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Q9Y6R1 (S4A4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:SLC4A4
Synonyms:NBC, NBC1, NBCE1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1079 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.2 Ref.3 Ref.4

Enzyme regulation

Inhibited by stilbene derivatives and regulated by cyclic AMP.

Subunit structure

Interacts with CA2/carbonic anhydrase 2 and CA4/carbonic anhydrase 4 which may regulate transporter activity. Ref.12 Ref.16 Ref.20 Ref.21

Subcellular location

Basolateral cell membrane; Multi-pass membrane protein Ref.4 Ref.19.

Tissue specificity

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. Ref.1 Ref.2 Ref.3 Ref.4 Ref.11 Ref.14 Ref.18

Post-translational modification

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.

Involvement in disease

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.

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

Sequence similarities

Belongs to the anion exchanger (TC 2.A.31) family. [View classification]

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CA4P482832EBI-6859278,EBI-6859264From a different organism.

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9Y6R1-1)

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.
Isoform 2 (identifier: Q9Y6R1-2)

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
Isoform 3 (identifier: Q9Y6R1-3)

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.
Isoform 4 (identifier: Q9Y6R1-4)

The sequence of this isoform differs from the canonical sequence as follows:
     813-896: Missing.
Isoform 5 (identifier: Q9Y6R1-5)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10791079Electrogenic sodium bicarbonate cotransporter 1
PRO_0000079227

Regions

Topological domain1 – 468468Cytoplasmic Potential
Transmembrane469 – 48820Helical; Potential
Topological domain489 – 50416Extracellular Potential
Transmembrane505 – 52622Helical; Potential
Topological domain527 – 55428Cytoplasmic Potential
Transmembrane555 – 58026Helical; Potential
Topological domain581 – 691111Extracellular Potential
Transmembrane692 – 71019Helical; Potential
Topological domain711 – 72515Cytoplasmic Potential
Transmembrane726 – 74823Helical; Potential
Topological domain749 – 77729Extracellular Potential
Transmembrane778 – 79720Helical; Potential
Topological domain798 – 82225Cytoplasmic Potential
Transmembrane823 – 84725Helical; Potential
Topological domain848 – 88134Extracellular Potential
Transmembrane882 – 90120Helical; Potential
Topological domain902 – 94948Cytoplasmic Potential
Transmembrane950 – 96718Helical; Potential
Topological domain968 – 9703Extracellular Potential
Transmembrane971 – 98616Helical; Potential
Topological domain987 – 107993Cytoplasmic Potential
Region748 – 77932Interaction with CA4
Region1002 – 10043CA2-binding
Region1030 – 10334CA2-binding
Region1057 – 10593Required for basolateral targeting
Compositional bias1009 – 102416Lys-rich

Amino acid modifications

Modified residue301Phosphotyrosine By similarity
Modified residue491Phosphothreonine; by PKA Ref.17
Modified residue2541Phosphothreonine By similarity
Modified residue2571Phosphoserine By similarity
Modified residue2621Phosphoserine By similarity
Modified residue10261Phosphoserine; by PKA Ref.9
Modified residue10291Phosphoserine By similarity
Modified residue10341Phosphoserine By similarity
Glycosylation6411N-linked (GlcNAc...) By similarity
Glycosylation6611N-linked (GlcNAc...) By similarity

Natural variations

Alternative sequence1 – 4444Missing in isoform 2 and isoform 3.
VSP_016704
Alternative sequence45 – 8541HKRKT…LKPLI → MSTENVEGKPSNLGERGRAR SSTFLRVVQPMFNHSIFTSA V in isoform 2 and isoform 3.
VSP_016705
Alternative sequence635 – 69056ANISI…CNFVP → GEGITLCVYARFVFGGRCRL HACKFSTCCHGPQELVLFFS LKNSATEFDVSLPEVF in isoform 3.
VSP_016706
Alternative sequence691 – 1079389Missing in isoform 3.
VSP_016707
Alternative sequence813 – 89684Missing in isoform 4.
VSP_016708
Alternative sequence1034 – 107946SDCPY…RHTSC → EKDHQHSLNATHHADKIPFL QSLGMPSPPRTPVKVVPQIR IELEPEDNDYFWRSKGTETT L in isoform 5.
VSP_041003
Natural variant3421R → S in pRTA-OA; mistargeting and altered function. Ref.23 Ref.25 Ref.26
VAR_024751
Natural variant4711S → L in pRTA-OA; mistargeting to the apical membrane and altered function. Ref.24 Ref.25
VAR_024752
Natural variant5291T → S in pRTA-OA; mistargeting and altered function. Ref.26
VAR_024753
Natural variant5541R → H in pRTA-OA; mistargeting and altered function. Ref.23 Ref.25 Ref.26
VAR_024754
Natural variant8431A → V in pRTA-OA; altered function. Ref.26
VAR_024755
Natural variant9251R → C in pRTA-OA; altered function. Ref.26
VAR_024756

Experimental info

Mutagenesis491T → A: Loss of conductance regulation by cAMP; isoform 1. Ref.17
Mutagenesis491T → D: Loss of conductance regulation by cAMP; isoform 1. Ref.17
Mutagenesis1351E → R: Mistargeting and altered function. Ref.25
Mutagenesis4771Y → F: Moderate reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis4931D → N: Prevents membrane targeting. Ref.22
Mutagenesis4941A → K: Prevents membrane targeting. Ref.22
Mutagenesis5031E → Q: Strong reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis5041S → L: Prevents membrane targeting. Ref.22
Mutagenesis5361E → Q: Prevents membrane targeting. Ref.22
Mutagenesis5521E → N: Prevents membrane targeting. Ref.22
Mutagenesis5541R → D: Prevents membrane targeting. Ref.22
Mutagenesis5821R → N: Moderate reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis5821R → Q: Strong reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis5861E → Q: Moderate reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis5991D → N: Moderate reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis6001A → T: Strong reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis6021K → Q: Moderate reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis6031K → Q: Strong reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis6911D → R: Strong reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis7001F → M: Strong reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis7111K → E, N or Q: Strong reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis7111K → R: No effect on the sodium-dependent ion transport activity. Ref.22
Mutagenesis7121K → N: Strong reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis7141K → Q: Moderate reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis7151T → N: Strong reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis7211T → G: Moderate reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis7241R → E: Strong reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis7251K → N: Strong reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis7281S → G: Strong reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis7291D → N or R: Strong reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis7431D → K or N: Prevents membrane targeting. Ref.22
Mutagenesis7491D → N: Moderate reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis7521K → Q: Prevents membrane targeting. Ref.22
Mutagenesis7661R → Q: Moderate reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis7671G → T: Alters interaction with CA4. Ref.16
Mutagenesis7751E → N: Moderate reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis7981D → E, N or R: Strong reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis808 – 8092RK → NN: Strong reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis814 – 8152KK → NN: Moderate reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis8201H → D, N, S or R: Moderate reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis8221D → N: Moderate reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis8511H → N: Prevents membrane targeting. Ref.22
Mutagenesis8531D → N: Moderate reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis858 – 8603ETE → MSK: Moderate reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis875 – 8773EQR → QQQ: Prevents membrane targeting. Ref.22
Mutagenesis8751E → Q: Strong reduction of the sodium-dependent ion transport activity.
Mutagenesis8981K → E: Strong reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis925 – 9273RLK → NLN: Prevents membrane targeting. Ref.22
Mutagenesis9481R → E: Strong reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis9491R → E: Moderate reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis9511H → D: Moderate reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis9511H → N or R: Prevents membrane targeting. Ref.22
Mutagenesis9681K → Q: Moderate reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis9871R → E or N: Moderate reduction of the sodium-dependent ion transport activity. Ref.22
Mutagenesis10021L → N: Partial loss of interaction with CA2.
Mutagenesis10031D → N: Abolishes interaction with CA2.
Mutagenesis10041D → N: Partial loss of interaction with CA2.
Mutagenesis10261S → A: Prevents phosphorylation by PKA. Loss of regulation by cAMP of the transporter stoichiometry. Ref.9 Ref.17
Mutagenesis10261S → D: Loss of regulation by cAMP of the transporter stoichiometry. Shifts transporter stoichiometry from 3:1 to 2:1. Ref.9 Ref.17
Mutagenesis1030 – 10334DNDD → NNNN: Abolishes interaction with CA2. Ref.12 Ref.20
Mutagenesis10301D → N: Loss of regulation by cAMP of the transporter stoichiometry. Abolishes interaction with CA2. Ref.12
Mutagenesis10321D → N: Loss of regulation by cAMP of the transporter stoichiometry. Partial loss of interaction with CA2. Ref.12
Mutagenesis10331D → N: No effect on regulation by cAMP of the transporter stoichiometry. Partial loss of interaction with CA2. Ref.12
Mutagenesis10571F → A: Targeting to apical membrane. Ref.19
Sequence conflict61V → A in AAG47773. Ref.4
Sequence conflict491T → A in BAH58226. Ref.6
Sequence conflict781S → G in AAF21718. Ref.3
Sequence conflict2561S → F in AAD42020. Ref.3
Sequence conflict2631D → E in AAF21718. Ref.3
Sequence conflict2981P → H in BAH58226. Ref.6
Sequence conflict3641H → R in AAF21719. Ref.3
Sequence conflict6051I → V in AAF21718. Ref.3
Sequence conflict6541S → P in AAF21718. Ref.3
Sequence conflict7491D → G in AAF21719. Ref.3
Sequence conflict7991Q → R in AAG47773. Ref.4
Sequence conflict8561K → R in AAG47773. Ref.4
Sequence conflict9121M → R in AAF21718. Ref.3
Sequence conflict9131G → R in AAF21719. Ref.3
Sequence conflict9401I → V in AAF21718. Ref.3
Sequence conflict10071P → S in AAF21719. Ref.3
Sequence conflict10691S → P in AAF21719. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (hcNBC) (hhNBC) (hNBC1) (pNBC) (pNCB1) (pNBC-1) (NBC1b) [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: 14B981A94DD64293

