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 24-JAN-2024, entry version 181. 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. 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 a coactivator of RARA and RXRA through association with NCOA1 CC (PubMed:16606617). Acts as a 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="https://atlasgeneticsoncology.org/gene/44553/ASXL1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 8H1T; EM; 3.00 A; N=1-378. DR PDB; 8SVF; EM; 3.20 A; L=1-1541. DR PDBsum; 8H1T; -. DR PDBsum; 8SVF; -. DR AlphaFoldDB; Q8IXJ9; -. DR EMDB; EMD-34431; -. DR EMDB; EMD-40789; -. DR SMR; Q8IXJ9; -. DR BioGRID; 128104; 285. DR ComplexPortal; CPX-414; PR-DUB complex. DR CORUM; Q8IXJ9; -. DR DIP; DIP-46910N; -. DR IntAct; Q8IXJ9; 43. DR MINT; Q8IXJ9; -. DR STRING; 9606.ENSP00000364839; -. DR GlyCosmos; Q8IXJ9; 1 site, 1 glycan. 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; 9606-ENSP00000364839; -. DR PeptideAtlas; Q8IXJ9; -. DR ProteomicsDB; 71012; -. [Q8IXJ9-1] DR ProteomicsDB; 71013; -. [Q8IXJ9-2] DR Pumba; Q8IXJ9; -. DR Antibodypedia; 10384; 134 antibodies from 26 providers. DR DNASU; 171023; -. DR Ensembl; ENST00000375687.10; ENSP00000364839.4; ENSG00000171456.22. [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 AGR; HGNC:18318; -. 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; 86845; Acute myeloid leukaemia with myelodysplasia-related features. 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; VEVEMCF; -. DR OrthoDB; 3642313at2759; -. 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; 25 hits in 1174 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 200 other cell types or tissues. DR ExpressionAtlas; Q8IXJ9; baseline and differential. 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: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; IPR007759; Asxl_HARE-HTH. DR InterPro; IPR044867; DEUBAD_dom. DR PANTHER; PTHR13578; ADDITIONAL SEX COMBS LIKE PROTEIN ASXL; 1. DR PANTHER; PTHR13578:SF19; POLYCOMB GROUP PROTEIN ASXL1; 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. DR Genevisible; Q8IXJ9; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Chromatin regulator; Craniosynostosis; KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repressor; KW Transcription; Transcription regulation; Ubl conjugation; KW Ubl conjugation pathway; Zinc; 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" FT TURN 258..261 FT /evidence="ECO:0007829|PDB:8H1T" FT HELIX 264..267 FT /evidence="ECO:0007829|PDB:8H1T" FT HELIX 270..274 FT /evidence="ECO:0007829|PDB:8H1T" FT HELIX 278..285 FT /evidence="ECO:0007829|PDB:8H1T" FT STRAND 293..295 FT /evidence="ECO:0007829|PDB:8H1T" FT STRAND 301..303 FT /evidence="ECO:0007829|PDB:8H1T" FT STRAND 307..310 FT /evidence="ECO:0007829|PDB:8H1T" FT HELIX 311..326 FT /evidence="ECO:0007829|PDB:8H1T" FT TURN 327..329 FT /evidence="ECO:0007829|PDB:8H1T" FT HELIX 331..351 FT /evidence="ECO:0007829|PDB:8H1T" FT TURN 352..354 FT /evidence="ECO:0007829|PDB:8H1T" 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 //