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FLASH GENE
Symbol RLIM contributors: mct/pgu - updated : 17-11-2020
HGNC name ring finger protein, LIM domain interacting
HGNC id 13429
DNA
TYPE functioning gene
STRUCTURE 31.65 kb     4 Exon(s)    2 Copie(s)
regulatory sequence Promoter
alternative promoter
Binding site
text structure Sp1binding sites and others, several transcription initiation sites, maybe a copy at 15q21-q22
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
text several initiation sites
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
4 initiation site 10590 52 624 - 2002 11882901
4 initiation site 3315 67 483 highly in testis 2002 11882901
also called NY-Ren-43 antigen
4 - 10652 - 624 - 2009 19164295
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Reproductivemale systemtestis  highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one RING-type zinc finger
    • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine Rlim (89.2pc)
    homolog to rattus Rnf12 (89.9pc)
    Homologene
    FAMILY
  • RNF12 family
    • CATEGORY enzyme , regulatory , antigen
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text
  • RLIM shuttles between nucleus and cytoplasm and this is regulated by phosphorylation of serine S214 located within its nuclear localization sequence
    • basic FUNCTION
  • negative coregulator of LIM homeodomain proteins through recruitement of the SIN3A histone deacetylase complex
  • ubiquitin protein ligase able to target CLIM cofactors for degradation through the 26S proteasome pathway
  • RING H2 zinc finger protein with intrinsic ubiquitin ligase activity, as a TRF1-interacting protein
  • specific regulator of LDB1 to ensure its proper interactions with LIM-HD proteins and possibly other LDB1-interacting proteins in the organizer as well as in other tissues
  • represents a new pathway for modulating telomere length homeostasis by acting as a negative regulator of TERF1
  • regulate the biological activity of ESR1 during the development of breast cancer (Johnsen 2009)
  • dose-dependent activator of X-chromosome inactivation
  • indispensable factor in up-regulation of XIST transcription, thereby leading to initiation of random X chromosome inactivation (XCI)
  • enhances transcriptional activation of endogenous estrogen receptor alpha (ESR1) target genes
  • critical for the regulation of X-inactivation, and is negatively regulated by pluripotency factors in embryonic stem cells
  • is an important positive regulator in TGFB signaling pathway and cell migration
  • may play an important role during the development of human cancer
  • may possess similar cellular properties with R-Smads
  • acts at two subsequent steps: two active copies of RNF12 drive initiation of X chromosome inactivation (XCI), and one copy needs to remain active to maintain XCI toward establishment of the inactive X chromosome (Xi)
  • RLIM may function as a tumor suppressor by controlling the activity of MYC oncoprotein
  • RLIM-dependent and -independent pathways for X Chromosome inactivation in female ESCs
  • RLIM catalytic activity is required for proper stem cell maintenance and neural differentiation, and this is disrupted by patient-associated XLID mutation
  • key function for RLIM E3 ubiquitin ligase activity in stem cell and neural development
  • during female embryogenesis, major roles of RLIM have been identified in conjunction with REXO1 during X dosage compensation
  • crucial importance to the RLIM-REXO1 axis in controlling XCI
  • is involved in control of early embryogenesis, notably brain and neural tube development
  • is a dosage-sensitive gene and increased protein levels arising from duplications are associated with neurocognitive abnormalities
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding
    RNA
    small molecule metal binding,
  • Zn2+
    • protein
  • interacting with LIM homeodomain proteins, ubiquitination dependent association in the presence of CLIM cofactors
  • interacting with LHX3, LDB1, LDB2, SIN3A, TERF1, ESR1
  • is under the control of NANOG, POU5F1 and SOX2, the three factors lying at the heart of the pluripotency network
  • directly bind to SMURF2, enhancing TGFB responsiveness in osteosarcoma U2OS cells
  • RLIM targets REXO1, an inhibitor of X chromosome inactivation (XCI), for proteasomal degradation, regulating initiation of XCI
  • RLIM inhibits the transcriptional activity of MYC through which RLIM restrains cell proliferation
  • control of LHX2 function by LDB1 and RLIM underpins the coordinated differentiation of neurons and Müller glia in postnatal retina
  • act as a co-factor promoting or inhibiting transcription via binding to LIM-homeodomain (LIM-HD) transcription factors
    • cell & other
    REGULATION
    activated by Krüppel-like transcription factors
    Other its functional activity is regulated by phosphorylation-dependent nucleocytoplasmic shuttling
    ASSOCIATED DISORDERS
    corresponding disease(s) MRX61 , DUPXQ13
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    limb defect in chicken overexpressing Rnf12