FASTA1,079121,461
        10         20         30         40         50         60 
MEDEAVLDRG ASFLKHVCDE EEVEGHHTIY IGVHVPKSYR RRRRHKRKTG HKEKKEKERI 

        70         80         90        100        110        120 
SENYSDKSDI ENADESSSSI LKPLISPAAE RIRFILGEED DSPAPPQLFT ELDELLAVDG 

       130        140        150        160        170        180 
QEMEWKETAR WIKFEEKVEQ GGERWSKPHV ATLSLHSLFE LRTCMEKGSI MLDREASSLP 

       190        200        210        220        230        240 
QLVEMIVDHQ IETGLLKPEL KDKVTYTLLR KHRHQTKKSN LRSLADIGKT VSSASRMFTN 

       250        260        270        280        290        300 
PDNGSPAMTH RNLTSSSLND ISDKPEKDQL KNKFMKKLPR DAEASNVLVG EVDFLDTPFI 

       310        320        330        340        350        360 
AFVRLQQAVM LGALTEVPVP TRFLFILLGP KGKAKSYHEI GRAIATLMSD EVFHDIAYKA 

       370        380        390        400        410        420 
KDRHDLIAGI DEFLDEVIVL PPGEWDPAIR IEPPKSLPSS DKRKNMYSGG ENVQMNGDTP 

       430        440        450        460        470        480 
HDGGHGGGGH GDCEELQRTG RFCGGLIKDI KRKAPFFASD FYDALNIQAL SAILFIYLAT 

       490        500        510        520        530        540 
VTNAITFGGL LGDATDNMQG VLESFLGTAV SGAIFCLFAG QPLTILSSTG PVLVFERLLF 

       550        560        570        580        590        600 
NFSKDNNFDY LEFRLWIGLW SAFLCLILVA TDASFLVQYF TRFTEEGFSS LISFIFIYDA 

       610        620        630        640        650        660 
FKKMIKLADY YPINSNFKVG YNTLFSCTCV PPDPANISIS NDTTLAPEYL PTMSSTDMYH 

       670        680        690        700        710        720 
NTTFDWAFLS KKECSKYGGN LVGNNCNFVP DITLMSFILF LGTYTSSMAL KKFKTSPYFP 

       730        740        750        760        770        780 
TTARKLISDF AIILSILIFC VIDALVGVDT PKLIVPSEFK PTSPNRGWFV PPFGENPWWV 

       790        800        810        820        830        840 
CLAAAIPALL VTILIFMDQQ ITAVIVNRKE HKLKKGAGYH LDLFWVAILM VICSLMALPW 

       850        860        870        880        890        900 
YVAATVISIA HIDSLKMETE TSAPGEQPKF LGVREQRVTG TLVFILTGLS VFMAPILKFI 

       910        920        930        940        950        960 
PMPVLYGVFL YMGVASLNGV QFMDRLKLLL MPLKHQPDFI YLRHVPLRRV HLFTFLQVLC 

       970        980        990       1000       1010       1020 
LALLWILKST VAAIIFPVMI LALVAVRKGM DYLFSQHDLS FLDDVIPEKD KKKKEDEKKK 

      1030       1040       1050       1060       1070 
KKKKGSLDSD NDDSDCPYSE KVPSIKIPMD IMEQQPFLSD SKPSDRERSP TFLERHTSC 

« Hide

Isoform 2 (hkNBC) (hkNBCe1) (kNBC) (kNBC1) (kNBC-1) (NBC1a) [UniParc].

Checksum: 122096381B33D776
Show »

FASTA1,035116,040
Isoform 3 [UniParc].

Checksum: 285D5E23C540A516
Show »

FASTA64672,049
Isoform 4 [UniParc].

