Protein: Polycomb group protein ASXL1 (Additional sex combs-like protein 1) (Q8IXJ9)
Organism: Homo sapiens (Human)
Function: Probable Polycomb group (PcG) protein involved in transcriptional regulation mediated by ligand-bound nuclear hormone receptors, such as retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor gamma (PPARG). Acts as coactivator of RARA and RXRA through association with NCOA1. Acts as corepressor for PPARG and suppresses its adipocyte differentiation-inducing activity (By similarity). Non-catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1). Acts as a sensor of N(6)-methyladenosine methylation on DNA (m6A): recognizes and binds m6A DNA, leading to its ubiquitination and degradation by TRIP12, thereby inactivating the PR-DUB complex and regulating Polycomb silencing.
Subcellular location: Nucleus {ECO:0000305}.
Sequence: MKDKQKKKKERTWAEAARLVLENYSDAPMTPKQILQVIEAEGLKEMRSGTSPLACLNAMLHSNSRGGEGLFYKLPGRISLFTLKKDALQWSRHPATVEGEEPEDTADVESCGSNEASTVSGENDVSLDETSSNASCSTESQSRPLSNPRDSYRASSQANKQKKKTGVMLPRVVLTPLKVNGAHVESASGFSGCHADGESGSPSSSSSGSLALGSAAIRGQAEVTQDPAPLLRGFRKPATGQMKRNRGEEIDFETPGSILVNTNLRALINSRTFHALPSHFQQQLLFLLPEVDRQVGTDGLLRLSSSALNNEFFTHAAQSWRERLADGEFTHEMQVRIRQEMEKEKKVEQWKEKFFEDYYGQKLGLTKEESLQQNVGQEEAEIKSGLCVPGESVRIQRGPATRQRDGHFKKRSRPDLRTRARRNLYKKQESEQAGVAKDAKSVASDVPLYKDGEAKTDPAGLSSPHLPGTSSAAPDLEGPEFPVESVASRIQAEPDNLARASASPDRIPSLPQETVDQEPKDQKRKSFEQAASASFPEKKPRLEDRQSFRNTIESVHTEKPQPTKEEPKVPPIRIQLSRIKPPWVVKGQPTYQICPRIIPTTESSCRGWTGARTLADIKARALQVRGARGHHCHREAATTAIGGGGGPGGGGGGATDEGGGRGSSSGDGGEACGHPEPRGGPSTPGKCTSDLQRTQLLPPYPLNGEHTQAGTAMSRARREDLPSLRKEESCLLQRATVGLTDGLGDASQLPVAPTGDQPCQALPLLSSQTSVAERLVEQPQLHPDVRTECESGTTSWESDDEEQGPTVPADNGPIPSLVGDDTLEKGTGQALDSHPTMKDPVNVTPSSTPESSPTDCLQNRAFDDELGLGGSCPPMRESDTRQENLKTKALVSNSSLHWIPIPSNDEVVKQPKPESREHIPSVEPQVGEEWEKAAPTPPALPGDLTAEEGLDPLDSLTSLWTVPSRGGSDSNGSYCQQVDIEKLKINGDSEALSPHGESTDTASDFEGHLTEDSSEADTREAAVTKGSSVDKDEKPNWNQSAPLSKVNGDMRLVTRTDGMVAPQSWVSRVCAVRQKIPDSLLLASTEYQPRAVCLSMPGSSVEATNPLVMQLLQGSLPLEKVLPPAHDDSMSESPQVPLTKDQSHGSLRMGSLHGLGKNSGMVDGSSPSSLRALKEPLLPDSCETGTGLARIEATQAPGAPQKNCKAVPSFDSLHPVTNPITSSRKLEEMDSKEQFSSFSCEDQKEVRAMSQDSNSNAAPGKSPGDLTTSRTPRFSSPNVISFGPEQTGRALGDQSNVTGQGKKLFGSGNVAATLQRPRPADPMPLPAEIPPVFPSGKLGPSTNSMSGGVQTPREDWAPKPHAFVGSVKNEKTFVGGPLKANAENRKATGHSPLELVGHLEGMPFVMDLPFWKLPREPGKGLSEPLEPSSLPSQLSIKQAFYGKLSKLQLSSTSFNYSSSSPTFPKGLAGSVVQLSHKANFGASHSASLSLQMFTDSSTVESISLQCACSLKAMIMCQGCGAFCHDDCIGPSKLCVLCLVVR
InterPro domains: - IPR044867: DEUBAD domain (domain) [255-364]
- IPR026905: Protein ASX-like, PHD domain (domain) [1503-1539]
- IPR007759: ASXL, HARE-HTH domain (domain) [11-86]
- IPR024811: Polycomb protein ASX/ASX-like (family) [1-1541]
- IPR028020: ASX, DEUBAD domain (domain) [237-361]
Interaction partners: - Ubiquitin carboxyl-terminal hydrolase BAP1
- Histone-lysine N-methyltransferase EZH2
- Polycomb protein SUZ12
- Forkhead box protein K1
- UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit
- Methylcytosine dioxygenase TET2
- Histone-binding protein RBBP4
- Host cell factor 1
- E3 ubiquitin-protein ligase RING2
- Polycomb complex protein BMI-1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding), GO:0005102 (signaling receptor binding), GO:0042975 (peroxisome proliferator activated receptor binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0048519 (negative regulation of biological process), GO:0050793 (regulation of developmental process), GO:0023056 (positive regulation of signaling), GO:0023057 (negative regulation of signaling), GO:0048584 (positive regulation of response to stimulus), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0023051 (regulation of signaling), GO:0048523 (negative regulation of cellular process), GO:0048585 (negative regulation of response to stimulus), GO:0048522 (positive regulation of cellular process), GO:0009967 (positive regulation of signal transduction), GO:0009968 (negative regulation of signal transduction), GO:0010648 (negative regulation of cell communication), GO:0010646 (regulation of cell communication), GO:0009966 (regulation of signal transduction), GO:0022603 (regulation of anatomical structure morphogenesis), GO:0010647 (positive regulation of cell communication), GO:0030111 (regulation of Wnt signaling pathway), GO:0030178 (negative regulation of Wnt signaling pathway), GO:0030177 (positive regulation of Wnt signaling pathway), GO:2000027 (regulation of animal organ morphogenesis), GO:0090175 (regulation of establishment of planar polarity), GO:2000052 (positive regulation of non-canonical Wnt signaling pathway), GO:2000050 (regulation of non-canonical Wnt signaling pathway), GO:0090090 (negative regulation of canonical Wnt signaling pathway), GO:0060828 (regulation of canonical Wnt signaling pathway), GO:2000095 (regulation of Wnt signaling pathway, planar cell polarity pathway)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043229 (intracellular organelle), GO:0043233 (organelle lumen), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)