Reviewed, UniProtKB/Swiss-Prot O08550 (MLL4_MOUSE)

Names and origin

Protein names

Recommended name:
    Histone-lysine N-methyltransferase MLL4
    EC=2.1.1.43
Alternative name(s):
    Myeloid/lymphoid or mixed-lineage leukemia protein 4 homolog
    WW domain-binding protein 7
      Short name=WBP-7
    Trithorax homolog 2

Gene names

Name:	Wbp7
Synonyms:	Mll2, Trx2

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	2713 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Histone methyltransferase. Methylates 'Lys-4' of histone H3. H3 'Lys-4' methylation represents 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.
Subunit structure	Component of the MLL3/MLL4 complex, at least composed of MLL3, MLL4, ASH2L, RBBP5, DPY30, WDR5, NCOA6, KDM6A (or KDM6B), PAXIP1/PTIP and C16orf53/PA1 By similarity.
Subcellular location	Nucleus By similarity.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.3 Ref.4
Sequence similarities	Belongs to the histone-lysine methyltransferase family. TRX/MLL subfamily. Contains 3 A.T hook DNA-binding domains. Contains 1 CXXC-type zinc finger. Contains 3 PHD-type zinc fingers. Contains 1 post-SET domain. Contains 1 SET domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding S-adenosyl-L-methionine Zinc
Molecular function	Chromatin regulator Methyltransferase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	histone methyltransferase complex Inferred from direct assay. Source: MGI
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW histone methyltransferase activity (H3-K4 specific) Inferred from direct assay. Source: MGI 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 – 2713	2713	Histone-lysine N-methyltransferase MLL4		PRO_0000124882
Regions
	Domain	2572 – 2693	122	SET
	Domain	2697 – 2713	17	Post-SET
	DNA binding	37 – 44	8	A.T hook 1
	DNA binding	110 – 117	8	A.T hook 2
	DNA binding	357 – 365	9	A.T hook 3
	Zinc finger	964 – 1011	48	CXXC-type
	Zinc finger	1207 – 1258	52	PHD-type 1
	Zinc finger	1255 – 1309	55	PHD-type 2
	Zinc finger	1341 – 1402	62	PHD-type 3
	Compositional bias	6 – 106	101	Gly-rich
	Compositional bias	272 – 300	29	Gly-rich
	Compositional bias	347 – 410	64	Glu-rich
	Compositional bias	414 – 776	363	Pro-rich
	Compositional bias	1814 – 2296	483	Pro-rich
Amino acid modifications
	Modified residue	159	1	Phosphothreonine By similarity
	Modified residue	320	1	Phosphoserine Ref.4
	Modified residue	826	1	Phosphoserine By similarity
	Modified residue	849	1	Phosphoserine By similarity
	Modified residue	866	1	Phosphoserine By similarity
	Modified residue	1037	1	Phosphoserine By similarity
	Modified residue	1040	1	Phosphoserine By similarity
	Modified residue	1170	1	Phosphoserine By similarity
	Modified residue	1926	1	Phosphoserine By similarity
	Modified residue	1927	1	Phosphoserine Ref.3
	Modified residue	1931	1	Phosphothreonine By similarity

