NRF1

Not to be confused with nuclear factor (erythroid-derived 2)-like 1 or NFE2L1.

NRF1
Identifiers
Aliases	NRF1 , ALPHA-PAL, nuclear respiratory factor 1
External IDs	OMIM: 600879 MGI: 1332235 HomoloGene: 3674 GeneCards: NRF1
Gene location (Human) Chr. Chromosome 7 (human) [1] Band 7q32.2 Start 129,611,720 bp [1] End 129,757,082 bp [1]
Gene location (Mouse) Chr. Chromosome 6 (mouse) [2] Band 6 A3.3|6 12.47 cM Start 30,047,987 bp [2] End 30,153,457 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in cerebellar hemisphere right uterine tube anterior pituitary ganglionic eminence sural nerve gastrocnemius muscle canal of the cervix popliteal artery left uterine tube nucleus accumbens Top expressed in secondary oocyte Paneth cell thymus yolk sac morula primitive streak lip ganglionic eminence submandibular gland neural tube More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding protein homodimerization activity DNA-binding transcription activator activity, RNA polymerase II-specific RNA polymerase II cis-regulatory region sequence-specific DNA binding protein binding core promoter sequence-specific DNA binding RNA polymerase II core promoter sequence-specific DNA binding DNA-binding transcription factor activity Cellular component extracellular exosome nucleoplasm cytosol nucleus Biological process regulation of transcription, DNA-templated regulation of transcription by RNA polymerase II mitochondrion organization generation of precursor metabolites and energy transcription, DNA-templated positive regulation of transcription by RNA polymerase II transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4899 18181 Ensembl ENSG00000106459 ENSMUSG00000058440 UniProt Q16656 Q9WU00 RefSeq (mRNA) NM_005011 NM_001040110 NM_001293163 NM_001293164 NM_001164226 NM_001164227 NM_001164228 NM_001164229 NM_001164230 NM_010938 NM_001361692 NM_001361693 NM_001361694 NM_001361695 RefSeq (protein) NP_001035199 NP_001280092 NP_001280093 NP_005002 NP_001157698 NP_001157699 NP_001157700 NP_001157701 NP_001157702 NP_035068 NP_001348621 NP_001348622 NP_001348623 NP_001348624 Location (UCSC) Chr 7: 129.61 – 129.76 Mb Chr 6: 30.05 – 30.15 Mb PubMed search [3] [4]
Wikidata
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Nuclear respiratory factor 1, also known as Nrf1, Nrf-1, NRF1 and NRF-1, encodes a protein that homodimerizes and functions as a transcription factor which activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication. The protein has also been associated with the regulation of neurite outgrowth. Alternate transcriptional splice variants, which encode the same protein, have been characterized. Additional variants encoding different protein isoforms have been described but they have not been fully characterized. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene and for "nuclear factor (erythroid-derived 2)-like 1" which has an official symbol of NFE2L1.^{[ citation needed ]}

Function

Nrf1 functions as a transcription factor that activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for mitochondrial respiration, and mitochondrial DNA transcription and replication. Nrf1, together with Nrf2, mediates the biogenomic coordination between nuclear and mitochondrial genomes by directly regulating the expression of several nuclear-encoded ETC proteins, and indirectly regulating the three mitochondrial-encoded COX subunit genes by activating mtTFA, mtTFB1, and mtTFB2.

Nrf1 is associated with the regulation of neurite outgrowth. ^[5]

Alternate transcriptional splice variants, which encode the same protein, have been characterized. Additional variants encoding different protein isoforms have been described but they have not been fully characterized. ^[6]

Cyclin D1-dependent kinase, through phosphorylating NRF-1 at S47, coordinates nuclear DNA synthesis and mitochondrial function. ^[7]

Interactions

NRF1 has been shown to interact with DYNLL1, ^[8] PPARGC1A, ^[9] and PPRC1. ^[10]

