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Protein

E3 SUMO-protein ligase PIAS4

Gene

PIAS4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.7 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

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)DescriptionActionsGraphical viewLength
Zinc fingeri311 – 388SP-RING-typePROSITE-ProRule annotationAdd BLAST78

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Repressor, Transferase
Biological processTranscription, Transcription regulation, Ubl conjugation pathway, Wnt signaling pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-196791 Vitamin D (calciferol) metabolism
R-HSA-3108214 SUMOylation of DNA damage response and repair proteins
R-HSA-3232118 SUMOylation of transcription factors
R-HSA-3232142 SUMOylation of ubiquitinylation proteins
R-HSA-3899300 SUMOylation of transcription cofactors
R-HSA-4085377 SUMOylation of SUMOylation proteins
R-HSA-4090294 SUMOylation of intracellular receptors
R-HSA-4615885 SUMOylation of DNA replication proteins
R-HSA-4755510 SUMOylation of immune response proteins
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693571 Nonhomologous End-Joining (NHEJ)
R-HSA-5693607 Processing of DNA double-strand break ends
R-HSA-69473 G2/M DNA damage checkpoint
SignaLinkiQ8N2W9
SIGNORiQ8N2W9
UniPathwayi
UPA00886

Names & Taxonomyi

Protein namesi
Recommended name:
E3 SUMO-protein ligase PIAS4 (EC:2.3.2.27)
Alternative name(s):
PIASy
Protein inhibitor of activated STAT protein 4
Protein inhibitor of activated STAT protein gamma
Short name:
PIAS-gamma
RING-type E3 ubiquitin transferase PIAS4Curated
Gene namesi
Name:PIAS4
Synonyms:PIASG
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000105229.6
HGNCiHGNC:17002 PIAS4
MIMi605989 gene
neXtProtiNX_Q8N2W9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi23 – 24LL → AA: Loss of repression of AR- and STAT1-induced transcription; no effect on AR- and STAT1-binding. 2 Publications2
Mutagenesisi35K → R: Complete loss of sumoylation. No enhancement of TCF4 sumoylation. No effect on interaction with TCF4. Colocalizes with SUMO1 in nucleus but concentrated into nuclear granules. 2 Publications1
Mutagenesisi128K → R: Some loss of sumoylation. 2 Publications1
Mutagenesisi342C → A: Inhibits TCF4 sumoylation. Inhibits beta-catenin-mediated TCF7L2/TCF4 activity. No colocalization with TCF7L2/TCF4 in nuclear punctate structures; when associated with A-347. 1
Mutagenesisi347C → A: Inhibits TCF4 sumoylation. Inhibits beta-catenin-mediated TCF7L2/TCF4 activity. No colocalization with TCF7L2/TCF4 in nuclear punctate structures; when associated with A-342. AR- and STAT1-binding. 1

Organism-specific databases

DisGeNETi51588
OpenTargetsiENSG00000105229
PharmGKBiPA134945903

Polymorphism and mutation databases

BioMutaiPIAS4
DMDMi34922831

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002189822 – 510E3 SUMO-protein ligase PIAS4Add BLAST509

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Cross-linki9Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki35Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Cross-linki35Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Cross-linki56Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki59Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki68Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki69Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei114N6-acetyllysineCombined sources1
Cross-linki125Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki128Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)

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

Keywords - PTMi

Acetylation, Isopeptide bond, Ubl conjugation

Proteomic databases

EPDiQ8N2W9
MaxQBiQ8N2W9
PaxDbiQ8N2W9
PeptideAtlasiQ8N2W9
PRIDEiQ8N2W9
ProteomicsDBi71739

PTM databases

iPTMnetiQ8N2W9
PhosphoSitePlusiQ8N2W9

Expressioni

Tissue specificityi

Highly expressed in testis and, at lower levels, in spleen, prostate, ovary, colon and peripheral blood leukocytes.1 Publication

Gene expression databases

BgeeiENSG00000105229 Expressed in 182 organ(s), highest expression level in testis
CleanExiHS_PIAS4
GenevisibleiQ8N2W9 HS

Organism-specific databases

HPAiHPA010598

Interactioni

Subunit structurei

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 G1 phase. Interacts with MTA1.By similarity8 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi119624, 129 interactors
DIPiDIP-32499N
ELMiQ8N2W9
IntActiQ8N2W9, 65 interactors
MINTiQ8N2W9
STRINGi9606.ENSP00000262971

