ASH2L_MOUSE
ID ASH2L_MOUSE Reviewed; 623 AA.
AC Q91X20; Q3UIF9; Q9Z2X4;
DT 16-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Set1/Ash2 histone methyltransferase complex subunit ASH2;
DE AltName: Full=ASH2-like protein;
GN Name=Ash2l;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Amnion, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP IDENTIFICATION IN A COMPLEX WITH RBBP5; DPY30; KMT2A; KMT2D AND WDR5.
RX PubMed=21335234; DOI=10.1016/j.cell.2011.01.020;
RA Jiang H., Shukla A., Wang X., Chen W.Y., Bernstein B.E., Roeder R.G.;
RT "Role for Dpy-30 in ES cell-fate specification by regulation of H3K4
RT methylation within bivalent domains.";
RL Cell 144:513-525(2011).
CC -!- FUNCTION: Transcriptional regulator (By similarity). Component or
CC associated component of some histone methyltransferase complexes which
CC regulates transcription through recruitment of those complexes to gene
CC promoters (By similarity). 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 (By similarity). As part of the MLL1/MLL complex it
CC is involved in methylation and dimethylation at 'Lys-4' of histone H3
CC (By similarity). May play a role in hematopoiesis (By similarity). In
CC association with RBBP5 and WDR5, stimulates the histone
CC methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and
CC SETD1B (By similarity). {ECO:0000250|UniProtKB:Q9UBL3}.
CC -!- SUBUNIT: Interacts with HCFC1 (By similarity). Core component of
CC several methyltransferase-containing complexes including MLL1/MLL,
CC MLL2/3 (also named ASCOM complex) and MLL4/WBP7 (By similarity). Each
CC complex is at least composed of ASH2L, RBBP5, WDR5, DPY30, one or more
CC specific histone methyltransferases (KMT2A/MLL1, KMT2D/MLL2, KMT2C/MLL3
CC and KMT2B/MLL4), and the facultative components PAGR1, BAP18, CHD8,
CC E2F6, HCFC1, HCFC2, HSP70, INO80C, KDM6A, KANSL1, LAS1L, MAX, MCRS1,
CC MEN1, MGA, KAT8/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 (By similarity). Component of the SET1
CC complex, at least composed of the catalytic subunit (SETD1A or SETD1B),
CC WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30 (By
CC similarity). Found in a complex with RBBP5, ASH2L, DPY30, KMT2A, KMT2D
CC and WDR5 (PubMed:21335234). Component of a histone methylation complex
CC composed of at least ZNF335, RBBP5, ASH2L and WDR5; the complex may
CC have histone H3-specific methyltransferase activity, however does not
CC have specificity for 'Lys-4' of histone H3 (By similarity). Within the
CC complex, interacts with ZNF335 (By similarity). Interacts with RBBP5
CC (By similarity). Components of this complex may associate with
CC components of a nuclear receptor-mediated transcription complex to form
CC a complex at least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67,
CC RBBP5, ASH2L and WDR5 (By similarity). Within this complex also
CC interacts with CCAR2 and EMSY (By similarity). Interacts with DPY30 (By
CC similarity). Interacts with SETD1A and SETD1B (By similarity).
CC {ECO:0000250|UniProtKB:Q9UBL3, ECO:0000269|PubMed:21335234}.
CC -!- INTERACTION:
CC Q91X20; Q8BX09: Rbbp5; NbExp=10; IntAct=EBI-1556554, EBI-1556543;
CC Q91X20; Q91ZK0: Tfap2d; NbExp=4; IntAct=EBI-1556554, EBI-15703453;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with abundant expression in
CC the heart, skeletal muscle and kidney. Low expression is seen in
CC spleen, lung and testis. {ECO:0000269|PubMed:10393421}.
CC -!- PTM: Both monomethylated and dimethylated on arginine residues in the
CC C-terminus. Arg-291 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 (By similarity). {ECO:0000250}.
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DR EMBL; AB020983; BAA35128.1; -; mRNA.
DR EMBL; BC012957; AAH12957.1; -; mRNA.
DR EMBL; AK087934; BAC40047.1; -; mRNA.
DR EMBL; AK146938; BAE27547.1; -; mRNA.
DR CCDS; CCDS40307.1; -.
DR RefSeq; NP_035921.2; NM_011791.3.
DR AlphaFoldDB; Q91X20; -.
DR SMR; Q91X20; -.
DR BioGRID; 204728; 30.
DR CORUM; Q91X20; -.
DR DIP; DIP-39161N; -.
DR IntAct; Q91X20; 12.
DR MINT; Q91X20; -.
DR STRING; 10090.ENSMUSP00000070957; -.
DR iPTMnet; Q91X20; -.
DR PhosphoSitePlus; Q91X20; -.
DR EPD; Q91X20; -.
DR MaxQB; Q91X20; -.
DR PaxDb; Q91X20; -.
DR PRIDE; Q91X20; -.
DR ProteomicsDB; 281812; -.
DR Antibodypedia; 10852; 433 antibodies from 37 providers.
DR DNASU; 23808; -.
DR Ensembl; ENSMUST00000068892; ENSMUSP00000070957; ENSMUSG00000031575.
DR GeneID; 23808; -.
DR KEGG; mmu:23808; -.
DR UCSC; uc009lhc.2; mouse.
DR CTD; 9070; -.
DR MGI; MGI:1344416; Ash2l.
DR VEuPathDB; HostDB:ENSMUSG00000031575; -.
DR eggNOG; KOG2626; Eukaryota.
DR GeneTree; ENSGT00390000010474; -.
DR InParanoid; Q91X20; -.
DR OMA; SWYSTVQ; -.
DR OrthoDB; 444178at2759; -.
DR PhylomeDB; Q91X20; -.
DR TreeFam; TF314785; -.
DR Reactome; R-MMU-201722; Formation of the beta-catenin:TCF transactivating complex.
DR Reactome; R-MMU-3214841; PKMTs methylate histone lysines.
DR Reactome; R-MMU-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR BioGRID-ORCS; 23808; 21 hits in 80 CRISPR screens.
DR ChiTaRS; Ash2l; mouse.
DR PRO; PR:Q91X20; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q91X20; protein.
DR Bgee; ENSMUSG00000031575; Expressed in seminiferous tubule of testis and 254 other tissues.
DR ExpressionAtlas; Q91X20; baseline and differential.
DR Genevisible; Q91X20; MM.
DR GO; GO:0000791; C:euchromatin; IDA:BHF-UCL.
DR GO; GO:0035097; C:histone methyltransferase complex; ISS:UniProtKB.
DR GO; GO:0071339; C:MLL1 complex; IDA:UniProtKB.
DR GO; GO:0044665; C:MLL1/2 complex; ISO:MGI.
DR GO; GO:0044666; C:MLL3/4 complex; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0048188; C:Set1C/COMPASS complex; ISS:UniProtKB.
DR GO; GO:0008013; F:beta-catenin binding; ISO:MGI.
DR GO; GO:0042800; F:histone methyltransferase activity (H3-K4 specific); ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:MGI.
DR GO; GO:0045815; P:epigenetic maintenance of chromatin in transcription-competent conformation; NAS:BHF-UCL.
DR GO; GO:0051568; P:histone H3-K4 methylation; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0043627; P:response to estrogen; ISO:MGI.
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 Chromatin regulator; DNA-binding; Metal-binding; Methylation; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..623
FT /note="Set1/Ash2 histone methyltransferase complex subunit
FT ASH2"
FT /id="PRO_0000064698"
FT DOMAIN 355..578
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT ZN_FING 1..62
FT /note="PHD-type; atypical"
FT /evidence="ECO:0000250"
FT ZN_FING 112..145
FT /note="C4-type"
FT REGION 1..99
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 63..172
FT /note="DNA-binding"
FT /evidence="ECO:0000250"
FT REGION 230..326
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 311..623
FT /note="Interaction with RBBP5"
FT /evidence="ECO:0000250|UniProtKB:Q9UBL3"
FT COMPBIAS 67..99
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 230..250
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 259..282
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 298..312
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 96
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 291
FT /note="Asymmetric dimethylarginine; by PRMT1 and PRMT5"
FT /evidence="ECO:0000250|UniProtKB:Q9UBL3"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBL3"
FT CONFLICT 439
FT /note="L -> V (in Ref. 1; BAA35128)"
FT /evidence="ECO:0000305"
FT CONFLICT 455..458
FT /note="WRSK -> LAAS (in Ref. 1; BAA35128)"
FT /evidence="ECO:0000305"
FT CONFLICT 619..623
FT /note="PPWEP -> HPGNPNQSLLLVTL (in Ref. 1; BAA35128)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 623 AA; 68250 MW; BEB2A46B7F3E8BA2 CRC64;
MAAAGAGPGP GVSAGPGPGA AASATTAEDR ETEPVAAGAG EGPSAAPGAE PSSGEAESGD
ANLVDVSGLE TESSNGKDTL EGTGDTSEVM DTQAGSVDEE NGRQLGEVEL QCGICTKWFT
ADTFGIDTSS CLPFMTNYSF HCNVCHHSGN TYFLRKQANL KEMCLSALAN LTWQSRTQDE
HPKTMFSKDK DIIPFIDKYW ECMTTRQRPG KMTWPNNIVK TMSKERDVFL VKEHPDPGSK
DPEEDYPKFG LLDQDLSNIG PAYDNQKQSS AVSASGNLNG GIAAGSSGKG RGAKRKQQDG
GTTGTTKKAR SDPLFSAQRL PPHGYPLEHP FNKDGYRYIL AEPDPHAPDP EKLELDCWAG
KPIPGDLYRA CLYERVLLAL HDRAPQLKIS DDRLTVVGEK GYSMVRASHG VRKGAWYFEI
TVDEMPPDTA ARLGWSQPLG NLQAPLGYDK FSYSWRSKKG TKFHQSIGKH YSSGYGQGDV
LGFYINLPED TETAKSLPDT YKDKALIKFK SYLYFEEKDF VDKAEKSLKQ TPHSEIIFYK
NGVNQGVAYR DIFEGVYFPA ISLYKSCTVS INFGPSFKYP PKDLTYHPMS DMGWGAVVEH
TLADVLYHVE TEVDGRRSPP WEP
