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Protein

E3 SUMO-protein ligase PIAS4

Gene

Pias4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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, 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. Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation (By similarity).By similarity

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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri304 – 38178SP-RING-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • DNA binding Source: MGI
  • ligase activity Source: UniProtKB-KW
  • SUMO ligase activity Source: BHF-UCL
  • SUMO transferase activity Source: MGI
  • transcription corepressor activity Source: MGI
  • ubiquitin protein ligase binding Source: BHF-UCL
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ligase, Repressor

Keywords - Biological processi

Host-virus interaction, Transcription, Transcription regulation, Ubl conjugation pathway, Wnt signaling pathway

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-3108214. SUMOylation of DNA damage response and repair proteins.
R-MMU-3232118. SUMOylation of transcription factors.
R-MMU-4615885. SUMOylation of DNA replication proteins.
R-MMU-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
R-MMU-5693571. Nonhomologous End-Joining (NHEJ).
R-MMU-5693607. Processing of DNA double-strand break ends.
R-MMU-69473. G2/M DNA damage checkpoint.
UniPathwayiUPA00886.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 SUMO-protein ligase PIAS4 (EC:6.3.2.-)
Alternative name(s):
PIASy
Protein inhibitor of activated STAT protein 4
Protein inhibitor of activated STAT protein gamma
Short name:
PIAS-gamma
Gene namesi
Name:Pias4
Synonyms:Piasg
OrganismiMus musculus (Mouse)Imported
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:2136940. Pias4.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • nuclear matrix Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: UniProtKB
  • PML body Source: UniProtKB-SubCell
  • transferase complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi330 – 3301C → S: Abrogates sumoylation of LEF1 and increases LEF1-mediated transcriptional activity; when associated with S-335; A-337 and S-340. 1 Publication
Mutagenesisi335 – 3351C → S: Abrogates sumoylation of LEF1 and increases LEF1-mediated transcriptional activity; when associated with S-330; A-337 and S-340. 1 Publication
Mutagenesisi337 – 3371H → A: Abrogates sumoylation of LEF1 and increases LEF1-mediated transcriptional activity; when associated with S-330; S-335 and S-340. 1 Publication
Mutagenesisi340 – 3401C → S: Abrogates sumoylation of LEF1 and increases LEF1-mediated transcriptional activity; when associated with S-330; S-335 and A-337. 1 Publication
Mutagenesisi470 – 4745SSSSS → AAAAA: No effect on sumoylation of LEF1, nor on LEF1-binding. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 507506E3 SUMO-protein ligase PIAS4PRO_0000218983Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Cross-linki35 – 35Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Cross-linki59 – 59Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei107 – 1071N6-acetyllysineBy similarity
Cross-linki128 – 128Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

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.1 Publication
Ubiquitinated by TRIM32 upon treatment with UVB and TNF-alpha.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Ubl conjugation

Proteomic databases

EPDiQ9JM05.
MaxQBiQ9JM05.
PaxDbiQ9JM05.
PRIDEiQ9JM05.

PTM databases

iPTMnetiQ9JM05.
PhosphoSiteiQ9JM05.

Expressioni

Tissue specificityi

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.2 Publications

Developmental stagei

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.1 Publication

Gene expression databases

BgeeiQ9JM05.
CleanExiMM_PIAS4.
ExpressionAtlasiQ9JM05. baseline and differential.
GenevisibleiQ9JM05. MM.

Interactioni

Subunit structurei

Interacts with AR, AXIN1, GATA2, LEF1, TP53 and STAT1, after treatment with IFNG. Binds to AT-rich DNA sequences, known as matrix or scaffold attachment regions (MARs/SARs) (By similarity). Interacts with TICAM1 (By similarity). Interacts with Moloney murine leukemia virus CA. Interacts with KLF8; the interaction results in SUMO ligation and repression of KLF8 transcriptional activity and of its cell cycle progression into G1 phase. Interacts with MTA1 (By similarity). Interacts with TRIM32 upon treatment with UVB and TNF-alpha.By similarity3 Publications

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi208475. 7 interactions.
DIPiDIP-60971N.
IntActiQ9JM05. 1 interaction.
STRINGi10090.ENSMUSP00000005064.

Structurei

3D structure databases

ProteinModelPortaliQ9JM05.
SMRiQ9JM05. Positions 3-66, 123-400.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini12 – 4635SAPPROSITE-ProRule annotationCuratedAdd
BLAST
Domaini112 – 272161PINITPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi20 – 245LXXLL motif

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi462 – 48827Asp/Glu-rich (acidic)Add
BLAST

Domaini

The LXXLL motif is a coregulator signature that is essential for transcriptional corepression.

Sequence similaritiesi

Belongs to the PIAS family.Curated
Contains 1 PINIT domain.PROSITE-ProRule annotation
Contains 1 SAP domain.PROSITE-ProRule annotation
Contains 1 SP-RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri304 – 38178SP-RING-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG2169. Eukaryota.
ENOG410XQ2E. LUCA.
GeneTreeiENSGT00550000074410.
HOGENOMiHOG000230594.
HOVERGENiHBG053598.
InParanoidiQ9JM05.
KOiK16065.
OMAiSECEGAD.
OrthoDBiEOG7HF1JB.
PhylomeDBiQ9JM05.
TreeFamiTF323787.

Family and domain databases

Gene3Di1.10.720.30. 1 hit.
InterProiIPR027224. PIAS4.
IPR023321. PINIT.
IPR003034. SAP_dom.
IPR004181. Znf_MIZ.
[Graphical view]
PANTHERiPTHR10782:SF9. PTHR10782:SF9. 1 hit.
PfamiPF14324. PINIT. 1 hit.
PF02891. zf-MIZ. 1 hit.
[Graphical view]
SMARTiSM00513. SAP. 1 hit.
[Graphical view]
PROSITEiPS51466. PINIT. 1 hit.
PS50800. SAP. 1 hit.
PS51044. ZF_SP_RING. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9JM05-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAELVEAKN MVMSFRVSDL QMLLGFVGRS KSGLKHELVT RALQLVQFDC
60 70 80 90 100
SPELFKKIKE LYETRYAKKS AEPGPQAPRP LDPLALHSMP RTPLSGPTVD
110 120 130 140 150
YPVLYGKYLN GLGRLPTKTL KPEVRLVKLP FFNMLDELLK PTELVPQSAE
160 170 180 190 200
KLQESPCIFA LTPRQVEMIR NSRELQPGVK AVQVVLRICY SDTSCPQEDQ
210 220 230 240 250
YPPNIAVKVN HSYCSVPGYY PSNKPGVEPK RPCRPINLTH LMYLSSATNR
260 270 280 290 300
ITVTWGNYGK SYSVALYLVR QLTSSDLLQR LKTIGVKHPE LCKALVKEKL
310 320 330 340 350
RLDPDSEIAT TGVRVSLICP LVKMRLSVPC RAETCAHLQC FDAVFYLQMN
360 370 380 390 400
EKKPTWMCPV CDKPAAYDQL IIDGLLSKIL SECEGADEIE FLAEGSWRPI
410 420 430 440 450
RAEKEPSCSP QGPILVLGTS DANGLAPASS TPGIGSGLSG PGSAGSGAGA
460 470 480 490 500
AGSLENGKTG ADVVDLTLDS SSSSEDEDED EDDDEDEDEG PRPKRRCPFQ

KGLVPAC
Length:507
Mass (Da):55,570
Last modified:March 1, 2003 - v2
Checksum:iA8E5E6E3BAC76426
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti230 – 2301K → N in AAF72040 (PubMed:10854042).Curated
Sequence conflicti417 – 4171L → H in AAF72040 (PubMed:10854042).Curated
Sequence conflicti494 – 4941K → N in AAF72040 (PubMed:10854042).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF109174 mRNA. Translation: AAF72040.1.
BC025159 mRNA. Translation: AAH25159.1.
CCDSiCCDS35992.1.
RefSeqiNP_067476.2. NM_021501.4.
UniGeneiMm.34428.

Genome annotation databases

EnsembliENSMUST00000005064; ENSMUSP00000005064; ENSMUSG00000004934.
GeneIDi59004.
KEGGimmu:59004.
UCSCiuc007ggc.3. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF109174 mRNA. Translation: AAF72040.1.
BC025159 mRNA. Translation: AAH25159.1.
CCDSiCCDS35992.1.
RefSeqiNP_067476.2. NM_021501.4.
UniGeneiMm.34428.

3D structure databases

ProteinModelPortaliQ9JM05.
SMRiQ9JM05. Positions 3-66, 123-400.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi208475. 7 interactions.
DIPiDIP-60971N.
IntActiQ9JM05. 1 interaction.
STRINGi10090.ENSMUSP00000005064.

PTM databases

iPTMnetiQ9JM05.
PhosphoSiteiQ9JM05.

Proteomic databases

EPDiQ9JM05.
MaxQBiQ9JM05.
PaxDbiQ9JM05.
PRIDEiQ9JM05.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000005064; ENSMUSP00000005064; ENSMUSG00000004934.
GeneIDi59004.
KEGGimmu:59004.
UCSCiuc007ggc.3. mouse.

Organism-specific databases

CTDi51588.
MGIiMGI:2136940. Pias4.

Phylogenomic databases

eggNOGiKOG2169. Eukaryota.
ENOG410XQ2E. LUCA.
GeneTreeiENSGT00550000074410.
HOGENOMiHOG000230594.
HOVERGENiHBG053598.
InParanoidiQ9JM05.
KOiK16065.
OMAiSECEGAD.
OrthoDBiEOG7HF1JB.
PhylomeDBiQ9JM05.
TreeFamiTF323787.

Enzyme and pathway databases

UniPathwayiUPA00886.
ReactomeiR-MMU-3108214. SUMOylation of DNA damage response and repair proteins.
R-MMU-3232118. SUMOylation of transcription factors.
R-MMU-4615885. SUMOylation of DNA replication proteins.
R-MMU-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
R-MMU-5693571. Nonhomologous End-Joining (NHEJ).
R-MMU-5693607. Processing of DNA double-strand break ends.
R-MMU-69473. G2/M DNA damage checkpoint.

Miscellaneous databases

PROiQ9JM05.
SOURCEiSearch...

Gene expression databases

BgeeiQ9JM05.
CleanExiMM_PIAS4.
ExpressionAtlasiQ9JM05. baseline and differential.
GenevisibleiQ9JM05. MM.

Family and domain databases

Gene3Di1.10.720.30. 1 hit.
InterProiIPR027224. PIAS4.
IPR023321. PINIT.
IPR003034. SAP_dom.
IPR004181. Znf_MIZ.
[Graphical view]
PANTHERiPTHR10782:SF9. PTHR10782:SF9. 1 hit.
PfamiPF14324. PINIT. 1 hit.
PF02891. zf-MIZ. 1 hit.
[Graphical view]
SMARTiSM00513. SAP. 1 hit.
[Graphical view]
PROSITEiPS51466. PINIT. 1 hit.
PS50800. SAP. 1 hit.
PS51044. ZF_SP_RING. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and analysis of a murine Pias family member, Pias-gamma, in developing skin and neurons."
    Sturm S., Koch M., White F.A.
    J. Mol. Neurosci. 14:107-121(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    Tissue: Brain.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Kidney.
  3. "PIASy, a nuclear matrix-associated SUMO E3 ligase, represses LEF1 activity by sequestration into nuclear bodies."
    Sachdev S., Bruhn L., Sieber H., Pichler A., Melchior F., Grosschedl R.
    Genes Dev. 15:3088-3103(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH LEF1, DNA-BINDING, SUMOYLATION, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-330; CYS-335; HIS-337; CYS-340 AND 470-SER--SER-474.
  4. "Modification of GATA-2 transcriptional activity in endothelial cells by the SUMO E3 ligase PIASy."
    Chun T.-H., Itoh H., Subramanian L., Iniguez-Lluhi J.A., Nakao K.
    Circ. Res. 92:1201-1208(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  5. "The interaction of Piasy with Trim32, an E3-ubiquitin ligase mutated in limb-girdle muscular dystrophy type 2H, promotes Piasy degradation and regulates UVB-induced keratinocyte apoptosis through NFkappaB."
    Albor A., El-Hizawi S., Horn E.J., Laederich M., Frosk P., Wrogemann K., Kulesz-Martin M.
    J. Biol. Chem. 281:25850-25866(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH TRIM32, UBIQUITINATION.
  6. "Interaction of moloney murine leukemia virus capsid with Ubc9 and PIASy mediates SUMO-1 addition required early in infection."
    Yueh A., Leung J., Bhattacharyya S., Perrone L.A., de los Santos K., Pu S.-Y., Goff S.P.
    J. Virol. 80:342-352(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MOMLV CA.
  7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Testis.

Entry informationi

Entry nameiPIAS4_MOUSE
AccessioniPrimary (citable) accession number: Q9JM05
Secondary accession number(s): Q8R165
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: March 1, 2003
Last modified: June 8, 2016
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.