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FLASH GENE
Symbol ORC2 contributors: mct - updated : 31-01-2015
HGNC name origin recognition complex, subunit 2
HGNC id 8488
Location 2q33.1      Physical location : -
Synonym name
  • origin recognition complex, subunit 2-like (yeast)
  • origin of replication 2-like
  • Synonym symbol(s) ORC2L
    DNA
    TYPE functioning gene
    STRUCTURE 53.52 kb     18 Exon(s)
    MAPPING cloned Y linked   status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    18 - 3140 66 577 - 2010 : 201808
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
    Endocrineparathyroid   highly
    Lymphoid/Immunethymus   highly
    Reproductivemale systemtestis  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle, G1, S, G2, M
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal 230 AAs (GST-ORC2-N)
  • two nuclear localization signals (NLSs) required for ORC accumulation in the nucleus , and required for interaction with all other ORC subunit
  • multiple CBX5-interacting domains
  • C-terminal 347 AAs is a single ORC assembly domain
  • mono polymer heteromer , complex
    HOMOLOGY
    interspecies homolog to yeast (origin of replication recognition complex,subuni) ORC2-like
    homolog to murine Orc2
    homolog to C.elegans c33g3.6
    Homologene
    FAMILY
  • ORC family
  • CATEGORY regulatory , DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome,heterochromosome
    intracellular,nucleus,chromatin/chromosome,centromere
    intracellular,nucleus,chromatin/chromosome,kinetochore
    text
  • tightly bound to heterochromatin and heterochromatin protein 1alpha (HP1alpha) and HP1beta in G1 and early S phase, but during late S, G2 and M phases tight chromatin association was restricted to centromeres
  • also localized to centrosomes throughout the entire cell cycle
  • present only at the centromeres during late G2 and mitosis
  • gradually are displaced from chromatin during S phase, ending up exclusively at centric (and in some cells, also telomeric) heterochromatin in mitosis
  • shortly after fertilization, ORC2 was detectable at the metaphase II spindle poles and then between the separating chromosomes
  • during zygotic mitosis, ORC2 again localized first to the spindle poles, then to the area between the separating chromosomes
  • in G1 of the two-cell stage, both nuclei had salt-resistant ORC2 and MCM7
  • basic FUNCTION
  • regulator of the initiation of DNA replication and transcription
  • having a role in both chromosomal replication and mating type transcriptional silencing
  • implicated in many cellular activities, including DNA replication, transcriptional control, heterochromatin assembly, centromere and telomere function
  • involved in chromosome duplication, chromosome structure and centrosome copy number control, and may be coordinating all stages of the chromosome inheritance cycle
  • with ORC3 and CBX5, may be recruited to the chromatin as a single complex and require each other for their stable association to heterochromatin
  • with CBX5, are required for condensation of centric heterochromatic satellite repeats
  • involvement of ORC1, ORC2, ORC3 in the maintenance of constitutive heterochromatin
  • together with CBX proteins may be involved in organizing higher-order chromatin structure and centromere function
  • its phosphorylation might take place in a cell cycle-dependent manner
  • depletion of LRWD1 and ORC2 leads potentially to increased transcription of major satellite repeats
  • conserved role of ORC2 in modulating DNA structure to facilitate origin selection and helicase loading in eukaryotes
  • CELLULAR PROCESS nucleotide, replication
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • one of the six subunit of the origin recognition complex
  • INTERACTION
    DNA binding to autonomously replication sequence (ARS) consensus sequence (ACS)
    RNA
    small molecule
    protein
  • ORC3, ORC4 , ORC5
  • ORC2, MCM3, and DTD1 were bound at an ectopic MYC replicator, where deletion of sequences essential for origin activity was associated with the loss of DTD1 binding or the alteration of chromatin structure and loss of MCM3 binding
  • interaction of CDT1 with ORCs is involved in the formation of the prereplicative complex, rather than in regulation of the activity of ORCs
  • connection between ORCs and chromatin structure via the Set1 complex
  • associated with heterochromatin in a cell cycle-dependent manner, being present only at the centromeres during late G2 and mitosis
  • biochemically interacts indirectly with the heterochromatin protein 1 (CBX1, CBX3, CBX5)
  • LRWD1-mediated association of ORC1, ORC2 to chromatin is critical to initiate preRC assembly in G1 and chromatin organization in post-G1 cells
  • LRWD1 directly interacts with the N terminus of ORC2, and the stability of LRWD1 is dependent on its association with ORC2
  • ORC2 associates only with the non-ubiquitinated form of LRWD1, and ORC2 depletion results in the proteasome-mediated destabilization of LRWD1
  • cell & other
    REGULATION
    Phosphorylated by PLK1 that phosphorylates ORC2 at Ser188
    by CDK during the S phase, and phosphorylation of ORC2 controls chromatin binding of ORC, causing dissociation of the ORC from chromatin and the origin of replication in the S phase of human cells
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS