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Protein

E3 SUMO-protein ligase PIAS3

Gene

PIAS3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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). Diminishes the sumoylation of ZFHX3 by preventing the colocalization of ZFHX3 with SUMO1 in the nucleus (PubMed:24651376).4 Publications

Pathwayi: 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)DescriptionActionsGraphical viewLength
Zinc fingeri303 – 380SP-RING-typePROSITE-ProRule annotationAdd BLAST78

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processTranscription, Transcription regulation, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-3232118 SUMOylation of transcription factors
R-HSA-3899300 SUMOylation of transcription cofactors
R-HSA-4090294 SUMOylation of intracellular receptors
R-HSA-4615885 SUMOylation of DNA replication proteins
R-HSA-4755510 SUMOylation of immune response proteins
R-HSA-5696395 Formation of Incision Complex in GG-NER
SignaLinkiQ9Y6X2
SIGNORiQ9Y6X2
UniPathwayi
UPA00886

Names & Taxonomyi

Protein namesi
Recommended name:
E3 SUMO-protein ligase PIAS3 (EC:2.3.2.-)
Alternative name(s):
E3 SUMO-protein transferase PIAS3Curated
Protein inhibitor of activated STAT protein 3
Gene namesi
Name:PIAS3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000131788.15
HGNCiHGNC:16861 PIAS3
MIMi605987 gene
neXtProtiNX_Q9Y6X2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi10401
OpenTargetsiENSG00000131788
PharmGKBiPA134989011

Polymorphism and mutation databases

BioMutaiPIAS3
DMDMi56405390

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002189791 – 628E3 SUMO-protein ligase PIAS3Add BLAST628

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki46Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki56Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki230Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki307Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki466Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki482Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Post-translational modificationi

Sumoylated.By similarity

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

EPDiQ9Y6X2
MaxQBiQ9Y6X2
PaxDbiQ9Y6X2
PeptideAtlasiQ9Y6X2
PRIDEiQ9Y6X2
ProteomicsDBi86810

PTM databases

iPTMnetiQ9Y6X2
PhosphoSitePlusiQ9Y6X2

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Inductioni

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

Gene expression databases

BgeeiENSG00000131788 Expressed in 195 organ(s), highest expression level in right uterine tube
CleanExiHS_PIAS3
ExpressionAtlasiQ9Y6X2 baseline and differential
GenevisibleiQ9Y6X2 HS

Organism-specific databases

HPAiHPA006389
HPA067383

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). Interacts with TRIM8 (PubMed:20516148).By similarity8 Publications

Binary interactionsi

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115673, 55 interactors
CORUMiQ9Y6X2
DIPiDIP-5969N
ELMiQ9Y6X2
IntActiQ9Y6X2, 40 interactors
MINTiQ9Y6X2
STRINGi9606.ENSP00000376765

Structurei

Secondary structure

1628
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9Y6X2
SMRiQ9Y6X2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini11 – 45SAPPROSITE-ProRule annotationAdd BLAST35
Domaini115 – 280PINITPROSITE-ProRule annotationAdd BLAST166

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 200Interaction with CCAR21 PublicationAdd BLAST200
Regioni450 – 460SUMO1-bindingBy similarityAdd BLAST11

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi19 – 23LXXLL motif5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi81 – 133Pro-richAdd BLAST53

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri303 – 380SP-RING-typePROSITE-ProRule annotationAdd BLAST78

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG2169 Eukaryota
ENOG410XQ2E LUCA
GeneTreeiENSGT00550000074410
HOGENOMiHOG000230594
HOVERGENiHBG053598
InParanoidiQ9Y6X2
KOiK16064
OMAiTIVVNWS
OrthoDBiEOG091G08G5
PhylomeDBiQ9Y6X2
TreeFamiTF323787

Family and domain databases

Gene3Di1.10.720.30, 1 hit
2.60.120.780, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR027226 PIAS3
IPR023321 PINIT
IPR038654 PINIT_sf
IPR003034 SAP_dom
IPR036361 SAP_dom_sf
IPR004181 Znf_MIZ
IPR013083 Znf_RING/FYVE/PHD
PANTHERiPTHR10782:SF10 PTHR10782:SF10, 1 hit
PfamiView protein in Pfam
PF14324 PINIT, 1 hit
PF02891 zf-MIZ, 1 hit
SMARTiView protein in SMART
SM00513 SAP, 1 hit
SUPFAMiSSF68906 SSF68906, 1 hit
PROSITEiView protein in PROSITE
PS51466 PINIT, 1 hit
PS50800 SAP, 1 hit
PS51044 ZF_SP_RING, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PHH8E9PHH8_HUMAN
E3 SUMO-protein ligase PIAS3
PIAS3
593Annotation score:
E7ESB4E7ESB4_HUMAN
E3 SUMO-protein ligase PIAS3
PIAS3
259Annotation score:
U3KQV1U3KQV1_HUMAN
E3 SUMO-protein ligase PIAS3
PIAS3
92Annotation score:

Sequence cautioni

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050535390S → C. Corresponds to variant dbSNP:rs17354559Ensembl.1

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.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4MVTX-ray2.30A/B/C/D112-467[»]
ProteinModelPortaliQ9Y6X2
SMRiQ9Y6X2
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115673, 55 interactors
CORUMiQ9Y6X2
DIPiDIP-5969N
ELMiQ9Y6X2
IntActiQ9Y6X2, 40 interactors
MINTiQ9Y6X2
STRINGi9606.ENSP00000376765

PTM databases

iPTMnetiQ9Y6X2
PhosphoSitePlusiQ9Y6X2

Polymorphism and mutation databases

BioMutaiPIAS3
DMDMi56405390

Proteomic databases

EPDiQ9Y6X2
MaxQBiQ9Y6X2
PaxDbiQ9Y6X2
PeptideAtlasiQ9Y6X2
PRIDEiQ9Y6X2
ProteomicsDBi86810

Protocols and materials databases

DNASUi10401
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000393045; ENSP00000376765; ENSG00000131788
GeneIDi10401
KEGGihsa:10401
UCSCiuc001eoc.2 human

Organism-specific databases

CTDi10401
DisGeNETi10401
EuPathDBiHostDB:ENSG00000131788.15
GeneCardsiPIAS3
HGNCiHGNC:16861 PIAS3
HPAiHPA006389
HPA067383
MIMi605987 gene
neXtProtiNX_Q9Y6X2
OpenTargetsiENSG00000131788
PharmGKBiPA134989011
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2169 Eukaryota
ENOG410XQ2E LUCA
GeneTreeiENSGT00550000074410
HOGENOMiHOG000230594
HOVERGENiHBG053598
InParanoidiQ9Y6X2
KOiK16064
OMAiTIVVNWS
OrthoDBiEOG091G08G5
PhylomeDBiQ9Y6X2
TreeFamiTF323787

Enzyme and pathway databases

UniPathwayi
UPA00886

ReactomeiR-HSA-3232118 SUMOylation of transcription factors
R-HSA-3899300 SUMOylation of transcription cofactors
R-HSA-4090294 SUMOylation of intracellular receptors
R-HSA-4615885 SUMOylation of DNA replication proteins
R-HSA-4755510 SUMOylation of immune response proteins
R-HSA-5696395 Formation of Incision Complex in GG-NER
SignaLinkiQ9Y6X2
SIGNORiQ9Y6X2

Miscellaneous databases

ChiTaRSiPIAS3 human
GeneWikiiPIAS3
GenomeRNAii10401
PROiPR:Q9Y6X2
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000131788 Expressed in 195 organ(s), highest expression level in right uterine tube
CleanExiHS_PIAS3
ExpressionAtlasiQ9Y6X2 baseline and differential
GenevisibleiQ9Y6X2 HS

Family and domain databases

Gene3Di1.10.720.30, 1 hit
2.60.120.780, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR027226 PIAS3
IPR023321 PINIT
IPR038654 PINIT_sf
IPR003034 SAP_dom
IPR036361 SAP_dom_sf
IPR004181 Znf_MIZ
IPR013083 Znf_RING/FYVE/PHD
PANTHERiPTHR10782:SF10 PTHR10782:SF10, 1 hit
PfamiView protein in Pfam
PF14324 PINIT, 1 hit
PF02891 zf-MIZ, 1 hit
SMARTiView protein in SMART
SM00513 SAP, 1 hit
SUPFAMiSSF68906 SSF68906, 1 hit
PROSITEiView protein in PROSITE
PS51466 PINIT, 1 hit
PS50800 SAP, 1 hit
PS51044 ZF_SP_RING, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPIAS3_HUMAN
AccessioniPrimary (citable) accession number: Q9Y6X2
Secondary accession number(s): Q9UFI3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 5, 2002
Last sequence update: December 7, 2004
Last modified: September 12, 2018
This is version 168 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  4. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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