Human Gene CENPA (ENST00000233505.12) Description and Page Index
  Description: Homo sapiens centromere protein A (CENPA), transcript variant 2, mRNA. (from RefSeq NM_001042426)
RefSeq Summary (NM_001042426): Centromeres are the differentiated chromosomal domains that specify the mitotic behavior of chromosomes. This gene encodes a centromere protein which contains a histone H3 related histone fold domain that is required for targeting to the centromere. Centromere protein A is proposed to be a component of a modified nucleosome or nucleosome-like structure in which it replaces 1 or both copies of conventional histone H3 in the (H3-H4)2 tetrameric core of the nucleosome particle. The protein is a replication-independent histone that is a member of the histone H3 family. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Nov 2015].
Gencode Transcript: ENST00000233505.12
Gencode Gene: ENSG00000115163.15
Transcript (Including UTRs)
   Position: hg38 chr2:26,786,068-26,794,589 Size: 8,522 Total Exon Count: 4 Strand: +
Coding Region
   Position: hg38 chr2:26,786,197-26,793,279 Size: 7,083 Coding Exon Count: 3 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:26,786,068-26,794,589)mRNA (may differ from genome)Protein (114 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGIneXtProtOMIMPubMed
ReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: CENPA_HUMAN
DESCRIPTION: RecName: Full=Histone H3-like centromeric protein A; AltName: Full=Centromere autoantigen A; AltName: Full=Centromere protein A; Short=CENP-A;
FUNCTION: 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).
SUBUNIT: 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 MLF1IP/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.
INTERACTION: P62805:HIST2H4B; NbExp=4; IntAct=EBI-1751979, EBI-302023; Q8NCD3:HJURP; NbExp=14; IntAct=EBI-1751979, EBI-719429;
SUBCELLULAR LOCATION: Nucleus. Chromosome, centromere, kinetochore. 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.
DOMAIN: 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.
PTM: Ubiquitinated (Probable). Interaction with herpes virus HSV-1 ICP0 protein, leads to its degradation by the proteasome pathway.
PTM: 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.
PTM: Poly-ADP-ribosylated by PARP1 (By similarity).
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.

-  MalaCards Disease Associations
  MalaCards Gene Search: CENPA
Diseases sorted by gene-association score: systemic scleroderma (3), rheumatic disease (3), limited scleroderma (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D016604 Aflatoxin B1
  • D013749 Tetrachlorodibenzodioxin
  • C014175 pyrazolo(3,4-d)pyrimidine
  • C028474 1,4-bis(2-(3,5-dichloropyridyloxy))benzene
  • C072581 16-hydroxycleroda-3,13(14)-dien-15,16-olide
  • C029497 2,3-bis(3'-hydroxybenzyl)butyrolactone
  • C028451 3,4,3',4'-tetrachlorobiphenyl
  • C027576 4-hydroxy-2-nonenal
  • D015123 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
  • D000082 Acetaminophen
          more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 12.59 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 27.64 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -52.40129-0.406 Picture PostScript Text
3' UTR -199.20825-0.241 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR009072 - Histone-fold
IPR007125 - Histone_core_D
IPR000164 - Histone_H3

Pfam Domains:
PF00125 - Core histone H2A/H2B/H3/H4

Protein Data Bank (PDB) 3-D Structure
MuPIT help

3AN2
- X-ray MuPIT

3NQJ
- X-ray MuPIT

3NQU
- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
3R45 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P49450
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0005515 protein binding
GO:0031492 nucleosomal DNA binding
GO:0046982 protein heterodimerization activity

Biological Process:
GO:0000132 establishment of mitotic spindle orientation
GO:0000281 mitotic cytokinesis
GO:0006334 nucleosome assembly
GO:0007049 cell cycle
GO:0016032 viral process
GO:0034080 CENP-A containing nucleosome assembly
GO:0051301 cell division
GO:0051382 kinetochore assembly
GO:0071459 protein localization to chromosome, centromeric region

Cellular Component:
GO:0000775 chromosome, centromeric region
GO:0000776 kinetochore
GO:0000777 condensed chromosome kinetochore
GO:0000778 condensed nuclear chromosome kinetochore
GO:0000780 condensed nuclear chromosome, centromeric region
GO:0000786 nucleosome
GO:0000788 nuclear nucleosome
GO:0000939 condensed chromosome inner kinetochore
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005694 chromosome
GO:0005829 cytosol
GO:0031618 nuclear pericentric heterochromatin


