POMC (proopiomelanocortin)

Gene

• Entrez ID: 5443
• Gene name: Proopiomelanocortin
• Gene symbol: POMC
• Synonyms: ACTH, CLIP, LPH, MSH, NPP, OBAIRH, POC
• Chromosome: 2
• Chromosome location: 2p23.3
• Summary: This gene encodes a preproprotein that undergoes extensive, tissue-specific, post-translational processing via cleavage by subtilisin-like enzymes known as prohormone convertases. There are eight potential cleavage sites within the preproprotein and, depending on tissue type and the available convertases, processing may yield as many as ten biologically active peptides involved in diverse cellular functions. The encoded protein is synthesized mainly in corticotroph cells of the anterior pituitary where four cleavage sites are used; adrenocorticotrophin, essential for normal steroidogenesis and the maintenance of normal adrenal weight, and lipotropin beta are the major end products. In other tissues, including the hypothalamus, placenta, and epithelium, all cleavage sites may be used, giving rise to peptides with roles in pain and energy homeostasis, melanocyte stimulation, and immune modulation. These include several distinct melanotropins, lipotropins, and endorphins that are contained within the adrenocorticotrophin and beta-lipotropin peptides. The antimicrobial melanotropin alpha peptide exhibits antibacterial and antifungal activity. Mutations in this gene have been associated with early onset obesity, adrenal insufficiency, and red hair pigmentation. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jan 2016]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28932472	G>C	Risk-factor, benign, conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs121918111	C>A,G,T	Pathogenic	Stop gained, coding sequence variant, missense variant
rs121918112	T>A	Pathogenic	Stop gained, coding sequence variant
rs746815510	->CACCCGAGGGGCCCCCGAGGGCCCC	Pathogenic	Coding sequence variant, frameshift variant
rs753856820	G>T	Pathogenic	5 prime UTR variant
rs757720012	G>A	Likely-pathogenic	Stop gained, coding sequence variant
rs781244602	C>T	Pathogenic	Coding sequence variant, stop gained
rs796065034	G>-	Pathogenic	Frameshift variant, coding sequence variant
rs796065035	->CC	Pathogenic	Frameshift variant, coding sequence variant
rs1553400259	T>G	Pathogenic	Splice acceptor variant
rs1558628852	C>-	Pathogenic	Frameshift variant, coding sequence variant
rs1573250294	->T	Pathogenic	Coding sequence variant, stop gained
rs1573254045	G>T	Pathogenic	Coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005899	hsa-miR-488-3p	Luciferase reporter assay, Microarray	21168126
MIRT017417	hsa-miR-335-5p	Microarray	18185580

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001664	Function	G protein-coupled receptor binding	IBA	21873635
GO:0001664	Function	G protein-coupled receptor binding	IDA	19452503
GO:0005102	Function	Signaling receptor binding	IMP	9620771
GO:0005179	Function	Hormone activity	IMP	9620771
GO:0005179	Function	Hormone activity	ISS
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0005615	Component	Extracellular space	IDA	9620771
GO:0005737	Component	Cytoplasm	ISS
GO:0006091	Process	Generation of precursor metabolites and energy	IMP	9620771
GO:0007165	Process	Signal transduction	IMP	9620771
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007218	Process	Neuropeptide signaling pathway	IEA
GO:0007267	Process	Cell-cell signaling	IMP	9620771
GO:0008217	Process	Regulation of blood pressure	ISS
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0030141	Component	Secretory granule	IBA	21873635
GO:0030141	Component	Secretory granule	ISS
GO:0031781	Function	Type 3 melanocortin receptor binding	IPI	19743876
GO:0031782	Function	Type 4 melanocortin receptor binding	IPI	19743876
GO:0032098	Process	Regulation of appetite	IMP	9620771
GO:0032720	Process	Negative regulation of tumor necrosis factor production	IDA	10233018
GO:0033059	Process	Cellular pigmentation	IMP	9620771
GO:0034774	Component	Secretory granule lumen	TAS
GO:0042593	Process	Glucose homeostasis	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	18292087
GO:0070873	Process	Regulation of glycogen metabolic process	IEA
GO:0070996	Function	Type 1 melanocortin receptor binding	IDA	18292087
GO:0070996	Function	Type 1 melanocortin receptor binding	IPI	19743876
GO:2000852	Process	Regulation of corticosterone secretion	IBA	21873635

Other IDs

• MIM: 176830
• HGNC: 9201
• e!Ensembl: ENSG00000115138

Protein

• UniProt ID: P01189
• Protein name: Pro-opiomelanocortin (POMC) (Corticotropin-lipotropin) [Cleaved into: NPP; Melanotropin gamma (Gamma-MSH); Potential peptide; Corticotropin (Adrenocorticotropic hormone) (ACTH); Melanocyte-stimulating hormone alpha (Alpha-MSH) (Melanotropin alpha); Corticotropin-like intermediary peptide (CLIP); Lipotropin beta (Beta-LPH); Lipotropin gamma (Gamma-LPH); Melanocyte-stimulating hormone beta (Beta-MSH) (Melanotropin beta); Beta-endorphin; Met-enkephalin]
• Protein function: [Corticotropin]: Stimulates the adrenal glands to release cortisol.; [Melanocyte-stimulating hormone alpha]: Anorexigenic peptide. Increases the pigmentation of skin by increasing melanin production in melanocytes.; [Melanocyte-stimulating hormone beta]: Increases the pigmentation of skin by increasing melanin production in melanocytes.; [Beta-endorphin]: Endogenous orexigenic opiate.; [Met-enkephalin]: Endogenous opiate.
• PDB: 4XNH, 4XPD, 4Y49, 6TUB
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF08384	NPP	27 → 70	Pro-opiomelanocortin, N-terminal region	Family
  PF00976	ACTH_domain	74 → 91	Corticotropin ACTH domain	Family
  PF00976	ACTH_domain	136 → 155	Corticotropin ACTH domain	Family
  PF00976	ACTH_domain	218 → 236	Corticotropin ACTH domain	Family
  PF08035	Op_neuropeptide	237 → 264	Opioids neuropeptide	Family

• Sequence:

  MPRSCCSRSGALLLALLLQASMEVRGWCLESSQCQDLTTESNLLECIRACKPDLSAETPM
  FPGNGDEQPLTENPRKYVMGHFRWDRFGRRNSSSSGSSGAGQKREDVSAGEDCGPLPEGG
  PEPRSDGAKPGPREGKRSYSMEHFRWGKPVGKKRRPVKVYPNGAEDESAEAFPLEFKREL
  TGQRLREGDGPDGPADDGAGAQADLEHSLLVAAEKKDEGPYRMEHFRWGSPPKDKRYGGF
  MTSEKSQTPLVTLFKNAIIKNAYKKGE

• Sequence length: 267