ASH1L_HUMAN
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 03-AUG-2022, entry version 176.
DE RecName: Full=Histone-lysine N-methyltransferase ASH1L;
DE EC=2.1.1.359 {ECO:0000269|PubMed:21239497};
DE EC=2.1.1.367 {ECO:0000250|UniProtKB:Q99MY8};
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., Bullrich F.,
RA 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 cell-
RT 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., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., 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., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., 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., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., 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. The
RT complete sequences of 150 new cDNA clones from brain which code for large
RT 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., 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 [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., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22, AND IDENTIFICATION BY
RP 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 MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT 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 mammalian
RT 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 methyltransferase and
RT 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-modification
RT 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 catalytic
RT 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; TRP-1775
RP 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., Gilissen C.,
RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G.,
RA 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., Turner T.N.,
RA Liu Y., Zhao W., Hoekzema K., Vives L., Xia L., Tang M., Ou J., Chen B.,
RA Shen Y., Xun G., Long M., Lin J., Kronenberg Z.N., Peng Y., Bai T., Li H.,
RA Ke X., Hu Z., Zhao J., Zou X., Xia K., Eichler E.E.;
RT "De novo genic mutations among a Chinese autism spectrum disorder 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., Aten E.,
RA 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., Avola E.,
RA Giusto S., Courchesne E., Pramparo T., Pierce K., Nalabolu S., Amaral D.G.,
RA Scheffer I.E., Delatycki M.B., Lockhart P.J., Hormozdiari F., Harich B.,
RA Castells-Nobau A., Xia K., Peeters H., Nordenskjoeld M., Schenck A.,
RA Bernier R.A., Eichler E.E.;
RT "Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes
RT with autism and developmental-disability biases.";
RL Nat. Genet. 49:515-526(2017).
CC -!- FUNCTION: Histone methyltransferase specifically trimethylating 'Lys-
CC 36' of histone H3 forming H3K36me3 (PubMed:21239497). Also
CC monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro (By
CC similarity). The physiological significance of the H3K9me1 activity is
CC unclear (By similarity). {ECO:0000250|UniProtKB:Q99MY8,
CC ECO:0000269|PubMed:21239497}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(36)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+)
CC + N(6),N(6),N(6)-trimethyl-L-lysyl(36)-[histone H3] + 3 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60324, Rhea:RHEA-COMP:9785, Rhea:RHEA-
CC COMP:15536, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.359;
CC Evidence={ECO:0000269|PubMed:21239497};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine = H(+) +
CC N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:60280, Rhea:RHEA-COMP:15542, Rhea:RHEA-COMP:15546,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.367;
CC Evidence={ECO:0000250|UniProtKB:Q99MY8};
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 junction
CC localization is however unclear. {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. {ECO:0000269|PubMed:26797129}.
CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 52
CC (MRD52) [MIM:617796]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period.
CC {ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:27824329,
CC ECO:0000269|PubMed:28191889, ECO:0000269|PubMed:28394464}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. Histone-lysine methyltransferase family. SET2 subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00190}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA92658.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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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 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 PDB; 6AGO; X-ray; 3.10 A; A/B=2039-2293.
DR PDB; 6INE; X-ray; 2.60 A; A=2026-2293.
DR PDB; 6WZW; X-ray; 1.69 A; A=2074-2293.
DR PDB; 6X0P; X-ray; 1.69 A; A/B/C/D=2074-2293.
DR PDBsum; 3MQM; -.
DR PDBsum; 3OPE; -.
DR PDBsum; 4YNM; -.
DR PDBsum; 4YNP; -.
DR PDBsum; 4YPA; -.
DR PDBsum; 4YPE; -.
DR PDBsum; 4YPU; -.
DR PDBsum; 6AGO; -.
DR PDBsum; 6INE; -.
DR PDBsum; 6WZW; -.
DR PDBsum; 6X0P; -.
DR SMR; Q9NR48; -.
DR BioGRID; 120969; 44.
DR IntAct; Q9NR48; 19.
DR MINT; Q9NR48; -.
DR STRING; 9606.ENSP00000376204; -.
DR BindingDB; Q9NR48; -.
DR ChEMBL; CHEMBL3588739; -.
DR CarbonylDB; Q9NR48; -.
DR iPTMnet; Q9NR48; -.
DR PhosphoSitePlus; Q9NR48; -.
DR BioMuta; ASH1L; -.
DR DMDM; 117949323; -.
DR EPD; Q9NR48; -.
DR jPOST; Q9NR48; -.
DR MassIVE; Q9NR48; -.
DR MaxQB; Q9NR48; -.
DR PaxDb; Q9NR48; -.
DR PeptideAtlas; Q9NR48; -.
DR PRIDE; Q9NR48; -.
DR ProteomicsDB; 82273; -. [Q9NR48-1]
DR ProteomicsDB; 82274; -. [Q9NR48-2]
DR Antibodypedia; 1436; 184 antibodies from 19 providers.
DR DNASU; 55870; -.
DR Ensembl; ENST00000368346.7; ENSP00000357330.3; ENSG00000116539.14. [Q9NR48-1]
DR Ensembl; ENST00000392403.8; ENSP00000376204.3; ENSG00000116539.14. [Q9NR48-2]
DR Ensembl; ENST00000677213.1; ENSP00000503315.1; ENSG00000116539.14. [Q9NR48-2]
DR Ensembl; ENST00000678117.1; ENSP00000504629.1; ENSG00000116539.14. [Q9NR48-2]
DR Ensembl; ENST00000679097.1; ENSP00000503265.1; ENSG00000116539.14. [Q9NR48-2]
DR GeneID; 55870; -.
DR KEGG; hsa:55870; -.
DR MANE-Select; ENST00000392403.8; ENSP00000376204.3; NM_018489.3; NP_060959.2. [Q9NR48-2]
DR UCSC; uc001fkt.4; human. [Q9NR48-1]
DR CTD; 55870; -.
DR DisGeNET; 55870; -.
DR GeneCards; ASH1L; -.
DR HGNC; HGNC:19088; ASH1L.
DR HPA; ENSG00000116539; Low tissue specificity.
DR MalaCards; ASH1L; -.
DR MIM; 607999; gene.
DR MIM; 617796; phenotype.
DR neXtProt; NX_Q9NR48; -.
DR OpenTargets; ENSG00000116539; -.
DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability.
DR PharmGKB; PA134891064; -.
DR VEuPathDB; HostDB:ENSG00000116539; -.
DR eggNOG; KOG1083; Eukaryota.
DR GeneTree; ENSGT00940000156698; -.
DR HOGENOM; CLU_000657_0_0_1; -.
DR InParanoid; Q9NR48; -.
DR OMA; EPQPACT; -.
DR OrthoDB; 507784at2759; -.
DR PhylomeDB; Q9NR48; -.
DR TreeFam; TF106416; -.
DR BioCyc; MetaCyc:HS04019-MON; -.
DR BRENDA; 2.1.1.357; 2681.
DR PathwayCommons; Q9NR48; -.
DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines.
DR SignaLink; Q9NR48; -.
DR SIGNOR; Q9NR48; -.
DR BioGRID-ORCS; 55870; 42 hits in 1103 CRISPR screens.
DR ChiTaRS; ASH1L; human.
DR EvolutionaryTrace; Q9NR48; -.
DR GeneWiki; ASH1L; -.
DR GenomeRNAi; 55870; -.
DR Pharos; Q9NR48; Tbio.
DR PRO; PR:Q9NR48; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9NR48; protein.
DR Bgee; ENSG00000116539; Expressed in Brodmann (1909) area 23 and 186 other tissues.
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:0046975; F:histone methyltransferase activity (H3-K36 specific); IDA:HGNC.
DR GO; GO:0042800; F:histone methyltransferase activity (H3-K4 specific); IBA:GO_Central.
DR GO; GO:0046974; F:histone methyltransferase activity (H3-K9 specific); ISS:UniProtKB.
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:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0046697; P:decidualization; IEA:Ensembl.
DR GO; GO:0030317; P:flagellated sperm motility; IEA:Ensembl.
DR GO; GO:0097676; P:histone H3-K36 dimethylation; IDA:HGNC.
DR GO; GO:0051568; P:histone H3-K4 methylation; IBA:GO_Central.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
DR GO; GO:0000165; P:MAPK cascade; 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:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
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; IEA:Ensembl.
DR GO; GO:1903709; P:uterine gland development; IEA:Ensembl.
DR GO; GO:0061038; P:uterus morphogenesis; IEA:Ensembl.
DR CDD; cd05525; Bromo_ASH1; 1.
DR CDD; cd15548; PHD_ASH1L; 1.
DR Gene3D; 1.20.920.10; -; 1.
DR Gene3D; 2.170.270.10; -; 1.
DR Gene3D; 2.30.30.490; -; 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; IPR043151; BAH_sf.
DR InterPro; IPR043320; Bromo_ASH1L.
DR InterPro; IPR001487; Bromodomain.
DR InterPro; IPR036427; Bromodomain-like_sf.
DR InterPro; IPR043319; PHD_ASH1L.
DR InterPro; IPR003616; Post-SET_dom.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
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 SUPFAM; SSF82199; SSF82199; 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; Bromodomain;
KW Cell junction; Chromatin regulator; Chromosome; Disease variant;
KW Intellectual disability; Isopeptide bond; Metal-binding; Methylation;
KW Methyltransferase; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW S-adenosyl-L-methionine; Tight junction; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..2969
FT /note="Histone-lysine N-methyltransferase ASH1L"
FT /id="PRO_0000259516"
FT DOMAIN 2091..2142
FT /note="AWS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00562"
FT DOMAIN 2145..2261
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT DOMAIN 2269..2285
FT /note="Post-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155"
FT DOMAIN 2463..2533
FT /note="Bromo"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00035"
FT DOMAIN 2661..2798
FT /note="BAH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00370"
FT DNA_BIND 887..899
FT /note="A.T hook 1"
FT DNA_BIND 1347..1359
FT /note="A.T hook 2"
FT DNA_BIND 1847..1859
FT /note="A.T hook 3"
FT ZN_FING 2585..2631
FT /note="PHD-type"
FT REGION 1..70
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 118..143
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 501..525
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 537..583
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 824..845
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 878..966
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1100..1128
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1151..1231
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1243..1281
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1489..1508
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1580..1711
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1741..1761
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1911..1991
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2069..2288
FT /note="Catalytic domain"
FT REGION 2288..2346
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2825..2856
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2876..2919
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 17..31
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 34..63
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 123..143
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 541..583
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 824..841
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 922..937
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 946..966
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1100..1126
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1165..1214
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1215..1230
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1580..1640
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1653..1702
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1911..1943
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2289..2306
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2309..2326
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2838..2856
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2879..2904
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 375
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 1162
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99MY8"
FT MOD_RES 1170
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99MY8"
FT MOD_RES 1220
FT /note="N5-methylglutamine"
FT /evidence="ECO:0000269|PubMed:26797129"
FT MOD_RES 2317
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99MY8"
FT MOD_RES 2319
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99MY8"
FT MOD_RES 2323
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99MY8"
FT CROSSLNK 34
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 425
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 2035..2039
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_039421"
FT VARIANT 277
FT /note="S -> G (in dbSNP:rs186255422)"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069405"
FT VARIANT 724
FT /note="A -> S (in MRD52; unknown pathological significance;
FT dbSNP:rs1293246328)"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069406"
FT VARIANT 972
FT /note="K -> R (in MRD52; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069407"
FT VARIANT 1276
FT /note="Y -> H (in MRD52; unknown pathological significance;
FT dbSNP:rs539982914)"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069408"
FT VARIANT 1416
FT /note="S -> P (in dbSNP:rs13373934)"
FT /id="VAR_055905"
FT VARIANT 1771
FT /note="T -> A (in dbSNP:rs4971053)"
FT /evidence="ECO:0000269|PubMed:10860993"
FT /id="VAR_028949"
FT VARIANT 1775
FT /note="C -> W (in MRD52; unknown pathological significance;
FT dbSNP:rs753734834)"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069409"
FT VARIANT 2085
FT /note="V -> I (in MRD52; unknown pathological significance;
FT dbSNP:rs749494995)"
FT /evidence="ECO:0000269|PubMed:27824329"
FT /id="VAR_080559"
FT VARIANT 2148..2969
FT /note="Missing (in MRD52)"
FT /evidence="ECO:0000269|PubMed:28191889"
FT /id="VAR_080560"
FT VARIANT 2396
FT /note="R -> H (in MRD52; unknown pathological significance;
FT dbSNP:rs753029013)"
FT /evidence="ECO:0000269|PubMed:28191889"
FT /id="VAR_080561"
FT VARIANT 2791
FT /note="A -> P (in MRD52; dbSNP:rs1553241570)"
FT /evidence="ECO:0000269|PubMed:28394464"
FT /id="VAR_080562"
FT VARIANT 2853
FT /note="D -> G (in MRD52; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069410"
FT MUTAGEN 1220
FT /note="Q->R: Abolishes methylation by N6AMT1."
FT /evidence="ECO:0000269|PubMed:26797129"
FT CONFLICT 2594
FT /note="K -> N (in Ref. 1; AAF68983)"
FT /evidence="ECO:0000305"
FT CONFLICT 2697
FT /note="D -> H (in Ref. 1; AAF68983)"
FT /evidence="ECO:0000305"
FT HELIX 2040..2044
FT /evidence="ECO:0007829|PDB:6INE"
FT HELIX 2054..2065
FT /evidence="ECO:0007829|PDB:6INE"
FT STRAND 2081..2084
FT /evidence="ECO:0007829|PDB:6WZW"
FT STRAND 2104..2106
FT /evidence="ECO:0007829|PDB:3OPE"
FT STRAND 2108..2111
FT /evidence="ECO:0007829|PDB:6AGO"
FT HELIX 2116..2118
FT /evidence="ECO:0007829|PDB:6WZW"
FT TURN 2124..2126
FT /evidence="ECO:0007829|PDB:6WZW"
FT HELIX 2130..2132
FT /evidence="ECO:0007829|PDB:6WZW"
FT STRAND 2133..2135
FT /evidence="ECO:0007829|PDB:6WZW"
FT TURN 2137..2141
FT /evidence="ECO:0007829|PDB:6WZW"
FT STRAND 2147..2151
FT /evidence="ECO:0007829|PDB:6WZW"
FT STRAND 2155..2163
FT /evidence="ECO:0007829|PDB:6WZW"
FT STRAND 2170..2173
FT /evidence="ECO:0007829|PDB:6WZW"
FT STRAND 2177..2180
FT /evidence="ECO:0007829|PDB:6WZW"
FT HELIX 2181..2190
FT /evidence="ECO:0007829|PDB:6WZW"
FT HELIX 2192..2194
FT /evidence="ECO:0007829|PDB:6WZW"
FT HELIX 2195..2197
FT /evidence="ECO:0007829|PDB:6AGO"
FT STRAND 2200..2204
FT /evidence="ECO:0007829|PDB:6WZW"
FT STRAND 2207..2210
FT /evidence="ECO:0007829|PDB:6WZW"
FT STRAND 2212..2215
FT /evidence="ECO:0007829|PDB:6WZW"
FT HELIX 2217..2220
FT /evidence="ECO:0007829|PDB:6WZW"
FT STRAND 2228..2236
FT /evidence="ECO:0007829|PDB:6WZW"
FT STRAND 2239..2248
FT /evidence="ECO:0007829|PDB:6WZW"
FT HELIX 2260..2263
FT /evidence="ECO:0007829|PDB:6WZW"
FT STRAND 2282..2284
FT /evidence="ECO:0007829|PDB:4YNM"
FT HELIX 2438..2458
FT /evidence="ECO:0007829|PDB:3MQM"
FT HELIX 2469..2471
FT /evidence="ECO:0007829|PDB:3MQM"
FT HELIX 2477..2479
FT /evidence="ECO:0007829|PDB:3MQM"
FT HELIX 2483..2486
FT /evidence="ECO:0007829|PDB:3MQM"
FT HELIX 2493..2501
FT /evidence="ECO:0007829|PDB:3MQM"
FT HELIX 2508..2526
FT /evidence="ECO:0007829|PDB:3MQM"
FT HELIX 2531..2558
FT /evidence="ECO:0007829|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
