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Protein

E3 SUMO-protein ligase PIAS2

Gene

PIAS2

Organism
Homo sapiens (Human)
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 coregulator 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 the 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 PIAS2-beta, but not isoform PIAS2-alpha, promotes MDM2 sumoylation. Isoform PIAS2-alpha promotes PARK7 sumoylation. Isoform PIAS2-beta promotes NCOA2 sumoylation more efficiently than isoform PIAS2-alpha. Isoform PIAS2-alpha sumoylates PML at'Lys-65' and 'Lys-160'.3 Publications

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: UniProtKB
  • DNA binding Source: UniProtKB-KW
  • ligase activity Source: UniProtKB-KW
  • SUMO ligase activity Source: ParkinsonsUK-UCL
  • SUMO transferase activity Source: Reactome
  • transcription coactivator activity Source: UniProtKB
  • transcription factor binding Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase binding Source: Ensembl
  • zinc ion binding Source: ProtInc

GO - Biological processi

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

Keywordsi

Molecular functionDNA-binding, Ligase
Biological processTranscription, Transcription regulation, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-3108214. SUMOylation of DNA damage response and repair proteins.
R-HSA-3232118. SUMOylation of transcription factors.
R-HSA-4551638. SUMOylation of chromatin organization proteins.
R-HSA-5617472. Activation of anterior HOX genes in hindbrain development during early embryogenesis.
SignaLinkiO75928.
UniPathwayiUPA00886.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 SUMO-protein ligase PIAS2 (EC:6.3.2.-)
Alternative name(s):
Androgen receptor-interacting protein 3
Short name:
ARIP3
DAB2-interacting protein
Short name:
DIP
Msx-interacting zinc finger protein
Short name:
Miz1
PIAS-NY protein
Protein inhibitor of activated STAT x
Protein inhibitor of activated STAT2
Gene namesi
Name:PIAS2
Synonyms:PIASX
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

EuPathDBiHostDB:ENSG00000078043.15.
HGNCiHGNC:17311. 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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi362C → S or A: Loss of MDM2 and TP53 sumoylation and of autosumoylation; no loss of JUN- and TP53-binding. 2 Publications1
Mutagenesisi467V → A: Reduces affinity for SUMO1. 1 Publication1
Mutagenesisi469V → A: Abolishes binding to SUMO1. 1 Publication1
Mutagenesisi470I → A: Abolishes binding to SUMO1. 1 Publication1
Mutagenesisi472L → A: Abolishes binding to SUMO1. 1 Publication1
Mutagenesisi473T → A: Reduces affinity for SUMO1. 1 Publication1

Organism-specific databases

DisGeNETi9063.
OpenTargetsiENSG00000078043.
PharmGKBiPA134933292.

Polymorphism and mutation databases

BioMutaiPIAS2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002189761 – 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)Combined sources
Cross-linki249Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki430Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki435Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki443Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki452Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei476PhosphoserineCombined sources1
Modified residuei477PhosphoserineCombined sources1
Modified residuei478PhosphoserineCombined sources1
Cross-linki489Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei499PhosphoserineBy similarity1
Cross-linki502Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Isoform PIAS2-alpha (identifier: O75928-2)
Cross-linki562Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Post-translational modificationi

Sumoylated.2 Publications

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO75928.
MaxQBiO75928.
PaxDbiO75928.
PeptideAtlasiO75928.
PRIDEiO75928.

PTM databases

iPTMnetiO75928.
PhosphoSitePlusiO75928.

Expressioni

Tissue specificityi

Mainly expressed in testis. Isoform 3 is expressed predominantly in adult testis, weakly in pancreas, embryonic testis and sperm, and at very low levels in other organs.3 Publications

Developmental stagei

Isoform 3 expression in adult testis is 14.2-fold stronger than in embryonic testis.1 Publication

Inductioni

Up-regulated transiently during myeloid differentiation in various cells lines, such as HL-60, U-937, K-562, induced by either phorbol ester (TPA) or retinoic acid.

Gene expression databases

BgeeiENSG00000078043.
CleanExiHS_PIAS2.
ExpressionAtlasiO75928. baseline and differential.
GenevisibleiO75928. HS.

Organism-specific databases

HPAiHPA068792.

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 (By similarity). Sumoylation of a target protein seems to enhance the interaction. Binds to sumoylated ELK1. Binds DNA, such as CDKN1A promoter, in a sequence-specific manner. Interacts with PLAG1. Interacts with KLF8; the interaction results in SUMO ligation and repression of KLF8 transcriptional activity and of its cell cycle progression into G1 phase. PIAS2-beta interacts with IFIH1/MDA5. Isoform PIAS2-alpha interacts with PML (isoform PML-12).By similarity11 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • androgen receptor binding Source: UniProtKB
  • transcription factor binding Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase binding Source: Ensembl

Protein-protein interaction databases

BioGridi114523. 74 interactors.
ELMiO75928.
IntActiO75928. 97 interactors.
MINTiMINT-1455373.
STRINGi9606.ENSP00000465676.

Structurei

Secondary structure

1621
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi154 – 165Combined sources12
Beta strandi173 – 181Combined sources9
Helixi185 – 192Combined sources8
Beta strandi195 – 197Combined sources3
Beta strandi203 – 215Combined sources13
Beta strandi231 – 234Combined sources4
Beta strandi237 – 239Combined sources3
Helixi264 – 266Combined sources3
Beta strandi271 – 273Combined sources3
Beta strandi275 – 282Combined sources8
Beta strandi289 – 298Combined sources10
Helixi301 – 309Combined sources9
Helixi316 – 327Combined sources12
Beta strandi340 – 345Combined sources6
Turni347 – 349Combined sources3
Beta strandi354 – 359Combined sources6
Helixi370 – 379Combined sources10
Turni386 – 388Combined sources3
Helixi394 – 396Combined sources3
Beta strandi397 – 400Combined sources4
Helixi401 – 407Combined sources7
Beta strandi415 – 418Combined sources4
Beta strandi469 – 471Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ASQNMR-B466-488[»]
4FO9X-ray2.39A147-488[»]
ProteinModelPortaliO75928.
SMRiO75928.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO75928.

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-binding7

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi19 – 23LXXLL motif5
Motifi484 – 492Nuclear localization signalBy similarity9

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi571 – 612Ser-richAdd BLAST42
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.
HOGENOMiHOG000230594.
HOVERGENiHBG053598.
InParanoidiO75928.
KOiK16063.
OMAiPHESSTH.
OrthoDBiEOG091G08G5.
PhylomeDBiO75928.

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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform PIAS2-beta (identifier: O75928-1) [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 GLSDLSTIKS SVFSLDGGSS PVEPDLAVAG
110 120 130 140 150
IHSLPSTSVT 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 KEAMKVSSQP CTKIESSSVL
460 470 480 490 500
SKPCSVTVAS EASKKKVDVI DLTIESSSDE EEDPPAKRKC IFMSETQSSP
510 520 530 540 550
TKGVLMYQPS SVRVPSVTSV DPAAIPPSLT DYSVPFHHTP ISSMSSDLPG
560 570 580 590 600
LDFLSLIPVD PQYCPPMFLD SLTSPLTASS TSVTTTSSHE SSTHVSSSSS
610 620
RSETGVITSS GSNIPDIISL D
Length:621
Mass (Da):68,240
Last modified:May 5, 2009 - v3
Checksum:i6422B383345AD883
GO
Isoform PIAS2-alpha (identifier: O75928-2) [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 → EQRRNDINNELKLGTSSDTVQQ
     573-621: Missing.

Show »
Length:572
Mass (Da):63,396
Checksum:i63106D68C585F0ED
GO
Isoform 3 (identifier: O75928-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-8: MADFEELR → MNAGKQLQRTLH
     402-621: Missing.

Note: No experimental confirmation available.
Show »
Length:405
Mass (Da):45,057
Checksum:i6C16003BCDB6384E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti144P → L in AAK48938 (PubMed:15301740).Curated1
Sequence conflicti616D → E in AAC36705 (PubMed:9724754).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_056693207V → A. Corresponds to variant dbSNP:rs16940108Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0121961 – 8MADFEELR → MNAGKQLQRTLH in isoform 3. 1 Publication8
Alternative sequenceiVSP_012197402 – 621Missing in isoform 3. 1 PublicationAdd BLAST220
Alternative sequenceiVSP_050008551 – 572LDFLS…FLDSL → EQRRNDINNELKLGTSSDTV QQ in isoform PIAS2-alpha. 2 PublicationsAdd BLAST22
Alternative sequenceiVSP_050009573 – 621Missing in isoform PIAS2-alpha. 2 PublicationsAdd BLAST49

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF077953 mRNA. Translation: AAC36704.1.
AF077954 mRNA. Translation: AAC36705.1.
AF361054 mRNA. Translation: AAK48938.1.
AC090241 Genomic DNA. No translation available.
AC090373 Genomic DNA. No translation available.
BC015190 mRNA. Translation: AAH15190.1.
CCDSiCCDS32824.1. [O75928-1]
CCDS32825.1. [O75928-2]
RefSeqiNP_001310989.1. NM_001324060.1. [O75928-3]
NP_004662.2. NM_004671.4. [O75928-1]
NP_775298.1. NM_173206.3. [O75928-2]
UniGeneiHs.57769.
Hs.657844.

Genome annotation databases

EnsembliENST00000324794; ENSP00000317163; ENSG00000078043. [O75928-2]
ENST00000585916; ENSP00000465676; ENSG00000078043. [O75928-1]
GeneIDi9063.
KEGGihsa:9063.
UCSCiuc002lck.4. human. [O75928-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPIAS2_HUMAN
AccessioniPrimary (citable) accession number: O75928
Secondary accession number(s): O75927, Q96BT5, Q96KE3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: May 5, 2009
Last modified: October 25, 2017
This is version 170 of the entry and version 3 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families