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 27-MAR-2024, entry version 192. DE RecName: Full=Histone H3-like centromeric protein CSE4; DE AltName: Full=CENP-A homolog; DE AltName: Full=CENPA homolog {ECO:0000305}; 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 CENTROMERIC NUCLEOSOMES, INTERACTION WITH THE INNER RP KINETOCHORE, AND SUBCELLULAR LOCATION. 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). RN [23] {ECO:0007744|PDB:6UPH} RP STRUCTURE BY ELECTRON MICROSCOPY (2.70 ANGSTROMS), AND COMPONENT OF RP CENTROMERIC NUCLEOSOMES. RX PubMed=32004465; DOI=10.1016/j.str.2019.12.002; RA Migl D., Kschonsak M., Arthur C.P., Khin Y., Harrison S.C., Ciferri C., RA Dimitrova Y.N.; RT "Cryoelectron Microscopy Structure of a Yeast Centromeric Nucleosome at RT 2.7A Resolution."; RL Structure 28:363-370.e3(2020). CC -!- FUNCTION: Histone H3-like nucleosomal protein that is specifically CC found in centromeric nucleosomes. Replaces conventional H3 in the CC nucleosome core of centromeric chromatin that serves as an assembly CC site for the inner 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 centromeric nucleosomes, where DNA is wrapped CC around a histone octamer core (PubMed:32004465, PubMed:14581449). The CC octamer contains two molecules each of H2A, H2B, CSE4/CENPA and H4 CC assembled in one CSE4-H4 heterotetramer and two H2A-H2B heterodimers CC (PubMed:32004465, PubMed:14581449). Interacts with the inner CC kinetochore (PubMed:14581449). Interacts with the central kinetochore CC protein CTF19 (PubMed:10958698). Interacts with YTA7 (PubMed:32079723). CC {ECO:0000269|PubMed:10958698, ECO:0000269|PubMed:14581449, CC ECO:0000269|PubMed:32004465, 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 {ECO:0000269|PubMed:14581449}. CC Chromosome, centromere {ECO:0000269|PubMed:14581449}. CC -!- PTM: Ubiquitinated (Probable). Is degraded through ubiquitin-mediated CC proteolysis when not protected by its association to the kinetochore CC (Probable). {ECO:0000305|PubMed:15530401}. CC -!- MISCELLANEOUS: Mutation in CSE4 causes chromosome non-disjunction and CC cell cycle arrest at mitosis. {ECO:0000269|PubMed:7698647}. CC -!- SIMILARITY: Belongs to the histone H3 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA81884.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 8OW0; EM; 3.40 A; a/e=1-229. DR PDB; 8OW1; EM; 3.70 A; a/e=1-229. DR PDB; 8T0P; X-ray; 1.73 A; C=32-49. DR PDBsum; 2L5A; -. DR PDBsum; 2LY8; -. DR PDBsum; 6UPH; -. DR PDBsum; 7ON1; -. DR PDBsum; 8OW0; -. DR PDBsum; 8OW1; -. DR PDBsum; 8T0P; -. DR AlphaFoldDB; P36012; -. DR EMDB; EMD-17226; -. DR EMDB; EMD-17227; -. DR EMDB; EMD-20839; -. DR SMR; P36012; -. DR BioGRID; 34084; 1246. DR DIP; DIP-8048N; -. DR IntAct; P36012; 8. DR STRING; 4932.YKL049C; -. DR iPTMnet; P36012; -. DR MaxQB; P36012; -. DR PaxDb; 4932-YKL049C; -. DR PeptideAtlas; P36012; -. DR EnsemblFungi; YKL049C_mRNA; YKL049C; YKL049C. DR GeneID; 853817; -. DR KEGG; sce:YKL049C; -. DR AGR; SGD:S000001532; -. DR SGD; S000001532; CSE4. DR VEuPathDB; FungiDB:YKL049C; -. DR eggNOG; KOG1745; Eukaryota. DR GeneTree; ENSGT01100000263504; -. DR HOGENOM; CLU_078295_3_0_1; -. DR InParanoid; P36012; -. DR OMA; KRITIMR; -. DR OrthoDB; 5482964at2759; -. DR BioCyc; YEAST:G3O-31850-MONOMER; -. DR BioGRID-ORCS; 853817; 2 hits in 10 CRISPR screens. 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:UniProtKB. DR GO; GO:0000779; C:condensed chromosome, centromeric region; 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 GO; GO:0009303; P:rRNA transcription; IBA:GO_Central. DR Gene3D; 1.10.20.10; Histone, subunit A; 1. DR InterPro; IPR009072; Histone-fold. DR InterPro; IPR007125; Histone_H2A/H2B/H3. DR InterPro; IPR000164; Histone_H3/CENP-A. DR PANTHER; PTHR45810; HISTONE H3.2; 1. DR Pfam; PF00125; Histone; 1. DR PRINTS; PR00622; HISTONEH3. DR SMART; SM00428; H3; 1. DR SUPFAM; SSF47113; Histone-fold; 1. DR PROSITE; PS00959; HISTONE_H3_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Centromere; Chromosome; DNA-binding; Nucleosome core; KW Nucleus; 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 34..47 FT /evidence="ECO:0007829|PDB:8T0P" 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 //