Reviewed,
UniProtKB/Swiss-Prot P49450 (CENPA_HUMAN)
Last modified
November 25, 2008.
Version 82.
History...
Clusters with 100%,
90%,
50% identity |
Documents (3) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Histone H3-like centromeric protein A Short name=Centromere protein A Short name=CENP-A Alternative name(s): Centromere autoantigen A | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 140 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| 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. |
| Subunit structure | 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. Component of the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and MLF1IP/CENPU. Interacts directly with herpes virus HSV-1 ICP0 protein. |
| Subcellular location | Nucleus. Centromere. Kinetochore. Note= Localizes exclusively in the kinetochore domain of centromeres. |
| 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. |
| Post-translational modification | Ubiquitinated Probable. Interaction with herpes virus HSV-1 ICP0 protein, leads to its degradation by the proteasome pathway. Phosphorylation of Ser-7 by Aurora-A/STK6 and Aurora-B/STK12 during prophase is required for localization of Aurora-A/STK6 and Aurora-B/STK12 at inner centromere and is essential for kinetochore function. Initial phosphorylation during prophase is mediated by Aurora-A/STK6 and is maintained by Aurora-B/STK12. |
| Involvement in disease | Antibodies against CENPA are present in sera from patients with autoimmune diseases that developed autoantibodies against centrosomal proteins. |
| Sequence similarities | Belongs to the histone H3 family. |
Ontologies
Keywords | |
|---|---|
| Biological process | Host-virus interaction |
| Cellular component | Centromere Chromosomal protein Kinetochore Nucleosome core Nucleus |
| Coding sequence diversity | Alternative splicing |
| Ligand | DNA-binding |
| PTM | Phosphoprotein Ubl conjugation |
Gene Ontology (GO) | |
| Biological process | interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW nucleosome assemblyInferred from electronic annotation. Source: InterPro |
| Cellular component | nucleosome Inferred from electronic annotation. Source: InterPro nucleus Ref.1Traceable author statement. Source: ProtInc |
| Molecular function | DNA binding Inferred from electronic annotation. Source: InterPro chromatin binding Ref.1Traceable author statement. Source: ProtInc |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| ABL1 | P00519 | 1 | EBI-1751979,EBI-375543 | |
| FYN | P06241 | 1 | EBI-1751979,EBI-515315 |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: P49450-1) 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. | ||||||
| Isoform 2 (identifier: P49450-2) The sequence of this isoform differs from the canonical sequence as follows: 71-96: Missing. | ||||||
| Notes: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 140 | 140 | Histone H3-like centromeric protein A | PRO_0000221373 | |||||
Regions | |||||||||
| Region | 41 – 140 | 100 | H3-like | ||||||
| Region | 75 – 116 | 42 | CATD | ||||||
Amino acid modifications | |||||||||
| Modified residue | 7 | 1 | Phosphoserine; by STK6 and STK12 | ||||||
| Modified residue | 17 | 1 | Phosphoserine | ||||||
| Modified residue | 19 | 1 | Phosphoserine | ||||||
| Modified residue | 23 | 1 | Phosphothreonine | ||||||
| Modified residue | 27 | 1 | Phosphoserine | ||||||
Natural variations | |||||||||
| Alternative sequence | 71 – 96 | 26 | Missing in isoform 2. | VSP_020430 | |||||
Experimental info | |||||||||
| Mutagenesis | 7 | 1 | S → A: Induces a delay at the terminal stage of cytokinesis and chromosome misalignment during mitosis due to a defect in kinetochore attachment to microtubules | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Human CENP-A contains a histone H3 related histone fold domain that is required for targeting to the centromere." Sullivan K.F., Hechenberger M., Masri K. J. Cell Biol. 127:581-592(1994) [PubMed: 7962047] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [2] | "Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). |
| [3] | "Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. Wilson R.K.Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [4] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Uterus. |
| [5] | "Assembly of CENP-A into centromeric chromatin requires a cooperative array of nucleosomal DNA contact sites." Shelby R.D., Vafa O., Sullivan K.F. J. Cell Biol. 136:501-513(1997) [PubMed: 9024683] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33, SUBUNIT. |
| [6] | "Autoepitopes on autoantigen centromere protein-A (CENP-A) are restricted to the N-terminal region, which has no homology with histone H3." Muro Y., Azuma N., Onouchi H., Kunimatsu M., Tomita Y., Sasaki M., Sugimoto K. Clin. Exp. Immunol. 120:218-223(2000) [PubMed: 10759786] [Abstract] Cited for: DISEASE. |
| [7] | "Degradation of nucleosome-associated centromeric histone H3-like protein CENP-A induced by herpes simplex virus type 1 protein ICP0." Lomonte P., Sullivan K.F., Everett R.D. J. Biol. Chem. 276:5829-5835(2001) [PubMed: 11053442] [Abstract] Cited for: UBIQUITINATION, INTERACTION WITH HSV-1 ICP0. |
| [8] | "CENP-A is phosphorylated by Aurora B kinase and plays an unexpected role in completion of cytokinesis." Zeitlin S.G., Shelby R.D., Sullivan K.F. J. Cell Biol. 155:1147-1157(2001) [PubMed: 11756469] [Abstract] Cited for: PHOSPHORYLATION AT SER-7, MUTAGENESIS OF SER-7. |
| [9] | "CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and for kinetochore function." Kunitoku N., Sasayama T., Marumoto T., Zhang D., Honda S., Kobayashi O., Hatakeyama K., Ushio Y., Saya H., Hirota T. Dev. Cell 5:853-864(2003) [PubMed: 14667408] [Abstract] Cited for: PHOSPHORYLATION AT SER-7, MUTAGENESIS OF SER-7. |
| [10] | "Chromosome size and origin as determinants of the level of CENP-A incorporation into human centromeres." Irvine D.V., Amor D.J., Perry J., Sirvent N., Pedeutour F., Choo K.H., Saffery R. Chromosome Res. 12:805-815(2004) [PubMed: 15702419] [Abstract] Cited for: SUBCELLULAR LOCATION. |
| [11] | "Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin and heterochromatin." Sullivan B.A., Karpen G.H. Nat. Struct. Mol. Biol. 11:1076-1083(2004) [PubMed: 15475964] [Abstract] Cited for: SUBCELLULAR LOCATION. |
| [12] | "Structural determinants for generating centromeric chromatin." Black B.E., Foltz D.R., Chakravarthy S., Luger K., Woods V.L. Jr., Cleveland D.W. Nature 430:578-582(2004) [PubMed: 15282608] [Abstract] Cited for: SUBUNIT, DOMAIN CATD. |
| [13] | "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17 AND SER-19, MASS SPECTROMETRY. Tissue: Epithelium. |
| [14] | "The human CENP-A centromeric nucleosome-associated complex." Foltz D.R., Jansen L.E.T., Black B.E., Bailey A.O., Yates J.R. III, Cleveland D.W. Nat. Cell Biol. 8:458-469(2006) [PubMed: 16622419] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE CENPA-NAC COMPLEX WITH CENPC; CENPH; CENPM; CENPN; CENPT AND CENPU. |
| [15] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17; SER-19; THR-23 AND SER-27, MASS SPECTROMETRY. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| U14518 mRNA. Translation: AAA57416.1. BT007246 mRNA. Translation: AAP35910.1. AC011740 Genomic DNA. Translation: AAX93267.1. BC000881 mRNA. Translation: AAH00881.1. BC002703 mRNA. Translation: AAH02703.1. U82609 Genomic DNA. Translation: AAB47505.1. | |
| PIR | I38855. |
| RefSeq | NP_001035891.1. NP_001800.1. |
| UniGene | Hs.1594 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1KX3 based on UniProtKB P16105. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | P49450. |
PTM databases | |
| PhosphoSite | P49450. |
Genome annotation databases | |
| Ensembl | ENSG00000115163. Homo sapiens. [Contig view] |
| GeneID | 1058. |
| KEGG | hsa:1058. |
Organism-specific databases | |
| H-InvDB | HIX0001898. |
| HGNC | HGNC:1851. CENPA. |
| HPA | CAB008371. |
| MIM | 117139. gene. |
| PharmGKB | PA26396. |
| GenAtlas | Search... |
| GeneCards | Search... |
Phylogenomic databases | |
| HOVERGEN | P49450. |
Gene expression databases | |
| ArrayExpress | P49450. |
| CleanEx | HS_CENPA. |
| GermOnline | ENSG00000115163. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR009072. Histone-fold. IPR007125. Histone_core_D. IPR000164. Histone_H3. [Graphical view] |
| Gene3D | G3DSA:1.10.20.10. Histone-fold. 1 hit. |
| PANTHER | PTHR11426. Histone_H3. 1 hit. |
| Pfam | PF00125. Histone. 1 hit. [Graphical view] |
| PRINTS | PR00622. HISTONEH3. |
| SMART | SM00428. H3. 1 hit. [Graphical view] |
| PROSITE | PS00959. HISTONE_H3_2. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 4426. |
| SOURCE | Search... |
Entry information
| Entry name | CENPA_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P49450 Secondary accession number(s): Q53T74, Q9BVW2 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 2 Human chromosome 2: entries, gene names and cross-references to MIM |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


