| Aspect | Evidence-based summary | Key supporting papers |
|---|---|---|
| Identity / domains | Human **CALCOCO1** corresponds to UniProt **Q9P1Z2** and is also known as **Calphoglin / Coiled-coil coactivator protein (CoCoA) / NY-SAR-3**. Functional/domain analyses place it in the CALCOCO family and support an **N-terminal SKICH region**, a **canonical LIR**, a **non-canonical CLIR** that contributes to MAP1LC3C binding, and C-terminal ubiquitin-associated/zinc-finger features noted in domain annotations and selective-autophagy literature. Mutagenesis of **W47A** (LIR), **L140A/V142A** (CLIR), and **R12H** demonstrated motif-dependent LC3-family interactions. (pqac-00000002, pqac-00000004, pqac-00000010) | Stefely 2020, *Autophagy*, https://doi.org/10.1080/15548627.2020.1719746; Zhang 2024, *PNAS*, https://doi.org/10.1073/pnas.2315550121 (pqac-00000002, pqac-00000004, pqac-00000010) |
| Localization | Experimental fractionation and imaging show CALCOCO1 is **predominantly cytoplasmic**, associates with **vesicular/light membrane fractions**, and is **proximal to the ER**; some studies also detected **cytoplasmic and nuclear fractions**, whereas other analyses found little nuclear signal in several cell lines, suggesting context-dependent dual localization rather than a primarily nuclear protein in autophagy settings. A **minor Golgi-localized pool** has been proposed in Golgiphagy models. (pqac-00000000, pqac-00000001, pqac-00000002, pqac-00000009, pqac-00000010) | Stefely 2020, *Autophagy*, https://doi.org/10.1080/15548627.2020.1719746; Ma & Zhang 2024, *Life Metabolism*, https://doi.org/10.1093/lifemeta/load049 (pqac-00000000, pqac-00000001, pqac-00000002, pqac-00000009, pqac-00000010) |
| Key binding partners | Co-immunoprecipitation/mutagenesis support binding to **ATG8-family proteins**, with strongest reported preference for **MAP1LC3C**, plus interactions with **MAP1LC3B** and **GABARAPL2** that increase when autophagy is blocked. ER-phagy reviews further place CALCOCO1 in complexes with **VAPA/VAPB** on the ER, and Golgiphagy commentary links it to **ZDHHC17** at the Golgi. In transcriptional settings, CALCOCO1/CoCoA interacts functionally with **CCAR1**, **SRC2/GRIP1**, **β-catenin**, **p300**, **GATA1**, and mediator-linked machinery. (pqac-00000001, pqac-00000002, pqac-00000004, pqac-00000009, pqac-00000011, pqac-00000014, pqac-00000015, pqac-00000017) | Stefely 2020, *Autophagy*, https://doi.org/10.1080/15548627.2020.1719746; Kim 2008, *Molecular Cell*, https://doi.org/10.1016/j.molcel.2008.08.001; Mizuta 2014, *Genes to Cells*, https://doi.org/10.1111/gtc.12104; Wu 2014, *Nuclear Receptor Signaling*, https://doi.org/10.1621/nrs.12002 (pqac-00000001, pqac-00000002, pqac-00000004, pqac-00000009, pqac-00000011, pqac-00000014, pqac-00000015, pqac-00000017) |
| ER-phagy / reticulophagy role | The strongest primary-function evidence supports CALCOCO1 as a **soluble selective ER-phagy receptor/adaptor** in **MTOR-regulated reticulophagy**. CRISPR loss of CALCOCO1 reduced reporter-based ER-phagy by about **50%** in a GST-LSCS-GFP-cb5 assay and about **25%** in a Keima-cb5 assay, while altering ER protein turnover and MAP1LC3C-II accumulation. 2024 work indicates CALCOCO1 functions **in parallel with RTN3L and ATL3** to target misfolded ER cargo and maintain ER proteostasis, while neurogenesis studies suggest receptor redundancy and that CALCOCO1 alone is not universally essential for ER maintenance in all developmental contexts. (pqac-00000003, pqac-00000004, pqac-00000006, pqac-00000008, pqac-00000010) | Stefely 2020, *Autophagy*, https://doi.org/10.1080/15548627.2020.1719746; Kumar 2024, *Autophagy*, https://doi.org/10.1080/15548627.2024.2353502; Hoyer 2024, *Nature Cell Biology*, https://doi.org/10.1038/s41556-024-01356-4 (pqac-00000003, pqac-00000004, pqac-00000006, pqac-00000008, pqac-00000010) |
