CDYL_HUMAN
ID CDYL_HUMAN Reviewed; 598 AA.
AC Q9Y232; A8K6D6; B4DLG4; Q0VDG7; Q32NC5; Q5VX99; Q6P7T5; Q9BWZ2; Q9Y424;
DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2007, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Chromodomain Y-like protein {ECO:0000303|PubMed:10192397};
DE Short=CDY-like {ECO:0000303|PubMed:10192397};
DE AltName: Full=Crotonyl-CoA hydratase {ECO:0000303|PubMed:28803779};
DE EC=4.2.1.- {ECO:0000269|PubMed:28803779};
GN Name=CDYL {ECO:0000303|PubMed:10192397, ECO:0000312|HGNC:HGNC:1811};
GN Synonyms=CDYL1 {ECO:0000303|PubMed:19808672};
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 [MRNA] (ISOFORM 1), AND VARIANTS ALA-2; PRO-9; ALA-48
RP AND GLY-60.
RC TISSUE=Testis;
RX PubMed=10192397; DOI=10.1038/7771;
RA Lahn B.T., Page D.C.;
RT "Retroposition of autosomal mRNA yielded testis-specific gene family on
RT human Y chromosome.";
RL Nat. Genet. 21:429-433(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4).
RC TISSUE=Placenta, and Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 253-598 (ISOFORM 1).
RC TISSUE=Eye, and Uterus;
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 337-598.
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP CAUTION.
RX PubMed=12072557; DOI=10.1073/pnas.082248899;
RA Lahn B.T., Tang Z.L., Zhou J., Barndt R.J., Parvinen M., Allis C.D.,
RA Page D.C.;
RT "Previously uncharacterized histone acetyltransferases implicated in
RT mammalian spermatogenesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:8707-8712(2002).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=18450745; DOI=10.1074/jbc.m802655200;
RA Fischle W., Franz H., Jacobs S.A., Allis C.D., Khorasanizadeh S.;
RT "Specificity of the chromodomain Y chromosome family of chromodomains for
RT lysine-methylated ARK(S/T) motifs.";
RL J. Biol. Chem. 283:19626-19635(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [10]
RP FUNCTION, INTERACTION WITH REST; EHMT1 AND EHMT2, IDENTIFICATION IN A
RP COMPLEX WITH REST; WIZ; SETB1; EHMT1 AND EHMT2, AND IDENTIFICATION IN A
RP COMPLEX WITH MIER1; MIER2; HDAC1 AND HDAC2.
RX PubMed=19061646; DOI=10.1016/j.molcel.2008.10.025;
RA Mulligan P., Westbrook T.F., Ottinger M., Pavlova N., Chang B., Macia E.,
RA Shi Y.J., Barretina J., Liu J., Howley P.M., Elledge S.J., Shi Y.;
RT "CDYL bridges REST and histone methyltransferases for gene repression and
RT suppression of cellular transformation.";
RL Mol. Cell 32:718-726(2008).
RN [11]
RP METHYLATION AT LYS-135, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18438403; DOI=10.1038/nchembio.88;
RA Rathert P., Dhayalan A., Murakami M., Zhang X., Tamas R., Jurkowska R.,
RA Komatsu Y., Shinkai Y., Cheng X., Jeltsch A.;
RT "Protein lysine methyltransferase G9a acts on non-histone targets.";
RL Nat. Chem. Biol. 4:344-346(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88 AND SER-216, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP FUNCTION (ISOFORM2 1; 2 AND 3), SUBUNIT, SUBCELLULAR LOCATION, INTERACTION
RP WITH H3K9ME3, AND TISSUE SPECIFICITY.
RX PubMed=19808672; DOI=10.1074/jbc.m109.052332;
RA Franz H., Mosch K., Soeroes S., Urlaub H., Fischle W.;
RT "Multimerization and H3K9me3 binding are required for CDYL1b
RT heterochromatin association.";
RL J. Biol. Chem. 284:35049-35059(2009).
