Summary: Opioid growth factor receptor repeat
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|, OGFr, opioid growth factor receptor|
|Opioid growth factor receptor (OGFr) conserved region|
|Opioid growth factor receptor repeat|
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.
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.
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.
- GRCh38: Ensembl release 89: ENSG00000060491 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000049401 - Ensembl, May 2017
- "Human PubMed Reference:".
- "Mouse PubMed Reference:".
- "Entrez Gene: OGFR opioid growth factor receptor".
- Zagon IS, Verderame MF, Allen SS, McLaughlin PJ (February 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 Y, McLaughlin PJ, Zagon IS (April 1998). "Ontogeny of the opioid growth factor, Met5-enkephalin, preproenkephalin gene expression, and the zeta opioid receptor in the developing and adult aorta of rat". Dev. Dyn. 211 (4): 327–37. doi:10.1002/(SICI)1097-0177(199804)211:4<327::AID-AJA4>3.0.CO;2-J. PMID 9566952.
- Zagon IS, Verderame MF, McLaughlin PJ (February 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.
- Malendowicz LK, Rebuffat P, Tortorella C, Nussdorfer GG, Ziolkowska A, Hochol A (May 2005). "Effects of met-enkephalin on cell proliferation in different models of adrenocortical-cell growth". Int. J. Mol. Med. 15 (5): 841–5. doi:10.3892/ijmm.15.5.841. PMID 15806307.
- Cheng F, McLaughlin PJ, Verderame MF, Zagon IS (January 2009). "The OGF-OGFr axis utilizes the p16INK4a and p21WAF1/CIP1 pathways to restrict normal cell proliferation". Molecular Biology of the Cell. 20 (1): 319–27. doi:10.1091/mbc.E08-07-0681. PMC . PMID 18923142.
- Zagon IS, Wu Y, McLaughlin PJ (August 1999). "Opioid growth factor and organ development in rat and human embryos". Brain Res. 839 (2): 313–22. doi:10.1016/S0006-8993(99)01753-9. PMID 10519055.
- Sassani JW, Zagon IS, McLaughlin PJ (May 2003). "Opioid growth factor modulation of corneal epithelium: uppers and downers". Curr. Eye Res. 26 (5): 249–62. doi:10.1076/ceyr.220.127.116.1127. PMID 12854052.
- Zagon IS, Smith JP, McLaughlin PJ (March 1999). "Human pancreatic cancer cell proliferation in tissue culture is tonically inhibited by opioid growth factor". Int. J. Oncol. 14 (3): 577–84. doi:10.3892/ijo.14.3.577. PMID 10024694.
- McLaughlin PJ, Levin RJ, Zagon IS (May 1999). "Regulation of human head and neck squamous cell carcinoma growth in tissue culture by opioid growth factor". Int. J. Oncol. 14 (5): 991–8. doi:10.3892/ijo.14.5.991. PMID 10200353.
- Cheng F, Zagon IS, Verderame MF, McLaughlin PJ (November 2007). "The opioid growth factor (OGF)-OGF receptor axis uses the p16 pathway to inhibit head and neck cancer". Cancer Research. 67 (21): 10511–8. doi:10.1158/0008-5472.CAN-07-1922. PMID 17974995.
- Donahue RN, McLaughlin PJ, Zagon IS (March 2009). "Cell Proliferation of Human Ovarian Cancer is Regulated by the Opioid Growth Factor - Opioid Growth Factor Receptor Axis". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 296 (6): R1716–25. doi:10.1152/ajpregu.00075.2009. PMID 19297547.
- Zagon IS, Donahue RN, McLaughlin PJ (2009). "Opioid growth factor-opioid growth factor receptor axis is a physiological determinant of cell proliferation in diverse human cancers". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 297 (4): R1154–61. doi:10.1152/ajpregu.00414.2009. PMID 19675283.
- Avella DM, Kimchi ET, Donahue RN, Tagaram HR, McLaughlin PJ, Zagon IS, Staveley-O'Carroll KF (2010). "The opioid growth factor-opioid growth factor receptor axis regulates cell proliferation of human hepatocellular cancer". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 298 (2): R459–66. doi:10.1152/ajpregu.00646.2009. PMC . PMID 19923357.
- Zagon IS, Donahue RN, Rogosnitzky M, McLaughlin PJ (August 2008). "Imiquimod upregulates the opioid growth factor receptor to inhibit cell proliferation independent of immune function". Experimental Biology and Medicine (Maywood, N.J.). 233 (8): 968–79. doi:10.3181/0802-RM-58. PMID 18480416.
- 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 . 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 . 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 . 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 tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Opioid growth factor receptor repeat Provide feedback
Proline-rich repeat found only in a human opioid growth factor receptor .
This tab holds annotation information from the InterPro database.
InterPro entry IPR006770
Opioid peptides act as growth factors in neural and non-neural cells and tissues, in addition to serving for neurotransmission/neuromodulation in the nervous system. The native opioid growth factor (OGF), [Met(5)]-enkephalin, is an inhibitory peptide that plays a role in cell proliferation and tissue organisation during development, cancer, cellular renewal, wound healing, and angiogenesis. OGF action is mediated by a receptor mechanism, the receptor for OGF (OGFr) is an integral membrane protein associated with the nucleus.
OGFr is distinguished by containing a series of imperfect repeats. This entry describes a proline-rich repeat found in a human opioid growth factor receptor [PUBMED:11890982].
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|Seed source:||Pfam-B_4529 (release 7.5)|
|Author:||Waterfield DI , Finn RD|
|Number in seed:||3|
|Number in full:||81|
|Average length of the domain:||21.30 aa|
|Average identity of full alignment:||63 %|
|Average coverage of the sequence by the domain:||9.90 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||13|
|Download:||download the raw HMM for this family|
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Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
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