Reviewed, UniProtKB/Swiss-Prot P49450 (CENPA_HUMAN)

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

Name:

CENPA

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 assembly Inferred from electronic annotation. Source: InterPro
Cellular component	nucleosome Inferred from electronic annotation. Source: InterPro nucleus Ref.1 Traceable author statement. Source: ProtInc
Molecular function	DNA binding Inferred from electronic annotation. Source: InterPro chromatin binding Ref.1 Traceable 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

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: 11A28FEB54486489	FASTA	140	15,991
	10 20 30 40 50 60 MGPRRRSRKP EAPRRRSPSP TPTPGPSRRG PSLGASSHQH SRRRQGWLKE IRKLQKSTHL 70 80 90 100 110 120 LIRKLPFSRL AREICVKFTR GVDFNWQAQA LLALQEAAEA FLVHLFEDAY LLTLHAGRVT 130 140 LFPKDVQLAR RIRGLEEGLG
	Isoform 2 [UniParc]. Checksum: 9E0DB58DBB95C1CF		114	13,001
	10 20 30 40 50 60 MGPRRRSRKP EAPRRRSPSP TPTPGPSRRG PSLGASSHQH SRRRQGWLKE IRKLQKSTHL 70 80 90 100 110 LIRKLPFSRL AAEAFLVHLF EDAYLLTLHA GRVTLFPKDV QLARRIRGLE EGLG

References

	« Hide 'large scale' referencesShow '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. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.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
EMBLGenBankDDBJ	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

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	November 25, 2008
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)