RN [14]
RP ERRATUM OF PUBMED:19808672.
RA Franz H., Mosch K., Soeroes S., Urlaub H., Fischle W.;
RL J. Biol. Chem. 285:11754-11754(2010).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-201 AND SER-216, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP FUNCTION, AND INTERACTION WITH HISTONE H3K9ME3; HISTONE H3K27ME2; HISTONE
RP H3K27ME3; EZH2; EED AND SUZ12.
RX PubMed=22009739; DOI=10.1074/jbc.m111.271064;
RA Zhang Y., Yang X., Gui B., Xie G., Zhang D., Shang Y., Liang J.;
RT "Corepressor protein CDYL functions as a molecular bridge between polycomb
RT repressor complex 2 and repressive chromatin mark trimethylated histone
RT lysine 27.";
RL J. Biol. Chem. 286:42414-42425(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-170; SER-201 AND SER-216, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-201, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [20]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CHAF1A; CHAF1B; MCM3
RP AND MCM5.
RX PubMed=28402439; DOI=10.1093/jmcb/mjx013;
RA Liu Y., Liu S., Yuan S., Yu H., Zhang Y., Yang X., Xie G., Chen Z., Li W.,
RA Xu B., Sun L., Shang Y., Liang J.;
RT "Chromodomain protein CDYL is required for transmission/restoration of
RT repressive histone marks.";
RL J. Mol. Cell Biol. 9:178-194(2017).
RN [21]
RP FUNCTION (ISOFORM 2), CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP AND MUTAGENESIS OF SER-521.
RX PubMed=28803779; DOI=10.1016/j.molcel.2017.07.011;
RA Liu S., Yu H., Liu Y., Liu X., Zhang Y., Bu C., Yuan S., Chen Z., Xie G.,
RA Li W., Xu B., Yang J., He L., Jin T., Xiong Y., Sun L., Liu X., Han C.,
RA Cheng Z., Liang J., Shang Y.;
RT "Chromodomain protein CDYL acts as a crotonyl-CoA hydratase to regulate
RT histone crotonylation and spermatogenesis.";
RL Mol. Cell 67:853-866(2017).
RN [22]
RP TISSUE SPECIFICITY.
RX PubMed=28842554; DOI=10.1038/s41467-017-00368-z;
RA Liu Y., Lai S., Ma W., Ke W., Zhang C., Liu S., Zhang Y., Pei F., Li S.,
RA Yi M., Shu Y., Shang Y., Liang J., Huang Z.;
RT "CDYL suppresses epileptogenesis in mice through repression of axonal
RT Nav1.6 sodium channel expression.";
RL Nat. Commun. 8:355-355(2017).
RN [23]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-205.
RX PubMed=29177481; DOI=10.1093/jmcb/mjx050;
RA Abu-Zhayia E.R., Awwad S.W., Ben-Oz B.M., Khoury-Haddad H., Ayoub N.;
RT "CDYL1 fosters double-strand break-induced transcription silencing and
RT promotes homology-directed repair.";
RL J. Mol. Cell Biol. 10:341-357(2018).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 338-598.
RX PubMed=19507244; DOI=10.1002/prot.22472;
RA Wu H., Min J., Antoshenko T., Plotnikov A.N.;
RT "Crystal structures of human CDY proteins reveal a crotonase-like fold.";
RL Proteins 76:1054-1061(2009).
RN [25]
RP STRUCTURE BY NMR OF 55-120.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of RSGI RUH-064, a chromo domain from human cDNA.";
RL Submitted (OCT-2006) to the PDB data bank.
