Human Gene PIAS2 (ENST00000324794.11) from GENCODE V44
Description: Homo sapiens protein inhibitor of activated STAT 2 (PIAS2), transcript variant 22, non-coding RNA. (from RefSeq NR_148699) RefSeq Summary (NM_173206): This gene encodes a member of the protein inhibitor of activated STAT family, which function as SUMO E3 ligases and play important roles in many cellular processes by mediating the sumoylation of target proteins. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. Isoforms of the encoded protein enhance the sumoylation of specific target proteins including the p53 tumor suppressor protein, c-Jun, and the androgen receptor. A pseudogene of this gene is located on the short arm of chromosome 4. The symbol MIZ1 has also been associated with ZBTB17 which is a different gene located on chromosome 1. [provided by RefSeq, Aug 2017]. Gencode Transcript: ENST00000324794.11 Gencode Gene: ENSG00000078043.16 Transcript (Including UTRs) Position: hg38 chr18:46,815,711-46,917,503 Size: 101,793 Total Exon Count: 13 Strand: - Coding Region Position: hg38 chr18:46,818,377-46,917,345 Size: 98,969 Coding Exon Count: 13
ID:PIAS2_HUMAN DESCRIPTION: RecName: Full=E3 SUMO-protein ligase PIAS2; EC=6.3.2.-; AltName: Full=Androgen receptor-interacting protein 3; Short=ARIP3; AltName: Full=DAB2-interacting protein; Short=DIP; AltName: Full=Msx-interacting zinc finger protein; Short=Miz1; AltName: Full=PIAS-NY protein; AltName: Full=Protein inhibitor of activated STAT x; AltName: Full=Protein inhibitor of activated STAT2; 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. PATHWAY: Protein modification; protein sumoylation. SUBUNIT: 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 G(1) phase. PIAS2-beta interacts with IFIH1/MDA5. INTERACTION: P01106:MYC; NbExp=4; IntAct=EBI-348555, EBI-447544; Q96T51:RUFY1; NbExp=3; IntAct=EBI-348555, EBI-3941207; P63279:UBE2I; NbExp=5; IntAct=EBI-348555, EBI-80168; SUBCELLULAR LOCATION: Nucleus speckle. Nucleus, PML body. Note=Colocalizes at least partially with promyelocytic leukemia nuclear bodies (PML NBs). TISSUE SPECIFICITY: 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. DEVELOPMENTAL STAGE: Isoform 3 expression in adult testis is 14.2- fold stronger than in embryonic testis. 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. PTM: Sumoylated. SIMILARITY: Belongs to the PIAS family. SIMILARITY: Contains 1 PINIT domain. SIMILARITY: Contains 1 SAP domain. SIMILARITY: Contains 1 SP-RING-type zinc finger.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O75928
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AK308143 - Homo sapiens cDNA, FLJ98091. AF077954 - Homo sapiens protein inhibitor of activated STAT protein PIASx-beta mRNA, complete cds. AB527541 - Synthetic construct DNA, clone: pF1KB6117, Homo sapiens PIAS2 gene for protein inhibitor of activated STAT, 2, without stop codon, in Flexi system. JD130747 - Sequence 111771 from Patent EP1572962. AK294801 - Homo sapiens cDNA FLJ57366 complete cds, highly similar to Protein inhibitor of activated STAT2. BC015190 - Homo sapiens protein inhibitor of activated STAT, 2, mRNA (cDNA clone MGC:14633 IMAGE:4080297), complete cds. KJ897959 - Synthetic construct Homo sapiens clone ccsbBroadEn_07353 PIAS2 gene, encodes complete protein. AF077953 - Homo sapiens protein inhibitor of activated STAT protein PIASx-alpha mRNA, complete cds. DQ896421 - Synthetic construct Homo sapiens clone IMAGE:100010881; FLH194158.01L; RZPDo839G0169D protein inhibitor of activated STAT, 2 (PIAS2) gene, encodes complete protein. EU176432 - Synthetic construct Homo sapiens clone IMAGE:100006509; FLH194165.01X; RZPDo839C07252D protein inhibitor of activated STAT, 2 (PIAS2) gene, encodes complete protein. BC111060 - Homo sapiens protein inhibitor of activated STAT, 2, mRNA (cDNA clone MGC:102682 IMAGE:5745101), complete cds. AF361054 - Homo sapiens PIAS-NY protein mRNA, complete cds.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04120 - Ubiquitin mediated proteolysis hsa04630 - Jak-STAT signaling pathway hsa05200 - Pathways in cancer hsa05222 - Small cell lung cancer
BioCarta from NCI Cancer Genome Anatomy Project h_ranbp2Pathway - Sumoylation by RanBP2 Regulates Transcriptional Repression
Reactome (by CSHL, EBI, and GO)
Protein O75928 (Reactome details) participates in the following event(s):
US Server
