CENPA

Centromeres are the differentiated chromosomal domains that specify the mitotic behavior of chromosomes. This gene encodes a centromere protein which contains a histone H3 related histone fold domain that is required for targeting to the centromere. Centromere protein A is proposed to be a component of a modified nucleosome or nucleosome-like structure in which it replaces 1 or both copies of conventional histone H3 in the (H3-H4)2 tetrameric core of the nucleosome particle. The protein is a replication-independent histone that is a member of the histone H3 family. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Nov 2015]

Full Name

Centromere Protein A

Function

Histone H3-like nucleosomal protein that is specifically found in centromeric nucleosomes (PubMed:7962047, PubMed:9024683, PubMed:11756469, PubMed:14667408, PubMed:15702419, PubMed:15475964, PubMed:15282608, PubMed:17651496, PubMed:19114591, PubMed:27499292, PubMed:20739937).
Replaces conventional H3 in the nucleosome core of centromeric chromatin at the inner plate of the kinetochore (PubMed:18072184).
The presence of CENPA subtly modifies the nucleosome structure and the way DNA is wrapped around the nucleosome and gives rise to protruding DNA ends that are less well-ordered and rigid compared to nucleosomes containing histone H3 (PubMed:27499292, PubMed:26878239).
May serve as an epigenetic mark that propagates centromere identity through replication and cell division (PubMed:15475964, PubMed:15282608, PubMed:26878239, PubMed:20739937, PubMed:21478274).
Required for recruitment and assembly of kinetochore proteins, and as a consequence required for progress through mitosis, chromosome segregation and cytokinesis (PubMed:11756469, PubMed:14667408, PubMed:18072184, PubMed:23818633, PubMed:25556658, PubMed:27499292).

Biological Process

CENP-A containing nucleosome assembly Source: Reactome
Establishment of mitotic spindle orientation Source: UniProtKB
Kinetochore assembly Source: BHF-UCL
Mitotic cytokinesis Source: UniProtKB
Mitotic spindle organization Source: Reactome
Protein localization to chromosome, centromeric region Source: BHF-UCL
Viral process Source: UniProtKB-KW

Cellular Location

Nucleus; Kinetochore; Centromere. Localizes exclusively in the kinetochore domain of centromeres. Occupies a compact domain at the inner kinetochore plate stretching across 2 thirds of the length of the constriction but encompassing only one third of the constriction width and height (PubMed:19114591). Phosphorylation at Ser-68 during early mitosis abolishes association with chromatin and centromeres and results in dispersed nuclear location (PubMed:25556658).

PTM

Ubiquitinated (Probable). Interaction with herpes virus HSV-1 ICP0 protein, leads to its degradation by the proteasome pathway.
Trimethylated by NTMT1 at the N-terminal glycine after cleavage of Met-1. Methylation is low before incorporation into nucleosomes and increases with cell cycle progression, with the highest levels in mitotic nucleosomes.
Phosphorylated by CDK1 at Ser-68 during early mitosis; this abolishes association with chromatin and centromeres, prevents interaction with HJURP and thereby prevents premature assembly of CENPA into centromeres (PubMed:25556658). Dephosphorylated at Ser-68 by PPP1CA during late mitosis (PubMed:25556658). Phosphorylation of Ser-7 by AURKA and AURKB during prophase is required for localization of AURKA and AURKB at inner centromere and is essential for normal cytokinesis (PubMed:11756469, PubMed:14667408, PubMed:18239465). Initial phosphorylation during prophase is mediated by AURKA and is maintained by AURKB.
Poly-ADP-ribosylated by PARP1.