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FLASH GENE
Symbol GNL3 contributors: mct - updated : 23-08-2016
HGNC name guanine nucleotide binding protein-like 3 (nucleolar)
HGNC id 29931
Location 3p21.1      Physical location : 52.719.935 - 52.728.508
Synonym name
  • estradiol-induced nucleotide binding protein
  • nucleostemin 1
  • E2-induced gene 3 protein
  • novel nucleolar protein 47
  • Synonym symbol(s) NS1, E2IG3, C77032, MGC800, NNP47
    DNA
    TYPE functioning gene
    STRUCTURE 8.58 kb     15 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 splicing 2048 62 549 - 2003 14648588
    15 splicing 2159 60 537 - 2003 14648588
  • encoding the same protein than variant 3
  • 15 splicing 2012 60 537 - 2003 14648588
  • encoding the same protein than variant 2
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon moderately
     liver   moderately
     stomach   highly
    Reproductivefemale systemuterus  moderately
     female systemovary  moderately
     male systemprostate  moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    Connectivebone   
    Nervousperipherous   
    cell lineage in adult stem cells
    cell lines transformed cell lines, and tumors (Ma 2007)
    fluid/secretion
    at STAGE
    Text in embryo-derived stem cells (Ma 2007)
    PROTEIN
    PHYSICAL PROPERTIES acid ,basic
    STRUCTURE
    motifs/domains
  • an N-terminal basic domain
  • an intermediate domain
  • a C-terminal acidic domain
  • two GTP-binding motifs
  • HOMOLOGY
    interspecies homolog to S. cerevisiae NUG1
    ortholog to rattus Ns
    Homologene
    FAMILY MMR1/HSR1 GTP-binding protein family
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,nucleolus
    text Shuttling between the nucleus and nucleolus
    basic FUNCTION
  • may be required to maintain the proliferative capacity of stem cells
  • may play an important role in both tumorigenesis and transforming embryonic bone marrow mesenchymal stem cells
  • involved in the regulation of cell proliferation, and both depletion and overexpression of nucleostemin induce cell cycle arrest through the TP53 signaling pathway (Romanova 2009)
  • has a role as an integrated component of ribosome biogenesis, particularly pre-rRNA processing (Romanova 2009)
  • playing a role in ribosome biogenesis and in regulating cell proliferation (Romanova 2009)
  • has an unexpected role in post-mitotic terminal differentiation
  • is implicated in the control of stem and cancer cell proliferation
  • potential role in tumorogenesis of brain cancers
  • maintains self-renewal of embryonic stem cells and promotes reprogramming of somatic cells to pluripotency
  • implicated in the maintenance of ESC self-renewal, demonstrating the importance of rapid transit through G1 for this process
  • primary function of nucleostemin in maintaining the genomic stability of actively dividing stem/progenitor cells by promoting the recruitment of RAD51 to stalled replication-induced DNA damage foci
  • protects HSCs from DNA damage accumulation and is required for the maintenance of HSCs
  • nucleolus residing GTPase that is considered to be an important cancer stem/progenitor cell marker protein due to its high expression levels in breast cancer stem cells and its role in tumor-initiation of human mammary tumor cells
  • nucleolar GTP-binding protein that is involved in a plethora of functions including ribosomal biogenesis and maintenance of telomere integrity
  • participates in preservation of the viability and integrity of ESCs, which is distinct from that in other GNL3-expressing cells
  • nucleolar protein with pivotal functions in maintaining genomic integrity and determining cell fates of various normal and cancerous stem cells
  • nucleolar proteins GNL2 and GNL3 have similar but non-overlapping roles in the final maturation or nucleolar release of 60S ribosomal subunits
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component forms a large protein complex containing proteins related to pre-rRNA processing, such as PES1, DDX21, and EBNA1BP2, in addition to several ribosomal proteins (Romanova 2009)
    INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • GTP
  • protein
  • p53/TP53 via its basic domain
  • RSL1D1 is a GNL3-interacting protein
  • TERF1 dimerization is actively and oppositely regulated by GNL3 and GNL3L extrachromosomally
  • functions downstream of MYC as a rate-limiting regulator of cell proliferation and transformation, independently from its putative role within the TP53 pathway
  • prevents telomere damage by promoting PML-IV recruitment to SUMOylated TERF1
  • may play a significant role in the determination of breast cancer progression in association with TP53 alterations
  • stabilizes CDKN2A by inhibiting the ubiquitin ligase TRIP12
  • cell & other
    REGULATION
    induced by estrogen
    Other regulated by CDKN2A and the control of the G1/S transition by NS operates in a TP53-dependent manner (Ma 2007)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in lung cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS