EZHIP_MOUSE
ID EZHIP_MOUSE Reviewed; 589 AA.
AC B1B0V2; Q3TL73; Q3UWZ4; Q497U5;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 1.
DT 03-AUG-2022, entry version 80.
DE RecName: Full=EZH inhibitory protein {ECO:0000303|PubMed:31451685};
DE AltName: Full=K27M-like inhibitor of PRC2 {ECO:0000312|EMBL:QDN53947.1};
GN Name=Ezhip {ECO:0000303|PubMed:31451685, ECO:0000312|MGI:MGI:2147968};
GN Synonyms=AU022751 {ECO:0000312|MGI:MGI:2147968},
GN KIP75 {ECO:0000312|EMBL:QDN53947.1};
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 {ECO:0000312|Proteomes:UP000000589};
RN [1] {ECO:0000312|EMBL:QDN53947.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RX PubMed=31086175; DOI=10.1038/s41467-019-09981-6;
RA Jain S.U., Do T.J., Lund P.J., Rashoff A.Q., Diehl K.L., Cieslik M.,
RA Bajic A., Juretic N., Deshmukh S., Venneti S., Muir T.W., Garcia B.A.,
RA Jabado N., Lewis P.W.;
RT "PFA ependymoma-associated protein EZHIP inhibits PRC2 activity through a
RT H3 K27M-like mechanism.";
RL Nat. Commun. 10:2146-2146(2019).
RN [2] {ECO:0000312|Proteomes:UP000000589}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J {ECO:0000312|Proteomes:UP000000589};
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3] {ECO:0000312|EMBL:BAE22770.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE22770.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:BAE38919.1};
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 [4] {ECO:0000312|EMBL:AAI00378.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Oocyte {ECO:0000312|EMBL:AAI00378.1};
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 [5] {ECO:0007744|PubMed:21183079}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6] {ECO:0000305}
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH EZH1 AND
RP EZH2, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=31451685; DOI=10.1038/s41467-019-11800-x;
RA Ragazzini R., Perez-Palacios R., Baymaz I.H., Diop S., Ancelin K.,
RA Zielinski D., Michaud A., Givelet M., Borsos M., Aflaki S., Legoix P.,
RA Jansen P.W.T.C., Servant N., Torres-Padilla M.E., Bourc'his D., Fouchet P.,
RA Vermeulen M., Margueron R.;
RT "EZHIP constrains Polycomb Repressive Complex 2 activity in germ cells.";
RL Nat. Commun. 10:3858-3858(2019).
CC -!- FUNCTION: Inhibits PRC2/EED-EZH1 and PRC2/EED-EZH2 complex function by
CC inhibiting EZH1/EZH2 methyltransferase activity, thereby causing down-
CC regulation of histone H3 trimethylation at 'Lys-27' (H3K27me3)
CC (PubMed:31086175). Probably inhibits methyltransferase activity by
CC limiting the stimulatory effect of cofactors such as AEBP2 and JARID2
CC (By similarity). Inhibits H3K27me3 deposition during spermatogenesis
CC and oogenesis (PubMed:31451685). {ECO:0000250|UniProtKB:Q86X51,
CC ECO:0000269|PubMed:31086175, ECO:0000269|PubMed:31451685}.
CC -!- SUBUNIT: Interacts with PRC2/EED-EZH1 complex member EZH1 and with
CC PRC2/EED-EZH2 complex member EZH2; the interaction blocks EZH1/EZH2
CC methyltransferase activity (PubMed:31086175). Interacts (via C-
CC terminus) with SUZ12 which is a member of the PRC2/EED-EZH1 and
CC PRC2/EED-EZH2 complexes (By similarity). {ECO:0000250|UniProtKB:Q86X51,
CC ECO:0000269|PubMed:31086175}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q86X51}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q86X51}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=B1B0V2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=B1B0V2-2; Sequence=VSP_060652;
CC -!- TISSUE SPECIFICITY: Highly expressed in ovary with lower expression in
CC testis and very low levels in other tissues tested including prostate,
CC brain, kidney, spleen and liver (PubMed:31451685). During
CC spermatogenesis, expressed mainly in spermatogonia with very low
CC expression in spermatocytes I and II (PubMed:31451685).
CC {ECO:0000269|PubMed:31451685}.
CC -!- DISRUPTION PHENOTYPE: No overt developmental defects with mutant adults
CC appearing indistinguishable from wild-type (PubMed:31451685). Two-fold
CC increase in H3K27me2 and H3K27me3 levels in germ cells in testis but
CC males display normal testis-to-body weight ratio and normal fertility
CC (PubMed:31451685). Increased H3K27me3 levels in postnatal oocytes and
CC slight increase in the number of oocytes with lagging chromosomes
CC (PubMed:31451685). No significant differences in the number of
CC primordial, primary and secondary/antral follicles of pre-pubertal
CC females but older females show a reduced number of follicles at 16
CC weeks (PubMed:31451685). Females have smaller ovaries and give rise to
CC fewer progeny as they age (PubMed:31451685).
CC {ECO:0000269|PubMed:31451685}.
