Human Gene POMC (ENST00000380794.5) from GENCODE V41
  Description: ACTH stimulates the adrenal glands to release cortisol. (from UniProt P01189)
RefSeq Summary (NM_001035256): 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].
Gencode Transcript: ENST00000380794.5
Gencode Gene: ENSG00000115138.11
Transcript (Including UTRs)
   Position: hg38 chr2:25,160,853-25,168,690 Size: 7,838 Total Exon Count: 4 Strand: -
Coding Region
   Position: hg38 chr2:25,161,081-25,164,772 Size: 3,692 Coding Exon Count: 2 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2022-05-14 09:57:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:25,160,853-25,168,690)mRNA (may differ from genome)Protein (267 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSCGAPEnsemblExonPrimerGencodeGeneCards
HGNCLynxMGImyGene2neXtProtPubMed
ReactomeUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: COLI_HUMAN
DESCRIPTION: RecName: Full=Pro-opiomelanocortin; Short=POMC; AltName: Full=Corticotropin-lipotropin; Contains: RecName: Full=NPP; Contains: RecName: Full=Melanotropin gamma; AltName: Full=Gamma-MSH; Contains: RecName: Full=Potential peptide; Contains: RecName: Full=Corticotropin; AltName: Full=Adrenocorticotropic hormone; Short=ACTH; Contains: RecName: Full=Melanotropin alpha; AltName: Full=Alpha-MSH; Contains: RecName: Full=Corticotropin-like intermediary peptide; Short=CLIP; Contains: RecName: Full=Lipotropin beta; AltName: Full=Beta-LPH; Contains: RecName: Full=Lipotropin gamma; AltName: Full=Gamma-LPH; Contains: RecName: Full=Melanotropin beta; AltName: Full=Beta-MSH; Contains: RecName: Full=Beta-endorphin; Contains: RecName: Full=Met-enkephalin; Flags: Precursor;
FUNCTION: ACTH stimulates the adrenal glands to release cortisol.
FUNCTION: MSH (melanocyte-stimulating hormone) increases the pigmentation of skin by increasing melanin production in melanocytes.
FUNCTION: Beta-endorphin and Met-enkephalin are endogenous opiates.
SUBCELLULAR LOCATION: Secreted.
TISSUE SPECIFICITY: ACTH and MSH are produced by the pituitary gland.
PTM: Specific enzymatic cleavages at paired basic residues yield the different active peptides.
PTM: O-glycosylated; reducing sugar is probably N- acetylgalactosamine.
DISEASE: Defects in POMC may be associated with susceptibility to obesity (OBESITY) [MIM:601665]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.
DISEASE: Defects in POMC are the cause of pro-opiomelanocortinin deficiency (POMCD) [MIM:609734]. Affected individuals present early-onset obesity, adrenal insufficiency and red hair.
SIMILARITY: Belongs to the POMC family.
WEB RESOURCE: Name=Wikipedia; Note=Melanocyte-stimulating hormone entry; URL="http://en.wikipedia.org/wiki/Melanocyte-stimulating_hormone";

-  MalaCards Disease Associations
  MalaCards Gene Search: POMC
Diseases sorted by gene-association score: obesity, adrenal insufficiency, and red hair due to pomc deficiency* (1450), obesity* (232), monogenic non-syndromic obesity, autosomal recessive* (100), obesity susceptibility, pomc-related* (100), adrenal gland hyperfunction (31), cushing's syndrome (30), hypoadrenalism (26), ectopic cushing syndrome (25), pituitary carcinoma (25), adrenal adenoma (25), gonadal disease (24), opsoclonus-myoclonus syndrome (24), adrenal cortex disease (21), adrenal gland disease (21), chronic fatigue syndrome (21), nelson syndrome (20), endocrine organ benign neoplasm (19), cell type benign neoplasm (19), organ system benign neoplasm (19), 48,xxyy syndrome (18), glossopharyngeal neuralgia (18), myofascial pain syndrome (18), startle epilepsy (18), pituitary infarct (17), adrenocorticotropic hormone deficiency (17), acth deficiency (16), sheehan syndrome (16), central nervous system organ benign neoplasm (16), basophil adenoma (16), addison's disease (16), pituitary adenoma (15), bronchus adenoma (15), sick building syndrome (15), congenital adrenal hyperplasia (14), exophthalmic ophthalmoplegia (14), mediastinal lipomatosis (14), pituitary apoplexy (14), hyperprolactinemia (14), glucocorticoid deficiency, due to acth unresponsiveness (14), achalasia-addisonianism-alacrimia syndrome (14), steroid inherited metabolic disorder (13), adrenal cortical hypofunction (13), pituitary-dependent cushing's disease (13), hyperandrogenism (13), pituitary adenoma, acth-secreting (13), empty sella syndrome (12), pituitary gland disease (12), hypokalemia (12), primary pigmented nodular adrenocortical disease (11), hypopituitarism (11), hyperaldosteronism (11), aldosteronism, glucocorticoid-remediable (11), classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (11), post-vaccinal encephalitis (11), endocrine pancreas disease (10), lennox-gastaut syndrome (10), colon neuroendocrine neoplasm (10), small cell cancer of the lung, somatic (10), endocrine exophthalmos (10), euthyroid sick syndrome (10), subacute glomerulonephritis (10), prostate adenoid cystic carcinoma (9), diabetes insipidus (9), adrenal cortical adenoma (9), conn's syndrome (9), chromophobe adenoma (9), persistent fetal circulation syndrome (9), adrenal carcinoma (9), cocaine dependence (9), pain agnosia (9), agnosia (9), adenohypophysitis (9), anorexia nervosa (9), aromatase excess syndrome (9), diabetes insipidus, neurohypophyseal (9), lymphocytic hypophysitis (9), dowling-degos disease 1 (8), neurodermatitis (8), infantile epileptic encephalopathy (8), mood disorder (8), functioning pituitary adenoma (8), pituitary tumors (8), cytochrome p450 oxidoreductase deficiency (8), pituitary hormone deficiency, combined, 2 (8), pituitary adenoma, prolactin-secreting (8), acromegaly (8), inappropriate adh syndrome (8), acidophil adenoma (8), rhinitis (8), acute adrenal insufficiency (8), trichinosis (8), scleredema adultorum (8), panic disorder (7), premenstrual tension (7), familial glucocorticoid deficiency (7), acute thyroiditis (7), hypothalamic disease (7), hyperpituitarism (7), eating disorder (7), landau-kleffner syndrome (7), opiate dependence (7), verbal auditory agnosia (7), lipoid adrenal hyperplasia (7), hypoaldosteronism (7), orthostatic intolerance (7), shwartzman phenomenon (7), amenorrhea (7), sex differentiation disease (7), gynecomastia (7), substance dependence (6), hypothyroidism, congenital, nongoitrous 4 (6), thyroid crisis (6), sella turcica neoplasm (6), tuberculum sellae meningioma (6), phaeochromocytoma (6), adrenal insufficiency, congenital, with 46xy sex reversal, partial or complete (6), secondary hypertrophic osteoarthropathy (6), central nervous system germinoma (6), arachnoiditis (6), tuberculous epididymitis (6), suprasellar meningioma (6), pancreas disease (6), paracoccidioidomycosis (6), retrograde amnesia (6), infancy electroclinical syndrome (6), west syndrome (6), chiasmal syndrome (6), adenoma (6), adrenal rest tumor (6), drug dependence (6), fasting hypoglycemia (6), thymus cancer (5), malignant leydig cell tumor (5), rheumatic myocarditis (5), spontaneous ocular nystagmus (5), testicular leydig cell tumor (5), fetal erythroblastosis (5), corticosteroid-binding globulin deficiency (5), central nervous system germ cell tumor (5), laryngeal tuberculosis (5), vitiligo-associated multiple autoimmune disease susceptibility 1 (5), tuberculous empyema (5), specific developmental disorder (5), carney complex variant (5), nodular nonsuppurative panniculitis (5), pericardial tuberculosis (5), apparent mineralocorticoid excess (5), withdrawal disorder (5), tibial neuropathy (5), tarsal tunnel syndrome (5), cloacogenic carcinoma (5), cervix small cell carcinoma (5), childhood electroclinical syndrome (5), nervous system benign neoplasm (4), childhood disintegrative disease (4), thyroid gland disease (4), syndrome of inappropriate antidiuretic hormone (4), cutaneous solitary mastocytoma (4), mental depression (4), mineral metabolism disease (4), dyschromatosis universalis hereditaria (4), rh isoimmunization (4), aortic valve disease 1 (4), alcohol dependence (4), herpes gestationis (3), vernal conjunctivitis (3), image syndrome (3), kleine-levin hibernation syndrome (3), asthma (2), pheochromocytoma (2), acquired metabolic disease (2), bardet-biedl syndrome (2), disease of mental health (2), overnutrition (1), urinary system disease (1), female reproductive system disease (1), glucose metabolism disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 16633.30 RPKM in Pituitary
Total median expression: 16741.93 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -109.80263-0.417 Picture PostScript Text
3' UTR -66.50228-0.292 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001941 - Mcortin_ACTH
IPR013531 - Mcrtin_ACTH_cent
IPR013593 - Melanocortin_N
IPR013532 - Opioid_neuropept

