Reviewed,
UniProtKB/Swiss-Prot O75928 (PIAS2_HUMAN)
Last modified
June 16, 2009.
Version 80.
History...
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90%,
50% identity |
Documents (7) |
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Names and origin
| Protein names | Recommended name: E3 SUMO-protein ligase PIAS2 Alternative name(s): Protein inhibitor of activated STAT2 Protein inhibitor of activated STAT x Msx-interacting zinc finger protein Miz1 DAB2-interacting protein Short name=DIP Androgen receptor-interacting protein 3 Short name=ARIP3 PIAS-NY protein | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 621 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| 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. 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. Ref.13 Ref.14 |
| Pathway | |
| Subunit structure | Binds SUMO1 and UBE2I. Interacts with 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, 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. |
| Subcellular location | Nucleus speckle. Note: Colocalizes at least partially with promyelocytic leukemia nuclear bodies (PML NBs). Ref.7 Ref.9 Ref.11 |
| Tissue specificity | Mainly testis. Isoform 3 is expressed predominantly in adult testis, weakly in pancreas, embryonic testis and sperm, and at very low levels in other organs. Ref.2 Ref.5 Ref.8 |
| Developmental stage | Expression of isoform 3 in adult testis is 14.2-fold stronger than in embryonic testis. Ref.2 |
| Induction | 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. |
| Domain | The LXXLL motif is a transcriptional coregulator signature. |
| Post-translational modification | |
| Sequence similarities | Belongs to the PIAS family. Contains 1 SAP domain. Contains 1 SP-RING-type zinc finger. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| BAT1 | Q13838 | 1 | EBI-348555,EBI-348622 | |
| Ikzf1 | Q03267 | 1 | EBI-348567,EBI-908572 | From a different organism. |
| MYC | P01106 | 2 | EBI-348555,EBI-447544 |
Alternative products
| This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform PIAS2-beta (identifier: O75928-1) 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. | ||||||
| Isoform PIAS2-alpha (identifier: O75928-2) 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. | ||||||
| Isoform 3 (identifier: O75928-3) The sequence of this isoform differs from the canonical sequence as follows: 1-8: MADFEELR → MNAGKQLQRTLH 402-621: Missing. | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||
Molecule processing | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 621 | 621 | E3 SUMO-protein ligase PIAS2 | PRO_0000218976 | |||||||
Regions | |||||||||||
| Domain | 11 – 45 | 35 | SAP | ||||||||
| Zinc finger | 331 – 408 | 78 | SP-RING-type | ||||||||
| Region | 467 – 473 | 7 | SUMO1-binding | ||||||||
| Motif | 19 – 23 | 5 | LXXLL motif | ||||||||
| Motif | 484 – 492 | 9 | Nuclear localization signal By similarity | ||||||||
| Compositional bias | 571 – 612 | 42 | Ser-rich | ||||||||
| Compositional bias | 596 – 602 | 7 | Poly-Ser | ||||||||
Natural variations | |||||||||||
| Alternative sequence | 1 – 8 | 8 | MADFEELR → MNAGKQLQRTLH in isoform 3. | VSP_012196 | |||||||
| Alternative sequence | 402 – 621 | 220 | Missing in isoform 3. | VSP_012197 | |||||||
| Alternative sequence | 551 – 572 | 22 | LDFLS…FLDSL → EQRRNDINNELKLGTSSDTV QQ in isoform PIAS2-alpha. | VSP_050008 | |||||||
| Alternative sequence | 573 – 621 | 49 | Missing in isoform PIAS2-alpha. | VSP_050009 | |||||||
| Natural variant | 207 | 1 | V → A: dbSNP rs16940108. | VAR_056693 | |||||||
Experimental info | |||||||||||
| Mutagenesis | 362 | 1 | C → S or A: Loss of MDM2 and TP53 sumoylation and of autosumoylation; no loss of JUN-and TP53-binding. Ref.9 Ref.10 | ||||||||
| Mutagenesis | 467 | 1 | V → A: Reduces affinity for SUMO1. Ref.16 | ||||||||
| Mutagenesis | 469 | 1 | V → A: Abolishes binding to SUMO1. Ref.16 | ||||||||
| Mutagenesis | 470 | 1 | I → A: Abolishes binding to SUMO1. Ref.16 | ||||||||
| Mutagenesis | 472 | 1 | L → A: Abolishes binding to SUMO1. Ref.16 | ||||||||
| Mutagenesis | 473 | 1 | T → A: Reduces affinity for SUMO1. Ref.16 | ||||||||
| Sequence conflict | 144 | 1 | P → L in AAK48938. Ref.2 | ||||||||
| Sequence conflict | 616 | 1 | D → E in AAC36705. Ref.1 | ||||||||
Secondary structure | |||||||||||
Helix Strand Turn | |||||||||||
| Beta strand | 469 – 471 | 3 | |||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Inhibition of Stat1-mediated gene activation by PIAS1." Liu B., Liao J., Rao X., Kushner S.A., Chung C.D., Chang D.D., Shuai K. Proc. Natl. Acad. Sci. U.S.A. 95:10626-10631(1998) [PubMed: 9724754] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PIAS2-ALPHA AND PIAS2-BETA). Tissue: B-cell. |
| [2] | "Molecular cloning and characterization of a novel splicing variant of PIASx." Zheng Y., Zhou Z.-M., Yin L.-L., Li J.-M., Sha J.-H. Acta Pharmacol. Sin. 25:1058-1064(2004) [PubMed: 15301740] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Tissue: Testis. |
| [3] | "DNA sequence and analysis of human chromosome 18." Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. Lander E.S.Nature 437:551-555(2005) [PubMed: 16177791] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [4] | "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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PIAS2-ALPHA). Tissue: Brain. |
| [5] | "A testis-specific androgen receptor coregulator that belongs to a novel family of nuclear proteins." Moilanen A.-M., Karvonen U., Poukka H., Yan W., Toppari J., Jaenne O.A., Palvimo J.J. J. Biol. Chem. 274:3700-3704(1999) [PubMed: 9920921] [Abstract] Cited for: TISSUE SPECIFICITY. |
| [6] | "Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73 identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction motif." Minty A., Dumont X., Kaghad M., Caput D. J. Biol. Chem. 275:36316-36323(2000) [PubMed: 10961991] [Abstract] Cited for: INTERACTION WITH SUMO1; TP73 AND TP53. |
| [7] | "DJ-1 positively regulates the androgen receptor by impairing the binding of PIASx alpha to the receptor." Takahashi K., Taira T., Niki T., Seino C., Iguchi-Ariga S.M.M., Ariga H. J. Biol. Chem. 276:37556-37563(2001) [PubMed: 11477070] [Abstract] Cited for: INTERACTION WITH PARK7, SUBCELLULAR LOCATION. |
| [8] | "Distinct effects of PIAS proteins on androgen-mediated gene activation in prostate cancer cells." Gross M., Liu B., Tan J.-A., French F.S., Carey M., Shuai K. Oncogene 20:3880-3887(2001) [PubMed: 11439351] [Abstract] Cited for: TISSUE SPECIFICITY. |
| [9] | "Sumoylation of Mdm2 by protein inhibitor of activated STAT (PIAS) and RanBP2 enzymes." Miyauchi Y., Yogosawa S., Honda R., Nishida T., Yasuda H. J. Biol. Chem. 277:50131-50136(2002) [PubMed: 12393906] [Abstract] Cited for: SUMOYLATION OF MDM2, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-362. |
| [10] | "Members of the PIAS family act as SUMO ligases for c-Jun and p53 and repress p53 activity." Schmidt D., Mueller S. Proc. Natl. Acad. Sci. U.S.A. 99:2872-2877(2002) [PubMed: 11867732] [Abstract] Cited for: INTERACTION WITH JUN; TP53 AND UBE2I, SUMOYLATION, MUTAGENESIS OF CYS-362. |
| [11] | "PIASx is a transcriptional co-repressor of signal transducer and activator of transcription 4." Arora T., Liu B., He H., Kim J., Murphy T.L., Murphy K.M., Modlin R.L., Shuai K. J. Biol. Chem. 278:21327-21330(2003) [PubMed: 12716907] [Abstract] Cited for: INTERACTION WITH STAT4, SUBCELLULAR LOCATION. |
| [12] | "Repression of the transactivating capacity of the oncoprotein PLAG1 by SUMOylation." Van Dyck F., Delvaux E.L.D., Van de Ven W.J.M., Chavez M.V. J. Biol. Chem. 279:36121-36131(2004) [PubMed: 15208321] [Abstract] Cited for: INTERACTION WITH PLAG1. |
| [13] | "PIASx acts as an Elk-1 coactivator by facilitating derepression." Yang S.-H., Sharrocks A.D. EMBO J. 24:2161-2171(2005) [PubMed: 15920481] [Abstract] Cited for: FUNCTION, INTERACTION WITH ELK1. |
| [14] | "Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities." Shinbo Y., Niki T., Taira T., Ooe H., Takahashi-Niki K., Maita C., Seino C., Iguchi-Ariga S.M.M., Ariga H. Cell Death Differ. 13:96-108(2006) [PubMed: 15976810] [Abstract] Cited for: FUNCTION IN PARK7 SUMOYLATION. |
| [15] | "Sumoylation delimits KLF8 transcriptional activity associated with the cell cycle regulation." Wei H., Wang X., Gan B., Urvalek A.M., Melkoumian Z.K., Guan J.-L., Zhao J. J. Biol. Chem. 281:16664-16671(2006) [PubMed: 16617055] [Abstract] Cited for: INTERACTION WITH KLF8. |
| [16] | "Small ubiquitin-like modifier (SUMO) recognition of a SUMO binding motif: a reversal of the bound orientation." Song J., Zhang Z., Hu W., Chen Y. J. Biol. Chem. 280:40122-40129(2005) [PubMed: 16204249] [Abstract] Cited for: STRUCTURE BY NMR OF 466-488 IN COMPLEX WITH SUMO1, MUTAGENESIS OF VAL-467; VAL-469; ILE-470; LEU-472 AND THR-473. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | |||||||||||||
| IPI | IPI00005836. IPI00244407. IPI00477352. | ||||||||||||
| RefSeq | NP_004662.2. NP_775298.1. | ||||||||||||
| UniGene | Hs.658013 | ||||||||||||
3D structure databases | |||||||||||||
| |||||||||||||
| SMR | O75928. Positions 1-65. | ||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| IntAct | O75928. 6 interactions. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | O75928. | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENSG00000078043. Homo sapiens. [Contig view] | ||||||||||||
| GeneID | 9063. | ||||||||||||
| KEGG | hsa:9063. | ||||||||||||
Organism-specific databases | |||||||||||||
| GeneCards | GC18M042646. | ||||||||||||
| HGNC | HGNC:17311. PIAS2. | ||||||||||||
| MIM | 603567. gene. | ||||||||||||
| PharmGKB | PA134933292. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| HOGENOM | O75928. | ||||||||||||
| HOVERGEN | O75928. | ||||||||||||
Enzyme and pathway databases | |||||||||||||
| Pathway_Interaction_DB | il12_stat4pathway. IL12 signaling mediated by STAT4. ranbp2pathway. Sumoylation by RanBP2 regulates transcriptional repression. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | O75928. | ||||||||||||
| Bgee | O75928. | ||||||||||||
| CleanEx | HS_PIAS2. | ||||||||||||
| GermOnline | ENSG00000078043. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| InterPro | IPR003034. SAP_DNA_bd. IPR004181. Znf_MIZ. [Graphical view] | ||||||||||||
| Pfam | PF02037. SAP. 1 hit. PF02891. zf-MIZ. 1 hit. [Graphical view] | ||||||||||||
| SMART | SM00513. SAP. 1 hit. [Graphical view] | ||||||||||||
| PROSITE | PS50800. SAP. 1 hit. PS51044. ZF_SP_RING. 1 hit. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other Resources | |||||||||||||
| NextBio | 33959. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | PIAS2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: O75928 Secondary accession number(s): O75927, Q96BT5, Q96KE3 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 18 Human chromosome 18: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PATHWAY comments Index of metabolic and biosynthesis pathways |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


