ASXL1_MOUSE
ID ASXL1_MOUSE Reviewed; 1514 AA.
AC P59598;
DT 23-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-APR-2003, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Polycomb group protein ASXL1;
DE AltName: Full=Additional sex combs-like protein 1;
GN Name=Asxl1; Synonyms=Kiaa0978;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA Nakajima D., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:35-48(2003).
RN [2]
RP FUNCTION, AND INTERACTION WITH RARA AND RXRA.
RX PubMed=16606617; DOI=10.1074/jbc.m512616200;
RA Cho Y.S., Kim E.J., Park U.H., Sin H.S., Um S.J.;
RT "Additional sex comb-like 1 (ASXL1), in cooperation with SRC-1, acts as a
RT ligand-dependent coactivator for retinoic acid receptor.";
RL J. Biol. Chem. 281:17588-17598(2006).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP RETRACTED PAPER.
RX PubMed=19880879; DOI=10.1074/jbc.m109.065862;
RA Lee S.W., Cho Y.S., Na J.M., Park U.H., Kang M., Kim E.J., Um S.J.;
RT "ASXL1 represses retinoic acid receptor-mediated transcription through
RT associating with HP1 and LSD1.";
RL J. Biol. Chem. 285:18-29(2010).
RN [5]
RP RETRACTION NOTICE OF PUBMED:19880879 NOTICE FOR PUBMED:19880879.
RX PubMed=25750265; DOI=10.1074/jbc.a109.065862;
RA Lee S.W., Cho Y.S., Na J.M., Park U.H., Kang M., Kim E.J., Um S.J.;
RT "Retraction: 'ASXL1 represses retinoic acid receptor-mediated transcription
RT through associating with HP1 and LSD1'.";
RL J. Biol. Chem. 290:6008-6008(2015).
RN [6]
RP FUNCTION, AND INTERACTION WITH PPARA AND PPARG.
RX PubMed=21047783; DOI=10.1074/jbc.m110.177816;
RA Park U.H., Yoon S.K., Park T., Kim E.J., Um S.J.;
RT "Additional sex comb-like (ASXL) proteins 1 and 2 play opposite roles in
RT adipogenesis via reciprocal regulation of peroxisome proliferator-activated
RT receptor {gamma}.";
RL J. Biol. Chem. 286:1354-1363(2011).
CC -!- FUNCTION: Probable Polycomb group (PcG) protein involved in
CC transcriptional regulation mediated by ligand-bound retinoic acid
CC receptors (RARs) and peroxisome proliferator-activated receptor gamma
CC (PPARG) (PubMed:16606617). Acts as a coactivator of RARA and RXRA
CC through association with NCOA1 (PubMed:16606617). Acts as a corepressor
CC for PPARG and suppresses its adipocyte differentiation-inducing
CC activity (PubMed:21047783). Non-catalytic component of the PR-DUB
CC complex, a complex that specifically mediates deubiquitination of
CC histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1) (By
CC similarity). Acts as a sensor of N(6)-methyladenosine methylation on
CC DNA (m6A): recognizes and binds m6A DNA, leading to its ubiquitination
CC and degradation by TRIP12, thereby inactivating the PR-DUB complex and
CC regulating Polycomb silencing (By similarity).
CC {ECO:0000250|UniProtKB:Q8IXJ9, ECO:0000269|PubMed:16606617,
CC ECO:0000269|PubMed:21047783}.
CC -!- SUBUNIT: Component of the PR-DUB complex, at least composed of BAP1 and
CC ASXL1 (By similarity). Interacts with RARA, RXRA (PubMed:16606617).
CC Interacts with NCOA1 (By similarity). Interacts with PPARA and PPARG
CC (PubMed:21047783). {ECO:0000250|UniProtKB:Q8IXJ9,
CC ECO:0000269|PubMed:16606617, ECO:0000269|PubMed:21047783}.
CC -!- INTERACTION:
CC P59598; P28700: Rxra; NbExp=2; IntAct=EBI-5743705, EBI-346715;
CC P59598; P03372: ESR1; Xeno; NbExp=2; IntAct=EBI-5743705, EBI-78473;
CC P59598; Q15788: NCOA1; Xeno; NbExp=2; IntAct=EBI-5743705, EBI-455189;
CC P59598; P04150: NR3C1; Xeno; NbExp=2; IntAct=EBI-5743705, EBI-493507;
CC P59598; P10276: RARA; Xeno; NbExp=4; IntAct=EBI-5743705, EBI-413374;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- DOMAIN: Contains two Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs, which may be
CC required for an association with nuclear receptors. {ECO:0000250}.
CC -!- DOMAIN: The HARE HTH-type domain recognizes and binds N(6)-
CC methyladenosine methylated DNA (m6A). {ECO:0000250|UniProtKB:Q8IXJ9}.
CC -!- PTM: Ubiquitinated by TRIP12, leading to its subsequent degradation
CC following binding N(6)-methyladenosine methylated DNA (m6A).
CC {ECO:0000250|UniProtKB:Q8IXJ9}.
CC -!- SIMILARITY: Belongs to the Asx family. {ECO:0000305}.
CC -!- CAUTION: Was reported to act as a corepressor through recruitment of
CC KDM1A and CBX; this publication has been retracted.
CC {ECO:0000269|PubMed:19880879}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC65695.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK122413; BAC65695.1; ALT_INIT; mRNA.
DR CCDS; CCDS38285.1; -.
DR RefSeq; NP_001035028.1; NM_001039939.1.
DR AlphaFoldDB; P59598; -.
DR SMR; P59598; -.
DR BioGRID; 230772; 2.
DR ComplexPortal; CPX-423; PR-DUB complex.
DR IntAct; P59598; 8.
DR STRING; 10090.ENSMUSP00000105413; -.
DR iPTMnet; P59598; -.
DR PhosphoSitePlus; P59598; -.
DR EPD; P59598; -.
DR PaxDb; P59598; -.
DR PeptideAtlas; P59598; -.
DR PRIDE; P59598; -.
DR ProteomicsDB; 277262; -.
DR Antibodypedia; 10384; 113 antibodies from 26 providers.
DR Ensembl; ENSMUST00000109790; ENSMUSP00000105413; ENSMUSG00000042548.
DR GeneID; 228790; -.
DR KEGG; mmu:228790; -.
DR UCSC; uc033hqx.1; mouse.
DR CTD; 171023; -.
DR MGI; MGI:2684063; Asxl1.
DR VEuPathDB; HostDB:ENSMUSG00000042548; -.
DR eggNOG; ENOG502QWT2; Eukaryota.
DR GeneTree; ENSGT00520000055578; -.
DR HOGENOM; CLU_247862_0_0_1; -.
DR InParanoid; P59598; -.
DR OMA; EDWVPKP; -.
DR OrthoDB; 53757at2759; -.
DR PhylomeDB; P59598; -.
DR TreeFam; TF328464; -.
DR Reactome; R-MMU-5689603; UCH proteinases.
DR BioGRID-ORCS; 228790; 2 hits in 78 CRISPR screens.
DR ChiTaRS; Asxl1; mouse.
DR PRO; PR:P59598; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P59598; protein.
DR Bgee; ENSMUSG00000042548; Expressed in respiratory primordium and 260 other tissues.
DR ExpressionAtlas; P59598; baseline and differential.
DR Genevisible; P59598; MM.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0035517; C:PR-DUB complex; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042974; F:nuclear retinoic acid receptor binding; IDA:UniProtKB.
DR GO; GO:0042975; F:peroxisome proliferator activated receptor binding; IDA:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI.
DR GO; GO:0060348; P:bone development; IMP:MGI.
DR GO; GO:0048539; P:bone marrow development; IMP:MGI.
DR GO; GO:0000902; P:cell morphogenesis; IMP:MGI.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0003007; P:heart morphogenesis; IMP:MGI.
DR GO; GO:0048534; P:hematopoietic or lymphoid organ development; IMP:MGI.
DR GO; GO:0030097; P:hemopoiesis; IMP:MGI.
DR GO; GO:0048872; P:homeostasis of number of cells; IMP:MGI.
DR GO; GO:0060430; P:lung saccule development; IMP:MGI.
DR GO; GO:0035522; P:monoubiquitinated histone H2A deubiquitination; ISS:UniProtKB.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IDA:UniProtKB.
DR GO; GO:0035359; P:negative regulation of peroxisome proliferator activated receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0072015; P:podocyte development; IMP:CACAO.
DR GO; GO:0048386; P:positive regulation of retinoic acid receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0035564; P:regulation of kidney size; IMP:CACAO.
DR GO; GO:0032526; P:response to retinoic acid; IDA:UniProtKB.
DR GO; GO:0048538; P:thymus development; IMP:MGI.
DR InterPro; IPR026905; ASX-like_PHD.
DR InterPro; IPR024811; ASX/ASX-like.
DR InterPro; IPR028020; ASX_DEUBAD_dom.
DR InterPro; IPR024815; ASXL1.
DR InterPro; IPR007759; Asxl_HARE-HTH.
DR InterPro; IPR044867; DEUBAD_dom.
DR PANTHER; PTHR13578; PTHR13578; 1.
DR PANTHER; PTHR13578:SF19; PTHR13578:SF19; 1.
DR Pfam; PF13919; ASXH; 1.
DR Pfam; PF05066; HARE-HTH; 1.
DR Pfam; PF13922; PHD_3; 1.
DR PROSITE; PS51916; DEUBAD; 1.
DR PROSITE; PS51913; HTH_HARE; 1.
