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Protein

Histone H3-like centromeric protein A

Gene

CENPA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).1 Publication15 Publications

GO - Molecular functioni

  • centromeric DNA binding Source: GO_Central
  • chromatin binding Source: ProtInc
  • nucleosomal DNA binding Source: GO_Central

GO - Biological processi

  • CENP-A containing nucleosome assembly Source: Reactome
  • establishment of mitotic spindle orientation Source: UniProtKB
  • kinetochore assembly Source: BHF-UCL
  • mitotic cytokinesis Source: UniProtKB
  • mitotic sister chromatid segregation Source: GO_Central
  • nucleosome assembly Source: GO_Central
  • protein localization to chromosome, centromeric region Source: BHF-UCL
  • sister chromatid cohesion Source: Reactome
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Cell cycle, Cell division, Host-virus interaction, Mitosis

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000115163-MONOMER.
ReactomeiR-HSA-2467813. Separation of Sister Chromatids.
R-HSA-2500257. Resolution of Sister Chromatid Cohesion.
R-HSA-5663220. RHO GTPases Activate Formins.
R-HSA-606279. Deposition of new CENPA-containing nucleosomes at the centromere.
R-HSA-68877. Mitotic Prometaphase.
SIGNORiP49450.

Names & Taxonomyi

Protein namesi
Recommended name:
Histone H3-like centromeric protein A
Alternative name(s):
Centromere autoantigen A
Centromere protein A
Short name:
CENP-A
Gene namesi
Name:CENPA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:1851. CENPA.

Subcellular locationi

GO - Cellular componenti

  • chromosome, centromeric region Source: UniProtKB
  • condensed chromosome inner kinetochore Source: Ensembl
  • condensed nuclear chromosome, centromeric region Source: BHF-UCL
  • condensed nuclear chromosome kinetochore Source: BHF-UCL
  • cytosol Source: Reactome
  • nuclear nucleosome Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleosome Source: GO_Central
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Centromere, Chromosome, Kinetochore, Nucleosome core, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi7S → A: Induces a delay at the terminal stage of cytokinesis and chromosome misalignment during mitosis due to a defect in kinetochore attachment to microtubules. 2 Publications1
Mutagenesisi17S → A: Impaired mitotic chromosome congression and chromosome segregation; when associated with A-19. 1 Publication1
Mutagenesisi19S → A: Impaired mitotic chromosome congression and chromosome segregation; when associated with A-17. 1 Publication1
Mutagenesisi68S → A: No effect on interaction with HJURP. Impairs localization at centromeres. 1 Publication1
Mutagenesisi68S → E or Q: Impairs interaction with HJURP, association with chromatin and localization at centromeres. 1 Publication1
Mutagenesisi80 – 81RG → AA: Impairs retention at centromeres, but not targeting to centromeres. 1 Publication2
Mutagenesisi104H → G: Reduces location at centromeres. Abolishes location at centromeres; when associated with C-112. 1 Publication1
Mutagenesisi112L → C: No effect on location at centromeres. Abolishes location at centromeres; when associated with G-104. 1 Publication1

Organism-specific databases

DisGeNETi1058.
OpenTargetsiENSG00000115163.
PharmGKBiPA26396.

Polymorphism and mutation databases

BioMutaiCENPA.
DMDMi1345726.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00002213732 – 140Histone H3-like centromeric protein AAdd BLAST139

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N,N,N-trimethylglycine2 Publications1
Modified residuei7Phosphoserine; by AURKA and AURKB3 Publications1
Modified residuei17PhosphoserineCombined sources1 Publication1
Modified residuei19PhosphoserineCombined sources1 Publication1
Modified residuei27PhosphoserineCombined sources1
Modified residuei68Phosphoserine1 Publication1

Post-translational modificationi

Ubiquitinated (Probable). Interaction with herpes virus HSV-1 ICP0 protein, leads to its degradation by the proteasome pathway.Curated1 Publication
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.1 Publication
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.4 Publications
Poly-ADP-ribosylated by PARP1.By similarity

Keywords - PTMi

ADP-ribosylation, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP49450.
PaxDbiP49450.
PeptideAtlasiP49450.
PRIDEiP49450.

PTM databases

iPTMnetiP49450.
PhosphoSitePlusiP49450.

Expressioni

Gene expression databases

BgeeiENSG00000115163.
CleanExiHS_CENPA.
ExpressionAtlasiP49450. baseline and differential.
GenevisibleiP49450. HS.

Organism-specific databases

HPAiCAB008371.
HPA073086.

Interactioni

Subunit structurei

Component of centromeric nucleosomes, where DNA is wrapped around a histone octamer core (PubMed:23818633, PubMed:26878239, PubMed:20739937, PubMed:21743476). The octamer contains two molecules each of H2A, H2B, CENPA and H4 assembled in one CENPA-H4 heterotetramer and two H2A-H2B heterodimers (PubMed:23818633, PubMed:26878239, PubMed:20739937, PubMed:21743476). CENPA modulates the DNA-binding characteristics of nucleosomes so that protruding DNA ends have higher flexibility than in nucleosomes containing conventional histone H3 (PubMed:27499292, PubMed:21743476). 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 H2AFY and H2A.Z/H2AFZ (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). Interacts directly with herpes virus HSV-1 ICP0 protein (PubMed:11053442).Curated17 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
HIST2H4BP628054EBI-1751979,EBI-302023
HJURPQ8NCD315EBI-1751979,EBI-719429

Protein-protein interaction databases

BioGridi107487. 87 interactors.
DIPiDIP-52297N.
IntActiP49450. 22 interactors.
MINTiMINT-4720873.
STRINGi9606.ENSP00000336868.

Structurei

Secondary structure

1140
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi47 – 56Combined sources10
Helixi64 – 79Combined sources16
Beta strandi85 – 87Combined sources3
Helixi88 – 115Combined sources28
Beta strandi119 – 121Combined sources3
Helixi123 – 133Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3AN2X-ray3.60A/E1-140[»]
3NQJX-ray2.10A60-140[»]
3NQUX-ray2.50A1-140[»]
3R45X-ray2.60A1-140[»]
3WTPX-ray2.67A1-140[»]
5CVDX-ray1.30D/E3-10[»]
ProteinModelPortaliP49450.
SMRiP49450.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP49450.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni39 – 54Important for flexibility of DNA ends that protrude from nucleosomes1 PublicationAdd BLAST16
Regioni75 – 116CATD2 PublicationsAdd BLAST42

Domaini

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:7962047, PubMed:15282608).2 Publications

Sequence similaritiesi

Belongs to the histone H3 family.Curated

Phylogenomic databases

eggNOGiKOG1745. Eukaryota.
COG2036. LUCA.
GeneTreeiENSGT00840000129844.
HOGENOMiHOG000155290.
HOVERGENiHBG001172.
InParanoidiP49450.
KOiK11495.
OMAiHLLIRKY.
OrthoDBiEOG091G13T2.
PhylomeDBiP49450.
TreeFamiTF354293.

Family and domain databases

Gene3Di1.10.20.10. 1 hit.
InterProiIPR009072. Histone-fold.
IPR007125. Histone_H2A/H2B/H3.
IPR000164. Histone_H3/CENP-A.
[Graphical view]
PANTHERiPTHR11426. PTHR11426. 1 hit.
PfamiPF00125. Histone. 1 hit.
[Graphical view]
PRINTSiPR00622. HISTONEH3.
SMARTiSM00428. H3. 1 hit.
[Graphical view]
SUPFAMiSSF47113. SSF47113. 1 hit.
PROSITEiPS00959. HISTONE_H3_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P49450-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGPRRRSRKP EAPRRRSPSP TPTPGPSRRG PSLGASSHQH SRRRQGWLKE
60 70 80 90 100
IRKLQKSTHL LIRKLPFSRL AREICVKFTR GVDFNWQAQA LLALQEAAEA
110 120 130 140
FLVHLFEDAY LLTLHAGRVT LFPKDVQLAR RIRGLEEGLG
Length:140
Mass (Da):15,991
Last modified:February 1, 1996 - v1
Checksum:i11A28FEB54486489
GO
Isoform 2 (identifier: P49450-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     71-96: Missing.

Note: No experimental confirmation available.
Show »
Length:114
Mass (Da):13,001
Checksum:i9E0DB58DBB95C1CF
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_02043071 – 96Missing in isoform 2. 1 PublicationAdd BLAST26

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U14518 mRNA. Translation: AAA57416.1.
BT007246 mRNA. Translation: AAP35910.1.
AC011740 Genomic DNA. Translation: AAX93267.1.
CH471053 Genomic DNA. Translation: EAX00669.1.
CH471053 Genomic DNA. Translation: EAX00670.1.
BC000881 mRNA. Translation: AAH00881.1.
BC002703 mRNA. Translation: AAH02703.1.
U82609 Genomic DNA. Translation: AAB47505.1.
CCDSiCCDS1729.1. [P49450-1]
CCDS42662.1. [P49450-2]
PIRiI38855.
RefSeqiNP_001035891.1. NM_001042426.1. [P49450-2]
NP_001800.1. NM_001809.3. [P49450-1]
UniGeneiHs.1594.

Genome annotation databases

EnsembliENST00000233505; ENSP00000233505; ENSG00000115163. [P49450-2]
ENST00000335756; ENSP00000336868; ENSG00000115163. [P49450-1]
GeneIDi1058.
KEGGihsa:1058.
UCSCiuc002rhr.4. human. [P49450-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U14518 mRNA. Translation: AAA57416.1.
BT007246 mRNA. Translation: AAP35910.1.
AC011740 Genomic DNA. Translation: AAX93267.1.
CH471053 Genomic DNA. Translation: EAX00669.1.
CH471053 Genomic DNA. Translation: EAX00670.1.
BC000881 mRNA. Translation: AAH00881.1.
BC002703 mRNA. Translation: AAH02703.1.
U82609 Genomic DNA. Translation: AAB47505.1.
CCDSiCCDS1729.1. [P49450-1]
CCDS42662.1. [P49450-2]
PIRiI38855.
RefSeqiNP_001035891.1. NM_001042426.1. [P49450-2]
NP_001800.1. NM_001809.3. [P49450-1]
UniGeneiHs.1594.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3AN2X-ray3.60A/E1-140[»]
3NQJX-ray2.10A60-140[»]
3NQUX-ray2.50A1-140[»]
3R45X-ray2.60A1-140[»]
3WTPX-ray2.67A1-140[»]
5CVDX-ray1.30D/E3-10[»]
ProteinModelPortaliP49450.
SMRiP49450.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107487. 87 interactors.
DIPiDIP-52297N.
IntActiP49450. 22 interactors.
MINTiMINT-4720873.
STRINGi9606.ENSP00000336868.

PTM databases

iPTMnetiP49450.
PhosphoSitePlusiP49450.

Polymorphism and mutation databases

BioMutaiCENPA.
DMDMi1345726.

Proteomic databases

EPDiP49450.
PaxDbiP49450.
PeptideAtlasiP49450.
PRIDEiP49450.

Protocols and materials databases

DNASUi1058.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000233505; ENSP00000233505; ENSG00000115163. [P49450-2]
ENST00000335756; ENSP00000336868; ENSG00000115163. [P49450-1]
GeneIDi1058.
KEGGihsa:1058.
UCSCiuc002rhr.4. human. [P49450-1]

Organism-specific databases

CTDi1058.
DisGeNETi1058.
GeneCardsiCENPA.
HGNCiHGNC:1851. CENPA.
HPAiCAB008371.
HPA073086.
MIMi117139. gene.
neXtProtiNX_P49450.
OpenTargetsiENSG00000115163.
PharmGKBiPA26396.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1745. Eukaryota.
COG2036. LUCA.
GeneTreeiENSGT00840000129844.
HOGENOMiHOG000155290.
HOVERGENiHBG001172.
InParanoidiP49450.
KOiK11495.
OMAiHLLIRKY.
OrthoDBiEOG091G13T2.
PhylomeDBiP49450.
TreeFamiTF354293.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000115163-MONOMER.
ReactomeiR-HSA-2467813. Separation of Sister Chromatids.
R-HSA-2500257. Resolution of Sister Chromatid Cohesion.
R-HSA-5663220. RHO GTPases Activate Formins.
R-HSA-606279. Deposition of new CENPA-containing nucleosomes at the centromere.
R-HSA-68877. Mitotic Prometaphase.
SIGNORiP49450.

Miscellaneous databases

EvolutionaryTraceiP49450.
GeneWikiiCENPA.
GenomeRNAii1058.
PROiP49450.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115163.
CleanExiHS_CENPA.
ExpressionAtlasiP49450. baseline and differential.
GenevisibleiP49450. HS.

Family and domain databases

Gene3Di1.10.20.10. 1 hit.
InterProiIPR009072. Histone-fold.
IPR007125. Histone_H2A/H2B/H3.
IPR000164. Histone_H3/CENP-A.
[Graphical view]
PANTHERiPTHR11426. PTHR11426. 1 hit.
PfamiPF00125. Histone. 1 hit.
[Graphical view]
PRINTSiPR00622. HISTONEH3.
SMARTiSM00428. H3. 1 hit.
[Graphical view]
SUPFAMiSSF47113. SSF47113. 1 hit.
PROSITEiPS00959. HISTONE_H3_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCENPA_HUMAN
AccessioniPrimary (citable) accession number: P49450
Secondary accession number(s): D6W544, Q53T74, Q9BVW2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: November 2, 2016
This is version 167 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Antibodies against CENPA are present in sera from patients with autoimmune diseases that developed autoantibodies against centrosomal proteins.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.