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Protein

E3 SUMO-protein ligase PIAS2

Gene

Pias2

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 pathway and the steroid hormone signaling pathway. The effects of this transcriptional coregulation, transactivation or silencing may vary depending upon the biological context and PIAS2 isoform studied. However, it seems to be mostly involved in gene silencing. Binds to sumoylated ELK1 and enhances its transcriptional activity by preventing recruitment of HDAC2 by ELK1, thus reversing SUMO-mediated repression of ELK1 transactivation activity. Isoform PIASx-beta, but not isoform PIASx-alpha, promotes MDM2 sumoylation. Isoform PIASx-alpha promotes PARK7 sumoylation. Isoform PIASx-beta promotes NCOA2 sumoylation more efficiently than isoform PIASx-alpha (By similarity). Sumoylates PML at'Lys-65' and 'Lys-160' (By similarity).By similarity

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 fingeri331 – 408SP-RING-typePROSITE-ProRule annotationAdd BLAST78

GO - Molecular functioni

  • androgen receptor binding Source: MGI
  • DNA binding Source: MGI
  • SUMO ligase activity Source: ParkinsonsUK-UCL
  • SUMO transferase activity Source: MGI
  • transcription factor binding Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase binding Source: BHF-UCL
  • zinc ion binding Source: InterPro

GO - Biological processi

  • negative regulation of androgen receptor signaling pathway Source: MGI
  • negative regulation of sequence-specific DNA binding transcription factor activity Source: MGI
  • positive regulation of transcription, DNA-templated Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • protein sumoylation Source: MGI
  • regulation of androgen receptor signaling pathway Source: MGI
  • regulation of osteoblast differentiation Source: MGI
  • regulation of transcription from RNA polymerase II promoter Source: MGI
  • transcription, DNA-templated Source: MGI

Keywordsi

Molecular functionDNA-binding, Transferase
Biological processTranscription, Transcription regulation, Ubl conjugation pathway
LigandMetal-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-4551638. SUMOylation of chromatin organization proteins.
UniPathwayiUPA00886.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 SUMO-protein ligase PIAS2 (EC:2.3.2.27)
Alternative name(s):
Androgen receptor-interacting protein 3
Short name:
ARIP3
DAB2-interacting protein
Short name:
DIP
Msx-interacting zinc finger protein
Protein inhibitor of activated STAT x
Protein inhibitor of activated STAT2
RING-type E3 ubiquitin transferase PIAS2Curated
Gene namesi
Name:Pias2
Synonyms:Miz1, Piasx
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:1096566. Pias2.

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002189771 – 621E3 SUMO-protein ligase PIAS2Add BLAST621

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki46Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki249Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki430Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki435Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki443Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki452Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei476PhosphoserineBy similarity1
Modified residuei477PhosphoserineBy similarity1
Modified residuei478PhosphoserineBy similarity1
Cross-linki489Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei499PhosphoserineCombined sources1
Cross-linki502Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity

Post-translational modificationi

Sumoylated.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ8C5D8.
PRIDEiQ8C5D8.

PTM databases

iPTMnetiQ8C5D8.
PhosphoSitePlusiQ8C5D8.

Expressioni

Gene expression databases

BgeeiENSMUSG00000025423.
CleanExiMM_PIAS2.
ExpressionAtlasiQ8C5D8. baseline and differential.
GenevisibleiQ8C5D8. MM.

Interactioni

Subunit structurei

Binds SUMO1 and UBE2I. Interacts with AXIN1, JUN, MDM2, PARK7, TP53 and TP73 isoform alpha, but not TP73 isoform beta. Interacts with STAT4 following IL12 and IFN-alpha stimulation of T-cells. Interacts also with GTF2I, GTF2IRD1, IKFZ1, DAB2 and MSX2, as well as with several steroid receptors, including ESR1, ESR2, NR3C1, PGR, AR, and with NCOA2. Sumoylation of a target protein seems to enhance the interaction. Binds to sumoylated ELK1. Interacts with PLAG1 (By similarity). Binds DNA, such as CDKN1A promoter, in a sequence-specific manner. Interacts with KLF8; the interaction results in SUMO ligation and repression of KLF8 transcriptional activity and of its cell cycle progression into G1 phase (By similarity). Interacts with IFIH1/MDA5 (By similarity). Interacts with PML (By similarity).By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

  • androgen receptor binding Source: MGI
  • transcription factor binding Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi201429. 14 interactors.
IntActiQ8C5D8. 5 interactors.
MINTiMINT-1782012.
STRINGi10090.ENSMUSP00000110425.

Structurei

3D structure databases

ProteinModelPortaliQ8C5D8.
SMRiQ8C5D8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini11 – 45SAPPROSITE-ProRule annotationAdd BLAST35
Domaini134 – 299PINITPROSITE-ProRule annotationAdd BLAST166

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni467 – 473SUMO1-bindingBy similarity7

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi19 – 23LXXLL motif5
Motifi484 – 492Nuclear localization signal1 Publication9

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi571 – 610Ser-richAdd BLAST40
Compositional biasi596 – 602Poly-Ser7

Domaini

The LXXLL motif is a transcriptional coregulator signature.

Sequence similaritiesi

Belongs to the PIAS family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri331 – 408SP-RING-typePROSITE-ProRule annotationAdd BLAST78

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG2169. Eukaryota.
ENOG410XQ2E. LUCA.
GeneTreeiENSGT00550000074410.
HOVERGENiHBG053598.
InParanoidiQ8C5D8.
KOiK16063.
OMAiPHESSTH.
OrthoDBiEOG091G08G5.
PhylomeDBiQ8C5D8.
TreeFamiTF323787.

Family and domain databases

Gene3Di1.10.720.30. 1 hit.
InterProiView protein in InterPro
IPR027228. PIAS2.
IPR023321. PINIT.
IPR003034. SAP_dom.
IPR036361. SAP_dom_sf.
IPR004181. Znf_MIZ.
PANTHERiPTHR10782:SF12. PTHR10782:SF12. 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.

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8C5D8-1) [UniParc]FASTAAdd to basket
Also known as: PIASx-beta, Miz1

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MADFEELRNM VSSFRVSELQ VLLGFAGRNK SGRKHDLLMR ALHLLKSGCS
60 70 80 90 100
PAVQIKIREL YRRRYPRTLE GLCDLSTIKS SVFSLDGSSS PVEPDLPVAG
110 120 130 140 150
IHSLPSTSIT PHSPSSPVGS VLLQDTKPTF EMQQPSPPIP PVHPDVQLKN
160 170 180 190 200
LPFYDVLDVL IKPTSLVQSS IQRFQEKFFI FALTPQQVRE ICISRDFLPG
210 220 230 240 250
GRRDYTVQVQ LRLCLAETSC PQEDNYPNSL CIKVNGKLFP LPGYAPPPKN
260 270 280 290 300
GIEQKRPGRP LNITSLVRLS SAVPNQISIS WASEIGKNYS MSVYLVRQLT
310 320 330 340 350
SAMLLQRLKM KGIRNPDHSR ALIKEKLTAD PDSEIATTSL RVSLMCPLGK
360 370 380 390 400
MRLTIPCRAV TCTHLQCFDA ALYLQMNEKK PTWICPVCDK KAAYESLILD
410 420 430 440 450
GLFMEILNDC SDVDEIKFQE DGSWCPMRPK KEAMKVTSQP CTKVESSSVF
460 470 480 490 500
SKPCSVTVAS DASKKKIDVI DLTIESSSDE EEDPPAKRKC IFMSETQSSP
510 520 530 540 550
TKGVLMYQPS SVRVPSVTSV DPAAIPPSLT DYSVPFHHTP VSSMSSDLPG
560 570 580 590 600
LDFLSLIPVD PQYCPPMFLD SLTSPLTASS TSVTTTSPHE SSTHVSSSSS
610 620
RSETGVITSS GRNIPDIISL D
Length:621
Mass (Da):68,426
Last modified:December 7, 2004 - v2
Checksum:iE980B834C2A9C58E
GO
Isoform 2 (identifier: Q8C5D8-2) [UniParc]FASTAAdd to basket
Also known as: PIASx-alpha, ARIP3

The sequence of this isoform differs from the canonical sequence as follows:
     551-572: LDFLSLIPVDPQYCPPMFLDSL → EQRRNDINNEVQLGASSDTVQQ
     573-621: Missing.

Show »
Length:572
Mass (Da):63,458
Checksum:i70668C1CEB3702EE
GO
Isoform 3 (identifier: Q8C5D8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: Missing.
     551-572: LDFLSLIPVDPQYCPPMFLDSL → EQRRNDINNEVQLGASSDTVQQ
     573-621: Missing.

Note: No experimental confirmation available.
Show »
Length:563
Mass (Da):62,352
Checksum:i25D6D636E852AA07
GO
Isoform 4 (identifier: Q8C5D8-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     563-580: YCPPMFLDSLTSPLTASS → SHLTLNSKQYVCHHHQPP
     581-621: Missing.

Note: No experimental confirmation available.
Show »
Length:580
Mass (Da):64,421
Checksum:i4461E5438EC68633
GO
Isoform 5 (identifier: Q8C5D8-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: Missing.

Note: No experimental confirmation available.
Show »
Length:612
Mass (Da):67,320
Checksum:i98EA1B83556CDE86
GO

Sequence cautioni

Q8C5D8: The sequence AAB96678 differs from that shown. Reason: Erroneous initiation.Curated
Q8C5D8: The sequence BAB29594 differs from that shown. Reason: Frameshift at position 34.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti73C → S in AAF12825 (PubMed:11104669).Curated1
Sequence conflicti97P → A in AAF12825 (PubMed:11104669).Curated1
Sequence conflicti110T → A in AAF12825 (PubMed:11104669).Curated1
Sequence conflicti119G → E in AAF12825 (PubMed:11104669).Curated1
Sequence conflicti150N → T in AAF12825 (PubMed:11104669).Curated1
Sequence conflicti158D → E in AAF12825 (PubMed:11104669).Curated1
Sequence conflicti173R → G in BAC26579 (PubMed:16141072).Curated1
Sequence conflicti243G → A in AAF12825 (PubMed:11104669).Curated1
Sequence conflicti288N → Q in AAF12825 (PubMed:11104669).Curated1
Sequence conflicti320R → K in AAF12825 (PubMed:11104669).Curated1
Sequence conflicti327L → P in AAF12825 (PubMed:11104669).Curated1
Sequence conflicti375Q → R in AAF12825 (PubMed:11104669).Curated1
Sequence conflicti413V → A in AAF12825 (PubMed:11104669).Curated1
Sequence conflicti438S → I in BAC37407 (PubMed:16141072).Curated1
Sequence conflicti458V → G in AAF12825 (PubMed:11104669).Curated1
Sequence conflicti464 – 466KKK → GTR in AAF12825 (PubMed:11104669).Curated3
Isoform 2 (identifier: Q8C5D8-2)
Sequence conflicti555N → T in AAF12825 (PubMed:11104669).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0121981 – 9Missing in isoform 3 and isoform 5. 1 Publication9
Alternative sequenceiVSP_012199551 – 572LDFLS…FLDSL → EQRRNDINNEVQLGASSDTV QQ in isoform 2 and isoform 3. 3 PublicationsAdd BLAST22
Alternative sequenceiVSP_012200563 – 580YCPPM…LTASS → SHLTLNSKQYVCHHHQPP in isoform 4. 1 PublicationAdd BLAST18
Alternative sequenceiVSP_012201573 – 621Missing in isoform 2 and isoform 3. 3 PublicationsAdd BLAST49
Alternative sequenceiVSP_012202581 – 621Missing in isoform 4. 1 PublicationAdd BLAST41

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF201391 mRNA. Translation: AAF12825.1.
AK029716 mRNA. Translation: BAC26579.1.
AK014871 mRNA. Translation: BAB29594.1. Frameshift.
AK078813 mRNA. Translation: BAC37407.1.
AK086653 mRNA. Translation: BAC39710.1.
BC005596 mRNA. Translation: AAH05596.1.
BC034711 mRNA. Translation: AAH34711.1.
AF039567 mRNA. Translation: AAB96678.1. Different initiation.
CCDSiCCDS37866.1. [Q8C5D8-1]
RefSeqiNP_001157639.1. NM_001164167.1. [Q8C5D8-4]
NP_001157640.1. NM_001164168.1.
NP_001157641.1. NM_001164169.1. [Q8C5D8-2]
NP_001157642.1. NM_001164170.1.
NP_032628.3. NM_008602.4. [Q8C5D8-1]
UniGeneiMm.6370.

Genome annotation databases

EnsembliENSMUST00000114777; ENSMUSP00000110425; ENSMUSG00000025423. [Q8C5D8-1]
GeneIDi17344.
KEGGimmu:17344.
UCSCiuc008frb.1. mouse. [Q8C5D8-2]
uc008frc.2. mouse. [Q8C5D8-1]
uc012bfb.1. mouse. [Q8C5D8-4]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPIAS2_MOUSE
AccessioniPrimary (citable) accession number: Q8C5D8
Secondary accession number(s): O54987
, Q8C384, Q8CDQ8, Q8K208, Q99JX5, Q9D5W7, Q9QZ63
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: December 7, 2004
Last modified: October 25, 2017
This is version 140 of the entry and version 2 of the sequence. See 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