Proenkephalin

Protein-coding gene in the species Homo sapiens
PENK
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

1PLW, 1PLX, 2LWC, 5E33, 5E3A

Identifiers
AliasesPENK, proenkephalin, PE, PENK-A
External IDsOMIM: 131330 MGI: 104629 HomoloGene: 4528 GeneCards: PENK
Gene location (Human)
Chromosome 8 (human)
Chr.Chromosome 8 (human)[1]
Chromosome 8 (human)
Genomic location for PENK
Genomic location for PENK
Band8q12.1Start56,436,674 bp[1]
End56,446,671 bp[1]
Gene location (Mouse)
Chromosome 4 (mouse)
Chr.Chromosome 4 (mouse)[2]
Chromosome 4 (mouse)
Genomic location for PENK
Genomic location for PENK
Band4 A1|4 2.31 cMStart4,133,531 bp[2]
End4,138,819 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • nucleus accumbens

  • putamen

  • caudate nucleus

  • ganglionic eminence

  • middle frontal gyrus

  • external globus pallidus

  • urethra

  • sperm

  • cerebellar vermis

  • superior vestibular nucleus
Top expressed in
  • ciliary body

  • olfactory tubercle

  • nucleus accumbens

  • globus pallidus

  • superior frontal gyrus

  • entorhinal cortex

  • calvaria

  • iris

  • amygdala

  • cerebellar cortex
More reference expression data
BioGPS
n/a
Gene ontology
Molecular function
  • opioid peptide activity
  • protein binding
  • neuropeptide hormone activity
  • opioid receptor binding
Cellular component
  • perikaryon
  • cell body fiber
  • axon
  • symmetric synapse
  • dendrite
  • plasma membrane
  • axon terminus
  • neuronal cell body
  • extracellular region
  • endoplasmic reticulum lumen
  • synaptic vesicle lumen
  • neuronal dense core vesicle lumen
Biological process
  • cellular response to transforming growth factor beta stimulus
  • cellular response to virus
  • general adaptation syndrome, behavioral process
  • response to estradiol
  • response to hypoxia
  • startle response
  • locomotory behavior
  • response to nicotine
  • human ageing
  • response to epinephrine
  • cellular response to vitamin D
  • behavioral fear response
  • locomotory exploration behavior
  • response to calcium ion
  • response to morphine
  • response to lipopolysaccharide
  • osteoblast differentiation
  • glial cell proliferation
  • sensory perception of pain
  • cellular response to oxidative stress
  • response to radiation
  • response to ethanol
  • positive regulation of behavioral fear response
  • response to toxic substance
  • cellular response to cAMP
  • aggressive behavior
  • signal transduction
  • sensory perception
  • neuropeptide signaling pathway
  • chemical synaptic transmission
  • post-translational protein modification
  • regulation of signaling receptor activity
  • G protein-coupled receptor signaling pathway
  • response to bacterium
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

5179

18619

Ensembl

ENSG00000181195

ENSMUSG00000045573

UniProt

P01210

P22005

RefSeq (mRNA)

NM_006211
NM_001135690

NM_001002927
NM_001348209

RefSeq (protein)

NP_001129162

NP_001002927
NP_001335138

Location (UCSC)Chr 8: 56.44 – 56.45 MbChr 4: 4.13 – 4.14 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Proenkephalin (PENK), formerly known as proenkephalin A (since proenkephalin B was renamed prodynorphin), is an endogenous opioid polypeptide hormone which, via proteolyic cleavage, produces the enkephalin peptides [Met]enkephalin, and to a lesser extent, [Leu]enkephalin.[5] Upon cleavage, each proenkephalin peptide results in the generation of four copies of [Met]enkephalin, two extended copies of [Met]enkephalin, and one copy of [Leu]enkephalin.[5] Contrarily, [Leu]enkephalin] is predominantly synthesized from prodynorphin, which produces three copies of it per cleavage, and no copies of [Met]enkephalin. Other endogenous opioid peptides produced by proenkephalin include adrenorphin,[6] amidorphin,[7] BAM-18,[8] BAM-20P,[9] BAM-22P,[9] peptide B,[10] peptide E,[11] and peptide F.[12]

Proenkephalin in human diseases

Proenkephalin is produced by the medium spiny neurons of the striatum which undergo neurodegeneration in early stages of Huntington's disease (HD). PENK[13] and related peptides[14][15] measured in cerebrospinal fluid are proposed as potential biomarkers of disease progression in HD.

