Ask about this productRelated genes to: CAB39 antibody
- Gene:
- CAB39 NIH gene
- Name:
- calcium binding protein 39
- Previous symbol:
- -
- Synonyms:
- CGI-66, MO25
- Chromosome:
- 2q37.1
- Locus Type:
- gene with protein product
- Date approved:
- 2004-07-02
- Date modifiied:
- 2015-08-26
Related products to: CAB39 antibody
Related articles to: CAB39 antibody
- The sodium-chloride cotransporter (NCC) in the distal convoluted tubule regulates renal sodium reabsorption, potassium homeostasis, and blood pressure. NCC phosphorylation is controlled by extracellular potassium via the with-no-lysine (WNK)-STE20/SPS1-related proline-alanine-rich kinase (SPAK) kinase cascade, proposed to initiate within biomolecular condensates termed WNK bodies. Kidney-specific with-no-lysine kinase (KS-WNK1) and calcium-binding protein 39 (Cab39) play different roles in WNK body formation and dissolution. Although KS-WNK1 is required for organizing WNK bodies, previous studies suggest that Cab39 promotes SPAK translocation from the WNK bodies to the apical membrane; Cab39 deletion traps phosphorylated SPAK in intracellular puncta and suppresses NCC phosphorylation. Whether these puncta represent bona fide WNK bodies or distinct condensates is unknown. To test whether SPAK puncta require KS-WNK1, we generated mice with distal convoluted tubule-specific deletion of both Cab39 isoforms and KS-WNK1 (triple knockout). NCC, phosphorylated SPAK, and WNK4 expression and localization were assessed by immunoblotting, immunofluorescence, and quantitative (PCR) under low- and high-potassium diets that activate or inhibit the WNK-SPAK-NCC pathway. Despite elevated WNK4, triple-knockout mice exhibited marked NCC hypo-phosphorylation. Phosphorylated SPAK accumulated in cytoplasmic puncta resembling WNK bodies even without KS-WNK1, indicating they are distinct from canonical WNK bodies. Under high-potassium conditions, when WNK4 and SPAK are dephosphorylated, these puncta were absent, suggesting dependence on upstream kinase activity. Thus, SPAK puncta form independently of KS-WNK1, previously considered necessary for WNK body formation, revealing distinct signaling condensates. In this study, we identify novel biomolecular condensates (puncta) that appear in the absence of KS-WNK1, a component of WNK bodies. Mice knockout for both KS-WNK1 and Cab39 adaptor proteins exhibit large SPAK-containing puncta that also comprise WNK4 and L-WNK1. These puncta are p62-positive and ubiquitin-negative, indicating that they are sequestrating rather than degrading structures. Formation of these puncta requires active phosphorylation, as they are not observed in mice fed with a high K diet. - Source: PubMed
Publication date: 2026/03/28
Ferdaus Mohammed ZubaerulInoue Masa-KiTerker Andrew SWelling Paul ADelpire Eric - Aging is a major risk factor for diabetic kidney disease (DKD), with both conditions exhibiting similar renal pathology. We identify the energy-sensing molecule Retinoic acid-related orphan receptor γ (RORγ) as significantly downregulated in diabetic and aged kidneys. Tubule-specific RORγ deficiency exacerbates kidney injury, whereas its overexpression protects. Mechanistically, RORγ stabilizes insulin-induced gene 1 (INSIG1) by upregulating the deubiquitinase YOD1 and enhancing AMPK activity via CAB39, which together promote INSIG1 phosphorylation and subsequent stabilization. Stabilized INSIG1 potently blocks the ER-to-Golgi transport and activation of SREBP2 (cholesterol synthesis) and STING (inflammatory signaling). In diabetes, RORγ itself is suppressed transcriptionally by CTCF and functionally by impaired AMPK/SIRT1 signaling, which hinders its activation. Importantly, administration of a RORγ agonist or RORγ-enriched exosomes effectively alleviates diabetic kidney injury. Thus, RORγ emerges as a key regulatory node that mitigates DKD and renal aging by co-regulating AMPK-mediated metabolic and STING-driven innate immune pathways through INSIG1 stabilization. - Source: PubMed
Publication date: 2026/02/18
Liang ZhenXiang JiaqingYang GuangyanLiu XiaomaiLi LixingLi YanchunLu YanKang LinChen YuanliMa ChuanruiYang Shu - In avian species, the chorioallantoic membrane (CAM) is a vital, highly vascularized extraembryonic structure that supports embryonic respiration, calcium transport, and innate immune defense. In this study, we applied LC/MS/MS-based proteomics to CAM tissue harvested at embryonic days (ED) 6, 8, 10, and 12 to characterize its protein profile during the expression of different CAM functionalities during embryonic development and gain insight into possible sex-based distinctions. A total of 2688 proteins were identified, with 2347, 2265, 2351, and 1267 proteins detected at ED 6, 8, 10, and 12, respectively. Notably, 1191 common proteins were identified across all stages, while 124, 47, 86, and 2 proteins were uniquely expressed at ED 6, 8, 10, and 