1. Gene Aliases

Carbonic Anhydrase 3, CAIII, Carbonic Anhydrase III, Muscle Specific, Carbonate Dehydratase III, Carbonic Anhydrase III, EC 4.2.1.1, CA-III, Car3, Epididymis Secretory Sperm Binding Protein Li 167mP, Carbonic Anhydrase IIII, HEL-S-167mP, CAR3

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=CA3&keywords=CA3]

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

Reversible hydration of carbon dioxide: Carbonic anhydrases reversibly catalyze the hydration of carbon dioxide and directly produce bicarbonate and protons, bypassing the formation of carbonic acid (reviewed in Lindskog 1997, Breton 2001, Esbaugh and Tufts 2006, Boron 2010, Gilmour 2010). Carbonic anhydrase deprotonates water to yield a zinc-hydroxyl group and a proton which is transferred to external buffer molecules via histidine or glutamate residues in carbonic anhydrase. The hydroxyl group reacts with carbon dioxide in the active site to yield bicarbonate. A water molecule displaces the bicarbonate, and the reaction cycle begins again. There are currently 12 known active carbonic anhydrases in humans. [https://reactome.org/PathwayBrowser/#/R-HSA-1475029]

GO terms:

one-carbon metabolic process [The chemical reactions and pathways involving the transfer of one-carbon units in various oxidation states. GO:0006730]

response to bacterium [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a bacterium. GO:0009617]

response to ethanol [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an ethanol stimulus. GO:0045471]

response to oxidative stress [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of oxidative stress, a state often resulting from exposure to high levels of reactive oxygen species, e.g. superoxide anions, hydrogen peroxide (H2O2), and hydroxyl radicals. GO:0006979]

MSigDB Signatures:

KEGG_NITROGEN_METABOLISM: Nitrogen metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_NITROGEN_METABOLISM.html]

MA_RAT_AGING_UP: Genes up-regulated across multiple cell types from nine tissues during rat aging. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/MA_RAT_AGING_UP.html]

7. Gene Descriptions

NCBI Gene Summary: Carbonic anhydrase III (CAIII) is a member of a multigene family (at least six separate genes are known) that encodes carbonic anhydrase isozymes. These carbonic anhydrases are a class of metalloenzymes that catalyze the reversible hydration of carbon dioxide and are differentially expressed in a number of cell types. The expression of the CA3 gene is strictly tissue specific and present at high levels in skeletal muscle and much lower levels in cardiac and smooth muscle. A proportion of carriers of Duchenne muscle dystrophy have a higher CA3 level than normal. The gene spans 10.3 kb and contains seven exons and six introns. [provided by RefSeq, Oct 2008]

GeneCards Summary: CA3 (Carbonic Anhydrase 3) is a Protein Coding gene. Diseases associated with CA3 include Acute Myocardial Infarction and Neuromuscular Disease. Among its related pathways are Metabolism and Reversible hydration of carbon dioxide. Gene Ontology (GO) annotations related to this gene include carbonate dehydratase activity and nickel cation binding. An important paralog of this gene is CA13.

UniProtKB/Swiss-Prot Summary: Reversible hydration of carbon dioxide.

8. Cellular Location of Gene Product

Selective cytoplasmic expression in muscle cells and adipocytes. Predicted location: Intracellular [https://www.proteinatlas.org/ENSG00000164879/subcellular]

9. Mechanistic Information

Summary

CA3 dysregulation in bone marrow diseases and toxicities can be explained through its established functions and responses to cellular stress [CS: 8]. CA3, as a carbonic anhydrase, is involved in the reversible hydration of carbon dioxide, aiding in maintaining cellular pH balance and ion transport [CS: 10]. In the context of bone marrow, where rapid cell division and metabolism occur, maintaining pH homeostasis is crucial [CS: 9]. When bone marrow cells are exposed to toxic events like oxidative stress or hypoxic conditions, they require efficient mechanisms to manage the altered pH and ionic environment [CS: 8].

The upregulation of CA3 in response to hypoxia, as indicated by its hypoxia-responsive expression, suggests a protective mechanism against acidic conditions often associated with low oxygen levels [CS: 7]. This aligns with CA3's role in converting CO2 to bicarbonate ions, thus counteracting acidosis [CS: 9]. Similarly, the increased expression of CA3 in conditions of oxidative stress, as seen in Evi1-associated repression of CA3 leading to increased apoptosis, underscores CA3's role in cellular defense [CS: 6]. By facilitating the rapid conversion of CO2, a byproduct of cellular metabolism, to less harmful bicarbonate, CA3 might help in mitigating the effects of oxidative stress, thereby promoting cell survival in the bone marrow during toxic events [CS: 8].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: skeletal muscle (tissue enriched) [https://www.proteinatlas.org/ENSG00000164879/tissue]

Cell type enchanced: skeletal myocytes (cell type enriched) [https://www.proteinatlas.org/ENSG00000164879/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

No biomarkers associated with disease or organ of interest were found.