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Q9Y6X2 (PIAS3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 SUMO-protein ligase PIAS3

EC=6.3.2.-
Alternative name(s):
Protein inhibitor of activated STAT protein 3
Gene names
Name:PIAS3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length628 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4

Pathway

Protein modification; protein sumoylation.

Subunit structure

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. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8

Subcellular location

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.

Tissue specificity

Isoform 1is expressed in most tissues except thymus and small intestine. Isoform 3is expressed only in brain, heart, thymus, muscle, lung, testis, lactating breast and embryonic stem cells. Ref.4

Induction

By dihydrotestosterone (DHT) in prostate cancer cells. Ref.5

Domain

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.

Post-translational modification

Sumoylated By similarity.

Sequence similarities

Belongs to the PIAS family.

Contains 1 PINIT domain.

Contains 1 SAP domain.

Contains 1 SP-RING-type zinc finger.

Sequence caution

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

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
Ubl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   DomainZinc-finger
   LigandMetal-binding
Zinc
   Molecular functionLigase
   PTMUbl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processpositive regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

positive regulation of membrane potential

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein sumoylation

Inferred from direct assay PubMed 17696781. Source: UniProtKB

protein sumoylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

response to hormone

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

dendrite

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

synapse

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionSUMO ligase activity

Inferred from electronic annotation. Source: Ensembl

enzyme binding

Inferred from physical interaction PubMed 17087506. Source: UniProtKB

nucleic acid binding

Inferred from electronic annotation. Source: InterPro

potassium channel regulator activity

Inferred from electronic annotation. Source: Ensembl

protein C-terminus binding

Inferred from physical interaction Ref.7. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MBD1Q9UIS93EBI-2803703,EBI-867196

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 628628E3 SUMO-protein ligase PIAS3
PRO_0000218979

Regions

Domain11 – 4535SAP
Domain115 – 280166PINIT
Zinc finger303 – 38078SP-RING-type
Region450 – 46011SUMO1-binding By similarity
Motif19 – 235LXXLL motif
Compositional bias81 – 13353Pro-rich

Natural variations

Natural variant3901S → C.
Corresponds to variant rs17354559 [ dbSNP | Ensembl ].
VAR_050535

Secondary structure

........................................... 628
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9Y6X2 [UniParc].

Last modified December 7, 2004. Version 2.
Checksum: 7C06EF599D48F87D

FASTA62868,017
        10         20         30         40         50         60 
MAELGELKHM VMSFRVSELQ VLLGFAGRNK SGRKHELLAK ALHLLKSSCA PSVQMKIKEL 

        70         80         90        100        110        120 
YRRRFPRKTL GPSDLSLLSL PPGTSPVGSP GPLAPIPPTL LAPGTLLGPK REVDMHPPLP 

       130        140        150        160        170        180 
QPVHPDVTMK PLPFYEVYGE LIRPTTLAST SSQRFEEAHF TFALTPQQVQ QILTSREVLP 

       190        200        210        220        230        240 
GAKCDYTIQV QLRFCLCETS CPQEDYFPPN LFVKVNGKLC PLPGYLPPTK NGAEPKRPSR 

       250        260        270        280        290        300 
PINITPLARL SATVPNTIVV NWSSEFGRNY SLSVYLVRQL TAGTLLQKLR AKGIRNPDHS 

       310        320        330        340        350        360 
RALIKEKLTA DPDSEVATTS LRVSLMCPLG KMRLTVPCRA LTCAHLQSFD AALYLQMNEK 

       370        380        390        400        410        420 
KPTWTCPVCD KKAPYESLII DGLFMEILSS CSDCDEIQFM EDGSWCPMKP KKEASEVCPP 

       430        440        450        460        470        480 
PGYGLDGLQY SPVQGGDPSE NKKKVEVIDL TIESSSDEED LPPTKKHCSV TSAAIPALPG 

       490        500        510        520        530        540 
SKGVLTSGHQ PSSVLRSPAM GTLGGDFLSS LPLHEYPPAF PLGADIQGLD LFSFLQTESQ 

       550        560        570        580        590        600 
HYGPSVITSL DEQDALGHFF QYRGTPSHFL GPLAPTLGSS HCSATPAPPP GRVSSIVAPG 

       610        620 
GALREGHGGP LPSGPSLTGC RSDIISLD 

« Hide

References

« Hide 'large scale' references
[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]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB021868 mRNA. Translation: BAA78533.1. Different initiation.
BC001154 mRNA. Translation: AAH01154.2.
BC030556 mRNA. Translation: AAH30556.2.
PIRT34525.
RefSeqNP_006090.2. NM_006099.3.
UniGeneHs.435761.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4MVTX-ray2.30A/B/C/D112-467[»]
ProteinModelPortalQ9Y6X2.
SMRQ9Y6X2. Positions 1-65, 126-408.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115673. 51 interactions.
DIPDIP-5969N.
IntActQ9Y6X2. 25 interactions.
MINTMINT-149343.
STRING9606.ENSP00000376765.

PTM databases

PhosphoSiteQ9Y6X2.

Polymorphism databases

DMDM56405390.

Proteomic databases

PaxDbQ9Y6X2.
PRIDEQ9Y6X2.

Protocols and materials databases

DNASU10401.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000393045; ENSP00000376765; ENSG00000131788.
ENST00000584381; ENSP00000464306; ENSG00000263461.
GeneID10401.
KEGGhsa:10401.
UCSCuc001eoc.1. human.

Organism-specific databases

CTD10401.
GeneCardsGC01P145575.
HGNCHGNC:16861. PIAS3.
MIM605987. gene.
neXtProtNX_Q9Y6X2.
PharmGKBPA134989011.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG125513.
HOGENOMHOG000230594.
HOVERGENHBG053598.
InParanoidQ9Y6X2.
KOK16064.
OMAKHMVMSF.
PhylomeDBQ9Y6X2.
TreeFamTF323787.

Enzyme and pathway databases

SignaLinkQ9Y6X2.
UniPathwayUPA00886.

Gene expression databases

ArrayExpressQ9Y6X2.
BgeeQ9Y6X2.
CleanExHS_PIAS3.
GenevestigatorQ9Y6X2.

Family and domain databases

Gene3D1.10.720.30. 1 hit.
InterProIPR027226. PIAS3.
IPR023321. PINIT.
IPR003034. SAP_dom.
IPR004181. Znf_MIZ.
[Graphical view]
PANTHERPTHR10782:SF10. PTHR10782:SF10. 1 hit.
PfamPF14324. PINIT. 1 hit.
PF02891. zf-MIZ. 1 hit.
[Graphical view]
SMARTSM00513. SAP. 1 hit.
[Graphical view]
PROSITEPS51466. PINIT. 1 hit.
PS50800. SAP. 1 hit.
PS51044. ZF_SP_RING. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPIAS3. human.
GeneWikiPIAS3.
GenomeRNAi10401.
NextBio39416.
PROQ9Y6X2.
SOURCESearch...

Entry information

Entry namePIAS3_HUMAN
AccessionPrimary (citable) accession number: Q9Y6X2
Secondary accession number(s): Q9UFI3
Entry history
Integrated into UniProtKB/Swiss-Prot: March 5, 2002
Last sequence update: December 7, 2004
Last modified: April 16, 2014
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM