Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Histone H3-like centromeric protein A

Gene

CENPA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Miscellaneous

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

Caution

GO - Molecular functioni

  • chromatin binding Source: ProtInc
  • nucleosomal DNA binding Source: GO_Central
  • protein heterodimerization activity Source: InterPro

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
  • nucleosome assembly Source: GO_Central
  • protein localization to chromosome, centromeric region Source: BHF-UCL
  • sister chromatid cohesion Source: Reactome
  • viral process Source: UniProtKB-KW

Keywordsi

Molecular functionDNA-binding
Biological processCell cycle, Cell division, Host-virus interaction, Mitosis

Enzyme and pathway databases

ReactomeiR-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-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

EuPathDBiHostDB:ENSG00000115163.14
HGNCiHGNC:1851 CENPA
MIMi117139 gene
neXtProtiNX_P49450

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

Developmental stagei

Expression varies across the cell cycle, with high levels in G2 phase (at the mRNA level).1 Publication

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

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi10748788 interactors.
CORUMiP49450
DIPiDIP-52297N
IntActiP49450 38 interactors.
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[»]
6BUZelectron microscopy3.92A/E1-140[»]
6C0Welectron microscopy4.00A/E1-140[»]
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
GeneTreeiENSGT00910000144321
HOGENOMiHOG000155290
HOVERGENiHBG001172
InParanoidiP49450
KOiK11495
OMAiVHLFEDC
OrthoDBiEOG091G13T2
PhylomeDBiP49450
TreeFamiTF354293

Family and domain databases

Gene3Di1.10.20.101 hit
InterProiView protein in InterPro
IPR009072 Histone-fold
IPR007125 Histone_H2A/H2B/H3
IPR000164 Histone_H3/CENP-A
PANTHERiPTHR11426 PTHR11426, 1 hit
PfamiView protein in Pfam
PF00125 Histone, 1 hit
PRINTSiPR00622 HISTONEH3
SMARTiView protein in SMART
SM00428 H3, 1 hit
SUPFAMiSSF47113 SSF47113, 1 hit
PROSITEiView protein in PROSITE
PS00959 HISTONE_H3_2, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiCENPA_HUMAN
AccessioniPrimary (citable) accession number: P49450
Secondary accession number(s): D6W544, Q53T74, Q9BVW2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: April 25, 2018
This is version 177 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome