CENPA_YEAST
ID CENPA_YEAST Reviewed; 229 AA.
AC P36012; D6VXN8;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Histone H3-like centromeric protein CSE4;
DE AltName: Full=CENP-A homolog;
DE AltName: Full=Chromosome segregation protein 4;
GN Name=CSE4; Synonyms=CSL2; OrderedLocusNames=YKL049C; ORFNames=YKL262;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=7698647; DOI=10.1101/gad.9.5.573;
RA Stoler S., Keith K.C., Curnick K.E., Fitzgerald-Hayes M.;
RT "A mutation in CSE4, an essential gene encoding a novel chromatin-
RT associated protein in yeast, causes chromosome nondisjunction and cell
RT cycle arrest at mitosis.";
RL Genes Dev. 9:573-586(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8154189; DOI=10.1002/yea.320091212;
RA Purnelle B., Tettelin H., van Dyck L., Skala J., Goffeau A.;
RT "The sequence of a 17.5 kb DNA fragment on the left arm of yeast chromosome
RT XI identifies the protein kinase gene ELM1, the DNA primase gene PRI2, a
RT new gene encoding a putative histone and seven new open reading frames.";
RL Yeast 9:1379-1384(1993).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8196765; DOI=10.1038/369371a0;
RA Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V.,
RA Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P.,
RA Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L.,
RA Daignan-Fornier B., del Rey F., Dion C., Domdey H., Duesterhoeft A.,
RA Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H.,
RA Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L.,
RA Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M.,
RA Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H.,
RA Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J.,
RA Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H.,
RA Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J.,
RA Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S.,
RA Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F.,
RA Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R.,
RA Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W.,
RA Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M.,
RA Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C.,
RA Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H.,
RA Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L.,
RA van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S.,
RA von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M.,
RA Becker I., Mewes H.-W.;
RT "Complete DNA sequence of yeast chromosome XI.";
RL Nature 369:371-378(1994).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=9741625; DOI=10.1016/s0092-8674(00)81602-5;
RA Meluh P.B., Yang P., Glowczewski L., Koshland D., Smith M.M.;
RT "Cse4p is a component of the core centromere of Saccharomyces cerevisiae.";
RL Cell 94:607-613(1998).
RN [6]
RP FUNCTION.
RX PubMed=9584087; DOI=10.1093/genetics/149.1.73;
RA Baker R.E., Harris K., Zhang K.;
RT "Mutations synthetically lethal with cep1 target S. cerevisiae kinetochore
RT components.";
RL Genetics 149:73-85(1998).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=10323865; DOI=10.1101/gad.13.9.1140;
RA Ortiz J., Stemmann O., Rank S., Lechner J.;
RT "A putative protein complex consisting of Ctf19, Mcm21, and Okp1 represents
RT a missing link in the budding yeast kinetochore.";
RL Genes Dev. 13:1140-1155(1999).
RN [8]
RP FUNCTION.
RX PubMed=10454560; DOI=10.1128/mcb.19.9.6130;
RA Keith K.C., Baker R.E., Chen Y., Harris K., Stoler S., Fitzgerald-Hayes M.;
RT "Analysis of primary structural determinants that distinguish the
RT centromere-specific function of histone variant Cse4p from histone H3.";
RL Mol. Cell. Biol. 19:6130-6139(1999).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11063678; DOI=10.1093/genetics/156.3.973;
RA Keith K.C., Fitzgerald-Hayes M.;
RT "CSE4 genetically interacts with the Saccharomyces cerevisiae centromere
RT DNA elements CDE I and CDE II but not CDE III. Implications for the path of
RT the centromere dna around a cse4p variant nucleosome.";
RL Genetics 156:973-981(2000).
RN [10]
RP FUNCTION, AND MUTAGENESIS OF LEU-176; LEU-194; LEU-197 AND MET-218.
RX PubMed=10891506; DOI=10.1128/mcb.20.15.5700-5711.2000;
RA Glowczewski L., Yang P., Kalashnikova T., Santisteban M.S., Smith M.M.;
RT "Histone-histone interactions and centromere function.";
RL Mol. Cell. Biol. 20:5700-5711(2000).
RN [11]
RP FUNCTION.
RX PubMed=10499801; DOI=10.1016/s0092-8674(00)81518-4;
RA Tanaka T., Cosma M.P., Wirth K., Nasmyth K.;
RT "Identification of cohesin association sites at centromeres and along
RT chromosome arms.";
RL Cell 98:847-858(1999).
RN [12]
RP INTERACTION WITH CTF19.
RX PubMed=10958698; DOI=10.1128/mcb.20.18.7037-7048.2000;
RA Chen Y., Baker R.E., Keith K.C., Harris K., Stoler S., Fitzgerald-Hayes M.;
RT "The N-terminus of the centromere H3-like protein Cse4p performs an
RT essential function distinct from that of the histone fold domain.";
RL Mol. Cell. Biol. 20:7037-7048(2000).
RN [13]
RP FUNCTION.
RX PubMed=11606525; DOI=10.1093/genetics/159.2.453;
RA Biggins S., Bhalla N., Chang A., Smith D.L., Murray A.W.;
RT "Genes involved in sister chromatid separation and segregation in the
RT budding yeast Saccharomyces cerevisiae.";
RL Genetics 159:453-470(2001).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=11257125; DOI=10.1083/jcb.152.6.1255;
RA Pearson C.G., Maddox P.S., Salmon E.D., Bloom K.S.;
RT "Budding yeast chromosome structure and dynamics during mitosis.";
RL J. Cell Biol. 152:1255-1266(2001).
RN [15]
RP IDENTIFICATION IN THE CORE KINETOCHORE.
RX PubMed=14581449; DOI=10.1083/jcb.200305100;
RA Westermann S., Cheeseman I.M., Anderson S., Yates J.R. III, Drubin D.G.,
RA Barnes G.;
RT "Architecture of the budding yeast kinetochore reveals a conserved
RT molecular core.";
RL J. Cell Biol. 163:215-222(2003).
RN [16]
RP SUBCELLULAR LOCATION, AND UBIQUITIN-MEDIATED PROTEOLYSIS.
RX PubMed=15530401; DOI=10.1016/j.cub.2004.10.024;
RA Collins K.A., Furuyama S., Biggins S.;
RT "Proteolysis contributes to the exclusive centromere localization of the
RT yeast Cse4/CENP-A histone H3 variant.";
RL Curr. Biol. 14:1968-1972(2004).
RN [17]
RP FUNCTION.
RX PubMed=15590827; DOI=10.1128/ec.3.6.1533-1543.2004;
RA Morey L., Barnes K., Chen Y., Fitzgerald-Hayes M., Baker R.E.;
RT "The histone fold domain of Cse4 is sufficient for CEN targeting and
RT propagation of active centromeres in budding yeast.";
RL Eukaryot. Cell 3:1533-1543(2004).
RN [18]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16207811; DOI=10.1091/mbc.e05-08-0771;
RA Collins K.A., Castillo A.R., Tatsutani S.Y., Biggins S.;
RT "De novo kinetochore assembly requires the centromeric histone H3
RT variant.";
RL Mol. Biol. Cell 16:5649-5660(2005).
RN [19]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16966420; DOI=10.1083/jcb.200603042;
RA Hajra S., Ghosh S.K., Jayaram M.;
RT "The centromere-specific histone variant Cse4p (CENP-A) is essential for
RT functional chromatin architecture at the yeast 2-micrometer circle
RT partitioning locus and promotes equal plasmid segregation.";
RL J. Cell Biol. 174:779-790(2006).
RN [20]
RP SUBCELLULAR LOCATION.
RX PubMed=16715078; DOI=10.1038/ncb1414;
RA Joglekar A.P., Bouck D.C., Molk J.N., Bloom K.S., Salmon E.D.;
RT "Molecular architecture of a kinetochore-microtubule attachment site.";
RL Nat. Cell Biol. 8:581-585(2006).
RN [21]
RP INTERACTION WITH YTA7.
RX PubMed=32079723; DOI=10.1073/pnas.1917814117;
RA Shahnejat-Bushehri S., Ehrenhofer-Murray A.E.;
RT "The ATAD2/ANCCA homolog Yta7 cooperates with Scm3HJURP to deposit
RT Cse4CENP-A at the centromere in yeast.";
RL Proc. Natl. Acad. Sci. U.S.A. 117:5386-5393(2020).
RN [22]
RP 3D-STRUCTURE MODELING OF 1-228.
RX PubMed=16631569; DOI=10.1016/j.cub.2006.03.054;
RA Bloom K.S., Sharma S., Dokholyan N.V.;
RT "The path of DNA in the kinetochore.";
RL Curr. Biol. 16:R276-R278(2006).