CC -!- FUNCTION: [Isoform 2]: Chromatin reader protein that recognizes and
CC binds histone H3 trimethylated at 'Lys-9', dimethylated at 'Lys-27' and
CC trimethylated at 'Lys-27' (H3K9me3, H3K27me2 and H3K27me3,
CC respectively) (PubMed:19808672, PubMed:28402439). Part of multimeric
CC repressive chromatin complexes, where it is required for transmission
CC and restoration of repressive histone marks, thereby preserving the
CC epigenetic landscape (PubMed:28402439). Required for chromatin
CC targeting and maximal enzymatic activity of Polycomb repressive complex
CC 2 (PRC2); acts as a positive regulator of PRC2 activity by bridging the
CC pre-existing histone H3K27me3 and newly recruited PRC2 on neighboring
CC nucleosomes (PubMed:22009739). Acts as a corepressor for REST by
CC facilitating histone-lysine N-methyltransferase EHMT2 recruitment and
CC H3K9 dimethylation at REST target genes for repression
CC (PubMed:19061646). Involved in X chromosome inactivation in females:
CC recruited to Xist RNA-coated X chromosome and facilitates propagation
CC of H3K9me2 by anchoring EHMT2 (By similarity). Promotes EZH2
CC accumulation and H3K27me3 methylation at DNA double strand breaks
CC (DSBs), thereby facilitating transcriptional repression at sites of DNA
CC damage and homology-directed repair of DSBs (PubMed:29177481). Required
CC for neuronal migration during brain development by repressing
CC expression of RHOA (By similarity). By repressing the expression of
CC SCN8A, contributes to the inhibition of intrinsic neuronal excitability
CC and epileptogenesis (By similarity). In addition to acting as a
CC chromatin reader, acts as a hydro-lyase (PubMed:28803779). Shows
CC crotonyl-coA hydratase activity by mediating the conversion of
CC crotonyl-CoA ((2E)-butenoyl-CoA) to beta-hydroxybutyryl-CoA (3-
CC hydroxybutanoyl-CoA), thereby acting as a negative regulator of histone
CC crotonylation (PubMed:28803779). Histone crotonylation is required
CC during spermatogenesis; down-regulation of histone crotonylation by
CC CDYL regulates the reactivation of sex chromosome-linked genes in round
CC spermatids and histone replacement in elongating spermatids (By
CC similarity). By regulating histone crotonylation and trimethylation of
CC H3K27, may be involved in stress-induced depression-like behaviors,
CC possibly by regulating VGF expression (By similarity).
CC {ECO:0000250|UniProtKB:Q9WTK2, ECO:0000269|PubMed:19061646,
CC ECO:0000269|PubMed:19808672, ECO:0000269|PubMed:22009739,
CC ECO:0000269|PubMed:28402439, ECO:0000269|PubMed:28803779,
CC ECO:0000269|PubMed:29177481}.
CC -!- FUNCTION: [Isoform 1]: Not able to recognize and bind histone H3K9me3,
CC histone H3K27me2 and histone H3K27me3, due to the presence of a N-
CC terminal extension that inactivates the chromo domain
CC (PubMed:19808672). {ECO:0000269|PubMed:19808672}.
CC -!- FUNCTION: [Isoform 3]: Not able to recognize and bind histone H3K9me3,
CC histone H3K27me2 and histone H3K27me3, due to the absence of the chromo
CC domain (PubMed:19808672). Acts as a negative regulator of isoform 2 by
CC displacing isoform 2 from chromatin. {ECO:0000269|PubMed:19808672}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-hydroxybutanoyl-CoA = (2E)-butenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:45584, ChEBI:CHEBI:15377, ChEBI:CHEBI:57332,
CC ChEBI:CHEBI:78611; Evidence={ECO:0000269|PubMed:28803779};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=73.75 uM for (2E)-butenoyl-CoA {ECO:0000269|PubMed:28803779};
CC -!- SUBUNIT: Forms multimers and multimerization is required for stable
CC binding to chromatin (PubMed:19808672). Interacts with HDAC1 and HDAC2
CC via its C-terminal acetyl-CoA-binding domain (By similarity). Interacts
CC with EZH2, EED, SUZ12, REST, EHMT1 and EHMT2 (PubMed:19061646). Part of
CC a complex containing at least CDYL, REST, WIZ, SETB1, EHMT1 and EHMT2.
CC Part of a complex containing at least CDYL, MIER1, MIER2, HDAC1 and
CC HDAC2 (PubMed:22009739). Interacts with CHAF1A and CHAF1B; bridging the
CC CAF-1 complex to the MCM2-7 (MCM) complex (PubMed:28402439). Interacts
CC with MCM3 and MCM5; bridging the CAF-1 complex to the MCM2-7 (MCM)
CC complex (PubMed:28402439). Recruited to Xist RNA-coated X chromosome
CC (By similarity). Interacts with EHMT2 and PRDM9; interaction only takes
CC place when PRDM9 is bound to hotspot DNA (By similarity).
CC {ECO:0000250|UniProtKB:Q9WTK2, ECO:0000269|PubMed:19061646,
CC ECO:0000269|PubMed:19808672, ECO:0000269|PubMed:22009739,
CC ECO:0000269|PubMed:28402439}.
CC -!- INTERACTION:
CC Q9Y232; P51114: FXR1; NbExp=2; IntAct=EBI-1387386, EBI-713291;
CC Q9Y232; P68431: H3C12; NbExp=5; IntAct=EBI-1387386, EBI-79722;
CC Q9Y232-2; Q9Y232-2: CDYL; NbExp=3; IntAct=EBI-10986891, EBI-10986891;
CC Q9Y232-2; Q8N5M4: TTC9C; NbExp=3; IntAct=EBI-10986891, EBI-2851213;
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus
CC {ECO:0000269|PubMed:18450745, ECO:0000269|PubMed:19808672,
CC ECO:0000269|PubMed:29177481}. Chromosome {ECO:0000269|PubMed:19808672,
CC ECO:0000269|PubMed:29177481}. Note=Recognizes and binds histone H3
CC trimethylated at 'Lys-9', dimethylated at 'Lys-27' and trimethylated at
CC 'Lys-27' (H3K9me3, H3K27me2 and H3K27me3, respectively) on chromatin
CC (PubMed:19808672). Multimerization is required for chromatin-binding
CC (PubMed:19808672). Recruited to sites of DNA double strand breaks in a
CC PARP1-dependent fashion (PubMed:29177481).
CC {ECO:0000269|PubMed:19808672, ECO:0000269|PubMed:29177481}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=a {ECO:0000303|PubMed:19808672}, CDYL1a
CC {ECO:0000303|PubMed:19808672};
CC IsoId=Q9Y232-1; Sequence=Displayed;
CC Name=2; Synonyms=b {ECO:0000303|PubMed:19808672}, CDYL1b
CC {ECO:0000303|PubMed:19808672};
CC IsoId=Q9Y232-2; Sequence=VSP_026383, VSP_026384;
CC Name=3; Synonyms=c {ECO:0000303|PubMed:19808672}, CDYL1c
CC {ECO:0000303|PubMed:19808672};
CC IsoId=Q9Y232-3; Sequence=VSP_026382;
CC Name=4;
CC IsoId=Q9Y232-4; Sequence=VSP_041025;
CC -!- TISSUE SPECIFICITY: Expressed in the hippocampus with reduced
CC expression in epileptic tissue compared to normal adjacent tissue (at
CC protein level) (PubMed:28842554). Ubiquitous (PubMed:19808672).
CC Expressed at moderate levels in all tissues examined (PubMed:19808672).
CC Isoform 2: Most abundantly expressed isoform (PubMed:19808672).
CC {ECO:0000269|PubMed:19808672, ECO:0000269|PubMed:28842554}.
CC -!- DOMAIN: The chromo domain recognizes and binds histone H3K9me3, histone
CC H3K27me2 and histone H3K27me3. {ECO:0000305|PubMed:19808672}.
