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Database: UniProt
Entry: Q9NR48
LinkDB: Q9NR48
Original site: Q9NR48 
ID   ASH1L_HUMAN             Reviewed;        2969 AA.
AC   Q9NR48; Q59GP1; Q5T714; Q5T715; Q9P2C7;
DT   31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   31-OCT-2006, sequence version 2.
DT   10-APR-2019, entry version 156.
DE   RecName: Full=Histone-lysine N-methyltransferase ASH1L;
DE            EC=2.1.1.43 {ECO:0000269|PubMed:21239497};
DE   AltName: Full=ASH1-like protein;
DE            Short=huASH1;
DE   AltName: Full=Absent small and homeotic disks protein 1 homolog;
DE   AltName: Full=Lysine N-methyltransferase 2H;
GN   Name=ASH1L; Synonyms=KIAA1420, KMT2H;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, AND VARIANT ALA-1771.
RX   PubMed=10860993; DOI=10.1073/pnas.97.13.7284;
RA   Nakamura T., Blechman J., Tada S., Rozovskaia T., Itoyama T.,
RA   Bullrich F., Mazo A., Croce C.M., Geiger B., Canaani E.;
RT   "huASH1 protein, a putative transcription factor encoded by a human
RT   homologue of the Drosophila ash1 gene, localizes to both nuclei and
RT   cell-cell tight junctions.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:7284-7289(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA   Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA   Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA   McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA   Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA   Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA   Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA   Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA   Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA   Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA   Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA   Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA   Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA   Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA   Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA   Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA   Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA   Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA   Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA   Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA   Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA   Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA   Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA   Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA   Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1345.
RC   TISSUE=Brain;
RX   PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA   Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XVI.
RT   The complete sequences of 150 new cDNA clones from brain which code
RT   for large proteins in vitro.";
RL   DNA Res. 7:65-73(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 710-1345.
RC   TISSUE=Brain;
RA   Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA   Ohara O., Nagase T., Kikuno R.F.;
RL   Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2000-2183 (ISOFORM 2).
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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18220336; DOI=10.1021/pr0705441;
RA   Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA   Yates J.R. III;
RT   "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT   efficient phosphoproteomic analysis.";
RL   J. Proteome Res. 7:1346-1351(2008).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [8]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-375, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA   Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT   a refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [9]
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=22939622; DOI=10.1016/j.cell.2012.06.048;
RA   Pinheiro I., Margueron R., Shukeir N., Eisold M., Fritzsch C.,
RA   Richter F.M., Mittler G., Genoud C., Goyama S., Kurokawa M., Son J.,
RA   Reinberg D., Lachner M., Jenuwein T.;
RT   "Prdm3 and Prdm16 are H3K9me1 methyltransferases required for
RT   mammalian heterochromatin integrity.";
RL   Cell 150:948-960(2012).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
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   [11]
RP   METHYLATION AT GLN-1220, AND MUTAGENESIS OF GLN-1220.
RX   PubMed=26797129; DOI=10.1074/jbc.M115.711952;
RA   Kusevic D., Kudithipudi S., Jeltsch A.;
RT   "Substrate specificity of the HEMK2 protein glutamine
RT   methyltransferase and identification of novel substrates.";
RL   J. Biol. Chem. 291:6124-6133(2016).
RN   [12]
RP   SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-34 AND LYS-425, 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-
RT   modification with phosphorylation.";
RL   Nat. Struct. Mol. Biol. 24:325-336(2017).
RN   [13]
RP   X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 2074-2293 IN COMPLEX WITH
RP   S-ADENOSYL-L-METHIONINE, FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=21239497; DOI=10.1074/jbc.M110.203380;
RA   An S., Yeo K.J., Jeon Y.H., Song J.J.;
RT   "Crystal structure of the human histone methyltransferase ASH1L
RT   catalytic domain and its implications for the regulatory mechanism.";
RL   J. Biol. Chem. 286:8369-8374(2011).
RN   [14]
RP   X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS) OF 2438-2561.
