

DMDMi74721543.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS3549.1. [Q9Y6R1-2 ]
CCDS43236.1. [Q9Y6R1-1 ]
CCDS47071.1. [Q9Y6R1-5 ]
RefSeqi NP_001091954.1. NM_001098484.2. [Q9Y6R1-1 ]
NP_003750.1. NM_003759.3. [Q9Y6R1-2 ]
UniGenei Hs.5462.

3D structure databases

ProteinModelPortali Q9Y6R1.
SMRi Q9Y6R1. Positions 107-382, 453-493.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114219. 1 interaction.
DIPi DIP-59373N.
IntActi Q9Y6R1. 4 interactions.
STRINGi 9606.ENSP00000393557.

Protein family/group databases

TCDBi 2.A.31.2.12. the anion exchanger (ae) family.

PTM databases

PhosphoSitei Q9Y6R1.

Polymorphism databases

DMDMi 74721543.

Proteomic databases

MaxQBi Q9Y6R1.
PaxDbi Q9Y6R1.
PRIDEi Q9Y6R1.

Protocols and materials databases

DNASUi 8671.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000264485 ; ENSP00000264485 ; ENSG00000080493 . [Q9Y6R1-1 ]
ENST00000340595 ; ENSP00000344272 ; ENSG00000080493 . [Q9Y6R1-2 ]
ENST00000351898 ; ENSP00000307349 ; ENSG00000080493 . [Q9Y6R1-4 ]
ENST00000425175 ; ENSP00000393557 ; ENSG00000080493 . [Q9Y6R1-5 ]
ENST00000512686 ; ENSP00000422400 ; ENSG00000080493 . [Q9Y6R1-3 ]
GeneIDi 8671.
KEGGi hsa:8671.
UCSCi uc003hfy.3. human. [Q9Y6R1-1 ]
uc003hga.2. human. [Q9Y6R1-3 ]
uc003hgc.4. human. [Q9Y6R1-2 ]
uc010iib.3. human. [Q9Y6R1-4 ]

Organism-specific databases

CTDi 8671.
GeneCardsi GC04P072017.
HGNCi HGNC:11030. SLC4A4.
HPAi CAB022493.
HPA035628.
HPA035629.
MIMi 603345. gene.
604278. phenotype.
neXtProti NX_Q9Y6R1.
Orphaneti 93607. Autosomal recessive proximal renal tubular acidosis.
PharmGKBi PA35898.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG251607.
HOVERGENi HBG004326.
InParanoidi Q9Y6R1.
KOi K13575.
OMAi VCSFMAL.
OrthoDBi EOG7TMZR0.
PhylomeDBi Q9Y6R1.
TreeFami TF313630.

Enzyme and pathway databases

Reactomei REACT_19298. Bicarbonate transporters.

Miscellaneous databases

ChiTaRSi SLC4A4. human.
GeneWikii SLC4A4.
GenomeRNAii 8671.
NextBioi 32523.
PROi Q9Y6R1.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9Y6R1.
Bgeei Q9Y6R1.
CleanExi HS_SLC4A4.
Genevestigatori Q9Y6R1.

Family and domain databases

Gene3Di 3.40.1100.10. 1 hit.
InterProi IPR013769. Band3_cytoplasmic_dom.
IPR011531. HCO3_transpt_C.
IPR003020. HCO3_transpt_euk.
IPR003024. Na/HCO3_transpt.
IPR016152. PTrfase/Anion_transptr.
[Graphical view ]
PANTHERi PTHR11453. PTHR11453. 1 hit.
Pfami PF07565. Band_3_cyto. 1 hit.
PF00955. HCO3_cotransp. 1 hit.
[Graphical view ]
PRINTSi PR01231. HCO3TRNSPORT.
PR01232. NAHCO3TRSPRT.
SUPFAMi SSF55804. SSF55804. 1 hit.
TIGRFAMsi TIGR00834. ae. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and functional expression of a human kidney Na+:HCO3-cotransporter."
    Burnham C.E., Amlal H., Wang Z., Shull G.E., Soleimani M.
    J. Biol. Chem. 272:19111-19114(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY.
    Tissue: Kidney.
  2. "Molecular cloning, chromosomal localization, tissue distribution, and functional expression of the human pancreatic sodium bicarbonate cotransporter."
    Abuladze N., Lee I., Newman D., Hwang J., Boorer K., Pushkin A., Kurtz I.
    J. Biol. Chem. 273:17689-17695(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
    Tissue: Pancreas.
  3. "Cloning and characterization of a human electrogenic Na+-HCO-3 cotransporter isoform (hhNBC)."
    Choi I., Romero M.F., Khandoudi N., Bril A., Boron W.F.
    Am. J. Physiol. 276:C576-C584(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
    Tissue: Heart, Kidney and Prostate.
  4. "Identification and cloning of the Na/HCO3- cotransporter (NBC) in human corneal endothelium."
    Sun X.C., Bonanno J.A.
    Exp. Eye Res. 77:287-295(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN CORNEAL ENDOTHELIAL CELLS, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
    Tissue: Corneal endothelium.
  5. "Homo sapiens sodium bicarbonate cotransporter NBC1 splice variant."
    Pushkin A., Abuladze N., Kurtz I.
    Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
    Tissue: Skeletal muscle.
  6. "cDNA cloning and characterization of human sodium bicarbonate cotransporter, bNBC, a brain type splicing variant of SLC4A4 gene."
    Yamada H., Nagayoshi A., Kuroda Y., Mizutani A., Ando H., Seki G., Mikoshiba K.
    Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
  7. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
    Tissue: Kidney.
  9. "Phosphorylation of Ser(982) in the sodium bicarbonate cotransporter kNBC1 shifts the HCO(3)(-):Na(+) stoichiometry from 3:1 to 2:1 in murine proximal tubule cells."
    Gross E., Hawkins K., Pushkin A., Sassani P., Dukkipati R., Abuladze N., Hopfer U., Kurtz I.
    J. Physiol. (Lond.) 537:659-665(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: REGULATION, MUTAGENESIS OF SER-1026, PHOSPHORYLATION AT SER-1026.
  10. Erratum
    Gross E., Hawkins K., Pushkin A., Sassani P., Dukkipati R., Abuladze N., Hopfer U., Kurtz I.
    J. Physiol. (Lond.) 538:1003-1003(2002)
  11. "Expression of a sodium bicarbonate cotransporter in human parotid salivary glands."
    Park K., Hurley P.T., Roussa E., Cooper G.J., Smith C.P., Thevenod F., Steward M.C., Case R.M.
    Arch. Oral Biol. 47:1-9(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  12. "Regulation of the sodium bicarbonate cotransporter kNBC1 function: role of Asp(986), Asp(988) and kNBC1-carbonic anhydrase II binding."
    Gross E., Pushkin A., Abuladze N., Fedotoff O., Kurtz I.
    J. Physiol. (Lond.) 544:679-685(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: REGULATION, MUTAGENESIS OF ASP-1030; ASP-1032 AND ASP-1033, INTERACTION WITH CA2.
  13. "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.
  14. Cited for: TISSUE SPECIFICITY.
  15. "Identification of membrane topography of the electrogenic sodium bicarbonate cotransporter pNBC1 by in vitro transcription/translation."
    Tatishchev S., Abuladze N., Pushkin A., Newman D., Liu W., Weeks D., Sachs G., Kurtz I.
    Biochemistry 42:755-765(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: TOPOLOGY.
  16. "Direct extracellular interaction between carbonic anhydrase IV and the human NBC1 sodium/bicarbonate co-transporter."
    Alvarez B.V., Loiselle F.B., Supuran C.T., Schwartz G.J., Casey J.R.
    Biochemistry 42:12321-12329(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: REGULATION, INTERACTION WITH CA2 AND CA4, MUTAGENESIS OF GLY-767.
  17. "Phosphorylation-induced modulation of pNBC1 function: distinct roles for the amino- and carboxy-termini."
    Gross E., Fedotoff O., Pushkin A., Abuladze N., Newman D., Kurtz I.
    J. Physiol. (Lond.) 549:673-682(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: REGULATION, MUTAGENESIS OF THR-49 AND SER-1026, PHOSPHORYLATION AT THR-49.
  18. "Expression of Na+/HCO3- co-transporter proteins (NBCs) in rat and human skeletal muscle."
    Kristensen J.M., Kristensen M., Juel C.
    Acta Physiol. Scand. 182:69-76(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  19. "Identification of a carboxyl-terminal motif essential for the targeting of Na+-HCO-3 cotransporter NBC1 to the basolateral membrane."
    Li H.C., Worrell R.T., Matthews J.B., Husseinzadeh H., Neumeier L., Petrovic S., Conforti L., Soleimani M.
    J. Biol. Chem. 279:43190-43197(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF PHE-1057, SUBCELLULAR LOCATION.
  20. "Molecular mechanism of kNBC1-carbonic anhydrase II interaction in proximal tubule cells."
    Pushkin A., Abuladze N., Gross E., Newman D., Tatishchev S., Lee I., Fedotoff O., Bondar G., Azimov R., Ngyuen M., Kurtz I.
    J. Physiol. (Lond.) 559:55-65(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CA2, MUTAGENESIS OF 1002-LEU--ASN-1004 AND 1030-ASP--ASP-1033.
  21. Cited for: INTERACTION WITH CA4.
  22. "Critical amino acid residues involved in the electrogenic sodium-bicarbonate cotransporter kNBC1-mediated transport."
    Abuladze N., Azimov R., Newman D., Sassani P., Liu W., Tatishchev S., Pushkin A., Kurtz I.
    J. Physiol. (Lond.) 565:717-730(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF TYR-477; ASP-493; ALA-494; GLU-503; SER-504; GLU-536; GLU-552; ARG-554; ARG-582; GLU-586; ASP-599; ALA-600; LYS-602; LYS-603; ASP-691; PHE-700; LYS-711; LYS-712; LYS-714; THR-715; THR-721; ARG-724; LYS-725; SER-728; ASP-729; ASP-743; ASP-749; LYS-752; ARG-766; GLU-775; ASP-798; 808-ARG--LYS-809; 814-LYS--LYS-815; HIS-820; ASP-822; HIS-851; ASP-853; 858-GLU--GLU-860; 875-GLU--ARG-877; LYS-898; 925-ARG--LYS-927; ARG-948; ARG-949; HIS-951; LYS-968 AND ARG-987.
  23. "Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities."
    Igarashi T., Inatomi J., Sekine T., Cha S.H., Kanai Y., Kunimi M., Tsukamoto K., Satoh H., Shimadzu M., Tozawa F., Mori T., Shiobara M., Seki G., Endou H.
    Nat. Genet. 23:264-266(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS PRTA-OA SER-342 AND HIS-554.
  24. "A novel missense mutation in the sodium bicarbonate cotransporter (NBCe1/SLC4A4) causes proximal tubular acidosis and glaucoma through ion transport defects."
    Dinour D., Chang M.-H., Satoh J., Smith B.L., Angle N., Knecht A., Serban I., Holtzman E.J., Romero M.F.
    J. Biol. Chem. 279:52238-52246(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT PRTA-OA LEU-471.
  25. "Missense mutations in Na+:HCO3- cotransporter NBC1 show abnormal trafficking in polarized kidney cells: a basis of proximal renal tubular acidosis."
    Li H.C., Szigligeti P., Worrell R.T., Matthews J.B., Conforti L., Soleimani M.
    Am. J. Physiol. 289:F61-F71(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS PRTA-OA SER-342; LEU-471 AND HIS-554, MUTAGENESIS OF GLU-135.
  26. "Functional analysis of NBC1 mutants associated with proximal renal tubular acidosis and ocular abnormalities."
    Horita S., Yamada H., Inatomi J., Moriyama N., Sekine T., Igarashi T., Endo Y., Dasouki M., Ekim M., Al-Gazali L., Shimadzu M., Seki G., Fujita T.
    J. Am. Soc. Nephrol. 16:2270-2278(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS PRTA-OA SER-342; SER-529; HIS-554; VAL-843 AND CYS-925.

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: September 3, 2014
This is version 116 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

External Data

Dasty 3

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