PIAS3 Gene (Protein Coding)

Protein Inhibitor Of Activated STAT 3

GC01M145848
GIFtS:
41
This gene encodes a member of the PIAS [protein inhibitor of activated STAT (signal transducer and activator of transcription)] family of transcriptional modulators. The protein functions as a SUMO (small ubiquitin-like modifier)-E3 ligase which catalyzes the covalent attachment of a SUMO protein to specific target substrates. It directly binds to several transcription factors ... See more...

Aliases for PIAS3 Gene

Aliases for PIAS3 Gene

  • Protein Inhibitor Of Activated STAT 3 2 3 5
  • Protein Inhibitor Of Activated STAT Protein 3 3 4
  • Zinc Finger, MIZ-Type Containing 5 2 3
  • E3 SUMO-Protein Transferase PIAS3 3 4
  • E3 SUMO-Protein Ligase PIAS3 3 4
  • ZMIZ5 2 3
  • EC 2.3.2.- 4
  • FLJ14651 2
  • PIAS3 5

External Ids for PIAS3 Gene

Previous GeneCards Identifiers for PIAS3 Gene

  • GC01P144096
  • GC01P142163
  • GC01P143302
  • GC01P143324
  • GC01P143065
  • GC01P144287
  • GC01P145575
  • GC01P119540

Summaries for PIAS3 Gene

Entrez Gene Summary for PIAS3 Gene

  • This gene encodes a member of the PIAS [protein inhibitor of activated STAT (signal transducer and activator of transcription)] family of transcriptional modulators. The protein functions as a SUMO (small ubiquitin-like modifier)-E3 ligase which catalyzes the covalent attachment of a SUMO protein to specific target substrates. It directly binds to several transcription factors and either blocks or enhances their activity. Alternatively spliced transcript variants of this gene have been identified, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

GeneCards Summary for PIAS3 Gene

PIAS3 (Protein Inhibitor Of Activated STAT 3) is a Protein Coding gene. Diseases associated with PIAS3 include Prostate Cancer and Microphthalmia. Among its related pathways are Interleukin-11 Signaling Pathway and C-MYB transcription factor network. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and ligase activity. An important paralog of this gene is PIAS1.

UniProtKB/Swiss-Prot Summary for PIAS3 Gene

  • 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).

Gene Wiki entry for PIAS3 Gene

Additional gene information for PIAS3 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PIAS3 Gene

Genomics for PIAS3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for PIAS3 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PIAS3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PIAS3

Top Transcription factor binding sites by QIAGEN in the PIAS3 gene promoter:
  • E47
  • GATA-1
  • GATA-2
  • HTF
  • MAZR
  • TBP
  • TFIID
  • YY1

Genomic Locations for PIAS3 Gene

Genomic Locations for PIAS3 Gene
chr1:145,848,522-145,859,836
(GRCh38/hg38)
Size:
11,315 bases
Orientation:
Minus strand
chr1:145,575,233-145,586,546
(GRCh37/hg19)
Size:
11,314 bases
Orientation:
Plus strand

Genomic View for PIAS3 Gene

Genes around PIAS3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PIAS3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PIAS3 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for PIAS3 Gene

Proteins for PIAS3 Gene

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  • Protein details for PIAS3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y6X2-PIAS3_HUMAN
    Recommended name:
    E3 SUMO-protein ligase PIAS3
    Protein Accession:
    Q9Y6X2
    Secondary Accessions:
    • Q9UFI3

    Protein attributes for PIAS3 Gene

    Size:
    628 amino acids
    Molecular mass:
    68017 Da
    Quaternary 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. Interacts with MTA1. Interacts with CCAR2 (via N-terminus). Interacts with TRIM8 (PubMed:20516148).
    SequenceCaution:
    • Sequence=BAA78533.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for PIAS3 Gene

neXtProt entry for PIAS3 Gene

Protein Expression for PIAS3 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for PIAS3 Gene

Other Protein References for PIAS3 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for PIAS3 Gene

Domains & Families for PIAS3 Gene

Gene Families for PIAS3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for PIAS3 Gene

InterPro:
Blocks:
  • DNA-binding SAP
  • Zn-finger, MIZ type
ProtoNet:

Suggested Antigen Peptide Sequences for PIAS3 Gene

GenScript: Design optimal peptide antigens:
  • Protein inhibitor of activated STAT protein 3 (PIAS3_HUMAN)
  • Protein inhibitor of activated STAT3 (Q6IAR4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9Y6X2

UniProtKB/Swiss-Prot:

PIAS3_HUMAN :
  • The PINIT domain of PIAS3 is required for STAT3-PIAS3 interaction and for transloaction to the nucleus.
  • Belongs to the PIAS family.
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.
Family:
  • Belongs to the PIAS family.
genes like me logo Genes that share domains with PIAS3: view

Function for PIAS3 Gene

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  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
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  6. Cell Line

Molecular function for PIAS3 Gene

UniProtKB/Swiss-Prot 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. 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).
UniProtKB/Swiss-Prot Induction:
By dihydrotestosterone (DHT) in prostate cancer cells.

