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

General

centromere protein phosphoprotein

Properties

SIZE: entity length = 140 aa MW = 16 kD COMPARTMENT: cell nucleus MOTIF: Ser phosphorylation site {S7} Ser phosphorylation site {S17} Ser phosphorylation site {S19} Thr phosphorylation site {T23} Ser phosphorylation site {S27} H3-like {41-140} MOTIF: CATD {75-116}

Database Correlations

OMIM 117139 UniProt P49450 Pfam PF00125 Entrez Gene 1058 Kegg hsa:1058

References

UniProt :accession P49450