Checksum: 38B4A37EA047E9AC
Show »

FASTA995112,272
Isoform 5 [UniParc].

Checksum: B02FF2193A5F95C9
Show »

FASTA1,094123,181

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Localization of NBC-1 variants in human kidney and renal cell carcinoma."
Yamada H., Yamazaki S., Moriyama N., Hara C., Horita S., Enomoto Y., Kudo A., Kawakami H., Tanaka Y., Fujita T., Seki G.
Biochem. Biophys. Res. Commun. 310:1213-1218(2003) [PubMed] [Europe PMC] [Abstract]
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]"Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal photoreceptor degeneration."
Yang Z., Alvarez B.V., Chakarova C., Jiang L., Karan G., Frederick J.M., Zhao Y., Sauve Y., Li X., Zrenner E., Wissinger B., Den Hollander A.I., Katz B., Baehr W., Cremers F.P., Casey J.R., Bhattacharya S.S., Zhang K.
Hum. Mol. Genet. 14:255-265(2005) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001091954.1. NM_001098484.2.
NP_003750.1. NM_003759.3.
UniGeneHs.5462.

3D structure databases

ProteinModelPortalQ9Y6R1.
SMRQ9Y6R1. Positions 107-382, 453-493, 920-952.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114219. 1 interaction.
DIPDIP-59373N.
IntActQ9Y6R1. 4 interactions.
STRING9606.ENSP00000393557.

Protein family/group databases

TCDB2.A.31.2.12. the anion exchanger (ae) family.

PTM databases

PhosphoSiteQ9Y6R1.

Polymorphism databases

DMDM74721543.

Proteomic databases

PaxDbQ9Y6R1.
PRIDEQ9Y6R1.

Protocols and materials databases

DNASU8671.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264485; ENSP00000264485; ENSG00000080493. [Q9Y6R1-1]
ENST00000340595; ENSP00000344272; ENSG00000080493. [Q9Y6R1-2]
ENST00000351898; ENSP00000307349; ENSG00000080493. [Q9Y6R1-4]
ENST00000425175; ENSP00000393557; ENSG00000080493. [Q9Y6R1-5]
ENST00000512686; ENSP00000422400; ENSG00000080493. [Q9Y6R1-3]
GeneID8671.
KEGGhsa:8671.
UCSCuc003hfy.3. human. [Q9Y6R1-1]
uc003hga.2. human. [Q9Y6R1-3]
uc003hgc.4. human. [Q9Y6R1-2]
uc010iib.3. human. [Q9Y6R1-4]

Organism-specific databases

CTD8671.
GeneCardsGC04P072017.
HGNCHGNC:11030. SLC4A4.
HPACAB022493.
HPA035628.
HPA035629.
MIM603345. gene.
604278. phenotype.
neXtProtNX_Q9Y6R1.
Orphanet93607. Autosomal recessive proximal renal tubular acidosis.
PharmGKBPA35898.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG251607.
HOVERGENHBG004326.
InParanoidQ9Y6R1.
KOK13575.
OMAVCSFMAL.
OrthoDBEOG7TMZR0.
PhylomeDBQ9Y6R1.
TreeFamTF313630.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ9Y6R1.
BgeeQ9Y6R1.
CleanExHS_SLC4A4.
GenevestigatorQ9Y6R1.

Family and domain databases

Gene3D3.40.1100.10. 1 hit.
InterProIPR013769. Band3_cytoplasmic_dom.
IPR011531. HCO3_transpt_C.
IPR003020. HCO3_transpt_euk.
IPR003024. Na/HCO3_transpt.
IPR016152. PTrfase/Anion_transptr.
[Graphical view]
PANTHERPTHR11453. PTHR11453. 1 hit.
PfamPF07565. Band_3_cyto. 1 hit.
PF00955. HCO3_cotransp. 1 hit.
[Graphical view]
PRINTSPR01231. HCO3TRNSPORT.
PR01232. NAHCO3TRSPRT.
SUPFAMSSF55804. SSF55804. 1 hit.
TIGRFAMsTIGR00834. ae. 1 hit.
ProtoNetSearch...

Other

ChiTaRSSLC4A4. human.
GeneWikiSLC4A4.
GenomeRNAi8671.
NextBio32523.
PROQ9Y6R1.
SOURCESearch...

Entry information

Entry nameS4A4_HUMAN
AccessionPrimary (citable) accession number: Q9Y6R1
Secondary accession number(s): C4B714 expand/collapse secondary AC list , O15153, Q8NEJ2, Q9H262, Q9NRZ1, Q9UIC0, Q9UIC1, Q9UP50
Entry history
Integrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: November 1, 1999
Last modified: April 16, 2014
This is version 112 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM