P36012 (CENPA_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone H3-like centromeric protein CSE4

Alternative name(s):
CENP-A homolog
Chromosome segregation protein 4

Gene names

Name:	CSE4
Synonyms:	CSL2
Ordered Locus Names:	YKL049C
ORF Names:	YKL262

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	229 AA.
Sequence status	Complete.
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. Required for functional chromatin architecture at the yeast 2-micron circle partitioning locus and promotes equal plasmid segregation. Ref.1 Ref.5 Ref.6 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.17 Ref.18 Ref.19
Subunit structure	Component of the core kinetochore. Interacts with the central kinetochore protein CTF19. Ref.12 Ref.15
Subcellular location	Nucleus. Chromosome › centromere › kinetochore. Note: Localizes exclusively in the kinetochore domain of centromeres. Ref.5 Ref.7 Ref.9 Ref.14 Ref.16 Ref.18 Ref.19 Ref.20
Post-translational modification	Ubiquitinated Probable. Is degraded through ubiquitin mediated proteolysis when not protected by its association to the kinetochore. This may ensure exclusive localization of CSE4 to the kinetochore.
Miscellaneous	Mutation in CSE4 causes chromosome non-disjunction and cell cycle arrest at mitosis.
Sequence similarities	Belongs to the histone H3 family.
Sequence caution	The sequence CAA81884.1 differs from that shown. Reason: Frameshift at position 28.

Ontologies

Keywords
Cellular component	Centromere Chromosome Kinetochore Nucleus
Ligand	DNA-binding
PTM	Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	2-micrometer plasmid partitioning Inferred from mutant phenotype Ref.19. Source: SGD mitotic sister chromatid segregation Inferred from mutant phenotype Ref.1. Source: SGD nucleosome assembly Inferred from electronic annotation. Source: InterPro
Cellular_component	centromere-specific nucleosome Inferred from direct assay PubMed 19782029. Source: SGD condensed chromosome kinetochore Inferred from electronic annotation. Source: UniProtKB-SubCell condensed nuclear chromosome, centromeric region Inferred from genetic interaction Ref.9. Source: SGD extrachromosomal circular DNA Inferred from direct assay Ref.19. Source: SGD kinetochore Inferred from genetic interaction Ref.12. Source: SGD nuclear nucleosome Inferred from direct assay Ref.9. Source: SGD
Molecular_function	centromeric DNA binding Inferred from direct assay Ref.9. Source: SGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DAM1	P53267	3	EBI-5182,EBI-23268

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 229

229

Histone H3-like centromeric protein CSE4

PRO_0000221376

Regions

Region

132 – 229

98

H3-like

Motif

115 – 132

18

Nuclear localization signal Potential

Compositional bias

1 – 66

66

Ser-rich

Experimental info

Mutagenesis

176

1

L → S in CSE4-102; impairs nuclear division by disrupting the core centromere structure; when associated with T-218. Ref.10

Mutagenesis

194

1

L → Q in CSE4-111; impairs nuclear division by disrupting the core centromere structure. Ref.10

Mutagenesis

197

1

L → S in CSE4-110; impairs nuclear division by disrupting the core centromere structure. Ref.10

Mutagenesis

218

1

M → T in CSE4-102; impairs nuclear division by disrupting the core centromere structure; when associated with S-176. Ref.10

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

229

Helix Strand Turn

Details...

