P59598 (ASXL1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Putative Polycomb group protein ASXL1

Alternative name(s):
Additional sex combs-like protein 1

Gene names

Name:	Asxl1
Synonyms:	Kiaa0978

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1514 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Probable Polycomb group (PcG) protein involved in transcriptional regulation mediated by ligand-bound retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor gamma (PPARG). Acts as a coactivator of RARA and RXRA through association with NCOA1. Acts as a corepressor through recruitment of KDM1A and CBX5 to target genes in a cell-type specific manner; the function seems to involve differential recruitment of methylated histone H3 to respective promoters. Acts as a corepressor for PPARG and suppresses its adipocyte differentiation-inducing activity. Non-catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1). Ref.2 Ref.4 Ref.5
Subunit structure	Component of the PR-DUB complex, at least composed of BAP1 and ASXL1 By similarity. Interacts with RARA, RXRA, NCOA1, KDM1A and CBX5. Interacts with PPARA, PPARG, CBX1 and CBX3. Ref.2 Ref.4 Ref.5
Subcellular location	Nucleus Ref.4.
Domain	Contains two Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs, which may be required for an association with nuclear receptors By similarity.
Sequence similarities	Belongs to the Asx family. Contains 1 PHD-type zinc finger.
Sequence caution	The sequence BAC65695.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Ubl conjugation pathway
Cellular component	Nucleus
Domain	Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Chromatin regulator Repressor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bone development Inferred from mutant phenotype PubMed 22876197. Source: MGI monoubiquitinated histone H2A deubiquitination Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of fat cell differentiation Inferred from direct assay Ref.5. Source: UniProtKB negative regulation of peroxisome proliferator activated receptor signaling pathway Inferred from direct assay Ref.5. Source: UniProtKB negative regulation of retinoic acid receptor signaling pathway Inferred from direct assay Ref.4. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.4. Source: UniProtKB positive regulation of retinoic acid receptor signaling pathway Inferred from direct assay Ref.2. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.2. Source: UniProtKB response to retinoic acid Inferred from direct assay Ref.2. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	PR-DUB complex Inferred from sequence or structural similarity. Source: UniProtKB nuclear chromatin Inferred from direct assay Ref.4. Source: UniProtKB
Molecular_function	DNA binding Inferred from electronic annotation. Source: InterPro metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW peroxisome proliferator activated receptor binding Inferred from direct assay Ref.5. Source: UniProtKB retinoic acid receptor binding Inferred from direct assay Ref.2. Source: UniProtKB transcription coactivator activity Inferred from direct assay Ref.2. Source: UniProtKB transcription corepressor activity Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CBX5	P45973	5	EBI-5743705,EBI-78219	From a different organism.
ESR1	P03372	2	EBI-5743705,EBI-78473	From a different organism.
KDM1A	O60341	2	EBI-5743705,EBI-710124	From a different organism.
NCOA1	Q15788	2	EBI-5743705,EBI-455189	From a different organism.
NR3C1	P04150	2	EBI-5743705,EBI-493507	From a different organism.
RARA	P10276	4	EBI-5743705,EBI-413374	From a different organism.
Rxra	P28700	2	EBI-5743705,EBI-346715

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1514	1514	Putative Polycomb group protein ASXL1		PRO_0000059322
Regions
	Zinc finger	1476 – 1513	38	PHD-type; atypical
	Region	170 – 174	5	Required for interaction with CBX5
	Region	175 – 370	196	Interaction with KDM1A
	Region	300 – 655	356	Interaction with NCOA1
	Region	1082 – 1087	6	Required for interaction with RARA By similarity
	Motif	284 – 288	5	LXXLL motif 1
	Motif	409 – 413	5	Nuclear localization signal Potential
	Motif	808 – 812	5	LXXLL motif 2
	Compositional bias	199 – 209	11	Poly-Ser
	Compositional bias	284 – 288	5	Poly-Leu
	Compositional bias	639 – 670	32	Gly-rich
	Compositional bias	1430 – 1433	4	Poly-Ser
Amino acid modifications
	Modified residue	500	1	Phosphoserine Ref.3
Experimental info
	Mutagenesis	170	1	P → A: Abolishes interaction with CBX1, CBX3 and CBX5; when associated with A-172 and A-174. Ref.4
	Mutagenesis	172	1	V → A: Abolishes interaction with CBX1, CBX3 and CBX5; when associated with A-170 and A-174. Ref.4
	Mutagenesis	174	1	L → A: Abolishes interaction with CBX1, CBX3 and CBX5; when associated with A-170 and A-172. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P59598 [UniParc]. Last modified April 23, 2003. Version 1. Checksum: 20D9FBE9D4CF9E74	FASTA	1,514	162,674
	10 20 30 40 50 60 MKDKQKRKKE RTWAEAARLV LENYSDAPMT PKQILQVIEA EGLKEMRSGT SPLACLNAML 70 80 90 100 110 120 HSNSRGGEGL FYKLPGRISL FTLKKDAVQW SRNAATVDGD EPEDSADVES CGSNEASTVS 130 140 150 160 170 180 GENDVSLDET SSNASCSTES QSRPLSNPRD SHRASSQANK QKKRTGVMLP RVVLTPLKVN 190 200 210 220 230 240 GAHVEPASGF SGRHADGESG SPSSSSSGSL ALGNSAIRGQ AEVTRDPAPL LRGFRKPATG 250 260 270 280 290 300 QMKRNRGEEV DFETPGSILV NTNLRALINS RTFHALPLHF QQQLLLLLPE VDRQVGTDGL 310 320 330 340 350 360 LRLSGSALNN EFFTHAAQSW RERLADGEFT HEMQVRLRQE MEKEKKVEQW KEKFFEDYYG 370 380 390 400 410 420 QKLGLTKEES LQQKEVQEEA KVKSGLCVSG ESVRPQRGPN TRQRDGHFKK RSRPDLRTRS 430 440 450 460 470 480 RRNIYKKQEP EQAGVAKDAS AAPDVSLSKD TKTDLAGVNS TPGPDVSSAT SGQEGPKCPS 490 500 510 520 530 540 EPVASQIQAE RDNLACASAS PDRIPTLPQD TVDQETKDQK RKSFEQEASA SFPEKKPRLE 550 560 570 580 590 600 DRQSFRNTIE SVHTEKPQPT KEEPKVPPIR IQLSRIKPPW VAKGRPTYQI CPRIVPITES 610 620 630 640 650 660 SCRGWTGART LADIKARALQ ARGARGYHCN RETATTAIGG GGGPGGGGSG AIDEGGGRDS 670 680 690 700 710 720 SSGDGSEACG HPEPRGAPST SGESASDLQR TQLLPPCPLN GEHTPAEAAM PRARREDSAS 730 740 750 760 770 780 LRKEESCLLK RVPGVLTSGL EDASQPPIAP TGDQPCQALP PLSSQTPVAE MLTEQPKLLL 790 800 810 820 830 840 DDRTECESSR EDQGPTIPSE SSSGRFPLGD LLGGGSDQAF DNMKEPVSMT PTFISELSLA 850 860 870 880 890 900 NYLQDRPDDD GLGLGATGLL IRESSRQEAL TEAFASGSPT SWVPILSNYE VIKTSDPESR 910 920 930 940 950 960 ENIPCPEPQD EKEWERAVPL IAATESVPQP ESCISHWTPP PAAVGSTGSD SEQVDLERLE 970 980 990 1000 1010 1020 MNGISEAPSP HSESTDTASD SEGHLSEDSS EVDASEVTVV KGSLGGDEKQ DWDPSASLSK 1030 1040 1050 1060 1070 1080 VNNDLSVLTR TGGVAASQSW VSRVCSVPHK IPDSLLLSST ECQPRSVCPL RPGSSVEVTN 1090 1100 1110 1120 1130 1140 PLVMHLLHGN LPLEKVLPPG HRSSRLESSQ LPLREQSQDR GTLQGTGENN RLAARINPGS 1150 1160 1170 1180 1190 1200 AQTLKESILA QSYGASAGLV RAMASKAPAM SQKIAKMVTS LDSQHPETEL TPSSGNLEEI 1210 1220 1230 1240 1250 1260 DSKEHLSSFL CEEQKEGHSL SQGSDPGAAP GQCLGDHTTS KVPCFSSTNV SLSFGSEQTD 1270 1280 1290 1300 1310 1320 GTLSDQNNAG GHEKKLFGPG NTVTTLQCPR SEEQTPLPAE VPPVFPSRKI