Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol NRL contributors: mct/shn/pgu - updated : 05-04-2016
HGNC name neural retina leucine zipper
HGNC id 8002
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