Affinage

CA2

Carbonic anhydrase 2 · UniProt P00918

Length
260 aa
Mass
29.2 kDa
Annotated
2026-06-09
100 papers in source corpus 13 papers cited in narrative 13 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CA2 (carbonic anhydrase II) is a cytoplasmic carbonic anhydrase isoenzyme that supports proton production and transepithelial acid-base homeostasis in specialized epithelia, and its loss-of-function mutations cause the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis (PMID:12566520). CAII is the dominant cytosolic carbonic anhydrase across diverse cell types, including gastric surface epithelium and parietal cells, intestinal villus epithelium (PMID:3920111), ocular ciliary epithelium, corneal endothelium, lens, and retinal Müller glia (PMID:3081459, PMID:6430181), and epididymal narrow cells, where it concentrates near apical H+ V-ATPase-bearing vesicles that recycle to deliver protons for luminal acidification (PMID:10819445). Genetic null studies in mice establish that CAII accounts for cytosolic but not membrane-associated carbonic anhydrase activity: in the absence of CAII, renal proximal tubule HCO3- reabsorption and ocular membrane CA activity persist and are attributable to a distinct membrane-bound isoenzyme (CA IV), with CAII-deficient kidneys showing only higher urine pH, increased Cl- excretion, and reduced titratable acid (PMID:1906751, PMID:8163345). CA2 transcription is directly controlled through its promoter by the thyroid hormone receptor c-erbA, which activates with T3, and the v-erbA oncoprotein, which represses; restoring CAII in v-erbA-transformed erythroblasts rescues the pH and ionic-strength tolerance phenotype but not the differentiation block, defining CAII suppression as causally responsible for altered pH/ion homeostasis (PMID:1682217, PMID:1354613). CAII is also upregulated downstream of VEGF-A/VEGFR signaling in tumor endothelial cells, where it supports survival under lactic acidosis (PMID:31847904).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1985 Medium

    Establishing which carbonic anhydrase isoenzyme dominates in acid-secreting epithelia was needed to assign function; CAII was identified as the predominant cytosolic isoenzyme in stomach and a major one in intestine, localized to acid-handling epithelial cells.

    Evidence Radioimmunoassay quantification, immunohistochemistry, and histochemical enzyme activity in gastrointestinal tissues

    PMID:3920111

    Open questions at the time
    • Does not directly demonstrate CAII contribution to acid secretion
    • Membrane activity ascribed to CA IV not genetically confirmed in this study
  2. 1986 Medium

    Defining the cellular compartments of CAII in the eye localized the enzyme to ciliary epithelium, corneal endothelium, lens, and Müller cells, framing its role in ocular fluid and acid-base handling.

    Evidence Immunofluorescence, immunoperoxidase, and cobalt-phosphate enzyme histochemistry in human eye with isoenzyme-specific antisera

    PMID:3081459

    Open questions at the time
    • Descriptive localization without functional perturbation
    • Cannot distinguish cytosolic CAII from co-localizing membrane isoenzymes by immunofluorescence alone
  3. 1986 Medium

    Mapping CA2 to chromosome 8 within a clustered locus alongside CA1 and CA3 placed it in a complex multigene family.

    Evidence Human-mouse somatic cell hybrid panel mapping and RNA blot

    PMID:3099285

    Open questions at the time
    • No functional consequence of genomic clustering established
    • Does not address regulatory coordination among the linked genes
  4. 1991 High

    How CA2 expression is transcriptionally controlled was unknown; v-erbA and c-erbA were shown to bind directly to the CAII promoter, with c-erbA/T3 activating and v-erbA repressing transcription, identifying a nuclear-receptor regulatory switch.

    Evidence Direct promoter binding assays, reporter assays, and stable erythroblast transformation with T3 induction

    PMID:1682217

    Open questions at the time
    • Cofactors mediating activation versus repression not defined
    • Physiological relevance of this regulation outside erythroblasts not tested
  5. 1991 High

    Whether CAII or a membrane isoenzyme drives renal acid-base handling was resolved by a Car2 null mouse, showing cytosolic CA activity is lost but proximal-tubule HCO3- reabsorption is preserved via membrane CA IV.

    Evidence Tissue fractionation CA activity assays, sulfonamide inhibition profiling, and in vivo renal function in CAII-deficient versus normal mice

    PMID:1906751

    Open questions at the time
    • Does not explain the residual urine pH and titratable acid phenotype mechanistically
    • Distal nephron contribution of CAII not separately resolved
  6. 1992 High

    It was unclear whether CAII loss caused the v-erbA pH/ion phenotype; retroviral re-expression of CAII rescued pH and ionic-strength sensitivity but not the differentiation block, causally linking CAII to ion homeostasis and separating it from the transformation phenotype.

    Evidence Retrovirus-mediated CAII re-expression and phenotypic rescue in v-erbA-transformed erythroblasts

    PMID:1354613

    Open questions at the time
    • Molecular mechanism by which CAII confers pH sensitivity not detailed
    • Other v-erbA targets contributing to phenotype not excluded
  7. 1994 Medium

    To determine whether ocular membrane CA activity depends on CAII, the null mouse showed persistent membrane activity across ciliary epithelium, corneal endothelium, and other ocular tissues without cytosolic CAII, assigning membrane activity to a distinct isoenzyme.

    Evidence Cobalt-phosphate histochemical CA activity in CAII-deficient versus normal mouse eyes

    PMID:8163345

    Open questions at the time
    • Membrane isoenzyme identity inferred, not directly identified
    • Does not quantify the cytosolic CAII contribution to ocular fluid dynamics
  8. 2000 Medium

    How CAII contributes to epididymal luminal acidification was addressed by localizing it to narrow-cell cytosol near apical V-ATPase-bearing vesicles that recycle to the membrane, supporting a coupled proton-delivery model.

    Evidence Light and electron microscopy immunohistochemistry, immunogold, and luminal fluid-phase tracer experiments in rodent epididymis

    PMID:10819445

    Open questions at the time
    • Direct functional coupling of CAII to V-ATPase activity not measured
    • Vesicle recycling model inferred from tracer co-localization
  9. 2003 Medium

    The molecular cause of combined osteopetrosis with renal tubular acidosis was established as loss-of-function CA2 mutations, with a phenocopy lacking CA2 mutations attributed to H+-ATPase defects.

    Evidence CA2 sequencing, CAII protein measurement, and genetic exclusion in a phenocopy kindred

    PMID:12566520

    Open questions at the time
    • Genotype-phenotype correlation across mutations not systematically defined
    • Tissue-specific basis of osteopetrosis versus RTA not dissected
  10. 2009 Medium

    Biophysical characterization of inhibitor binding showed ethoxzolamide binds hCAII with ~2 nM affinity and strongly stabilizes the protein, providing a quantitative framework for sulfonamide inhibitor interactions.

    Evidence Displacement isothermal titration calorimetry and thermal shift assay on purified hCAII

    PMID:19582223

    Open questions at the time
    • Single inhibitor characterized
    • No structural model of the binding mode reported in this study
  11. 2019 Medium

    A role for CAII in tumor vasculature was identified: it is upregulated in tumor endothelial cells downstream of VEGF-A/VEGFR signaling and required for endothelial survival under lactic acidosis, with inhibition reducing metastasis.

    Evidence siRNA knockdown, qRT-PCR/Western/ELISA, proliferation assays, and xenograft models with acetazolamide treatment

    PMID:31847904

    Open questions at the time
    • Direct enzymatic mechanism of acidosis protection not defined
    • On-target versus broad CA inhibition of acetazolamide in vivo not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CAII is mechanistically coupled to membrane transporters (V-ATPase, Cl-/HCO3- exchangers) to form functional acid-base transport metabolons in specific epithelia remains unresolved.
  • No reconstitution of CAII-transporter coupling in the timeline
  • Tissue-specific molecular partners of CAII not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 2 GO:0016829 lyase activity 2
Localization
GO:0005829 cytosol 3 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-74160 Gene expression (Transcription) 2 R-HSA-1643685 Disease 1 R-HSA-382551 Transport of small molecules 1

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 CA II (CAII) protein is localized in the ciliary processes of the human eye (both pigmented and nonpigmented epithelium), corneal endothelium, lens epithelium and fibers, and Müller cells of the retina, as determined by immunofluorescence and immunoperoxidase with isoenzyme-specific antisera, with histochemical enzyme activity confirmed in cytoplasm and basolateral membranes of nonpigmented ciliary epithelium. Immunofluorescence, immunoperoxidase histochemistry, cobalt-phosphate histochemical enzyme activity assay Investigative ophthalmology & visual science Medium 3081459
1985 CA II is the dominant carbonic anhydrase isoenzyme in the stomach, while both CA I and CA II are present in jejunum and colon; CA II immunofluorescence is localized to gastric surface epithelium and parietal cells, jejunal villus epithelium, and colonic surface epithelium, with enzyme activity additionally detected at membranes of gastric chief cells and intestinal crypt cells (attributed to membrane-bound CA IV). Radioimmunoassay for isoenzyme quantification, immunohistochemistry, histochemical enzyme activity assay Gastroenterology Medium 3920111
1991 v-erbA oncoprotein and c-erbA (thyroid hormone receptor) bind directly to sequences within the CAII promoter; v-erbA efficiently suppresses CAII transcription, while c-erbA with T3 activates CAII transcription through the same binding site; suppression of CAII transcription by v-erbA requires overexpression relative to c-erbA, as equimolar c-erbA is dominant. Direct promoter binding assays, transient expression reporter assays, stable transformation of erythroblasts with v-erbA and c-erbA constructs, T3 induction experiments Genes & development High 1682217
1992 Retroviral re-expression of CAII in v-erbA-transformed erythroblasts restores sensitivity to pH and ionic strength of culture medium (abrogating v-erbA-induced pH/ion tolerance), demonstrating that CAII suppression by v-erbA is causally responsible for the pH/ion tolerance phenotype; however, re-expression of CAII does not reverse the v-erbA-induced differentiation block. Retrovirus-mediated gene re-expression in transformed erythroblasts, phenotypic rescue assay The EMBO journal High 1354613
2003 Loss-of-function mutations in CA2 (including a novel homozygous frameshift) cause the Guibaud-Vainsel syndrome of osteopetrosis with mixed renal tubular acidosis; a phenocopy with normal CAII levels was identified in a separate kindred, attributed to mutations in H+-ATPase subunits, establishing CA2 deficiency as the primary molecular cause of the combined osteopetrosis-RTA phenotype. Molecular genetic analysis (sequencing of CA2), CAII protein level measurement, genetic exclusion of CA2 mutations in phenocopy kindred Journal of medical genetics Medium 12566520
1991 In CA II-deficient mice (null allele at Car2 locus), renal cytosolic carbonic anhydrase activity is absent while membrane-associated CA activity (attributed to CA IV based on sulfonamide sensitivity) is preserved; despite CA II deficiency, baseline urinary electrolyte excretion is largely normal except for higher urine pH, higher Cl- excretion, and lower titratable acid output; response to CA inhibition (methazolamide) is equivalent in deficient and normal mice, indicating that membrane-bound CA IV is the principal isoenzyme for proximal tubule HCO3- reabsorption. Tissue fractionation with CA activity assays, sulfonamide inhibition profiling, in vivo renal function measurements in CA II-deficient vs. normal mice Biochimica et biophysica acta High 1906751