RX   PubMed=22464331; DOI=10.1016/j.cell.2012.02.013;
RA   Filippakopoulos P., Picaud S., Mangos M., Keates T., Lambert J.P.,
RA   Barsyte-Lovejoy D., Felletar I., Volkmer R., Muller S., Pawson T.,
RA   Gingras A.C., Arrowsmith C.H., Knapp S.;
RT   "Histone recognition and large-scale structural analysis of the human
RT   bromodomain family.";
RL   Cell 149:214-231(2012).
RN   [15]
RP   INVOLVEMENT IN MRD52, VARIANTS MRD52 SER-724; ARG-972; HIS-1276;
RP   TRP-1775 AND GLY-2853, AND VARIANT GLY-277.
RX   PubMed=23033978; DOI=10.1056/NEJMoa1206524;
RA   de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA   Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P.,
RA   Gilissen C., del Rosario M., Hoischen A., Scheffer H., de Vries B.B.,
RA   Brunner H.G., Veltman J.A., Vissers L.E.;
RT   "Diagnostic exome sequencing in persons with severe intellectual
RT   disability.";
RL   N. Engl. J. Med. 367:1921-1929(2012).
RN   [16]
RP   VARIANT MRD52 ILE-2085.
RX   PubMed=27824329; DOI=10.1038/ncomms13316;
RA   Wang T., Guo H., Xiong B., Stessman H.A., Wu H., Coe B.P.,
RA   Turner T.N., Liu Y., Zhao W., Hoekzema K., Vives L., Xia L., Tang M.,
RA   Ou J., Chen B., Shen Y., Xun G., Long M., Lin J., Kronenberg Z.N.,
RA   Peng Y., Bai T., Li H., Ke X., Hu Z., Zhao J., Zou X., Xia K.,
RA   Eichler E.E.;
RT   "De novo genic mutations among a Chinese autism spectrum disorder
RT   cohort.";
RL   Nat. Commun. 7:13316-13316(2016).
RN   [17]
RP   VARIANT MRD52 PRO-2791.
RX   PubMed=28394464; DOI=10.1002/ajmg.a.38193;
RA   Okamoto N., Miya F., Tsunoda T., Kato M., Saitoh S., Yamasaki M.,
RA   Kanemura Y., Kosaki K.;
RT   "Novel MCA/ID syndrome with ASH1L mutation.";
RL   Am. J. Med. Genet. A 173:1644-1648(2017).
RN   [18]
RP   VARIANTS MRD52 2148-GLU--LYS-2969 DEL AND HIS-2396.
RX   PubMed=28191889; DOI=10.1038/ng.3792;
RA   Stessman H.A., Xiong B., Coe B.P., Wang T., Hoekzema K., Fenckova M.,
RA   Kvarnung M., Gerdts J., Trinh S., Cosemans N., Vives L., Lin J.,
RA   Turner T.N., Santen G., Ruivenkamp C., Kriek M., van Haeringen A.,
RA   Aten E., Friend K., Liebelt J., Barnett C., Haan E., Shaw M., Gecz J.,
RA   Anderlid B.M., Nordgren A., Lindstrand A., Schwartz C., Kooy R.F.,
RA   Vandeweyer G., Helsmoortel C., Romano C., Alberti A., Vinci M.,
RA   Avola E., Giusto S., Courchesne E., Pramparo T., Pierce K.,
RA   Nalabolu S., Amaral D.G., Scheffer I.E., Delatycki M.B.,
RA   Lockhart P.J., Hormozdiari F., Harich B., Castells-Nobau A., Xia K.,
RA   Peeters H., Nordenskjoeld M., Schenck A., Bernier R.A., Eichler E.E.;
RT   "Targeted sequencing identifies 91 neurodevelopmental-disorder risk
RT   genes with autism and developmental-disability biases.";
RL   Nat. Genet. 49:515-526(2017).
CC   -!- FUNCTION: Histone methyltransferase specifically methylating 'Lys-
CC       36' of histone H3 (H3K36me) (PubMed:21239497). Also monomethylates
CC       'Lys-9' of histone H3 (H3K9me1) in vitro (By similarity). The
CC       physiological significance of the H3K9me1 activity is unclear (By
CC       similarity). {ECO:0000250|UniProtKB:Q99MY8,
CC       ECO:0000269|PubMed:21239497}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl-[histone] + S-adenosyl-L-methionine = H(+) +
CC         N(6)-methyl-L-lysyl-[histone] + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:10024, Rhea:RHEA-COMP:9845, Rhea:RHEA-COMP:9846,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.43;
CC         Evidence={ECO:0000269|PubMed:21239497};
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10860993}. Cell
CC       junction, tight junction {ECO:0000269|PubMed:10860993}. Chromosome
CC       {ECO:0000305|PubMed:10860993}. Note=The relevance of tight
CC       junction localization is however unclear.