-  Descriptions from all associated GenBank mRNAs
  BC011013 - Homo sapiens centromere protein A, mRNA (cDNA clone IMAGE:4286607), **** WARNING: chimeric clone ****.
U14518 - Human centromere protein-A (CENP-A) mRNA, complete cds.
BC000881 - Homo sapiens centromere protein A, mRNA (cDNA clone MGC:5165 IMAGE:3461992), complete cds.
JD148475 - Sequence 129499 from Patent EP1572962.
JD382053 - Sequence 363077 from Patent EP1572962.
BC002703 - Homo sapiens centromere protein A, mRNA (cDNA clone MGC:3892 IMAGE:3626578), complete cds.
JD127768 - Sequence 108792 from Patent EP1572962.
CU674442 - Synthetic construct Homo sapiens gateway clone IMAGE:100017911 5' read CENPA mRNA.
HQ448742 - Synthetic construct Homo sapiens clone IMAGE:100072188; CCSB002737_02 centromere protein A (CENPA) gene, encodes complete protein.
JF432571 - Synthetic construct Homo sapiens clone IMAGE:100073806 centromere protein A (CENPA) gene, encodes complete protein.
KJ890897 - Synthetic construct Homo sapiens clone ccsbBroadEn_00291 CENPA gene, encodes complete protein.
KJ890898 - Synthetic construct Homo sapiens clone ccsbBroadEn_00292 CENPA gene, encodes complete protein.
BT007246 - Homo sapiens centromere protein A, 17kDa mRNA, complete cds.
JD385354 - Sequence 366378 from Patent EP1572962.
JD174291 - Sequence 155315 from Patent EP1572962.
JD313921 - Sequence 294945 from Patent EP1572962.
JD273204 - Sequence 254228 from Patent EP1572962.
JD082333 - Sequence 63357 from Patent EP1572962.
JD466412 - Sequence 447436 from Patent EP1572962.
JD172975 - Sequence 153999 from Patent EP1572962.
JD448985 - Sequence 430009 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P49450 (Reactome details) participates in the following event(s):

R-HSA-141409 Mad1 binds kinetochore
R-HSA-375302 Kinetochore capture of astral microtubules
R-HSA-5666129 CDC42:GTP recruits DIAPH2-2 to kinetochores
R-HSA-5666169 Kinetochore capture of astral microtubules is positively regulated by CDC42:GTP:p-S196-DIAPH2-2
R-HSA-141431 MAD2 associates with the Mad1 kinetochore complex
R-HSA-141439 Release of activated MAD2 from kinetochores
R-HSA-2467811 Separation of sister chromatids
R-HSA-2467809 ESPL1 (Separase) cleaves centromeric cohesin
R-HSA-5666160 AURKB phosphorylates DIAPH2-2 at kinetochores
R-HSA-606326 HJURP:CENPA complex localizes to the centromere
R-HSA-141422 MAD2 converted to an inhibitory state via interaction with Mad1
R-HSA-1638821 PP2A-B56 dephosphorylates centromeric cohesin
R-HSA-1638803 Phosphorylation of cohesin by PLK1 at centromeres
R-HSA-2468287 CDK1 phosphorylates CDCA5 (Sororin) at centromeres
R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-68877 Mitotic Prometaphase
R-HSA-5663220 RHO GTPases Activate Formins
R-HSA-2500257 Resolution of Sister Chromatid Cohesion
R-HSA-2467813 Separation of Sister Chromatids
R-HSA-141424 Amplification of signal from the kinetochores
R-HSA-68886 M Phase
R-HSA-195258 RHO GTPase Effectors
R-HSA-606279 Deposition of new CENPA-containing nucleosomes at the centromere
R-HSA-68882 Mitotic Anaphase
R-HSA-69618 Mitotic Spindle Checkpoint
R-HSA-69278 Cell Cycle (Mitotic)
R-HSA-194315 Signaling by Rho GTPases
R-HSA-774815 Nucleosome assembly
R-HSA-2555396 Mitotic Metaphase and Anaphase
R-HSA-69620 Cell Cycle Checkpoints
R-HSA-1640170 Cell Cycle
R-HSA-162582 Signal Transduction
R-HSA-73886 Chromosome Maintenance

-  Other Names for This Gene
  Alternate Gene Symbols: CENPA_HUMAN, D6W544, NM_001042426, P49450, Q53T74, Q9BVW2, uc002rhs.1, uc002rhs.2, uc002rhs.3, uc002rhs.4
UCSC ID: uc002rhs.4
RefSeq Accession: NM_001042426
Protein: P49450 (aka CENPA_HUMAN)
CCDS: CCDS42662.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.