ASXL1_HUMAN
ID ASXL1_HUMAN Reviewed; 1541 AA.
AC Q8IXJ9; B2RP59; Q5JWS9; Q8IYY7; Q9H466; Q9NQF8; Q9UFJ0; Q9UFP8; Q9Y2I4;
DT 23-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 4.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Polycomb group protein ASXL1;
DE AltName: Full=Additional sex combs-like protein 1;
GN Name=ASXL1; Synonyms=KIAA0978;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RX PubMed=12657473; DOI=10.1016/s0378-1119(03)00430-x;
RA Fisher C.L., Berger J., Randazzo F., Brock H.W.;
RT "A human homolog of Additional sex combs, additional sex combs-like 1, maps
RT to chromosome 20q11.";
RL Gene 306:115-126(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 174-1541, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [5]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 201-1541 (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP FUNCTION, INTERACTION WITH RARA; RXRA AND NCOA1, AND MUTAGENESIS OF
RP VAL-1108 AND LEU-1111.
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP INVOLVEMENT IN MDS.
RX PubMed=19388938; DOI=10.1111/j.1365-2141.2009.07697.x;
RA Gelsi-Boyer V., Trouplin V., Adelaide J., Bonansea J., Cervera N.,
RA Carbuccia N., Lagarde A., Prebet T., Nezri M., Sainty D., Olschwang S.,
RA Xerri L., Chaffanet M., Mozziconacci M.J., Vey N., Birnbaum D.;
RT "Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes
RT and chronic myelomonocytic leukaemia.";
RL Br. J. Haematol. 145:788-800(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [11]
RP INVOLVEMENT IN MDS.
RX PubMed=20182461; DOI=10.1038/leu.2010.20;
RA Boultwood J., Perry J., Pellagatti A., Fernandez-Mercado M.,
RA Fernandez-Santamaria C., Calasanz M.J., Larrayoz M.J., Garcia-Delgado M.,
RA Giagounidis A., Malcovati L., Della Porta M.G., Jadersten M., Killick S.,
RA Hellstrom-Lindberg E., Cazzola M., Wainscoat J.S.;
RT "Frequent mutation of the polycomb-associated gene ASXL1 in the
RT myelodysplastic syndromes and in acute myeloid leukemia.";
RL Leukemia 24:1062-1065(2010).
RN [12]
RP FUNCTION, IDENTIFICATION IN THE PR-DUB COMPLEX, AND INTERACTION WITH BAP1.
RX PubMed=20436459; DOI=10.1038/nature08966;
RA Scheuermann J.C., de Ayala Alonso A.G., Oktaba K., Ly-Hartig N.,
RA McGinty R.K., Fraterman S., Wilm M., Muir T.W., Muller J.;
RT "Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-
RT DUB.";
RL Nature 465:243-247(2010).
RN [13]
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 [14]
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 [15]
RP INVOLVEMENT IN BOPS.
RX PubMed=21706002; DOI=10.1038/ng.868;
RA Hoischen A., van Bon B.W., Rodriguez-Santiago B., Gilissen C.,
RA Vissers L.E., de Vries P., Janssen I., van Lier B., Hastings R.,
RA Smithson S.F., Newbury-Ecob R., Kjaergaard S., Goodship J., McGowan R.,
RA Bartholdi D., Rauch A., Peippo M., Cobben J.M., Wieczorek D.,
RA Gillessen-Kaesbach G., Veltman J.A., Brunner H.G., de Vries B.B.;
RT "De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome.";
RL Nat. Genet. 43:729-731(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-501 AND SER-503, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP FUNCTION, DOMAIN, AND UBIQUITINATION.
RX PubMed=30982744; DOI=10.1016/j.molcel.2019.03.018;
RA Kweon S.M., Chen Y., Moon E., Kvederaviciute K., Klimasauskas S.,
RA Feldman D.E.;
RT "An adversarial DNA N6-methyladenine-sensor network preserves Polycomb
RT silencing.";
RL Mol. Cell 74:1138-1147(2019).
CC -!- FUNCTION: Probable Polycomb group (PcG) protein involved in
CC transcriptional regulation mediated by ligand-bound nuclear hormone
CC receptors, such as retinoic acid receptors (RARs) and peroxisome
CC proliferator-activated receptor gamma (PPARG) (PubMed:16606617). Acts
CC as coactivator of RARA and RXRA through association with NCOA1
CC (PubMed:16606617). Acts as corepressor for PPARG and suppresses its
CC adipocyte differentiation-inducing activity (By similarity). Non-
CC catalytic component of the PR-DUB complex, a complex that specifically
CC mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119'
CC (H2AK119ub1) (PubMed:20436459). Acts as a sensor of N(6)-
CC methyladenosine methylation on DNA (m6A): recognizes and binds m6A DNA,
CC leading to its ubiquitination and degradation by TRIP12, thereby
CC inactivating the PR-DUB complex and regulating Polycomb silencing
CC (PubMed:30982744). {ECO:0000250|UniProtKB:P59598,
CC ECO:0000269|PubMed:16606617, ECO:0000269|PubMed:20436459,
CC ECO:0000269|PubMed:30982744}.
CC -!- SUBUNIT: Component of the PR-DUB complex, at least composed of BAP1 and
CC ASXL1 (PubMed:20436459). Interacts with RARA, RXRA and NCOA1
CC (PubMed:16606617). Interacts with PPARA and PPARG (By similarity).
CC {ECO:0000250|UniProtKB:P59598, ECO:0000269|PubMed:16606617}.
CC -!- INTERACTION:
CC Q8IXJ9; P31749: AKT1; NbExp=2; IntAct=EBI-1646500, EBI-296087;
CC Q8IXJ9; Q92560: BAP1; NbExp=7; IntAct=EBI-1646500, EBI-1791447;
CC Q8IXJ9; O75530: EED; NbExp=5; IntAct=EBI-1646500, EBI-923794;
CC Q8IXJ9; P03372: ESR1; NbExp=2; IntAct=EBI-1646500, EBI-78473;
CC Q8IXJ9; Q15910: EZH2; NbExp=6; IntAct=EBI-1646500, EBI-530054;
CC Q8IXJ9; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-1646500, EBI-5916454;
CC Q8IXJ9; P28700: Rxra; Xeno; NbExp=2; IntAct=EBI-1646500, EBI-346715;
CC Q8IXJ9; P68306: THRB; Xeno; NbExp=2; IntAct=EBI-1646500, EBI-5743841;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8IXJ9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IXJ9-2; Sequence=VSP_007219, VSP_007220;
CC -!- TISSUE SPECIFICITY: Widely expressed at low level. Expressed in heart,
CC brain, skeletal muscle, placenta, pancreas, spleen, prostate, small
CC intestine, colon, peripheral blood, leukocytes, bone marrow and fetal
CC liver. Highly expressed in testes. {ECO:0000269|PubMed:10231032,
CC ECO:0000269|PubMed:12657473}.
CC -!- DOMAIN: The HARE HTH-type domain recognizes and binds N(6)-
CC methyladenosine methylated DNA (m6A). {ECO:0000269|PubMed:30982744}.
CC -!- DOMAIN: Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif, which may be
CC required for an association with nuclear receptors.
CC -!- PTM: Ubiquitinated by TRIP12, leading to its subsequent degradation
CC following binding N(6)-methyladenosine methylated DNA (m6A).
CC {ECO:0000269|PubMed:30982744}.
CC -!- DISEASE: Bohring-Opitz syndrome (BOPS) [MIM:605039]: A syndrome
CC characterized by severe intrauterine growth retardation, poor feeding,
CC profound intellectual disability, trigonocephaly, prominent metopic
CC suture, exophthalmos, nevus flammeus of the face, upslanting palpebral
CC fissures, hirsutism, and flexion of the elbows and wrists with
CC deviation of the wrists and metacarpophalangeal joints.
CC {ECO:0000269|PubMed:21706002}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Myelodysplastic syndrome (MDS) [MIM:614286]: A heterogeneous
CC group of closely related clonal hematopoietic disorders. All are
CC characterized by a hypercellular or hypocellular bone marrow with
CC impaired morphology and maturation, dysplasia of the myeloid,
CC megakaryocytic and/or erythroid lineages, and peripheral blood
CC cytopenias resulting from ineffective blood cell production. Included
CC diseases are: refractory anemia (RA), refractory anemia with ringed
CC sideroblasts (RARS), refractory anemia with excess blasts (RAEB),
CC refractory cytopenia with multilineage dysplasia and ringed
CC sideroblasts (RCMD-RS); chronic myelomonocytic leukemia (CMML) is a
CC myelodysplastic/myeloproliferative disease. MDS is considered a
CC premalignant condition in a subgroup of patients that often progresses
CC to acute myeloid leukemia (AML). {ECO:0000269|PubMed:19388938,
CC ECO:0000269|PubMed:20182461}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the Asx family. {ECO:0000305}.