CC -!- FUNCTION: Histone H3-like variant which exclusively replaces
CC conventional H3 in the nucleosome core of centromeric chromatin at the
CC inner plate of the kinetochore. Required for recruitment and assembly
CC of kinetochore proteins, mitotic progression and chromosome
CC segregation. May serve as an epigenetic mark that propagates centromere
CC identity through replication and cell division. Required for functional
CC chromatin architecture at the yeast 2-micron circle partitioning locus
CC and promotes equal plasmid segregation. {ECO:0000269|PubMed:10454560,
CC ECO:0000269|PubMed:10499801, ECO:0000269|PubMed:10891506,
CC ECO:0000269|PubMed:11063678, ECO:0000269|PubMed:11606525,
CC ECO:0000269|PubMed:15590827, ECO:0000269|PubMed:16207811,
CC ECO:0000269|PubMed:16966420, ECO:0000269|PubMed:7698647,
CC ECO:0000269|PubMed:9584087, ECO:0000269|PubMed:9741625}.
CC -!- SUBUNIT: Component of the core kinetochore (PubMed:14581449). Interacts
CC with the central kinetochore protein CTF19 (PubMed:10958698). Interacts
CC with YTA7 (PubMed:32079723). {ECO:0000269|PubMed:10958698,
CC ECO:0000269|PubMed:14581449, ECO:0000269|PubMed:32079723}.
CC -!- INTERACTION:
CC P36012; P53267: DAM1; NbExp=2; IntAct=EBI-5182, EBI-23268;
CC P36012; Q12334: SCM3; NbExp=5; IntAct=EBI-5182, EBI-31788;
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome, centromere, kinetochore.
CC Note=Localizes exclusively in the kinetochore domain of centromeres.
CC -!- PTM: Ubiquitinated (Probable). Is degraded through ubiquitin mediated
CC proteolysis when not protected by its association to the kinetochore.
CC This may ensure exclusive localization of CSE4 to the kinetochore.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: Mutation in CSE4 causes chromosome non-disjunction and
CC cell cycle arrest at mitosis.
CC -!- SIMILARITY: Belongs to the histone H3 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA81884.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U20327; AAB60309.1; -; Genomic_DNA.
DR EMBL; X71621; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z28049; CAA81884.1; ALT_FRAME; Genomic_DNA.
DR EMBL; BK006944; DAA09108.1; -; Genomic_DNA.
DR PIR; S37870; S37870.
DR RefSeq; NP_012875.2; NM_001179615.1.
DR PDB; 2L5A; NMR; -; A=151-228.
DR PDB; 2LY8; NMR; -; A=152-225.
DR PDB; 6UPH; EM; 2.70 A; A/E=1-229.
DR PDB; 7ON1; EM; 3.35 A; a/e=1-229.
DR PDBsum; 2L5A; -.
DR PDBsum; 2LY8; -.
DR PDBsum; 6UPH; -.
DR PDBsum; 7ON1; -.
DR AlphaFoldDB; P36012; -.
DR SMR; P36012; -.
DR BioGRID; 34084; 840.
DR DIP; DIP-8048N; -.
DR IntAct; P36012; 8.
DR STRING; 4932.YKL049C; -.
DR iPTMnet; P36012; -.
DR MaxQB; P36012; -.
DR PaxDb; P36012; -.
DR PRIDE; P36012; -.
DR EnsemblFungi; YKL049C_mRNA; YKL049C; YKL049C.
DR GeneID; 853817; -.
DR KEGG; sce:YKL049C; -.
DR SGD; S000001532; CSE4.
DR VEuPathDB; FungiDB:YKL049C; -.
DR eggNOG; KOG1745; Eukaryota.
DR GeneTree; ENSGT01050000244918; -.
DR HOGENOM; CLU_078295_3_0_1; -.
DR InParanoid; P36012; -.
DR OMA; KRITIMR; -.
DR BioCyc; YEAST:G3O-31850-MON; -.
DR Reactome; R-SCE-2299718; Condensation of Prophase Chromosomes.
DR Reactome; R-SCE-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-SCE-3214815; HDACs deacetylate histones.
DR Reactome; R-SCE-3214841; PKMTs methylate histone lysines.
DR Reactome; R-SCE-3214842; HDMs demethylate histones.
DR Reactome; R-SCE-3214847; HATs acetylate histones.
DR Reactome; R-SCE-3214858; RMTs methylate histone arginines.
DR Reactome; R-SCE-427359; SIRT1 negatively regulates rRNA expression.