Pfam Domains:
PF00976 - Corticotropin ACTH domain
PF08384 - Pro-opiomelanocortin, N-terminal region
PF08035 - Opioids neuropeptide

ModBase Predicted Comparative 3D Structure on P01189
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001664 G-protein coupled receptor binding
GO:0005102 receptor binding
GO:0005179 hormone activity
GO:0005184 neuropeptide hormone activity
GO:0031781 type 3 melanocortin receptor binding
GO:0031782 type 4 melanocortin receptor binding
GO:0070996 type 1 melanocortin receptor binding

Biological Process:
GO:0006091 generation of precursor metabolites and energy
GO:0007165 signal transduction
GO:0007186 G-protein coupled receptor signaling pathway
GO:0007218 neuropeptide signaling pathway
GO:0007267 cell-cell signaling
GO:0008217 regulation of blood pressure
GO:0010469 regulation of receptor activity
GO:0019221 cytokine-mediated signaling pathway
GO:0031640 killing of cells of other organism
GO:0032098 regulation of appetite
GO:0032720 negative regulation of tumor necrosis factor production
GO:0033059 cellular pigmentation
GO:0035821 modification of morphology or physiology of other organism
GO:0042593 glucose homeostasis
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0070873 regulation of glycogen metabolic process
GO:0070965 positive regulation of neutrophil mediated killing of fungus
GO:2000852 regulation of corticosterone secretion

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005737 cytoplasm
GO:0005782 peroxisomal matrix
GO:0030141 secretory granule
GO:0034774 secretory granule lumen
GO:0005777 peroxisome


