Human Gene PIAS4 (ENST00000262971.3_4) from GENCODE V47lift37
  Description: protein inhibitor of activated STAT 4 (from RefSeq NM_015897.4)
Gencode Transcript: ENST00000262971.3_4
Gencode Gene: ENSG00000105229.7_7
Transcript (Including UTRs)
   Position: hg19 chr19:4,007,734-4,039,384 Size: 31,651 Total Exon Count: 11 Strand: +
Coding Region
   Position: hg19 chr19:4,007,759-4,037,873 Size: 30,115 Coding Exon Count: 11 

Page IndexSequence and LinksUniProtKB CommentsPrimersCTDGene Alleles
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr19:4,007,734-4,039,384)mRNA (may differ from genome)Protein (510 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
HGNCMGIOMIMPubMedReactomeUniProtKB
WikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: PIAS4_HUMAN
DESCRIPTION: RecName: Full=E3 SUMO-protein ligase PIAS4; EC=6.3.2.-; AltName: Full=PIASy; AltName: Full=Protein inhibitor of activated STAT protein 4; AltName: Full=Protein inhibitor of activated STAT protein gamma; Short=PIAS-gamma;
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, the p53/TP53 pathway, the Wnt pathway and the steroid hormone signaling pathway. Involved in gene silencing. Mediates sumoylation of CEBPA, PARK7, HERC2, MYB, TCF4 and RNF168. In Wnt signaling, represses LEF1 and enhances TCF4 transcriptional activities through promoting their sumoylations.
PATHWAY: Protein modification; protein sumoylation.
SUBUNIT: Interacts with AR, AXIN1, GATA2, LEF1, TP53 and STAT1 (IFNG-induced). Binds to AT-rich DNA sequences, known as matrix or scaffold attachment regions (MARs/SARs) (By similarity). Interacts with TICAM1. Interacts with KLF8; the interaction results in SUMO ligation and repression of KLF8 transcriptional activity and of its cell cycle progression into G(1) phase.
INTERACTION: Q16665:HIF1A; NbExp=3; IntAct=EBI-473160, EBI-447269; P42858:HTT; NbExp=3; IntAct=EBI-473160, EBI-466029; P61956:SUMO2; NbExp=3; IntAct=EBI-473160, EBI-473220; O75528:TADA3; NbExp=2; IntAct=EBI-473160, EBI-473249; P04637:TP53; NbExp=2; IntAct=EBI-473160, EBI-366083;
SUBCELLULAR LOCATION: Nucleus, PML body. Note=Colocalizes with SUMO1 and TCF7L2/TCF4 and LEF1 in a subset of PML (promyelocytic leukemia) nuclear bodies.
TISSUE SPECIFICITY: Highly expressed in testis and, at lower levels, in spleen, prostate, ovary, colon and peripheral blood leukocytes.
DOMAIN: The LXXLL motif is a coregulator signature that is essential for transcriptional corepression.
PTM: Sumoylated. Lys-35 is the main site of sumoylation. Sumoylation is required for TCF4 sumoylation and transcriptional activitation. Represses LEF1 transcriptional activity. SUMO1 is the preferred conjugate.
SIMILARITY: Belongs to the PIAS family.
SIMILARITY: Contains 1 PINIT domain.
SIMILARITY: Contains 1 SAP domain.
SIMILARITY: Contains 1 SP-RING-type zinc finger.
SEQUENCE CAUTION: Sequence=AAD45155.1; Type=Erroneous initiation;

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 42.53 RPKM in Testis
Total median expression: 423.88 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -8.5025-0.340 Picture PostScript Text
3' UTR -653.811511-0.433 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR023321 - PINIT
IPR003034 - SAP_DNA-bd
IPR004181 - Znf_MIZ
IPR013083 - Znf_RING/FYVE/PHD

Pfam Domains:
PF02891 - MIZ/SP-RING zinc finger
PF14324 - PINIT domain

SCOP Domains:
68906 - SAP domain
57850 - RING/U-box
57903 - FYVE/PHD zinc finger

ModBase Predicted Comparative 3D Structure on Q8N2W9
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologGenome Browser
Gene DetailsGene Details   Gene Details
Gene SorterGene Sorter   Gene Sorter
 RGDEnsembl  SGD
     Protein Sequence
     Alignment

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003677 DNA binding
GO:0003714 transcription corepressor activity
GO:0005515 protein binding
GO:0008022 protein C-terminus binding
GO:0008270 zinc ion binding
GO:0016740 transferase activity
GO:0019789 SUMO transferase activity
GO:0031625 ubiquitin protein ligase binding
GO:0046872 metal ion binding
GO:0061665 SUMO ligase activity

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0006303 double-strand break repair via nonhomologous end joining
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0010804 negative regulation of tumor necrosis factor-mediated signaling pathway
GO:0016055 Wnt signaling pathway
GO:0016925 protein sumoylation
GO:0032088 negative regulation of NF-kappaB transcription factor activity
GO:0033235 positive regulation of protein sumoylation
GO:0042359 vitamin D metabolic process
GO:0045892 negative regulation of transcription, DNA-templated
GO:1902174 positive regulation of keratinocyte apoptotic process
GO:1902231 positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0016363 nuclear matrix
GO:0016605 PML body
GO:1990234 transferase complex


-  Descriptions from all associated GenBank mRNAs
  AK315530 - Homo sapiens cDNA, FLJ96596.
BC066895 - Homo sapiens protein inhibitor of activated STAT, 4, mRNA (cDNA clone MGC:86982 IMAGE:5261627), complete cds.
AK022481 - Homo sapiens cDNA FLJ12419 fis, clone MAMMA1003047, highly similar to Protein inhibitor of activated STAT protein 4.
BC029874 - Homo sapiens protein inhibitor of activated STAT, 4, mRNA (cDNA clone MGC:35296 IMAGE:5176540), complete cds.
AK222726 - Homo sapiens mRNA for protein inhibitor of activated STAT, 4 variant, clone: COL08992.
DQ892419 - Synthetic construct clone IMAGE:100005049; FLH186174.01X; RZPDo839B0971D protein inhibitor of activated STAT, 4 (PIAS4) gene, encodes complete protein.
AB464092 - Synthetic construct DNA, clone: pF1KB7782, Homo sapiens PIAS4 gene for protein inhibitor of activated STAT, 4, without stop codon, in Flexi system.
DQ895633 - Synthetic construct Homo sapiens clone IMAGE:100010093; FLH186170.01L; RZPDo839B0961D protein inhibitor of activated STAT, 4 (PIAS4) gene, encodes complete protein.
AF077952 - Homo sapiens protein inhibitor of activated STAT protein PIASy mRNA, complete cds.
BC010047 - Homo sapiens protein inhibitor of activated STAT, 4, mRNA (cDNA clone IMAGE:3831616), partial cds.
AF164437 - Homo sapiens protein inhibitor of activated STAT mRNA, complete cds.
CU679589 - Synthetic construct Homo sapiens gateway clone IMAGE:100019694 5' read PIAS4 mRNA.
KJ902605 - Synthetic construct Homo sapiens clone ccsbBroadEn_11999 PIAS4 gene, encodes complete protein.
BC004389 - Homo sapiens protein inhibitor of activated STAT, 4, mRNA (cDNA clone MGC:10885 IMAGE:3621882), complete cds.
KJ902606 - Synthetic construct Homo sapiens clone ccsbBroadEn_12000 PIAS4 gene, encodes complete protein.
JD062726 - Sequence 43750 from Patent EP1572962.
JD230527 - Sequence 211551 from Patent EP1572962.
JD200349 - Sequence 181373 from Patent EP1572962.
JD271289 - Sequence 252313 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q8N2W9 (Reactome details) participates in the following event(s):

R-HSA-5682586 HERC2 and PIAS4 are recruited to DNA DSBs
R-HSA-5684071 RNF4 ubiquitinates MDC1
R-HSA-5693599 Association of Ku heterodimer with ends of DNA double-strand break
R-HSA-5682598 ATM phosphorylates HERC2
R-HSA-5682607 PIAS4 SUMOylates HERC2 with SUMO1 at DNA DSBs
R-HSA-5682629 HERC2 facilitates UBE2N:UBE2V2 binding to RNF8
R-HSA-5682863 RNF168 binds DNA DSBs
R-HSA-5683077 RNF8 and RNF168 ubiquitinate KDM4A,B
R-HSA-5682858 RNF8 and RNF168 ubiquitinate H2AFX
R-HSA-5693566 TP53BP1 associates with H4K20Me2 at DNA DSBs
R-HSA-2997723 PIAS4 SUMOylates TP53BP1 with SUMO1
R-HSA-4546387 PIAS4 SUMOylates VDR with SUMO2
R-HSA-4551604 PIAS4 SUMOylates PARP1 with SUMO1
R-HSA-4551661 PIAS4 SUMOylates RNF168 with SUMO1
R-HSA-4551724 PIAS4 SUMOylates HERC2 with SUMO1
R-HSA-4551768 PIAS4 SUMOylates PARP1 with SUMO2,3
R-HSA-4641350 PIAS4 SUMOylates TOP2A with SUMO2,3
R-HSA-5683384 UIMC1 and FAM175A bind DNA DSBs
R-HSA-5683405 PPP5C dephosphorylates TP53BP1
R-HSA-5683425 ATM phosphorylates TP53BP1 at DNA DSBs
R-HSA-2997616 PIAS1,4 SUMOylates BRCA1 with SUMO2,3
R-HSA-2997709 PIAS1,4 SUMOylates BRCA1 with SUMO1
R-HSA-3465545 PIAS1,3,4 SUMOylate MTA1 with SUMO2,3
R-HSA-5693551 Phosphorylation of BRCA1-A complex at multiple sites by ATM
R-HSA-5683385 Formation of BRCA1-A complex at DNA DSBs
R-HSA-5683735 CHEK2 is recruited to DNA DSBs
R-HSA-5683801 CHEK2 phosphorylates BRCA1
R-HSA-69891 Phosphorylation and activation of CHEK2 by ATM
R-HSA-5684052 PIAS4 SUMOylates MDC1
R-HSA-5686685 RIF1 and PAX1IP bind TP53BP1 at DNA DSBs
R-HSA-5686900 TP53BP1 recruits DCLRE1C to ATM
R-HSA-5686704 Activated ATM phosphorylates DCLRE1C
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693607 Processing of DNA double-strand break ends
R-HSA-5693571 Nonhomologous End-Joining (NHEJ)
R-HSA-5693606 DNA Double Strand Break Response
R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)
R-HSA-5693532 DNA Double-Strand Break Repair
R-HSA-3232118 SUMOylation of transcription factors
R-HSA-196791 Vitamin D (calciferol) metabolism
R-HSA-3108214 SUMOylation of DNA damage response and repair proteins
R-HSA-4615885 SUMOylation of DNA replication proteins
R-HSA-5693538 Homology Directed Repair
R-HSA-73894 DNA Repair
R-HSA-3108232 SUMO E3 ligases SUMOylate target proteins
R-HSA-209943 Steroid hormones
R-HSA-8957322 Metabolism of steroids
R-HSA-69473 G2/M DNA damage checkpoint
R-HSA-2990846 SUMOylation
R-HSA-556833 Metabolism of lipids
R-HSA-69481 G2/M Checkpoints
R-HSA-597592 Post-translational protein modification
R-HSA-1430728 Metabolism
R-HSA-69620 Cell Cycle Checkpoints
R-HSA-392499 Metabolism of proteins
R-HSA-1640170 Cell Cycle

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000262971.1, ENST00000262971.2, NM_015897, O75926, PIAS4 , PIAS4_HUMAN, PIASG, Q8N2W9, Q96G19, Q9UN16, uc317hfi.1, uc317hfi.2
UCSC ID: ENST00000262971.3_4
RefSeq Accession: NM_015897.4
Protein: Q8N2W9 (aka PIAS4_HUMAN or PIA4_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.