1984 In chicken retina, CA II expression is restricted to Müller glial cells at maturity but is broadly expressed in all retinoblasts during early embryonic development before becoming restricted; in mouse retina, CA II persists in both Müller cells and certain amacrine neurons at maturity; lower vertebrates show CA II in additional cell types (horizontal cells in fish and some amphibians), indicating species-specific compartmentalization of CA II expression during retinal development. Immunohistochemistry with polyclonal and monoclonal antibodies to CA II across vertebrate species and developmental stages Annals of the New York Academy of Sciences Medium 6430181
1986 The human CAIII gene is located on chromosome 8, the same chromosome as the closely linked CAI and CAII genes, suggesting a complex multigene locus; CAII (and CAI) were previously mapped to chromosome 8. Human-mouse somatic cell hybrid panel chromosome mapping, RNA blot analysis Proceedings of the National Academy of Sciences of the United States of America Medium 3099285
2009 Ethoxzolamide binds to human CA II (hCAII) with a dissociation constant of ~2 nM, as measured by displacement isothermal titration calorimetry and thermal shift assay; ligand binding stabilizes the protein by >10°C in melting temperature, and ligand-free and ligand-bound CA II melt as distinct populations observable as two separate thermal transitions. Displacement isothermal titration calorimetry (ITC), thermal shift assay (TSA), protein melting temperature analysis International journal of molecular sciences Medium 19582223
1994 In CA II-deficient mice, membrane-associated carbonic anhydrase activity is present in multiple ocular cell types (apical and basolateral membranes of pigmented and nonpigmented ciliary epithelium, corneal endothelium, retinal pigment epithelium, Müller cell borders, lens epithelium and fibers, choroidal and retinal capillary endothelium) in the absence of cytoplasmic CA II, demonstrating that membrane-associated CA activity in these ocular tissues is independent of CA II and is attributable to a distinct membrane-bound isoenzyme. Cobalt-phosphate histochemical CA activity assay in CA II-deficient vs. normal mouse eyes Investigative ophthalmology & visual science Medium 8163345
2000 CA II is immunolocalized specifically to narrow cells of the initial segment and intermediate zone of the mouse and rat epididymis, where it is found in the cytosol near cup-shaped apical vesicles; these vesicles also express H+ V-ATPase on their delimiting membranes, and fluid-phase tracers introduced luminally label these vesicles, supporting a model in which CA II-containing vesicles recycle to the apical plasma membrane to deliver protons for luminal acidification. Light microscopy immunohistochemistry, electron microscopy with immunogold labeling, electron-dense fluid-phase tracer experiments Journal of andrology Medium 10819445
2019 CA II (CAII) is upregulated in tumor endothelial cells (TECs) compared to normal endothelial cells both in vitro and in vivo; CAII knockdown decreases TEC survival under lactic acidosis; VEGF-A/VEGFR signaling induces CAII expression in normal endothelial cells; acetazolamide-mediated CAII inhibition in vivo increased matured blood vessel number and decreased lung metastasis. siRNA knockdown, qRT-PCR, Western blot, ELISA, MTS proliferation assay, human tumor xenograft models, immunohistochemistry Cell communication and signaling : CCS Medium 31847904
1996 Human erythrocyte CAII protein concentration increases with gestational age from ~53 μg/g Hb at 20 weeks to ~120 μg/g Hb at 38 weeks gestation, with adult levels of ~1.59 mg/g Hb; the CAI/CAII ratio increases from 0.9 in early fetal life to 2.5 at term and 8.8 in adults, establishing a developmental regulation pattern for CAII protein in erythrocytes. Enzyme-linked immunosorbent assay (ELISA) for CAII quantification in fetal, neonatal, and adult erythrocytes Clinical biochemistry Low 8601325