Enzyme Numbers (IUBMB) for PIAS3 Gene

Phenotypes From GWAS Catalog for PIAS3 Gene

Gene Ontology (GO) - Molecular Function for PIAS3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001085 RNA polymerase II transcription factor binding IBA 21873635
GO:0003712 transcription coregulator activity IBA 21873635
GO:0005515 protein binding IPI 11060035
GO:0008022 protein C-terminus binding IEA,IPI 14715251
GO:0008270 zinc ion binding IEA --
genes like me logo Genes that share ontologies with PIAS3: view
genes like me logo Genes that share phenotypes with PIAS3: view

Animal Models for PIAS3 Gene

MGI Knock Outs for PIAS3:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PIAS3

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for PIAS3 Gene

Localization for PIAS3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PIAS3 Gene

Cytoplasm. Nucleus. Nucleus speckle. Note=Colocalizes with MITF in the nucleus. Colocalizes with GFI1 in nuclear dots. Colocalizes with SUMO1 in nuclear granules. {ECO:0000250 UniProtKB:O54714}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PIAS3 gene
Compartment Confidence
nucleus 5
cytosol 3
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for PIAS3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA 21873635
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IEA --
GO:0016607 nuclear speck IEA --
GO:0030425 dendrite IEA --
genes like me logo Genes that share ontologies with PIAS3: view

Pathways & Interactions for PIAS3 Gene

genes like me logo Genes that share pathways with PIAS3: view

Pathways by source for PIAS3 Gene

2 GeneGo (Thomson Reuters) pathways for PIAS3 Gene
  • Development_Leptin signaling via JAK/STAT and MAPK cascades
  • Development_Thrombopoetin signaling via JAK-STAT pathway
2 Qiagen pathways for PIAS3 Gene
  • IL-6 Pathway
  • JAK-STAT Pathway
1 Cell Signaling Technology pathway for PIAS3 Gene

UniProtKB/Swiss-Prot Q9Y6X2-PIAS3_HUMAN

  • Pathway: Protein modification; protein sumoylation.

SIGNOR curated interactions for PIAS3 Gene

Activates:
Inactivates:

Gene Ontology (GO) - Biological Process for PIAS3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IEA --
GO:0006357 regulation of transcription by RNA polymerase II IBA 21873635
GO:0009725 response to hormone IEA --
GO:0010628 positive regulation of gene expression IEA --
GO:0010629 negative regulation of gene expression IEA --
genes like me logo Genes that share ontologies with PIAS3: view

Drugs & Compounds for PIAS3 Gene

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  1. Drug
No Compound Related Data Available

Transcripts for PIAS3 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for PIAS3 Gene

1 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
9 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PIAS3

Alternative Splicing Database (ASD) splice patterns (SP) for PIAS3 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3a · 3b ^ 4 ^ 5a · 5b · 5c · 5d ^ 6a · 6b ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11a · 11b ^ 12a · 12b ^ 13a · 13b · 13c ^ 14 ^
SP1: - - - - -
SP2: - - -
SP3: -
SP4: - - - - - - - -
SP5: - - - - - -
SP6:
SP7:
SP8: - - - -
SP9:
SP10:
SP11: - - -
SP12: - -
SP13: -

ExUns: 15a · 15b ^ 16a · 16b · 16c ^ 17a · 17b
SP1: - - -
SP2:
SP3: - - -
SP4:
SP5:
SP6: -
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:

Relevant External Links for PIAS3 Gene

GeneLoc Exon Structure for
PIAS3

Expression for PIAS3 Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PIAS3 Gene

mRNA expression in normal human tissues for PIAS3 Gene
mRNA expression by GTEx for PIAS3 GenemRNA expression by BioGPS for PIAS3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for PIAS3 Gene

This gene is overexpressed in Serum (55.8) and Heart (13.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for PIAS3 Gene



Protein tissue co-expression partners for PIAS3 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PIAS3

SOURCE GeneReport for Unigene cluster for PIAS3 Gene:

Hs.435761

mRNA Expression by UniProt/SwissProt for PIAS3 Gene:

Q9Y6X2-PIAS3_HUMAN
Tissue specificity: Widely expressed.

