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 27-MAR-2024, entry version 203. 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 INTERACTION WITH HUMAN HERPESVIRUS 8/HHV-8 PROTEIN LANA1, AND SUBCELLULAR RP LOCATION. RX PubMed=34850113; DOI=10.1093/nar/gkab1094; RA Tan M., Li S., Juillard F., Chitas R., Custodio T.F., Xue H., Szymula A., RA Sun Q., Liu B., Alvarez A.L., Chen S., Huang J., Simas J.P., McVey C.E., RA Kaye K.M.; RT "MLL1 is regulated by KSHV LANA and is important for virus latency."; RL Nucleic Acids Res. 49:12895-12911(2021). RN [25] 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 [26] 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 [27] 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 [28] 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 [29] 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 [30] {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 [31] {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 [32] {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 [33] {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 [34] 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 -!- SUBUNIT: (Microbial infection) Interacts with herpes virus 8/HHV-8 CC protein LANA1; this interaction regulates the MLL1 histone CC methyltransferase activity on viral DNA. {ECO:0000269|PubMed:34850113}. 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=13; IntAct=EBI-540834, EBI-591370; CC P61964; PRO_0000390950 [Q03164]: KMT2A; NbExp=2; IntAct=EBI-540834, EBI-2638616; CC P61964; Q9UMN6: KMT2B; NbExp=8; 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: Bmal1; Xeno; NbExp=2; IntAct=EBI-540834, EBI-644534; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17355966, CC ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:34850113}. 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 PDB; 7U9Y; X-ray; 1.90 A; A=30-334. DR PDB; 7UAS; X-ray; 1.81 A; A/B=22-334. DR PDB; 7UD5; EM; 4.25 A; L=2-334. DR PDB; 7WVK; X-ray; 1.42 A; A=22-334. DR PDB; 8BB2; X-ray; 2.05 A; B=33-334. DR PDB; 8BB3; X-ray; 1.80 A; B=33-334. DR PDB; 8BB4; X-ray; 2.80 A; Q=33-334. DR PDB; 8BB5; X-ray; 2.20 A; D=33-334. DR PDB; 8DU4; EM; 3.55 A; L=2-334. DR PDB; 8E9F; X-ray; 1.55 A; A=30-334. DR PDB; 8F1G; X-ray; 2.14 A; A/B=22-334. DR PDB; 8F93; X-ray; 2.30 A; A/B=22-334. DR PDB; 8G3C; X-ray; 1.80 A; A=22-334. DR PDB; 8G3E; X-ray; 1.33 A; A/B=22-334. DR PDB; 8Q1N; X-ray; 1.84 A; A/B=22-334. DR PDB; 8T5I; X-ray; 1.70 A; A/B=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 PDBsum; 7U9Y; -. DR PDBsum; 7UAS; -. DR PDBsum; 7UD5; -. DR PDBsum; 7WVK; -. DR PDBsum; 8BB2; -. DR PDBsum; 8BB3; -. DR PDBsum; 8BB4; -. DR PDBsum; 8BB5; -. DR PDBsum; 8DU4; -. DR PDBsum; 8E9F; -. DR PDBsum; 8F1G; -. DR PDBsum; 8F93; -. DR PDBsum; 8G3C; -. DR PDBsum; 8G3E; -. DR PDBsum; 8Q1N; -. DR PDBsum; 8T5I; -. DR AlphaFoldDB; P61964; -. DR EMDB; EMD-0693; -. DR EMDB; EMD-0694; -. DR EMDB; EMD-0695; -. DR EMDB; EMD-20512; -. DR EMDB; EMD-20513; -. DR EMDB; EMD-21542; -. DR EMDB; EMD-21543; -. DR EMDB; EMD-21544; -. DR EMDB; EMD-23738; -. DR EMDB; EMD-23739; -. DR EMDB; EMD-26454; -. DR EMDB; EMD-27715; -. DR EMDB; EMD-9998; -. DR EMDB; EMD-9999; -. DR SASBDB; P61964; -. DR SMR; P61964; -. DR BioGRID; 116272; 1083. 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; 189. DR MINT; P61964; -. DR STRING; 9606.ENSP00000351446; -. DR BindingDB; P61964; -. DR ChEMBL; CHEMBL1075317; -. DR GuidetoPHARMACOLOGY; 2831; -. DR MoonProt; P61964; -. DR GlyGen; P61964; 2 sites, 1 O-linked glycan (2 sites). 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; 9606-ENSP00000351446; -. DR PeptideAtlas; P61964; -. DR ProteomicsDB; 57347; -. DR Pumba; P61964; -. DR ABCD; P61964; 4 sequenced antibodies. DR Antibodypedia; 31978; 490 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 AGR; HGNC:12757; -. 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; LIKIWGS; -. DR OrthoDB; 989707at2759; -. 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 Reactome; R-HSA-9733709; Cardiogenesis. DR Reactome; R-HSA-9772755; Formation of WDR5-containing histone-modifying complexes. DR SignaLink; P61964; -. DR SIGNOR; P61964; -. DR BioGRID-ORCS; 11091; 721 hits in 1177 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 182 other cell types or tissues. DR ExpressionAtlas; P61964; baseline and differential. 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; NAS: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:0042800; F:histone H3K4 methyltransferase activity; IEA:Ensembl. DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB. DR GO; GO:0006094; P:gluconeogenesis; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; NAS:ComplexPortal. 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:0051726; P:regulation of cell cycle; IMP:ComplexPortal. DR GO; GO:0051302; P:regulation of cell division; IDA:ComplexPortal. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IMP:ComplexPortal. DR GO; GO:0045995; P:regulation of embryonic development; ISO:ComplexPortal. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:ComplexPortal. DR GO; GO:0090043; P:regulation of tubulin deacetylation; IMP:ComplexPortal. DR GO; GO:0001501; P:skeletal system development; IEA:Ensembl. DR GO; GO:0045815; P:transcription initiation-coupled chromatin remodeling; IDA:UniProtKB. DR CDD; cd00200; WD40; 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1. DR IDEAL; IID00377; -. DR InterPro; IPR020472; G-protein_beta_WD-40_rep. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR019775; WD40_repeat_CS. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR InterPro; IPR001680; WD40_rpt. DR PANTHER; PTHR19879:SF1; CANNONBALL-RELATED; 1. DR PANTHER; PTHR19879; TRANSCRIPTION INITIATION FACTOR TFIID; 1. DR Pfam; PF00400; WD40; 7. DR PIRSF; PIRSF002394; GN-bd_beta; 1. DR PRINTS; PR00320; GPROTEINBRPT. DR SMART; SM00320; WD40; 7. DR SUPFAM; SSF50978; WD40 repeat-like; 1. DR PROSITE; PS00678; WD_REPEATS_1; 4. DR PROSITE; PS50082; WD_REPEATS_2; 6. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. DR Genevisible; P61964; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Chromatin regulator; Disease variant; KW Host-virus interaction; Isopeptide bond; Nucleus; Reference proteome; KW Repeat; Transcription; Transcription regulation; Ubl conjugation; KW 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 (found in a patient with childhood apraxia of FT speech; uncertain 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 31..33 FT /evidence="ECO:0007829|PDB:8Q1N" 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 //