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HighlightsIntroduction of SLC4A4
Solute carrier family 4 member 4 (SLC4A4) is an electrogenic sodium bicarbonate cotransporter 1 (NBCe1) that is involved in the regulation of bicarbonate secretion/absorption and intracellular pH. There are two identified electrogenic Na+-HCO3- cotransporters in mammals: NBCe1 (SLC4A4) and NBCe2 (NBC4/SLC4A5). And a third NBCe is found in the invertebrate nervous system. These NBCe proteins cotransport Na+ and 2-3 HCO3- across epithelial membranes or neuronal membranes.
| Basic Information of SLC4A4 | |
| Protein Name | Electrogenic sodium bicarbonate cotransporter 1 |
| Gene Name | SLC4A4 |
| Aliases | KNBC, NBC1, NBC2, pNBC, HNBC1, kNBC1, SLC4A5, NBCe1-A |
| Organism | Homo sapiens (Human) |
| UniProt ID | Q9Y6R1 |
| Transmembrane Times | 12 |
| Length (aa) | 1079 |
| Sequence | MEDEAVLDRGASFLKHVCDEEEVEGHHTIYIGVHVPKSYRRRRRHKRKTGHKEKKEKERISENYSDKSDIENADESSSSILKPLISPAAERIRFILGEEDDSPAPPQLFTELDELLAVDGQEMEWKETARWIKFEEKVEQGGERWSKPHVATLSLHSLFELRTCMEKGSIMLDREASSLPQLVEMIVDHQIETGLLKPELKDKVTYTLLRKHRHQTKKSNLRSLADIGKTVSSASRMFTNPDNGSPAMTHRNLTSSSLNDISDKPEKDQLKNKFMKKLPRDAEASNVLVGEVDFLDTPFIAFVRLQQAVMLGALTEVPVPTRFLFILLGPKGKAKSYHEIGRAIATLMSDEVFHDIAYKAKDRHDLIAGIDEFLDEVIVLPPGEWDPAIRIEPPKSLPSSDKRKNMYSGGENVQMNGDTPHDGGHGGGGHGDCEELQRTGRFCGGLIKDIKRKAPFFASDFYDALNIQALSAILFIYLATVTNAITFGGLLGDATDNMQGVLESFLGTAVSGAIFCLFAGQPLTILSSTGPVLVFERLLFNFSKDNNFDYLEFRLWIGLWSAFLCLILVATDASFLVQYFTRFTEEGFSSLISFIFIYDAFKKMIKLADYYPINSNFKVGYNTLFSCTCVPPDPANISISNDTTLAPEYLPTMSSTDMYHNTTFDWAFLSKKECSKYGGNLVGNNCNFVPDITLMSFILFLGTYTSSMALKKFKTSPYFPTTARKLISDFAIILSILIFCVIDALVGVDTPKLIVPSEFKPTSPNRGWFVPPFGENPWWVCLAAAIPALLVTILIFMDQQITAVIVNRKEHKLKKGAGYHLDLFWVAILMVICSLMALPWYVAATVISIAHIDSLKMETETSAPGEQPKFLGVREQRVTGTLVFILTGLSVFMAPILKFIPMPVLYGVFLYMGVASLNGVQFMDRLKLLLMPLKHQPDFIYLRHVPLRRVHLFTFLQVLCLALLWILKSTVAAIIFPVMILALVAVRKGMDYLFSQHDLSFLDDVIPEKDKKKKEDEKKKKKKKGSLDSDNDDSDCPYSEKVPSIKIPMDIMEQQPFLSDSKPSDRERSPTFLERHTSC |
Function of SLC4A4 Membrane Protein
SLC4A4 (NBCe1) functions as a sodium bicarbonate cotransporter that mediates the coupled movement of sodium and bicarbonate ions across the plasma membrane of many cells. This is an electrogenic process with Na+:HCO3- stoichiometry varying from 1:2 to 1:3. Sodium bicarbonate cotransport is associated with bicarbonate influx/efflux at the basolateral membrane of cells and intracellular pH regulation. NBCe1 has been associated with pH regulation in enamel organ cells during enamel development in the mouse. Some NBCe1 variants may lead to the impairment of bicarbonate reabsorption in the renal proximal tubules, causing a decrease in the threshold of renal bicarbonate, resulting in proximal renal tubular acidosis. Besides, patients with the autosomal recessive manner proximal renal tubular acidosis may display the inactivative basolateral sodium bicarbonate cotransporter. And these patients also exert eye abnormalities, such as band keratopathy, glaucoma, and cataracts. In addition, other NBCe1 mutations have been related to familial hemiplegic migraine.
Fig.1 Topology of NBCe1. (Huynh, 2018)
Application of SLC4A4 Membrane Protein in Literature
The experimental results suggest that SLC4A4 helps to the HCO3(-) transport and tumor cell phenotype, suggesting it can act as a potential target for tumor treatment.
The present findings support the view that both SLC4A4 and TMEM16A may be involved in the regulation of anion fluxes in insulin-producing cells in humans.
The article indicates that the expression of NBCe1 in ameloblasts and the papillary layer cell depends on the developmental stage and possibly responds to pH changes.
In the present study, authors identify a novel, homozygous, missense SLC4A4 mutation (Leu522Pro in kNBCe1) in patients with proximal renal tubular acidosis, short stature, and ocular pathology.
This article expands the range of kNBC1 mutations in permanent isolated proximal renal tubular acidosis with eye abnormalities and increases our understanding of the renal tubular mechanism that is essential for acid-base homeostasis.
SLC4A4 Preparation Options
Based on the versatile Magic™ membrane protein production platform, Creative Biolabs can help you to obtain the best soluble and functional target protein to make your project a success. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-SLC4A4 antibody development services.
As a forward-looking biotech company as well as a leading custom service provider in the field of membrane protein, Creative Biolabs has won good reputation among our worldwide customers for successfully accomplishing numerous challenging projects including generation of many functional membrane proteins. Our scientists are glad to offer a comprehensive range of solutions for membrane protein studies for our clients all over the world. Please feel free to contact us for more information.
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