Evidence on tissue expression from TISSUES for PIAS3 Gene

  • Nervous system(4.4)
  • Muscle(4.4)
  • Blood(4.4)
  • Skin(2.6)
  • Lung(2.5)
  • Kidney(2.4)
  • Intestine(2.3)
  • Spleen(2.2)
  • Lymph node(2.2)
  • Heart(2.2)
  • Thyroid gland(2.1)
  • Liver(2)
genes like me logo Genes that share expression patterns with PIAS3: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for PIAS3 Gene

Orthologs for PIAS3 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for PIAS3 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia PIAS3 30 31
  • 95.59 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia PIAS3 30 31
  • 93.31 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia PIAS3 30 31
  • 92.78 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Pias3 30 17 31
  • 90.39 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Pias3 30
  • 90.23 (n)
Oppossum
(Monodelphis domestica)
 Mammalia PIAS3 31
  • 84 (a)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia -- 31
  • 43 (a)
 OneToMany
-- 31
  • 38 (a)
 OneToMany
-- 31
  • 32 (a)
 OneToMany
-- 31
  • 27 (a)
 OneToMany
-- 31
  • 23 (a)
 OneToMany
-- 31
  • 22 (a)
 OneToMany
-- 31
  • 20 (a)
 OneToMany
-- 31
  • 15 (a)
 OneToMany
Chicken
(Gallus gallus)
 Aves PIAS3 31
  • 59 (a)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia PIAS3 31
  • 66 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia pias3 30
  • 69.57 (n)
Fruit Fly
(Drosophila melanogaster)
 Insecta Su(var)2-10 31 32
  • 34 (a)
 OneToMany
Worm
(Caenorhabditis elegans)
 Secernentea W10D5.3a 32
  • 35 (a)
W10D5.3d 32
  • 35 (a)
gei-17 31 32
  • 20 (a)
 OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
 Saccharomycetes NFI1 31
  • 14 (a)
 ManyToMany
SIZ1 31
  • 11 (a)
 ManyToMany
Sea Squirt
(Ciona savignyi)
 Ascidiacea -- 31
  • 30 (a)
 OneToMany
Sea Vase
(Ciona intestinalis)
 Ascidiacea Cin.2754 30
Species where no ortholog for PIAS3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Zebrafish (Danio rerio)

Evolution for PIAS3 Gene

ENSEMBL:
Gene Tree for PIAS3 (if available)
TreeFam:
Gene Tree for PIAS3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PIAS3: view image

Paralogs for PIAS3 Gene

Paralogs for PIAS3 Gene

(5) SIMAP similar genes for PIAS3 Gene using alignment to 6 proteins:

  • PIAS3_HUMAN
  • E7ESB4_HUMAN
  • E9PHH8_HUMAN
  • F8WA94_HUMAN
  • Q6IAR4_HUMAN
  • U3KQV1_HUMAN
genes like me logo Genes that share paralogs with PIAS3: view

Variants for PIAS3 Gene

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Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PIAS3 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
726837 Likely Benign: not provided 145,850,884(-) G/C SYNONYMOUS_VARIANT
728990 Benign: not provided 145,856,094(-) A/G SYNONYMOUS_VARIANT
756016 Likely Benign: not provided 145,850,277(-) G/A INTRON_VARIANT
773151 Benign: not provided 145,849,550(-) T/G MISSENSE_VARIANT
829799 Uncertain Significance: not provided 145,856,375(-) G/A NONSENSE

Additional dbSNP identifiers (rs#s) for PIAS3 Gene

Structural Variations from Database of Genomic Variants (DGV) for PIAS3 Gene

Variant ID Type Subtype PubMed ID
esv3587420 CNV gain 21293372
nsv1005055 CNV loss 25217958
nsv1015025 CNV gain 25217958
nsv831381 CNV gain 17160897

Variation tolerance for PIAS3 Gene

Residual Variation Intolerance Score: 22.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.03; 60.44% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PIAS3 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
PIAS3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PIAS3 Gene

Disorders for PIAS3 Gene

MalaCards: The human disease database

(2) MalaCards diseases for PIAS3 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
prostate cancer
  • prostate cancer, somatic
microphthalmia
  • microphthalmos
- elite association - COSMIC cancer census association via MalaCards
Search PIAS3 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for PIAS3

ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with PIAS3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PIAS3 Gene

Publications for PIAS3 Gene

  1. Protein inhibitor of activated STAT3 regulates androgen receptor signaling in prostate carcinoma cells. (PMID: 11071847) Junicho A … Muraguchi A (Biochemical and biophysical research communications 2000) 3 4 23
  2. Isolation and chromosomal assignment of a human gene encoding protein inhibitor of activated STAT3 (PIAS3). (PMID: 10319586) Ueki N … Muramatsu M (Journal of human genetics 1999) 2 3 4
  3. Specific inhibition of Stat3 signal transduction by PIAS3. (PMID: 9388184) Chung CD … Shuai K (Science (New York, N.Y.) 1997) 3 4 23
  4. Characterization of nuclear localization and SUMOylation of the ATBF1 transcription factor in epithelial cells. (PMID: 24651376) Sun X … Dong JT (PloS one 2014) 3 4
  5. SUMOylation and SUMO-interacting motif (SIM) of metastasis tumor antigen 1 (MTA1) synergistically regulate its transcriptional repressor function. (PMID: 21965678) Cong L … Kumar R (The Journal of biological chemistry 2011) 3 4

ExternalLinks

View latest publications for PIAS3 gene in Mastermind

Products for PIAS3 Gene

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  • Signalway Proteins for PIAS3

Sources for PIAS3 Gene