CA12

CA12
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1JCZ, 1JD0, 4HT2, 4KP5, 4KP8, 4Q0L, 4QJ0, 4QJO, 4QJW, 4WW8
Identifiers
Aliases	CA12, CAXII, HsT18816, CA-XII, T18816, carbonic anhydrase 12
External IDs	MGI: 1923709 HomoloGene: 20327 GeneCards: CA12
Targeted by Drug
acetazolamide, brinzolamide, celecoxib, chlorthalidone, dichlorphenamide, dorzolamide, ethoxzolamide, methazolamide, sulpiride, topiramate, valdecoxib[1]
Gene ontology Molecular function • carbonate dehydratase activity • zinc ion binding • lyase activity • metal ion binding Cellular component • integral component of membrane • plasma membrane • membrane Biological process • bicarbonate transport • chloride ion homeostasis • one-carbon metabolic process Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	771	76459
Ensembl	ENSG00000074410	ENSMUSG00000032373
UniProt	O43570	Q8CI85
RefSeq (mRNA)	NM_206925 NM_001218 NM_001293642	NM_178396 NM_001306148
RefSeq (protein)	NP_001209.1 NP_996808.1	NP_001293077.1 NP_848483.3
Location (UCSC)	Chr 15: 63.32 – 63.38 Mb	Chr 9: 66.71 – 66.77 Mb
PubMed search	[2]	[3]
Wikidata

Carbonic anhydrase 12 is an enzyme that in humans is encoded by the CA12 gene.^[4][5]

Function

Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. This gene product is a type I membrane protein that is highly expressed in normal tissues, such as kidney, colon and pancreas, and has been found to be overexpressed in 10% of clear cell renal carcinomas. Two transcript variants encoding different isoforms have been identified for this gene.^[5]

Pathology

Loss of function mutations in the CAXII gene result in defects in fluids and carbonate secretions in the following diseases:

1) Cystic fibrosis-like syndrome with normal cystic fibrosis transmembrane conductance regulator (CFTR) protein levels ^{[6][7][8][9][10][11]}

2) Pancreatitis^[12][13]

3) Sjögren's syndrome^[13][14]

4) Xerostomia or dry mouth syndrome^[8][9][10]

Molecular Basis of Cystic Fibrosis-like Syndrome

CAXII, with either the His121Gln or Glu143Lys mutation, localizes to basolateral membranes of polarized MDCK cells similar to the wild type enzyme, indicating no deleterious effect on subcellular location.^[13]

However, CAXII mutant enzymes show reduced activity. These observations made it very hard to explain the mechanism for the autosomal recessive disorder of hyponatremia, causing salt wasting in sweat due to mutant CAXII.^[6][7]

In a separate study, researchers observed that mutant enzyme activity is completely reduced at physiological concentrations of sodium chloride.^[13] Thus, loss of the function of CAXII in sweat glands and lungs is the molecular basis for cystic fibrosis patients with normal CFTR levels.^[13]

High Impact Information on CAXII

Differential modulation of the active site environment of CAXII by cationic quantum dots and polylysine helps design CAXII specific activators and inhibitors of the enzyme.^[15] CAXII specific inhibition provides a tool to interfere with cell proliferation, resulting in cell apoptosis in T-cell lymphomas.^[16]

Analytical, Diagnostic, and Therapeutic Context of CAXII

Serum CAXII levels should be applicable as a sero-diagnostic marker for lung cancer.^[17]

References

Further reading

PDB gallery
1jcz: CRYSTAL STRUCTURE OF THE EXTRACELLULAR DOMAIN OF HUMAN CARBONIC ANHYDRASE XII  1jd0: CRYSTAL STRUCTURE OF THE EXTRACELLULAR DOMAIN OF HUMAN CARBONIC ANHYDRASE XII COMPLEXED WITH ACETAZOLAMIDE