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. Current biology : CB 1812 16005298
2008 Ca2+ signalling checkpoints in cancer: remodelling Ca2+ for cancer cell proliferation and survival. Nature reviews. Cancer 591 18432251
1996 Calcineurin inhibits VCX1-dependent H+/Ca2+ exchange and induces Ca2+ ATPases in Saccharomyces cerevisiae. Molecular and cellular biology 380 8628289
2000 CDPKs - a kinase for every Ca2+ signal? Trends in plant science 349 10740296
1994 Effects of rapid buffers on Ca2+ diffusion and Ca2+ oscillations. Biophysical journal 305 7919018
2007 Na+/Ca2+ exchangers: three mammalian gene families control Ca2+ transport. The Biochemical journal 295 17716241
1990 Receptor-activated cytoplasmic Ca2+ spiking mediated by inositol trisphosphate is due to Ca2(+)-induced Ca2+ release. Cell 263 1701691
1990 Glutamate receptors activate Ca2+ mobilization and Ca2+ influx into astrocytes. Proceedings of the National Academy of Sciences of the United States of America 237 1970637
1991 Ca2+ waves in astrocytes. Cell calcium 213 1647876
1985 Ca2+-dependent and Ca2+-independent phagocytosis in human neutrophils. Nature 202 3158824
2002 Luminal Ca2+ controls termination and refractory behavior of Ca2+-induced Ca2+ release in cardiac myocytes. Circulation research 190 12215490
1993 Regulation by Ca2+ in the Yersinia low-Ca2+ response. Molecular microbiology 177 8361348
1989 Caffeine-induced Ca2+ release activates Ca2+ extrusion via Na+-Ca2+ exchanger in cardiac myocytes. The American journal of physiology 154 2750887
1994 Signaling between intracellular Ca2+ stores and depletion-activated Ca2+ channels generates [Ca2+]i oscillations in T lymphocytes. The Journal of general physiology 152 8195779
1986 Carbonic anhydrase isoenzymes CA I and CA II in the human eye. Investigative ophthalmology & visual science 143 3081459
2008 NAADP: a universal Ca2+ trigger. Science signaling 140 18984909
1998 Inositol trisphosphate receptors: Ca2+-modulated intracellular Ca2+ channels. Biochimica et biophysica acta 131 9838027
1998 The Ca2+ transport mechanisms of mitochondria and Ca2+ uptake from physiological-type Ca2+ transients. Biochimica et biophysica acta 130 9714709
2006 Ca2+ shuttling between endoplasmic reticulum and mitochondria underlying Ca2+ oscillations. EMBO reports 129 16415789
1988 Epinephrine enhances Ca2+ current-regulated Ca2+ release and Ca2+ reuptake in rat ventricular myocytes. Proceedings of the National Academy of Sciences of the United States of America 129 3162323
1996 Ryanodine receptor adaptation and Ca2+(-)induced Ca2+ release-dependent Ca2+ oscillations. Biophysical journal 127 8968617
2006 Ca2+-dependent rapid Ca2+ sensitization of contraction in arterial smooth muscle. Circulation research 123 17158339
1990 Ca2(+)-induced conformational change and aggregation of chromogranin A. The Journal of biological chemistry 122 2387861
1996 Ca2+ signaling and intracellular Ca2+ binding proteins. Journal of biochemistry 117 8947828
2007 Ca2+ stores regulate ryanodine receptor Ca2+ release channels via luminal and cytosolic Ca2+ sites. Biophysical journal 113 17351009
1997 Enhanced Ca2+ current and decreased Ca2+ efflux restore sarcoplasmic reticulum Ca2+ content after depletion. Circulation research 109 9314828
2003 Function of caveolae in Ca2+ entry and Ca2+-dependent signal transduction. Traffic (Copenhagen, Denmark) 108 14617355
2005 A cAMP and Ca2+ coincidence detector in support of Ca2+-induced Ca2+ release in mouse pancreatic beta cells. The Journal of physiology 105 15860526
2005 Endogenous Ca2+ buffer concentration and Ca2+ microdomains in hippocampal neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 97 15659591
1990 Ca2+/calmodulin kinase is activated by the phosphatidylinositol signaling pathway and becomes Ca2(+)-independent in PC12 cells. The Journal of biological chemistry 96 2211681
2003 Epithelial Ca2+ entry channels: transcellular Ca2+ transport and beyond. The Journal of physiology 94 12869611
2011 Ca2+-dependent modulation of voltage-gated Ca2+ channels. Biochimica et biophysica acta 89 22223119
1991 v-erbA overexpression is required to extinguish c-erbA function in erythroid cell differentiation and regulation of the erbA target gene CAII. Genes & development 89 1682217
1985 Amount and distribution of carbonic anhydrases CA I and CA II in the gastrointestinal tract. Gastroenterology 88 3920111
1994 Properties of intracellular Ca2+ waves generated by a model based on Ca(2+)-induced Ca2+ release. Biophysical journal 84 7696462
