WDR5_HUMAN
ID WDR5_HUMAN Reviewed; 334 AA.
AC P61964; Q91VA5; Q9NWX7; Q9UGP9;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 1.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=WD repeat-containing protein 5;
DE AltName: Full=BMP2-induced 3-kb gene protein;
GN Name=WDR5; Synonyms=BIG3;
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].
RC TISSUE=Uterus;
RA Young J.M., Woodward K.J., Aziz S., Burley M., Kwiatkowski D.J., Povey S.;
RT "Cloning of a sugar transporter gene, a G-beta subunit like gene and three
RT novel genes in human chromosome 9q34.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 MRNA].
RC TISSUE=Lung;
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 INTERACTION WITH HCFC1.
RX PubMed=12670868; DOI=10.1101/gad.252103;
RA Wysocka J., Myers M.P., Laherty C.D., Eisenman R.N., Herr W.;
RT "Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4
RT methyltransferase are tethered together selectively by the cell-
RT proliferation factor HCF-1.";
RL Genes Dev. 17:896-911(2003).
RN [5]
RP IDENTIFICATION IN THE MEN1-ASSOCIATED HISTONE METHYLTRANSFERASE COMPLEX.
RX PubMed=14992727; DOI=10.1016/s1097-2765(04)00081-4;
RA Hughes C.M., Rozenblatt-Rosen O., Milne T.A., Copeland T.D., Levine S.S.,
RA Lee J.C., Hayes D.N., Shanmugam K.S., Bhattacharjee A., Biondi C.A.,
RA Kay G.F., Hayward N.K., Hess J.L., Meyerson M.;
RT "Menin associates with a trithorax family histone methyltransferase complex
RT and with the hoxc8 locus.";
RL Mol. Cell 13:587-597(2004).
RN [6]
RP IDENTIFICATION IN THE MLL-LIKE COMPLEX.
RX PubMed=15199122; DOI=10.1128/mcb.24.13.5639-5649.2004;
RA Yokoyama A., Wang Z., Wysocka J., Sanyal M., Aufiero D.J., Kitabayashi I.,
RA Herr W., Cleary M.L.;
RT "Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase
RT complex with menin to regulate Hox gene expression.";
RL Mol. Cell. Biol. 24:5639-5649(2004).
RN [7]
RP IDENTIFICATION IN THE SET1 COMPLEX.
RX PubMed=16253997; DOI=10.1074/jbc.m508312200;
RA Lee J.-H., Skalnik D.G.;
RT "CpG-binding protein (CXXC finger protein 1) is a component of the
RT mammalian Set1 histone H3-Lys4 methyltransferase complex, the analogue of
RT the yeast Set1/COMPASS complex.";
RL J. Biol. Chem. 280:41725-41731(2005).
RN [8]
RP IDENTIFICATION IN THE MLL1/MLL COMPLEX.
RX PubMed=15960975; DOI=10.1016/j.cell.2005.04.031;
RA Dou Y., Milne T.A., Tackett A.J., Smith E.R., Fukuda A., Wysocka J.,
RA Allis C.D., Chait B.T., Hess J.L., Roeder R.G.;
RT "Physical association and coordinate function of the H3 K4
RT methyltransferase MLL1 and the H4 K16 acetyltransferase MOF.";
RL Cell 121:873-885(2005).
RN [9]
RP IDENTIFICATION IN THE MLL2/3 (ASCOM) COMPLEX.
RX PubMed=17021013; DOI=10.1073/pnas.0607313103;
RA Lee S., Lee D.K., Dou Y., Lee J., Lee B., Kwak E., Kong Y.Y., Lee S.K.,
RA Roeder R.G., Lee J.W.;
RT "Coactivator as a target gene specificity determinant for histone H3 lysine
RT 4 methyltransferases.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:15392-15397(2006).
RN [10]
RP SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE SET1 COMPLEX.
RX PubMed=17355966; DOI=10.1074/jbc.m609809200;
RA Lee J.-H., Tate C.M., You J.-S., Skalnik D.G.;
RT "Identification and characterization of the human Set1B histone H3-Lys4
RT methyltransferase complex.";
RL J. Biol. Chem. 282:13419-13428(2007).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MLL2/3
RP COMPLEX.
RX PubMed=17500065; DOI=10.1074/jbc.m701574200;
RA Cho Y.-W., Hong T., Hong S., Guo H., Yu H., Kim D., Guszczynski T.,
RA Dressler G.R., Copeland T.D., Kalkum M., Ge K.;
RT "PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4
RT methyltransferase complex.";
RL J. Biol. Chem. 282:20395-20406(2007).
RN [12]
RP IDENTIFICATION IN SET1 COMPLEX, AND INTERACTION WITH SETD1A.
RX PubMed=17998332; DOI=10.1128/mcb.01356-07;
RA Lee J.H., Skalnik D.G.;
RT "Wdr82 is a C-terminal domain-binding protein that recruits the Setd1A
RT Histone H3-Lys4 methyltransferase complex to transcription start sites of
RT transcribed human genes.";
RL Mol. Cell. Biol. 28:609-618(2008).
RN [13]
RP IDENTIFICATION IN A COMPLEX WITH CHD8.
RX PubMed=18378692; DOI=10.1128/mcb.00322-08;
RA Thompson B.A., Tremblay V., Lin G., Bochar D.A.;
RT "CHD8 is an ATP-dependent chromatin remodeling factor that regulates beta-
RT catenin target genes.";
RL Mol. Cell. Biol. 28:3894-3904(2008).
RN [14]
RP IDENTIFICATION IN SET1 COMPLEX.
RX PubMed=18838538; DOI=10.1128/mcb.00976-08;
RA Wu M., Wang P.F., Lee J.S., Martin-Brown S., Florens L., Washburn M.,
RA Shilatifard A.;
RT "Molecular regulation of H3K4 trimethylation by Wdr82, a component of human
RT Set1/COMPASS.";
RL Mol. Cell. Biol. 28:7337-7344(2008).
RN [15]
RP FUNCTION, IDENTIFICATION IN A HISTONE METHYLATION COMPLEX, AND INTERACTION
RP WITH ZNF335.
RX PubMed=19131338; DOI=10.1074/jbc.m805872200;
RA Garapaty S., Xu C.F., Trojer P., Mahajan M.A., Neubert T.A., Samuels H.H.;
RT "Identification and characterization of a novel nuclear protein complex
RT involved in nuclear hormone receptor-mediated gene regulation.";
RL J. Biol. Chem. 284:7542-7552(2009).
RN [16]
RP FUNCTION, CHARACTERIZATION OF THE MLL1/MLL COMPLEX, AND INTERACTION WITH
RP KMT2A AND RBBP5.
RX PubMed=19556245; DOI=10.1074/jbc.m109.014498;
RA Patel A., Dharmarajan V., Vought V.E., Cosgrove M.S.;
RT "On the mechanism of multiple lysine methylation by the human mixed lineage
RT leukemia protein-1 (MLL1) core complex.";
RL J. Biol. Chem. 284:24242-24256(2009).