Structurei

3D structure databases

ProteinModelPortaliQ8N2W9
SMRiQ8N2W9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini12 – 46SAPPROSITE-ProRule annotationCuratedAdd BLAST35
Domaini119 – 279PINITPROSITE-ProRule annotationAdd BLAST161

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi20 – 24LXXLL motif5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi464 – 492Asp/Glu-rich (acidic)Add BLAST29

Domaini

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

Sequence similaritiesi

Belongs to the PIAS family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri311 – 388SP-RING-typePROSITE-ProRule annotationAdd BLAST78

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG2169 Eukaryota
ENOG410XQ2E LUCA
GeneTreeiENSGT00550000074410
HOGENOMiHOG000230594
HOVERGENiHBG053598
InParanoidiQ8N2W9
KOiK16065
OMAiLRICYTD
OrthoDBiEOG091G08G5
PhylomeDBiQ8N2W9
TreeFamiTF323787

Family and domain databases

Gene3Di1.10.720.30, 1 hit
2.60.120.780, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR027224 PIAS4
IPR023321 PINIT
IPR038654 PINIT_sf
IPR003034 SAP_dom
IPR036361 SAP_dom_sf
IPR004181 Znf_MIZ
IPR013083 Znf_RING/FYVE/PHD
PANTHERiPTHR10782:SF9 PTHR10782:SF9, 1 hit
PfamiView protein in Pfam
PF14324 PINIT, 1 hit
PF02891 zf-MIZ, 1 hit
SMARTiView protein in SMART
SM00513 SAP, 1 hit
SUPFAMiSSF68906 SSF68906, 1 hit
PROSITEiView protein in PROSITE
PS51466 PINIT, 1 hit
PS50800 SAP, 1 hit
PS51044 ZF_SP_RING, 1 hit

Sequencei

Sequence statusi: Complete.

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

Q8N2W9-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAAELVEAKN MVMSFRVSDL QMLLGFVGRS KSGLKHELVT RALQLVQFDC
60 70 80 90 100
SPELFKKIKE LYETRYAKKN SEPAPQPHRP LDPLTMHSTY DRAGAVPRTP
110 120 130 140 150
LAGPNIDYPV LYGKYLNGLG RLPAKTLKPE VRLVKLPFFN MLDELLKPTE
160 170 180 190 200
LVPQNNEKLQ ESPCIFALTP RQVELIRNSR ELQPGVKAVQ VVLRICYSDT
210 220 230 240 250
SCPQEDQYPP NIAVKVNHSY CSVPGYYPSN KPGVEPKRPC RPINLTHLMY
260 270 280 290 300
LSSATNRITV TWGNYGKSYS VALYLVRQLT SSELLQRLKT IGVKHPELCK
310 320 330 340 350
ALVKEKLRLD PDSEIATTGV RVSLICPLVK MRLSVPCRAE TCAHLQCFDA
360 370 380 390 400
VFYLQMNEKK PTWMCPVCDK PAPYDQLIID GLLSKILSEC EDADEIEYLV
410 420 430 440 450
DGSWCPIRAE KERSCSPQGA ILVLGPSDAN GLLPAPSVNG SGALGSTGGG
460 470 480 490 500
GPVGSMENGK PGADVVDLTL DSSSSSEDEE EEEEEEEDED EEGPRPKRRC
510
PFQKGLVPAC
Length:510
Mass (Da):56,504
Last modified:October 1, 2002 - v1
Checksum:i26AAA18246E1ACE3
GO

Sequence cautioni

The sequence AAD45155 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti178N → K (PubMed:9724754).Curated1
Sequence conflicti179 – 182SREL → FQGM (PubMed:9724754).Curated4
Sequence conflicti179 – 182SREL → FQGM (PubMed:11388671).Curated4
Sequence conflicti482E → G in AAH66895 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF077952 mRNA Translation: AAC36703.1
BC010047 mRNA Translation: AAH10047.2
BC029874 mRNA Translation: AAH29874.1
BC066895 mRNA Translation: AAH66895.1
AF164437 mRNA Translation: AAD45155.1 Different initiation.
CCDSiCCDS12118.1
RefSeqiNP_056981.2, NM_015897.3
UniGeneiHs.105779

Genome annotation databases

EnsembliENST00000262971; ENSP00000262971; ENSG00000105229
GeneIDi51588
KEGGihsa:51588
UCSCiuc002lzg.4 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF077952 mRNA Translation: AAC36703.1
BC010047 mRNA Translation: AAH10047.2
BC029874 mRNA Translation: AAH29874.1
BC066895 mRNA Translation: AAH66895.1
AF164437 mRNA Translation: AAD45155.1 Different initiation.
CCDSiCCDS12118.1
RefSeqiNP_056981.2, NM_015897.3
UniGeneiHs.105779

3D structure databases

ProteinModelPortaliQ8N2W9
SMRiQ8N2W9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119624, 129 interactors
DIPiDIP-32499N
ELMiQ8N2W9
IntActiQ8N2W9, 65 interactors
MINTiQ8N2W9
STRINGi9606.ENSP00000262971

PTM databases

iPTMnetiQ8N2W9
PhosphoSitePlusiQ8N2W9

Polymorphism and mutation databases

BioMutaiPIAS4
DMDMi34922831

Proteomic databases

EPDiQ8N2W9
MaxQBiQ8N2W9
PaxDbiQ8N2W9
PeptideAtlasiQ8N2W9
PRIDEiQ8N2W9
ProteomicsDBi71739

Protocols and materials databases

DNASUi51588
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262971; ENSP00000262971; ENSG00000105229
GeneIDi51588
KEGGihsa:51588
UCSCiuc002lzg.4 human

Organism-specific databases

CTDi51588
DisGeNETi51588
EuPathDBiHostDB:ENSG00000105229.6
GeneCardsiPIAS4
HGNCiHGNC:17002 PIAS4
HPAiHPA010598
MIMi605989 gene
neXtProtiNX_Q8N2W9
OpenTargetsiENSG00000105229
PharmGKBiPA134945903
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2169 Eukaryota
ENOG410XQ2E LUCA
GeneTreeiENSGT00550000074410
HOGENOMiHOG000230594
HOVERGENiHBG053598
InParanoidiQ8N2W9
KOiK16065
OMAiLRICYTD
OrthoDBiEOG091G08G5
PhylomeDBiQ8N2W9
TreeFamiTF323787

Enzyme and pathway databases

UniPathwayi
UPA00886

ReactomeiR-HSA-196791 Vitamin D (calciferol) metabolism
R-HSA-3108214 SUMOylation of DNA damage response and repair proteins
R-HSA-3232118 SUMOylation of transcription factors
R-HSA-3232142 SUMOylation of ubiquitinylation proteins
R-HSA-3899300 SUMOylation of transcription cofactors
R-HSA-4085377 SUMOylation of SUMOylation proteins
R-HSA-4090294 SUMOylation of intracellular receptors
R-HSA-4615885 SUMOylation of DNA replication proteins
R-HSA-4755510 SUMOylation of immune response proteins
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693571 Nonhomologous End-Joining (NHEJ)
R-HSA-5693607 Processing of DNA double-strand break ends
R-HSA-69473 G2/M DNA damage checkpoint
SignaLinkiQ8N2W9
SIGNORiQ8N2W9

Miscellaneous databases

ChiTaRSiPIAS4 human
GeneWikiiPIAS4
GenomeRNAii51588
PROiPR:Q8N2W9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105229 Expressed in 182 organ(s), highest expression level in testis
CleanExiHS_PIAS4
GenevisibleiQ8N2W9 HS

Family and domain databases

Gene3Di1.10.720.30, 1 hit
2.60.120.780, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR027224 PIAS4
IPR023321 PINIT
IPR038654 PINIT_sf
IPR003034 SAP_dom
IPR036361 SAP_dom_sf
IPR004181 Znf_MIZ
IPR013083 Znf_RING/FYVE/PHD
PANTHERiPTHR10782:SF9 PTHR10782:SF9, 1 hit
PfamiView protein in Pfam
PF14324 PINIT, 1 hit
PF02891 zf-MIZ, 1 hit
SMARTiView protein in SMART
SM00513 SAP, 1 hit
SUPFAMiSSF68906 SSF68906, 1 hit
PROSITEiView protein in PROSITE
PS51466 PINIT, 1 hit
PS50800 SAP, 1 hit
PS51044 ZF_SP_RING, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPIAS4_HUMAN
AccessioniPrimary (citable) accession number: Q8N2W9
Secondary accession number(s): O75926, Q96G19, Q9UN16
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: October 1, 2002
Last modified: September 12, 2018
This is version 164 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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