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FLASH GENE
Symbol CENPA contributors: mct/npt/pgu - updated : 01-09-2015
HGNC name centromere protein A
HGNC id 1851
Location 2p23.3      Physical location : 27.008.881 - 27.017.453
Synonym name
  • kinetochore specific antigen
  • centromere protein A, 17kDa
  • centromere autoantigen A
  • Synonym symbol(s) CNP1, CENP-A, Cenh3
    DNA
    TYPE functioning gene
    STRUCTURE 8.57 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map see OTOF
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 1431 - 140 - 2010 20080577
    4 - 1352 - 114 - 2010 20080577
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node   highly
    Reproductivefemale systemuteruscervix highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminus of CENPA is essential for mitotic progression and localization of CENPC, another key centromeric protein, requires only phosphorylation of the CENPA N-terminus
  • a histone H3 related histone fold domain
  • a conserved motif, the CATD, defined by loop 1 and helix 2 of the histone fold, is necessary and sufficient for specifying centromere functions , and contributes hydrophobic stitches that rigidify the interface between CENPA and H4
  • mono polymer octamer
    HOMOLOGY
    intraspecies homolog to histone H3
    Homologene
    FAMILY
  • histone H3 family
  • CATEGORY structural protein
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome,nucleosome
    text
  • colocalizes with alpha-satellite DNA (alphoid DNA)
  • is maintained at centromeres by the chromatin remodeler RSF1 and the small GTPase regulator MgcRacGAP
  • basic FUNCTION
  • likely replaying H3 to form a centromere unique nucleosomal structure
  • required to nucleate and maintain centromeric chromatin, but the mechanism by which it promotes and stabilizes the centromere in eukaryotic cells is not yet known
  • required for epigenetic specification of centromere identity through a loading mechanism independent of DNA sequence
  • may have a function in DNA repair
  • central in centromeric chromatin to ensure proper chromosome segregation
  • role of CENPA assembly into centromeres and the potential contribution of this kinetochore protein to autoimmune and cancer diseases
  • centromere replication involves the re-establishment of a CENPA-mediated nucleosome architecture within a constrained framework, requiring integration of multiple assembly and disassembly events
  • CENPA and H3-CENPT/W nucleosome components of the centromere are specialized for centromeric and kinetochore activities, respectively
  • CENPA nucleosome assembly activity of HJURP is responsible for centromeric chromatin assembly to maintain the epigenetic mark
  • the flexibility exclusively observed in the DNA regions located at the entrance and the exit of the CENPA nucleosome and the loop 1 region protruding from the CENPA nucleosome may have an essential role in the centromeric chromatin architecture
  • histone H3 variant that marks centromere location on the chromosome
  • CENPA-containing nucleosomes coalesce on the face of the chromosome to define the location of the mitotic kinetochore assembly, but they are not arranged in a linear context
  • cyclical nature to CENPA nucleosome structure, having implications for the maintenance of epigenetic memory after centromere replication
  • is a key epigenetic determinant of centromere identity and function
  • cyclical nature for CENPA nucleosomes that is likely to play a critical role in centromere inheritance
  • functions as a mark for kinetochore assembly
  • CENPB functions positively in the de novo assembly of centromeric nucleosomes, containing the centromere-specific histone H3 variant, CENPA
  • intrinsic properties of the CENPA protein direct its cell cycle-restricted assembly and induces quantitative mitotic transmission of the CENPA/H4 nucleosome core, ensuring long-term stability and epigenetic maintenance of centromere position
  • CENPA chromatin acts as an epigenetic mark to direct both centromere and kinetochore assembly
  • octameric CENPA nucleosomes mark the centromeric region to ensure proper epigenetic inheritance and kinetochore assembly
  • in response to DNA damage, MAD2L1 and the histone variant CENPA become enriched at the nuclear periphery in a DNA damage response (DDR)-dependent manner
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • directly recruit a proximal CENPA nucleosome associated complex (NAC) comprised of three new human centromere proteins (CENPM, CENPN and CENPT), along with MLF1IP, CENPC1 and CENPH
  • forms a complex with prenucleosomal CENPA
  • forms a histone octamer containing two each of histones H2A, H2B, H4
  • CENPA nucleosomes oscillate between stable tetramers and stable octamers in human cells
  • CENPA and CENPB are major components of centromeric chromatin
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • CENPA NAC is essential, as disruption of the complex causes errors of chromosome alignment and segregation that preclude cell survival despite continued centromere-derived mitotic checkpoint signaling
  • cooperative action of CENPA NAC/CAD subunits and the KMN (KNL1/MIND/NDC80) network drives efficient chromosome segregation and bipolar spindle assembly during mitosis
  • HJURP is a key factor for CENPA deposition and maintenance at centromeres
  • interacting with HJURP through ite CATD domain (HJURP is a major partner in the CENP-A nuclear soluble complex)
  • CENPA-binding protein called HJURP
  • interacting with MIS18 complex (centromeric localization of MIS18 complex is essential for the subsequent recruitment of de novo-synthesized CENPA)
  • HJURP is binding partner of CENPA and is functionally required for its deposition at centromeres
  • HJURP is a CENPA histone chaperone
  • WDHD1 is a new factor that is required for the assembly of CENPA nucleosomes
  • 14-3-3 proteins could act as specific mitotic "bridges," linking phosphorylated CENPA and CENPC, which are necessary for the platform function of CENPA centromeric chromatin in the assembly and maintenance of active kinetochores
  • CENPA pre-nucleosomal complex achieves assembly of the octameric CENPA nucleosome through the dimerization of the CENPA chaperone HJURP
  • CENPB binding in the vicinity of the CENPA nucleosome substantially stabilizes the CENPA nucleosome on alphoid DNA in human cells
  • CENPB directly binds both CENPA N-terminal tail and CENPC1, a key nucleator of kinetochore assembly
  • SUGT1-HSP90AA1 complex contributes to the E3 ligase activity of the CUL4A complex that is necessary for CENPA ubiquitylation and CENPA deposition at the centromere
  • cell & other
    REGULATION
    Other major modifications on the N-terminal tail of CENPA alter the physical properties of the chromatin fiber at the centromere
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    cells overexpressing CENPA are more tolerant of DNA damage
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS