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Protein

E3 SUMO-protein ligase PIAS3

Gene

PIAS3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 (PubMed:21965678, PubMed:9388184). Sumoylates CCAR2 which promotes its interaction with SIRT1 (PubMed:25406032).3 Publications

Pathway: protein sumoylation

This protein is involved in the pathway protein sumoylation, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein sumoylation and in Protein modification.

Regions

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

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • ligase activity Source: UniProtKB-KW
  • potassium channel regulator activity Source: Ensembl
  • protein C-terminus binding Source: UniProtKB
  • SUMO transferase activity Source: Ensembl
  • zinc ion binding Source: InterPro

GO - Biological processi

Complete GO annotation...

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 Componenti: 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

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134989011.

Polymorphism and mutation databases

BioMutaiPIAS3.
DMDMi56405390.

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

BgeeiQ9Y6X2.
CleanExiHS_PIAS3.
ExpressionAtlasiQ9Y6X2. baseline and differential.
GenevisibleiQ9Y6X2. HS.

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. Interacts with CCAR2 (via N-terminus).By similarity7 Publications

Binary interactionsi

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

Protein-protein interaction databases

BioGridi115673. 55 interactions.
DIPiDIP-5969N.
IntActiQ9Y6X2. 25 interactions.
MINTiMINT-149343.

Structurei

Secondary structure

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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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
Regioni1 – 200200Interaction with CCAR21 PublicationAdd
BLAST
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.
GeneTreeiENSGT00550000074410.
HOGENOMiHOG000230594.
HOVERGENiHBG053598.
InParanoidiQ9Y6X2.
KOiK16064.
OMAiGELKHMV.
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

        10         20         30         40         50
MAELGELKHM VMSFRVSELQ VLLGFAGRNK SGRKHELLAK ALHLLKSSCA
60 70 80 90 100
PSVQMKIKEL YRRRFPRKTL GPSDLSLLSL PPGTSPVGSP GPLAPIPPTL
110 120 130 140 150
LAPGTLLGPK REVDMHPPLP QPVHPDVTMK PLPFYEVYGE LIRPTTLAST
160 170 180 190 200
SSQRFEEAHF TFALTPQQVQ QILTSREVLP GAKCDYTIQV QLRFCLCETS
210 220 230 240 250
CPQEDYFPPN LFVKVNGKLC PLPGYLPPTK NGAEPKRPSR PINITPLARL
260 270 280 290 300
SATVPNTIVV NWSSEFGRNY SLSVYLVRQL TAGTLLQKLR AKGIRNPDHS
310 320 330 340 350
RALIKEKLTA DPDSEVATTS LRVSLMCPLG KMRLTVPCRA LTCAHLQSFD
360 370 380 390 400
AALYLQMNEK KPTWTCPVCD KKAPYESLII DGLFMEILSS CSDCDEIQFM
410 420 430 440 450
EDGSWCPMKP KKEASEVCPP PGYGLDGLQY SPVQGGDPSE NKKKVEVIDL
460 470 480 490 500
TIESSSDEED LPPTKKHCSV TSAAIPALPG SKGVLTSGHQ PSSVLRSPAM
510 520 530 540 550
GTLGGDFLSS LPLHEYPPAF PLGADIQGLD LFSFLQTESQ HYGPSVITSL
560 570 580 590 600
DEQDALGHFF QYRGTPSHFL GPLAPTLGSS HCSATPAPPP GRVSSIVAPG
610 620
GALREGHGGP LPSGPSLTGC RSDIISLD
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. Curated

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:
EMBLi
GenBanki
DDBJi
Links Updated
AB021868 mRNA. Translation: BAA78533.1. Different initiation.
BC001154 mRNA. Translation: AAH01154.2.
BC030556 mRNA. Translation: AAH30556.2.
CCDSiCCDS72866.1.
PIRiT34525.
RefSeqiNP_006090.2. NM_006099.3.
UniGeneiHs.435761.

Genome annotation databases

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

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB021868 mRNA. Translation: BAA78533.1. Different initiation.
BC001154 mRNA. Translation: AAH01154.2.
BC030556 mRNA. Translation: AAH30556.2.
CCDSiCCDS72866.1.
PIRiT34525.
RefSeqiNP_006090.2. NM_006099.3.
UniGeneiHs.435761.

3D structure databases

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

Protein-protein interaction databases

BioGridi115673. 55 interactions.
DIPiDIP-5969N.
IntActiQ9Y6X2. 25 interactions.
MINTiMINT-149343.

PTM databases

PhosphoSiteiQ9Y6X2.

Polymorphism and mutation databases

BioMutaiPIAS3.
DMDMi56405390.

Proteomic databases

MaxQBiQ9Y6X2.
PaxDbiQ9Y6X2.
PRIDEiQ9Y6X2.

Protocols and materials databases

DNASUi10401.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi10401.
GeneCardsiGC01P145575.
HGNCiHGNC:16861. PIAS3.
MIMi605987. gene.
neXtProtiNX_Q9Y6X2.
PharmGKBiPA134989011.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG125513.
GeneTreeiENSGT00550000074410.
HOGENOMiHOG000230594.
HOVERGENiHBG053598.
InParanoidiQ9Y6X2.
KOiK16064.
OMAiGELKHMV.
PhylomeDBiQ9Y6X2.
TreeFamiTF323787.

Enzyme and pathway databases

UniPathwayiUPA00886.
SignaLinkiQ9Y6X2.

Miscellaneous databases

ChiTaRSiPIAS3. human.
GeneWikiiPIAS3.
GenomeRNAii10401.
NextBioi39416.
PROiQ9Y6X2.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y6X2.
CleanExiHS_PIAS3.
ExpressionAtlasiQ9Y6X2. baseline and differential.
GenevisibleiQ9Y6X2. HS.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
  10. "Modification of DBC1 by SUMO2/3 is crucial for p53-mediated apoptosis in response to DNA damage."
    Park J.H., Lee S.W., Yang S.W., Yoo H.M., Park J.M., Seong M.W., Ka S.H., Oh K.H., Jeon Y.J., Chung C.H.
    Nat. Commun. 5:5483-5483(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH CCAR2.

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: June 24, 2015
This is version 138 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.