CC -!- DOMAIN: The acetyl-CoA-binding domain mediates crotonyl-coA hydratase
CC activity (PubMed:28803779). The acetyl-CoA-binding domain is required
CC for recruitment to sites of DNA double strand breaks and for binding to
CC poly (ADP ribose) moieties (PubMed:29177481).
CC {ECO:0000269|PubMed:28803779, ECO:0000269|PubMed:29177481}.
CC -!- MISCELLANEOUS: [Isoform 2]: Major isoform.
CC {ECO:0000269|PubMed:19808672}.
CC -!- CAUTION: Was initially reported to display histone acetyltransferase
CC activity, with a preference for histone H4 (PubMed:12072557). Such
CC activity is however unsure in vivo. Histone acetyltransferase activity
CC would be in contradiction with the function of the protein in
CC corepressor complexes (PubMed:19061646, PubMed:22009739). Moreover,
CC crystallographic studies demonstrated that it does not share any
CC similarity with other acetyltransferases and instead forms a crotonase-
CC like fold (PubMed:19507244). {ECO:0000269|PubMed:12072557,
CC ECO:0000269|PubMed:19061646, ECO:0000269|PubMed:19507244,
CC ECO:0000269|PubMed:22009739}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB43304.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};
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DR EMBL; AF081258; AAD22734.1; -; mRNA.
DR EMBL; AF081259; AAD22735.1; -; mRNA.
DR EMBL; AK291601; BAF84290.1; -; mRNA.
DR EMBL; AK296985; BAG59526.1; -; mRNA.
DR EMBL; AL022725; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356747; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359643; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC061516; AAH61516.1; -; mRNA.
DR EMBL; BC108725; AAI08726.1; -; mRNA.
DR EMBL; BC119682; AAI19683.1; -; mRNA.
DR EMBL; AL050164; CAB43304.1; ALT_SEQ; mRNA.
DR CCDS; CCDS4491.2; -. [Q9Y232-2]
DR CCDS; CCDS47364.1; -. [Q9Y232-4]
DR PIR; T08789; T08789.
DR RefSeq; NP_001137442.1; NM_001143970.1. [Q9Y232-4]
DR RefSeq; NP_001137443.1; NM_001143971.1. [Q9Y232-4]
DR RefSeq; NP_004815.3; NM_004824.3. [Q9Y232-2]
DR PDB; 2DNT; NMR; -; A=63-119.
DR PDB; 2GTR; X-ray; 1.90 A; A/B/C=338-598.
DR PDB; 7N27; X-ray; 1.85 A; A/B/C/D/E/F=62-113.
DR PDBsum; 2DNT; -.
DR PDBsum; 2GTR; -.
DR PDBsum; 7N27; -.
DR AlphaFoldDB; Q9Y232; -.
DR SMR; Q9Y232; -.
DR BioGRID; 114818; 85.
DR CORUM; Q9Y232; -.
DR IntAct; Q9Y232; 36.
DR MINT; Q9Y232; -.
DR STRING; 9606.ENSP00000380718; -.
DR BindingDB; Q9Y232; -.
DR ChEMBL; CHEMBL3879827; -.
DR iPTMnet; Q9Y232; -.
DR PhosphoSitePlus; Q9Y232; -.
DR BioMuta; CDYL; -.
DR DMDM; 150421527; -.
DR EPD; Q9Y232; -.
DR jPOST; Q9Y232; -.
DR MassIVE; Q9Y232; -.
DR MaxQB; Q9Y232; -.
DR PaxDb; Q9Y232; -.
DR PeptideAtlas; Q9Y232; -.
DR PRIDE; Q9Y232; -.
