| Topic | Key findings | Evidence type (review/primary, in vitro/in vivo) | Year | Citation (DOI URL where available) | Context ID |
|---|---|---|---|---|---|
| Molecular function | Human PGRMC1 (UniProt O00264) is a MAPR-family, cytochrome b5-like heme-binding protein with a surface-exposed heme site; recent work confirms heme binding stabilizes the cytosolic domain and supports interaction models relevant to downstream partners. | Primary biochemical/structural; in vitro | 2024 | Badve & Meier, *Biochemistry* (2024), https://doi.org/10.1021/acs.biochem.3c00718 | (pqac-00000003) |
| Key residues | Tyr113 is the canonical heme-coordinating residue in the crystal model; Tyr107, Lys163, Tyr164, Asp99-Lys102, and Asp120 also influence heme binding or partner effects. Y113F abolishes direct Fe coordination, while Cys129 is central to disulfide-linked dimerization. | Review synthesizing primary mutagenesis/structural studies; in vitro | 2024 | Barata et al., *Journal of Xenobiotics* (2024), https://doi.org/10.3390/jox14020034; Badve & Meier, *Biochemistry* (2024), https://doi.org/10.1021/acs.biochem.3c00718 | (pqac-00000001, pqac-00000004) |
| Dimerization | PGRMC1 can form dimers/oligomers through two nonexclusive mechanisms: intermolecular disulfide formation centered on Cys129 and heme–heme stacking; earlier heme-dependent dimer models are being refined rather than simply accepted. | Primary spectroscopy/mutagenesis; in vitro | 2024 | Badve & Meier, *Biochemistry* (2024), https://doi.org/10.1021/acs.biochem.3c00718 | (pqac-00000004, pqac-00000005) |
| CYP modulation | PGRMC1 interacts with multiple CYPs and can modulate activity in an isoform-dependent manner. Reported partners include CYP7A1, CYP21A2, CYP51A1, CYP3A4, CYP2C8, CYP2C2, and CPR; effects include altered Km/kcat and either stimulation or inhibition depending on CYP and expression level. | Review of primary biochemical/cellular studies; in vitro and in vivo | 2024 | Barata et al., *Journal of Xenobiotics* (2024), https://doi.org/10.3390/jox14020034 | (pqac-00000000, pqac-00000006, pqac-00000007) |
| Heme trafficking / ferrochelatase | PGRMC1 has been proposed as a heme-transfer or heme-buffering factor and a partner/regulator of ferrochelatase (FECH). Recent reviews emphasize that this remains plausible but incompletely resolved in vivo. | Review of primary studies; biochemical/cellular | 2024 | Barata et al., *Journal of Xenobiotics* (2024), https://doi.org/10.3390/jox14020034; Dunaway et al., *JBC* (2024), https://doi.org/10.1016/j.jbc.2024.107132 | (pqac-00000000, pqac-00000003) |
| EGFR / progesterone signaling | PGRMC1 has been implicated in progesterone anti-apoptotic signaling via SERBP1/PAIRBP1 and in EGFR-associated oncogenic signaling, including links to Wnt/β-catenin and NF-κB pathways and erlotinib resistance. | Review of primary cell biology/cancer studies; mostly in vitro/in vivo models | 2024 | Barata et al., *Journal of Xenobiotics* (2024), https://doi.org/10.3390/jox14020034 | (pqac-00000002) |
| TMEM97 / sigma-2 complex | Recent literature places PGRMC1 in a TMEM97 (sigma-2 receptor)-LDLR-PGRMC1 membrane complex relevant to cholesterol biology and Alzheimer’s disease drug development. A graphical mechanism for CT1812 proposes that binding to this complex indirectly displaces synaptotoxic Aβ oligomers. | Review/clinical translational reports; human clinical biomarker study and mechanistic model | 2024 | Lizama et al., *Alzheimer’s & Dementia* (2024), https://doi.org/10.1002/alz.14152; Lizama et al., *bioRxiv* (2024), https://doi.org/10.1101/2024.02.16.578765 | (pqac-00000013) |
| Localization | PGRMC1 localizes across multiple compartments depending on cell type: ER/endomembranes are most consistent, with additional reports at plasma membrane, nucleus/nuclear membrane, Golgi, endosomes, and mitochondria. | Review and primary studies; microscopy/fractionation; in vitro and in vivo | 2023-2024 | Barata et al., *Journal of Xenobiotics* (2024), https://doi.org/10.3390/jox14020034; Jo et al., *AJP Gastrointest Liver Physiol* (2023), https://doi.org/10.1152/ajpgi.00206.2022; Jo & Hong, *Antioxidants* (2024), https://doi.org/10.3390/antiox13020230 | (pqac-00000009, pqac-00000010, pqac-00000011) |
| Mitochondrial function / liver injury | In a 2023 ethanol liver-injury study, loss of Pgrmc1 increased acetaldehyde, ALT, ER stress, and apoptosis in mice, supporting a protective hepatic role linked to alcohol metabolism and oxidative stress. | Primary mouse study; in vivo | 2023 | Jo et al., *AJP Gastrointest Liver Physiol* (2023), https://doi.org/10.1152/ajpgi.00206.2022 | (pqac-00000010) |
| Stress / inflammation | In chronic neuroinflammation models, Pgrmc1 knockout increased inflammatory cytokines, NF-κB signaling, ER-stress markers, and apoptosis, consistent with a protective role in cellular stress and inflammatory control. | Primary mouse/cell study; in vivo and in vitro | 2024 | Jo & Hong, *Antioxidants* (2024), https://doi.org/10.3390/antiox13020230 | (pqac-00000009) |
| Reproductive physiology | In human endometrial stromal cell decidualization models, PGRMC1 shows a progesterone-induced rise-to-decline program; knockdown before induction blocks decidualization, and PHB1/PHB2 emerge as inducible partners. | Primary human cell study; in vitro | 2024 | Liu et al., *Reproductive Biology and Endocrinology* (2024), https://doi.org/10.1186/s12958-024-01188-9 | (pqac-00000012) |
| Disease / application | PGRMC1 remains a candidate biomarker or functional node in cancer, neurodegeneration, liver injury, and reproductive disease, but direct clinical targeting is less mature than targeting the associated sigma-2/TMEM97 axis (e.g., CT1812 in AD; sigma-2 ligands in cancer). | Review + translational/clinical studies | 2024 | Takchi et al., *Cell Death & Disease* (2024), https://doi.org/10.1038/s41419-024-06693-8; Hagi et al., *Scientific Reports* (2024), https://doi.org/10.1038/s41598-024-56928-z; Lizama et al., *Alzheimer’s & Dementia* (2024), https://doi.org/10.1002/alz.14152 | (pqac-00000013, pqac-00000008) |


*Table: This table summarizes experimentally supported functions, partners, localization, and recent 2023-2024 developments for human PGRMC1 (UniProt O00264). It is useful as a compact evidence map linking molecular mechanism to physiological and translational relevance.*