Helix

157 – 167

11

Helix

171 – 173

3

Helix

180 – 206

27

Turn

208 – 210

3

Helix

212 – 214

3

Helix

217 – 222

6

Sequences

	Sequence		Length	Mass (Da)
	P36012 [UniParc]. Last modified November 1, 1995. Version 2. Checksum: 0170A10060EEC309	FASTA	229	26,841
	10 20 30 40 50 60 MSSKQQWVSS AIQSDSSGRS LSNVNRLAGD QQSINDRALS LLQRTRATKN LFPRREERRR 70 80 90 100 110 120 YESSKSDLDI ETDYEDQAGN LEIETENEEE AEMETEVPAP VRTHSYALDR YVRQKRREKQ 130 140 150 160 170 180 RKQSLKRVEK KYTPSELALY EIRKYQRSTD LLISKIPFAR LVKEVTDEFT TKDQDLRWQS 190 200 210 220 MAIMALQEAS EAYLVGLLEH TNLLALHAKR ITIMKKDMQL ARRIRGQFI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A mutation in CSE4, an essential gene encoding a novel chromatin-associated protein in yeast, causes chromosome nondisjunction and cell cycle arrest at mitosis." Stoler S., Keith K.C., Curnick K.E., Fitzgerald-Hayes M. Genes Dev. 9:573-586(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION.
[2]	"The sequence of a 17.5 kb DNA fragment on the left arm of yeast chromosome XI identifies the protein kinase gene ELM1, the DNA primase gene PRI2, a new gene encoding a putative histone and seven new open reading frames." Purnelle B., Tettelin H., van Dyck L., Skala J., Goffeau A. Yeast 9:1379-1384(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[3]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[4]	"Complete DNA sequence of yeast chromosome XI." Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V., Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P., Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L., Daignan-Fornier B., del Rey F., Dion C. , Domdey H., Duesterhoeft A., Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H., Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L., Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M., Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H., Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J., Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H., Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J., Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S., Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F., Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R., Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W., Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M., Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C., Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H., Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L., van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S., von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M., Becker I., Mewes H.-W. Nature 369:371-378(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[5]	"Cse4p is a component of the core centromere of Saccharomyces cerevisiae." Meluh P.B., Yang P., Glowczewski L., Koshland D., Smith M.M. Cell 94:607-613(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[6]	"Mutations synthetically lethal with cep1 target S. cerevisiae kinetochore components." Baker R.E., Harris K., Zhang K. Genetics 149:73-85(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"A putative protein complex consisting of Ctf19, Mcm21, and Okp1 represents a missing link in the budding yeast kinetochore." Ortiz J., Stemmann O., Rank S., Lechner J. Genes Dev. 13:1140-1155(1999) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[8]	"Analysis of primary structural determinants that distinguish the centromere-specific function of histone variant Cse4p from histone H3." Keith K.C., Baker R.E., Chen Y., Harris K., Stoler S., Fitzgerald-Hayes M. Mol. Cell. Biol. 19:6130-6139(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"CSE4 genetically interacts with the Saccharomyces cerevisiae centromere DNA elements CDE I and CDE II but not CDE III. Implications for the path of the centromere dna around a cse4p variant nucleosome." Keith K.C., Fitzgerald-Hayes M. Genetics 156:973-981(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[10]	"Histone-histone interactions and centromere function." Glowczewski L., Yang P., Kalashnikova T., Santisteban M.S., Smith M.M. Mol. Cell. Biol. 20:5700-5711(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LEU-176; LEU-194; LEU-197 AND MET-218.
[11]	"Identification of cohesin association sites at centromeres and along chromosome arms." Tanaka T., Cosma M.P., Wirth K., Nasmyth K. Cell 98:847-858(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"The N-terminus of the centromere H3-like protein Cse4p performs an essential function distinct from that of the histone fold domain." Chen Y., Baker R.E., Keith K.C., Harris K., Stoler S., Fitzgerald-Hayes M. Mol. Cell. Biol. 20:7037-7048(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CTF19.
[13]	"Genes involved in sister chromatid separation and segregation in the budding yeast Saccharomyces cerevisiae." Biggins S., Bhalla N., Chang A., Smith D.L., Murray A.W. Genetics 159:453-470(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[14]	"Budding yeast chromosome structure and dynamics during mitosis." Pearson C.G., Maddox P.S., Salmon E.D., Bloom K.S. J. Cell Biol. 152:1255-1266(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[15]	"Architecture of the budding yeast kinetochore reveals a conserved molecular core." Westermann S., Cheeseman I.M., Anderson S., Yates J.R. III, Drubin D.G., Barnes G. J. Cell Biol. 163:215-222(2003) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE CORE KINETOCHORE.
[16]	"Proteolysis contributes to the exclusive centromere localization of the yeast Cse4/CENP-A histone H3 variant." Collins K.A., Furuyama S., Biggins S. Curr. Biol. 14:1968-1972(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, UBIQUITIN-MEDIATED PROTEOLYSIS.
[17]	"The histone fold domain of Cse4 is sufficient for CEN targeting and propagation of active centromeres in budding yeast." Morey L., Barnes K., Chen Y., Fitzgerald-Hayes M., Baker R.E. Eukaryot. Cell 3:1533-1543(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[18]	"De novo kinetochore assembly requires the centromeric histone H3 variant." Collins K.A., Castillo A.R., Tatsutani S.Y., Biggins S. Mol. Biol. Cell 16:5649-5660(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, FUNCTION.
[19]	"The centromere-specific histone variant Cse4p (CENP-A) is essential for functional chromatin architecture at the yeast 2-micrometer circle partitioning locus and promotes equal plasmid segregation." Hajra S., Ghosh S.K., Jayaram M. J. Cell Biol. 174:779-790(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[20]	"Molecular architecture of a kinetochore-microtubule attachment site." Joglekar A.P., Bouck D.C., Molk J.N., Bloom K.S., Salmon E.D. Nat. Cell Biol. 8:581-585(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[21]	"The path of DNA in the kinetochore." Bloom K.S., Sharma S., Dokholyan N.V. Curr. Biol. 16:R276-R278(2006) [PubMed] [Europe PMC] [Abstract] Cited for: 3D-STRUCTURE MODELING OF 1-228.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U20327 Genomic DNA. Translation: AAB60309.1.
X71621 Genomic DNA. No translation available.
Z28049 Genomic DNA. Translation: CAA81884.1. Frameshift.
BK006944 Genomic DNA. Translation: DAA09108.1.