2003 Mitochondrial Ca2+ uptake requires sustained Ca2+ release from the endoplasmic reticulum. The Journal of biological chemistry 80 12586823
2014 Evolution of acidic Ca²⁺ stores and their resident Ca²⁺-permeable channels. Cell calcium 78 25591931
2009 Compartmentalized signalling: Ca2+ compartments, microdomains and the many facets of Ca2+ signalling. The FEBS journal 78 19243429
2003 A phenocopy of CAII deficiency: a novel genetic explanation for inherited infantile osteopetrosis with distal renal tubular acidosis. Journal of medical genetics 74 12566520
2009 Presenilin-2 dampens intracellular Ca2+ stores by increasing Ca2+ leakage and reducing Ca2+ uptake. Journal of cellular and molecular medicine 73 19382908
2004 Ca2+ release via ryanodine receptors and Ca2+ entry: major mechanisms in NAADP-mediated Ca2+ signaling in T-lymphocytes. Cellular signalling 73 15337527
2008 Nuclear Ca2+ regulates cardiomyocyte function. Cell calcium 70 18201761
2007 Local Ca2+ influx through Ca2+ release-activated Ca2+ (CRAC) channels stimulates production of an intracellular messenger and an intercellular pro-inflammatory signal. The Journal of biological chemistry 70 18156181
1985 Relationships between Ca2+ release, Ca2+ cycling, and Ca2+-mediated permeability changes in mitochondria. The Journal of biological chemistry 67 2413023
2002 Amino acids and Ca2+ stimulate different patterns of Ca2+ oscillations through the Ca2+-sensing receptor. American journal of physiology. Cell physiology 66 11997256
2001 Na+-Ca2+ exchanger remodeling in pressure overload cardiac hypertrophy. The Journal of biological chemistry 66 11279089
1990 Ca2(+)-induced Ca2+ release as examined by photolysis of caged Ca2+ in single ventricular myocytes. The American journal of physiology 65 2301565
2011 Microdomain [Ca²⁺] near ryanodine receptors as reported by L-type Ca²⁺ and Na+/Ca²⁺ exchange currents. The Journal of physiology 64 21486798
2005 Presynaptic Ca2+ dynamics, Ca2+ buffers and synaptic efficacy. Cell calcium 61 15820398
2000 Effects of the immunosuppressant FK506 on intracellular Ca2+ release and Ca2+ accumulation mechanisms. The Journal of physiology 61 10856121
2005 Ca2+ dysregulation induces mitochondrial depolarization and apoptosis: role of Na+/Ca2+ exchanger and AKT. The Journal of biological chemistry 60 16061478
2005 Ca2+ and synaptic plasticity. Cell calcium 60 16154476
2001 Plasticity and adaptation of Ca2+ signaling and Ca2+-dependent exocytosis in SERCA2(+/-) mice. The EMBO journal 60 11387203
2007 Fortilin binds Ca2+ and blocks Ca2+-dependent apoptosis in vivo. The Biochemical journal 59 17705784
1991 Localization and activity of renal carbonic anhydrase (CA) in CA-II deficient mice. Biochimica et biophysica acta 59 1906751
2004 Ca2+ dependence of the Ca2+-selective TRPV6 channel. The Journal of biological chemistry 58 15184369
2012 Ca2+-dependent transcriptional control of Ca2+ homeostasis. The Journal of biological chemistry 56 22822058
1992 Transcriptional repression of band 3 and CAII in v-erbA transformed erythroblasts accounts for an important part of the leukaemic phenotype. The EMBO journal 56 1354613
2019 Carbonic anhydrase 2 (CAII) supports tumor blood endothelial cell survival under lactic acidosis in the tumor microenvironment. Cell communication and signaling : CCS 55 31847904
2007 Ca2+ stores regulate ryanodine receptor Ca2+ release channels via luminal and cytosolic Ca2+ sites. Clinical and experimental pharmacology & physiology 55 17645636
1984 Variable CA II compartmentalization in vertebrate retina. Annals of the New York Academy of Sciences 52 6430181
1995 Na+/H+ and Na+/Ca2+ exchange in regulation of [Na+]i and [Ca2+]i during metabolic inhibition. The American journal of physiology 51 7900878
2002 Plasma membrane Ca2+-ATPase and NCX1 Na+/Ca2+ exchanger expression in distal convoluted tubule cells. American journal of physiology. Renal physiology 48 12060584
1998 Thyroid control of sarcolemmal Na+/Ca2+ exchanger and SR Ca2+-ATPase in developing rat heart. The American journal of physiology 47 9688923
1986 Nucleotide sequence, tissue-specific expression, and chromosome location of human carbonic anhydrase III: the human CAIII gene is located on the same chromosome as the closely linked CAI and CAII genes. Proceedings of the National Academy of Sciences of the United States of America 47 3099285
2009 Measurement of nanomolar dissociation constants by titration calorimetry and thermal shift assay - radicicol binding to Hsp90 and ethoxzolamide binding to CAII. International journal of molecular sciences 46 19582223
