Pias4 protein inhibitor of activated STAT 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Pias4provided by MGI
Official Full Name: protein inhibitor of activated STAT 4provided by MGI
Primary source: MGI:MGI:2136940
See related: Ensembl:ENSMUSG00000004934 AllianceGenome:MGI:2136940
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: PIASY; Piasg; Pias-gamma
Summary: Enables several functions, including SUMO ligase activity; transcription corepressor activity; and ubiquitin protein ligase binding activity. Involved in negative regulation of NF-kappaB transcription factor activity; negative regulation of transcription by RNA polymerase II; and positive regulation of keratinocyte apoptotic process. Acts upstream of or within negative regulation of tumor necrosis factor-mediated signaling pathway; positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage; and protein sumoylation. Located in nuclear matrix and nucleoplasm. Part of transferase complex. Is expressed in several structures, including central nervous system; early conceptus; genitourinary system; hair follicle; and heart. Orthologous to human PIAS4 (protein inhibitor of activated STAT 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in testis adult (RPKM 63.4), colon adult (RPKM 20.2) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 10 C1; 10 39.72 cM

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	10	NC_000076.7 (80989795..81003554, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	10	NC_000076.6 (81153961..81167720, complement)

Chromosome 10 - NC_000076.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

study demonstrates that Piasy may prevent exaggerated transcription of IFNI by Rbp2-mediated demethylation of H3K4me3 of IFNI, avoiding excessive immune responses
Title: Chromatin remodeling: demethylating H3K4me3 of type I IFNs gene by Rbp2 through interacting with Piasy for transcriptional attenuation.
PIAS4 mediated SIRT1 repression led to SMAD3 hyperacetylation and enhanced SMAD3 binding to fibrogenic gene promoters and PIAS4 promoted hepatic stellate cells activation in a SIRT1-dependent manner in vitro.
Title: Transcriptional repression of SIRT1 by protein inhibitor of activated STAT 4 (PIAS4) in hepatic stellate cells contributes to liver fibrosis.
Findings indicate that protein inhibitor of activated STAT 4 (PIAS4) mediated SIRT1 repression in response to nutrient surplus contributes to the pathogenesis of Nonalcoholic Steatohepatitis (NASH).
Title: Protein inhibitor of activated STAT 4 (PIAS4) regulates pro-inflammatory transcription in hepatocytes by repressing SIRT1.
new protein isoform encoded by KIAA0317, termed fibrosis-inducing E3 ligase 1 (FIEL1), which potently stimulates the TGFbeta signaling pathway through the site-specific ubiquitination of PIAS4.
Title: Ubiquitin E3 ligase FIEL1 regulates fibrotic lung injury through SUMO-E3 ligase PIAS4.
PKA-induced SREBP1c sumoylation by PIASy.
Title: PIASy-mediated sumoylation of SREBP1c regulates hepatic lipid metabolism upon fasting signaling.
the SUMO E3 ligase PIASy (also known as PIAS4) was induced by hypoxia and prevented Sp1 from binding to the SIRT1 promoter.
Title: PIASy mediates hypoxia-induced SIRT1 transcriptional repression and epithelial-to-mesenchymal transition in ovarian cancer cells.
Piasy represses the synergistic activation of PITX2 with interacting co-factors and Piasy represses Pias1 activation of PITX2 transcriptional activity.
Title: Protein inhibitors of activated STAT (Pias1 and Piasy) differentially regulate pituitary homeobox 2 (PITX2) transcriptional activity.
Protein inhibitor of activated STAT, PIASy regulates alpha-smooth muscle actin expression by interacting with E12 in mesangial cells.
Title: Protein inhibitor of activated STAT, PIASy regulates α-smooth muscle actin expression by interacting with E12 in mesangial cells.
PIASy negatively regulates both IFN transcription and IFN-stimulated gene expression through multiple mechanisms utilizing the function of different domains.
Title: PIASy inhibits virus-induced and interferon-stimulated transcription through distinct mechanisms.
Studies define an important role of PIASy in hypoxia signaling through promoting HIF1alpha SUMOylation.
Title: PIASy stimulates HIF1α SUMOylation and negatively regulates HIF1α activity in response to hypoxia.

Submit: New GeneRIF Correction See all GeneRIFs (18)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (3) 1 citation
Endonuclease-mediated (1)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH130259 (e-PCR)
- UniSTS:213546

NoName (e-PCR)
- UniSTS:548416

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables SUMO ligase activity	IBA Inferred from Biological aspect of Ancestor more info
enables SUMO ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables SUMO ligase activity	ISO Inferred from Sequence Orthology more info
enables SUMO transferase activity	IDA Inferred from Direct Assay more info	PubMed
enables SUMO transferase activity	ISO Inferred from Sequence Orthology more info
enables SUMO transferase activity	TAS Traceable Author Statement more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transcription coregulator activity	IBA Inferred from Biological aspect of Ancestor more info
enables transcription corepressor activity	IDA Inferred from Direct Assay more info	PubMed
enables transcription corepressor activity	ISA Inferred from Sequence Alignment more info	PubMed
enables transferase activity	IEA Inferred from Electronic Annotation more info
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin protein ligase binding	ISO Inferred from Sequence Orthology more info
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cell surface receptor signaling pathway via JAK-STAT	ISA Inferred from Sequence Alignment more info	PubMed
acts_upstream_of_or_within central nervous system development	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within hair follicle development	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within limb epidermis development	IEP Inferred from Expression Pattern more info	PubMed
involved_in negative regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of NF-kappaB transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of protein localization to chromatin	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of tumor necrosis factor-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of double-strand break repair via homologous recombination	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of keratinocyte apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein sumoylation	ISO Inferred from Sequence Orthology more info
involved_in protein sumoylation	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within protein sumoylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein sumoylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein sumoylation	ISO Inferred from Sequence Orthology more info
involved_in regulation of mRNA stability	ISO Inferred from Sequence Orthology more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
part_of chromatin	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in nuclear matrix	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	ISO Inferred from Sequence Orthology more info
part_of transferase complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: E3 SUMO-protein ligase PIAS4

Names: RING-type E3 ubiquitin transferase PIAS4; protein inhibitor of activated STAT PIASy; protein inhibitor of activated STAT protein 4; protein inhibitor of activated STAT protein gamma

NP_067476.2

EC 2.3.2.27

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_021501.4 → NP_067476.2 E3 SUMO-protein ligase PIAS4

See identical proteins and their annotated locations for NP_067476.2

Status: PROVISIONAL

Source sequence(s)

BC025159

Consensus CDS

CCDS35992.1

UniProtKB/Swiss-Prot

Q8R165, Q9JM05

UniProtKB/TrEMBL

Q3UGQ2, Q3ULQ6

Related

ENSMUSP00000005064.8, ENSMUST00000005064.14

Conserved Domains (3) summary

smart00513
Location:12 → 46

SAP; Putative DNA-binding (bihelical) motif predicted to be involved in chromosomal organisation

pfam02891
Location:315 → 364

zf-MIZ; MIZ/SP-RING zinc finger

pfam14324
Location:124 → 262

PINIT; PINIT domain