Reviewed, UniProtKB/Swiss-Prot P01189 (COLI_HUMAN)

Names and origin

Protein names

Recommended name:
    Corticotropin-lipotropin
Alternative name(s):
    Pro-opiomelanocortin
      Short name(s)=POMC
Cleaved into 11 chains:
  Recommended name:
      NPP
  Recommended name:
      Melanotropin gamma
  Alternative name(s):
      Gamma-MSH
  Recommended name:
      Potential peptide
  Recommended name:
      Corticotropin
  Alternative name(s):
      Adrenocorticotropic hormone
        Short name(s)=ACTH
  Recommended name:
      Melanotropin alpha
  Alternative name(s):
      Alpha-MSH
  Recommended name:
      Corticotropin-like intermediary peptide
        Short name(s)=CLIP
  Recommended name:
      Lipotropin beta
  Alternative name(s):
      Beta-LPH
  Recommended name:
      Lipotropin gamma
  Alternative name(s):
      Gamma-LPH
  Recommended name:
      Melanotropin beta
  Alternative name(s):
      Beta-MSH
  Recommended name:
      Beta-endorphin
  Recommended name:
      Met-enkephalin

Gene names

Name:

POMC

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	267 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	ACTH stimulates the adrenal glands to release cortisol. MSH (melanocyte-stimulating hormone) increases the pigmentation of skin by increasing melanin production in melanocytes. Beta-endorphin and Met-enkephalin are endogenous opiates.
Tissue specificity	ACTH and MSH are produced by the pituitary gland.
Post-translational modification	Specific enzymatic cleavages at paired basic residues yield the different active peptides. O-glycosylated; reducing sugar is probably N-acetylgalactosamine.
Polymorphism	Genetic variation in POMC may influence abdominal body fat distribution [MIM:609830].
Involvement in disease	Defects in POMC may be associated with susceptibility to obesity [MIM:601665]. Defects in POMC are the cause of pro-opiomelanocortinin deficiency [MIM:609734]. Affected individuals present early-onset obesity, adrenal insufficiency and red hair.
Sequence similarities	Belongs to the POMC family.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Disease	Obesity
Domain	Signal
Molecular function	Endorphin Hormone
PTM	Amidation Cleavage on pair of basic residues Glycoprotein Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	cell-cell signaling Ref.22 Traceable author statement. Source: ProtInc generation of precursor metabolites and energy Ref.22 Traceable author statement. Source: ProtInc signal transduction Ref.22 Traceable author statement. Source: ProtInc
Cellular component	soluble fraction Ref.22 Traceable author statement. Source: ProtInc
Molecular function	hormone activity Ref.22 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Signal peptide	1 – 26	26
	Peptide	27 – 102	76	NPP
	Peptide	77 – 87	11	Melanotropin gamma
	Peptide	105 – 134	30	Potential peptide
	Peptide	138 – 176	39	Corticotropin
	Peptide	138 – 150	13	Melanotropin alpha
	Peptide	156 – 176	21	Corticotropin-like intermediary peptide
	Peptide	179 – 267	89	Lipotropin beta
	Peptide	179 – 234	56	Lipotropin gamma
	Peptide	217 – 234	18	Melanotropin beta
	Peptide	237 – 267	31	Beta-endorphin
	Peptide	237 – 241	5	Met-enkephalin
Amino acid modifications
	Modified residue	87	1	Phenylalanine amide
	Modified residue	134	1	Glutamic acid 1-amide
	Modified residue	150	1	Valine amide
	Modified residue	168	1	Phosphoserine
	Glycosylation	71	1	O-linked (HexNAc...)
	Glycosylation	91	1	N-linked (GlcNAc...)
	Disulfide bond	28 ↔ 50		By similarity
Natural variations
	Natural variant	7	1	S → T
	Natural variant	9	1	S → L
	Natural variant	62	1	P → L: dbSNP rs28932471.
	Natural variant	97 – 99	3	Missing
	Natural variant	106	1	D → N
	Natural variant	132	1	P → A: dbSNP rs8192606.
	Natural variant	214	1	E → G
	Natural variant	236	1	R → G May confer susceptibility to obesity; reduces the ability to activate melanocortin receptor 4. dbSNP rs28932472.
	Natural variant	236	1	R → Q
Experimental info
	Sequence conflict	48	1	R → G Ref.6
	Sequence conflict	115	1	P → T Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P01189-1 [UniParc]. Last modified February 1, 1991. Version 2. Checksum: B927323474A67536	FASTA	267	29,424
	10 20 30 40 50 60 MPRSCCSRSG ALLLALLLQA SMEVRGWCLE SSQCQDLTTE SNLLECIRAC KPDLSAETPM 70 80 90 100 110 120 FPGNGDEQPL TENPRKYVMG HFRWDRFGRR NSSSSGSSGA GQKREDVSAG EDCGPLPEGG 130 140 150 160 170 180 PEPRSDGAKP GPREGKRSYS MEHFRWGKPV GKKRRPVKVY PNGAEDESAE AFPLEFKREL 190 200 210 220 230 240 TGQRLREGDG PDGPADDGAG AQADLEHSLL VAAEKKDEGP YRMEHFRWGS PPKDKRYGGF 250 260 MTSEKSQTPL VTLFKNAIIK NAYKKGE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and structural organization of the human corticotropin-beta-lipotropin precursor gene." Takahashi H., Teranishi Y., Nakanishi S., Numa S. FEBS Lett. 135:97-102(1981) [PubMed: 6274691] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The human pro-opiomelanocortin gene: organization, sequence, and interspersion with repetitive DNA." Whitfeld P.L., Seeburg P.H., Shine J. DNA 1:133-143(1982) [PubMed: 6299668] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Complete nucleotide sequence of the human corticotropin-beta-lipotropin precursor gene." Takahashi H., Hakamata Y., Watanabe Y., Kikuno R., Miyata T., Numa S. Nucleic Acids Res. 11:6847-6858(1983) [PubMed: 6314261] [Abstract] Cited for: NUCLEOTIDE SEQUENCE.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pituitary.
[5]	"Synthesis, cloning and primary structure of DNA complementary to mRNA for human pituitary pro-opiomelanocortin." Golovin S.Y., Karginov V.A., Bondar A.A., Beklemishev A.B., Chekhranova M.K., Mertvetsov N.P., Pankov Y.A. Bioorg. Khim. 13:562-564(1987) [PubMed: 3606677] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 6-267.
[6]	"Structural organization of human genomic DNA encoding the pro-opiomelanocortin peptide." Chang A.C.Y., Cochet M., Cohen S.N. Proc. Natl. Acad. Sci. U.S.A. 77:4890-4894(1980) [PubMed: 6254047] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 46-267.
[7]	"Complete amino acid sequence of a human pituitary glycopeptide: an important maturation product of pro-opiomelanocortin." Seidah N.G., Chretien M. Proc. Natl. Acad. Sci. U.S.A. 78:4236-4240(1981) [PubMed: 6945581] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-102.
[8]	"Primary structure of the major human pituitary pro-opiomelanocortin NH2-terminal glycopeptide. Evidence for an aldosterone-stimulating activity." Seidah N.G., Rochemont J., Hamelin J., Lis M., Chretien M. J. Biol. Chem. 256:7977-7984(1981) [PubMed: 6267033] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-102.
[9]	"The missing fragment of the pro-sequence of human pro-opiomelanocortin: sequence and evidence for C-terminal amidation." Seidah N.G., Rochemont J., Hamelin J., Benjannet S., Chretien M. Biochem. Biophys. Res. Commun. 102:710-716(1981) [PubMed: 6272808] [Abstract] Cited for: PROTEIN SEQUENCE OF 105-134.
[10]	"Confirmation of the 1-20 amino acid sequence of human adrenocorticotrophin." Bennett H.P.J., Lowry P.J., McMartin C. Biochem. J. 133:11-13(1973) [PubMed: 4352834] [Abstract] Cited for: PROTEIN SEQUENCE OF 138-176.
[11]	"On the structure of human corticotropin (adrenocorticotropic hormone)." Lee T.H., Lerner A.B., Buettner-Janusch V. J. Biol. Chem. 236:2970-2974(1961) [PubMed: 14463577] [Abstract] Cited for: PROTEIN SEQUENCE OF 138-176.
[12]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-41.
[13]	"Revised amino-acid sequences for porcine and human adrenocorticotrophic hormone." Riniker B., Sieber P., Rittel W., Zuber H. Nature New Biol. 235:114-115(1972) [PubMed: 4334191] [Abstract] Cited for: SEQUENCE REVISION (CORTICOTROPIN).
[14]	"Synthesis of the human adrenal cortex hormone (alpha-h-ACTH) with a revised amino-acid sequence." Sieber P., Rittel W., Riniker B. Helv. Chim. Acta 55:1243-1248(1972) [PubMed: 4338630] [Abstract] Cited for: SYNTHESIS OF CORTICOTROPIN.
[15]	"Adrenocorticotropins. 44. Total synthesis of the human hormone by the solid-phase method." Yamashiro D., Li C.H. J. Am. Chem. Soc. 95:1310-1315(1973) [PubMed: 4347148] [Abstract] Cited for: SYNTHESIS OF CORTICOTROPIN.
[16]	"Primary structure of human beta-lipotropin." Li C.H., Chung D. Nature 260:622-624(1976) [PubMed: 1264228] [Abstract] Cited for: PROTEIN SEQUENCE OF 179-267.
[17]	"Structure of a melanocyte-stimulating hormone from the human pituitary gland." Harris J.I. Nature 184:167-169(1959) Cited for: PROTEIN SEQUENCE OF 217-234.
[18]	"Primary structure and morphine-like activity of human beta-endorphin." Dragon N., Seidah N.G., Lis M., Routhier R., Chretien M. Can. J. Biochem. 55:666-670(1977) [PubMed: 195688] [Abstract] Cited for: PROTEIN SEQUENCE OF 237-267.
[19]	"Gamma-endorphin and schizophrenia: amino acid composition of gamma-endorphin and nucleotide sequence of gamma-endorphin cDNA from pituitary glands of schizophrenic patients." Bovenberg R.A.L., Burbach J.P.H., Wiegant V.M., Veeneman G.H., van Boom J.H., Baas P.D., Jansz H.S., de Wied D. Brain Res. 376:29-37(1986) [PubMed: 2424570] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 235-256.
[20]	"Alpha-amidated peptides derived from pro-opiomelanocortin in normal human pituitary." Fenger M., Johnsen A.H. Biochem. J. 250:781-788(1988) [PubMed: 2839146] [Abstract] Cited for: PROTEOLYTIC PROCESSING.
[21]	"Reduced expression of a naturally deleted form of human proopiomelanocortin complementary deoxyribonucleic acid after transfection into Chinese hamster ovary cells." Morris J.C., Savva D., Lowry P.J. Endocrinology 136:195-201(1995) [PubMed: 7828531] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 75-104, VARIANT 97-SER--GLY-99 DEL. Tissue: Pituitary.
[22]	"Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans." Krude H., Biebermann H., Luck W., Horn R., Brabant G., Grueters A. Nat. Genet. 19:155-157(1998) [PubMed: 9620771] [Abstract] Cited for: INVOLVEMENT IN PRO-OPIOMELANOCORTININ DEFICIENCY.
[23]	"Association between common polymorphisms of the proopiomelanocortin gene and body fat distribution: a family study." Baker M., Gaukrodger N., Mayosi B.M., Imrie H., Farrall M., Watkins H., Connell J.M.C., Avery P.J., Keavney B. Diabetes 54:2492-2496(2005) [PubMed: 16046320] [Abstract] Cited for: INVOLVEMENT IN ABDOMINAL BODY FAT DISTRIBUTION.
[24]	"Phosphoproteomic analysis of the human pituitary." Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F. Pituitary 9:109-120(2006) [PubMed: 16807684] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168, MASS SPECTROMETRY. Tissue: Pituitary.
[25]	"Systematic mutation screening of the pro-opiomelanocortin gene: identification of several genetic variants including three different insertions, one nonsense and two missense point mutations in probands of different weight extremes." Hinney A., Becker I., Heibult O., Nottebom K., Schmidt A., Ziegler A., Mayer H., Siegfried W., Blum W.F., Remschmidt H., Hebebrand J. J. Clin. Endocrinol. Metab. 83:3737-3741(1998) [PubMed: 9768693] [Abstract] Cited for: VARIANTS ASN-106; GLY-214 AND 97-SER--GLY-99 DEL.
[26]	"Mutational analysis of the proopiomelanocortin gene in Caucasians with early onset obesity." Echwald S.M., Sorensen T.I., Andersen T., Tybjaerg-Hansen A., Clausen J.O., Pedersen O. Int. J. Obes. Relat. Metab. Disord. 23:293-298(1999) [PubMed: 10193875] [Abstract] Cited for: VARIANT GLN-236.
[27]	"Molecular screening of the proopiomelanocortin (POMC) gene in Italian obese children: report of three new mutations." del Giudice E.M., Cirillo G., Santoro N., D'Urso L., Carbone M.T., Toro R.D., Perrone L. Int. J. Obes. Relat. Metab. Disord. 25:61-67(2001) [PubMed: 11244459] [Abstract] Cited for: VARIANTS THR-7; LEU-9; GLY-236 AND 97-SER--GLY-99 DEL.
[28]	"A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism." Challis B.G., Pritchard L.E., Creemers J.W.M., Delplanque J., Keogh J.M., Luan J., Wareham N.J., Yeo G.S.H., Bhattacharyya S., Froguel P., White A., Farooqi I.S., O'Rahilly S. Hum. Mol. Genet. 11:1997-2004(2002) [PubMed: 12165561] [Abstract] Cited for: VARIANT GLY-236, CHARACTERIZATION OF VARIANT GLY-236, POSSIBLE INVOLVEMENT IN OBESITY.