DR Reactome; R-SCE-5625886; Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3.
DR Reactome; R-SCE-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-SCE-68616; Assembly of the ORC complex at the origin of replication.
DR Reactome; R-SCE-73772; RNA Polymerase I Promoter Escape.
DR Reactome; R-SCE-9018519; Estrogen-dependent gene expression.
DR PRO; PR:P36012; -.
DR Proteomes; UP000002311; Chromosome XI.
DR RNAct; P36012; protein.
DR GO; GO:0005729; C:2-micrometer circle DNA; IDA:SGD.
DR GO; GO:0043505; C:CENP-A containing nucleosome; IDA:SGD.
DR GO; GO:0000779; C:condensed chromosome, centromeric region; IDA:SGD.
DR GO; GO:0000776; C:kinetochore; IDA:SGD.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0019237; F:centromeric DNA binding; IDA:SGD.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:InterPro.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:SGD.
DR GO; GO:0030527; F:structural constituent of chromatin; IEA:InterPro.
DR GO; GO:0030543; P:2-micrometer plasmid partitioning; IMP:SGD.
DR GO; GO:0051382; P:kinetochore assembly; IMP:SGD.
DR GO; GO:0000070; P:mitotic sister chromatid segregation; IMP:SGD.
DR GO; GO:0061644; P:protein localization to CENP-A containing chromatin; IMP:SGD.
DR Gene3D; 1.10.20.10; -; 1.
DR InterPro; IPR009072; Histone-fold.
DR InterPro; IPR007125; Histone_H2A/H2B/H3.
DR InterPro; IPR000164; Histone_H3/CENP-A.
DR PANTHER; PTHR11426; PTHR11426; 1.
DR Pfam; PF00125; Histone; 1.
DR PRINTS; PR00622; HISTONEH3.
DR SMART; SM00428; H3; 1.
DR SUPFAM; SSF47113; SSF47113; 1.
DR PROSITE; PS00959; HISTONE_H3_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Centromere; Chromosome; DNA-binding; Kinetochore; Nucleus;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..229
FT /note="Histone H3-like centromeric protein CSE4"
FT /id="PRO_0000221376"
FT REGION 1..78
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 132..229
FT /note="H3-like"
FT MOTIF 115..132
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 1..47
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..72
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 176
FT /note="L->S: In CSE4-102; impairs nuclear division by
FT disrupting the core centromere structure; when associated
FT with T-218."
FT /evidence="ECO:0000269|PubMed:10891506"
FT MUTAGEN 194
FT /note="L->Q: In CSE4-111; impairs nuclear division by
FT disrupting the core centromere structure."
FT /evidence="ECO:0000269|PubMed:10891506"
FT MUTAGEN 197
FT /note="L->S: In CSE4-110; impairs nuclear division by
FT disrupting the core centromere structure."
FT /evidence="ECO:0000269|PubMed:10891506"
FT MUTAGEN 218
FT /note="M->T: In CSE4-102; impairs nuclear division by
FT disrupting the core centromere structure; when associated
FT with S-176."
FT /evidence="ECO:0000269|PubMed:10891506"
FT HELIX 137..145
FT /evidence="ECO:0007829|PDB:6UPH"
FT HELIX 155..166
FT /evidence="ECO:0007829|PDB:6UPH"
FT STRAND 172..174
FT /evidence="ECO:0007829|PDB:6UPH"
FT HELIX 180..206
FT /evidence="ECO:0007829|PDB:6UPH"
FT TURN 207..209
FT /evidence="ECO:0007829|PDB:6UPH"
FT STRAND 211..213
FT /evidence="ECO:0007829|PDB:6UPH"
FT HELIX 215..225
FT /evidence="ECO:0007829|PDB:6UPH"
SQ SEQUENCE 229 AA; 26841 MW; 0170A10060EEC309 CRC64;
MSSKQQWVSS AIQSDSSGRS LSNVNRLAGD QQSINDRALS LLQRTRATKN LFPRREERRR
YESSKSDLDI ETDYEDQAGN LEIETENEEE AEMETEVPAP VRTHSYALDR YVRQKRREKQ
RKQSLKRVEK KYTPSELALY EIRKYQRSTD LLISKIPFAR LVKEVTDEFT TKDQDLRWQS
MAIMALQEAS EAYLVGLLEH TNLLALHAKR ITIMKKDMQL ARRIRGQFI