References

1. GRCh38: Ensembl release 89: ENSG00000106459 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000058440 - 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. Chang WT, Chen HI, Chiou RJ, Chen CY, Huang AM (August 2005). "A novel function of transcription factor alpha-Pal/NRF-1: increasing neurite outgrowth". Biochem. Biophys. Res. Commun. 334 (1): 199–206. doi:10.1016/j.bbrc.2005.06.079. PMID   15992771.
6. "Entrez Gene: NRF1 nuclear respiratory factor 1".
7. Wang C, Li Z, Lu Y, Du R, Katiyar S, Yang J, Fu M, Leader JE, Quong A, Novikoff PM, Pestell RG (2006). "Cyclin D1 repression of nuclear respiratory factor 1 integrates nuclear DNA synthesis and mitochondrial function". Proceedings of the National Academy of Sciences. 103 (31): 11567–72. Bibcode:2006PNAS..10311567W. doi: 10.1073/pnas.0603363103 . JSTOR   30051572. PMC   1518800 . PMID   16864783.
8. Herzig RP, Andersson U, Scarpulla RC (December 2000). "Dynein light chain interacts with NRF-1 and EWG, structurally and functionally related transcription factors from humans and drosophila". J. Cell Sci. 113 (23): 4263–73. doi:10.1242/jcs.113.23.4263. PMID   11069771.
9. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM (July 1999). "Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1". Cell. 98 (1): 115–24. doi: 10.1016/S0092-8674(00)80611-X . PMID   10412986. S2CID   16143809.
10. Andersson U, Scarpulla RC (May 2001). "PGC-1-related coactivator, a novel, serum-inducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells". Mol. Cell. Biol. 21 (11): 3738–49. doi:10.1128/MCB.21.11.3738-3749.2001. PMC   87014 . PMID   11340167.