CC -!- CAUTION: Was previously reported to interact with KDM1A, CBX1, CBX3 and
CC CBX5. However, this publication has been retracted.
CC {ECO:0000305|PubMed:19880879, ECO:0000305|PubMed:25750265}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ASXL1ID44553ch20q11.html";
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DR EMBL; AJ438952; CAD27708.1; -; mRNA.
DR EMBL; AL121583; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL034550; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF495689; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC033284; AAH33284.1; -; mRNA.
DR EMBL; BC137278; AAI37279.1; -; mRNA.
DR EMBL; BC137280; AAI37281.1; -; mRNA.
DR EMBL; AB023195; BAA76822.2; -; mRNA.
DR EMBL; AL117518; CAB55975.1; -; mRNA.
DR EMBL; AL117647; CAB56029.2; -; mRNA.
DR CCDS; CCDS13201.1; -. [Q8IXJ9-1]
DR PIR; T17285; T17285.
DR PIR; T17339; T17339.
DR RefSeq; NP_056153.2; NM_015338.5. [Q8IXJ9-1]
DR AlphaFoldDB; Q8IXJ9; -.
DR SMR; Q8IXJ9; -.
DR BioGRID; 128104; 145.
DR ComplexPortal; CPX-414; PR-DUB complex.
DR CORUM; Q8IXJ9; -.
DR DIP; DIP-46910N; -.
DR IntAct; Q8IXJ9; 45.
DR MINT; Q8IXJ9; -.
DR STRING; 9606.ENSP00000364839; -.
DR GlyGen; Q8IXJ9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8IXJ9; -.
DR PhosphoSitePlus; Q8IXJ9; -.
DR BioMuta; ASXL1; -.
DR DMDM; 317373477; -.
DR EPD; Q8IXJ9; -.
DR jPOST; Q8IXJ9; -.
DR MassIVE; Q8IXJ9; -.
DR MaxQB; Q8IXJ9; -.
DR PaxDb; Q8IXJ9; -.
DR PeptideAtlas; Q8IXJ9; -.
DR PRIDE; Q8IXJ9; -.
DR ProteomicsDB; 71012; -. [Q8IXJ9-1]
DR ProteomicsDB; 71013; -. [Q8IXJ9-2]
DR Antibodypedia; 10384; 113 antibodies from 26 providers.
DR DNASU; 171023; -.
DR Ensembl; ENST00000375687.10; ENSP00000364839.4; ENSG00000171456.21. [Q8IXJ9-1]
DR Ensembl; ENST00000613218.4; ENSP00000480487.1; ENSG00000171456.21. [Q8IXJ9-1]
DR Ensembl; ENST00000620121.4; ENSP00000481978.1; ENSG00000171456.21. [Q8IXJ9-1]
DR GeneID; 171023; -.
DR KEGG; hsa:171023; -.
DR MANE-Select; ENST00000375687.10; ENSP00000364839.4; NM_015338.6; NP_056153.2.
DR UCSC; uc061wei.1; human. [Q8IXJ9-1]
DR CTD; 171023; -.
DR DisGeNET; 171023; -.
DR GeneCards; ASXL1; -.
DR GeneReviews; ASXL1; -.
DR HGNC; HGNC:18318; ASXL1.
DR HPA; ENSG00000171456; Low tissue specificity.
DR MalaCards; ASXL1; -.
DR MIM; 605039; phenotype.
DR MIM; 612990; gene.
DR MIM; 614286; phenotype.
DR neXtProt; NX_Q8IXJ9; -.
DR OpenTargets; ENSG00000171456; -.
DR Orphanet; 98850; Aggressive systemic mastocytosis.
DR Orphanet; 97297; Bohring-Opitz syndrome.
DR Orphanet; 98823; Chronic myelomonocytic leukemia.
DR Orphanet; 98849; Systemic mastocytosis with associated hematologic neoplasm.
DR PharmGKB; PA25078; -.
DR VEuPathDB; HostDB:ENSG00000171456; -.
DR eggNOG; ENOG502QWT2; Eukaryota.
DR GeneTree; ENSGT00520000055578; -.
DR HOGENOM; CLU_247862_0_0_1; -.
DR InParanoid; Q8IXJ9; -.
DR OMA; EDWVPKP; -.
DR OrthoDB; 53757at2759; -.