-  Descriptions from all associated GenBank mRNAs
  BC065832 - Homo sapiens proopiomelanocortin, mRNA (cDNA clone MGC:75488 IMAGE:30392189), complete cds.
KJ891851 - Synthetic construct Homo sapiens clone ccsbBroadEn_01245 POMC gene, encodes complete protein.
M28636 - Human proopiomelanocortin (POMC) mRNA, 3' end.
M38297 - Human proopiomelanocortin (POMC) mRNA, 3' end.
JD431826 - Sequence 412850 from Patent EP1572962.
JD157560 - Sequence 138584 from Patent EP1572962.
JD191757 - Sequence 172781 from Patent EP1572962.
JD335979 - Sequence 317003 from Patent EP1572962.
JD310209 - Sequence 291233 from Patent EP1572962.
JD227461 - Sequence 208485 from Patent EP1572962.
JD373348 - Sequence 354372 from Patent EP1572962.
DQ884404 - Homo sapiens clone BFC06035 proopiomelanocortin preproprotein mRNA, complete cds.
BT019918 - Homo sapiens proopiomelanocortin (adrenocorticotropin/ beta-lipotropin/ alpha-melanocyte stimulating hormone/ beta-melanocyte stimulating hormone/ beta-endorphin) mRNA, complete cds.
AB587590 - Synthetic construct DNA, clone: pF1KB8920, Homo sapiens POMC gene for proopiomelanocortin, without stop codon, in Flexi system.
CR541826 - Homo sapiens full open reading frame cDNA clone RZPDo834C0532D for gene POMC, proopiomelanocortin (adrenocorticotropin/ beta-lipotropin/ alpha-melanocyte stimulating hormone/ beta-melanocyte stimulating hor; complete cds, without stopcodon.
M25896 - H.sapiens gamma-endorphin region of pro-opiomelanocortin (POMC) mRNA, complete cds.
S76492 - proopiomelanocortin [human, pituitary glands, mRNA Partial, 255 nt].
JD336763 - Sequence 317787 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04080 - Neuroactive ligand-receptor interaction
hsa04916 - Melanogenesis
hsa04920 - Adipocytokine signaling pathway

Reactome (by CSHL, EBI, and GO)

Protein P01189 (Reactome details) participates in the following event(s):

R-HSA-265301 Corticotropin cleavage from POMC
R-HSA-388605 POMC(138-176) binds MC2R
R-HSA-112042 Opioid binds MOR
R-HSA-167427 Opioid dissociates from MOR
R-HSA-374298 Opioid receptors bind opioid peptides
R-HSA-388596 Melanocortin receptors bind melanocortins
R-HSA-744886 The Ligand:GPCR:Gs complex dissociates
R-HSA-167408 The high affinity receptor complex binds to G-protein
R-HSA-112271 The receptor:G-protein complex dissociates
R-HSA-749454 The Ligand:GPCR:Gi complex dissociates
R-HSA-744887 Liganded Gs-activating GPCRs bind inactive heterotrimeric Gs
R-HSA-167419 The receptor:G-protein complex releases GDP
R-HSA-167429 The receptor:G-protein complex binds GTP
R-HSA-749456 Liganded Gi-activating GPCRs bind inactive heterotrimeric G-protein Gi
R-HSA-379044 Liganded Gs-activating GPCR acts as a GEF for Gs
R-HSA-380073 Liganded Gi-activating GPCR acts as a GEF for Gi
R-HSA-209952 Peptide hormone biosynthesis
R-HSA-375276 Peptide ligand-binding receptors
R-HSA-111885 Opioid Signalling
R-HSA-2980736 Peptide hormone metabolism
R-HSA-418555 G alpha (s) signalling events
R-HSA-6785807 Interleukin-4 and 13 signaling
R-HSA-373076 Class A/1 (Rhodopsin-like receptors)
R-HSA-5579031 Defective ACTH causes Obesity and Pro-opiomelanocortinin deficiency (POMCD)
R-HSA-202040 G-protein activation
R-HSA-418594 G alpha (i) signalling events
R-HSA-392499 Metabolism of proteins
R-HSA-388396 GPCR downstream signalling
R-HSA-449147 Signaling by Interleukins
R-HSA-500792 GPCR ligand binding
R-HSA-5579029 Metabolic disorders of biological oxidation enzymes
R-HSA-372790 Signaling by GPCR
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-5668914 Diseases of metabolism
R-HSA-162582 Signal Transduction
R-HSA-168256 Immune System
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: BC065832, COLI_HUMAN, ENST00000380794.1, ENST00000380794.2, ENST00000380794.3, ENST00000380794.4, P01189, P78442, Q53T23, Q9UD39, Q9UD40, uc002rfy.1
UCSC ID: ENST00000380794.5
RefSeq Accession: NM_001035256
Protein: P01189 (aka COLI_HUMAN)
CCDS: CCDS1717.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.