CC       {ECO:0000269|PubMed:10860993}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9NR48-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9NR48-2; Sequence=VSP_039421;
CC   -!- TISSUE SPECIFICITY: Widely expressed, with highest level in brain,
CC       heart and kidney. {ECO:0000269|PubMed:10860993}.
CC   -!- PTM: Methylated at Gln-1220 by N6AMT1.
CC       {ECO:0000269|PubMed:26797129}.
CC   -!- DISEASE: Mental retardation, autosomal dominant 52 (MRD52)
CC       [MIM:617796]: A form of mental retardation, a disorder
CC       characterized by significantly below average general intellectual
CC       functioning associated with impairments in adaptive behavior and
CC       manifested during the developmental period.
CC       {ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:27824329,
CC       ECO:0000269|PubMed:28191889, ECO:0000269|PubMed:28394464}.
CC       Note=The disease is caused by mutations affecting the gene
CC       represented in this entry.
CC   -!- SIMILARITY: Belongs to the class V-like SAM-binding
CC       methyltransferase superfamily. Histone-lysine methyltransferase
CC       family. SET2 subfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA92658.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
DR   EMBL; AF257305; AAF68983.1; -; mRNA.
DR   EMBL; AL139410; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL353807; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AB037841; BAA92658.1; ALT_INIT; mRNA.
DR   EMBL; AB209068; BAD92305.1; -; mRNA.
DR   EMBL; DB282357; -; NOT_ANNOTATED_CDS; mRNA.
DR   CCDS; CCDS1113.2; -. [Q9NR48-2]
DR   RefSeq; NP_060959.2; NM_018489.2. [Q9NR48-2]
DR   RefSeq; XP_006711513.1; XM_006711450.3. [Q9NR48-2]
DR   RefSeq; XP_006711514.1; XM_006711451.3. [Q9NR48-2]
DR   RefSeq; XP_016857273.1; XM_017001784.1. [Q9NR48-2]
DR   RefSeq; XP_016857274.1; XM_017001785.1. [Q9NR48-2]
DR   UniGene; Hs.491060; -.
DR   PDB; 3MQM; X-ray; 2.54 A; A/B=2438-2561.
DR   PDB; 3OPE; X-ray; 2.90 A; A/B=2074-2293.
DR   PDB; 4YNM; X-ray; 2.19 A; A/B=2074-2293.
DR   PDB; 4YNP; X-ray; 2.90 A; A/B=2074-2293.
DR   PDB; 4YPA; X-ray; 2.30 A; A/B/C/D=2074-2293.
DR   PDB; 4YPE; X-ray; 2.20 A; A/B=2074-2293.
DR   PDB; 4YPU; X-ray; 2.60 A; A/B=2074-2293.
DR   PDBsum; 3MQM; -.
DR   PDBsum; 3OPE; -.
DR   PDBsum; 4YNM; -.
DR   PDBsum; 4YNP; -.
DR   PDBsum; 4YPA; -.
DR   PDBsum; 4YPE; -.
DR   PDBsum; 4YPU; -.
DR   ProteinModelPortal; Q9NR48; -.
DR   SMR; Q9NR48; -.
DR   BioGrid; 120969; 13.
DR   IntAct; Q9NR48; 11.
DR   MINT; Q9NR48; -.
DR   STRING; 9606.ENSP00000376204; -.
DR   ChEMBL; CHEMBL3588739; -.
DR   CarbonylDB; Q9NR48; -.
DR   iPTMnet; Q9NR48; -.
DR   PhosphoSitePlus; Q9NR48; -.
DR   BioMuta; ASH1L; -.
DR   DMDM; 117949323; -.
DR   jPOST; Q9NR48; -.
DR   MaxQB; Q9NR48; -.
