OGFr

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Identifiers
Aliases
External IDs	GeneCards: [1]
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Species	Human	Mouse
Entrez	n/a	n/a
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UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
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Opioid growth factor receptor (OGFr) conserved region
Identifiers
Symbol	OGFr_N
Pfam	PF04664
InterPro	IPR006757
Available protein structures: Pfam structures 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 PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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. 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.

Function

The natural function of this receptor appears to be in regulation of tissue growth, and it has been shown to be important in embryonic development, wound repair, and certain forms of cancer.

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.

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 activated through the phosphorylation from 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 retinoblastmoa proteins, retardation of the G₁ phase occurs, which prevents the cell from further dividing.

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.

Structure

OGF contains a conserved N-terminal domain followed by a series of imperfect repeats.

Further reading

• Zagon IS, Verderame MF, McLaughlin PJ (2002). "The biology of the opioid growth factor receptor (OGFr)". Brain Res. Brain Res. Rev. 38 (3): 351–76. doi:10.1016/S0165-0173(01)00160-6. PMID 11890982.
• Zagon IS, Verderame MF, Allen SS, McLaughlin PJ (2000). "Cloning, sequencing, chromosomal location, and function of cDNAs encoding an opioid growth factor receptor (OGFr) in humans". Brain Res. 856 (1–2): 75–83. doi:10.1016/S0006-8993(99)02330-6. PMID 10677613.
• Wu CJ, Yang XF, McLaughlin S, et al. (2000). "Detection of a potent humoral response associated with immune-induced remission of chronic myelogenous leukemia". J. Clin. Invest. 106 (5): 705–14. doi:10.1172/JCI10196. PMC 381287. PMID 10974024.
• Hattori A, Okumura K, Nagase T, et al. (2001). "Characterization of long cDNA clones from human adult spleen". DNA Res. 7 (6): 357–66. doi:10.1093/dnares/7.6.357. PMID 11214971.
• Deloukas P, Matthews LH, Ashurst J, et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20". Nature. 414 (6866): 865–71. doi:10.1038/414865a. PMID 11780052.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Zagon IS, Ruth TB, Leure-duPree AE, et al. (2003). "Immunoelectron microscopic localization of the opioid growth factor receptor (OGFr) and OGF in the cornea". Brain Res. 967 (1–2): 37–47. doi:10.1016/S0006-8993(02)04172-0. PMID 12650964.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• McLaughlin PJ, Zagon IS (2006). "Progression of squamous cell carcinoma of the head and neck is associated with down-regulation of the opioid growth factor receptor". Int. J. Oncol. 28 (6): 1577–83. doi:10.3892/ijo.28.6.1577. PMID 16685459.
• Zagon IS, McLaughlin PJ (2006). "Opioid growth factor receptor is unaltered with the progression of human pancreatic and colon cancers". Int. J. Oncol. 29 (2): 489–94. doi:10.3892/ijo.29.2.489. PMID 16820893.
• Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
• McLaughlin PJ, Verderame MF, Hankins JL, Zagon IS (2007). "Overexpression of the opioid growth factor receptor downregulates cell proliferation of human squamous carcinoma cells of the head and neck". Int. J. Mol. Med. 19 (3): 421–8. doi:10.3892/ijmm.19.3.421. PMID 17273790.

This article incorporates text from the public domain Pfam and InterPro: IPR006757

This article incorporates text from the public domain Pfam and InterPro: IPR006770