CA4 Antibodies

Background

CA4 is a zinc metalloenzyme anchored to the cell membrane, mainly expressed on the surface of endothelial cells in the capillaries of the kidneys, lungs and certain tissues. This enzyme participates in maintaining acid-base balance, ion transport and gas exchange during cellular respiration by catalyzing the reversible hydration of carbon dioxide to bicarbonate ions. CA4 was first identified in the early 1990s and is the first isoenzyme in the carbonic anhydrase family to be confirmed as a glycosylated phosphatidylinositol anchored protein. Its membrane-binding characteristics are of great value for the study of local pH regulation and metabolic microenvironment. Due to its clear positioning and key physiological functions, the research on the structure and mechanism of CA4 has deepened people's understanding of enzyme anchoring methods, tissue-specific metabolic regulation, and the molecular basis of related diseases (such as renal tubular acidosis).

Structure Function Application Advantage Our Products

Structure of CA4

CA4 (carbonic anhydrase IV) is a glycosylated protein with a molecular weight of approximately 35 kDa. Its precise molecular weight varies slightly among species due to differences in the degree of glycosylation modification.

Species	Human	Mouse	Bovine
Molecular Weight (kDa)	~35	~34	~36
Primary Structural Differences	Has a GPI-anchored domain	Homologous sequences are highly conserved	Glycosylation sites exist nuances

This protein is composed of approximately 260 amino acid residues and exhibits a typical carbonic anhydrase folding structure. Its active center is composed of a zinc ion, which is coordinated and fixed by three histidine residues. This is the core that catalyzes the reversible hydration reaction of carbon dioxide. The positively charged channels on the surface of proteins are responsible for guiding substrate molecules into the active center, thereby efficiently performing their physiological functions.

Fig. 1:Design of derivative CA4 from aligned CTX and BmKCT sequences. Fig. 1 Multiple sequence alignments of CTX, BmKCT and the two derivatives CA4 and CTX-23.¹

Key structural properties of CA4:

Typical β -folding conformation of carbonic anhydrase
Active center three histidine residues by zinc ions and coordination
Surface hydrophilic channels guide substrate diffusion to the catalytic site
Glycosylated phosphatidylinositol (GPI) is anchored to the cell membrane

Functions of CA4

The CA4 gene encodes carbonic anhydrase IV, which mainly functions to catalyze the reversible hydration reaction of carbon dioxide and also participates in many important physiological regulatory processes in the body.

Function	Description
Acid-base balance regulation	Maintain the acid-base homeostasis of the extracellular microenvironment by rapidly converting CO₂ and HCO₃⁻.
Respiratory gas exchange	Promote CO₂ transport and discharge in lung capillaries and tissue capillaries to support respiratory efficiency.
Ion transport assistance	Provides substrate support for processes such as Na + /H + exchange in the renal tubules and secretory epithelium.
Regulation of cerebrospinal fluid secretion	The production and pH of cerebrospinal fluid are affected by regulating the concentration of bicarbonate in the choroid plexus.
Cell metabolic support	By maintaining an appropriate pH environment, the normal activity of enzymes related to metabolism is guaranteed.

The activity of this enzyme depends on the zinc ions in its active center. It has an extremely high catalytic efficiency and, due to its characteristic of being anchored to the cell membrane, can play a crucial metabolic guiding role in specific local areas.

Applications of CA4 and CA4 Antibody in Literature

1. Schmitt, Andrea, et al. "Decreased oligodendrocyte number in hippocampal subfield CA4 in schizophrenia: a replication study." Cells 11.20 (2022): 3242. https://doi.org/10.3390/cells11203242

This study verified that the number and density of oligodendrocytes in the bilateral hippocampal CA4 region of patients with schizophrenia were decreased, while there were no significant changes in the volume of CA4 and dentate gyrus, as well as the number of neurons and astrocytes. The results indicate that oligodendrocyte maturation disorders or loss may lead to abnormal myelin formation, thereby causing cognitive dysfunction.

2. Berni, Matteo, et al. "Assessment of CA4+ Impact on Mechanical Properties of Articular Cartilage." Materials 18.13 (2025): 2943. https://doi.org/10.3390/ma18132943

This study explored the influence of CA4+ contrast agent containing tetravalent positive charge on the mechanical properties of articular cartilage. Experiments have found that CA4+ solution significantly reduces the instantaneous stiffness (about -25%) and equilibrium stiffness (about -38%) of cartilage. Its softening effect may stem from the disruption of proteoglycan interactions caused by the positive charge of the contrast agent.

3. Xu, Tengfei, et al. "Erratum: Identification of two novel Chlorotoxin derivatives CA4 and CTX-23 with chemotherapeutic and anti-angiogenic potential." Scientific reports 6.1 (2016): 22206. https://doi.org/10.1038/srep19799

Based on scorpion venom chlorotoxin (CTX), a novel derivative peptide CA4 was designed in this study. CA4 can effectively inhibit the proliferation and migration of glioma cells and exhibit anti-angiogenic activity. It still has anti-tumor effects in the complex tumor microenvironment and has low toxicity to normal neurons, showing potential as a targeted therapeutic drug.

4. Svichar, Nataliya, et al. "Carbonic anhydrases CA4 and CA14 both enhance AE3-mediated Cl−–HCO3− exchange in hippocampal neurons." Journal of Neuroscience 29.10 (2009): 3252-3258. https://doi.org/10.1523/JNEUROSCI.0036-09.2009

This study confirmed that the carbonic anhydrase CA4 and CA14 outside the brain cells jointly regulate the intracellular pH of hippocampal neurons by promoting the Cl⁻-HCO ₃⁻exchange mediated by the AE3 anion exchanger. In AE3 knockout neurons, the regulatory effect of CA4/CA14 disappears, indicating that its function depends on AE3.

5. Su, Min, et al. "The anti-angiogenic effect and novel mechanisms of action of Combretastatin A-4." Scientific reports 6.1 (2016): 28139. https://doi.org/10.1038/srep28139

This study confirmed that CA4 (Combretastatin A-4) demonstrated anti-angiogenic activity in both in vivo and in vitro by inhibiting the proliferation, migration and tubation induced by vascular endothelial growth factor (VEGF). The mechanism is related to down-regulating the expression of VEGF/VEGFR-2 and blocking the downstream signal transduction of this pathway.

Creative Biolabs: CA4 Antibodies for Research

Creative Biolabs specializes in the production of high-quality CA4 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom CA4 Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our CA4 antibodies, custom preparations, or technical support, contact us at email.

Reference

Xu, Tengfei, et al. "Erratum: Identification of two novel Chlorotoxin derivatives CA4 and CTX-23 with chemotherapeutic and anti-angiogenic potential." Scientific reports 6.1 (2016): 22206. https://doi.org/10.1038/srep19799