OGFr

Opioid growth factor receptor, also known as OGFr or the ζ-opioid receptor, is a protein which in humans is encoded by the OGFR gene.^[5][6] The protein encoded by this gene is a receptor for opioid growth factor (OGF), also known as [Met(5)]-enkephalin. The endogenous ligand is thus a known opioid peptide, and OGFr was originally discovered and named as a new opioid receptor zeta (ζ). However it was subsequently found that it shares little sequence similarity with the other opioid receptors, and has quite different function.

OGFR
Identifiers
Aliases	OGFR, OGFr, opioid growth factor receptor
External IDs	OMIM: 606459; MGI: 1919325; HomoloGene: 7199; GeneCards: OGFR; OMA:OGFR - orthologs
Gene location (Human) Chr. Chromosome 20 (human)[1] Band 20q13.33 Start 62,804,835 bp[1] End 62,814,000 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 H4 Start 180,231,038 bp[2] End 180,237,629 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte monocyte sural nerve right frontal lobe right lobe of liver spleen right lung right uterine tube cingulate gyrus olfactory zone of nasal mucosa Top expressed in yolk sac granulocyte ventricular zone mandibular prominence maxillary prominence thymus internal carotid artery ganglionic eminence mesenteric lymph nodes neural layer of retina More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding G protein-coupled opioid receptor activity signaling receptor activity Cellular component membrane cytoplasm nucleus cellular component Biological process regulation of growth regulation of cell growth G protein-coupled opioid receptor signaling pathway signal transduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 11054 72075 Ensembl ENSG00000060491 ENSMUSG00000049401 UniProt Q9NZT2 Q99PG2 RefSeq (mRNA) NM_007346 NM_031373 RefSeq (protein) NP_031372 NP_113550 Location (UCSC) Chr 20: 62.8 – 62.81 Mb Chr 2: 180.23 – 180.24 Mb PubMed search [3] [4]
Wikidata
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Opioid growth factor receptor (OGFr) conserved region
Identifiers
Symbol	OGFr_N
Pfam	PF04664
InterPro	IPR006757
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Opioid growth factor receptor repeat
Identifiers
Symbol	OGFr_III
Pfam	PF04680
InterPro	IPR006770
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Function

The natural function of this receptor appears to be in regulation of tissue growth,^{[7][8][9][10]} and it has been shown to be important in embryonic development,^[11] wound repair,^[12] and certain forms of cancer.^{[13][14][15][16]}

OGF is a negative regulator of cell proliferation and tissue organization in a variety of processes. The encoded unbound receptor for OGF has been localized to the outer nuclear envelope, where it binds OGF and is translocated into the nucleus. The coding sequence of this gene contains a polymorphic region of 60 nt tandem imperfect repeat units. Several transcripts containing between zero and eight repeat units have been reported.^[5]

Mechanism of activation

The opioid growth factor receptor consists of a chain of 677 amino acids, which includes a nuclear localization sequence region. When OGF binds to the receptor, an OGF-OGFr complex is formed, which leads to the increase in the synthesis of the selective cyclin-dependent kinase (CDK) inhibitor proteins, p12 and p16. Retinoblastoma protein becomes inactivated through phosphorylation by CDKs, and leads to the progression of the cell cycle from the G1 phase to the S phase. Because the activation of the OGF receptor, blocks the phosphorylation of retinoblastoma proteins, retardation of the G₁ phase occurs, which prevents the cell from further dividing.^[17][18]

Therapeutic applications

Upregulation of OGFr and consequent stimulation of the OGF-OGFr system are important for the anti-proliferative effects of imidazoquinoline drugs like imiquimod and resiquimod, which are immune response modifiers with potent antiviral and antitumour effects, used as topical creams for the treatment of skin cancers and warts.^[19]

Structure

OGF contains a conserved N-terminal domain followed by a series of imperfect repeats.^[8]