DR ProteomicsDB; 85621; -. [Q9Y232-1]
DR ProteomicsDB; 85622; -. [Q9Y232-2]
DR ProteomicsDB; 85623; -. [Q9Y232-3]
DR ProteomicsDB; 85624; -. [Q9Y232-4]
DR ABCD; Q9Y232; 2 sequenced antibodies.
DR Antibodypedia; 24514; 268 antibodies from 34 providers.
DR DNASU; 9425; -.
DR Ensembl; ENST00000328908.9; ENSP00000330512.5; ENSG00000153046.18. [Q9Y232-1]
DR Ensembl; ENST00000343762.5; ENSP00000340908.5; ENSG00000153046.18. [Q9Y232-4]
DR Ensembl; ENST00000397588.8; ENSP00000380718.3; ENSG00000153046.18. [Q9Y232-2]
DR Ensembl; ENST00000449732.6; ENSP00000394076.2; ENSG00000153046.18. [Q9Y232-4]
DR GeneID; 9425; -.
DR KEGG; hsa:9425; -.
DR MANE-Select; ENST00000397588.8; ENSP00000380718.3; NM_004824.4; NP_004815.3. [Q9Y232-2]
DR UCSC; uc003mwi.4; human. [Q9Y232-1]
DR CTD; 9425; -.
DR DisGeNET; 9425; -.
DR GeneCards; CDYL; -.
DR HGNC; HGNC:1811; CDYL.
DR HPA; ENSG00000153046; Low tissue specificity.
DR MIM; 603778; gene.
DR neXtProt; NX_Q9Y232; -.
DR OpenTargets; ENSG00000153046; -.
DR PharmGKB; PA26356; -.
DR VEuPathDB; HostDB:ENSG00000153046; -.
DR eggNOG; KOG0016; Eukaryota.
DR eggNOG; KOG1911; Eukaryota.
DR GeneTree; ENSGT00940000155106; -.
DR HOGENOM; CLU_009834_24_0_1; -.
DR InParanoid; Q9Y232; -.
DR OMA; VPRSPMN; -.
DR OrthoDB; 1471901at2759; -.
DR PhylomeDB; Q9Y232; -.
DR TreeFam; TF313375; -.
DR BRENDA; 4.2.1.150; 2681.
DR PathwayCommons; Q9Y232; -.
DR SignaLink; Q9Y232; -.
DR BioGRID-ORCS; 9425; 54 hits in 1094 CRISPR screens.
DR ChiTaRS; CDYL; human.
DR EvolutionaryTrace; Q9Y232; -.
DR GenomeRNAi; 9425; -.
DR Pharos; Q9Y232; Tchem.
DR PRO; PR:Q9Y232; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9Y232; protein.
DR Bgee; ENSG00000153046; Expressed in calcaneal tendon and 208 other tissues.
DR ExpressionAtlas; Q9Y232; baseline and differential.
DR Genevisible; Q9Y232; HS.
DR GO; GO:0005694; C:chromosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0120092; F:crotonyl-CoA hydratase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IPI:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IMP:UniProtKB.
DR GO; GO:0120094; P:negative regulation of peptidyl-lysine crotonylation; IDA:UniProtKB.
DR GO; GO:0060816; P:random inactivation of X chromosome; ISS:UniProtKB.
DR GO; GO:0007286; P:spermatid development; ISS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; TAS:ProtInc.
DR Gene3D; 1.10.12.10; -; 1.
DR InterPro; IPR016197; Chromo-like_dom_sf.
DR InterPro; IPR000953; Chromo/chromo_shadow_dom.
DR InterPro; IPR023780; Chromo_domain.
DR InterPro; IPR023779; Chromodomain_CS.
DR InterPro; IPR029045; ClpP/crotonase-like_dom_sf.
DR InterPro; IPR001753; Enoyl-CoA_hydra/iso.
DR InterPro; IPR014748; Enoyl-CoA_hydra_C.
DR Pfam; PF00385; Chromo; 1.
DR Pfam; PF00378; ECH_1; 1.