Sequences

	Sequence		Length	Mass (Da)
	O08550-1 [UniParc]. Last modified January 9, 2007. Version 2. Checksum: B24BCA2D019EB055	FASTA	2,713	294,836
	10 20 30 40 50 60 MAAAAGGGSC PGPGSARVRF PGRPLGCGGG GGRGGRGNGA ERVRVALRRG GGAAGPGGAE 70 80 90 100 110 120 PGEDTALLRL LGLRRGLRRL RRLWAGARVQ RGRGRGRGRG WGPNRGCMPE EESSDGESEE 130 140 150 160 170 180 EEFQGFHSDE DVAPSSLRSA LRSQRGRAPR GRGRKHKTTP LPPRLADVTP VPPKAPTRKR 190 200 210 220 230 240 GEEGTERMVQ ALTELLRRSQ APQPPRSRAR AREPSTPRRS RGRPPGRPAG PCRKKQQAVV 250 260 270 280 290 300 LAEAAVTIPK PEPPPPVVPV KNKAGSWKCK EGPGPGPGTP KRGGQPGRGG RGGRGRGRGG 310 320 330 340 350 360 LPLMIKFVSK AKKVKMGQLS QELESGQGHG QRGESWQDAP QRKDGDEPER GSCRKKQEQK 370 380 390 400 410 420 LEEEEEEEEK EGEEKEEKDD NEDNNKQEEE EETERAVAEE EAMLAKEKEE AKLPSPPLTP 430 440 450 460 470 480 PVPSPPPPLP PPSTSPPPPA SPLPPPVSPP PPLSPPPYPA PEKQEESPPL VPATCSRKRG 490 500 510 520 530 540 RPPLTPSQRA EREAARSGPE GTLSPTPNPS TTTGSPLEDS PTVVPKSTTF LKNIRQFIMP 550 560 570 580 590 600 VVSARSSRVI KTPRRFMDED PPKPPKVEAS IVRPPVATSP PAPQEPVPVS SPPRVPTPPS 610 620 630 640 650 660 TPVPLPEKRR SILREPTFRW TSLTRELPPP PPAPPPAPSP PPAPATPSRR PLLLRAPQFT 670 680 690 700 710 720 PSEAHLKIYE SVLTPPPLGA LETPEPELPP ADDSPAEPEP RAVGRTNHLS LPRFVPVVTS 730 740 750 760 770 780 PVKVEVPPHG APALSEGQQL QLQQPPQALQ TQLLPQALPP QQPQAQPPPS PQHTPPLEKA 790 800 810 820 830 840 RVASLGSLPL SGVEEKMFSL LKRAKVQLFK IDQQQQQKVA ASMPLSPAVQ TEEAVGTVKQ 850 860 870 880 890 900 TPDRGCVRSE DESMEAKRDR ASGPESPLQG PRIKHVCRHA AVALGQARAM VPEDVPRLSA 910 920 930 940 950 960 LPLRDRQDLA TEDTSSASET ESVPSRSQRE KVESAGPGGD SEPTGSTGAL AHTPRRSLPS 970 980 990 1000 1010 1020 HHGKKMRMAR CGHCRGCLRV QDCGSCVNCL DKPKFGGPNT KKQCCVYRKC DKIEARKMER 1030 1040 1050 1060 1070 1080 LAKKGRTIVK TLLPWDSDES PEASPGPPGP RRGAGAGGSR EEVGATPGPE EQDSLLLQRK 1090 1100 1110 1120 1130 1140 SARRCVKQRP SYDVFEDSDD SEPGGPPAPR RRTPREHELP VLEPEEQSRP RKPTLQPVLQ 1150 1160 1170 1180 1190 1200 LKARRRLDKD ALAPGPFASF PNGWTGKQKS PDGVHRVRVD FKEDCDLENV WLMGGLSVLT 1210 1220 1230 1240 1250 1260 SVPGGPPMVC LLCASKGLHE LVFCQVCCDP FHPFCLEEAE RPSPQHRDTW CCRRCKFCHV 1270 1280 1290 1300 1310 1320 CGRKGRGSKH LLECERCRHA YHPACLGPSY PTRATRRRRH WICSACVRCK SCGATPGKNW 1330 1340 1350 1360 1370 1380 DVEWSGDYSL CPRCTELYEK GNYCPICTRC YEDNDYESKM MQCAQCDHWV HAKCEGLSDE 1390 1400 1410 1420 1430 1440 DYEILSGLPD SVLYTCGPCA GATQPRWREA LSGALQGGLR QVLQGLLSSK VAGPLLLCTQ 1450 1460 1470 1480 1490 1500 CGQDGKQLHP GPCDLQAVGK RFEEGLYKSV HSFMEDVVAI LMRHSEEGET PERRAGSQMK 1510 1520 1530 1540 1550 1560 GLLLKLLESA FCWFDAHDPK YWRRSTRLPN GVLPNAVLPP SLDHVYAQWR QQESETPESG 1570 1580 1590 1600 1610 1620 QPPGDPSAAF QSKDPAAFSH LDDPRQCALC LKYGDADSKE AGRLLYIGQN EWTHVNCAIW 1630 1640 1650 1660 1670 1680 SAEVFEENDG SLKNVHAAVA RGRQMRCELC LKPGATVGCC LSSCLSNFHF MCARASYCIF 1690 1700 1710 1720 1730 1740 QDDKKVFCQK HTDLLDGKEI VTPDGFDVLR RVYVDFEGIN FKRKFLTGLE PDVINVLIGS 1750 1760 1770 1780 1790 1800 IRINSLGTLS DLSDCEGRLF PIGYQCSRLY WSTVDARRRC WYRCRILEYR PWGPREEPVH 1810 1820 1830 1840 1850 1860 LEAAEENQTI VHSPTPSSDT DSLIPGDPVH HSPIQNLDPP LRTDSSNGPP PTPRSFSGAR 1870 1880 1890 1900 1910 1920 IKVPNYSPSR RPLGGVSFGP LPSPGSPSSL THHIPTVGDS DFPAPPRRSR RPSPLATRPP 1930 1940 1950 1960 1970 1980 PSRRTSSPLR TSPQLRVPLS TSVTALTPTS GELAPPDLAP SPLPPSEDLG PDFEDMEVVS 1990 2000 2010 2020 2030 2040 GLSAADLDFA ASLLGTEPFQ EEIVAAGAVG SSQGGPGDSS EEEASPTTHY VHFPVTVVSG 2050 2060 2070 2080 2090 2100 PALAPSSLAG APRIEQLDGV DDGTDSEAEA VQQPRGQGTP PSGPGVGRGG VLGAAGDRAQ 2110 2120 2130 2140 2150 2160 PPEDLPSEIV DFVLKNLGGP GEGAAGPRED SLPSAPPLAN GSQPPQSLST SPADPTRTFA 2170 2180 2190 2200 2210 2220 WLPGAPGVRV LSLGPAPEPP KPATSKIILV NKLGQVFVKM AGEGEPVAPP VKQPPLPPII 2230 2240 2250 2260 2270 2280 PPTAPTSWTL PPGPLLSVLP VVGVGVVRPA PPPPPPPLTL VFSSGPPSPP RQAIRVKRVS 2290 2300 2310 2320 2330 2340 TFSGRSPPVP PPNKTPRLDE DGESLEDAHH VPGISGSGFS RVRMKTPTVR GVLDLNNPGE 2350 2360 2370 2380 2390 2400 QPEEESPGRP QDRCPLLPLA EAPSQALDGS SDLLFESQWH HYSAGEASSS EEEPPSPEDK 2410 2420 2430 2440 2450 2460 ENQVPKRVGP HLRFEISSDD GFSVEAESLE VAWRTLIEKV QEARGHARLR HLSFSGMSGA 2470 2480 2490 2500 2510 2520 RLLGIHHDAV IFLAEQLPGA QRCQHYKFRY HQQGEGQEEP PLNPHGAARA EVYLRKCTFD 2530 2540 2550 2560 2570 2580 MFNFLASQHR VLPEGATCDE EEDEVQLRST RRATSLELPM AMRFRHLKKT SKEAVGVYRS 2590 2600 2610 2620 2630 2640 AIHGRGLFCK RNIDAGEMVI EYSGIVIRSV LTDKREKFYD GKGIGCYMFR MDDFDVVDAT 2650 2660 2670 2680 2690 2700 MHGNAARFIN HSCEPNCFSR VIHVEGQKHI VIFALRRILR GEELTYDYKF PIEDASNKLP 2710 CNCGAKRCRR FLN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Murine MLL2 gene and its expression." Yoshida K. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"FBP WW domains and the Abl SH3 domain bind to a specific class of proline-rich ligands." Bedford M.T., Chan D.C., Leder P. EMBO J. 16:2376-2383(1997) [PubMed: 9171351] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 379-657.
[3]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed: 17242355] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1927, MASS SPECTROMETRY. Tissue: Liver.
[4]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-320, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB182318 mRNA. Translation: BAD81031.1. U92455 mRNA. Translation: AAC53192.1. Sequence problems.
IPI	IPI00229651.
RefSeq	NP_083550.2.
UniGene	Mm.168688
3D structure databases
ModBase	Search...
Genome annotation databases
Ensembl	ENSMUSG00000006307. Mus musculus. [Contig view]
GeneID	75410.
KEGG	mmu:75410.
Organism-specific databases
MGI	MGI:109565. Wbp7.
Phylogenomic databases
HOVERGEN	O08550.
Gene expression databases
ArrayExpress	O08550.
Bgee	O08550.
CleanEx	MM_WBP7.
GermOnline	ENSMUSG00000006307. Mus musculus.
Family and domain databases
InterPro	IPR017956. AT_hook_DNA-bd_CS. IPR003889. FYrich_C. IPR018516. FYrich_C_sg. IPR003888. FYrich_N. IPR018518. FYrich_N_sg. IPR015722. MLL. IPR003616. Post-SET_Zn_bd. IPR001214. SET. IPR019786. Zinc_finger_PHD-type_CS. IPR002857. Znf_CXXC. IPR001965. Znf_PHD. IPR019787. Znf_PHD-finger. [Graphical view]
PANTHER	PTHR22884:SF10. MLL. 1 hit.
Pfam	PF05965. FYRC. 1 hit. PF05964. FYRN. 1 hit. PF00628. PHD. 3 hits. PF00856. SET. 1 hit. PF02008. zf-CXXC. 1 hit. [Graphical view]
SMART	SM00384. AT_hook. 3 hits. SM00542. FYRC. 1 hit. SM00541. FYRN. 1 hit. SM00249. PHD. 4 hits. SM00508. PostSET. 1 hit. SM00317. SET. 1 hit. [Graphical view]
PROSITE	PS50868. POST_SET. 1 hit. PS50280. SET. 1 hit. PS51058. ZF_CXXC. 1 hit. PS01359. ZF_PHD_1. 3 hits. PS50016. ZF_PHD_2. 3 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	342938.
SOURCE	Search...

Entry information

Entry name

MLL4_MOUSE

Accession

Primary (citable) accession number: O08550
Secondary accession number(s): Q5NU09

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	January 9, 2007
Last modified:	June 16, 2009
This is version 71 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)