Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity.
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt.
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara.
Combined Automated Annotation using Multiple IEA Methods.
Large-scale mapping of human protein-protein interactions by mass spectrometry.
Defining the membrane proteome of NK cells.
Progesterone receptor membrane component 1 inhibits the activity of drug-metabolizing cytochromes P450 and binds to cytochrome P450 reductase.
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PGRMC1 binds efficiently to drug-metabolising CYPs (CYP2C2, CYP2C8, CYP3A4) primarily via their cytoplasmic catalytic domains and inhibits their activities in a PGRMC1-concentration-dependent manner; this inhibition is partially reversed by elevated CPR expression. In contrast PGRMC1 stimulates sterol-biosynthetic CYP51, illustrating isoform-specific CYP modulation. PGRMC1 also binds directly to CPR.
"PGRMC1 bound efficiently to all three P450s ... Cotransfection of cells with P450s and PGRMC1 resulted in PGRMC1 concentration-dependent inhibition of the P450 activities, and this inhibition was partially reversed by increased expression of the P450 reductase (CPR). In contrast, CYP51 activity was decreased by down-regulation of PGRMC1 and expression of PGRMC1 in the PGRMC1-deficient cells increased CYP51 activity."
Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers II: Sigma-2/PGRMC1 receptors mediate Abeta 42 oligomer binding and synaptotoxicity.
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Sigma-2/PGRMC1 is enriched in post-synaptic density fractions; siRNA knockdown of PGRMC1 in cultured neurons reduces >90% of Abeta oligomer binding and downstream synaptotoxicity, identifying it as a key oligomer receptor (or receptor-complex component) in Alzheimer's disease.
"We have identified the sigma-2/PGRMC1 protein as a critical receptor mediating greater than 90% of Abeta oligomer binding to neurons and their downstream synaptotoxic effects."
The Cellular Phase of Alzheimer's Disease.
Haem-dependent dimerization of PGRMC1/Sigma-2 receptor facilitates cancer proliferation and chemoresistance.
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X-ray crystal structure (1.95 Å) of PGRMC1 cytosolic domain shows a stable dimer formed by hydrophobic stacking of two protruding haem moieties; haem iron is five-coordinated by Tyr113 alone. Heme Kd ~50 nM. CO binds the sixth coordination position and dissociates the dimer. Haem-mediated dimerisation is required for binding to EGFR and to cytochromes P450 (CYP1A2, CYP3A4, CYP51), for cancer proliferation and for chemoresistance.
"the haem iron is five-coordinated by Tyr113 (Y113) alone ... haem binding to PGRMC1 was of low affinity with a Kd value of 50 nmol l−1 ... Haem-mediated PGRMC1 dimerization is required for interactions with EGFR and cytochromes P450"
A Novel Role for Progesterone Receptor Membrane Component 1 (PGRMC1): A Partner and Regulator of Ferrochelatase.
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PGRMC1 (and PGRMC2) co-fractionate and co-localise with the mitochondrial heme metabolon; PGRMC1 sits on the outer face of the outer mitochondrial membrane and interacts with ferrochelatase (FECH). In vitro PGRMC1 inhibits FECH activity dose-dependently (saturating at ~60% reduction) preferentially in the product-release conformation, and purified PGRMC1 can donate heme to apo-cytochrome b5, supporting a heme-chaperone/sensor role.
"In the presence of PGRMC1, in vitro measured FECH activity decreased in a dose-dependent manner. Interactions between FECH and PGRMC1 were strongest for the conformation of FECH associated with product release ... In vitro heme transfer experiments showed that purified PGRMC1 was able to donate heme to apo-cytochrome b5."
Architecture of the human interactome defines protein communities and disease networks.
Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei.
Sigma-2 Receptor/TMEM97 and PGRMC-1 Increase the Rate of Internalization of LDL by LDL Receptor through the Formation of a Ternary Complex.
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CRISPR knockout of PGRMC1 or TMEM97 in HeLa cells each independently reduce LDL internalisation by LDLR to the same extent as the double knockout, indicating both proteins act as obligate components of a single LDLR-PGRMC1-TMEM97 ternary complex required for rapid LDL endocytosis. Confocal microscopy and proximity ligation assays confirm co-localisation/interaction of the three proteins.
"These data indicate that the formation of a ternary complex of LDLR-PGRMC1-TMEM97 is necessary for the rapid internalization of LDL by LDLR."
A reference map of the human binary protein interactome.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
OpenCell: Endogenous tagging for the cartography of human cellular organization.
Sigma-2 Receptor Ligand Binding Modulates Association between TSPO and TMEM97.
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In MIA PaCa-2 pancreatic cancer cells (high PGRMC1) co-IP detected TSPO/PGRMC1 association in addition to TSPO/TMEM97, but no such PGRMC1/TSPO association was found in MCF7 cells, indicating cell-type- dependent multiprotein complexes around the sigma-2 receptor.
"in MP cells, we observed that both TMEM97 (Figure 4C) and PGRMC1 (Figure 4D) co-immunoprecipitated with TSPO"
Multimodal cell maps as a foundation for structural and functional genomics.
Cloning and tissue expression of two putative steroid membrane receptors.
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Original cloning of human Hpr6.6 (PGRMC1) as a putative steroid-binding membrane protein; mRNA predominantly liver and kidney. Naming reflects homology to a porcine progesterone-binding protein rather than direct steroid-binding assays.
"We have cloned two human putative steroid binding membrane proteins, termed Hpr6.6 and Dg6."
Exocytosis of specific granule membrane proteins
Deep research on PGRMC1 function (perplexity sonar-deep-research)
Deep research on PGRMC1 function (Edison/falcon, 2026)
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Contemporary expert synthesis (2024) frames PGRMC1 as a single-pass membrane MAPR-family heme-binding protein with surface-exposed heme coordination by Tyr113, two-mechanism (heme-stacking and Cys129 disulfide) dimerisation, and a primary functional role as a haem- dependent regulator of microsomal CYP systems (CYP7A1, CYP21A2, CYP51A1, CYP3A4, CYP2C8, CYP2C2) and CPR. ER/endomembranes are the dominant subcellular location with additional plasma membrane, nuclear, Golgi, endosomal, and mitochondrial pools. Translational relevance is most mature for sigma-2/TMEM97 complex biology (CT1812 in Alzheimer's disease) and CYP-mediated drug-metabolism modulation.
"Human **PGRMC1 (O00264)** is a **single-pass membrane MAPR protein** with a **cytochrome b5-like heme-binding domain** that supports **heme-dependent and redox-sensitive oligomerization** and enables **regulatory interactions** with (at least) the **cytochrome P450 system** (CYPs and CPR) and membrane signaling complexes."