Web resources

Wikipedia

Melanocyte-stimulating hormone entry

Cross-references

Sequence databases
EMBLGenBankDDBJ	M38297 mRNA. Translation: AAA60140.1. J00292, J00291 Genomic DNA. Translation: AAB59621.1. V01510 Genomic DNA. Translation: CAA24754.1. BC065832 mRNA. Translation: AAH65832.1. M25896 mRNA. Translation: AAA35799.1.
PIR	CTHUP. A17229.
RefSeq	NP_000930.1. NP_001030333.1.
UniGene	Hs.1897
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	P01189.
Genome annotation databases
Ensembl	ENSG00000115138. Homo sapiens. [Contig view]
GeneID	5443.
KEGG	hsa:5443.
Organism-specific databases
H-InvDB	HIX0029971.
HGNC	HGNC:9201. POMC.
HPA	CAB002765.
MIM	176830. gene. 601665. phenotype. 609734. phenotype. 609830. phenotype.
Orphanet	71526. Obesity due to pro-opiomelanocortin deficiency.
PharmGKB	PA33526.
GenAtlas	Search...
GeneCards	Search...
GeneLynx	Search...
Phylogenomic databases
HOGENOM	P01189.
HOVERGEN	P01189.
Gene expression databases
ArrayExpress	P01189.
CleanEx	HS_POMC.
GermOnline	ENSG00000115138. Homo sapiens.
Family and domain databases
InterPro	IPR001941. Mcortin_ACTH. IPR013533. Mcortin_ACTH_C. IPR013531. Mcrtin_ACTH_cent. IPR013593. Melanocortin_N. IPR013532. Opioid_neuropept. [Graphical view]
PANTHER	PTHR11416. Mcortin_ACTH. 1 hit.
Pfam	PF00976. ACTH_domain. 1 hit. PF08384. NPP. 1 hit. PF08035. Op_neuropeptide. 1 hit. [Graphical view]
PRINTS	PR00383. MELANOCORTIN.
ProDom	PD003250. Mcortin_ACTH. 1 hit. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
DrugBank	DB00741. Hydrocortisone. DB00836. Loperamide. DB01108. Trilostane.
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

COLI_HUMAN

Accession

Primary (citable) accession number: P01189
Secondary accession number(s): P78442, Q9UD39, Q9UD40

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	February 1, 1991
Last modified:	July 22, 2008
This is version 96 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)