2005 Ca2+ signalling in cardiogenesis. Cell calcium 44 16099501
2002 Ca2+-stimulated Ca2+ oscillations produced by the Ca2+-sensing receptor require negative feedback by protein kinase C. The Journal of biological chemistry 44 12356761
2000 Immunolocalization of CA II and H+ V-ATPase in epithelial cells of the mouse and rat epididymis. Journal of andrology 44 10819445
1998 Ca2+ entry in CHO cells, after Ca2+ stores depletion, is mediated by arachidonic acid. Cell calcium 44 9883283
1996 Protein kinase C mediates Ca2(+)-induced cardioadaptation to ischemia-reperfusion injury. The American journal of physiology 44 8853396
1990 Alterations in heart sarcolemmal Ca2(+)-ATPase and Ca2(+)-binding activities due to oxygen free radicals. Basic research in cardiology 44 2158297
2010 RyR1-mediated Ca2+ leak and Ca2+ entry determine resting intracellular Ca2+ in skeletal myotubes. The Journal of biological chemistry 43 20207743
2004 Bax affects intracellular Ca2+ stores and induces Ca2+ wave propagation. Cell death and differentiation 41 15499375
2009 Ca2+ waves initiate antigen-stimulated Ca2+ responses in mast cells. Journal of immunology (Baltimore, Md. : 1950) 40 19864608
2002 Ca2+-dependent and Ca2+-independent regulation of smooth muscle contraction. Journal of muscle research and cell motility 40 12363284
1996 Na+/Ca2+ exchange currents and SR Ca2+ contents in postinfarction myocytes. The American journal of physiology 39 8997179
1990 Cyclic AMP- and Ca2(+)-dependent protein kinases in Plasmodium falciparum. Experimental parasitology 39 2191871
2007 Ca2+-pumps and Na2+-Ca2+-exchangers in coronary artery endothelium versus smooth muscle. Journal of cellular and molecular medicine 38 17367507
1998 Na+/Ca2+ exchange and cellular Ca2+ homeostasis. Journal of bioenergetics and biomembranes 38 9672237
1990 Monomeric state and Ca2+ transport by sarcoplasmic reticulum Ca2(+)-ATPase, reconstituted with an excess of phospholipid. The Journal of biological chemistry 38 2142157
1994 Membrane-associated CA activity in the eye of the CA II-deficient mouse. Investigative ophthalmology & visual science 37 8163345
1990 Ca2+ channels and intracellular Ca2+ stores in neuronal and neuroendocrine cells. Cell calcium 37 2162259
1998 The Ca2+ pumps and the Na+/Ca2+ exchangers. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 35 10191496
2016 Cell-Permeable Esterase-Activated Ca(II)-Sensitive MRI Contrast Agent. Bioconjugate chemistry 33 26689452
2010 Ca2+ extrusion via Na+-Ca2+ exchangers in rat odontoblasts. Journal of endodontics 33 20307742
2007 The role of the Na+/Ca2+ exchangers in Ca2+ dynamics in ventricular myocytes. Progress in biophysics and molecular biology 33 17959231
2006 Hypertension, Na+/Ca2+ exchanger, and Na+, K+-ATPase. Kidney international 33 16641927
2004 Ca2+-calmodulin-dependent facilitation and Ca2+ inactivation of Ca2+ release-activated Ca2+ channels. The Journal of biological chemistry 33 15611075
1994 Compartmentalization of Ca2+ signaling and Ca2+ pools in pancreatic acini. Implications for the quantal behavior of Ca2+ release. The Journal of biological chemistry 33 7961950
2007 Reversed Na+/Ca2+ exchange contributes to Ca2+ influx and respiratory burst in microglia. Channels (Austin, Tex.) 32 18690036
1993 Increased intracellular Ca2+ induces Ca2+ influx in human T lymphocytes. Molecular biology of the cell 32 8443415
2007 Regulation of cardiac Na+/Ca2+ exchanger by phospholemman. Annals of the New York Academy of Sciences 31 17446450
1996 Ca2+ oscillations and intercellular Ca2+ waves in ATP-stimulated articular chondrocytes. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 31 8797115
1997 Na+/Ca2+ exchanger in Drosophila: cloning, expression, and transport differences. The American journal of physiology 30 9252464
1996 Measurement of human erythrocyte CAI and CAII in adult, newborn, and fetal blood. Clinical biochemistry 29 8601325
1987 Pituitary Ca2+ channels: blockade by conventional and novel Ca2+ antagonists. The American journal of physiology 29 2440312
2012 Ca²⁺ influx-dependent refilling of intracellular Ca²⁺ stores determines the frequency of Ca²⁺ oscillations in fertilized mouse eggs. Biochemical and biophysical research communications 28 23159627
1994 Temporal relationships between Ca2+ store mobilization and Ca2+ entry in an exocrine cell. Cell calcium 28 8082129
1991 Ca(2+)-induced Ca2+ release amplifies the Ca2+ response elicited by inositol trisphosphate in macrophages. Cell regulation 28 1782213

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