RN [17]
RP FUNCTION, AND IDENTIFICATION IN ATAC COMPLEX.
RX PubMed=19103755; DOI=10.1128/mcb.01599-08;
RA Guelman S., Kozuka K., Mao Y., Pham V., Solloway M.J., Wang J., Wu J.,
RA Lill J.R., Zha J.;
RT "The double-histone-acetyltransferase complex ATAC is essential for
RT mammalian development.";
RL Mol. Cell. Biol. 29:1176-1188(2009).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-112, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [19]
RP FUNCTION IN HISTONE H4 ACETYLATION, IDENTIFICATION IN NSL COMPLEX, AND
RP SUBCELLULAR LOCATION.
RX PubMed=20018852; DOI=10.1074/jbc.c109.087981;
RA Cai Y., Jin J., Swanson S.K., Cole M.D., Choi S.H., Florens L.,
RA Washburn M.P., Conaway J.W., Conaway R.C.;
RT "Subunit composition and substrate specificity of a MOF-containing histone
RT acetyltransferase distinct from the male-specific lethal (MSL) complex.";
RL J. Biol. Chem. 285:4268-4272(2010).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP INTERACTION WITH ZNF335.
RX PubMed=23178126; DOI=10.1016/j.cell.2012.10.043;
RA Yang Y.J., Baltus A.E., Mathew R.S., Murphy E.A., Evrony G.D.,
RA Gonzalez D.M., Wang E.P., Marshall-Walker C.A., Barry B.J., Murn J.,
RA Tatarakis A., Mahajan M.A., Samuels H.H., Shi Y., Golden J.A., Mahajnah M.,
RA Shenhav R., Walsh C.A.;
RT "Microcephaly gene links trithorax and REST/NRSF to control neural stem
RT cell proliferation and differentiation.";
RL Cell 151:1097-1112(2012).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [23]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-7; LYS-27 AND LYS-46, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH HISTONE H3 PEPTIDE,
RP AND INTERACTION WITH HISTONE H3.
RX PubMed=16946699; DOI=10.1038/sj.emboj.7601316;
RA Schuetz A., Allali-Hassani A., Martin F., Loppnau P., Vedadi M.,
RA Bochkarev A., Plotnikov A.N., Arrowsmith C.H., Min J.;
RT "Structural basis for molecular recognition and presentation of histone H3
RT by WDR5.";
RL EMBO J. 25:4245-4252(2006).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 27-334 IN COMPLEX WITH HISTONE H3
RP PEPTIDE, INTERACTION WITH HISTONE H3, MUTAGENESIS OF ALA-47; SER-91;
RP ASP-107; PHE-133 AND GLU-322, AND FUNCTION.
RX PubMed=16600877; DOI=10.1016/j.molcel.2006.03.018;
RA Han Z., Guo L., Wang H., Shen Y., Deng X.W., Chai J.;
RT "Structural basis for the specific recognition of methylated histone H3
RT lysine 4 by the WD-40 protein WDR5.";
RL Mol. Cell 22:137-144(2006).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) OF 22-334 IN COMPLEX WITH HISTONE H3
RP PEPTIDE, INTERACTION WITH HISTONE H3, MUTAGENESIS OF ASP-107; PHE-133;
RP PHE-263 AND LEU-321, AND FUNCTION.
RX PubMed=16829960; DOI=10.1038/nsmb1116;
RA Couture J.F., Collazo E., Trievel R.C.;
RT "Molecular recognition of histone H3 by the WD40 protein WDR5.";
RL Nat. Struct. Mol. Biol. 13:698-703(2006).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 20-334 IN COMPLEX WITH HISTONE H3
RP PEPTIDE, AND INTERACTION WITH HISTONE H3.
RX PubMed=16829959; DOI=10.1038/nsmb1119;
RA Ruthenburg A.J., Wang W., Graybosch D.M., Li H., Allis C.D., Patel D.J.,
RA Verdine G.L.;
RT "Histone H3 recognition and presentation by the WDR5 module of the MLL1
RT complex.";
RL Nat. Struct. Mol. Biol. 13:704-712(2006).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 23-334 IN COMPLEX WITH KMT2A.
RX PubMed=18829459; DOI=10.1074/jbc.c800164200;
RA Patel A., Dharmarajan V., Cosgrove M.S.;
RT "Structure of WDR5 bound to mixed lineage leukemia protein-1 peptide.";
RL J. Biol. Chem. 283:32158-32161(2008).
RN [29] {ECO:0007744|PDB:3EMH}
RP X-RAY CRYSTALLOGRAPHY (1.37 ANGSTROMS) OF 25-334 IN COMPLEX WITH KMT2A,
RP FUNCTION, INTERACTION WITH KMT2A AND KMT2B, AND MUTAGENESIS OF ASP-107;
RP PHE-133; PHE-149; PHE-263 AND GLU-322.
RX PubMed=18840606; DOI=10.1074/jbc.m806900200;
RA Song J.J., Kingston R.E.;
RT "WDR5 interacts with mixed lineage leukemia (MLL) protein via the histone
RT H3-binding pocket.";
RL J. Biol. Chem. 283:35258-35264(2008).
RN [30] {ECO:0007744|PDB:3P4F}
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 22-334 IN COMPLEX WITH KMT2A AND
RP RBBP5, FUNCTION, INTERACTION WITH RBBP5, AND MUTAGENESIS OF ASN-225;
RP LEU-240 AND GLN-289.
RX PubMed=21220120; DOI=10.1016/j.str.2010.09.022;
RA Avdic V., Zhang P., Lanouette S., Groulx A., Tremblay V., Brunzelle J.,
RA Couture J.F.;
RT "Structural and biochemical insights into MLL1 core complex assembly.";
RL Structure 19:101-108(2011).
RN [31] {ECO:0007744|PDB:4ERQ, ECO:0007744|PDB:4ERY, ECO:0007744|PDB:4ERZ, ECO:0007744|PDB:4ES0, ECO:0007744|PDB:4ESG, ECO:0007744|PDB:4EWR}
RP X-RAY CRYSTALLOGRAPHY (1.30 ANGSTROMS) OF 23-334 IN COMPLEX WITH KMT2A;
RP KMT2B; KMT2C; KMT2D; SETD1A AND SETD1B, AND INTERACTION WITH KMT2A; KMT2B;
RP KMT2C; KMT2D; SETD1A AND SETD1B.
RX PubMed=22665483; DOI=10.1074/jbc.m112.364125;
RA Dharmarajan V., Lee J.H., Patel A., Skalnik D.G., Cosgrove M.S.;
RT "Structural basis for WDR5 interaction (Win) motif recognition in human
RT SET1 family histone methyltransferases.";
RL J. Biol. Chem. 287:27275-27289(2012).
RN [32] {ECO:0007744|PDB:3UVK, ECO:0007744|PDB:3UVL, ECO:0007744|PDB:3UVM, ECO:0007744|PDB:3UVN, ECO:0007744|PDB:3UVO}
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 21-334 IN COMPLEX WITH KMT2B;
RP KMT2C; KMT2D; SETD1A AND SETD1B, INTERACTION WITH KMT2B; KMT2C; KMT2D;
RP SETD1A AND SETD1B, AND FUNCTION.
RX PubMed=22266653; DOI=10.1093/nar/gkr1235;
RA Zhang P., Lee H., Brunzelle J.S., Couture J.F.;
RT "The plasticity of WDR5 peptide-binding cleft enables the binding of the
RT SET1 family of histone methyltransferases.";
RL Nucleic Acids Res. 40:4237-4246(2012).
RN [33]
RP VARIANT MET-208.
RX PubMed=29463886; DOI=10.1038/s41380-018-0020-x;
RA Eising E., Carrion-Castillo A., Vino A., Strand E.A., Jakielski K.J.,
RA Scerri T.S., Hildebrand M.S., Webster R., Ma A., Mazoyer B., Francks C.,
RA Bahlo M., Scheffer I.E., Morgan A.T., Shriberg L.D., Fisher S.E.;
RT "A set of regulatory genes co-expressed in embryonic human brain is
RT implicated in disrupted speech development.";
RL Mol. Psychiatry 24:1065-1078(2019).
CC -!- FUNCTION: Contributes to histone modification (PubMed:19131338,
CC PubMed:19556245, PubMed:19103755, PubMed:20018852, PubMed:16600877,
CC PubMed:16829960). May position the N-terminus of histone H3 for
CC efficient trimethylation at 'Lys-4' (PubMed:16829960). As part of the
CC MLL1/MLL complex it is involved in methylation and dimethylation at
CC 'Lys-4' of histone H3 (PubMed:19556245). H3 'Lys-4' methylation
CC represents a specific tag for epigenetic transcriptional activation
CC (PubMed:18840606). As part of the NSL complex it may be involved in
CC acetylation of nucleosomal histone H4 on several lysine residues
CC (PubMed:19103755, PubMed:20018852). May regulate osteoblasts
CC differentiation (By similarity). In association with RBBP5 and ASH2L,
CC stimulates the histone methyltransferase activities of KMT2A, KMT2B,
CC KMT2C, KMT2D, SETD1A and SETD1B (PubMed:21220120, PubMed:22266653).
CC {ECO:0000250|UniProtKB:P61965, ECO:0000269|PubMed:16600877,
CC ECO:0000269|PubMed:16829960, ECO:0000269|PubMed:18840606,
CC ECO:0000269|PubMed:19103755, ECO:0000269|PubMed:19131338,
CC ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:20018852,
CC ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:22266653}.
CC -!- SUBUNIT: Interacts with PAXBP1; the interaction is direct and links a
CC WDR5-containing histone methyltransferase complex to PAX7 and PAX3 (By
CC similarity). Interacts with HCFC1 (PubMed:12670868). Component of the
CC ATAC complex, a complex with histone acetyltransferase activity on
CC histones H3 and H4 (PubMed:19103755). Component of the SET1 complex, at
CC least composed of the catalytic subunit (SETD1A or SETD1B), WDR5,
CC WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30 (PubMed:16253997,
CC PubMed:17355966, PubMed:17998332, PubMed:18838538). Core component of
CC several methyltransferase-containing complexes including MLL1/MLL,
CC MLL2/3 (also named ASCOM complex) and MLL4/WBP7 (PubMed:15199122,
CC PubMed:15960975, PubMed:17021013, PubMed:17500065). Each complex is at
CC least composed of ASH2L, RBBP5, WDR5, DPY30, one or more specific
CC histone methyltransferases (KMT2A/MLL1, KMT2D/MLL2, KMT2C/MLL3 and
CC KMT2B/MLL4), and the facultative components PAGR1, BAP18, CHD8, E2F6,
CC HCFC1, HCFC2, HSP70, INO80C, KDM6A, KANSL1, LAS1L, MAX, MCRS1, MEN1,
CC MGA, MYST1/MOF, NCOA6, PAXIP1/PTIP, PELP1, PHF20, PRP31, RING2,
CC RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9, TEX10
CC and alpha- and beta-tubulin (PubMed:14992727, PubMed:18378692).
CC Component of the NSL complex at least composed of MOF/KAT8, KANSL1,
CC KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1
CC (PubMed:20018852). Interacts with KMT2A/MLL1 (via WIN motif) and RBBP5;
CC the interaction is direct (PubMed:19556245, PubMed:21220120,
CC PubMed:22665483, PubMed:22266653, PubMed:18840606, PubMed:18829459).
CC Component of the ADA2A-containing complex (ATAC), composed of KAT14,
CC KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1
CC (PubMed:19103755). In the complex, it probably interacts directly with
CC KAT2A, MBIP and KAT14 (PubMed:19103755). Interacts with histone H3
CC (PubMed:16946699, PubMed:16600877, PubMed:16829960, PubMed:16829959).
CC Interacts with SETD1A (via WIN motif) (PubMed:17998332,
CC PubMed:22665483, PubMed:22266653). Component of a histone methylation
CC complex composed of at least ZNF335, RBBP5, ASH2L and WDR5; the complex
CC may have histone H3-specific methyltransferase activity, however does
CC not have specificity for 'Lys-4' of histone H3 (PubMed:19131338).
CC Interacts with ZNF335 (PubMed:19131338, PubMed:23178126). Components of
CC this complex may associate with components of the ZNF335-CCAR2-EMSY
CC nuclear receptor-mediated transcription complex to form a complex at
CC least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and
CC WDR5 (PubMed:19131338). Interacts with PER1 (By similarity). Interacts
CC with KMT2B (via WIN motif), KMT2C (via WIN motif), KMT2D (via WIN
CC motif) and SETD1B (via WIN motif) (PubMed:22665483, PubMed:22266653,
CC PubMed:18840606). {ECO:0000250|UniProtKB:P61965,
CC ECO:0000250|UniProtKB:Q498M4, ECO:0000269|PubMed:12670868,
CC ECO:0000269|PubMed:14992727, ECO:0000269|PubMed:15199122,
CC ECO:0000269|PubMed:15960975, ECO:0000269|PubMed:16253997,
CC ECO:0000269|PubMed:16600877, ECO:0000269|PubMed:16829959,
CC ECO:0000269|PubMed:16829960, ECO:0000269|PubMed:16946699,
CC ECO:0000269|PubMed:17021013, ECO:0000269|PubMed:17355966,
CC ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:17998332,
CC ECO:0000269|PubMed:18378692, ECO:0000269|PubMed:18829459,
CC ECO:0000269|PubMed:18838538, ECO:0000269|PubMed:18840606,
CC ECO:0000269|PubMed:19103755, ECO:0000269|PubMed:19131338,
CC ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:20018852,
CC ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:22266653,
CC ECO:0000269|PubMed:22665483, ECO:0000269|PubMed:23178126}.
CC -!- INTERACTION:
CC P61964; O43823: AKAP8; NbExp=3; IntAct=EBI-540834, EBI-1237481;
CC P61964; Q9UJX6: ANAPC2; NbExp=3; IntAct=EBI-540834, EBI-396211;
CC P61964; P54259: ATN1; NbExp=4; IntAct=EBI-540834, EBI-945980;
CC P61964; Q86V38: ATN1; NbExp=3; IntAct=EBI-540834, EBI-11954292;
CC P61964; Q96PG8: BBC3; NbExp=3; IntAct=EBI-540834, EBI-17289784;
CC P61964; Q8NFC6: BOD1L1; NbExp=4; IntAct=EBI-540834, EBI-2654318;
CC P61964; A2RRG2: C1orf104; NbExp=3; IntAct=EBI-540834, EBI-10173042;
CC P61964; Q9HCK8: CHD8; NbExp=3; IntAct=EBI-540834, EBI-1169146;
CC P61964; Q14204: DYNC1H1; NbExp=3; IntAct=EBI-540834, EBI-356015;
CC P61964; Q6PEV8: FAM199X; NbExp=4; IntAct=EBI-540834, EBI-4280426;
CC P61964; P68431: H3C12; NbExp=11; IntAct=EBI-540834, EBI-79722;
CC P61964; P51610: HCFC1; NbExp=6; IntAct=EBI-540834, EBI-396176;
CC P61964; Q03933: HSF2; NbExp=7; IntAct=EBI-540834, EBI-2556750;
CC P61964; Q7Z3B3: KANSL1; NbExp=12; IntAct=EBI-540834, EBI-740244;
CC P61964; Q9H9L4: KANSL2; NbExp=4; IntAct=EBI-540834, EBI-2560840;
CC P61964; Q92794: KAT6A; NbExp=4; IntAct=EBI-540834, EBI-948013;
CC P61964; O15550: KDM6A; NbExp=6; IntAct=EBI-540834, EBI-4292203;
CC P61964; Q92876: KLK6; NbExp=3; IntAct=EBI-540834, EBI-2432309;
CC P61964; Q03164: KMT2A; NbExp=14; IntAct=EBI-540834, EBI-591370;
CC P61964; PRO_0000390950 [Q03164]: KMT2A; NbExp=2; IntAct=EBI-540834, EBI-2638616;
CC P61964; Q9UMN6: KMT2B; NbExp=7; IntAct=EBI-540834, EBI-765774;
CC P61964; Q8NEZ4: KMT2C; NbExp=5; IntAct=EBI-540834, EBI-1042997;
CC P61964; O14686: KMT2D; NbExp=9; IntAct=EBI-540834, EBI-996065;
CC P61964; Q9Y4F3: MARF1; NbExp=6; IntAct=EBI-540834, EBI-5235902;
CC P61964; Q7Z434-1: MAVS; NbExp=3; IntAct=EBI-540834, EBI-15577799;
CC P61964; Q9NS73: MBIP; NbExp=6; IntAct=EBI-540834, EBI-741953;
CC P61964; Q9NS73-5: MBIP; NbExp=4; IntAct=EBI-540834, EBI-10182361;
CC P61964; O15151: MDM4; NbExp=3; IntAct=EBI-540834, EBI-398437;
CC P61964; O00255: MEN1; NbExp=4; IntAct=EBI-540834, EBI-592789;
CC P61964; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-540834, EBI-16439278;
CC P61964; Q14686: NCOA6; NbExp=9; IntAct=EBI-540834, EBI-78670;
CC P61964; Q9Y5X4: NR2E3; NbExp=5; IntAct=EBI-540834, EBI-7216962;
CC P61964; Q6ZW49: PAXIP1; NbExp=10; IntAct=EBI-540834, EBI-743225;
CC P61964; O76083-2: PDE9A; NbExp=3; IntAct=EBI-540834, EBI-11524542;
CC P61964; Q15291: RBBP5; NbExp=15; IntAct=EBI-540834, EBI-592823;
CC P61964; A7MD48: SRRM4; NbExp=3; IntAct=EBI-540834, EBI-3867173;
CC P61964; Q9Y2D8: SSX2IP; NbExp=3; IntAct=EBI-540834, EBI-2212028;
CC P61964; Q9NYB0: TERF2IP; NbExp=2; IntAct=EBI-540834, EBI-750109;
CC P61964; Q13114: TRAF3; NbExp=2; IntAct=EBI-540834, EBI-357631;
CC P61964; Q9Y4K3: TRAF6; NbExp=2; IntAct=EBI-540834, EBI-359276;
CC P61964; O00308: WWP2; NbExp=3; IntAct=EBI-540834, EBI-743923;
CC P61964; P10074: ZBTB48; NbExp=3; IntAct=EBI-540834, EBI-744864;
CC P61964; Q2QGD7: ZXDC; NbExp=5; IntAct=EBI-540834, EBI-1538838;
CC P61964; Q8IYH5: ZZZ3; NbExp=3; IntAct=EBI-540834, EBI-2795524;
CC P61964; Q9H891; NbExp=3; IntAct=EBI-540834, EBI-10218875;
CC P61964; Q9WTL8: Arntl; Xeno; NbExp=2; IntAct=EBI-540834, EBI-644534;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17355966,
CC ECO:0000269|PubMed:20018852}.
CC -!- SIMILARITY: Belongs to the WD repeat WDR5/wds family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB66159.1; Type=Erroneous initiation; Note=Extended N-terminus.; 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; AJ011376; CAB66159.1; ALT_INIT; mRNA.
DR EMBL; AK000552; BAA91248.1; -; mRNA.
DR EMBL; BC001635; AAH01635.1; -; mRNA.
DR CCDS; CCDS6981.1; -.
DR RefSeq; NP_060058.1; NM_017588.2.
DR RefSeq; NP_438172.1; NM_052821.3.
DR RefSeq; XP_005272220.1; XM_005272163.1.
DR PDB; 2CNX; X-ray; 2.10 A; A=20-334.
DR PDB; 2CO0; X-ray; 2.25 A; A/C=20-334.
DR PDB; 2G99; X-ray; 1.90 A; A/B=27-334.
DR PDB; 2G9A; X-ray; 2.70 A; A=29-334.
DR PDB; 2GNQ; X-ray; 1.80 A; A=1-334.
DR PDB; 2H13; X-ray; 1.58 A; A=22-334.
DR PDB; 2H14; X-ray; 1.48 A; A=22-334.
DR PDB; 2H68; X-ray; 1.79 A; A/B=23-334.
DR PDB; 2H6K; X-ray; 1.89 A; A/B=23-334.
DR PDB; 2H6N; X-ray; 1.50 A; A/B=23-334.
DR PDB; 2H6Q; X-ray; 1.87 A; A/B=23-334.
DR PDB; 2H9L; X-ray; 1.75 A; A=24-334.
DR PDB; 2H9M; X-ray; 1.90 A; A/C=24-334.
DR PDB; 2H9N; X-ray; 2.00 A; A/C=24-334.
DR PDB; 2H9P; X-ray; 1.91 A; A=24-334.
DR PDB; 2O9K; X-ray; 1.90 A; A/C=24-334.
DR PDB; 3EG6; X-ray; 1.72 A; A=23-334.
