ASH2L_HUMAN
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 03-AUG-2022, entry version 193.
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="http://atlasgeneticsoncology.org/Genes/ASH2LID44404ch8p11.html";
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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 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 AlphaFoldDB; Q9UBL3; -.
DR SASBDB; Q9UBL3; -.
DR SMR; Q9UBL3; -.
DR BioGRID; 114528; 180.
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; 103.
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 BioMuta; ASH2L; -.
DR DMDM; 32141382; -.
DR EPD; Q9UBL3; -.
DR jPOST; Q9UBL3; -.
DR MassIVE; Q9UBL3; -.
DR MaxQB; Q9UBL3; -.
DR PaxDb; Q9UBL3; -.
DR PeptideAtlas; Q9UBL3; -.
DR PRIDE; Q9UBL3; -.
DR ProteomicsDB; 83994; -. [Q9UBL3-1]
DR ProteomicsDB; 83995; -. [Q9UBL3-2]
DR ProteomicsDB; 83996; -. [Q9UBL3-3]
DR Antibodypedia; 10852; 433 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 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; SWYSTVQ; -.
DR OrthoDB; 444178at2759; -.
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 SignaLink; Q9UBL3; -.
DR SIGNOR; Q9UBL3; -.
DR BioGRID-ORCS; 9070; 311 hits in 1105 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 209 other tissues.
DR ExpressionAtlas; Q9UBL3; baseline and differential.
DR Genevisible; Q9UBL3; HS.
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:cellular response to DNA damage stimulus; IDA:MGI.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0030097; P:hemopoiesis; NAS:UniProtKB.
DR GO; GO:0051568; P:histone H3-K4 methylation; IDA: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 Gene3D; 2.60.120.920; -; 1.
DR InterPro; IPR037353; ASH2.
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; PTHR10598; 1.
DR Pfam; PF00622; SPRY; 1.
DR SMART; SM00449; SPRY; 1.
DR SUPFAM; SSF49899; SSF49899; 1.
DR PROSITE; PS50188; B302_SPRY; 1.
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
