Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1)

Calcium-binding and coiled-coil domain-containing protein 1 (CALCOCO1) is a multifunctional cytosolic and nuclear protein involved in selective autophagy and transcriptional coactivation. CALCOCO1 acts as a soluble endoplasmic reticulum (ER)-phagy receptor, specifically facilitating the autophagic degradation of tubular ER subdomains during proteotoxic and nutrient stress. It interacts directly with ER membrane tethering proteins VAPA and VAPB via a conserved FFAT-like motif, and with ATG8-family autophagy proteins (preferentially GABARAPs) via LIR and UIR motifs, thereby serving as a platform for autophagosome formation and cargo specificity. CALCOCO1 is also known as a coactivator for aryl hydrocarbon and nuclear receptors, recruited to gene promoters either directly or via interaction with additional coactivators, contributing to the activation of transcriptional programs (such as Wnt/CTNNB1 signaling and gamma-globin promoter activation in erythroid cells). The protein has paralogs TAX1BP1 and NDP52, sharing domain architecture and autophagy functions. Disease associations include roles in cancer dynamics—particularly sarcoma and pancreatic cancer—potentially linking autophagy, cell stress adaptation, and transcriptional regulation. CALCOCO1 has not been directly drugged or validated as a clinical biomarker but remains a molecular node at the interface of cell metabolism, stress response, and gene expression.

Other names

CALCOCO1KIAA1536PP13275CocoaCalphoglinCoiled-coil coactivator proteinSarcoma antigen NY-SAR-3Coiled-coil leucine zipper coactivator 1Inorganic pyrophosphatase activator

No current therapeutic drugs act directly on this protein; mechanistically, would mediate selective autophagy and transcription regulation if targeted