DR PDB; 3EMH; X-ray; 1.37 A; A=25-334.
DR PDB; 3MXX; X-ray; 2.05 A; A=31-334.
DR PDB; 3N0D; X-ray; 2.30 A; A=31-334.
DR PDB; 3N0E; X-ray; 2.50 A; A=31-334.
DR PDB; 3P4F; X-ray; 2.35 A; A=22-334.
DR PDB; 3PSL; X-ray; 1.70 A; A/B=21-334.
DR PDB; 3SMR; X-ray; 1.82 A; A/B/C/D=24-334.
DR PDB; 3UR4; X-ray; 1.80 A; A/B=24-334.
DR PDB; 3UVK; X-ray; 1.40 A; A=21-334.
DR PDB; 3UVL; X-ray; 2.20 A; A=21-334.
DR PDB; 3UVM; X-ray; 1.57 A; A=21-334.
DR PDB; 3UVN; X-ray; 1.79 A; A/C=21-334.
DR PDB; 3UVO; X-ray; 2.20 A; A=21-334.
DR PDB; 4A7J; X-ray; 1.90 A; A=21-334.
DR PDB; 4CY1; X-ray; 1.50 A; A/B=23-334.
DR PDB; 4CY2; X-ray; 2.00 A; A=23-334.
DR PDB; 4ERQ; X-ray; 1.91 A; A/B/C=23-334.
DR PDB; 4ERY; X-ray; 1.30 A; A=23-334.
DR PDB; 4ERZ; X-ray; 1.75 A; A/B/C=23-334.
DR PDB; 4ES0; X-ray; 1.82 A; A=23-334.
DR PDB; 4ESG; X-ray; 1.70 A; A/B=23-334.
DR PDB; 4EWR; X-ray; 1.50 A; A=23-334.
DR PDB; 4GM3; X-ray; 3.39 A; A/B/C/D/E/F/G/H=22-334.
DR PDB; 4GM8; X-ray; 2.60 A; A/B/C/D=22-334.
DR PDB; 4GM9; X-ray; 2.10 A; A/B=22-334.
DR PDB; 4GMB; X-ray; 2.78 A; A=22-334.
DR PDB; 4IA9; X-ray; 1.66 A; A=24-334.
DR PDB; 4O45; X-ray; 1.87 A; A=24-334.
DR PDB; 4QL1; X-ray; 1.50 A; A/B=24-334.
DR PDB; 4Y7R; X-ray; 1.90 A; A=22-334.
DR PDB; 5EAL; X-ray; 1.80 A; A/B=24-334.
DR PDB; 5EAM; X-ray; 1.80 A; A/B=24-334.
DR PDB; 5EAP; X-ray; 1.73 A; A=24-334.
DR PDB; 5EAR; X-ray; 1.80 A; A/B=24-334.
DR PDB; 5M23; X-ray; 1.97 A; A=22-334.
DR PDB; 5M25; X-ray; 2.43 A; A=22-334.
DR PDB; 5SXM; X-ray; 2.00 A; A/B=23-334.
DR PDB; 5VFC; X-ray; 1.64 A; A=24-334.
DR PDB; 6BYN; X-ray; 2.69 A; W=31-334.
DR PDB; 6D9X; X-ray; 1.83 A; A=22-334.
DR PDB; 6DAI; X-ray; 1.63 A; A=22-334.
DR PDB; 6DAK; X-ray; 1.60 A; A=22-334.
DR PDB; 6DAR; X-ray; 1.88 A; A=22-334.
DR PDB; 6DAS; X-ray; 1.80 A; A/B=22-334.
DR PDB; 6DY7; X-ray; 1.90 A; A=31-334.
DR PDB; 6DYA; X-ray; 2.56 A; A=30-334.
DR PDB; 6E1Y; X-ray; 1.22 A; A/B=22-334.
DR PDB; 6E1Z; X-ray; 1.10 A; A/B=22-334.
DR PDB; 6E22; X-ray; 1.60 A; A/B=22-334.
DR PDB; 6E23; X-ray; 1.66 A; A/B=22-334.
DR PDB; 6IAM; X-ray; 1.51 A; A=29-334.
DR PDB; 6KIU; EM; 3.20 A; R=1-334.
DR PDB; 6KIV; EM; 4.00 A; R=1-334.
DR PDB; 6KIW; EM; 4.00 A; R=1-334.
DR PDB; 6KIX; EM; 4.10 A; R=1-334.
DR PDB; 6KIZ; EM; 4.50 A; R=1-334.
DR PDB; 6OFZ; X-ray; 1.85 A; A=22-334.
DR PDB; 6OI0; X-ray; 1.92 A; A=22-334.
DR PDB; 6OI1; X-ray; 1.68 A; A=22-334.
DR PDB; 6OI2; X-ray; 1.68 A; A=22-334.
DR PDB; 6OI3; X-ray; 1.66 A; A=22-334.
DR PDB; 6PG3; X-ray; 2.04 A; A/B=22-334.
DR PDB; 6PG4; X-ray; 1.60 A; A=32-334.
DR PDB; 6PG5; X-ray; 1.99 A; A=32-334.
DR PDB; 6PG6; X-ray; 1.68 A; A/B=22-334.
DR PDB; 6PG7; X-ray; 2.45 A; A=32-334.
DR PDB; 6PG8; X-ray; 1.67 A; A/B/C/D=22-334.
DR PDB; 6PG9; X-ray; 1.75 A; A/B=22-334.
DR PDB; 6PGA; X-ray; 2.45 A; A=32-334.
DR PDB; 6PGB; X-ray; 1.73 A; A=32-334.
DR PDB; 6PGC; X-ray; 1.81 A; A=32-334.
DR PDB; 6PGD; X-ray; 1.50 A; A=32-334.
DR PDB; 6PGE; X-ray; 1.76 A; A=32-334.
DR PDB; 6PGF; X-ray; 1.54 A; A=32-334.
DR PDB; 6PWV; EM; 6.20 A; B=22-334.
DR PDB; 6PWW; EM; 4.40 A; B=22-334.
DR PDB; 6U5M; X-ray; 1.80 A; A/B=31-334.
DR PDB; 6U5Y; X-ray; 1.53 A; A/B=31-334.
DR PDB; 6U6W; X-ray; 1.20 A; A/B=24-334.
DR PDB; 6U80; X-ray; 1.55 A; A/B=24-334.
DR PDB; 6U8B; X-ray; 1.26 A; A/B=24-334.
DR PDB; 6U8L; X-ray; 1.57 A; A/B=31-334.
DR PDB; 6U8O; X-ray; 1.60 A; A=31-334.
DR PDB; 6UCS; X-ray; 1.85 A; A/B=22-334.
DR PDB; 6UFX; X-ray; 2.02 A; A=32-334.
DR PDB; 6UHY; X-ray; 1.26 A; A/B=31-334.
DR PDB; 6UHZ; X-ray; 1.26 A; A/B=31-334.
DR PDB; 6UIF; X-ray; 1.60 A; A/B=31-334.
DR PDB; 6UIK; X-ray; 1.60 A; A/B=31-334.
DR PDB; 6UJ4; X-ray; 1.53 A; A/B=31-334.
DR PDB; 6UJH; X-ray; 1.49 A; A/B=22-334.
DR PDB; 6UJJ; X-ray; 1.73 A; A=22-334.
DR PDB; 6UJL; X-ray; 1.60 A; A=22-334.
DR PDB; 6UOZ; X-ray; 1.53 A; A/B=31-334.
DR PDB; 6W5I; EM; 6.90 A; B=22-334.
DR PDB; 6W5M; EM; 4.60 A; B=22-334.
DR PDB; 6W5N; EM; 6.00 A; B=22-334.
DR PDB; 6WJQ; X-ray; 2.71 A; A/B=22-334.
DR PDB; 7AXP; X-ray; 2.43 A; A=1-334.
DR PDB; 7AXQ; X-ray; 1.56 A; A=1-334.
DR PDB; 7AXS; X-ray; 1.88 A; A=1-334.
DR PDB; 7AXU; X-ray; 1.68 A; A=1-334.
DR PDB; 7AXX; X-ray; 1.79 A; A=1-334.
DR PDB; 7BCY; X-ray; 1.50 A; A/B=25-334.
DR PDB; 7BED; X-ray; 1.26 A; A/B=1-334.
DR PDB; 7CFP; X-ray; 1.60 A; A=1-334.
DR PDB; 7CFQ; X-ray; 1.60 A; A=1-334.
DR PDB; 7DNO; X-ray; 2.03 A; A/B=24-334.
DR PDB; 7JTO; X-ray; 1.70 A; B=31-334.
DR PDB; 7JTP; X-ray; 2.12 A; A=31-334.
DR PDB; 7MBM; EM; -; B=22-334.
DR PDB; 7MBN; EM; -; B=22-334.
DR PDB; 7Q2J; X-ray; 2.50 A; D=24-334.
DR PDBsum; 2CNX; -.
DR PDBsum; 2CO0; -.
DR PDBsum; 2G99; -.
DR PDBsum; 2G9A; -.
DR PDBsum; 2GNQ; -.
DR PDBsum; 2H13; -.
DR PDBsum; 2H14; -.
DR PDBsum; 2H68; -.
DR PDBsum; 2H6K; -.
DR PDBsum; 2H6N; -.
DR PDBsum; 2H6Q; -.
DR PDBsum; 2H9L; -.
DR PDBsum; 2H9M; -.
DR PDBsum; 2H9N; -.
DR PDBsum; 2H9P; -.
DR PDBsum; 2O9K; -.
DR PDBsum; 3EG6; -.
DR PDBsum; 3EMH; -.
DR PDBsum; 3MXX; -.
DR PDBsum; 3N0D; -.
DR PDBsum; 3N0E; -.
DR PDBsum; 3P4F; -.
DR PDBsum; 3PSL; -.
DR PDBsum; 3SMR; -.
DR PDBsum; 3UR4; -.
DR PDBsum; 3UVK; -.
DR PDBsum; 3UVL; -.
DR PDBsum; 3UVM; -.
DR PDBsum; 3UVN; -.
DR PDBsum; 3UVO; -.
DR PDBsum; 4A7J; -.
DR PDBsum; 4CY1; -.
DR PDBsum; 4CY2; -.
DR PDBsum; 4ERQ; -.
DR PDBsum; 4ERY; -.
DR PDBsum; 4ERZ; -.
DR PDBsum; 4ES0; -.
DR PDBsum; 4ESG; -.
DR PDBsum; 4EWR; -.
DR PDBsum; 4GM3; -.
DR PDBsum; 4GM8; -.
DR PDBsum; 4GM9; -.
DR PDBsum; 4GMB; -.
DR PDBsum; 4IA9; -.
DR PDBsum; 4O45; -.
DR PDBsum; 4QL1; -.
DR PDBsum; 4Y7R; -.
DR PDBsum; 5EAL; -.
DR PDBsum; 5EAM; -.
DR PDBsum; 5EAP; -.
DR PDBsum; 5EAR; -.
DR PDBsum; 5M23; -.
DR PDBsum; 5M25; -.
DR PDBsum; 5SXM; -.
DR PDBsum; 5VFC; -.
DR PDBsum; 6BYN; -.
DR PDBsum; 6D9X; -.
DR PDBsum; 6DAI; -.
DR PDBsum; 6DAK; -.
DR PDBsum; 6DAR; -.
DR PDBsum; 6DAS; -.
DR PDBsum; 6DY7; -.
DR PDBsum; 6DYA; -.
DR PDBsum; 6E1Y; -.
DR PDBsum; 6E1Z; -.
DR PDBsum; 6E22; -.
DR PDBsum; 6E23; -.
DR PDBsum; 6IAM; -.
DR PDBsum; 6KIU; -.
DR PDBsum; 6KIV; -.
DR PDBsum; 6KIW; -.
DR PDBsum; 6KIX; -.
DR PDBsum; 6KIZ; -.
DR PDBsum; 6OFZ; -.
DR PDBsum; 6OI0; -.
DR PDBsum; 6OI1; -.
DR PDBsum; 6OI2; -.
DR PDBsum; 6OI3; -.
DR PDBsum; 6PG3; -.
DR PDBsum; 6PG4; -.
DR PDBsum; 6PG5; -.
DR PDBsum; 6PG6; -.
DR PDBsum; 6PG7; -.
DR PDBsum; 6PG8; -.
DR PDBsum; 6PG9; -.
DR PDBsum; 6PGA; -.
DR PDBsum; 6PGB; -.
DR PDBsum; 6PGC; -.
DR PDBsum; 6PGD; -.
DR PDBsum; 6PGE; -.
DR PDBsum; 6PGF; -.
DR PDBsum; 6PWV; -.
DR PDBsum; 6PWW; -.
DR PDBsum; 6U5M; -.
DR PDBsum; 6U5Y; -.
DR PDBsum; 6U6W; -.
DR PDBsum; 6U80; -.
DR PDBsum; 6U8B; -.
DR PDBsum; 6U8L; -.
DR PDBsum; 6U8O; -.
DR PDBsum; 6UCS; -.
DR PDBsum; 6UFX; -.
DR PDBsum; 6UHY; -.
DR PDBsum; 6UHZ; -.
DR PDBsum; 6UIF; -.
DR PDBsum; 6UIK; -.
DR PDBsum; 6UJ4; -.
DR PDBsum; 6UJH; -.
DR PDBsum; 6UJJ; -.
DR PDBsum; 6UJL; -.
DR PDBsum; 6UOZ; -.
DR PDBsum; 6W5I; -.
DR PDBsum; 6W5M; -.
DR PDBsum; 6W5N; -.
DR PDBsum; 6WJQ; -.
DR PDBsum; 7AXP; -.
DR PDBsum; 7AXQ; -.
DR PDBsum; 7AXS; -.
DR PDBsum; 7AXU; -.
DR PDBsum; 7AXX; -.