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000181195 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000045573 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Donald W. Pfaff (2002). Hormones, brain, and behavior. Elsevier. p. 173. ISBN 978-0-12-532109-9. Retrieved 25 November 2011.
  6. ^ Matsuo H, Miyata A, Mizuno K (1983). "Novel C-terminally amidated opioid peptide in human phaeochromocytoma tumour". Nature. 305 (5936): 721–723. Bibcode:1983Natur.305..721M. doi:10.1038/305721a0. PMID 6633641. S2CID 4320171.
  7. ^ Seizinger BR, Liebisch DC, Gramsch C, Herz A, Weber E, Evans CJ, et al. (1985). "Isolation and structure of a novel C-terminally amidated opioid peptide, amidorphin, from bovine adrenal medulla". Nature. 313 (5997): 57–59. Bibcode:1985Natur.313...57S. doi:10.1038/313057a0. PMID 3965972. S2CID 4363051.
  8. ^ Hurlbut DE, Evans CJ, Barchas JD, Leslie FM (June 1987). "Pharmacological properties of a proenkephalin A-derived opioid peptide: BAM 18". European Journal of Pharmacology. 138 (3): 359–366. doi:10.1016/0014-2999(87)90474-2. PMID 3040439.
  9. ^ a b Mizuno K, Minamino N, Kangawa K, Matsuo H (December 1980). "A new family of endogenous "big" Met-enkephalins from bovine adrenal medulla: purification and structure of docosa- (BAM-22P) and eicosapeptide (BAM-20P) with very potent opiate activity". Biochemical and Biophysical Research Communications. 97 (4): 1283–1290. doi:10.1016/S0006-291X(80)80005-2. PMID 7213356.
  10. ^ Micanovic R, Kruggel W, Ray P, Lewis RV (1984). "Purification and sequence of a non-opioid peptide derived from ovine proenkephalin: implications for possible species specific processing". Peptides. 5 (5): 853–856. doi:10.1016/0196-9781(84)90105-0. PMID 6504720. S2CID 3869685.
  11. ^ Boarder MR, Evans C, Adams M, Erdelyi E, Barchas JD (December 1987). "Peptide E and its products, BAM 18 and Leu-enkephalin, in bovine adrenal medulla and cultured chromaffin cells: release in response to stimulation". Journal of Neurochemistry. 49 (6): 1824–1832. doi:10.1111/j.1471-4159.1987.tb02443.x. PMID 3681299. S2CID 19919675.
  12. ^ Jones BN, Stern AS, Lewis RV, Kimura S, Stein S, Udenfriend S, Shively JE (October 1980). "Structure of two adrenal polypeptides containing multiple enkephalin sequences". Archives of Biochemistry and Biophysics. 204 (1): 392–395. doi:10.1016/0003-9861(80)90048-X. PMID 7425644.
  13. ^ Niemela V, Landtblom AM, Nyholm D, Kneider M, Constantinescu R, Paucar M, et al. (February 2021). "Proenkephalin Decreases in Cerebrospinal Fluid with Symptom Progression of Huntington's Disease". Movement Disorders. 36 (2): 481–491. doi:10.1002/mds.28391. PMC 7984171. PMID 33247616.
  14. ^ Iadarola MJ, Mouradian MM (February 1989). "Decrease in a proenkephalin peptide in cerebrospinal fluid in Huntington's disease and progressive supranuclear palsy". Brain Research. 479 (2): 397–401. doi:10.1016/0006-8993(89)91648-X. PMID 2522341. S2CID 11033749.
  15. ^ Barschke P, Abu-Rumeileh S, Al Shweiki MH, Barba L, Paolini Paoletti F, Oeckl P, et al. (June 2022). "Cerebrospinal fluid levels of proenkephalin and prodynorphin are differentially altered in Huntington's and Parkinson's disease". Journal of Neurology. 269 (9): 5136–5143. doi:10.1007/s00415-022-11187-8. PMC 9363351. PMID 35737109. S2CID 249930318.

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