CENPA_MOUSE
ID CENPA_MOUSE Reviewed; 134 AA.
AC O35216; Q545C9;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Histone H3-like centromeric protein A;
DE AltName: Full=Centromere protein A;
DE Short=CENP-A;
GN Name=Cenpa;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC STRAIN=129/Sv, and C57BL/6J;
RX PubMed=9465302; DOI=10.1006/geno.1997.5109;
RA Kalitsis P., Macdonald A.C., Newson A.J., Hudson D.F., Choo K.H.A.;
RT "Gene structure and sequence analysis of mouse centromere proteins A and
RT C.";
RL Genomics 47:108-114(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Eye, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP POLY-ADP-RIBOSYLATION BY PARP1.
RX PubMed=12011073; DOI=10.1074/jbc.m200620200;
RA Saxena A., Saffery R., Wong L.H., Kalitsis P., Choo K.H.;
RT "Centromere proteins Cenpa, Cenpb, and Bub3 interact with poly(ADP-ribose)
RT polymerase-1 protein and are poly(ADP-ribosyl)ated.";
RL J. Biol. Chem. 277:26921-26926(2002).
RN [5]
RP FUNCTION.
RX PubMed=27499292; DOI=10.1016/j.molcel.2016.06.023;
RA Roulland Y., Ouararhni K., Naidenov M., Ramos L., Shuaib M., Syed S.H.,
RA Lone I.N., Boopathi R., Fontaine E., Papai G., Tachiwana H., Gautier T.,
RA Skoufias D., Padmanabhan K., Bednar J., Kurumizaka H., Schultz P.,
RA Angelov D., Hamiche A., Dimitrov S.;
RT "The flexible ends of CENP-A nucleosome are required for mitotic
RT fidelity.";
RL Mol. Cell 63:674-685(2016).
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 at the inner plate of the
CC kinetochore. The presence of CENPA subtly modifies the nucleosome
CC structure and the way DNA is wrapped around the nucleosome and gives
CC rise to protruding DNA ends that are less well-ordered and rigid
CC compared to nucleosomes containing histone H3. May serve as an
CC epigenetic mark that propagates centromere identity through replication
CC and cell division (By similarity). Required for recruitment and
CC assembly of kinetochore proteins, and as a consequence required for
CC progress through mitosis, chromosome segregation and cytokinesis
CC (PubMed:27499292). {ECO:0000250|UniProtKB:P49450,
CC ECO:0000269|PubMed:27499292}.
CC -!- SUBUNIT: Component of centromeric nucleosomes, where DNA is wrapped
CC around a histone octamer core. The octamer contains two molecules each
CC of H2A, H2B, CENPA and H4 assembled in one CENPA-H4 heterotetramer and
CC two H2A-H2B heterodimers. CENPA modulates the DNA-binding
CC characteristics of nucleosomes so that protruding DNA ends have higher
CC flexibility than in nucleosomes containing conventional histone H3.
CC Inhibits binding of histone H1 to nucleosomes, since histone H1 binds
CC preferentially to rigid DNA linkers that protrude from nucleosomes.
CC Nucleosomes containing CENPA also contain histone H2A variants such as
CC MACROH2A and H2A.Z/H2AZ1. The CENPA-H4 heterotetramer is more compact
CC and structurally more rigid than corresponding H3-H4 heterotetramers.
CC Can assemble into nucleosomes that contain both CENPA and histone H3.3;
CC these nucleosomes interact with a single CENPC chain. Heterotrimer
CC composed of HJURP, CENPA and histone H4, where HJURP interacts with the
CC dimer formed by CENPA and histone H4 and prevents tetramerization of
CC CENPA and H4. Component of the CENPA-NAC complex, at least composed of
CC CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU. Interacts (via CATD
CC domain) with HJURP; the interaction is direct and is required for its
CC localization to centromeres. Interacts with CENPC, CENPN and CENPT;
CC interaction is direct. Part of a centromere complex consisting of
CC CENPA, CENPT and CENPW. Identified in centromere complexes containing
CC histones H2A, H2B and H4, and at least CENPA, CENPB, CENPC, CENPT,
CC CENPN, HJURP, SUPT16H, SSRP1 and RSF1. Can self-associate. The CENPA-H4
CC heterotetramer can bind DNA by itself (in vitro). Interacts with CDK1,
CC PPP1CA and RBBP7. {ECO:0000250|UniProtKB:P49450}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P49450}.
CC Chromosome, centromere, kinetochore {ECO:0000250|UniProtKB:P49450}.
CC Chromosome, centromere {ECO:0000250|UniProtKB:P49450}. Note=Localizes
CC exclusively in the kinetochore domain of centromeres. Occupies a
CC compact domain at the inner kinetochore plate stretching across 2
CC thirds of the length of the constriction but encompassing only one
CC third of the constriction width and height. Phosphorylation at Ser-62
CC during early mitosis abolishes association with chromatin and
CC centromeres and results in dispersed nuclear location.
CC {ECO:0000250|UniProtKB:P49450}.
CC -!- DOMAIN: The CATD (CENPA targeting domain) region is responsible for the
CC more compact structure of nucleosomes containing CENPA. It is necessary
CC and sufficient to mediate the localization into centromeres.
CC {ECO:0000250|UniProtKB:P49450}.
CC -!- PTM: Poly-ADP-ribosylated by PARP1.
CC -!- PTM: Trimethylated by NTMT1 at the N-terminal glycine after cleavage of
CC Met-1. Methylation is low before incorporation into nucleosomes and
CC increases with cell cycle progression, with the highest levels in
CC mitotic nucleosomes. {ECO:0000250|UniProtKB:P49450}.
CC -!- PTM: Phosphorylated by CDK1 at Ser-62 during early mitosis; this
CC abolishes association with chromatin and centromeres, prevents
CC interaction with HJURP and thereby prevents premature assembly of CENPA
CC into centromeres. Dephosphorylated at Ser-62 by PPP1CA during late
CC mitosis. {ECO:0000250|UniProtKB:P49450}.
CC -!- SIMILARITY: Belongs to the histone H3 family. {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; AF012709; AAC39957.1; -; mRNA.
DR EMBL; AF012710; AAC39958.1; -; Genomic_DNA.
DR EMBL; AK010718; BAB27140.1; -; mRNA.
DR EMBL; AK011399; BAB27591.1; -; mRNA.
DR EMBL; AK053763; BAC35512.1; -; mRNA.
DR EMBL; AK089033; BAC40710.1; -; mRNA.
DR EMBL; BC011038; AAH11038.1; -; mRNA.
DR CCDS; CCDS19162.1; -.
DR RefSeq; NP_001289058.1; NM_001302129.1.
DR RefSeq; NP_001289059.1; NM_001302130.1.
DR RefSeq; NP_001289060.1; NM_001302131.1.
DR RefSeq; NP_001289061.1; NM_001302132.1.
DR RefSeq; NP_031707.1; NM_007681.3.
DR AlphaFoldDB; O35216; -.
DR SMR; O35216; -.
DR BioGRID; 198674; 1.
DR ComplexPortal; CPX-5705; CENP-A nucleosome complex.
DR IntAct; O35216; 2.
DR MINT; O35216; -.
DR STRING; 10090.ENSMUSP00000122831; -.
DR iPTMnet; O35216; -.
DR PhosphoSitePlus; O35216; -.
DR EPD; O35216; -.
DR jPOST; O35216; -.
DR MaxQB; O35216; -.
DR PaxDb; O35216; -.
DR PeptideAtlas; O35216; -.
DR PRIDE; O35216; -.
DR ProteomicsDB; 281535; -.
DR Antibodypedia; 3643; 544 antibodies from 36 providers.
DR DNASU; 12615; -.
DR Ensembl; ENSMUST00000144742; ENSMUSP00000122831; ENSMUSG00000029177.
DR GeneID; 12615; -.
DR KEGG; mmu:12615; -.