EPSKNSVSGG 1330 1340 1350 1360 1370 1380 VQTTRENRMP KPPPVSADSI KTEQTFLRDP IKADAENRKA AGYSSLELVG HLQGMPFVVD 1390 1400 1410 1420 1430 1440 LPFWKLPREP GKGFSQPLEP SSIPSQLNIK QALYGKLSKL QLSPTSFNYS SSSATFPKGL 1450 1460 1470 1480 1490 1500 AGGVVQLSHK ASFGTGHTAS LSLQMFADSS AVESISLQCA CSLKAMIMCQ GCGAFCHDDC 1510 IGPSKLCVLC LVVR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of mouse homologues of KIAA gene: II. The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S., Nakajima D., Nagase T., Ohara O., Koga H. DNA Res. 10:35-48(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[2]	"Additional sex comb-like 1 (ASXL1), in cooperation with SRC-1, acts as a ligand-dependent coactivator for retinoic acid receptor." Cho Y.S., Kim E.J., Park U.H., Sin H.S., Um S.J. J. Biol. Chem. 281:17588-17598(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH RARA AND RXRA.
[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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-500, MASS SPECTROMETRY. Tissue: Liver.
[4]	"ASXL1 represses retinoic acid receptor-mediated transcription through associating with HP1 and LSD1." Lee S.W., Cho Y.S., Na J.M., Park U.H., Kang M., Kim E.J., Um S.J. J. Biol. Chem. 285:18-29(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH KDM1A; CBX1; CBX3 AND CBX5, MUTAGENESIS OF PRO-170; VAL-172 AND LEU-174.
[5]	"Additional sex comb-like (ASXL) proteins 1 and 2 play opposite roles in adipogenesis via reciprocal regulation of peroxisome proliferator-activated receptor {gamma}." Park U.H., Yoon S.K., Park T., Kim E.J., Um S.J. J. Biol. Chem. 286:1354-1363(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PPARA AND PPARG.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK122413 mRNA. Translation: BAC65695.1. Different initiation.
IPI	IPI00281565.
RefSeq	NP_001035028.1. NM_001039939.1.
UniGene	Mm.330677.
3D structure databases
ProteinModelPortal	P59598.
ModBase	Search...
Protein-protein interaction databases
IntAct	P59598. 12 interactions.
PTM databases
PhosphoSite	P59598.
Proteomic databases
PaxDb	P59598.
PRIDE	P59598.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000109790; ENSMUSP00000105413; ENSMUSG00000042548.
GeneID	228790.
KEGG	mmu:228790.
Organism-specific databases
CTD	171023.
MGI	MGI:2684063. Asxl1.
Rouge	Search...
Phylogenomic databases
eggNOG	NOG81527.
HOGENOM	HOG000293301.
HOVERGEN	HBG050598.
InParanoid	P59598.
KO	K11471.
OMA	SKLCVLC.
OrthoDB	EOG4GQQ44.
Gene expression databases
ArrayExpress	P59598.
Bgee	P59598.
CleanEx	MM_ASXL1.
Genevestigator	P59598.
GermOnline	ENSMUSG00000042548. Mus musculus.
Family and domain databases
InterPro	IPR026905. ASX-like_PHD. IPR024811. ASX/ASX-like. IPR024815. ASXL1. [Graphical view]
PANTHER	PTHR13578. PTHR13578. 1 hit. PTHR13578:SF11. PTHR13578:SF11. 1 hit.
Pfam	PF13922. PHD_3. 1 hit. [Graphical view]
PROSITE	PS01359. ZF_PHD_1. False negative. PS50016. ZF_PHD_2. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	379148.
SOURCE	Search...

Entry information

Entry name

ASXL1_MOUSE

Accession

Primary (citable) accession number: P59598

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 23, 2003
Last sequence update:	April 23, 2003
Last modified:	April 3, 2013
This is version 79 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program