Reviewed, UniProtKB/Swiss-Prot Q9UBL3 (ASH2L_HUMAN)

Names and origin

Protein names

Recommended name:
    Set1/Ash2 histone methyltransferase complex subunit ASH2
Alternative name(s):
    ASH2-like protein

Gene names

Name:	ASH2L
Synonyms:	ASH2L1

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

General annotation (Comments)

Function	Component of the Set1/Ash2 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3, but not if the neighboring 'Lys-9' residue is already methylated. May function as a transcriptional regulator. May play a role in hematopoiesis. Ref.4
Subunit structure	Interacts with HCFC1. Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2/ASH2L and CXXC1/CFP1. Component of MLL-containing complexes (named MLL, ASCOM, MLL2/MLL3 or MLL3/MLL4 complex): at least composed ASH2L, RBBP5, DPY30, WDR5, one or several histone methyltransferases (MLL, MLL2, MLL3 and/or MLL4), and the facultative components MEN1, HCFC1, HCFC2, NCOA6, KDM6A, PAXIP1/PTIP and C16orf53/PA1. Ref.4
Subcellular location	Nucleus Probable.
Tissue specificity	Ubiquitously expressed. Predominantly expressed in adult heart and testis and fetal lung and liver, with barely detectable expression in adult lung, liver, kidney, prostate, and peripheral leukocytes. Ref.2
Sequence similarities	Contains 1 B30.2/SPRY domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	hemopoiesis Ref.1 Non-traceable author statement. Source: UniProtKB regulation of transcription, DNA-dependent Ref.2 Non-traceable author statement. Source: UniProtKB transcription from RNA polymerase II promoter Ref.2 Traceable author statement. Source: ProtInc
Cellular component	histone methyltransferase complex Inferred from physical interaction. Source: MGI
Molecular function	DNA binding Ref.2 Inferred by curator. Source: UniProtKB protein binding Ref.4 Inferred from physical interaction. Source: UniProtKB transcription regulator activity Ref.2 Non-traceable author statement. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HCFC1	P51610	2	EBI-540797,EBI-396176
Mll2	Q6PDK2	1	EBI-540797,EBI-996317	From a different organism.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UBL3-1)

Also known as: ASH2L1;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9UBL3-2)

Also known as: ASH2L2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-94: Missing.
     541-573: Missing.

Isoform 3 (identifier: Q9UBL3-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-94: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 628	628	Set1/Ash2 histone methyltransferase complex subunit ASH2		PRO_0000064697
Regions
	Domain	360 – 583	224	B30.2/SPRY
	Zinc finger	117 – 150	34	C4-type
Natural variations
	Alternative sequence	1 – 94	94	Missing in isoform 2 and isoform 3.		VSP_007577
	Alternative sequence	541 – 573	33	Missing in isoform 2.		VSP_007578
	Natural variant	478	1	S → F: dbSNP rs34167006.		VAR_050679
Experimental info
	Sequence conflict	212	1	Q → H in AAC13564. Ref.1
	Sequence conflict	217	1	M → T in AAC13564. Ref.1
	Sequence conflict	292	1	S → T in AAC13563. Ref.1
	Sequence conflict	351	1	H → Q in AAC13564. Ref.1
	Sequence conflict	360	1	L → I in AAC13564. Ref.1
	Sequence conflict	369	1	P → S in AAC13564. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (ASH2L1) [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 8F5F007430D4B863	FASTA	628	68,723
	10 20 30 40 50 60 MAAAGAGPGQ EAGAGPGPGA VANATGAEEG EMKPVAAGAA APPGEGISAA PTVEPSSGEA 70 80 90 100 110 120 EGGEANLVDV SGGLETESSN GKDTLEGAGD TSEVMDTQAG SVDEENGRQL GEVELQCGIC 130 140 150 160 170 180 TKWFTADTFG IDTSSCLPFM TNYSFHCNVC HHSGNTYFLR KQANLKEMCL SALANLTWQS 190 200 210 220 230 240 RTQDEHPKTM FSKDKDIIPF IDKYWECMTT RQRPGKMTWP NNIVKTMSKE RDVFLVKEHP 250 260 270 280 290 300 DPGSKDPEED YPKFGLLDQD LSNIGPAYDN QKQSSAVSTS GNLNGGIAAG SSGKGRGAKR 310 320 330 340 350 360 KQQDGGTTGT TKKARSDPLF SAQRLPPHGY PLEHPFNKDG YRYILAEPDP HAPDPEKLEL 370 380 390 400 410 420 DCWAGKPIPG DLYRACLYER VLLALHDRAP QLKISDDRLT VVGEKGYSMV RASHGVRKGA 430 440 450 460 470 480 WYFEITVDEM PPDTAARLGW SQPLGNLQAP LGYDKFSYSW RSKKGTKFHQ SIGKHYSSGY 490 500 510 520 530 540 GQGDVLGFYI NLPEDTETAK SLPDTYKDKA LIKFKSYLYF EEKDFVDKAE KSLKQTPHSE 550 560 570 580 590 600 IIFYKNGVNQ GVAYKDIFEG VYFPAISLYK SCTVSINFGP CFKYPPKDLT YRPMSDMGWG 610 620 AVVEHTLADV LYHVETEVDG RRSPPWEP
	Isoform 2 (ASH2L2). Checksum: BD76059C4DE39703	FASTA	501	56,477
	10 20 30 40 50 60 MDTQAGSVDE ENGRQLGEVE LQCGICTKWF TADTFGIDTS SCLPFMTNYS FHCNVCHHSG 70 80 90 100 110 120 NTYFLRKQAN LKEMCLSALA NLTWQSRTQD EHPKTMFSKD KDIIPFIDKY WECMTTRQRP 130 140 150 160 170 180 GKMTWPNNIV KTMSKERDVF LVKEHPDPGS KDPEEDYPKF GLLDQDLSNI GPAYDNQKQS 190 200 210 220 230 240 SAVSTSGNLN GGIAAGSSGK GRGAKRKQQD GGTTGTTKKA RSDPLFSAQR LPPHGYPLEH 250 260 270 280 290 300 PFNKDGYRYI LAEPDPHAPD PEKLELDCWA GKPIPGDLYR ACLYERVLLA LHDRAPQLKI 310 320 330 340 350 360 SDDRLTVVGE KGYSMVRASH GVRKGAWYFE ITVDEMPPDT AARLGWSQPL GNLQAPLGYD 370 380 390 400 410 420 KFSYSWRSKK GTKFHQSIGK HYSSGYGQGD VLGFYINLPE DTETAKSLPD TYKDKALIKF 430 440 450 460 470 480 KSYLYFEEKD FVDKAEKSLK QTPHSEVSIN FGPCFKYPPK DLTYRPMSDM GWGAVVEHTL 490 500 ADVLYHVETE VDGRRSPPWE P
	Isoform 3. Checksum: 4317F1206E97C897	FASTA	534	60,208
	10 20 30 40 50 60 MDTQAGSVDE ENGRQLGEVE LQCGICTKWF TADTFGIDTS SCLPFMTNYS FHCNVCHHSG 70 80 90 100 110 120 NTYFLRKQAN LKEMCLSALA NLTWQSRTQD EHPKTMFSKD KDIIPFIDKY WECMTTRQRP 130 140 150 160 170 180 GKMTWPNNIV KTMSKERDVF LVKEHPDPGS KDPEEDYPKF GLLDQDLSNI GPAYDNQKQS 190 200 210 220 230 240 SAVSTSGNLN GGIAAGSSGK GRGAKRKQQD GGTTGTTKKA RSDPLFSAQR LPPHGYPLEH 250 260 270 280 290 300 PFNKDGYRYI LAEPDPHAPD PEKLELDCWA GKPIPGDLYR ACLYERVLLA LHDRAPQLKI 310 320 330 340 350 360 SDDRLTVVGE KGYSMVRASH GVRKGAWYFE ITVDEMPPDT AARLGWSQPL GNLQAPLGYD 370 380 390 400 410 420 KFSYSWRSKK GTKFHQSIGK HYSSGYGQGD VLGFYINLPE DTETAKSLPD TYKDKALIKF 430 440 450 460 470 480 KSYLYFEEKD FVDKAEKSLK QTPHSEIIFY KNGVNQGVAY KDIFEGVYFP AISLYKSCTV 490 500 510 520 530 SINFGPCFKY PPKDLTYRPM SDMGWGAVVE HTLADVLYHV ETEVDGRRSP PWEP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"ASH2L: alternative splicing and downregulation during induced megakaryocytic differentiation of multipotential leukemia cell lines." Wang J., Zhou Y., Yin B., Du G., Huang X., Li G., Shen Y., Yuan J., Qiang B. J. Mol. Med. 79:399-405(2001) [PubMed: 11466562] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Fetal brain.
[2]	"Cloning and characterization of ASH2L and ash2l, human and mouse homologs of the Drosophila ash2 gene." Ikegawa S., Isomura M., Koshizuka Y., Nakamura Y. Cytogenet. Cell Genet. 84:167-172(1999) [PubMed: 10393421] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), TISSUE SPECIFICITY.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Skin.
[4]	"Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1." Wysocka J., Myers M.P., Laherty C.D., Eisenman R.N., Herr W. Genes Dev. 17:896-911(2003) [PubMed: 12670868] [Abstract] Cited for: FUNCTION, INTERACTION WITH HCFC1.
[5]	"Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression." Yokoyama A., Wang Z., Wysocka J., Sanyal M., Aufiero D.J., Kitabayashi I., Herr W., Cleary M.L. Mol. Cell. Biol. 24:5639-5649(2004) [PubMed: 15199122] [Abstract] Cited for: IDENTIFICATION IN THE MLL-LIKE COMPLEX.
[6]	"CpG-binding protein (CXXC finger protein 1) is a component of the mammalian Set1 histone H3-Lys4 methyltransferase complex, the analogue of the yeast Set1/COMPASS complex." Lee J.-H., Skalnik D.G. J. Biol. Chem. 280:41725-41731(2005) [PubMed: 16253997] [Abstract] Cited for: IDENTIFICATION IN THE SET1 COMPLEX.
[7]	"Identification and characterization of the human Set1B histone H3-Lys4 methyltransferase complex." Lee J.-H., Tate C.M., You J.-S., Skalnik D.G. J. Biol. Chem. 282:13419-13428(2007) [PubMed: 17355966] [Abstract] Cited for: SUBCELLULAR LOCATION, IDENTIFICATION IN THE SET1 COMPLEX.
[8]	"PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 methyltransferase complex." Cho Y.-W., Hong T., Hong S., Guo H., Yu H., Kim D., Guszczynski T., Dressler G.R., Copeland T.D., Kalkum M., Ge K. J. Biol. Chem. 282:20395-20406(2007) [PubMed: 17500065] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MLL-LIKE COMPLEX.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF056718 mRNA. Translation: AAC13564.1. AF056717 mRNA. Translation: AAC13563.1. AB022785 Genomic DNA. Translation: BAA74520.1. AB020982 mRNA. Translation: BAA35127.1. BC015936 mRNA. Translation: AAH15936.1.
IPI	IPI00328658. IPI00328659. IPI00333837.
RefSeq	NP_001098684.1. NP_004665.2.
UniGene	Hs.521530
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UBL3. 20 interactions.
STRING	Q9UBL3.
PTM databases
PhosphoSite	Q9UBL3.
Proteomic databases
PRIDE	Q9UBL3.
Genome annotation databases
Ensembl	ENST00000343823; ENSP00000340896; ENSG00000129691; Homo sapiens. [Genome view]
GeneID	9070.
KEGG	hsa:9070.
UCSC	uc003xkt.2. human. uc003xku.2. human. uc010lwa.1. human.
Organism-specific databases
CTD	9070.
GeneCards	GC08P038082.
H-InvDB	HIX0007454.
HGNC	HGNC:744. ASH2L.
MIM	604782. gene.
PharmGKB	PA25044.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9UBL3.
HOVERGEN	Q9UBL3.
OMA	DPGSKDP
OrthoDB	EOG9FXTTH
Enzyme and pathway databases
BioCyc	CATTLE:ENSBTAG00000000978-MON.
Gene expression databases
ArrayExpress	Q9UBL3.
Bgee	Q9UBL3.
CleanEx	HS_ASH2L.
Genevestigator	Q9UBL3.
Family and domain databases
InterPro	IPR001870. B302. IPR018355. SPla/RYanodine_receptor_sg. IPR003877. SPRY_rcpt. [Graphical view]
Pfam	PF00622. SPRY. 1 hit. [Graphical view]
SMART	SM00449. SPRY. 1 hit. [Graphical view]
PROSITE	PS50188. B302_SPRY. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	33985.
SOURCE	Search...

Entry information

Entry name

ASH2L_HUMAN

Accession

Primary (citable) accession number: Q9UBL3
Secondary accession number(s): O60659, O60660, Q96B62

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 16, 2003
Last sequence update:	May 1, 2000
Last modified:	November 24, 2009
This is version 80 of the entry and version 1 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.