DR   PaxDb; Q9NR48; -.
DR   PeptideAtlas; Q9NR48; -.
DR   PRIDE; Q9NR48; -.
DR   ProteomicsDB; 82273; -.
DR   ProteomicsDB; 82274; -. [Q9NR48-2]
DR   Ensembl; ENST00000368346; ENSP00000357330; ENSG00000116539. [Q9NR48-1]
DR   Ensembl; ENST00000392403; ENSP00000376204; ENSG00000116539. [Q9NR48-2]
DR   GeneID; 55870; -.
DR   KEGG; hsa:55870; -.
DR   UCSC; uc001fkt.4; human. [Q9NR48-1]
DR   CTD; 55870; -.
DR   DisGeNET; 55870; -.
DR   EuPathDB; HostDB:ENSG00000116539.10; -.
DR   GeneCards; ASH1L; -.
DR   HGNC; HGNC:19088; ASH1L.
DR   HPA; HPA004806; -.
DR   MalaCards; ASH1L; -.
DR   MIM; 607999; gene.
DR   MIM; 617796; phenotype.
DR   neXtProt; NX_Q9NR48; -.
DR   OpenTargets; ENSG00000116539; -.
DR   PharmGKB; PA134891064; -.
DR   eggNOG; KOG1083; Eukaryota.
DR   eggNOG; COG2940; LUCA.
DR   eggNOG; COG5076; LUCA.
DR   GeneTree; ENSGT00940000156698; -.
DR   HOGENOM; HOG000034094; -.
DR   HOVERGEN; HBG080871; -.
DR   InParanoid; Q9NR48; -.
DR   KO; K06101; -.
DR   OMA; HSEMTDY; -.
DR   OrthoDB; 507784at2759; -.
DR   PhylomeDB; Q9NR48; -.
DR   TreeFam; TF106416; -.
DR   Reactome; R-HSA-3214841; PKMTs methylate histone lysines.
DR   SIGNOR; Q9NR48; -.
DR   ChiTaRS; ASH1L; human.
DR   EvolutionaryTrace; Q9NR48; -.
DR   GeneWiki; ASH1L; -.
DR   GenomeRNAi; 55870; -.
DR   PRO; PR:Q9NR48; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   Bgee; ENSG00000116539; Expressed in 211 organ(s), highest expression level in amniotic fluid.
DR   ExpressionAtlas; Q9NR48; baseline and differential.
DR   Genevisible; Q9NR48; HS.
DR   GO; GO:0005923; C:bicellular tight junction; TAS:ProtInc.
DR   GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR   GO; GO:0003682; F:chromatin binding; IEA:InterPro.
DR   GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISM:NTNU_SB.
DR   GO; GO:0046975; F:histone methyltransferase activity (H3-K36 specific); IDA:HGNC.
DR   GO; GO:0042800; F:histone methyltransferase activity (H3-K4 specific); IEA:Ensembl.
DR   GO; GO:0018024; F:histone-lysine N-methyltransferase activity; TAS:Reactome.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR   GO; GO:0046697; P:decidualization; IEA:Ensembl.
DR   GO; GO:0006323; P:DNA packaging; TAS:ProtInc.
DR   GO; GO:0030317; P:flagellated sperm motility; IEA:Ensembl.
DR   GO; GO:0097676; P:histone H3-K36 dimethylation; IDA:HGNC.
DR   GO; GO:0032635; P:interleukin-6 production; IEA:Ensembl.
DR   GO; GO:0002674; P:negative regulation of acute inflammatory response; IEA:Ensembl.
DR   GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR   GO; GO:0043409; P:negative regulation of MAPK cascade; IEA:Ensembl.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR   GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR   GO; GO:0007338; P:single fertilization; IEA:Ensembl.
DR   GO; GO:0001501; P:skeletal system development; IEA:Ensembl.
DR   GO; GO:1903699; P:tarsal gland development; IEA:Ensembl.
DR   GO; GO:0006366; P:transcription by RNA polymerase II; TAS:ProtInc.
DR   GO; GO:1903709; P:uterine gland development; IEA:Ensembl.
DR   GO; GO:0061038; P:uterus morphogenesis; IEA:Ensembl.
DR   Gene3D; 1.20.920.10; -; 1.
DR   Gene3D; 3.30.40.10; -; 1.
DR   InterPro; IPR017956; AT_hook_DNA-bd_motif.
DR   InterPro; IPR006560; AWS_dom.
DR   InterPro; IPR001025; BAH_dom.
DR   InterPro; IPR001487; Bromodomain.
DR   InterPro; IPR036427; Bromodomain-like_sf.
DR   InterPro; IPR003616; Post-SET_dom.
DR   InterPro; IPR001214; SET_dom.
DR   InterPro; IPR019786; Zinc_finger_PHD-type_CS.
DR   InterPro; IPR011011; Znf_FYVE_PHD.
DR   InterPro; IPR001965; Znf_PHD.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   Pfam; PF17907; AWS; 1.
DR   Pfam; PF01426; BAH; 1.
DR   Pfam; PF00439; Bromodomain; 1.
DR   Pfam; PF00856; SET; 1.
DR   SMART; SM00384; AT_hook; 4.
DR   SMART; SM00570; AWS; 1.
DR   SMART; SM00439; BAH; 1.
DR   SMART; SM00297; BROMO; 1.
DR   SMART; SM00249; PHD; 1.
DR   SMART; SM00317; SET; 1.
DR   SUPFAM; SSF47370; SSF47370; 1.
DR   SUPFAM; SSF57903; SSF57903; 1.
DR   PROSITE; PS51215; AWS; 1.
DR   PROSITE; PS51038; BAH; 1.
DR   PROSITE; PS50014; BROMODOMAIN_2; 1.
DR   PROSITE; PS50868; POST_SET; 1.
DR   PROSITE; PS50280; SET; 1.
DR   PROSITE; PS01359; ZF_PHD_1; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Activator; Alternative splicing;
KW   Bromodomain; Cell junction; Chromatin regulator; Chromosome;
KW   Complete proteome; Disease mutation; Isopeptide bond;
KW   Mental retardation; Metal-binding; Methylation; Methyltransferase;
KW   Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat;
KW   S-adenosyl-L-methionine; Tight junction; Transcription;
KW   Transcription regulation; Transferase; Ubl conjugation; Zinc;
KW   Zinc-finger.
FT   CHAIN         1   2969       Histone-lysine N-methyltransferase ASH1L.
FT                                /FTId=PRO_0000259516.
FT   DOMAIN     2091   2142       AWS. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00562}.
FT   DOMAIN     2145   2261       SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00190}.
FT   DOMAIN     2269   2285       Post-SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00155}.
FT   DOMAIN     2463   2533       Bromo. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00035}.
FT   DOMAIN     2661   2798       BAH. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00370}.
FT   DNA_BIND    887    899       A.T hook 1.
FT   DNA_BIND   1347   1359       A.T hook 2.
FT   DNA_BIND   1847   1859       A.T hook 3.
FT   ZN_FING    2585   2631       PHD-type.
FT   REGION     2069   2288       Catalytic domain.
FT   COMPBIAS   1380   1424       Pro-rich.
FT   COMPBIAS   1580   1791       Ser-rich.
FT   MOD_RES      22     22       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648}.
FT   MOD_RES     375    375       N6-acetyllysine.
FT                                {ECO:0000244|PubMed:19413330}.
FT   MOD_RES    1162   1162       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q99MY8}.
FT   MOD_RES    1170   1170       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q99MY8}.
FT   MOD_RES    1220   1220       N5-methylglutamine.
FT                                {ECO:0000269|PubMed:26797129}.
FT   MOD_RES    2317   2317       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q99MY8}.
FT   MOD_RES    2319   2319       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q99MY8}.
FT   MOD_RES    2323   2323       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q99MY8}.
FT   CROSSLNK     34     34       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO2).
FT                                {ECO:0000244|PubMed:28112733}.
FT   CROSSLNK    425    425       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO2).
FT                                {ECO:0000244|PubMed:28112733}.
FT   VAR_SEQ    2035   2039       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:14702039}.
FT                                /FTId=VSP_039421.
FT   VARIANT     277    277       S -> G (in dbSNP:rs186255422).
FT                                {ECO:0000269|PubMed:23033978}.
FT                                /FTId=VAR_069405.
FT   VARIANT     724    724       A -> S (in MRD52; unknown pathological
FT                                significance; dbSNP:rs1293246328).
FT                                {ECO:0000269|PubMed:23033978}.
FT                                /FTId=VAR_069406.
FT   VARIANT     972    972       K -> R (in MRD52; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:23033978}.
FT                                /FTId=VAR_069407.
FT   VARIANT    1276   1276       Y -> H (in MRD52; unknown pathological
FT                                significance; dbSNP:rs539982914).
FT                                {ECO:0000269|PubMed:23033978}.
FT                                /FTId=VAR_069408.
FT   VARIANT    1416   1416       S -> P (in dbSNP:rs13373934).
FT                                /FTId=VAR_055905.
FT   VARIANT    1771   1771       T -> A (in dbSNP:rs4971053).
FT                                {ECO:0000269|PubMed:10860993}.
FT                                /FTId=VAR_028949.
FT   VARIANT    1775   1775       C -> W (in MRD52; unknown pathological
FT                                significance; dbSNP:rs753734834).
FT                                {ECO:0000269|PubMed:23033978}.
FT                                /FTId=VAR_069409.
FT   VARIANT    2085   2085       V -> I (in MRD52; unknown pathological
FT                                significance; dbSNP:rs749494995).
FT                                {ECO:0000269|PubMed:27824329}.
FT                                /FTId=VAR_080559.
FT   VARIANT    2148   2969       Missing (in MRD52).
FT                                {ECO:0000269|PubMed:28191889}.
FT                                /FTId=VAR_080560.
FT   VARIANT    2396   2396       R -> H (in MRD52; unknown pathological
FT                                significance; dbSNP:rs753029013).
FT                                {ECO:0000269|PubMed:28191889}.
FT                                /FTId=VAR_080561.
FT   VARIANT    2791   2791       A -> P (in MRD52).
FT                                {ECO:0000269|PubMed:28394464}.
FT                                /FTId=VAR_080562.
FT   VARIANT    2853   2853       D -> G (in MRD52; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:23033978}.
FT                                /FTId=VAR_069410.
FT   MUTAGEN    1220   1220       Q->R: Abolishes methylation by N6AMT1.
FT                                {ECO:0000269|PubMed:26797129}.
FT   CONFLICT   2594   2594       K -> N (in Ref. 1; AAF68983).
FT                                {ECO:0000305}.
FT   CONFLICT   2697   2697       D -> H (in Ref. 1; AAF68983).
FT                                {ECO:0000305}.
FT   STRAND     2081   2084       {ECO:0000244|PDB:4YPA}.
FT   STRAND     2104   2106       {ECO:0000244|PDB:3OPE}.
FT   HELIX      2114   2117       {ECO:0000244|PDB:4YNM}.
FT   TURN       2124   2126       {ECO:0000244|PDB:4YNM}.
FT   HELIX      2130   2132       {ECO:0000244|PDB:4YNM}.
FT   STRAND     2133   2135       {ECO:0000244|PDB:4YPU}.
FT   TURN       2137   2141       {ECO:0000244|PDB:4YNM}.
FT   STRAND     2147   2151       {ECO:0000244|PDB:4YNM}.
FT   STRAND     2155   2163       {ECO:0000244|PDB:4YNM}.
FT   STRAND     2170   2173       {ECO:0000244|PDB:4YNM}.
FT   STRAND     2177   2180       {ECO:0000244|PDB:4YNM}.
FT   HELIX      2181   2190       {ECO:0000244|PDB:4YNM}.
FT   TURN       2191   2194       {ECO:0000244|PDB:4YPE}.
FT   STRAND     2200   2204       {ECO:0000244|PDB:4YNM}.
FT   STRAND     2207   2210       {ECO:0000244|PDB:4YNM}.
FT   STRAND     2212   2215       {ECO:0000244|PDB:4YNM}.
FT   HELIX      2217   2220       {ECO:0000244|PDB:4YNM}.
FT   STRAND     2228   2236       {ECO:0000244|PDB:4YNM}.
FT   STRAND     2239   2248       {ECO:0000244|PDB:4YNM}.
FT   HELIX      2260   2263       {ECO:0000244|PDB:4YNM}.
FT   STRAND     2282   2284       {ECO:0000244|PDB:4YNM}.
FT   HELIX      2438   2458       {ECO:0000244|PDB:3MQM}.
FT   HELIX      2469   2471       {ECO:0000244|PDB:3MQM}.
FT   HELIX      2477   2479       {ECO:0000244|PDB:3MQM}.
FT   HELIX      2483   2486       {ECO:0000244|PDB:3MQM}.
FT   HELIX      2493   2501       {ECO:0000244|PDB:3MQM}.
FT   HELIX      2508   2526       {ECO:0000244|PDB:3MQM}.
FT   HELIX      2531   2558       {ECO:0000244|PDB:3MQM}.
SQ   SEQUENCE   2969 AA;  332790 MW;  DA0135C72A2E2065 CRC64;
     MDPRNTAMLG LGSDSEGFSR KSPSAISTGT LVSKREVELE KNTKEEEDLR KRNRERNIEA
     GKDDGLTDAQ QQFSVKETNF SEGNLKLKIG LQAKRTKKPP KNLENYVCRP AIKTTIKHPR
     KALKSGKMTD EKNEHCPSKR DPSKLYKKAD DVAAIECQSE EVIRLHSQGE NNPLSKKLSP
     VHSEMADYIN ATPSTLLGSR DPDLKDRALL NGGTSVTEKL AQLIATCPPS KSSKTKPKKL
     GTGTTAGLVS KDLIRKAGVG SVAGIIHKDL IKKPTISTAV GLVTKDPGKK PVFNAAVGLV
     NKDSVKKLGT GTTAVFINKN LGKKPGTITT VGLLSKDSGK KLGIGIVPGL VHKESGKKLG
     LGTVVGLVNK DLGKKLGSTV GLVAKDCAKK IVASSAMGLV NKDIGKKLMS CPLAGLISKD
     AINLKAEALL PTQEPLKASC STNINNQESQ ELSESLKDSA TSKTFEKNVV RQNKESILEK
     FSVRKEIINL EKEMFNEGTC IQQDSFSSSE KGSYETSKHE KQPPVYCTSP DFKMGGASDV
     STAKSPFSAV GESNLPSPSP TVSVNPLTRS PPETSSQLAP NPLLLSSTTE LIEEISESVG
     KNQFTSESTH LNVGHRSVGH SISIECKGID KEVNDSKTTH IDIPRISSSL GKKPSLTSES
     SIHTITPSVV NFTSLFSNKP FLKLGAVSAS DKHCQVAESL STSLQSKPLK KRKGRKPRWT
     KVVARSTCRS PKGLELERSE LFKNVSCSSL SNSNSEPAKF MKNIGPPSFV DHDFLKRRLP
     KLSKSTAPSL ALLADSEKPS HKSFATHKLS SSMCVSSDLL SDIYKPKRGR PKSKEMPQLE
     GPPKRTLKIP ASKVFSLQSK EEQEPPILQP EIEIPSFKQG LSVSPFPKKR GRPKRQMRSP
     VKMKPPVLSV APFVATESPS KLESESDNHR SSSDFFESED QLQDPDDLDD SHRPSVCSMS
     DLEMEPDKKI TKRNNGQLMK TIIRKINKMK TLKRKKLLNQ ILSSSVESSN KGKVQSKLHN
     TVSSLAATFG SKLGQQINVS KKGTIYIGKR RGRKPKTVLN GILSGSPTSL AVLEQTAQQA
     AGSALGQILP PLLPSSASSS EILPSPICSQ SSGTSGGQSP VSSDAGFVEP SSVPYLHLHS
     RQGSMIQTLA MKKASKGRRR LSPPTLLPNS PSHLSELTSL KEATPSPISE SHSDETIPSD
     SGIGTDNNST SDRAEKFCGQ KKRRHSFEHV SLIPPETSTV LSSLKEKHKH KCKRRNHDYL
