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Symbol NRF1 contributors: mct/shn - updated : 28-08-2017
HGNC name nuclear respiratory factor 1
HGNC id 7996
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
10 - 3440 - 342 - 2016 27416755
12 - 3612 - 522 - 2016 27416755
11 - 3540 - 503 - 2016 27416755
11 - 3523 - 503 - 2016 27416755
Type ubiquitous
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivepharynx   highly
Lymphoid/Immunelymph node   highly
Visualeyeretina    Rattus norvegicus
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectiveadipose  highly
cell lineage
cell lines
  • an atypical nuclear localization signal (NLS) in the N terminus region
  • a DSGLS similar to the canonical BTRC recognition motif
  • a transactivation domains (TADs), including its Asn/Ser/Thr-rich (NST) glycodomain, are transiently translocated into the ER lumen, where it is glycosylated in the presence of glucose to become a 120-kDa isoform
  • a bipartite C terminal hydrophobic region
  • mono polymer homomer
    interspecies ortholog to Nrf1, Mus musculus
    ortholog to Nrf1, Rattus norvegicus
    ortholog to nrf1, Danio rerio
    ortholog to NRF1, Pan troglodytes
    FAMILY nuclear respiratory factor 1 family, NRF1/EWG family
    CATEGORY regulatory , transcription factor
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • primarily a membrane-bound protein localized in the endoplasmic reticulum
  • deletion of N-terminal domain resulted in a predominantly nuclear localization that significantly increased the activation of reporter gene expression
  • targeted to the endoplasmic reticulum (ER), implying that it translocates into the nucleus in response to an activating signal
  • is integrated within endoplasmic reticulum (ER) membranes through its NHB1-associated TM1 in cooperation with other semihydrophobic amphipathic regions
  • basic FUNCTION
  • regulates expression of genes involved in mitochondrial function, and coregulates a large number of E2F target genes
  • respiratory factor 1, involved in the regulation of mitochondrial biogenesis and in oxidative phosphorylation
  • implicated in the control of nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication
  • regulate neuronal differentiation, and this function is mediated partly via its downstream IAP gene
  • transcription factor that acts on nuclear genes encoding respiratory subunits and components of the mitochondrial transcription and replication machinery
  • dominant transcription factor regulating mitochondrial biogenesis and respiration
  • central transcription factor that promotes the expression of nuclear-encoded respiratory genes
  • could be a regulatory factor for gene expression of the other visinin-like subfamily members including HPCAL4, HPCAL1, HPCA, and NCALD
  • pivotal transcriptional modulator controlling gene expression of mitochondrial proteins
  • transcriptional inhibitor of the human ACACB gene promoter in the mammalian heart
  • major inducible transcriptional regulator of SLC46A1 gene expression
  • its activity in the minimal SLC46A1 promoter is not essential for the transactivation capacity of upstream enhancer elements in the SLC46A1 promoter
  • functionally regulates mediators of energy consumption in neurons
  • regulates key Na(+)/K(+)-ATPase subunits and plays an important role in mediating the tight coupling between energy consumption, energy generation, and neuronal activity at the molecular level
  • fulfils important functions in maintaining cellular homeostasis and organ integrity
  • is important in cellular stress pathway
  • NRF1 acts through antioxidant response elements located in the HERPUD1 promoter
  • transcription factor NRF1 occupies several thousand additional sites in the unmethylated genome, resulting in increased transcription; restoring de novo methyltransferase activity initiates remethylation at these sites and outcompetes NRF1 binding
  • likely is a key player in the regulation of the ER stress response in cells
  • transcriptional regulation factor that plays a central role in the regulation of mitochondrial biogenesis
  • might act as a novel renal fibrosis antagonist by down-regulating fibrosis signaling in renal fibroblast cells
  • key transcription factor for mitochondrial biogenesis, cooperated with DNA methylation to directly regulate the expression of multiple germ cell-specific genes including ASZ1
  • role of NRF1 in spermatogenesis
  • NRF1 regulates likely the expression of CXCR4 in normal retinal development and in pathologic processes of retinal hypoxia and neovascularization
  • novel functions of the NGLY1-NRF1 pathway in mitochondrial homeostasis and inflammation
  • CELLULAR PROCESS nucleotide, transcription
    metabolism energetic
  • novel functions of the NGLY1-NRF1 pathway in mitochondrial homeostasis and inflammation
  • a component
  • VSNL1 promoter
  • RNA
    small molecule
  • PGC-1
  • Dynein light chain
  • MafF
  • CCAAT enhancer-binding protein (C/EBP)beta
  • Poly(ADP-ribose) Polymerase 1, PARP-1
  • SLC46A1
  • in the nucleus, BTRC promotes the degradation of NRF1 by catalyzing its polyubiquitination
  • NRF1 could be a regulatory factor for VSNL1 gene expression and for other visinin-like subfamily members including HPCAL4, HPCAL1, HPCA, and NCALD
  • NRF1 co-regulates oxidative enzymes that generate energy and neurochemicals that consume energy related to glutamatergic neurotransmission, such as KIF17, GRIN1, and GRIN2B, thereby ensuring that energy production matches energy utilization at the molecular and cellular levels
  • both BTRC- and SYVN1-dependent degradation mechanisms regulate the transcriptional activity of NRF1 to maintain cellular homeostasis
  • RETREG3, BRK1 and ENOX1 are regulated by NRF1 and differentially regulate neurite outgrowth in neuroblastoma cells and hippocampal neurons
  • HERPUD1 is a direct NRF1 target gene, and NRF1 is a transcriptional activator of HERPUD1 expression during ER stress
  • NRF1 together with the transcriptional co-activator PPARGC1A stimulates the expression of a broad set of nuclear genes (as COX6C) which are involved in mitochondrial biogenesis and functions
  • TIGAR enhanced the expression of LDHB and the mitochondrial biogenesis and oxidative phosphorylation (OXPHOS) markers, PPARGC1A, and NRF1, during neural stem cells (NSCs) diferentiation
  • cell & other
    Other endoplasmic reticulum stress may play a role in modulating NRF1 function as a transcriptional activator
    degraded and suppressed by the ER-associated degradation (ERAD) ubiquitin ligase SYVN1 and valosin-containing protein (VCP) under normal conditions
    corresponding disease(s)
    related resource MITOP database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    results in decreased HERPUD1 expression in cells and liver tissues
    constitutional     --low  
    NRF1 and COX6C are down-regulated in Chronic kidney disease (CKD) patients
    Susceptibility to type 2 diabetes mellitus
    Variant & Polymorphism other haplotypes associated with type 2 diabetes mellitus
    Candidate gene
    Therapy target
  • expression levels of NRF1 is significantly decreased in both Alzheimer's disease hippocampal tissues and AD-causing amyloid precursor protein mutant cells