POMC

Protein identityUniProt · HPA

UniProt accession

P01189

Gene

POMC

Ensembl

ENSG00000115138

Chromosome

2

Canonical length

267 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Predicted secreted proteins

Secretome location

Secreted to blood

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

267 residues, UniProt reviewed canonical sequence.

>P01189|POMC
     1  MPRSCCSRSG ALLLALLLQA SMEVRGWCLE SSQCQDLTTE SNLLECIRAC KPDLSAETPM
    61  FPGNGDEQPL TENPRKYVMG HFRWDRFGRR NSSSSGSSGA GQKREDVSAG EDCGPLPEGG
   121  PEPRSDGAKP GPREGKRSYS MEHFRWGKPV GKKRRPVKVY PNGAEDESAE AFPLEFKREL
   181  TGQRLREGDG PDGPADDGAG AQADLEHSLL VAAEKKDEGP YRMEHFRWGS PPKDKRYGGF
   241  MTSEKSQTPL VTLFKNAIIK NAYKKGE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against POMC can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.66

Highest tissue expression

30,727 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about POMC.

Disease | AllUniProt

Conditions POMC is implicated in, by any mechanism.

• Obesity (OBESITY) MIM:601665
• Obesity, early-onset, with adrenal insufficiency and red hair (OBAIRH) MIM:609734

Disease | GeneticClinVar

21 pathogenic / likely-pathogenic of 212 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Obesity due to pro-opiomelanocortin deficiency
• Early onset severe obesity
• POMC-related disorder
• Obesity
• Inborn genetic diseases

Disease | AutoantibodyPubMed

Conditions in which antibodies against POMC are reported. Each links to that disease's full target list.

Showing 0 of 1 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for POMC from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.38

gnomAD pLI

0

gnomAD missense Z

0.1

DepMap mean gene effect

-0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• calcium-mediated signaling
• cell-cell signaling
• generation of precursor metabolites and energy
• glucose homeostasis
• negative regulation of tumor necrosis factor production
• neuropeptide signaling pathway
• positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway
• positive regulation of transcription by RNA polymerase II
• regulation of appetite
• regulation of blood pressure
• regulation of corticosterone secretion
• regulation of glycogen metabolic process
• response to melanocyte-stimulating hormone
• signal transduction
• cellular pigmentation
• positive regulation of oxytocin production

Molecular functions

• G protein-coupled receptor binding
• hormone activity
• signaling receptor binding
• type 1 melanocortin receptor binding
• type 3 melanocortin receptor binding
• type 4 melanocortin receptor binding

Cellular components

• cytoplasm
• extracellular region
• extracellular space
• secretory granule
• secretory granule lumen

Protein domainsUniProt · Pfam · InterPro

• Pro-opiomelanocortin
• Pro-opiomelanocortin/corticotropin, ACTH, central region
• Opiodes neuropeptide
• Pro-opiomelanocortin N-terminal
• Pro-opiomelanocortin-derived peptides
• Corticotropin ACTH domain
• Opioids neuropeptide
• Pro-opiomelanocortin, N-terminal region

KeywordsUniProt

• Acetylation
• Amidation
• Cleavage on pair of basic residues
• Disulfide bond
• Endorphin
• Glycoprotein
• Hormone
• Obesity
• Phosphoprotein
• Secreted
• Signal