histone H3-like centromeric protein A; centromere protein A; centromere autoantigen A; CENP-A (CENPA)

Function

• histone H3-like variant
• exclusively replaces conventional H3 in the nucleosome core of centromeric chromatin at the inner plate of the kinetochore
• required for recruitment & assembly of kinetochore proteins, mitotic progression & chromosome segregation
• may serve as an epigenetic mark that propagates centromere identity through replication & cell division
• the CENPA-H4 heterotetramer can bind DNA by itself (in vitro)
• ubiquitinated (probable)
• phosphorylation of Ser-7 by AURKA & AURKB during prophase is required for localization of AURKA & AURKB at inner centromere & is essential for kinetochore function
• initial phosphorylation during prophase is mediated by AURKA & is maintained by AURKB
• poly-ADP-ribosylated by PARP1 (putative)
• forms a nucleosome-like histone octamer containing two molecules each of H2A, H2B, CENPA & H4 assembled in one CENPA-H4 heterotetramer & two H2A-H2B heterodimers
• nucleosomes containing CENPA also contain histone H2A variants such as macroH2A H2AFY & H2A.Z/H2AFZ
• the CENPA-H4 heterotetramer is more compact & structurally more rigid than corresponding H3-H4 heterotetramers
• heterotrimer composed of HJURP, CENPA & histone H4, where HJURP interacts with the dimer formed by CENPA & histone H4 & prevents tetramerization of CENPA & H4
• component of the CENPA-NAC complex
• interacts (via CATD domain) with HJURP
  • interaction is required for its localization to centromeres
• interacts with CENPC, CENPN & CENPT
• part of a centromere complex consisting of CENPA, CENPT & CENPW

Structure

• the CATD (CENPA targeting domain) region is responsible for the more compact structure of nucleosomes containing CENPA & is necessary & sufficient to mediate the localization into centromeres
• belongs to the histone H3 family

Compartment

• nucleus. chromosome, centromere, kinetochore
• localizes exclusively in the kinetochore domain of centromeres
• occupies a compact domain at the inner kinetochore plate stretching across 2/3 of the length of the constriction but encompassing only 1/3 of the constriction width & height

Alternative splicing

named isoforms=2

Pathology

• interaction with herpes virus HSV-1 ICP0 protein, leads to its degradation by the proteasome pathway
• antibodies against CENPA are present in sera from patients with autoimmune diseases that developed autoantibodies against centrosomal proteins

Laboratory

• centromere protein A Ab in serum
  • centromere protein A IgG in serum

More general terms

• centromere protein
• phosphoprotein

Component of

• CENPA-NAC (nucleosome-associated) complex

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1058
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1058
• OMIM: https://mirror.omim.org/entry/117139
• UniProt: http://www.uniprot.org/uniprot/P49450.html