DR UCSC; uc008wvt.2; mouse.
DR CTD; 1058; -.
DR MGI; MGI:88375; Cenpa.
DR VEuPathDB; HostDB:ENSMUSG00000029177; -.
DR eggNOG; KOG1745; Eukaryota.
DR GeneTree; ENSGT01050000244889; -.
DR HOGENOM; CLU_078295_3_2_1; -.
DR InParanoid; O35216; -.
DR OMA; VHLFEDC; -.
DR OrthoDB; 1564596at2759; -.
DR PhylomeDB; O35216; -.
DR TreeFam; TF354293; -.
DR Reactome; R-MMU-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
DR Reactome; R-MMU-2467813; Separation of Sister Chromatids.
DR Reactome; R-MMU-2500257; Resolution of Sister Chromatid Cohesion.
DR Reactome; R-MMU-5663220; RHO GTPases Activate Formins.
DR Reactome; R-MMU-606279; Deposition of new CENPA-containing nucleosomes at the centromere.
DR Reactome; R-MMU-68877; Mitotic Prometaphase.
DR Reactome; R-MMU-9648025; EML4 and NUDC in mitotic spindle formation.
DR BioGRID-ORCS; 12615; 26 hits in 78 CRISPR screens.
DR ChiTaRS; Cenpa; mouse.
DR PRO; PR:O35216; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; O35216; protein.
DR Bgee; ENSMUSG00000029177; Expressed in urogenital fold and 191 other tissues.
DR ExpressionAtlas; O35216; baseline and differential.
DR Genevisible; O35216; MM.
DR GO; GO:0043505; C:CENP-A containing nucleosome; ISO:MGI.
DR GO; GO:0000775; C:chromosome, centromeric region; IDA:MGI.
DR GO; GO:0000779; C:condensed chromosome, centromeric region; IDA:MGI.
DR GO; GO:0000939; C:inner kinetochore; IDA:MGI.
DR GO; GO:0000776; C:kinetochore; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0000786; C:nucleosome; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005721; C:pericentric heterochromatin; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:InterPro.
DR GO; GO:0030527; F:structural constituent of chromatin; IEA:InterPro.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; ISO:MGI.
DR GO; GO:0051382; P:kinetochore assembly; ISO:MGI.
DR GO; GO:0000281; P:mitotic cytokinesis; ISO:MGI.
DR GO; GO:0061644; P:protein localization to CENP-A containing chromatin; IC:ComplexPortal.
DR GO; GO:0071459; P:protein localization to chromosome, centromeric region; ISO:MGI.
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 Pfam; PF00125; Histone; 1.
DR PRINTS; PR00622; HISTONEH3.
DR SMART; SM00428; H3; 1.
DR SUPFAM; SSF47113; SSF47113; 1.
PE 2: Evidence at transcript level;
KW ADP-ribosylation; Centromere; Chromosome; DNA-binding; Kinetochore;
KW Methylation; Nucleosome core; Nucleus; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P49450"
FT CHAIN 2..134
FT /note="Histone H3-like centromeric protein A"
FT /id="PRO_0000221374"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 34..48
FT /note="Important for flexibility of DNA ends that protrude
FT from nucleosomes"
FT /evidence="ECO:0000250|UniProtKB:P49450"
FT REGION 35..134
FT /note="H3-like"
FT REGION 69..110
FT /note="CATD"
FT COMPBIAS 18..34
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N,N,N-trimethylglycine"
FT /evidence="ECO:0000250|UniProtKB:P49450"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49450"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49450"
FT MOD_RES 62
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49450"
SQ SEQUENCE 134 AA; 15509 MW; 0381FA6492E43C3D CRC64;
MGPRRKPQTP RRRPSSPAPG PSRQSSSVGS QTLRRRQKFM WLKEIKTLQK STDLLFRKKP
FSMVVREICE KFSRGVDFWW QAQALLALQE AAEAFLIHLF EDAYLLSLHA GRVTLFPKDI
QLTRRIRGFE GGLP
