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Details on Person UniProt:P49450 CENPA

Class:IdReferenceGeneProduct:51884
_chainChangeLogchain:1-140 added on Fri February 6 2015;chain:1-140 removed on Fri November 4 2016;initiator methionine:1 added on Fri November 4 2016;chain:2-140 added on Fri November 4 2016;initiator methionine:1 for 51884 removed on Fri Nov 03 2023;initiator methionine: for 51884 added on Fri Nov 03 2023;initiator methionine: for 51884 removed on Fri Aug 15 2025;initiator methionine:1 for 51884 added on Fri Aug 15 2025
_displayNameUniProt:P49450 CENPA
_timestamp2025-08-15 21:21:29
chaininitiator methionine:1
chain:2-140
checksum11A28FEB54486489
commentFUNCTION Histone H3-like nucleosomal protein that is specifically found in centromeric nucleosomes (PubMed:11756469, PubMed:14667408, PubMed:15282608, PubMed:15475964, PubMed:15702419, PubMed:17651496, PubMed:19114591, PubMed:20739937, PubMed:27499292, PubMed:7962047, PubMed:9024683). Replaces conventional H3 in the nucleosome core of centromeric chromatin that serves as an assembly site for the inner 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:26878239, PubMed:27499292). May serve as an epigenetic mark that propagates centromere identity through replication and cell division (PubMed:15282608, PubMed:15475964, PubMed:20739937, PubMed:21478274, PubMed:26878239). 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).SUBUNIT Component of centromeric nucleosomes, where DNA is wrapped around a histone octamer core (PubMed:20739937, PubMed:21743476, PubMed:23818633, PubMed:26878239). The octamer contains two molecules each of H2A, H2B, CENPA and H4 assembled in one CENPA-H4 heterotetramer and two H2A-H2B heterodimers (PubMed:20739937, PubMed:21743476, PubMed:23818633, PubMed:26878239). CENPA modulates the DNA-binding characteristics of nucleosomes so that protruding DNA ends have higher flexibility than in nucleosomes containing conventional histone H3 (PubMed:21743476, PubMed:27499292). Inhibits binding of histone H1 to nucleosomes, since histone H1 binds preferentially to rigid DNA linkers that protrude from nucleosomes (PubMed:27499292). Nucleosomes containing CENPA also contain histone H2A variants such as MACROH2A and H2A.Z/H2AZ1 (Probable). The CENPA-H4 heterotetramer is more compact and structurally more rigid than corresponding H3-H4 heterotetramers (PubMed:15282608, PubMed:20739937). Can assemble into nucleosomes that contain both CENPA and histone H3.3; these nucleosomes interact with a single CENPC chain (PubMed:25408271). Heterotrimer composed of HJURP, CENPA and histone H4, where HJURP interacts with the dimer formed by CENPA and histone H4 and prevents tetramerization of CENPA and H4 (PubMed:21478274). Component of the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU (PubMed:16622419). Interacts (via CATD domain) with HJURP; the interaction is direct and is required for its localization to centromeres (PubMed:15282608, PubMed:19410544, PubMed:19410545, PubMed:23818633, PubMed:25556658). Interacts with CENPC, CENPN and CENPT; interaction is direct. Part of a centromere complex consisting of CENPA, CENPT and CENPW (PubMed:19533040). Identified in centromere complexes containing histones H2A, H2B and H4, and at least CENPA, CENPB, CENPC, CENPT, CENPN, HJURP, SUPT16H, SSRP1 and RSF1 (PubMed:27499292). Can self-associate (PubMed:9024683). The CENPA-H4 heterotetramer can bind DNA by itself (in vitro) (PubMed:20739937). Interacts with CDK1, PPP1CA and RBBP7 (PubMed:25556658).SUBUNIT (Microbial infection) Interacts directly with herpes virus HHV-1 protein ICP0.INTERACTION Localizes exclusively to sites of kinetochore assembly in 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).ALTERNATIVE PRODUCTS Expression varies across the cell cycle, with high levels in G2 phase (at the mRNA level).DOMAIN The CATD (CENPA targeting domain) region is responsible for the more compact structure of nucleosomes containing CENPA (PubMed:15282608). It is necessary and sufficient to mediate the localization into centromeres (PubMed:15282608, PubMed:7962047).PTM Ubiquitinated (Probable). Interaction with herpes virus HSV-1 ICP0 protein, leads to its degradation by the proteasome pathway.PTM 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.PTM 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.PTM Poly-ADP-ribosylated by PARP1.MISCELLANEOUS Antibodies against CENPA are present in sera from patients with autoimmune diseases that developed autoantibodies against centrosomal proteins.SIMILARITY Belongs to the histone H3 family.
descriptionrecommendedName: Histone H3-like centromeric protein A alternativeName: Centromere autoantigen A alternativeName: Centromere protein A shortName: CENP-A
geneNameCENPA
identifierP49450
isSequenceChangedFALSE
keyword3D-structure
ADP-ribosylation
Alternative splicing
Cell cycle
Cell division
Centromere
Chromosome
DNA-binding
Host-virus interaction
Methylation
Mitosis
Nucleosome core
Nucleus
Phosphoprotein
Proteomics identification
Reference proteome
Ubl conjugation
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
nameCENPA
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:9002851] ENSEMBL:ENSG00000115163 CENPA [Homo sapiens]
secondaryIdentifierCENPA_HUMAN
D6W544
Q53T74
Q9BVW2
sequenceLength140
species[Species:48887] Homo sapiens
(isoformParent)[ReferenceIsoform:222823] UniProt:P49450-2 CENPA [Homo sapiens]
[ReferenceIsoform:404184] UniProt:P49450-1 CENPA [Homo sapiens]
(referenceEntity)[EntityWithAccessionedSequence:375317] CENPA [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:606322] CENPA [nucleoplasm] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:P49450 CENPA (51884)