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FLASH GENE
Symbol NRL contributors: mct/shn/pgu - updated : 05-04-2016
HGNC name neural retina leucine zipper
HGNC id 8002
Corresponding disease
RP27 retinitis pigmentosa 27
Location 14q11.2      Physical location : 24.549.316 - 24.553.832
Synonym name
  • neural retina-specific leucine zipper protein
  • neural retinal-specific leucine zipper
    • Synonym symbol(s) NRS1, D14S46E, NRL-MAF, D14S46E-MAF, RP27
    DNA
    TYPE functioning gene
    STRUCTURE 4.52 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    motif repetitive sequence   other
    text structure
  • microsatellite repeat repeat at the NRL locus
  • RARE (retnoic acid response element) in the promoter
  • CRX, OTX2, and RORB directly regulate NRL transcription by binding to critical sites within the NRL promoter
    • MAPPING cloned Y linked Y status confirmed
    Map cen - D14S581 - D14S972 - NRL - D14S64 - D14S264 - qter
    RNA
    TRANSCRIPTS type messenger
    text multiple phosphorylated isoforms of NRL in rod photoreceptors (PMID: 12566383)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 1974 - 237 - 2003 12566383
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Visualeyeretina  specific
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Visualamacrine cell
    Visualbipolar cell
    Visualcone photoreceptor
    Visualganglion cell
    Visualhorizontal association cell
    VisualMuller cell
    Visualrod photoreceptor
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a MTD (inimal transcription domain) N terminal domain, playing an important role in assembling the transcription initiation complex
  • a basic leucine zipper (bZIP) domains
  • a minimal transactivation domain (MTD)
    • HOMOLOGY
    interspecies ortholog to Nrl, Mus musculus
    ortholog to Nrl, Rattus norvegicus
    ortholog to NRL, Pan troglodytes
    ortholog to nrl, Danio rerio
    Homologene
    FAMILY
  • Maf-Nrl subfamily of bZIP transcription factors
  • Maf-family leucine zipper transcription factor
    • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • regulator of photoceptor development and function
  • signaling by RA via RA receptors regulates the expression of NRL, providing a framework for delineating early steps in photoreceptor cell fate determination
  • regulator of rhodopsin expression synergistically with Crx
  • basic motif leucine zipper transcription factor that regulates the expression of several rod-specific genes, including rhodopsin and cGMP phosphodiesterase beta-subunit, in synergy with other transcription factors
  • regulates the expression of several rod-specific genes such as rhodopsin and cGMP phosphodiesterase beta-subunit
  • is essential for rod photoreceptor specification in the mammalian retina as its loss of function converts rod precursors to functional cones
  • critical for rod versus cone photoreceptor cell fate choice during retinal development and acts as a molecular switch to produce rods from postmitotic precursors
  • essential transcription factor for cell fate specification and functional maintenance of rod photoreceptors in the mammalian retina
  • is a critical determinant of rod photoreceptor cell fate and a key regulator of rod differentiation
  • transcription factor, modulating rod photoreceptor differentiation by activating rod-specific target genes
  • activated rhodopsin and PPP2R5C transcription by recruiting KAT5 to promote histone H3/H4 acetylation
  • is essential for rod photoreceptor development and functional maintenance in the mammalian retina
    • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling sensory transduction/vision
    a component
    INTERACTION
    DNA induces rhodopsin promoter activity
    RNA
    small molecule other,
  • signaling by RA via RA receptors regulates the expression of NRL, providing a framework for delineating early steps in photoreceptor cell fate determination
    • protein
  • CRX homeodomain
  • NRL and NR2E3 have overlapping functions, and NRL binds to a sequence element in the NR2E3 promoter and enhances its activity synergistically with the homeodomain protein CRX
  • PPP2R5C expression is regulated by NRL during retinogenesis through direct binding to the promoter region of PPP2R5C
  • direct transcriptional target of RORB, suggesting that combinatorial action of multiple regulatory factors modulates the expression of NRL in developing and mature retina
  • CRX, OTX2, and cyclic AMP response element-binding protein (CREB) are implicated in modulating NRL expression
  • MEF2C expression from an alternative promoter in the retina is regulated by NRL
  • interactions of NRL with c-Jun N-terminal kinase 1 (MAPK8) and HIV Tat-interacting protein 60 (KAT5)
  • NRL is the first OPTN-binding protein to show eye-specific expression
  • OTX2 maintains NRL expression in developing rods to consolidate rod fate
  • KCNV2 is controlled by cone-rod homeobox (CRX) and neural retina leucine zipper (NRL)
  • NRL binding within the REEP6 intron 1
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) RP27
    related resource Retinal Information Network
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurosensorialvisualretina
    identification of a small NRL promoter/enhancer sequence of <0.3 kb that can specifically direct the target gene to both developing and mature rod photoreceptors should be of interest in the design of adeno-associated virus-based therapies for retinal dis
    ANIMAL & CELL MODELS
  • deletion of Nrl in mice results in the complete loss of rod function and super-normal cone function, retina have cone-like nuclear morphology and short, sparse outer segments with abnormal disks
  • Loss of Nrl in mouse leads to a cone-only retina
  • in the Nrl(-/-) mouse retina, photoreceptor precursors fail to produce rods and generate functional cone photoreceptors that predominantly express S-opsin
  • loss of Nrl in mice leads to a cone-only retina with the complete absence of rods