| Golgiphagy role | CALCOCO1 has been proposed as a **Golgiphagy receptor** under starvation/stress, likely via Golgi-associated interactions such as **ZDHHC17**. However, 2024 Golgiphagy studies indicate **YIPF3/YIPF4** are major Golgiphagy receptors in HeLa cells, and **CALCOCO1 knockdown alone did not decrease Golgiphagy** in that reporter system; commentary therefore supports a model where CALCOCO1 contributes in a **distinct, non-redundant or context-specific pathway** rather than serving as the dominant Golgi receptor in all cells. (pqac-00000006, pqac-00000009) | Kitta 2024, *EMBO Journal*, https://doi.org/10.1038/s44318-024-00131-3; Ma & Zhang 2024, *Life Metabolism*, https://doi.org/10.1093/lifemeta/load049 (pqac-00000006, pqac-00000009) |
| Transcriptional coactivator role | Independently of autophagy, CALCOCO1 was originally characterized as **CoCoA**, a **transcriptional coactivator/coregulator**. Its **central coiled-coil** binds p160 coactivators, while C-terminal activation regions support transcriptional activation. CALCOCO1/CoCoA cooperates with **CCAR1** to help recruit **Mediator** and RNA polymerase II to target genes, supporting transcription driven by **nuclear receptors**, **p53**, **β-catenin**, and **GATA1**. In K562 erythroid differentiation, CoCoA expression rose about **4-fold**, and knockdown reduced globin-gene expression. (pqac-00000011, pqac-00000012, pqac-00000013, pqac-00000014, pqac-00000016, pqac-00000017, pqac-00000018) | Kim 2008, *Molecular Cell*, https://doi.org/10.1016/j.molcel.2008.08.001; Mizuta 2014, *Genes to Cells*, https://doi.org/10.1111/gtc.12104; Wu 2014, *Nuclear Receptor Signaling*, https://doi.org/10.1621/nrs.12002 (pqac-00000011, pqac-00000012, pqac-00000013, pqac-00000014, pqac-00000016, pqac-00000017, pqac-00000018) |
| Disease / biomarker links | Evidence for direct disease causality remains limited, but CALCOCO1 has several **emerging disease links**. It was originally identified as the cancer antigen **NY-SAR-3**. In breast-cancer models, CALCOCO1 depletion reduced mammosphere formation by about **50%**, suggesting a role in cancer stem-like traits. In a 2024 multi-omics study of **87 Alzheimer’s disease patients**, CALCOCO1 was among the **top five significantly downregulated plasma proteins** in the high-severity (high ADAS-Cog) group. A 2023 LUAD bioinformatic study associated **low CALCOCO1 expression** with poorer prognosis, although exact HRs/p-values were not available in the extracted text. (pqac-00000000, pqac-00000008, pqac-00000019, pqac-00000020) | Stefely 2020, *Autophagy*, https://doi.org/10.1080/15548627.2020.1719746; Meng 2024, *Alzheimer’s Research & Therapy*, https://doi.org/10.1186/s13195-024-01578-6; Wei 2023, *Hereditas*, https://doi.org/10.1186/s41065-023-00289-6 (pqac-00000000, pqac-00000008, pqac-00000019, pqac-00000020) |
| Regulation | CALCOCO1 is regulated by **MTOR-dependent autophagy and lysosomal flux**. **MLN0128**-mediated MTOR inhibition decreased CALCOCO1 abundance, whereas **chloroquine** or **bafilomycin A1** increased it; CALCOCO1 also accumulated in **ATG7/ATG3-deficient** cells, indicating autophagy-dependent turnover. Cycloheximide chase suggested a half-life of about **24 h**. Interactions with LC3-family proteins strengthened when autophagy was blocked, and recent literature places CALCOCO1 within broader nutrient/starvation and organelle-stress response networks affecting ER and Golgi homeostasis. (pqac-00000001, pqac-00000002, pqac-00000003, pqac-00000007, pqac-00000010) | Stefely 2020, *Autophagy*, https://doi.org/10.1080/15548627.2020.1719746 (pqac-00000001, pqac-00000002, pqac-00000003, pqac-00000007, pqac-00000010) |


*Table: This table summarizes the main experimentally supported functions, localization, interactions, and disease links of human CALCOCO1 (UniProt Q9P1Z2). It is useful as a compact evidence map spanning both its autophagy-receptor and transcriptional-coactivator roles.*