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Q9Y6X2

- PIAS3_HUMAN

UniProt

Q9Y6X2 - PIAS3_HUMAN

Protein

E3 SUMO-protein ligase PIAS3

Gene

PIAS3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 131 (01 Oct 2014)
      Sequence version 2 (07 Dec 2004)
      Previous versions | rss
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    Functioni

    Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor. Plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway and the steroid hormone signaling pathway. Involved in regulating STAT3 signaling via inhibiting STAT3 DNA-binding and suppressing cell growth. Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation.2 Publications

    Pathwayi

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri303 – 38078SP-RING-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. enzyme binding Source: UniProtKB
    2. nucleic acid binding Source: InterPro
    3. potassium channel regulator activity Source: Ensembl
    4. protein binding Source: UniProtKB
    5. protein C-terminus binding Source: UniProtKB
    6. SUMO ligase activity Source: Ensembl
    7. zinc ion binding Source: InterPro

    GO - Biological processi

    1. positive regulation of gene expression Source: Ensembl
    2. positive regulation of membrane potential Source: Ensembl
    3. positive regulation of protein sumoylation Source: UniProtKB
    4. protein sumoylation Source: UniProtKB
    5. regulation of transcription, DNA-templated Source: UniProtKB-KW
    6. response to hormone Source: Ensembl
    7. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Ligase

    Keywords - Biological processi

    Transcription, Transcription regulation, Ubl conjugation pathway

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    SignaLinkiQ9Y6X2.
    UniPathwayiUPA00886.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    E3 SUMO-protein ligase PIAS3 (EC:6.3.2.-)
    Alternative name(s):
    Protein inhibitor of activated STAT protein 3
    Gene namesi
    Name:PIAS3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:16861. PIAS3.

    Subcellular locationi

    Cytoplasm. Nucleus
    Note: Mainly cytoplasmic but shuttles between the nucleus and cytoplasm. Transported to the nucleus on interaction with phosphorylated STAT3. Colocalizes with GFI1 in nuclear dots By similarity.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. dendrite Source: Ensembl
    3. nucleus Source: UniProtKB-SubCell
    4. synapse Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134989011.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 628628E3 SUMO-protein ligase PIAS3PRO_0000218979Add
    BLAST

    Post-translational modificationi

    Sumoylated.By similarity

    Keywords - PTMi

    Ubl conjugation

    Proteomic databases

    MaxQBiQ9Y6X2.
    PaxDbiQ9Y6X2.
    PRIDEiQ9Y6X2.

    PTM databases

    PhosphoSiteiQ9Y6X2.

    Expressioni

    Tissue specificityi

    Isoform 1 is expressed in most tissues except thymus and small intestine. Isoform 3 is expressed only in brain, heart, thymus, muscle, lung, testis, lactating breast and embryonic stem cells.1 Publication

    Inductioni

    By dihydrotestosterone (DHT) in prostate cancer cells.1 Publication

    Gene expression databases

    ArrayExpressiQ9Y6X2.
    BgeeiQ9Y6X2.
    CleanExiHS_PIAS3.
    GenevestigatoriQ9Y6X2.

    Interactioni

    Subunit structurei

    Monomer By similarity. Binds SUMO1 and UBE2I. Interacts with BCL11A, HMGA2, IRF1, MITF and NCOA2. Interacts with STAT5; the interaction occurs on stimulation by PRL. Interacts with GFI1; the interaction relieves the inhibitory effect of PIAS3 on STAT3-mediated transcriptional activity By similarity. Interacts with AR, PLAG1 and ZFHX3. Interacts with STAT3; the interaction occurs on stimulation by IL6, CNTF or OSM and inhibits the DNA binding activity of STAT3. Interacts with MTA1.By similarity6 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    MBD1Q9UIS93EBI-2803703,EBI-867196

    Protein-protein interaction databases

    BioGridi115673. 52 interactions.
    DIPiDIP-5969N.
    IntActiQ9Y6X2. 25 interactions.
    MINTiMINT-149343.
    STRINGi9606.ENSP00000376765.

    Structurei

    Secondary structure

    1
    628
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi135 – 14713
    Beta strandi155 – 1628
    Helixi166 – 1738
    Beta strandi187 – 19711
    Beta strandi212 – 2154
    Beta strandi218 – 2203
    Helixi245 – 2473
    Beta strandi252 – 2543
    Beta strandi256 – 2649
    Beta strandi268 – 27912
    Helixi282 – 29110
    Helixi297 – 30711
    Beta strandi320 – 3267
    Turni328 – 3303
    Beta strandi335 – 3406
    Helixi351 – 36010
    Turni367 – 3693
    Helixi375 – 3773
    Beta strandi378 – 3814
    Helixi382 – 3909
    Beta strandi395 – 4006
    Beta strandi405 – 4073

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4MVTX-ray2.30A/B/C/D112-467[»]
    ProteinModelPortaliQ9Y6X2.
    SMRiQ9Y6X2. Positions 1-65, 126-408.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini11 – 4535SAPPROSITE-ProRule annotationAdd
    BLAST
    Domaini115 – 280166PINITPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni450 – 46011SUMO1-bindingBy similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi19 – 235LXXLL motif

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi81 – 13353Pro-richAdd
    BLAST

    Domaini

    The PINIT domain of PIAS3 is required for STAT3-PIAS3 interaction and for transloaction to the nucleus.
    The LXXLL motif is a transcriptional coregulator signature.

    Sequence similaritiesi

    Belongs to the PIAS family.Curated
    Contains 1 PINIT domain.PROSITE-ProRule annotation
    Contains 1 SAP domain.PROSITE-ProRule annotation
    Contains 1 SP-RING-type zinc finger.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri303 – 38078SP-RING-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiNOG125513.
    HOGENOMiHOG000230594.
    HOVERGENiHBG053598.
    InParanoidiQ9Y6X2.
    KOiK16064.
    OMAiKHMVMSF.
    PhylomeDBiQ9Y6X2.
    TreeFamiTF323787.

    Family and domain databases

    Gene3Di1.10.720.30. 1 hit.
    InterProiIPR027226. PIAS3.
    IPR023321. PINIT.
    IPR003034. SAP_dom.
    IPR004181. Znf_MIZ.
    [Graphical view]
    PANTHERiPTHR10782:SF10. PTHR10782:SF10. 1 hit.
    PfamiPF14324. PINIT. 1 hit.
    PF02891. zf-MIZ. 1 hit.
    [Graphical view]
    SMARTiSM00513. SAP. 1 hit.
    [Graphical view]
    PROSITEiPS51466. PINIT. 1 hit.
    PS50800. SAP. 1 hit.
    PS51044. ZF_SP_RING. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9Y6X2-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAELGELKHM VMSFRVSELQ VLLGFAGRNK SGRKHELLAK ALHLLKSSCA    50
    PSVQMKIKEL YRRRFPRKTL GPSDLSLLSL PPGTSPVGSP GPLAPIPPTL 100
    LAPGTLLGPK REVDMHPPLP QPVHPDVTMK PLPFYEVYGE LIRPTTLAST 150
    SSQRFEEAHF TFALTPQQVQ QILTSREVLP GAKCDYTIQV QLRFCLCETS 200
    CPQEDYFPPN LFVKVNGKLC PLPGYLPPTK NGAEPKRPSR PINITPLARL 250
    SATVPNTIVV NWSSEFGRNY SLSVYLVRQL TAGTLLQKLR AKGIRNPDHS 300
    RALIKEKLTA DPDSEVATTS LRVSLMCPLG KMRLTVPCRA LTCAHLQSFD 350
    AALYLQMNEK KPTWTCPVCD KKAPYESLII DGLFMEILSS CSDCDEIQFM 400
    EDGSWCPMKP KKEASEVCPP PGYGLDGLQY SPVQGGDPSE NKKKVEVIDL 450
    TIESSSDEED LPPTKKHCSV TSAAIPALPG SKGVLTSGHQ PSSVLRSPAM 500
    GTLGGDFLSS LPLHEYPPAF PLGADIQGLD LFSFLQTESQ HYGPSVITSL 550
    DEQDALGHFF QYRGTPSHFL GPLAPTLGSS HCSATPAPPP GRVSSIVAPG 600
    GALREGHGGP LPSGPSLTGC RSDIISLD 628
    Length:628
    Mass (Da):68,017
    Last modified:December 7, 2004 - v2
    Checksum:i7C06EF599D48F87D
    GO

    Sequence cautioni

    The sequence BAA78533.1 differs from that shown. Reason: Erroneous initiation.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti390 – 3901S → C.
    Corresponds to variant rs17354559 [ dbSNP | Ensembl ].
    VAR_050535

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB021868 mRNA. Translation: BAA78533.1. Different initiation.
    BC001154 mRNA. Translation: AAH01154.2.
    BC030556 mRNA. Translation: AAH30556.2.
    CCDSiCCDS920.2.
    PIRiT34525.
    RefSeqiNP_006090.2. NM_006099.3.
    UniGeneiHs.435761.

    Genome annotation databases

    EnsembliENST00000393045; ENSP00000376765; ENSG00000131788.
    GeneIDi10401.
    KEGGihsa:10401.
    UCSCiuc001eoc.1. human.

    Polymorphism databases

    DMDMi56405390.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB021868 mRNA. Translation: BAA78533.1 . Different initiation.
    BC001154 mRNA. Translation: AAH01154.2 .
    BC030556 mRNA. Translation: AAH30556.2 .
    CCDSi CCDS920.2.
    PIRi T34525.
    RefSeqi NP_006090.2. NM_006099.3.
    UniGenei Hs.435761.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4MVT X-ray 2.30 A/B/C/D 112-467 [» ]
    ProteinModelPortali Q9Y6X2.
    SMRi Q9Y6X2. Positions 1-65, 126-408.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 115673. 52 interactions.
    DIPi DIP-5969N.
    IntActi Q9Y6X2. 25 interactions.
    MINTi MINT-149343.
    STRINGi 9606.ENSP00000376765.

    PTM databases

    PhosphoSitei Q9Y6X2.

    Polymorphism databases

    DMDMi 56405390.

    Proteomic databases

    MaxQBi Q9Y6X2.
    PaxDbi Q9Y6X2.
    PRIDEi Q9Y6X2.

    Protocols and materials databases

    DNASUi 10401.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000393045 ; ENSP00000376765 ; ENSG00000131788 .
    GeneIDi 10401.
    KEGGi hsa:10401.
    UCSCi uc001eoc.1. human.

    Organism-specific databases

    CTDi 10401.
    GeneCardsi GC01P145575.
    HGNCi HGNC:16861. PIAS3.
    MIMi 605987. gene.
    neXtProti NX_Q9Y6X2.
    PharmGKBi PA134989011.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG125513.
    HOGENOMi HOG000230594.
    HOVERGENi HBG053598.
    InParanoidi Q9Y6X2.
    KOi K16064.
    OMAi KHMVMSF.
    PhylomeDBi Q9Y6X2.
    TreeFami TF323787.

    Enzyme and pathway databases

    UniPathwayi UPA00886 .
    SignaLinki Q9Y6X2.

    Miscellaneous databases

    ChiTaRSi PIAS3. human.
    GeneWikii PIAS3.
    GenomeRNAii 10401.
    NextBioi 39416.
    PROi Q9Y6X2.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9Y6X2.
    Bgeei Q9Y6X2.
    CleanExi HS_PIAS3.
    Genevestigatori Q9Y6X2.

    Family and domain databases

    Gene3Di 1.10.720.30. 1 hit.
    InterProi IPR027226. PIAS3.
    IPR023321. PINIT.
    IPR003034. SAP_dom.
    IPR004181. Znf_MIZ.
    [Graphical view ]
    PANTHERi PTHR10782:SF10. PTHR10782:SF10. 1 hit.
    Pfami PF14324. PINIT. 1 hit.
    PF02891. zf-MIZ. 1 hit.
    [Graphical view ]
    SMARTi SM00513. SAP. 1 hit.
    [Graphical view ]
    PROSITEi PS51466. PINIT. 1 hit.
    PS50800. SAP. 1 hit.
    PS51044. ZF_SP_RING. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Isolation and chromosomal assignment of a human gene encoding protein inhibitor of activated STAT3 (PIAS3)."
      Ueki N., Seki N., Yano K., Saito T., Masuho Y., Muramatsu M.-A.
      J. Hum. Genet. 44:193-196(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-628.
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Blood and Muscle.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 310-628.
      Tissue: Mammary cancer.
    4. "Specific inhibition of Stat3 signal transduction by PIAS3."
      Chung C.D., Liao J., Liu B., Rao X., Jay P., Berta P., Shuai K.
      Science 278:1803-1805(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH STAT3, TISSUE SPECIFICITY.
    5. "Protein inhibitor of activated STAT3 regulates androgen receptor signaling in prostate carcinoma cells."
      Junicho A., Matsuda T., Yamamoto T., Kishi H., Korkmaz K., Saatcioglu F., Fuse H., Muraguchi A.
      Biochem. Biophys. Res. Commun. 278:9-13(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AR, INDUCTION.
    6. "The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3."
      Roedel B., Tavassoli K., Karsunky H., Schmidt T., Bachmann M., Schaper F., Heinrich P., Shuai K., Elsaesser H.-P., Moeroey T.
      EMBO J. 19:5845-5855(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH GFI1.
    7. "ATBF1 enhances the suppression of STAT3 signaling by interaction with PIAS3."
      Nojiri S., Joh T., Miura Y., Sakata N., Nomura T., Nakao H., Sobue S., Ohara H., Asai K., Ito M.
      Biochem. Biophys. Res. Commun. 314:97-103(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ZFHX3.
    8. "Repression of the transactivating capacity of the oncoprotein PLAG1 by SUMOylation."
      Van Dyck F., Delvaux E.L.D., Van de Ven W.J.M., Chavez M.V.
      J. Biol. Chem. 279:36121-36131(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PLAG1.
    9. "SUMOylation and SUMO-interacting motif (SIM) of metastasis tumor antigen 1 (MTA1) synergistically regulate its transcriptional repressor function."
      Cong L., Pakala S.B., Ohshiro K., Li D.Q., Kumar R.
      J. Biol. Chem. 286:43793-43808(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH MTA1.

    Entry informationi

    Entry nameiPIAS3_HUMAN
    AccessioniPrimary (citable) accession number: Q9Y6X2
    Secondary accession number(s): Q9UFI3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 5, 2002
    Last sequence update: December 7, 2004
    Last modified: October 1, 2014
    This is version 131 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3