PIR

S37870.

RefSeq

NP_012875.2. NM_001179615.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2FSB	model	-	E	1-228	[»]
2FSC	model	-	A	1-228	[»]
2L5A	NMR	-	A	151-228	[»]
2LY8	NMR	-	A	152-207	[»]

ProteinModelPortal

P36012.

SMR

P36012. Positions 152-229.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-8048N.

IntAct

P36012. 7 interactions.

STRING

4932.YKL049C.

Proteomic databases

PaxDb

P36012.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YKL049C; YKL049C; YKL049C.

GeneID

853817.

KEGG

sce:YKL049C.

Organism-specific databases

CYGD

YKL049c.

SGD

S000001532. CSE4.

Phylogenomic databases

eggNOG

COG2036.

GeneTree

ENSGT00690000102181.

HOGENOM

HOG000155290.

OMA

RITIMKK.

OrthoDB

EOG4TJ03R.

Gene expression databases

Genevestigator

P36012.

GermOnline

YKL049C. Saccharomyces cerevisiae.

Family and domain databases

Gene3D

1.10.20.10. 1 hit.

InterPro

IPR009072. Histone-fold.
IPR007125. Histone_core_D.
IPR000164. Histone_H3.
[Graphical view]

PANTHER

PTHR11426. PTHR11426. 1 hit.

Pfam

PF00125. Histone. 1 hit.
[Graphical view]

PRINTS

PR00622. HISTONEH3.

SMART

SM00428. H3. 1 hit.
[Graphical view]

SUPFAM

SSF47113. Histone-fold. 1 hit.

PROSITE

PS00959. HISTONE_H3_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

974993.

Entry information

Entry name

CENPA_YEAST

Accession

Primary (citable) accession number: P36012
Secondary accession number(s): D6VXN8

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 115 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program