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DR EMBL; MK321328; QDN53947.1; -; mRNA.
DR EMBL; BX649475; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK136005; BAE22770.1; -; mRNA.
DR EMBL; AK166653; BAE38919.1; -; mRNA.
DR EMBL; BC100377; AAI00378.1; -; mRNA.
DR CCDS; CCDS52981.1; -. [B1B0V2-1]
DR CCDS; CCDS52982.1; -. [B1B0V2-2]
DR RefSeq; NP_001028383.2; NM_001033211.3. [B1B0V2-2]
DR RefSeq; NP_001159905.1; NM_001166433.1. [B1B0V2-1]
DR AlphaFoldDB; B1B0V2; -.
DR STRING; 10090.ENSMUSP00000114041; -.
DR iPTMnet; Q3TL73; -.
DR PhosphoSitePlus; B1B0V2; -.
DR PaxDb; B1B0V2; -.
DR PRIDE; B1B0V2; -.
DR ProteomicsDB; 330557; -. [B1B0V2-1]
DR ProteomicsDB; 338731; -.
DR Ensembl; ENSMUST00000101698; ENSMUSP00000099222; ENSMUSG00000073294. [B1B0V2-2]
DR Ensembl; ENSMUST00000117544; ENSMUSP00000114041; ENSMUSG00000073294. [B1B0V2-1]
DR GeneID; 102991; -.
DR KEGG; mmu:102991; -.
DR UCSC; uc009skv.2; mouse.
DR UCSC; uc012hdw.1; mouse. [B1B0V2-1]
DR CTD; 340602; -.
DR MGI; MGI:2147968; Ezhip.
DR VEuPathDB; HostDB:ENSMUSG00000073294; -.
DR GeneTree; ENSGT00730000112586; -.
DR HOGENOM; CLU_033305_0_0_1; -.
DR InParanoid; B1B0V2; -.
DR OMA; RETKMEP; -.
DR OrthoDB; 1393630at2759; -.
DR TreeFam; TF350538; -.
DR BioGRID-ORCS; 102991; 2 hits in 71 CRISPR screens.
DR PRO; PR:B1B0V2; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; B1B0V2; protein.
DR Bgee; ENSMUSG00000073294; Expressed in animal zygote and 15 other tissues.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:MGI.
DR GO; GO:0061086; P:negative regulation of histone H3-K27 methylation; ISO:MGI.
DR GO; GO:1902465; P:negative regulation of histone H3-K27 trimethylation; IMP:MGI.
DR GO; GO:0048599; P:oocyte development; IMP:MGI.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..589
FT /note="EZH inhibitory protein"
FT /id="PRO_0000450617"
FT REGION 1..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 61..548
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 482..490
FT /note="Sufficient for interaction with EZH2"
FT /evidence="ECO:0000250|UniProtKB:Q86X51"
FT REGION 484..503
FT /note="Necessary and sufficient for inhibition of PRC2/EED-
FT EZH1 and PRC2/EED-EZH2 complex activity"
FT /evidence="ECO:0000250|UniProtKB:Q86X51"
FT REGION 561..589
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 190..205
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 216..230
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 381..415
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 416..435
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 451..469
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 509..545
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 573..589
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86X51"
FT VAR_SEQ 62..182
FT /note="Missing (in isoform 2)"
FT /id="VSP_060652"
FT CONFLICT 341
FT /note="S -> G (in Ref. 3; BAE38919)"
FT /evidence="ECO:0000305"
FT CONFLICT 348
FT /note="P -> S (in Ref. 4; AAI00378)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 589 AA; 61798 MW; CFF3DFA06A89DA6F CRC64;
MASSSSPERG LEALRDTDES EGEAPGPSGP RGRGGPSGAG SALRLRSLEA EMAAACVTST
AGEDLGTFSE PGSQHGDPEG GGGPDLELGH ARPMMRSQRE LGLTPKGGGK ADQGGKGRKG
GSGSPPHTKS SRKREQPNPN RSLMAQGAAG PPLPGARGSP AMPQPESSLS PRPDQSHHFD
FPVGNLEAPG PTLRSSTSQG SGSTPVPEAL RCAESSRAES DQSSPAGREL RQQASPRAPD
DDDDGDGGPD PRGSGTPEGW VLRSGVVPFG RRSSASEVSP EEVRPEAQCT GWNLRPRPRS
SASAVSPEAR PKAQSAGRNL RPRPRSSASV VSPEARPKAQ SAGRNLRPRP RSSASVVSPE
ARPEAQSAGR NLRPRATPRV PVAPSSTTRS SSDRGSSRAP RSRSRSRSCS TPRLGSDHQR
SRKIKMRLDL QVDREPESEA EQEEQELESE PGPSSRPQAS RSSSRFAVPG RSSLAAEDSP
PRRPVRMRAS SPSPPGRLYP LPKHYFEGVH SPSSSSSESS SVSSSHSPLN KAPDPGSSPP
LSSLSGPNPF WLALIADLDN LDSSSPRVPG EEIEAAPHTR EEEDKKCRG