DR SMART; SM00298; CHROMO; 1.
DR SUPFAM; SSF52096; SSF52096; 1.
DR SUPFAM; SSF54160; SSF54160; 1.
DR PROSITE; PS00598; CHROMO_1; 1.
DR PROSITE; PS50013; CHROMO_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromosome; Differentiation; Lyase;
KW Methylation; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW Spermatogenesis; Transcription; Transcription regulation.
FT CHAIN 1..598
FT /note="Chromodomain Y-like protein"
FT /id="PRO_0000080221"
FT DOMAIN 61..121
FT /note="Chromo"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00053"
FT REGION 1..76
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 61..309
FT /note="Interaction with EZH2"
FT /evidence="ECO:0000269|PubMed:22009739"
FT REGION 112..149
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 204..226
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 362..594
FT /note="Acetyl-CoA-binding domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 27..59
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 123..149
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 88
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 135
FT /note="N6,N6,N6-trimethyllysine; by EHMT2; alternate"
FT /evidence="ECO:0000269|PubMed:18438403"
FT MOD_RES 135
FT /note="N6,N6-dimethyllysine; by EHMT2; alternate"
FT /evidence="ECO:0000269|PubMed:18438403"
FT MOD_RES 135
FT /note="N6-methyllysine; by EHMT2; alternate"
FT /evidence="ECO:0000269|PubMed:18438403"
FT MOD_RES 170
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 201
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 216
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..289
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_026382"
FT VAR_SEQ 1..186
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041025"
FT VAR_SEQ 1..54
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_026383"
FT VAR_SEQ 55..62
FT /note="AQQPPALQ -> MASEELYE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_026384"
FT VARIANT 2
FT /note="T -> A (in dbSNP:rs3812179)"
FT /evidence="ECO:0000269|PubMed:10192397"
FT /id="VAR_032936"
FT VARIANT 9
FT /note="S -> P (in dbSNP:rs3812178)"
FT /evidence="ECO:0000269|PubMed:10192397"
FT /id="VAR_032937"
FT VARIANT 48
FT /note="V -> A (in dbSNP:rs13196069)"
FT /evidence="ECO:0000269|PubMed:10192397"
FT /id="VAR_032938"
FT VARIANT 60
FT /note="A -> G (in dbSNP:rs28360500)"
FT /evidence="ECO:0000269|PubMed:10192397"
FT /id="VAR_032939"
FT MUTAGEN 205
FT /note="S->A: No impact on recruitment to DNA double strand
FT breaks."
FT /evidence="ECO:0000269|PubMed:29177481"
FT MUTAGEN 521
FT /note="S->A: Abolishes CoA-binding and ability to inhibit
FT histone crotonylation."
FT /evidence="ECO:0000269|PubMed:28803779"
FT CONFLICT 205
FT /note="S -> N (in Ref. 2; BAF84290)"