     SYDKMKRQKR KRKKKYPQLR NRQDPDFIAE LEELISRLSE IRITHRSHHF IPRDLLPTIF
     RINFNSFYTH PSFPLDPLHY IRKPDLKKKR GRPPKMREAM AEMPFMHSLS FPLSSTGFYP
     SYGMPYSPSP LTAAPIGLGY YGRYPPTLYP PPPSPSFTTP LPPPSYMHAG HLLLNPAKYH
     KKKHKLLRQE AFLTTSRTPL LSMSTYPSVP PEMAYGWMVE HKHRHRHKHR EHRSSEQPQV
     SMDTGSSRSV LESLKRYRFG KDAVGERYKH KEKHRCHMSC PHLSPSKSLI NREEQWVHRE
     PSESSPLALG LQTPLQIDCS ESSPSLSLGG FTPNSEPASS DEHTNLFTSA IGSCRVSNPN
     SSGRKKLTDS PGLFSAQDTS LNRLHRKESL PSNERAVQTL AGSQPTSDKP SQRPSESTNC
     SPTRKRSSSE STSSTVNGVP SRSPRLVASG DDSVDSLLQR MVQNEDQEPM EKSIDAVIAT
     ASAPPSSSPG RSHSKDRTLG KPDSLLVPAV TSDSCNNSIS LLSEKLTSSC SPHHIKRSVV
     EAMQRQARKM CNYDKILATK KNLDHVNKIL KAKKLQRQAR TGNNFVKRRP GRPRKCPLQA
     VVSMQAFQAA QFVNPELNRD EEGAALHLSP DTVTDVIEAV VQSVNLNPEH KKGLKRKGWL
     LEEQTRKKQK PLPEEEEQEN NKSFNEAPVE IPSPSETPAK PSEPESTLQP VLSLIPREKK
     PPRPPKKKYQ KAGLYSDVYK TTDPKSRLIQ LKKEKLEYTP GEHEYGLFPA PIHVVFFVSG
     KYLRQKRIDF QLPYDILWQW KHNQLYKKPD VPLYKKIRSN VYVDVKPLSG YEATTCNCKK
     PDDDTRKGCV DDCLNRMIFA ECSPNTCPCG EQCCNQRIQR HEWVQCLERF RAEEKGWGIR
     TKEPLKAGQF IIEYLGEVVS EQEFRNRMIE QYHNHSDHYC LNLDSGMVID SYRMGNEARF
     INHSCDPNCE MQKWSVNGVY RIGLYALKDM PAGTELTYDY NFHSFNVEKQ QLCKCGFEKC
     RGIIGGKSQR VNGLTSSKNS QPMATHKKSG RSKEKRKSKH KLKKRRGHLS EEPSENINTP
     TRLTPQLQMK PMSNRERNFV LKHHVFLVRN WEKIRQKQEE VKHTSDNIHS ASLYTRWNGI
     CRDDGNIKSD VFMTQFSALQ TARSVRTRRL AAAEENIEVA RAARLAQIFK EICDGIISYK
     DSSRQALAAP LLNLPPKKKN ADYYEKISDP LDLITIEKQI LTGYYKTVEA FDADMLKVFR
     NAEKYYGRKS PVGRDVCRLR KAYYNARHEA SAQIDEIVGE TASEADSSET SVSEKENGHE
     KDDDVIRCIC GLYKDEGLMI QCDKCMVWQH CDCMGVNSDV EHYLCEQCDP RPVDREVPMI
     PRPHYAQPGC VYFICLLRDD LLLRQGDCVY LMRDSRRTPD GHPVRQSYRL LSHINRDKLD
     IFRIEKLWKN EKEERFAFGH HYFRPHETHH SPSRRFYHNE LFRVPLYEII PLEAVVGTCC
     VLDLYTYCKG RPKGVKEQDV YICDYRLDKS AHLFYKIHRN RYPVCTKPYA FDHFPKKLTP
     KKDFSPHYVP DNYKRNGGRS SWKSERSKPP LKDLGQEDDA LPLIEEVLAS QEQAANEIPS
     LEEPEREGAT ANVSEGEKKT EESSQEPQST CTPEERRHNQ RERLNQILLN LLEKIPGKNA
     IDVTYLLEEG SGRKLRRRTL FIPENSFRK
//
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