EZHIP_HUMAN
ID EZHIP_HUMAN Reviewed; 503 AA.
AC Q86X51;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=EZH inhibitory protein {ECO:0000305};
GN Name=EZHIP {ECO:0000312|HGNC:HGNC:33738};
GN Synonyms=CXorf67 {ECO:0000312|HGNC:HGNC:33738};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [4]
RP FUNCTION, INTERACTION WITH EZH2 AND SUZ12, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF THR-73; ILE-88 AND TYR-184.
RX PubMed=29909548; DOI=10.1007/s00401-018-1877-0;
RA Pajtler K.W., Wen J., Sill M., Lin T., Orisme W., Tang B., Huebner J.M.,
RA Ramaswamy V., Jia S., Dalton J.D., Haupfear K., Rogers H.A., Punchihewa C.,
RA Lee R., Easton J., Wu G., Ritzmann T.A., Chapman R., Chavez L., Boop F.A.,
RA Klimo P., Sabin N.D., Ogg R., Mack S.C., Freibaum B.D., Kim H.J., Witt H.,
RA Jones D.T.W., Vo B., Gajjar A., Pounds S., Onar-Thomas A., Roussel M.F.,
RA Zhang J., Taylor J.P., Merchant T.E., Grundy R., Tatevossian R.G.,
RA Taylor M.D., Pfister S.M., Korshunov A., Kool M., Ellison D.W.;
RT "Molecular heterogeneity and CXorf67 alterations in posterior fossa group A
RT (PFA) ependymomas.";
RL Acta Neuropathol. 136:211-226(2018).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH EZH2, REGION, AND
RP MUTAGENESIS OF ASP-81; ARG-405; MET-406 AND ARG-407.
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 [6]
RP FUNCTION, INTERACTION WITH EZH1 AND EZH2, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF 394-SER--PHE-417.
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).
RN [7]
RP FUNCTION, INTERACTION WITH EZH2 AND SUZ12, AND SUBCELLULAR LOCATION.
RX PubMed=30923826; DOI=10.1093/neuonc/noz058;
RA Huebner J.M., Mueller T., Papageorgiou D.N., Mauermann M., Krijgsveld J.,
RA Russell R.B., Ellison D.W., Pfister S.M., Pajtler K.W., Kool M.;
RT "EZHIP / CXorf67 mimics K27M mutated oncohistones and functions as an
RT intrinsic inhibitor of PRC2 function in aggressive posterior fossa
RT ependymoma.";
RL Neuro-oncol. 21:878-889(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 on 'Lys-27' (H3K27me3)
CC (PubMed:29909548, PubMed:31086175, PubMed:31451685, PubMed:30923826).
CC Probably inhibits methyltransferase activity by limiting the
CC stimulatory effect of cofactors such as AEBP2 and JARID2
CC (PubMed:30923826). Inhibits H3K27me3 deposition during spermatogenesis
CC and oogenesis (By similarity). {ECO:0000250|UniProtKB:B1B0V2,
CC ECO:0000269|PubMed:29909548, ECO:0000269|PubMed:30923826,
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:29909548, PubMed:31086175,
CC PubMed:31451685, PubMed:30923826). Interacts (via C-terminus) with
CC SUZ12 which is a member of the PRC2/EED-EZH1 and PRC2/EED-EZH2
CC complexes (PubMed:29909548, PubMed:30923826).
CC {ECO:0000269|PubMed:29909548, ECO:0000269|PubMed:30923826,
CC ECO:0000269|PubMed:31086175, ECO:0000269|PubMed:31451685}.
CC -!- INTERACTION:
CC Q86X51; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-12827735, EBI-744099;
CC Q86X51; Q9BWG6: SCNM1; NbExp=3; IntAct=EBI-12827735, EBI-748391;
CC Q86X51; Q9BUZ4: TRAF4; NbExp=3; IntAct=EBI-12827735, EBI-3650647;
CC Q86X51; Q8WV44: TRIM41; NbExp=3; IntAct=EBI-12827735, EBI-725997;
CC Q86X51; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-12827735, EBI-740727;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:29909548,
CC ECO:0000269|PubMed:30923826, ECO:0000269|PubMed:31086175}. Cytoplasm
CC {ECO:0000269|PubMed:30923826}.
