Falcon deep research report for human POMC
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POMC is best curated as a secreted, tissue-specifically processed prohormone precursor, with most receptor-binding functions belonging to mature cleavage products.
"**Pro-opiomelanocortin (POMC)** is best curated in GO as a **secreted prohormone precursor** that is sorted to regulated secretory granules and **proteolytically processed in a tissue-specific manner** to yield multiple bioactive peptides (ACTH, α/β/γ-MSH, β-endorphin; enkephalin motifs embedded in the β-LPH/β-endorphin region)."
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Gene-level POMC curation should avoid conflating distinct cleavage-product functions.
"**Gene-level conflation:** Avoid annotating POMC (precursor) directly with all cleavage-product functions (e.g., both “melanocortin receptor binding” and “opioid receptor binding”) unless the annotation model explicitly supports product-level entities."
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Melanocortin receptor specificity should be preferred over generic GPCR-binding assertions.
"**Melanocortin receptor binding vs generic GPCR binding:** Prefer **melanocortin receptor binding** terms, with **MC2R specificity for ACTH** explicitly supported; do not use generic “GPCR binding” for POMC gene product as a catch-all."
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
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
alpha-MSH and its receptors in regulation of tumor necrosis factor-alpha production by human monocyte/macrophages.
Melanocortin-1 receptor signaling markedly induces the expression of the NR4A nuclear receptor subgroup in melanocytic cells.
Aberrant trafficking of human melanocortin 1 receptor variants associated with red hair and skin cancer: Steady-state retention of mutant forms in the proximal golgi.
Novel binding motif of ACTH analogues at the melanocortin receptors.
Peroxisomal localization of the proopiomelanocortin-derived peptides beta-lipotropin and beta-endorphin.
A reference map of the human binary protein interactome.
Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans.
The receptor:G-protein complex dissociates
The high affinity receptor complex binds to G-protein
The receptor:G-protein complex releases GDP
Opioid dissociates from MOR
The receptor:G-protein complex binds GTP
Corticotropin cleavage from POMC
Opioid receptors bind opioid peptides
Liganded Gs-activating GPCR acts as a GEF for Gs
Liganded Gi-activating GPCR acts as a GEF for Gi
Melanocortin receptors bind melanocortins
Defective ACTH does not bind MCR2
Expression of STAT3-upregulated extracellular proteins
The Ligand:GPCR:Gs complex dissociates
Liganded Gs-activating GPCRs bind inactive heterotrimeric Gs
The Ligand:GPCR:Gi complex dissociates
Liganded Gi-activating GPCRs bind inactive heterotrimeric G-protein Gi