ID ASH2L_HUMAN Reviewed; 628 AA. AC Q9UBL3; A8K7C3; D3DSW9; O60659; O60660; Q96B62; DT 16-JUN-2003, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 27-MAR-2024, entry version 202. DE RecName: Full=Set1/Ash2 histone methyltransferase complex subunit ASH2; DE AltName: Full=ASH2-like protein; GN Name=ASH2L; Synonyms=ASH2L1; 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] (ISOFORMS 1 AND 2). RC TISSUE=Fetal brain; RX PubMed=11466562; DOI=10.1007/s001090100222; RA Wang J., Zhou Y., Yin B., Du G., Huang X., Li G., Shen Y., Yuan J., RA Qiang B.; RT "ASH2L: alternative splicing and downregulation during induced RT megakaryocytic differentiation of multipotential leukemia cell lines."; RL J. Mol. Med. 79:399-405(2001). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RX PubMed=10393421; DOI=10.1159/000015248; RA Ikegawa S., Isomura M., Koshizuka Y., Nakamura Y.; RT "Cloning and characterization of ASH2L and ash2l, human and mouse homologs RT of the Drosophila ash2 gene."; RL Cytogenet. Cell Genet. 84:167-172(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION, AND 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 [7] 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 [8] 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 [9] 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 [10] 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 [11] 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 [12] 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 [13] RP IDENTIFICATION IN SET1 COMPLEX, AND INTERACTION WITH SETD1A AND SETD1B. 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 [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; CCAR2; RBBP5 AND EMSY. 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 DPY30 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-101, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [18] 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 [19] RP METHYLATION AT ARG-296 BY PRMT1 AND PRMT5, AND MUTAGENESIS OF ARG-296 AND RP ARG-300. RX PubMed=21285357; DOI=10.1074/jbc.m110.202416; RA Butler J.S., Zurita-Lopez C.I., Clarke S.G., Bedford M.T., Dent S.Y.; RT "Protein-arginine methyltransferase 1 (PRMT1) methylates Ash2L, a shared RT component of mammalian histone H3K4 methyltransferase complexes."; RL J. Biol. Chem. 286:12234-12244(2011). RN [20] RP FUNCTION, AND INTERACTION WITH RBBP5. 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 [21] RP 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 [22] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 (ISOFORMS 2 AND 3), AND RP IDENTIFICATION BY MASS SPECTROMETRY [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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [24] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 96-271, DOMAIN PHD, AND RP DNA-BINDING REGION. RX PubMed=21660059; DOI=10.1038/embor.2011.101; RA Chen Y., Wan B., Wang K.C., Cao F., Yang Y., Protacio A., Dou Y., RA Chang H.Y., Lei M.; RT "Crystal structure of the N-terminal region of human Ash2L shows a winged- RT helix motif involved in DNA binding."; RL EMBO Rep. 12:797-803(2011). CC -!- FUNCTION: Transcriptional regulator (PubMed:12670868). Component or CC associated component of some histone methyltransferase complexes which CC regulates transcription through recruitment of those complexes to gene CC promoters (PubMed:19131338). Component of the Set1/Ash2 histone CC methyltransferase (HMT) complex, a complex that specifically methylates CC 'Lys-4' of histone H3, but not if the neighboring 'Lys-9' residue is CC already methylated (PubMed:19556245). As part of the MLL1/MLL complex CC it is involved in methylation and dimethylation at 'Lys-4' of histone CC H3 (PubMed:19556245). May play a role in hematopoiesis CC (PubMed:12670868). In association with RBBP5 and WDR5, stimulates the CC histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, CC SETD1A and SETD1B (PubMed:21220120, PubMed:22266653). CC {ECO:0000269|PubMed:12670868, ECO:0000269|PubMed:19131338, CC ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:21220120, CC ECO:0000269|PubMed:22266653}. CC -!- SUBUNIT: Interacts with HCFC1 (PubMed:12670868). 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:17500065). Each complex is at least composed of CC ASH2L, RBBP5, WDR5, DPY30, one or more specific histone CC methyltransferases (KMT2A/MLL1, KMT2D/MLL2, KMT2C/MLL3 and KMT2B/MLL4), CC and the facultative components PAGR1, BAP18, CHD8, E2F6, HCFC1, HCFC2, CC HSP70, INO80C, KDM6A, KANSL1, LAS1L, MAX, MCRS1, MEN1, MGA, KAT8/MOF, CC NCOA6, PAXIP1/PTIP, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, CC RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9, TEX10 and alpha- and CC beta-tubulin (PubMed:14992727, PubMed:15199122, PubMed:15960975, CC PubMed:17500065). Component of the SET1 complex, at least composed of CC the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, CC ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30 (PubMed:16253997, CC PubMed:17355966, PubMed:17998332, PubMed:18838538). Found in a complex CC with RBBP5, ASH2L, DPY30, KMT2A, KMT2D and WDR5 (By similarity). CC Component of a histone methylation complex composed of at least ZNF335, CC RBBP5, ASH2L and WDR5; the complex may have histone H3-specific CC methyltransferase activity, however does not have specificity for 'Lys- CC 4' of histone H3 (PubMed:19131338). Within the complex, interacts with CC ZNF335 (PubMed:19131338). Interacts with RBBP5 (PubMed:19131338, CC PubMed:19556245, PubMed:21220120). Components of this complex may CC associate with components of a nuclear receptor-mediated transcription CC complex to form a complex at least composed of ZNF335, HCFC1, CCAR2, CC EMSY, MKI67, RBBP5, ASH2L and WDR5 (PubMed:19131338). Within this CC complex also interacts with CCAR2 and EMSY (PubMed:19131338). Interacts CC with DPY30 (PubMed:19556245). Interacts with SETD1A and SETD1B CC (PubMed:17998332). {ECO:0000250|UniProtKB:Q91X20, CC ECO:0000269|PubMed:12670868, ECO:0000269|PubMed:14992727, CC ECO:0000269|PubMed:15199122, ECO:0000269|PubMed:15960975, CC ECO:0000269|PubMed:16253997, ECO:0000269|PubMed:17355966, CC ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:17998332, CC ECO:0000269|PubMed:18838538, ECO:0000269|PubMed:19131338, CC ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:21220120}. CC -!- INTERACTION: CC Q9UBL3; O43823: AKAP8; NbExp=3; IntAct=EBI-540797, EBI-1237481; CC Q9UBL3; P10275: AR; NbExp=3; IntAct=EBI-540797, EBI-608057; CC Q9UBL3; P24863: CCNC; NbExp=3; IntAct=EBI-540797, EBI-395261; CC Q9UBL3; Q8TAP6: CEP76; NbExp=3; IntAct=EBI-540797, EBI-742887; CC Q9UBL3; Q9HCK8: CHD8; NbExp=2; IntAct=EBI-540797, EBI-1169146; CC Q9UBL3; Q9C005: DPY30; NbExp=22; IntAct=EBI-540797, EBI-744973; CC Q9UBL3; Q09472: EP300; NbExp=5; IntAct=EBI-540797, EBI-447295; CC Q9UBL3; O75460-2: ERN1; NbExp=3; IntAct=EBI-540797, EBI-25852368; CC Q9UBL3; Q0VDC6: FKBP1A; NbExp=3; IntAct=EBI-540797, EBI-10226858; CC Q9UBL3; P51610: HCFC1; NbExp=6; IntAct=EBI-540797, EBI-396176; CC Q9UBL3; P54652: HSPA2; NbExp=3; IntAct=EBI-540797, EBI-356991; CC Q9UBL3; Q14696: MESD; NbExp=3; IntAct=EBI-540797, EBI-6165891; CC Q9UBL3; Q14686: NCOA6; NbExp=14; IntAct=EBI-540797, EBI-78670; CC Q9UBL3; Q6ZW49: PAXIP1; NbExp=12; IntAct=EBI-540797, EBI-743225; CC Q9UBL3; Q15291: RBBP5; NbExp=37; IntAct=EBI-540797, EBI-592823; CC Q9UBL3; P04637: TP53; NbExp=7; IntAct=EBI-540797, EBI-366083; CC Q9UBL3-3; Q9C005: DPY30; NbExp=7; IntAct=EBI-16130425, EBI-744973; CC Q9UBL3-3; Q03164: KMT2A; NbExp=4; IntAct=EBI-16130425, EBI-591370; CC Q9UBL3-3; Q9UMN6: KMT2B; NbExp=2; IntAct=EBI-16130425, EBI-765774; CC Q9UBL3-3; Q8NEZ4: KMT2C; NbExp=5; IntAct=EBI-16130425, EBI-1042997; CC Q9UBL3-3; O14686: KMT2D; NbExp=2; IntAct=EBI-16130425, EBI-996065; CC Q9UBL3-3; Q15291: RBBP5; NbExp=9; IntAct=EBI-16130425, EBI-592823; CC Q9UBL3-3; O15047: SETD1A; NbExp=2; IntAct=EBI-16130425, EBI-540779; CC Q9UBL3-3; Q9UPS6-2: SETD1B; NbExp=2; IntAct=EBI-16130425, EBI-16197836; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305|PubMed:17355966}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=ASH2L1; CC IsoId=Q9UBL3-1; Sequence=Displayed; CC Name=2; Synonyms=ASH2L2; CC IsoId=Q9UBL3-2; Sequence=VSP_007577, VSP_007578; CC Name=3; CC IsoId=Q9UBL3-3; Sequence=VSP_007577; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Predominantly expressed in CC adult heart and testis and fetal lung and liver, with barely detectable CC expression in adult lung, liver, kidney, prostate, and peripheral CC leukocytes. {ECO:0000269|PubMed:10393421}. CC -!- PTM: Both monomethylated and dimethylated on arginine residues in the CC C-terminus. Arg-296 is the major site. Methylation is not required for CC nuclear localization, nor for MLL complex integrity or maintenance of CC global histone H3K4me3 levels. {ECO:0000269|PubMed:21285357}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/44404/ASH2L"; 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; AF056718; AAC13564.1; -; mRNA. DR EMBL; AF056717; AAC13563.1; -; mRNA. DR EMBL; AB022785; BAA74520.1; -; Genomic_DNA. DR EMBL; AB020982; BAA35127.1; -; mRNA. DR EMBL; AK291938; BAF84627.1; -; mRNA. DR EMBL; CH471080; EAW63337.1; -; Genomic_DNA. DR EMBL; CH471080; EAW63336.1; -; Genomic_DNA. DR EMBL; CH471080; EAW63340.1; -; Genomic_DNA. DR EMBL; BC015936; AAH15936.1; -; mRNA. DR CCDS; CCDS47840.1; -. [Q9UBL3-3] DR CCDS; CCDS59100.1; -. [Q9UBL3-2] DR CCDS; CCDS6101.1; -. [Q9UBL3-1] DR RefSeq; NP_001098684.1; NM_001105214.2. [Q9UBL3-3] DR RefSeq; NP_001248761.1; NM_001261832.1. [Q9UBL3-2] DR RefSeq; NP_004665.2; NM_004674.4. [Q9UBL3-1] DR PDB; 3RSN; X-ray; 2.10 A; A=96-271. DR PDB; 3S32; X-ray; 2.45 A; A=95-280. DR PDB; 3TOJ; X-ray; 2.07 A; A/B=370-496, A/B=539-617. DR PDB; 4RIQ; X-ray; 2.23 A; C/F/I/L/O/R/U/X=603-618. DR PDB; 4X8N; X-ray; 2.10 A; A=380-495, A=539-598. DR PDB; 4X8P; X-ray; 2.20 A; A=380-495, A=539-598. DR PDB; 5F6K; X-ray; 2.41 A; A/B=380-496, A/B=539-598. DR PDB; 5F6L; X-ray; 1.90 A; B=380-496, B=539-598. DR PDB; 6E2H; X-ray; 2.24 A; D=380-622. DR PDB; 6KIU; EM; 3.20 A; T=95-628. DR PDB; 6KIV; EM; 4.00 A; T=95-628. DR PDB; 6KIW; EM; 4.00 A; T=95-628. DR PDB; 6KIX; EM; 4.10 A; T=95-628. DR PDB; 6KIZ; EM; 4.50 A; T=95-628. DR PDB; 6PWV; EM; 6.20 A; D=96-628. DR PDB; 6W5I; EM; 6.90 A; D=96-628. DR PDB; 6W5M; EM; 4.60 A; D=96-628. DR PDB; 6W5N; EM; 6.00 A; D=96-628. DR PDB; 7BRE; X-ray; 2.80 A; A/D=380-496, A/D=516-598. DR PDB; 7MBM; EM; -; D=96-628. DR PDB; 7MBN; EM; -; D=96-628. DR PDB; 7UD5; EM; 4.25 A; M=95-628. DR PDB; 7W67; X-ray; 2.19 A; A=380-496, A=516-598. DR PDB; 7W6A; X-ray; 2.21 A; A=380-496, A=516-598. DR PDB; 7W6I; X-ray; 2.56 A; A=380-496, A=516-598. DR PDB; 7W6J; X-ray; 2.68 A; A=380-496, A=516-598. DR PDB; 7W6L; X-ray; 2.26 A; A/B=380-496, A/B=516-598. DR PDBsum; 3RSN; -. DR PDBsum; 3S32; -. DR PDBsum; 3TOJ; -. DR PDBsum; 4RIQ; -. DR PDBsum; 4X8N; -. DR PDBsum; 4X8P; -. DR PDBsum; 5F6K; -. DR PDBsum; 5F6L; -. DR PDBsum; 6E2H; -. DR PDBsum; 6KIU; -. DR PDBsum; 6KIV; -. DR PDBsum; 6KIW; -. DR PDBsum; 6KIX; -. DR PDBsum; 6KIZ; -. DR PDBsum; 6PWV; -. DR PDBsum; 6W5I; -. DR PDBsum; 6W5M; -. DR PDBsum; 6W5N; -. DR PDBsum; 7BRE; -. DR PDBsum; 7MBM; -. DR PDBsum; 7MBN; -. DR PDBsum; 7UD5; -. DR PDBsum; 7W67; -. DR PDBsum; 7W6A; -. DR PDBsum; 7W6I; -. DR PDBsum; 7W6J; -. DR PDBsum; 7W6L; -. DR AlphaFoldDB; Q9UBL3; -. DR EMDB; EMD-0693; -. DR EMDB; EMD-0694; -. DR EMDB; EMD-0695; -. DR EMDB; EMD-20512; -. 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-9998; -. DR EMDB; EMD-9999; -. DR SASBDB; Q9UBL3; -. DR SMR; Q9UBL3; -. DR BioGRID; 114528; 230. 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 CORUM; Q9UBL3; -. DR DIP; DIP-29222N; -. DR IntAct; Q9UBL3; 105. DR MINT; Q9UBL3; -. DR STRING; 9606.ENSP00000340896; -. DR BindingDB; Q9UBL3; -. DR ChEMBL; CHEMBL3137282; -. DR GlyGen; Q9UBL3; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9UBL3; -. DR PhosphoSitePlus; Q9UBL3; -. DR SwissPalm; Q9UBL3; -. DR BioMuta; ASH2L; -. DR DMDM; 32141382; -. DR EPD; Q9UBL3; -. DR jPOST; Q9UBL3; -. DR MassIVE; Q9UBL3; -. DR MaxQB; Q9UBL3; -. DR PaxDb; 9606-ENSP00000340896; -. DR PeptideAtlas; Q9UBL3; -. DR ProteomicsDB; 83994; -. [Q9UBL3-1] DR ProteomicsDB; 83995; -. [Q9UBL3-2] DR ProteomicsDB; 83996; -. [Q9UBL3-3] DR Pumba; Q9UBL3; -. DR Antibodypedia; 10852; 500 antibodies from 37 providers. DR DNASU; 9070; -. DR Ensembl; ENST00000343823.11; ENSP00000340896.5; ENSG00000129691.16. [Q9UBL3-1] DR Ensembl; ENST00000428278.6; ENSP00000395310.2; ENSG00000129691.16. [Q9UBL3-3] DR Ensembl; ENST00000521652.5; ENSP00000430259.1; ENSG00000129691.16. [Q9UBL3-2] DR GeneID; 9070; -. DR KEGG; hsa:9070; -. DR MANE-Select; ENST00000343823.11; ENSP00000340896.5; NM_004674.5; NP_004665.2. DR UCSC; uc003xkt.6; human. [Q9UBL3-1] DR AGR; HGNC:744; -. DR CTD; 9070; -. DR DisGeNET; 9070; -. DR GeneCards; ASH2L; -. DR HGNC; HGNC:744; ASH2L. DR HPA; ENSG00000129691; Low tissue specificity. DR MIM; 604782; gene. DR neXtProt; NX_Q9UBL3; -. DR OpenTargets; ENSG00000129691; -. DR PharmGKB; PA25044; -. DR VEuPathDB; HostDB:ENSG00000129691; -. DR eggNOG; KOG2626; Eukaryota. DR GeneTree; ENSGT00390000010474; -. DR InParanoid; Q9UBL3; -. DR OMA; CATCSRW; -. DR OrthoDB; 5479497at2759; -. DR PhylomeDB; Q9UBL3; -. DR TreeFam; TF314785; -. DR PathwayCommons; Q9UBL3; -. DR Reactome; R-HSA-201722; Formation of the beta-catenin:TCF transactivating complex. DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines. DR Reactome; R-HSA-3769402; Deactivation of the beta-catenin transactivating complex. 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-9772755; Formation of WDR5-containing histone-modifying complexes. DR SignaLink; Q9UBL3; -. DR SIGNOR; Q9UBL3; -. DR BioGRID-ORCS; 9070; 344 hits in 1201 CRISPR screens. DR ChiTaRS; ASH2L; human. DR GeneWiki; ASH2L; -. DR GenomeRNAi; 9070; -. DR Pharos; Q9UBL3; Tbio. DR PRO; PR:Q9UBL3; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q9UBL3; Protein. DR Bgee; ENSG00000129691; Expressed in superficial temporal artery and 211 other cell types or tissues. DR ExpressionAtlas; Q9UBL3; baseline and differential. DR GO; GO:0000791; C:euchromatin; IEA:Ensembl. DR GO; GO:0035097; C:histone methyltransferase complex; IDA:UniProtKB. DR GO; GO:0071339; C:MLL1 complex; IPI:ComplexPortal. DR GO; GO:0044665; C:MLL1/2 complex; IPI:ComplexPortal. DR GO; GO:0044666; C:MLL3/4 complex; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048188; C:Set1C/COMPASS complex; IDA:UniProtKB. DR GO; GO:0008013; F:beta-catenin binding; IPI:BHF-UCL. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB. DR GO; GO:0006974; P:DNA damage response; IDA:MGI. DR GO; GO:0030097; P:hemopoiesis; NAS:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0043627; P:response to estrogen; IDA:UniProtKB. DR GO; GO:0045815; P:transcription initiation-coupled chromatin remodeling; IDA:UniProtKB. DR CDD; cd15583; PHD_ash2p_like; 1. DR CDD; cd12872; SPRY_Ash2; 1. DR Gene3D; 2.60.120.920; -; 1. DR Gene3D; 3.90.980.20; -; 1. DR InterPro; IPR037353; ASH2. DR InterPro; IPR049455; ASH2-like_PHD. DR InterPro; IPR001870; B30.2/SPRY. DR InterPro; IPR043136; B30.2/SPRY_sf. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR003877; SPRY_dom. DR PANTHER; PTHR10598; SET1/ASH2 HISTONE METHYLTRANSFERASE COMPLEX SUBUNIT ASH2; 1. DR PANTHER; PTHR10598:SF0; SET1_ASH2 HISTONE METHYLTRANSFERASE COMPLEX SUBUNIT ASH2; 1. DR Pfam; PF21198; ASH2L-like_WH; 1. DR Pfam; PF21257; PHD_ash2p_like; 1. DR Pfam; PF00622; SPRY; 1. DR SMART; SM00449; SPRY; 1. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1. DR PROSITE; PS50188; B302_SPRY; 1. DR Genevisible; Q9UBL3; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Chromatin regulator; KW DNA-binding; Metal-binding; Methylation; Nucleus; Phosphoprotein; KW Reference proteome; Transcription; Transcription regulation; Zinc; KW Zinc-finger. FT CHAIN 1..628 FT /note="Set1/Ash2 histone methyltransferase complex subunit FT ASH2" FT /id="PRO_0000064697" FT DOMAIN 360..583 FT /note="B30.2/SPRY" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548" FT ZN_FING 1..66 FT /note="PHD-type; atypical" FT ZN_FING 117..150 FT /note="C4-type" FT REGION 1..107 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 67..177 FT /note="DNA-binding" FT REGION 235..331 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 316..628 FT /note="Interaction with RBBP5" FT /evidence="ECO:0000269|PubMed:21220120" FT COMPBIAS 72..86 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 235..255 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 264..287 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 303..317 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 101 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 296 FT /note="Asymmetric dimethylarginine; by PRMT1 and PRMT5" FT /evidence="ECO:0000269|PubMed:21285357" FT MOD_RES 316 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..94 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:11466562, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334" FT /id="VSP_007577" FT VAR_SEQ 541..573 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11466562" FT /id="VSP_007578" FT VARIANT 478 FT /note="S -> F (in dbSNP:rs34167006)" FT /id="VAR_050679" FT MUTAGEN 296 FT /note="R->K: Abolishes methylation." FT /evidence="ECO:0000269|PubMed:21285357" FT MUTAGEN 300 FT /note="R->K: Slightly decreased methylation." FT /evidence="ECO:0000269|PubMed:21285357" FT CONFLICT 212 FT /note="Q -> H (in Ref. 1; AAC13564)" FT /evidence="ECO:0000305" FT CONFLICT 217 FT /note="M -> T (in Ref. 1; AAC13564)" FT /evidence="ECO:0000305" FT CONFLICT 292 FT /note="S -> T (in Ref. 1; AAC13563)" FT /evidence="ECO:0000305" FT CONFLICT 351 FT /note="H -> Q (in Ref. 1; AAC13564)" FT /evidence="ECO:0000305" FT CONFLICT 360 FT /note="L -> I (in Ref. 1; AAC13564)" FT /evidence="ECO:0000305" FT CONFLICT 369 FT /note="P -> S (in Ref. 1; AAC13564)" FT /evidence="ECO:0000305" FT STRAND 114..116 FT /evidence="ECO:0007829|PDB:3RSN" FT TURN 118..120 FT /evidence="ECO:0007829|PDB:3RSN" FT STRAND 123..125 FT /evidence="ECO:0007829|PDB:3RSN" FT HELIX 126..129 FT /evidence="ECO:0007829|PDB:3RSN" FT STRAND 142..146 FT /evidence="ECO:0007829|PDB:3RSN" FT TURN 148..150 FT /evidence="ECO:0007829|PDB:3RSN" FT STRAND 157..160 FT /evidence="ECO:0007829|PDB:3RSN" FT HELIX 165..183 FT /evidence="ECO:0007829|PDB:3RSN" FT TURN 193..196 FT /evidence="ECO:0007829|PDB:3RSN" FT HELIX 197..203 FT /evidence="ECO:0007829|PDB:3RSN" FT HELIX 205..207 FT /evidence="ECO:0007829|PDB:3RSN" FT HELIX 219..221 FT /evidence="ECO:0007829|PDB:3RSN" FT HELIX 223..228 FT /evidence="ECO:0007829|PDB:3RSN" FT TURN 231..233 FT /evidence="ECO:0007829|PDB:3RSN" FT STRAND 234..239 FT /evidence="ECO:0007829|PDB:3RSN" FT HELIX 248..250 FT /evidence="ECO:0007829|PDB:3RSN" FT STRAND 252..257 FT /evidence="ECO:0007829|PDB:3RSN" FT HELIX 261..263 FT /evidence="ECO:0007829|PDB:3RSN" FT HELIX 371..373 FT /evidence="ECO:0007829|PDB:3TOJ" FT STRAND 376..378 FT /evidence="ECO:0007829|PDB:3TOJ" FT STRAND 379..381 FT /evidence="ECO:0007829|PDB:7MBN" FT STRAND 383..388 FT /evidence="ECO:0007829|PDB:5F6L" FT STRAND 392..394 FT /evidence="ECO:0007829|PDB:5F6L" FT STRAND 398..402 FT /evidence="ECO:0007829|PDB:5F6L" FT STRAND 408..413 FT /evidence="ECO:0007829|PDB:5F6L" FT STRAND 416..429 FT /evidence="ECO:0007829|PDB:5F6L" FT STRAND 435..441 FT /evidence="ECO:0007829|PDB:5F6L" FT STRAND 451..454 FT /evidence="ECO:0007829|PDB:7MBN" FT STRAND 457..461 FT /evidence="ECO:0007829|PDB:5F6L" FT TURN 462..465 FT /evidence="ECO:0007829|PDB:5F6L" FT STRAND 467..469 FT /evidence="ECO:0007829|PDB:5F6L" FT STRAND 472..474 FT /evidence="ECO:0007829|PDB:5F6L" FT STRAND 485..492 FT /evidence="ECO:0007829|PDB:5F6L" FT HELIX 495..499 FT /evidence="ECO:0007829|PDB:7MBN" FT STRAND 510..514 FT /evidence="ECO:0007829|PDB:7MBN" FT STRAND 517..521 FT /evidence="ECO:0007829|PDB:7MBN" FT STRAND 540..545 FT /evidence="ECO:0007829|PDB:5F6L" FT STRAND 548..556 FT /evidence="ECO:0007829|PDB:5F6L" FT STRAND 562..571 FT /evidence="ECO:0007829|PDB:5F6L" FT STRAND 573..577 FT /evidence="ECO:0007829|PDB:5F6L" FT STRAND 579..581 FT /evidence="ECO:0007829|PDB:3TOJ" FT STRAND 587..589 FT /evidence="ECO:0007829|PDB:4X8P" FT HELIX 594..597 FT /evidence="ECO:0007829|PDB:5F6L" FT STRAND 599..602 FT /evidence="ECO:0007829|PDB:3TOJ" FT HELIX 603..615 FT /evidence="ECO:0007829|PDB:4RIQ" FT MOD_RES Q9UBL3-2:1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES Q9UBL3-3:1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" SQ SEQUENCE 628 AA; 68723 MW; 8F5F007430D4B863 CRC64; MAAAGAGPGQ EAGAGPGPGA VANATGAEEG EMKPVAAGAA APPGEGISAA PTVEPSSGEA EGGEANLVDV SGGLETESSN GKDTLEGAGD TSEVMDTQAG SVDEENGRQL GEVELQCGIC TKWFTADTFG IDTSSCLPFM TNYSFHCNVC HHSGNTYFLR KQANLKEMCL SALANLTWQS RTQDEHPKTM FSKDKDIIPF IDKYWECMTT RQRPGKMTWP NNIVKTMSKE RDVFLVKEHP DPGSKDPEED YPKFGLLDQD LSNIGPAYDN QKQSSAVSTS GNLNGGIAAG SSGKGRGAKR KQQDGGTTGT TKKARSDPLF SAQRLPPHGY PLEHPFNKDG YRYILAEPDP HAPDPEKLEL DCWAGKPIPG DLYRACLYER VLLALHDRAP QLKISDDRLT VVGEKGYSMV RASHGVRKGA WYFEITVDEM PPDTAARLGW SQPLGNLQAP LGYDKFSYSW RSKKGTKFHQ SIGKHYSSGY GQGDVLGFYI NLPEDTETAK SLPDTYKDKA LIKFKSYLYF EEKDFVDKAE KSLKQTPHSE IIFYKNGVNQ GVAYKDIFEG VYFPAISLYK SCTVSINFGP CFKYPPKDLT YRPMSDMGWG AVVEHTLADV LYHVETEVDG RRSPPWEP //