Further reading

• Tiranti V, Rossi E, Rocchi M, DiDonato S, Zuffardi O, Zeviani M (1995). "The gene (NFE2L1) for human NRF-1, an activator involved in nuclear-mitochondrial interactions, maps to 7q32". Genomics. 27 (3): 555–7. doi:10.1006/geno.1995.1094. PMID   7558044.
• Gopalakrishnan L, Scarpulla RC (1995). "Structure, expression, and chromosomal assignment of the human gene encoding nuclear respiratory factor 1". J. Biol. Chem. 270 (30): 18019–25. doi: 10.1074/jbc.270.30.18019 . PMID   7629110.
• Efiok BJ, Chiorini JA, Safer B (1994). "A key transcription factor for eukaryotic initiation factor-2 alpha is strongly homologous to developmental transcription factors and may link metabolic genes to cellular growth and development". J. Biol. Chem. 269 (29): 18921–30. doi: 10.1016/S0021-9258(17)32255-X . PMID   8034649.
• Virbasius JV, Scarpulla RC (1994). "Activation of the human mitochondrial transcription factor A gene by nuclear respiratory factors: a potential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis". Proc. Natl. Acad. Sci. U.S.A. 91 (4): 1309–13. Bibcode:1994PNAS...91.1309V. doi: 10.1073/pnas.91.4.1309 . PMC   43147 . PMID   8108407.
• Virbasius CA, Virbasius JV, Scarpulla RC (1994). "NRF-1, an activator involved in nuclear-mitochondrial interactions, utilizes a new DNA-binding domain conserved in a family of developmental regulators". Genes Dev. 7 (12A): 2431–45. doi: 10.1101/gad.7.12a.2431 . PMID   8253388.
• Spelbrink JN, Van den Bogert C (1996). "The pre-mRNA of nuclear respiratory factor 1, a regulator of mitochondrial biogenesis, is alternatively spliced in human tissues and cell lines". Hum. Mol. Genet. 4 (9): 1591–6. doi: 10.1093/hmg/4.9.1591 . PMID   8541844.
• Johnsen O, Skammelsrud N, Luna L, Nishizawa M, Prydz H, Kolstø AB (1996). "Small Maf proteins interact with the human transcription factor TCF11/Nrf1/LCR-F1". Nucleic Acids Res. 24 (21): 4289–97. doi:10.1093/nar/24.21.4289. PMC   146217 . PMID   8932385.
• Venugopal R, Jaiswal AK (1997). "Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H:quinone oxidoreductase1 gene". Proc. Natl. Acad. Sci. U.S.A. 93 (25): 14960–5. Bibcode:1996PNAS...9314960V. doi: 10.1073/pnas.93.25.14960 . PMC   26245 . PMID   8962164.
• Chen S, Nagy PL, Zalkin H (1997). "Role of NRF-1 in bidirectional transcription of the human GPAT-AIRC purine biosynthesis locus". Nucleic Acids Res. 25 (9): 1809–16. doi:10.1093/nar/25.9.1809. PMC   146651 . PMID   9108165.
• Toki T, Itoh J, Kitazawa J, Arai K, Hatakeyama K, Akasaka J, Igarashi K, Nomura N, Yokoyama M, Yamamoto M, Ito E (1997). "Human small Maf proteins form heterodimers with CNC family transcription factors and recognize the NF-E2 motif". Oncogene. 14 (16): 1901–10. doi: 10.1038/sj.onc.1201024 . PMID   9150357.
• Marini MG, Chan K, Casula L, Kan YW, Cao A, Moi P (1997). "hMAF, a small human transcription factor that heterodimerizes specifically with Nrf1 and Nrf2". J. Biol. Chem. 272 (26): 16490–7. doi: 10.1074/jbc.272.26.16490 . PMID   9195958.
• Gugneja S, Scarpulla RC (1997). "Serine phosphorylation within a concise amino-terminal domain in nuclear respiratory factor 1 enhances DNA binding". J. Biol. Chem. 272 (30): 18732–9. doi: 10.1074/jbc.272.30.18732 . PMID   9228045.
• Johnsen O, Murphy P, Prydz H, Kolsto AB (1998). "Interaction of the CNC-bZIP factor TCF11/LCR-F1/Nrf1 with MafG: binding-site selection and regulation of transcription". Nucleic Acids Res. 26 (2): 512–20. doi:10.1093/nar/26.2.512. PMC   147270 . PMID   9421508.
• Au HC, Scheffler IE (1998). "Promoter analysis of the human succinate dehydrogenase iron-protein gene--both nuclear respiratory factors NRF-1 and NRF-2 are required". Eur. J. Biochem. 251 (1–2): 164–74. doi: 10.1046/j.1432-1327.1998.2510164.x . PMID   9492280.
• Miranda S, Foncea R, Guerrero J, Leighton F (1999). "Oxidative stress and upregulation of mitochondrial biogenesis genes in mitochondrial DNA-depleted HeLa cells". Biochem. Biophys. Res. Commun. 258 (1): 44–9. doi:10.1006/bbrc.1999.0580. PMID   10222232.
• Li B, Holloszy JO, Semenkovich CF (1999). "Respiratory uncoupling induces delta-aminolevulinate synthase expression through a nuclear respiratory factor-1-dependent mechanism in HeLa cells". J. Biol. Chem. 274 (25): 17534–40. doi: 10.1074/jbc.274.25.17534 . PMID   10364186.
• Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM (1999). "Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1". Cell. 98 (1): 115–24. doi: 10.1016/S0092-8674(00)80611-X . PMID   10412986. S2CID   16143809.
• Solecki D, Bernhardt G, Lipp M, Wimmer E (2000). "Identification of a nuclear respiratory factor-1 binding site within the core promoter of the human polio virus receptor/CD155 gene". J. Biol. Chem. 275 (17): 12453–62. doi: 10.1074/jbc.275.17.12453 . PMID   10777530.
• Kumari D, Usdin K (2001). "Interaction of the transcription factors USF1, USF2, and alpha -Pal/Nrf-1 with the FMR1 promoter. Implications for Fragile X mental retardation syndrome". J. Biol. Chem. 276 (6): 4357–64. doi: 10.1074/jbc.M009629200 . PMID   11058604.

External links

• NRF1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook Nrf1

This article incorporates text from the United States National Library of Medicine, which is in the public domain.