PIAS2 (protein inhibitor of activated STAT 2)

Gene

• Entrez ID: 9063
• Gene name: Protein inhibitor of activated STAT 2
• Gene symbol: PIAS2
• Synonyms (NCBI Gene): ARIP3, DIP, MIZ1, PIASX, SIZ2, ZMIZ4
• Chromosome: 18
• Chromosome location: 18q21.1
• Summary: 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

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT029164	hsa-miR-26b-5p	Microarray	19088304
MIRT715734	hsa-miR-4722-3p	HITS-CLIP	19536157
MIRT715733	hsa-miR-6727-3p	HITS-CLIP	19536157
MIRT715732	hsa-miR-6747-3p	HITS-CLIP	19536157
MIRT715731	hsa-miR-6742-3p	HITS-CLIP	19536157
MIRT715730	hsa-miR-150-5p	HITS-CLIP	19536157
MIRT715729	hsa-miR-532-3p	HITS-CLIP	19536157
MIRT715728	hsa-miR-2116-3p	HITS-CLIP	19536157
MIRT715727	hsa-miR-3653-5p	HITS-CLIP	19536157
MIRT715726	hsa-miR-1976	HITS-CLIP	19536157
MIRT715725	hsa-miR-23a-5p	HITS-CLIP	19536157
MIRT715724	hsa-miR-23b-5p	HITS-CLIP	19536157
MIRT715723	hsa-miR-4713-5p	HITS-CLIP	19536157
MIRT715722	hsa-miR-4279	HITS-CLIP	19536157
MIRT715721	hsa-miR-498	HITS-CLIP	19536157
MIRT700794	hsa-miR-497-3p	HITS-CLIP	23313552
MIRT700793	hsa-miR-605-3p	HITS-CLIP	23313552
MIRT700792	hsa-miR-4493	HITS-CLIP	23313552
MIRT700791	hsa-miR-3140-3p	HITS-CLIP	23313552
MIRT700790	hsa-miR-6126	HITS-CLIP	23313552
MIRT448582	hsa-miR-6507-5p	PAR-CLIP	22100165
MIRT448581	hsa-miR-4720-3p	PAR-CLIP	22100165
MIRT448580	hsa-miR-3653-3p	PAR-CLIP	22100165
MIRT448579	hsa-miR-3658	PAR-CLIP	22100165
MIRT448582	hsa-miR-6507-5p	PAR-CLIP	22100165
MIRT448581	hsa-miR-4720-3p	PAR-CLIP	22100165
MIRT448580	hsa-miR-3653-3p	PAR-CLIP	22100165
MIRT448579	hsa-miR-3658	PAR-CLIP	22100165
MIRT715726	hsa-miR-1976	PAR-CLIP	27292025
MIRT715725	hsa-miR-23a-5p	PAR-CLIP	27292025
MIRT715724	hsa-miR-23b-5p	PAR-CLIP	27292025
MIRT715727	hsa-miR-3653-5p	PAR-CLIP	27292025
MIRT715722	hsa-miR-4279	PAR-CLIP	27292025
MIRT715734	hsa-miR-4722-3p	PAR-CLIP	27292025
MIRT715721	hsa-miR-498	PAR-CLIP	27292025
MIRT715733	hsa-miR-6727-3p	PAR-CLIP	27292025
MIRT715731	hsa-miR-6742-3p	PAR-CLIP	27292025
MIRT715732	hsa-miR-6747-3p	PAR-CLIP	27292025
MIRT715734	hsa-miR-4722-3p	HITS-CLIP	19536157
MIRT715733	hsa-miR-6727-3p	HITS-CLIP	19536157
MIRT715732	hsa-miR-6747-3p	HITS-CLIP	19536157
MIRT715731	hsa-miR-6742-3p	HITS-CLIP	19536157
MIRT715730	hsa-miR-150-5p	HITS-CLIP	19536157
MIRT715729	hsa-miR-532-3p	HITS-CLIP	19536157
MIRT715728	hsa-miR-2116-3p	HITS-CLIP	19536157
MIRT715727	hsa-miR-3653-5p	HITS-CLIP	19536157
MIRT715726	hsa-miR-1976	HITS-CLIP	19536157
MIRT715725	hsa-miR-23a-5p	HITS-CLIP	19536157
MIRT715724	hsa-miR-23b-5p	HITS-CLIP	19536157
MIRT715723	hsa-miR-4713-5p	HITS-CLIP	19536157
MIRT715722	hsa-miR-4279	HITS-CLIP	19536157
MIRT715721	hsa-miR-498	HITS-CLIP	19536157
MIRT700794	hsa-miR-497-3p	HITS-CLIP	23313552
MIRT700793	hsa-miR-605-3p	HITS-CLIP	23313552
MIRT700792	hsa-miR-4493	HITS-CLIP	23313552
MIRT700791	hsa-miR-3140-3p	HITS-CLIP	23313552
MIRT700790	hsa-miR-6126	HITS-CLIP	23313552
MIRT448582	hsa-miR-6507-5p	PAR-CLIP	22100165
MIRT448581	hsa-miR-4720-3p	PAR-CLIP	22100165
MIRT448580	hsa-miR-3653-3p	PAR-CLIP	22100165
MIRT448579	hsa-miR-3658	PAR-CLIP	22100165
MIRT448582	hsa-miR-6507-5p	PAR-CLIP	22100165
MIRT448581	hsa-miR-4720-3p	PAR-CLIP	22100165
MIRT448580	hsa-miR-3653-3p	PAR-CLIP	22100165
MIRT448579	hsa-miR-3658	PAR-CLIP	22100165
MIRT2295673	hsa-miR-4277	CLIP-seq
MIRT2295674	hsa-miR-4502	CLIP-seq
MIRT2295675	hsa-miR-4762-3p	CLIP-seq
MIRT2295673	hsa-miR-4277	CLIP-seq
MIRT2295674	hsa-miR-4502	CLIP-seq
MIRT2295675	hsa-miR-4762-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	IBA
GO:0003677	Function	DNA binding	IEA
GO:0003712	Function	Transcription coregulator activity	IBA
GO:0003714	Function	Transcription corepressor activity	IDA	20408817
GO:0005515	Function	Protein binding	IPI	11477070, 14752048, 16154161, 16189514, 16204249, 19549727, 20936779, 21156324, 21516116, 21988832, 22210188, 22406621, 25416956, 25910212, 28842558, 32296183
GO:0005634	Component	Nucleus	HDA	21630459
GO:0005634	Component	Nucleus	IDA	11477070, 14752048
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0006351	Process	DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IEA
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	IDA	16777850
GO:0008270	Function	Zinc ion binding	IEA
GO:0008270	Function	Zinc ion binding	TAS	9256341
GO:0016605	Component	PML body	IDA	22406621
GO:0016605	Component	PML body	IEA
GO:0016607	Component	Nuclear speck	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0016925	Process	Protein sumoylation	IBA
GO:0016925	Process	Protein sumoylation	IDA	20408817, 22406621
GO:0016925	Process	Protein sumoylation	IEA
GO:0016925	Process	Protein sumoylation	IEA
GO:0016925	Process	Protein sumoylation	TAS
GO:0019789	Function	SUMO transferase activity	EXP	12393906, 17283066, 18628979, 19041634, 20972456, 23145142
GO:0019789	Function	SUMO transferase activity	IEA
GO:0030968	Process	Endoplasmic reticulum unfolded protein response	IDA	20408817
GO:0031625	Function	Ubiquitin protein ligase binding	IEA
GO:0045892	Process	Negative regulation of DNA-templated transcription	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0060255	Process	Regulation of macromolecule metabolic process	IEA
GO:0060395	Process	SMAD protein signal transduction	IDA	16777850
GO:0060766	Process	Negative regulation of androgen receptor signaling pathway	IDA	11477070
GO:0061629	Function	RNA polymerase II-specific DNA-binding transcription factor binding	IEA
GO:0061629	Function	RNA polymerase II-specific DNA-binding transcription factor binding	IPI	20408817
GO:0061665	Function	SUMO ligase activity	IBA
GO:0061665	Function	SUMO ligase activity	IDA	18579533, 20408817