FT /evidence="ECO:0000305"
FT CONFLICT 291
FT /note="D -> N (in Ref. 2; BAG59526)"
FT /evidence="ECO:0000305"
FT CONFLICT 443
FT /note="V -> L (in Ref. 2; BAF84290)"
FT /evidence="ECO:0000305"
FT CONFLICT 558
FT /note="N -> S (in Ref. 2; BAG59526)"
FT /evidence="ECO:0000305"
FT CONFLICT 584
FT /note="M -> T (in Ref. 4; AAI19683)"
FT /evidence="ECO:0000305"
FT CONFLICT 591
FT /note="L -> M (in Ref. 4; AAI19683)"
FT /evidence="ECO:0000305"
FT STRAND 66..71
FT /evidence="ECO:0007829|PDB:2DNT"
FT STRAND 77..81
FT /evidence="ECO:0007829|PDB:2DNT"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:2DNT"
FT STRAND 92..95
FT /evidence="ECO:0007829|PDB:2DNT"
FT TURN 96..98
FT /evidence="ECO:0007829|PDB:2DNT"
FT HELIX 103..113
FT /evidence="ECO:0007829|PDB:2DNT"
FT STRAND 342..349
FT /evidence="ECO:0007829|PDB:2GTR"
FT STRAND 352..357
FT /evidence="ECO:0007829|PDB:2GTR"
FT STRAND 360..363
FT /evidence="ECO:0007829|PDB:2GTR"
FT HELIX 369..384
FT /evidence="ECO:0007829|PDB:2GTR"
FT STRAND 390..397
FT /evidence="ECO:0007829|PDB:2GTR"
FT HELIX 405..414
FT /evidence="ECO:0007829|PDB:2GTR"
FT HELIX 416..436
FT /evidence="ECO:0007829|PDB:2GTR"
FT STRAND 441..445
FT /evidence="ECO:0007829|PDB:2GTR"
FT HELIX 452..455
FT /evidence="ECO:0007829|PDB:2GTR"
FT HELIX 457..459
FT /evidence="ECO:0007829|PDB:2GTR"
FT STRAND 460..466
FT /evidence="ECO:0007829|PDB:2GTR"
FT STRAND 470..472
FT /evidence="ECO:0007829|PDB:2GTR"
FT TURN 475..479
FT /evidence="ECO:0007829|PDB:2GTR"
FT HELIX 486..494
FT /evidence="ECO:0007829|PDB:2GTR"
FT HELIX 496..505
FT /evidence="ECO:0007829|PDB:2GTR"
FT HELIX 511..516
FT /evidence="ECO:0007829|PDB:2GTR"
FT STRAND 521..524
FT /evidence="ECO:0007829|PDB:2GTR"
FT HELIX 526..528
FT /evidence="ECO:0007829|PDB:2GTR"
FT HELIX 529..541
FT /evidence="ECO:0007829|PDB:2GTR"
FT HELIX 545..556
FT /evidence="ECO:0007829|PDB:2GTR"
FT TURN 557..559
FT /evidence="ECO:0007829|PDB:2GTR"
FT HELIX 560..579
FT /evidence="ECO:0007829|PDB:2GTR"
FT TURN 581..584
FT /evidence="ECO:0007829|PDB:2GTR"
FT HELIX 585..596
FT /evidence="ECO:0007829|PDB:2GTR"
SQ SEQUENCE 598 AA; 66482 MW; A34E7221130626EC CRC64;
MTFQASHRSA WGKSRKKNWQ YEGPTQKLFL KRNNVSAPDG PSDPSISVSS EQSGAQQPPA
LQVERIVDKR KNKKGKTEYL VRWKGYDSED DTWEPEQHLV NCEEYIHDFN RRHTEKQKES
TLTRTNRTSP NNARKQISRS TNSNFSKTSP KALVIGKDHE SKNSQLFAAS QKFRKNTAPS
LSSRKNMDLA KSGIKILVPK SPVKSRTAVD GFQSESPEKL DPVEQGQEDT VAPEVAAEKP
VGALLGPGAE RARMGSRPRI HPLVPQVPGP VTAAMATGLA VNGKGTSPFM DALTANGTTN
IQTSVTGVTA SKRKFIDDRR DQPFDKRLRF SVRQTESAYR YRDIVVRKQD GFTHILLSTK
SSENNSLNPE VMREVQSALS TAAADDSKLV LLSAVGSVFC CGLDFIYFIR RLTDDRKRES
TKMAEAIRNF VNTFIQFKKP IIVAVNGPAI GLGASILPLC DVVWANEKAW FQTPYTTFGQ
SPDGCSTVMF PKIMGGASAN EMLLSGRKLT AQEACGKGLV SQVFWPGTFT QEVMVRIKEL
ASCNPVVLEE SKALVRCNMK MELEQANERE CEVLKKIWGS AQGMDSMLKY LQRKIDEF
