Reviewed, UniProtKB/Swiss-Prot Q9NR48 (ASH1L_HUMAN)

Names and origin

Protein names

Recommended name:
    Probable histone-lysine N-methyltransferase ASH1L
    EC=2.1.1.43
Alternative name(s):
    Absent small and homeotic disks protein 1 homolog
    ASH1-like protein
      Short name=huASH1
    Lysine N-methyltransferase 2H

Gene names

Name:	ASH1L
Synonyms:	KIAA1420, KMT2H

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	2969 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Histone methyltransferase. Probably methylates 'Lys-4' of histone H3, a specific tag for epigenetic transcriptional activation By similarity.
Catalytic activity	S-adenosyl-L-methionine + histone L-lysine = S-adenosyl-L-homocysteine + histone N(6)-methyl-L-lysine.
Subcellular location	Nucleus. Cell junction › tight junction. Note: The relevance of tight junction localization is however unclear. Ref.1
Tissue specificity	Widely expressed, with highest level in brain, heart and kidney. Ref.1
Sequence similarities	Belongs to the histone-lysine methyltransferase family. SET2 subfamily. Contains 3 A.T hook DNA-binding domains. Contains 1 AWS domain. Contains 1 BAH domain. Contains 1 bromo domain. Contains 1 PHD-type zinc finger. Contains 1 post-SET domain. Contains 1 SET domain.
Sequence caution	The sequence CAI12716.2 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI13211.2 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cell junction Nucleus Tight junction
Coding sequence diversity	Polymorphism
Domain	Bromodomain Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Activator Chromatin regulator Methyltransferase Transferase
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	DNA packaging Ref.1 Traceable author statement. Source: ProtInc cell-cell signaling Ref.1 Traceable author statement. Source: ProtInc chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription Inferred from electronic annotation. Source: UniProtKB-KW transcription from RNA polymerase II promoter Ref.1 Traceable author statement. Source: ProtInc
Cellular component	nucleus Ref.1 Traceable author statement. Source: ProtInc tight junction Ref.1 Traceable author statement. Source: ProtInc
Molecular function	DNA binding Inferred from electronic annotation. Source: InterPro RNA polymerase II transcription factor activity Ref.1 Traceable author statement. Source: ProtInc histone-lysine N-methyltransferase activity Inferred from electronic annotation. Source: EC protein binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 2969	2969	Probable histone-lysine N-methyltransferase ASH1L		PRO_0000259516
Regions
	Domain	2091 – 2142	52	AWS
	Domain	2144 – 2265	122	SET
	Domain	2269 – 2285	17	Post-SET
	Domain	2463 – 2533	71	Bromo
	Domain	2661 – 2798	138	BAH
	DNA binding	887 – 899	13	A.T hook 1
	DNA binding	1347 – 1359	13	A.T hook 2
	DNA binding	1847 – 1859	13	A.T hook 3
	Zinc finger	2585 – 2631	47	PHD-type
	Compositional bias	1380 – 1424	45	Pro-rich
	Compositional bias	1580 – 1791	212	Ser-rich
Amino acid modifications
	Modified residue	22	1	Phosphoserine Ref.8
	Modified residue	1649	1	Phosphoserine Ref.6
	Modified residue	1681	1	Phosphoserine Ref.7
	Cross-link	402		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.5
	Cross-link	406		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.5
Natural variations
	Natural variant	1416	1	S → P: dbSNP rs13373934.		VAR_055905
	Natural variant	1771	1	T → A: dbSNP rs4971053. Ref.1		VAR_028949
Experimental info
	Sequence conflict	2594	1	K → N in AAF68983. Ref.1
	Sequence conflict	2697	1	D → H in AAF68983. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9NR48-1 [UniParc]. Last modified October 31, 2006. Version 2. Checksum: DA0135C72A2E2065	FASTA	2,969	332,790
	10 20 30 40 50 60 MDPRNTAMLG LGSDSEGFSR KSPSAISTGT LVSKREVELE KNTKEEEDLR KRNRERNIEA 70 80 90 100 110 120 GKDDGLTDAQ QQFSVKETNF SEGNLKLKIG LQAKRTKKPP KNLENYVCRP AIKTTIKHPR 130 140 150 160 170 180 KALKSGKMTD EKNEHCPSKR DPSKLYKKAD DVAAIECQSE EVIRLHSQGE NNPLSKKLSP 190 200 210 220 230 240 VHSEMADYIN ATPSTLLGSR DPDLKDRALL NGGTSVTEKL AQLIATCPPS KSSKTKPKKL 250 260 270 280 290 300 GTGTTAGLVS KDLIRKAGVG SVAGIIHKDL IKKPTISTAV GLVTKDPGKK PVFNAAVGLV 310 320 330 340 350 360 NKDSVKKLGT GTTAVFINKN LGKKPGTITT VGLLSKDSGK KLGIGIVPGL VHKESGKKLG 370 380 390 400 410 420 LGTVVGLVNK DLGKKLGSTV GLVAKDCAKK IVASSAMGLV NKDIGKKLMS CPLAGLISKD 430 440 450 460 470 480 AINLKAEALL PTQEPLKASC STNINNQESQ ELSESLKDSA TSKTFEKNVV RQNKESILEK 490 500 510 520 530 540 FSVRKEIINL EKEMFNEGTC IQQDSFSSSE KGSYETSKHE KQPPVYCTSP DFKMGGASDV 550 560 570 580 590 600 STAKSPFSAV GESNLPSPSP TVSVNPLTRS PPETSSQLAP NPLLLSSTTE LIEEISESVG 610 620 630 640 650 660 KNQFTSESTH LNVGHRSVGH SISIECKGID KEVNDSKTTH IDIPRISSSL GKKPSLTSES 670 680 690 700 710 720 SIHTITPSVV NFTSLFSNKP FLKLGAVSAS DKHCQVAESL STSLQSKPLK KRKGRKPRWT 730 740 750 760 770 780 KVVARSTCRS PKGLELERSE LFKNVSCSSL SNSNSEPAKF MKNIGPPSFV DHDFLKRRLP 790 800 810 820 830 840 KLSKSTAPSL ALLADSEKPS HKSFATHKLS SSMCVSSDLL SDIYKPKRGR PKSKEMPQLE 850 860 870 880 890 900 GPPKRTLKIP ASKVFSLQSK EEQEPPILQP EIEIPSFKQG LSVSPFPKKR GRPKRQMRSP 910 920 930 940 950 960 VKMKPPVLSV APFVATESPS KLESESDNHR SSSDFFESED QLQDPDDLDD SHRPSVCSMS 970 980 990 1000 1010 1020 DLEMEPDKKI TKRNNGQLMK TIIRKINKMK TLKRKKLLNQ ILSSSVESSN KGKVQSKLHN 1030 1040 1050 1060 1070 1080 TVSSLAATFG SKLGQQINVS KKGTIYIGKR RGRKPKTVLN GILSGSPTSL AVLEQTAQQA 1090 1100 1110 1120 1130 1140 AGSALGQILP PLLPSSASSS EILPSPICSQ SSGTSGGQSP VSSDAGFVEP SSVPYLHLHS 1150 1160 1170 1180 1190 1200 RQGSMIQTLA MKKASKGRRR LSPPTLLPNS PSHLSELTSL KEATPSPISE SHSDETIPSD 1210 1220 1230 1240 1250 1260 SGIGTDNNST SDRAEKFCGQ KKRRHSFEHV SLIPPETSTV LSSLKEKHKH KCKRRNHDYL 1270 1280 1290 1300 1310 1320 SYDKMKRQKR KRKKKYPQLR NRQDPDFIAE LEELISRLSE IRITHRSHHF IPRDLLPTIF 1330 1340 1350 1360 1370 1380 RINFNSFYTH PSFPLDPLHY IRKPDLKKKR GRPPKMREAM AEMPFMHSLS FPLSSTGFYP 1390 1400 1410 1420 1430 1440 SYGMPYSPSP LTAAPIGLGY YGRYPPTLYP PPPSPSFTTP LPPPSYMHAG HLLLNPAKYH 1450 1460 1470 1480 1490 1500 KKKHKLLRQE AFLTTSRTPL LSMSTYPSVP PEMAYGWMVE HKHRHRHKHR EHRSSEQPQV 1510 1520 1530 1540 1550 1560 SMDTGSSRSV LESLKRYRFG KDAVGERYKH KEKHRCHMSC PHLSPSKSLI NREEQWVHRE 1570 1580 1590 1600 1610 1620 PSESSPLALG LQTPLQIDCS ESSPSLSLGG FTPNSEPASS DEHTNLFTSA IGSCRVSNPN 1630 1640 1650 1660 1670 1680 SSGRKKLTDS PGLFSAQDTS LNRLHRKESL PSNERAVQTL AGSQPTSDKP SQRPSESTNC 1690 1700 1710 1720 1730 1740 SPTRKRSSSE STSSTVNGVP SRSPRLVASG DDSVDSLLQR MVQNEDQEPM EKSIDAVIAT 1750 1760 1770 1780 1790 1800 ASAPPSSSPG RSHSKDRTLG KPDSLLVPAV TSDSCNNSIS LLSEKLTSSC SPHHIKRSVV 1810 1820 1830 1840 1850 1860 EAMQRQARKM CNYDKILATK KNLDHVNKIL KAKKLQRQAR TGNNFVKRRP GRPRKCPLQA 1870 1880 1890 1900 1910 1920 VVSMQAFQAA QFVNPELNRD EEGAALHLSP DTVTDVIEAV VQSVNLNPEH KKGLKRKGWL 1930 1940 1950 1960 1970 1980 LEEQTRKKQK PLPEEEEQEN NKSFNEAPVE IPSPSETPAK PSEPESTLQP VLSLIPREKK 1990 2000 2010 2020 2030 2040 PPRPPKKKYQ KAGLYSDVYK TTDPKSRLIQ LKKEKLEYTP GEHEYGLFPA PIHVVFFVSG 2050 2060 2070 2080 2090 2100 KYLRQKRIDF QLPYDILWQW KHNQLYKKPD VPLYKKIRSN VYVDVKPLSG YEATTCNCKK 2110 2120 2130 2140 2150 2160 PDDDTRKGCV DDCLNRMIFA ECSPNTCPCG EQCCNQRIQR HEWVQCLERF RAEEKGWGIR 2170 2180 2190 2200 2210 2220 TKEPLKAGQF IIEYLGEVVS EQEFRNRMIE QYHNHSDHYC LNLDSGMVID SYRMGNEARF 2230 2240 2250 2260 2270 2280 INHSCDPNCE MQKWSVNGVY RIGLYALKDM PAGTELTYDY NFHSFNVEKQ QLCKCGFEKC 2290 2300 2310 2320 2330 2340 RGIIGGKSQR VNGLTSSKNS QPMATHKKSG RSKEKRKSKH KLKKRRGHLS EEPSENINTP 2350 2360 2370 2380 2390 2400 TRLTPQLQMK PMSNRERNFV LKHHVFLVRN WEKIRQKQEE VKHTSDNIHS ASLYTRWNGI 2410 2420 2430 2440 2450 2460 CRDDGNIKSD VFMTQFSALQ TARSVRTRRL AAAEENIEVA RAARLAQIFK EICDGIISYK 2470 2480 2490 2500 2510 2520 DSSRQALAAP LLNLPPKKKN ADYYEKISDP LDLITIEKQI LTGYYKTVEA FDADMLKVFR 2530 2540 2550 2560 2570 2580 NAEKYYGRKS PVGRDVCRLR KAYYNARHEA SAQIDEIVGE TASEADSSET SVSEKENGHE 2590 2600 2610 2620 2630 2640 KDDDVIRCIC GLYKDEGLMI QCDKCMVWQH CDCMGVNSDV EHYLCEQCDP RPVDREVPMI 2650 2660 2670 2680 2690 2700 PRPHYAQPGC VYFICLLRDD LLLRQGDCVY LMRDSRRTPD GHPVRQSYRL LSHINRDKLD 2710 2720 2730 2740 2750 2760 IFRIEKLWKN EKEERFAFGH HYFRPHETHH SPSRRFYHNE LFRVPLYEII PLEAVVGTCC 2770 2780 2790 2800 2810 2820 VLDLYTYCKG RPKGVKEQDV YICDYRLDKS AHLFYKIHRN RYPVCTKPYA FDHFPKKLTP 2830 2840 2850 2860 2870 2880 KKDFSPHYVP DNYKRNGGRS SWKSERSKPP LKDLGQEDDA LPLIEEVLAS QEQAANEIPS 2890 2900 2910 2920 2930 2940 LEEPEREGAT ANVSEGEKKT EESSQEPQST CTPEERRHNQ RERLNQILLN LLEKIPGKNA 2950 2960 IDVTYLLEEG SGRKLRRRTL FIPENSFRK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"huASH1 protein, a putative transcription factor encoded by a human homologue of the Drosophila ash1 gene, localizes to both nuclei and cell-cell tight junctions." Nakamura T., Blechman J., Tada S., Rozovskaia T., Itoyama T., Bullrich F., Mazo A., Croce C.M., Geiger B., Canaani E. Proc. Natl. Acad. Sci. U.S.A. 97:7284-7289(2000) [PubMed: 10860993] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT ALA-1771.
[2]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:65-73(2000) [PubMed: 10718198] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1345. Tissue: Brain.
[4]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 710-1345. Tissue: Brain.
[5]	"The proteomic reactor facilitates the analysis of affinity-purified proteins by mass spectrometry: application for identifying ubiquitinated proteins in human cells." Vasilescu J., Zweitzig D.R., Denis N.J., Smith J.C., Ethier M., Haines D.S., Figeys D. J. Proteome Res. 6:298-305(2007) [PubMed: 17203973] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-402 AND LYS-406, MASS SPECTROMETRY. Tissue: Lung adenocarcinoma.
[6]	"Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis." Wang B., Malik R., Nigg E.A., Korner R. Anal. Chem. 80:9526-9533(2008) [PubMed: 19007248] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1649, MASS SPECTROMETRY.
[7]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1681, MASS SPECTROMETRY.
[8]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF257305 mRNA. Translation: AAF68983.1. AL139410, AL353807 Genomic DNA. Translation: CAI12716.2. Sequence problems. AL139410, AL353807 Genomic DNA. Translation: CAI12722.1. AL353807, AL139410 Genomic DNA. Translation: CAI13211.2. Sequence problems. AL353807, AL139410 Genomic DNA. Translation: CAI13212.1. AB037841 mRNA. Translation: BAA92658.1. Different initiation. AB209068 mRNA. Translation: BAD92305.1.
IPI	IPI00020546.
RefSeq	NP_060959.2.
UniGene	Hs.491060
3D structure databases
HSSP	HSSP built from PDB template 1PEG based on UniProtKB Q8X225.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9NR48.
PTM databases
PhosphoSite	Q9NR48.
Proteomic databases
PRIDE	Q9NR48.
Genome annotation databases
Ensembl	ENST00000368346; ENSP00000357330; ENSG00000116539; Homo sapiens. [Genome view] ENST00000392403; ENSP00000376204; ENSG00000116539; Homo sapiens. [Genome view]
GeneID	55870.
KEGG	hsa:55870.
NMPDR	fig|9606.3.peg.2232.
UCSC	uc001fkt.1. human.
Organism-specific databases
CTD	55870.
GeneCards	GC01M153571.
H-InvDB	HIX0001130.
HGNC	HGNC:19088. ASH1L.
HPA	HPA004806.
MIM	607999. gene.
PharmGKB	PA134891064.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q9NR48.
OMA	SKLHNTV.
Enzyme and pathway databases
BRENDA	2.1.1.43. 247.
Gene expression databases
ArrayExpress	Q9NR48.
Bgee	Q9NR48.
CleanEx	HS_ASH1L.
Genevestigator	Q9NR48.
GermOnline	ENSG00000116539. Homo sapiens.
Family and domain databases
InterPro	IPR017956. AT_hook_DNA-bd_motif. IPR006560. AWS. IPR001025. BAH. IPR001487. Bromodomain. IPR018359. Bromodomain_CS. IPR003616. Post-SET_Zn_bd. IPR001214. SET. IPR019786. Zinc_finger_PHD-type_CS. IPR001965. Znf_PHD. IPR019787. Znf_PHD-finger. [Graphical view]
Gene3D	G3DSA:1.20.920.10. Bromodomain. 1 hit.
Pfam	PF02178. AT_hook. 1 hit. PF01426. BAH. 1 hit. PF00439. Bromodomain. 1 hit. PF00628. PHD. 1 hit. PF00856. SET. 1 hit. [Graphical view]
SMART	SM00384. AT_hook. 4 hits. SM00570. AWS. 1 hit. SM00439. BAH. 1 hit. SM00297. BROMO. 1 hit. SM00249. PHD. 1 hit. SM00508. PostSET. 1 hit. SM00317. SET. 1 hit. [Graphical view]
PROSITE	PS51215. AWS. 1 hit. PS51038. BAH. 1 hit. PS00633. BROMODOMAIN_1. False negative. PS50014. BROMODOMAIN_2. 1 hit. PS50868. POST_SET. 1 hit. PS50280. SET. 1 hit. PS01359. ZF_PHD_1. 1 hit. PS50016. ZF_PHD_2. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	61186.
SOURCE	Search...

Entry information

Entry name

ASH1L_HUMAN

Accession

Primary (citable) accession number: Q9NR48
Secondary accession number(s): Q59GP1 , Q5T714, Q5T715, Q9P2C7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2006
Last sequence update:	October 31, 2006
Last modified:	November 3, 2009
This is version 67 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.