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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 variant which exclusively replaces conventional H3 in the nucleosome core of centromeric chromatin at the inner plate of the kinetochore. Required for recruitment and assembly of kinetochore proteins, mitotic progression and chromosome segregation. May serve as an epigenetic mark that propagates centromere identity through replication and cell division. The CENPA-H4 heterotetramer can bind DNA by itself (in vitro).2 Publications

GO - Molecular functioni

  • chromatin binding Source: ProtInc
  • DNA binding Source: UniProtKB-KW

GO - Biological processi

  • CENP-A containing nucleosome assembly Source: Reactome
  • establishment of mitotic spindle orientation Source: UniProtKB
  • kinetochore assembly Source: BHF-UCL
  • 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

Host-virus interaction

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

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.

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

  • Nucleus
  • Chromosomecentromerekinetochore

  • Note: 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.

GO - Cellular componenti

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

Keywords - Cellular componenti

Centromere, Chromosome, Kinetochore, Nucleosome core, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi7 – 71S → 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 Publications

Organism-specific databases

PharmGKBiPA26396.

Polymorphism and mutation databases

BioMutaiCENPA.
DMDMi1345726.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 140140Histone H3-like centromeric protein APRO_0000221373Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei7 – 71Phosphoserine; by AURKA and AURKB3 Publications
Modified residuei17 – 171PhosphoserineCombined sources
Modified residuei19 – 191PhosphoserineCombined sources
Modified residuei27 – 271PhosphoserineCombined sources

Post-translational modificationi

Ubiquitinated (Probable). Interaction with herpes virus HSV-1 ICP0 protein, leads to its degradation by the proteasome pathway.Curated1 Publication
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 kinetochore function. Initial phosphorylation during prophase is mediated by AURKA and is maintained by AURKB.3 Publications
Poly-ADP-ribosylated by PARP1.By similarity

Keywords - PTMi

ADP-ribosylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP49450.
PaxDbiP49450.
PeptideAtlasiP49450.
PRIDEiP49450.

PTM databases

iPTMnetiP49450.
PhosphoSiteiP49450.

Expressioni

Gene expression databases

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

Organism-specific databases

HPAiCAB008371.
HPA073086.

Interactioni

Subunit structurei

Forms a nucleosome-like histone octamer containing two molecules each of H2A, H2B, CENPA and H4 assembled in one CENPA-H4 heterotetramer and two H2A-H2B heterodimers. Nucleosomes containing CENPA also contain histone H2A variants such as macroH2A H2AFY and H2A.Z/H2AFZ. The CENPA-H4 heterotetramer is more compact and structurally more rigid than corresponding H3-H4 heterotetramers. 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. Component of the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU. Interacts (via CATD domain) with HJURP; the interaction is direct and is required for its localization to centromeres. Interacts with CENPC, CENPN and CENPT; interaction is direct. Interacts directly with herpes virus HSV-1 ICP0 protein. Part of a centromere complex consisting of CENPA, CENPT and CENPW.12 Publications

Binary interactionsi

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

Protein-protein interaction databases

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

Structurei

Secondary structure

1
140
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi47 – 5610Combined sources
Helixi64 – 7916Combined sources
Beta strandi85 – 873Combined sources
Helixi88 – 11528Combined sources
Beta strandi119 – 1213Combined sources
Helixi123 – 13311Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 46-134.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP49450.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni41 – 140100H3-likeAdd
BLAST
Regioni75 – 11642CATDAdd
BLAST

Domaini

The CATD (CENPA targeting domain) region is responsible for the more compact structure of nucleosomes containing CENPA and is necessary and sufficient to mediate the localization into centromeres.1 Publication

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.

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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei71 – 9626Missing in isoform 2. 1 PublicationVSP_020430Add
BLAST

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
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. Positions 46-134.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

iPTMnetiP49450.
PhosphoSiteiP49450.

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

Phylogenomic databases

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

Enzyme and pathway databases

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.

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: September 7, 2016
This is version 165 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.