DR PhylomeDB; Q8IXJ9; -.
DR TreeFam; TF328464; -.
DR PathwayCommons; Q8IXJ9; -.
DR Reactome; R-HSA-5689603; UCH proteinases.
DR SignaLink; Q8IXJ9; -.
DR SIGNOR; Q8IXJ9; -.
DR BioGRID-ORCS; 171023; 24 hits in 1089 CRISPR screens.
DR ChiTaRS; ASXL1; human.
DR GeneWiki; ASXL1; -.
DR GenomeRNAi; 171023; -.
DR Pharos; Q8IXJ9; Tbio.
DR PRO; PR:Q8IXJ9; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q8IXJ9; protein.
DR Bgee; ENSG00000171456; Expressed in sural nerve and 198 other tissues.
DR ExpressionAtlas; Q8IXJ9; baseline and differential.
DR Genevisible; Q8IXJ9; HS.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0035517; C:PR-DUB complex; IDA: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; ISS:UniProtKB.
DR GO; GO:0042975; F:peroxisome proliferator activated receptor binding; ISS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0048539; P:bone marrow development; IEA:Ensembl.
DR GO; GO:0000902; P:cell morphogenesis; IEA:Ensembl.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0003007; P:heart morphogenesis; IEA:Ensembl.
DR GO; GO:0030097; P:hemopoiesis; IEA:Ensembl.
DR GO; GO:0048872; P:homeostasis of number of cells; IEA:Ensembl.
DR GO; GO:0060430; P:lung saccule development; IEA:Ensembl.
DR GO; GO:0035522; P:monoubiquitinated histone H2A deubiquitination; IDA:UniProtKB.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0035359; P:negative regulation of peroxisome proliferator activated receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0072015; P:podocyte development; IEA:Ensembl.
DR GO; GO:0048386; P:positive regulation of retinoic acid receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0035564; P:regulation of kidney size; IEA:Ensembl.
DR GO; GO:0032526; P:response to retinoic acid; ISS:UniProtKB.
DR GO; GO:0048538; P:thymus development; IEA:Ensembl.
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 Alternative splicing; Chromatin regulator; Craniosynostosis; Metal-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..1541
FT /note="Polycomb group protein ASXL1"
FT /id="PRO_0000059321"
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 1503..1540
FT /note="PHD-type; atypical"
FT REGION 94..169
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 193..212
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 300..658
FT /note="Interaction with NCOA1"
FT /evidence="ECO:0000269|PubMed:16606617"
FT REGION 393..546
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 637..719
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 775..883
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 902..950
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 989..1044
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1107..1112
FT /note="Required for interaction with RARA"
FT /evidence="ECO:0000269|PubMed:16606617"
FT REGION 1125..1145
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1195..1304
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 160..164
FT /note="Nuclear localization signal 1"
FT /evidence="ECO:0000255"
FT MOTIF 284..288
FT /note="LXXLL motif"
FT MOTIF 409..413
FT /note="Nuclear localization signal 2"
FT /evidence="ECO:0000255"
FT COMPBIAS 110..163
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 197..212
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 398..434
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 839..858
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 909..925
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1001..1032
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1225..1248
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1249..1303
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 501
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 503
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 433..479
FT /note="AGVAKDAKSVASDVPLYKDGEAKTDPAGLSSPHLPGTSSAAPDLEGP -> S
FT KLWCEPQCITFLANVHQQHGGKHLAPVCVQPESHDHVPRLRCVLSR (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:12657473"
FT /id="VSP_007219"
FT VAR_SEQ 480..1541
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12657473"
FT /id="VSP_007220"
FT VARIANT 751
FT /note="V -> I (in dbSNP:rs6058693)"
FT /id="VAR_051602"
FT VARIANT 815
FT /note="P -> L (in dbSNP:rs6058694)"
FT /id="VAR_028157"
FT VARIANT 983
FT /note="L -> R (in dbSNP:rs34359205)"
FT /id="VAR_051603"
FT VARIANT 1325
FT /note="L -> F (in dbSNP:rs6057581)"
FT /id="VAR_028158"
FT MUTAGEN 1108
FT /note="V->A: Abolishes interaction with RARA."
FT /evidence="ECO:0000269|PubMed:16606617"
FT MUTAGEN 1111
FT /note="L->A: Abolishes interaction with RARA."