PE 1: Evidence at protein level;
KW Chromatin regulator; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..1514
FT /note="Polycomb group protein ASXL1"
FT /id="PRO_0000059322"
FT DOMAIN 11..86
FT /note="HTH HARE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01261"
FT DOMAIN 255..364
FT /note="DEUBAD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01264"
FT ZN_FING 1476..1513
FT /note="PHD-type; atypical"
FT REGION 95..170
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 183..249
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 300..655
FT /note="Interaction with NCOA1"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ9"
FT REGION 378..543
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 635..823
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 895..914
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 926..952
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 964..995
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1082..1087
FT /note="Required for interaction with RARA"
FT /evidence="ECO:0000250"
FT REGION 1095..1131
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1213..1234
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1256..1338
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 284..288
FT /note="LXXLL motif 1"
FT MOTIF 409..413
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 808..812
FT /note="LXXLL motif 2"
FT COMPBIAS 110..154
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 197..214
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 398..433
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 452..475
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 513..543
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 679..693
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 708..729
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 757..771
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 776..790
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 977..991
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1103..1131
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1311..1325
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 498
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ9"
FT MOD_RES 500
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ9"
SQ SEQUENCE 1514 AA; 162674 MW; 20D9FBE9D4CF9E74 CRC64;
MKDKQKRKKE RTWAEAARLV LENYSDAPMT PKQILQVIEA EGLKEMRSGT SPLACLNAML
HSNSRGGEGL FYKLPGRISL FTLKKDAVQW SRNAATVDGD EPEDSADVES CGSNEASTVS
GENDVSLDET SSNASCSTES QSRPLSNPRD SHRASSQANK QKKRTGVMLP RVVLTPLKVN
GAHVEPASGF SGRHADGESG SPSSSSSGSL ALGNSAIRGQ AEVTRDPAPL LRGFRKPATG
QMKRNRGEEV DFETPGSILV NTNLRALINS RTFHALPLHF QQQLLLLLPE VDRQVGTDGL
LRLSGSALNN EFFTHAAQSW RERLADGEFT HEMQVRLRQE MEKEKKVEQW KEKFFEDYYG
QKLGLTKEES LQQKEVQEEA KVKSGLCVSG ESVRPQRGPN TRQRDGHFKK RSRPDLRTRS
RRNIYKKQEP EQAGVAKDAS AAPDVSLSKD TKTDLAGVNS TPGPDVSSAT SGQEGPKCPS
EPVASQIQAE RDNLACASAS PDRIPTLPQD TVDQETKDQK RKSFEQEASA SFPEKKPRLE
DRQSFRNTIE SVHTEKPQPT KEEPKVPPIR IQLSRIKPPW VAKGRPTYQI CPRIVPITES
SCRGWTGART LADIKARALQ ARGARGYHCN RETATTAIGG GGGPGGGGSG AIDEGGGRDS
SSGDGSEACG HPEPRGAPST SGESASDLQR TQLLPPCPLN GEHTPAEAAM PRARREDSAS
LRKEESCLLK RVPGVLTSGL EDASQPPIAP TGDQPCQALP PLSSQTPVAE MLTEQPKLLL
DDRTECESSR EDQGPTIPSE SSSGRFPLGD LLGGGSDQAF DNMKEPVSMT PTFISELSLA
NYLQDRPDDD GLGLGATGLL IRESSRQEAL TEAFASGSPT SWVPILSNYE VIKTSDPESR
ENIPCPEPQD EKEWERAVPL IAATESVPQP ESCISHWTPP PAAVGSTGSD SEQVDLERLE
MNGISEAPSP HSESTDTASD SEGHLSEDSS EVDASEVTVV KGSLGGDEKQ DWDPSASLSK
VNNDLSVLTR TGGVAASQSW VSRVCSVPHK IPDSLLLSST ECQPRSVCPL RPGSSVEVTN
PLVMHLLHGN LPLEKVLPPG HRSSRLESSQ LPLREQSQDR GTLQGTGENN RLAARINPGS
AQTLKESILA QSYGASAGLV RAMASKAPAM SQKIAKMVTS LDSQHPETEL TPSSGNLEEI
DSKEHLSSFL CEEQKEGHSL SQGSDPGAAP GQCLGDHTTS KVPCFSSTNV SLSFGSEQTD
GTLSDQNNAG GHEKKLFGPG NTVTTLQCPR SEEQTPLPAE VPPVFPSRKI EPSKNSVSGG
VQTTRENRMP KPPPVSADSI KTEQTFLRDP IKADAENRKA AGYSSLELVG HLQGMPFVVD
LPFWKLPREP GKGFSQPLEP SSIPSQLNIK QALYGKLSKL QLSPTSFNYS SSSATFPKGL
AGGVVQLSHK ASFGTGHTAS LSLQMFADSS AVESISLQCA CSLKAMIMCQ GCGAFCHDDC
IGPSKLCVLC LVVR
