Q9JM05 · PIAS4_MOUSE
- ProteinE3 SUMO-protein ligase PIAS4
- GenePias4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids507 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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 (By similarity).
Mediates sumoylation of ALKBH5, AXIN1, CEBPA, KLF8, GATA2, PARK7, HERC2, MYB, TCF4 and RNF168 (By similarity).
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 (By similarity).
Involved in gene silencing (By similarity).
In Wnt signaling, represses LEF1 and enhances TCF4 transcriptional activities through promoting their sumoylations (By similarity).
Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation (By similarity).
Binds to AT-rich DNA sequences, known as matrix or scaffold attachment regions (MARs/SARs) (PubMed:11731474).
Catalyzes conjugation of SUMO2 to KAT5 in response to DNA damage, facilitating repair of DNA double-strand breaks (DSBs) via homologous recombination (HR) (By similarity).
Mediates sumoylation of PARP1 in response to PARP1 trapping to chromatin (By similarity).
Mediates sumoylation of KLF8, repressiing KLF8 transcriptional activity and cell cycle progression into G1 phase (By similarity).
Sumoylates ALKBH5 downstream of MAPK8/JNK1 and MAPK9/JNK2 in response to reactive oxygen species (ROS), inhibiting ALKBH5 RNA demethylase activity (By similarity).
Mediates sumoylation of ALKBH5, AXIN1, CEBPA, KLF8, GATA2, PARK7, HERC2, MYB, TCF4 and RNF168 (By similarity).
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 (By similarity).
Involved in gene silencing (By similarity).
In Wnt signaling, represses LEF1 and enhances TCF4 transcriptional activities through promoting their sumoylations (By similarity).
Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation (By similarity).
Binds to AT-rich DNA sequences, known as matrix or scaffold attachment regions (MARs/SARs) (PubMed:11731474).
Catalyzes conjugation of SUMO2 to KAT5 in response to DNA damage, facilitating repair of DNA double-strand breaks (DSBs) via homologous recombination (HR) (By similarity).
Mediates sumoylation of PARP1 in response to PARP1 trapping to chromatin (By similarity).
Mediates sumoylation of KLF8, repressiing KLF8 transcriptional activity and cell cycle progression into G1 phase (By similarity).
Sumoylates ALKBH5 downstream of MAPK8/JNK1 and MAPK9/JNK2 in response to reactive oxygen species (ROS), inhibiting ALKBH5 RNA demethylase activity (By similarity).
Catalytic activity
Pathway
Protein modification; protein sumoylation.
Features
Showing features for binding site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameE3 SUMO-protein ligase PIAS4
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9JM05
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Colocalizes with SUMO1 and TCF7L2/TCF4 and LEF1 in a subset of PML (promyelocytic leukemia) nuclear bodies. Accumulates in the cytoplasm upon treatment with UVB and TNF-alpha.
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 330 | Abrogates sumoylation of LEF1 and increases LEF1-mediated transcriptional activity; when associated with S-335; A-337 and S-340. | ||||
Sequence: C → S | ||||||
Mutagenesis | 335 | Abrogates sumoylation of LEF1 and increases LEF1-mediated transcriptional activity; when associated with S-330; A-337 and S-340. | ||||
Sequence: C → S | ||||||
Mutagenesis | 337 | Abrogates sumoylation of LEF1 and increases LEF1-mediated transcriptional activity; when associated with S-330; S-335 and S-340. | ||||
Sequence: H → A | ||||||
Mutagenesis | 340 | Abrogates sumoylation of LEF1 and increases LEF1-mediated transcriptional activity; when associated with S-330; S-335 and A-337. | ||||
Sequence: C → S | ||||||
Mutagenesis | 470-474 | No effect on sumoylation of LEF1, nor on LEF1-binding. | ||||
Sequence: SSSSS → AAAAA |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 19 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000218983 | 2-507 | E3 SUMO-protein ligase PIAS4 | |||
Sequence: AAELVEAKNMVMSFRVSDLQMLLGFVGRSKSGLKHELVTRALQLVQFDCSPELFKKIKELYETRYAKKSAEPGPQAPRPLDPLALHSMPRTPLSGPTVDYPVLYGKYLNGLGRLPTKTLKPEVRLVKLPFFNMLDELLKPTELVPQSAEKLQESPCIFALTPRQVEMIRNSRELQPGVKAVQVVLRICYSDTSCPQEDQYPPNIAVKVNHSYCSVPGYYPSNKPGVEPKRPCRPINLTHLMYLSSATNRITVTWGNYGKSYSVALYLVRQLTSSDLLQRLKTIGVKHPELCKALVKEKLRLDPDSEIATTGVRVSLICPLVKMRLSVPCRAETCAHLQCFDAVFYLQMNEKKPTWMCPVCDKPAAYDQLIIDGLLSKILSECEGADEIEFLAEGSWRPIRAEKEPSCSPQGPILVLGTSDANGLAPASSTPGIGSGLSGPGSAGSGAGAAGSLENGKTGADVVDLTLDSSSSSEDEDEDEDDDEDEDEGPRPKRRCPFQKGLVPAC | ||||||
Cross-link | 9 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 35 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate | ||||
Sequence: K | ||||||
Cross-link | 35 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate | ||||
Sequence: K | ||||||
Cross-link | 56 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 59 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 68 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 69 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 107 | N6-acetyllysine | ||||
Sequence: K | ||||||
Cross-link | 118 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 128 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||||
Sequence: K |
Post-translational modification
Sumoylated. Lys-35 is the main site of sumoylation. Sumoylation is required for TCF4 sumoylation and transcriptional activation. Represses LEF1 transcriptional activity. SUMO1 is the preferred conjugate.
Ubiquitinated by TRIM32 upon treatment with UVB and TNF-alpha.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Widely expressed, with highest levels in testis. Also expressed in vascular endothelial cells, in primary keratinocytes and in the CNS, including cortex, olfactory bulb, spinal cord, thalamus and trigeminal ganglion. Low expression, if any, in liver and lung.
Developmental stage
At 8.5 dpc, expressed primarily in the anterior part of the neural tube. At 10.5 dpc, expressed in the neuroepithelium of the forebrain and hindbrain. At 11.5 dpc, detected in the neural tube, eye, limb buds and brachial arches. At 12.5 dpc, expressed in the hindlimbs and forelimbs, as well as in the forebrain. At 12.5 and 13.5 dpc, detected in single cells in the marginal zone of the developing cortex, as well as in other developing tissues and organs. At 13.5 dpc, expressed in the developing limb buds, in single cells in the mesenchyme surrounding future digit structures. At 15.5 dpc, detected in the inner root sheath of vibrissa hair follicle. Expression in the inner root sheath of the hair follicle continues later in life as it can also be detected in the back skin of newborn at postnatal day 3. At 16.5 dpc, expressed in the epithelium of olfactory and in the retina.
Gene expression databases
Interaction
Subunit
Interacts with AR, GATA2, LEF1, TP53 and STAT1 (IFNG-induced) (PubMed:11731474).
Interacts with TICAM1 (By similarity).
Interacts with MTA1 (By similarity).
Interacts with PRDM1/Blimp-1 (By similarity).
Interacts with TRIM32 upon treatment with UVB and TNF-alpha (PubMed:16816390).
Interacts with TICAM1 (By similarity).
Interacts with MTA1 (By similarity).
Interacts with PRDM1/Blimp-1 (By similarity).
Interacts with TRIM32 upon treatment with UVB and TNF-alpha (PubMed:16816390).
(Microbial infection) Interacts ewith Moloney murine leukemia virus Capsid protein p30.
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, motif, zinc finger, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 12-46 | SAP | ||||
Sequence: VMSFRVSDLQMLLGFVGRSKSGLKHELVTRALQLV | ||||||
Motif | 20-24 | LXXLL motif | ||||
Sequence: LQMLL | ||||||
Domain | 112-272 | PINIT | ||||
Sequence: LGRLPTKTLKPEVRLVKLPFFNMLDELLKPTELVPQSAEKLQESPCIFALTPRQVEMIRNSRELQPGVKAVQVVLRICYSDTSCPQEDQYPPNIAVKVNHSYCSVPGYYPSNKPGVEPKRPCRPINLTHLMYLSSATNRITVTWGNYGKSYSVALYLVRQL | ||||||
Zinc finger | 304-385 | SP-RING-type | ||||
Sequence: PDSEIATTGVRVSLICPLVKMRLSVPCRAETCAHLQCFDAVFYLQMNEKKPTWMCPVCDKPAAYDQLIIDGLLSKILSECEG | ||||||
Region | 426-507 | Disordered | ||||
Sequence: APASSTPGIGSGLSGPGSAGSGAGAAGSLENGKTGADVVDLTLDSSSSSEDEDEDEDDDEDEDEGPRPKRRCPFQKGLVPAC | ||||||
Compositional bias | 471-488 | Acidic residues | ||||
Sequence: SSSSEDEDEDEDDDEDED |
Domain
The LXXLL motif is a coregulator signature that is essential for transcriptional corepression.
Sequence similarities
Belongs to the PIAS family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length507
- Mass (Da)55,570
- Last updated2003-03-01 v2
- ChecksumA8E5E6E3BAC76426
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
F6RKH8 | F6RKH8_MOUSE | Pias4 | 71 |
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 230 | in Ref. 1; AAF72040 | ||||
Sequence: K → N | ||||||
Sequence conflict | 417 | in Ref. 1; AAF72040 | ||||
Sequence: L → H | ||||||
Compositional bias | 471-488 | Acidic residues | ||||
Sequence: SSSSEDEDEDEDDDEDED | ||||||
Sequence conflict | 494 | in Ref. 1; AAF72040 | ||||
Sequence: K → N |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF109174 EMBL· GenBank· DDBJ | AAF72040.1 EMBL· GenBank· DDBJ | mRNA | ||
BC025159 EMBL· GenBank· DDBJ | AAH25159.1 EMBL· GenBank· DDBJ | mRNA |