CC -!- TISSUE SPECIFICITY: In testis, detected in male germ cells inside the
CC seminiferous tubules, especially in spermatogonia and round spermatids
CC (at protein level) (PubMed:31451685). In the ovary, expressed in
CC primordial follicles and oocytes but not the external follicle cells
CC (at protein level) (PubMed:31451685). {ECO:0000269|PubMed:31451685}.
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DR EMBL; CH471180; EAW89908.1; -; Genomic_DNA.
DR EMBL; BC046248; AAH46248.1; -; mRNA.
DR CCDS; CCDS78485.1; -.
DR RefSeq; NP_981952.1; NM_203407.2.
DR AlphaFoldDB; Q86X51; -.
DR BioGRID; 131086; 11.
DR IntAct; Q86X51; 7.
DR STRING; 9606.ENSP00000342680; -.
DR iPTMnet; Q86X51; -.
DR PhosphoSitePlus; Q86X51; -.
DR BioMuta; CXorf67; -.
DR DMDM; 74727770; -.
DR EPD; Q86X51; -.
DR MassIVE; Q86X51; -.
DR MaxQB; Q86X51; -.
DR PaxDb; Q86X51; -.
DR PeptideAtlas; Q86X51; -.
DR PRIDE; Q86X51; -.
DR ProteomicsDB; 70238; -.
DR Antibodypedia; 57010; 34 antibodies from 11 providers.
DR DNASU; 340602; -.
DR Ensembl; ENST00000342995.4; ENSP00000342680.2; ENSG00000187690.4.
DR GeneID; 340602; -.
DR KEGG; hsa:340602; -.
DR MANE-Select; ENST00000342995.4; ENSP00000342680.2; NM_203407.3; NP_981952.1.
DR UCSC; uc064zgx.1; human.
DR CTD; 340602; -.
DR DisGeNET; 340602; -.
DR GeneCards; EZHIP; -.
DR HGNC; HGNC:33738; EZHIP.
DR HPA; ENSG00000187690; Tissue enriched (testis).
DR MIM; 301036; gene.
DR neXtProt; NX_Q86X51; -.
DR OpenTargets; ENSG00000187690; -.
DR VEuPathDB; HostDB:ENSG00000187690; -.
DR eggNOG; ENOG502SFSJ; Eukaryota.
DR GeneTree; ENSGT00390000008621; -.
DR HOGENOM; CLU_028741_0_0_1; -.
DR InParanoid; Q86X51; -.
DR OMA; IRRCTAQ; -.
DR OrthoDB; 779527at2759; -.
DR PhylomeDB; Q86X51; -.
DR TreeFam; TF341924; -.
DR PathwayCommons; Q86X51; -.
DR SignaLink; Q86X51; -.
DR BioGRID-ORCS; 340602; 1 hit in 136 CRISPR screens.
DR GenomeRNAi; 340602; -.
DR Pharos; Q86X51; Tdark.
DR PRO; PR:Q86X51; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q86X51; protein.
DR Bgee; ENSG00000187690; Expressed in secondary oocyte and 57 other tissues.
DR ExpressionAtlas; Q86X51; baseline and differential.
DR Genevisible; Q86X51; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0061086; P:negative regulation of histone H3-K27 methylation; IDA:UniProtKB.
DR GO; GO:1902465; P:negative regulation of histone H3-K27 trimethylation; IBA:GO_Central.
PE 1: Evidence at protein level;
KW Cytoplasm; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..503
FT /note="EZH inhibitory protein"
FT /id="PRO_0000319058"
FT REGION 1..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 97..462
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 401..409
FT /note="Sufficient for interaction with EZH2"
FT /evidence="ECO:0000269|PubMed:30923826"
FT REGION 403..423
FT /note="Necessary and sufficient for inhibition of PRC2/EED-
FT EZH1 and PRC2/EED-EZH2 complex activity"
FT /evidence="ECO:0000269|PubMed:31086175"
FT REGION 483..503
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..16
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 17..72
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 164..180
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 181..201
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 332..390
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 423..462
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 259
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 470
FT /note="R -> K (in dbSNP:rs1875755)"
FT /id="VAR_038938"
FT MUTAGEN 73
FT /note="T->S: Decreases inhibition of H3K27me3."
FT /evidence="ECO:0000269|PubMed:29909548"
FT MUTAGEN 81
FT /note="D->Y: No effect on H3K27me3 levels."
FT /evidence="ECO:0000269|PubMed:31086175"
FT MUTAGEN 88
FT /note="I->F: Slightly decreases inhibition of H3K27me3."
FT /evidence="ECO:0000269|PubMed:29909548"
FT MUTAGEN 184
FT /note="Y->C: Decreases inhibition of H3K27me3."
FT /evidence="ECO:0000269|PubMed:29909548"
FT MUTAGEN 394..417
FT /note="Missing: Abolishes interaction with the PRC2 complex
FT and causes increased H3K27me3 levels."
FT /evidence="ECO:0000269|PubMed:31451685"
FT MUTAGEN 405
FT /note="R->E: Does not inhibit PRC2/EED-EZH2 complex
FT activity and abolishes ability to decrease H3K27me3
FT levels."
FT /evidence="ECO:0000269|PubMed:31086175"
FT MUTAGEN 406
FT /note="M->A: Does not act as a substrate of the PRC2/EED-
FT EZH2 complex."
FT /evidence="ECO:0000269|PubMed:31086175"
FT MUTAGEN 406
FT /note="M->E,R: Does not reduce H3K27me3 levels."
FT /evidence="ECO:0000269|PubMed:31086175"
FT MUTAGEN 406
FT /note="M->I: Does not affect inhibition of H3K27me3
FT levels."
FT /evidence="ECO:0000269|PubMed:31086175"
FT MUTAGEN 406
FT /note="M->K: Acts as a substrate of the PRC2/EED-EZH2
FT complex and does not reduce H3K27me3 levels."
FT /evidence="ECO:0000269|PubMed:31086175"
FT MUTAGEN 407
FT /note="R->E: No effect on H3K27me3 levels."
FT /evidence="ECO:0000269|PubMed:31086175"
SQ SEQUENCE 503 AA; 51894 MW; 7EF3E1DF72AAD497 CRC64;
MATQSDMEKE QKHQQDEGQG GLNNETALAS GDACGTGNQD PAASVTTVSS QASPSGGAAL
SSSTAGSSAA AATSAAIFIT DEASGLPIIA AVLTERHSDR QDCRSPHEVF GCVVPEGGSQ
AAVGPQKATG HADEHLAQTK SPGNSRRRKQ PCRNQAAPAQ KPPGRRLFPE PLPPSSPGFR
PSSYPCSGAS TSSQATQPGP ALLSHASEAR PATRSRITLV ASALRRRASG PGPVIRGCTA
QPGPAFPHRA THLDPARLSP ESAPGPARRG RASVPGPARR GCDSAPGPAR RGRDSAPVSA
PRGRDSAPGS ARRGRDSAPG PALRVRTARS DAGHRSTSTT PGTGLRSRST QQRSALLSRR
SLSGSADENP SCGTGSERLA FQSRSGSPDP EVPSRASPPV WHAVRMRASS PSPPGRFFLP
IPQQWDESSS SSYASNSSSP SRSPGLSPSS PSPEFLGLRS ISTPSPESLR YALMPEFYAL
SPVPPEEQAE IESTAHPATP PEP