DR PDBsum; 7BCY; -.
DR PDBsum; 7BED; -.
DR PDBsum; 7CFP; -.
DR PDBsum; 7CFQ; -.
DR PDBsum; 7DNO; -.
DR PDBsum; 7JTO; -.
DR PDBsum; 7JTP; -.
DR PDBsum; 7MBM; -.
DR PDBsum; 7MBN; -.
DR PDBsum; 7Q2J; -.
DR AlphaFoldDB; P61964; -.
DR SASBDB; P61964; -.
DR SMR; P61964; -.
DR BioGRID; 116272; 966.
DR ComplexPortal; CPX-1004; PCAF-containing ATAC complex.
DR ComplexPortal; CPX-5850; Histone-lysine N-methyltransferase complex, KMT2A variant.
DR ComplexPortal; CPX-7062; Histone-lysine N-methyltransferase complex, KMT2B variant.
DR ComplexPortal; CPX-7091; Histone-lysine N-methyltransferase complex, KMT2C variant.
DR ComplexPortal; CPX-7104; Histone-lysine N-methyltransferase complex, KMT2D variant.
DR ComplexPortal; CPX-7110; Histone-lysine N-methyltransferase complex, SET1A variant.
DR ComplexPortal; CPX-7111; Histone-lysine N-methyltransferase complex, SET1B variant.
DR ComplexPortal; CPX-809; NSL histone acetyltransferase complex.
DR ComplexPortal; CPX-997; GCN5-containing ATAC complex.
DR CORUM; P61964; -.
DR DIP; DIP-29223N; -.
DR ELM; P61964; -.
DR IntAct; P61964; 196.
DR MINT; P61964; -.
DR STRING; 9606.ENSP00000351446; -.
DR BindingDB; P61964; -.
DR ChEMBL; CHEMBL1075317; -.
DR GuidetoPHARMACOLOGY; 2831; -.
DR GlyGen; P61964; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P61964; -.
DR PhosphoSitePlus; P61964; -.
DR SwissPalm; P61964; -.
DR BioMuta; WDR5; -.
DR DMDM; 48429182; -.
DR EPD; P61964; -.
DR jPOST; P61964; -.
DR MassIVE; P61964; -.
DR MaxQB; P61964; -.
DR PaxDb; P61964; -.
DR PeptideAtlas; P61964; -.
DR PRIDE; P61964; -.
DR ProteomicsDB; 57347; -.
DR ABCD; P61964; 4 sequenced antibodies.
DR Antibodypedia; 31978; 441 antibodies from 42 providers.
DR DNASU; 11091; -.
DR Ensembl; ENST00000358625.4; ENSP00000351446.3; ENSG00000196363.10.
DR GeneID; 11091; -.
DR KEGG; hsa:11091; -.
DR MANE-Select; ENST00000358625.4; ENSP00000351446.3; NM_017588.3; NP_060058.1.
DR UCSC; uc004cey.4; human.
DR CTD; 11091; -.
DR DisGeNET; 11091; -.
DR GeneCards; WDR5; -.
DR HGNC; HGNC:12757; WDR5.
DR HPA; ENSG00000196363; Low tissue specificity.
DR MIM; 609012; gene.
DR neXtProt; NX_P61964; -.
DR OpenTargets; ENSG00000196363; -.
DR PharmGKB; PA37361; -.
DR VEuPathDB; HostDB:ENSG00000196363; -.
DR eggNOG; KOG0266; Eukaryota.
DR GeneTree; ENSGT00940000154143; -.
DR HOGENOM; CLU_000288_57_1_1; -.
DR InParanoid; P61964; -.
DR OMA; RLWNYHT; -.
DR OrthoDB; 957291at2759; -.
DR PhylomeDB; P61964; -.
DR TreeFam; TF314125; -.
DR PathwayCommons; P61964; -.
DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines.
DR Reactome; R-HSA-3214847; HATs acetylate histones.
DR Reactome; R-HSA-3214858; RMTs methylate histone arginines.
DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis.
DR Reactome; R-HSA-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR Reactome; R-HSA-8951664; Neddylation.
DR SignaLink; P61964; -.
DR SIGNOR; P61964; -.
DR BioGRID-ORCS; 11091; 694 hits in 1097 CRISPR screens.
DR ChiTaRS; WDR5; human.
DR EvolutionaryTrace; P61964; -.
DR GeneWiki; WDR5; -.
DR GenomeRNAi; 11091; -.
DR Pharos; P61964; Tchem.
DR PRO; PR:P61964; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P61964; protein.
DR Bgee; ENSG00000196363; Expressed in upper arm skin and 180 other tissues.
DR ExpressionAtlas; P61964; baseline and differential.
DR Genevisible; P61964; HS.
DR GO; GO:0140672; C:ATAC complex; IDA:BHF-UCL.
DR GO; GO:0000123; C:histone acetyltransferase complex; IDA:UniProtKB.
DR GO; GO:0035097; C:histone methyltransferase complex; IDA:UniProtKB.
DR GO; GO:0072686; C:mitotic spindle; IC:ComplexPortal.
DR GO; GO:0071339; C:MLL1 complex; IDA:UniProtKB.
DR GO; GO:0044665; C:MLL1/2 complex; IPI:ComplexPortal.
DR GO; GO:0044666; C:MLL3/4 complex; IDA:UniProtKB.
DR GO; GO:0044545; C:NSL complex; IDA:ComplexPortal.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0048188; C:Set1C/COMPASS complex; IDA:UniProtKB.
DR GO; GO:0042393; F:histone binding; IBA:GO_Central.
DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0006094; P:gluconeogenesis; IEA:Ensembl.
DR GO; GO:0043966; P:histone H3 acetylation; IDA:BHF-UCL.
DR GO; GO:0044154; P:histone H3-K14 acetylation; IDA:ComplexPortal.
DR GO; GO:0051568; P:histone H3-K4 methylation; IDA:UniProtKB.
DR GO; GO:0043984; P:histone H4-K16 acetylation; IDA:UniProtKB.
DR GO; GO:0043981; P:histone H4-K5 acetylation; IDA:UniProtKB.
DR GO; GO:0043982; P:histone H4-K8 acetylation; IDA:UniProtKB.
DR GO; GO:0051572; P:negative regulation of histone H3-K4 methylation; IDA:CACAO.
DR GO; GO:0031175; P:neuron projection development; IEA:Ensembl.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; IEA:Ensembl.
DR GO; GO:0051571; P:positive regulation of histone H3-K4 methylation; IDA:ComplexPortal.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IC:ComplexPortal.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:ComplexPortal.
DR GO; GO:0051302; P:regulation of cell division; IDA:ComplexPortal.
DR GO; GO:1900095; P:regulation of dosage compensation by inactivation of X chromosome; IEA:Ensembl.
DR GO; GO:0045995; P:regulation of embryonic development; IC:ComplexPortal.
DR GO; GO:0031063; P:regulation of histone deacetylation; IMP:ComplexPortal.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:ComplexPortal.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:ComplexPortal.
DR GO; GO:0090043; P:regulation of tubulin deacetylation; IMP:ComplexPortal.
DR GO; GO:0001501; P:skeletal system development; IEA:Ensembl.
DR Gene3D; 2.130.10.10; -; 1.
DR IDEAL; IID00377; -.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF00400; WD40; 7.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00320; WD40; 7.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 4.
DR PROSITE; PS50082; WD_REPEATS_2; 6.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Chromatin regulator; Disease variant;
KW Isopeptide bond; Nucleus; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Ubl conjugation; WD repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..334
FT /note="WD repeat-containing protein 5"
FT /id="PRO_0000051350"
FT REPEAT 43..82
FT /note="WD 1"
FT REPEAT 85..126
FT /note="WD 2"
FT REPEAT 128..168
FT /note="WD 3"
FT REPEAT 169..208
FT /note="WD 4"
FT REPEAT 212..253
FT /note="WD 5"
FT REPEAT 256..296
FT /note="WD 6"
FT REPEAT 299..333
FT /note="WD 7"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 14..31
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 107
FT /note="Important for interaction with histone H3"
FT SITE 133
FT /note="Important for interaction with histone H3"
FT SITE 263
FT /note="Important for interaction with histone H3"
FT SITE 322
FT /note="Important for interaction with histone H3"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 112
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT CROSSLNK 7
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 27
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 46
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 208
FT /note="T -> M (de novo variant found in a patient with
FT childhood apraxia of speech; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:29463886"
FT /id="VAR_081531"
FT MUTAGEN 47
FT /note="A->E: Strongly reduced affinity for histone H3."
FT /evidence="ECO:0000269|PubMed:16600877"
FT MUTAGEN 91
FT /note="S->F: Strongly reduced affinity for histone H3."
FT /evidence="ECO:0000269|PubMed:16600877"
FT MUTAGEN 107
FT /note="D->A: Strongly reduced affinity for histone H3.
FT Significant decrease in interaction with KMT2A."
FT /evidence="ECO:0000269|PubMed:16600877,
FT ECO:0000269|PubMed:16829960, ECO:0000269|PubMed:18840606"
FT MUTAGEN 107
FT /note="D->N: Strongly reduced affinity for histone H3."
FT /evidence="ECO:0000269|PubMed:16829960"
FT MUTAGEN 133
FT /note="F->A: Strongly reduced affinity for histone H3.
FT Significant decrease in interaction with KMT2A."
FT /evidence="ECO:0000269|PubMed:16829960,
FT ECO:0000269|PubMed:18840606"
FT MUTAGEN 133
FT /note="F->D: Strongly reduced affinity for histone H3."
FT /evidence="ECO:0000269|PubMed:16600877"
FT MUTAGEN 133
FT /note="F->L: Strongly reduced affinity for histone H3."
FT /evidence="ECO:0000269|PubMed:16829960"
FT MUTAGEN 149
FT /note="F->A: Significant decrease in interaction with
FT KMT2A."
FT /evidence="ECO:0000269|PubMed:18840606"
FT MUTAGEN 225
FT /note="N->A: Loss of interaction with RBBP5 and reduced
FT ability to stimulate KMT2A methyltransferase activity in
FT association with RBBP5 and ASH2L."
FT /evidence="ECO:0000269|PubMed:21220120"
FT MUTAGEN 240
FT /note="L->K: Loss of interaction with RBBP5 and reduced
FT ability to stimulate KMT2A methyltransferase activity in
FT association with RBBP5 and ASH2L."
FT /evidence="ECO:0000269|PubMed:21220120"
FT MUTAGEN 263
FT /note="F->A: Strongly reduced affinity for histone H3.
FT Significant decrease in interaction with KMT2A."
FT /evidence="ECO:0000269|PubMed:16829960,
FT ECO:0000269|PubMed:18840606"
FT MUTAGEN 263
FT /note="F->W: Strongly reduced affinity for histone H3."
FT /evidence="ECO:0000269|PubMed:16829960"
FT MUTAGEN 289
FT /note="Q->A: Reduced interaction with RBBP5 and reduced
FT ability to stimulate KMT2A methyltransferase activity in
FT association with RBBP5 and ASH2L."
FT /evidence="ECO:0000269|PubMed:21220120"
FT MUTAGEN 321
FT /note="L->A: Abolishes histone H3 binding."
FT /evidence="ECO:0000269|PubMed:16829960"
FT MUTAGEN 322
FT /note="E->A: Strongly reduced affinity for histone H3. No
FT effect on interaction with KMT2A."
FT /evidence="ECO:0000269|PubMed:16600877,
FT ECO:0000269|PubMed:18840606"
FT HELIX 13..15
FT /evidence="ECO:0007829|PDB:7BED"
FT STRAND 25..27
FT /evidence="ECO:0007829|PDB:5EAP"
FT STRAND 36..41
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 48..53
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 57..64
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 67..73
FT /evidence="ECO:0007829|PDB:6E1Z"
FT TURN 74..76
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 79..84
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 90..95
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 99..106
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 109..115
FT /evidence="ECO:0007829|PDB:6E1Z"
FT TURN 116..118
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 121..126
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 132..137
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 141..148
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 153..157
FT /evidence="ECO:0007829|PDB:6E1Z"
FT TURN 158..160
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 163..167
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 174..179
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 183..190
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 193..199
FT /evidence="ECO:0007829|PDB:6E1Z"
FT TURN 200..202
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 205..211
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 213..215
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 217..222
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 226..233
FT /evidence="ECO:0007829|PDB:6E1Z"
FT TURN 234..236
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 237..242
FT /evidence="ECO:0007829|PDB:6E1Z"
FT TURN 243..246
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 247..252
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 258..260
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 264..267
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 269..271
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 273..276
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:2G9A"
FT STRAND 283..287
FT /evidence="ECO:0007829|PDB:6E1Z"
FT TURN 288..290
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 293..297
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 304..309
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 311..320
FT /evidence="ECO:0007829|PDB:6E1Z"
FT TURN 322..324
FT /evidence="ECO:0007829|PDB:6E1Z"
FT STRAND 327..331
FT /evidence="ECO:0007829|PDB:6E1Z"
SQ SEQUENCE 334 AA; 36588 MW; 4BF30914A2250286 CRC64;
MATEEKKPET EAARAQPTPS SSATQSKPTP VKPNYALKFT LAGHTKAVSS VKFSPNGEWL
ASSSADKLIK IWGAYDGKFE KTISGHKLGI SDVAWSSDSN LLVSASDDKT LKIWDVSSGK
CLKTLKGHSN YVFCCNFNPQ SNLIVSGSFD ESVRIWDVKT GKCLKTLPAH SDPVSAVHFN
RDGSLIVSSS YDGLCRIWDT ASGQCLKTLI DDDNPPVSFV KFSPNGKYIL AATLDNTLKL
WDYSKGKCLK TYTGHKNEKY CIFANFSVTG GKWIVSGSED NLVYIWNLQT KEIVQKLQGH
TDVVISTACH PTENIIASAA LENDKTIKLW KSDC