12, respectively. Functional annotation revealed correlations with abundant CAM protein constituents (as per their emPAI); for example: calcium mobilization - v-type proton ATPase subunit E1 (ATP6V1E1) and G1 (ATP6V1G1); intracellular transport-calcium-binding protein 39 (CAB39); vascular system and gaseous exchange - annexin A2 (ANXA2); lymphatics-actin, gamma 1 (ACTG1); blood elements-hemoglobin subunit alpha-1 (HBA1); immune defense-cathelicidin-1 (CATH1), cathelicidin-2 (CATH2); and protection against luminal toxic contents-thioredoxin (TXN). Notably, a sex-specific analysis identified 614, 320, 314, and 212 proteins that were uniquely expressed in female embryos, and 212, 273, 144, and 56 proteins only in male embryos at ED 6, 8, 10, and 12, respectively. The identification of sex-linked proteins during early CAM development may provide insight into their functional roles and highlight the CAM's potential as a target for the development of sex identification technology. - Source: PubMed
Publication date: 2025/12/24
Ali SofhianAhmed Tamer A EShrestha AgrimaHincke Maxwell T - : Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations, leading to deficient α-galactosidase A (α-Gal A) activity and progressive glycosphingolipid accumulation. While α-Gal A activity is the diagnostic gold standard, its sensitivity is reduced in late-onset or heterozygous patients. Conventional biomarkers such as lyso-Gb3 provide only limited insight into disease progression and therapeutic response. Exosomes, as stable carriers of disease-specific proteins, may offer complementary biomarkers for early detection and longitudinal monitoring. : Twenty-one pediatric FD patients with confirmed GLA mutations were enrolled. Clinical, enzymatic, renal, and cardiac parameters were assessed. Plasma-derived exosomes were characterized by transmission electron microscopy and proteomic profiling. Differentially expressed proteins were identified using mass spectrometry, analyzed using GO/KEGG enrichment, and validated using RT-PCR, ELISA, and immunofluorescence in patient samples and mice. : Male patients showed markedly reduced α-Gal A activity and elevated lyso-Gb3 compared with females. Although overt renal and cardiac dysfunction was uncommon, several patients exhibited early abnormalities such as proteinuria, an elevated LVMI, or increased cTnI levels. Proteomic analysis identified 2553 proteins, of which 188 were differentially expressed. Fibrosis- and inflammation-related proteins, including THBS1 and CFHR5, were upregulated, while protective factors such as APM1, SERPINA10, and CAB39 were downregulated. IGFBP3 was also elevated and closely linked to tissue remodeling. Enriched pathways were involved in PPAR/AMPK signaling, lipid metabolism, and complement activation. : Exosomal proteomic profiling revealed early molecular signatures of cardiorenal involvement in pediatric FD. Key proteins such as THBS1, CFHR5, IGFBP3, APM1, and CAB39 show strong potential as biomarkers for risk stratification, disease monitoring, and therapeutic evaluation. - Source: PubMed
Publication date: 2025/10/23
Lu ZhihongXia YuWang BingyingJiang PingpingMao Jianhua - MicroRNA 451 (miR-451) is emerging as a pivotal mediator of cardiac damage in experimental models of diabetic cardiomyopathy. Whether miR-451 plays a detrimental role in the human diabetic myocardium is unknown. The present study investigates miR-451's role in patients with type 2 diabetes (T2D). We show that miR-451 is upregulated in myocardial specimens from T2D patients compared to controls without diabetes and correlates with cardiometabolic parameters, the myocardial triglyceride content and cardiac expression of lipotoxic genes as well as echocardiographic indices of left ventricular dysfunction. Calcium-binding protein 39 (Cab39)-a known target of miR-451 in mouse hearts-was downregulated in T2D patients vs. controls, and its expression negatively correlated with that of miR-451. In cultured human cardiomyocytes (CMs), Ago2 immunoprecipitation confirmed Cab39 to be a direct target of miR-451. Treatment with a high amount of glucose (25mM) and palmitic acid (PA) mimicked miR-451 upregulation and Cab39 downregulation in human CMs. These changes were associated with increased TGs and markers of lipotoxic injury, such as elevated oxidative stress levels, mitochondrial dysfunction and apoptosis. Targeting miR-451 led to restoration of Cab39 levels while rescuing diabetes-induced lipotoxic injury and metabolic dysfunction. By contrast, miR-451 overexpression recapitulated features of lipotoxic damage. Our findings indicate miR-451 to be a potential target for the prevention of myocardial lipotoxic injury in diabetes. - Source: PubMed
Publication date: 2025/09/08
Costantino SarahMohammed Shafeeq ARanocchi FedericoZito FrancescoDelfine ValentinaHamdani NazhaVinci Maria CristinaMelina GiovanniPaneni Francesco