FT /evidence="ECO:0000269|PubMed:16606617"
FT CONFLICT 454
FT /note="A -> T (in Ref. 1; CAD27708)"
FT /evidence="ECO:0000305"
FT CONFLICT 880..882
FT /note="TRQ -> ASE (in Ref. 6; CAB56029)"
FT /evidence="ECO:0000305"
FT CONFLICT 1102
FT /note="E -> D (in Ref. 6; CAB55975)"
FT /evidence="ECO:0000305"
FT CONFLICT 1466
FT /note="G -> A (in Ref. 3; AAH33284)"
FT /evidence="ECO:0000305"
FT CONFLICT 1470
FT /note="S -> C (in Ref. 3; AAH33284)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1541 AA; 165432 MW; 8FCE072F3295AA34 CRC64;
MKDKQKKKKE RTWAEAARLV LENYSDAPMT PKQILQVIEA EGLKEMRSGT SPLACLNAML
HSNSRGGEGL FYKLPGRISL FTLKKDALQW SRHPATVEGE EPEDTADVES CGSNEASTVS
GENDVSLDET SSNASCSTES QSRPLSNPRD SYRASSQANK QKKKTGVMLP RVVLTPLKVN
GAHVESASGF SGCHADGESG SPSSSSSGSL ALGSAAIRGQ AEVTQDPAPL LRGFRKPATG
QMKRNRGEEI DFETPGSILV NTNLRALINS RTFHALPSHF QQQLLFLLPE VDRQVGTDGL
LRLSSSALNN EFFTHAAQSW RERLADGEFT HEMQVRIRQE MEKEKKVEQW KEKFFEDYYG
QKLGLTKEES LQQNVGQEEA EIKSGLCVPG ESVRIQRGPA TRQRDGHFKK RSRPDLRTRA
RRNLYKKQES EQAGVAKDAK SVASDVPLYK DGEAKTDPAG LSSPHLPGTS SAAPDLEGPE
FPVESVASRI QAEPDNLARA SASPDRIPSL PQETVDQEPK DQKRKSFEQA ASASFPEKKP
RLEDRQSFRN TIESVHTEKP QPTKEEPKVP PIRIQLSRIK PPWVVKGQPT YQICPRIIPT
TESSCRGWTG ARTLADIKAR ALQVRGARGH HCHREAATTA IGGGGGPGGG GGGATDEGGG
RGSSSGDGGE ACGHPEPRGG PSTPGKCTSD LQRTQLLPPY PLNGEHTQAG TAMSRARRED
LPSLRKEESC LLQRATVGLT DGLGDASQLP VAPTGDQPCQ ALPLLSSQTS VAERLVEQPQ
LHPDVRTECE SGTTSWESDD EEQGPTVPAD NGPIPSLVGD DTLEKGTGQA LDSHPTMKDP
VNVTPSSTPE SSPTDCLQNR AFDDELGLGG SCPPMRESDT RQENLKTKAL VSNSSLHWIP
IPSNDEVVKQ PKPESREHIP SVEPQVGEEW EKAAPTPPAL PGDLTAEEGL DPLDSLTSLW
TVPSRGGSDS NGSYCQQVDI EKLKINGDSE ALSPHGESTD TASDFEGHLT EDSSEADTRE
AAVTKGSSVD KDEKPNWNQS APLSKVNGDM RLVTRTDGMV APQSWVSRVC AVRQKIPDSL
LLASTEYQPR AVCLSMPGSS VEATNPLVMQ LLQGSLPLEK VLPPAHDDSM SESPQVPLTK
DQSHGSLRMG SLHGLGKNSG MVDGSSPSSL RALKEPLLPD SCETGTGLAR IEATQAPGAP
QKNCKAVPSF DSLHPVTNPI TSSRKLEEMD SKEQFSSFSC EDQKEVRAMS QDSNSNAAPG
KSPGDLTTSR TPRFSSPNVI SFGPEQTGRA LGDQSNVTGQ GKKLFGSGNV AATLQRPRPA
DPMPLPAEIP PVFPSGKLGP STNSMSGGVQ TPREDWAPKP HAFVGSVKNE KTFVGGPLKA
NAENRKATGH SPLELVGHLE GMPFVMDLPF WKLPREPGKG LSEPLEPSSL PSQLSIKQAF
YGKLSKLQLS STSFNYSSSS PTFPKGLAGS VVQLSHKANF GASHSASLSL QMFTDSSTVE
SISLQCACSL KAMIMCQGCG AFCHDDCIGP SKLCVLCLVV R
