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P59598

- ASXL1_MOUSE

UniProt

P59598 - ASXL1_MOUSE

Protein

Putative Polycomb group protein ASXL1

Gene

Asxl1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 91 (01 Oct 2014)
      Sequence version 1 (23 Apr 2003)
      Previous versions | rss
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    Functioni

    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).3 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri1476 – 151338PHD-type; atypicalAdd
    BLAST

    GO - Molecular functioni

    1. DNA binding Source: InterPro
    2. metal ion binding Source: UniProtKB-KW
    3. peroxisome proliferator activated receptor binding Source: UniProtKB
    4. protein binding Source: IntAct
    5. retinoic acid receptor binding Source: UniProtKB
    6. transcription coactivator activity Source: UniProtKB
    7. transcription corepressor activity Source: UniProtKB

    GO - Biological processi

    1. bone development Source: MGI
    2. monoubiquitinated histone H2A deubiquitination Source: UniProtKB
    3. negative regulation of fat cell differentiation Source: UniProtKB
    4. negative regulation of peroxisome proliferator activated receptor signaling pathway Source: UniProtKB
    5. negative regulation of retinoic acid receptor signaling pathway Source: UniProtKB
    6. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    7. positive regulation of retinoic acid receptor signaling pathway Source: UniProtKB
    8. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    9. response to retinoic acid Source: UniProtKB
    10. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Chromatin regulator, Repressor

    Keywords - Biological processi

    Transcription, Transcription regulation, Ubl conjugation pathway

    Keywords - Ligandi

    Metal-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Putative Polycomb group protein ASXL1
    Alternative name(s):
    Additional sex combs-like protein 1
    Gene namesi
    Name:Asxl1
    Synonyms:Kiaa0978
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 2

    Organism-specific databases

    MGIiMGI:2684063. Asxl1.

    Subcellular locationi

    Nucleus 1 Publication

    GO - Cellular componenti

    1. nuclear chromatin Source: UniProtKB
    2. PR-DUB complex Source: UniProtKB

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi170 – 1701P → A: Abolishes interaction with CBX1, CBX3 and CBX5; when associated with A-172 and A-174. 1 Publication
    Mutagenesisi172 – 1721V → A: Abolishes interaction with CBX1, CBX3 and CBX5; when associated with A-170 and A-174. 1 Publication
    Mutagenesisi174 – 1741L → A: Abolishes interaction with CBX1, CBX3 and CBX5; when associated with A-170 and A-172. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 15141514Putative Polycomb group protein ASXL1PRO_0000059322Add
    BLAST

    Proteomic databases

    PaxDbiP59598.
    PRIDEiP59598.

    PTM databases

    PhosphoSiteiP59598.

    Expressioni

    Gene expression databases

    ArrayExpressiP59598.
    BgeeiP59598.
    CleanExiMM_ASXL1.
    GenevestigatoriP59598.

    Interactioni

    Subunit structurei

    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.By similarity3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CBX5P459735EBI-5743705,EBI-78219From a different organism.
    ESR1P033722EBI-5743705,EBI-78473From a different organism.
    KDM1AO603412EBI-5743705,EBI-710124From a different organism.
    NCOA1Q157882EBI-5743705,EBI-455189From a different organism.
    NR3C1P041502EBI-5743705,EBI-493507From a different organism.
    RARAP102764EBI-5743705,EBI-413374From a different organism.
    RxraP287002EBI-5743705,EBI-346715

    Protein-protein interaction databases

    BioGridi230772. 3 interactions.
    IntActiP59598. 12 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliP59598.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni170 – 1745Required for interaction with CBX5
    Regioni175 – 370196Interaction with KDM1AAdd
    BLAST
    Regioni300 – 655356Interaction with NCOA1Add
    BLAST
    Regioni1082 – 10876Required for interaction with RARABy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi284 – 2885LXXLL motif 1
    Motifi409 – 4135Nuclear localization signalSequence Analysis
    Motifi808 – 8125LXXLL motif 2

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi199 – 20911Poly-SerAdd
    BLAST
    Compositional biasi284 – 2885Poly-Leu
    Compositional biasi639 – 67032Gly-richAdd
    BLAST
    Compositional biasi1430 – 14334Poly-Ser

    Domaini

    Contains two Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs, which may be required for an association with nuclear receptors.By similarity

    Sequence similaritiesi

    Belongs to the Asx family.Curated
    Contains 1 PHD-type zinc finger.Curated

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri1476 – 151338PHD-type; atypicalAdd
    BLAST

    Keywords - Domaini

    Repeat, Zinc-finger

    Phylogenomic databases

    eggNOGiNOG81527.
    HOGENOMiHOG000293301.
    HOVERGENiHBG050598.
    InParanoidiP59598.
    KOiK11471.
    OMAiSLKAMIM.
    OrthoDBiEOG7SXW2P.
    PhylomeDBiP59598.
    TreeFamiTF328464.

    Family and domain databases

    InterProiIPR026905. ASX-like_PHD.
    IPR024811. ASX/ASX-like.
    IPR028020. ASXH.
    IPR024815. ASXL1.
    IPR007759. DNA-dir_RNA_pol_delta/Asxl.
    [Graphical view]
    PANTHERiPTHR13578. PTHR13578. 1 hit.
    PTHR13578:SF19. PTHR13578:SF19. 1 hit.
    PfamiPF13919. ASXH. 1 hit.
    PF05066. HARE-HTH. 1 hit.
    PF13922. PHD_3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P59598-1 [UniParc]FASTAAdd to Basket

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    MKDKQKRKKE RTWAEAARLV LENYSDAPMT PKQILQVIEA EGLKEMRSGT     50
    SPLACLNAML HSNSRGGEGL FYKLPGRISL FTLKKDAVQW SRNAATVDGD 100
    EPEDSADVES CGSNEASTVS GENDVSLDET SSNASCSTES QSRPLSNPRD 150
    SHRASSQANK QKKRTGVMLP RVVLTPLKVN GAHVEPASGF SGRHADGESG 200
    SPSSSSSGSL ALGNSAIRGQ AEVTRDPAPL LRGFRKPATG QMKRNRGEEV 250
    DFETPGSILV NTNLRALINS RTFHALPLHF QQQLLLLLPE VDRQVGTDGL 300
    LRLSGSALNN EFFTHAAQSW RERLADGEFT HEMQVRLRQE MEKEKKVEQW 350
    KEKFFEDYYG QKLGLTKEES LQQKEVQEEA KVKSGLCVSG ESVRPQRGPN 400
    TRQRDGHFKK RSRPDLRTRS RRNIYKKQEP EQAGVAKDAS AAPDVSLSKD 450
    TKTDLAGVNS TPGPDVSSAT SGQEGPKCPS EPVASQIQAE RDNLACASAS 500
    PDRIPTLPQD TVDQETKDQK RKSFEQEASA SFPEKKPRLE DRQSFRNTIE 550
    SVHTEKPQPT KEEPKVPPIR IQLSRIKPPW VAKGRPTYQI CPRIVPITES 600
    SCRGWTGART LADIKARALQ ARGARGYHCN RETATTAIGG GGGPGGGGSG 650
    AIDEGGGRDS SSGDGSEACG HPEPRGAPST SGESASDLQR TQLLPPCPLN 700
    GEHTPAEAAM PRARREDSAS LRKEESCLLK RVPGVLTSGL EDASQPPIAP 750
    TGDQPCQALP PLSSQTPVAE MLTEQPKLLL DDRTECESSR EDQGPTIPSE 800
    SSSGRFPLGD LLGGGSDQAF DNMKEPVSMT PTFISELSLA NYLQDRPDDD 850
    GLGLGATGLL IRESSRQEAL TEAFASGSPT SWVPILSNYE VIKTSDPESR 900
    ENIPCPEPQD EKEWERAVPL IAATESVPQP ESCISHWTPP PAAVGSTGSD 950
    SEQVDLERLE MNGISEAPSP HSESTDTASD SEGHLSEDSS EVDASEVTVV 1000
    KGSLGGDEKQ DWDPSASLSK VNNDLSVLTR TGGVAASQSW VSRVCSVPHK 1050
    IPDSLLLSST ECQPRSVCPL RPGSSVEVTN PLVMHLLHGN LPLEKVLPPG 1100
    HRSSRLESSQ LPLREQSQDR GTLQGTGENN RLAARINPGS AQTLKESILA 1150
    QSYGASAGLV RAMASKAPAM SQKIAKMVTS LDSQHPETEL TPSSGNLEEI 1200
    DSKEHLSSFL CEEQKEGHSL SQGSDPGAAP GQCLGDHTTS KVPCFSSTNV 1250
    SLSFGSEQTD GTLSDQNNAG GHEKKLFGPG NTVTTLQCPR SEEQTPLPAE 1300
    VPPVFPSRKI EPSKNSVSGG VQTTRENRMP KPPPVSADSI KTEQTFLRDP 1350
    IKADAENRKA AGYSSLELVG HLQGMPFVVD LPFWKLPREP GKGFSQPLEP 1400
    SSIPSQLNIK QALYGKLSKL QLSPTSFNYS SSSATFPKGL AGGVVQLSHK 1450
    ASFGTGHTAS LSLQMFADSS AVESISLQCA CSLKAMIMCQ GCGAFCHDDC 1500
    IGPSKLCVLC LVVR 1514
    Length:1,514
    Mass (Da):162,674
    Last modified:April 23, 2003 - v1
    Checksum:i20D9FBE9D4CF9E74
    GO

    Sequence cautioni

    The sequence BAC65695.1 differs from that shown. Reason: Erroneous initiation.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK122413 mRNA. Translation: BAC65695.1. Different initiation.
    CCDSiCCDS38285.1.
    RefSeqiNP_001035028.1. NM_001039939.1.
    UniGeneiMm.330677.

    Genome annotation databases

    EnsembliENSMUST00000109790; ENSMUSP00000105413; ENSMUSG00000042548.
    GeneIDi228790.
    KEGGimmu:228790.
    UCSCiuc008nhs.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK122413 mRNA. Translation: BAC65695.1 . Different initiation.
    CCDSi CCDS38285.1.
    RefSeqi NP_001035028.1. NM_001039939.1.
    UniGenei Mm.330677.

    3D structure databases

    ProteinModelPortali P59598.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 230772. 3 interactions.
    IntActi P59598. 12 interactions.

    PTM databases

    PhosphoSitei P59598.

    Proteomic databases

    PaxDbi P59598.
    PRIDEi P59598.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000109790 ; ENSMUSP00000105413 ; ENSMUSG00000042548 .
    GeneIDi 228790.
    KEGGi mmu:228790.
    UCSCi uc008nhs.1. mouse.

    Organism-specific databases

    CTDi 171023.
    MGIi MGI:2684063. Asxl1.
    Rougei Search...

    Phylogenomic databases

    eggNOGi NOG81527.
    HOGENOMi HOG000293301.
    HOVERGENi HBG050598.
    InParanoidi P59598.
    KOi K11471.
    OMAi SLKAMIM.
    OrthoDBi EOG7SXW2P.
    PhylomeDBi P59598.
    TreeFami TF328464.

    Miscellaneous databases

    NextBioi 379148.
    PROi P59598.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P59598.
    Bgeei P59598.
    CleanExi MM_ASXL1.
    Genevestigatori P59598.

    Family and domain databases

    InterProi IPR026905. ASX-like_PHD.
    IPR024811. ASX/ASX-like.
    IPR028020. ASXH.
    IPR024815. ASXL1.
    IPR007759. DNA-dir_RNA_pol_delta/Asxl.
    [Graphical view ]
    PANTHERi PTHR13578. PTHR13578. 1 hit.
    PTHR13578:SF19. PTHR13578:SF19. 1 hit.
    Pfami PF13919. ASXH. 1 hit.
    PF05066. HARE-HTH. 1 hit.
    PF13922. PHD_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      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.

    Entry informationi

    Entry nameiASXL1_MOUSE
    AccessioniPrimary (citable) accession number: P59598
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 23, 2003
    Last sequence update: April 23, 2003
    Last modified: October 1, 2014
    This is version 91 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3