Other IDs

• MIM: 603567
• HGNC: 17311
• e!Ensembl: ENSG00000078043

Protein

• UniProt ID: O75928
• Protein name: E3 SUMO-protein ligase PIAS2 (EC 2.3.2.-) (Androgen receptor-interacting protein 3) (ARIP3) (DAB2-interacting protein) (DIP) (E3 SUMO-protein transferase PIAS2) (Msx-interacting zinc finger protein) (Miz1) (PIAS-NY protein) (Protein inhibitor of activated
• Protein 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,
• PDB: 2ASQ, 4FO9
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF14324	PINIT	145 → 297	PINIT domain	Domain
  PF02891	zf-MIZ	342 → 391	MIZ/SP-RING zinc finger	Domain

• Tissue specificity: 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. {ECO:0000269|PubMed:11439351, ECO:0000269|PubMed:15301740, ECO:00
• Sequence:

  MADFEELRNMVSSFRVSELQVLLGFAGRNKSGRKHDLLMRALHLLKSGCSPAVQIKIREL
  YRRRYPRTLEGLSDLSTIKSSVFSLDGGSSPVEPDLAVAGIHSLPSTSVTPHSPSSPVGS
  VLLQDTKPTFEMQQPSPPIPPVHPDVQLKNLPFYDVLDVLIKPTSLVQSSIQRFQEKFFI
  FALTPQQVREICISRDFLPGGRRDYTVQVQLRLCLAETSCPQEDNYPNSLCIKVNGKLFP
  LPGYAPPPKNGIEQKRPGRPLNITSLVRLSSAVPNQISISWASEIGKNYSMSVYLVRQLT
  SAMLLQRLKMKGIRNPDHSRALIKEKLTADPDSEIATTSLRVSLMCPLGKMRLTIPCRAV
  TCTHLQCFDAALYLQMNEKKPTWICPVCDKKAAYESLILDGLFMEILNDCSDVDEIKFQE
  DGSWCPMRPKKEAMKVSSQPCTKIESSSVLSKPCSVTVASEASKKKVDVIDLTIESSSDE
  EEDPPAKRKCIFMSETQSSPTKGVLMYQPSSVRVPSVTSVDPAAIPPSLTDYSVPFHHTP
  ISSMSSDLPGLDFLSLIPVDPQYCPPMFLDSLTSPLTASSTSVTTTSSHESSTHVSSSSS
  RSETGVITSSGSNIPDIISLD

• Sequence length: 621

Pathways

KEGG:

Ubiquitin mediated proteolysis
JAK-STAT signaling pathway

Reactome:

SUMOylation of DNA damage response and repair proteins
SUMOylation of transcription factors
SUMOylation of ubiquitinylation proteins
SUMOylation of transcription cofactors
SUMOylation of intracellular receptors
SUMOylation of chromatin organization proteins

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
UPPER AERODIGESTIVE TRACT NEOPLASM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute lymphocytic leukemia	Lymphocytic Leukemia	BEFREE	31273062		★☆☆☆☆ Found in Text Mining only
Adult Acute Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	31273062		★☆☆☆☆ Found in Text Mining only
Adult Diffuse Large B-Cell Lymphoma	B-cell Lymphoma	BEFREE	19549844		★☆☆☆☆ Found in Text Mining only
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	35473503	Associate	★☆☆☆☆ Found in Text Mining only
B-Cell Lymphomas	B-Cell Lymphoma	BEFREE	21804610		★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	36748193	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	24702277		★☆☆☆☆ Found in Text Mining only
Childhood Acute Lymphoblastic Leukemia	Lymphoblastic Leukemia	BEFREE	31273062		★☆☆☆☆ Found in Text Mining only
Conventional (Clear Cell) Renal Cell Carcinoma	Renal Carcinoma	BEFREE	22159222		★☆☆☆☆ Found in Text Mining only
Diffuse Large B-Cell Lymphoma	Diffuse Lymphoma	BEFREE	19549844		★☆☆☆☆ Found in Text Mining only
Down Syndrome	Down syndrome	Pubtator	29049012	Associate	★☆☆☆☆ Found in Text Mining only
Esophageal carcinoma	Esophageal Carcinoma	BEFREE	27109891		★☆☆☆☆ Found in Text Mining only
Esophageal Neoplasms	Esophagus Neoplasm	BEFREE	27109891		★☆☆☆☆ Found in Text Mining only
Infertility Male	Male infertility	Pubtator	31103287	Associate	★☆☆☆☆ Found in Text Mining only
Lymphoma	Lymphoma	BEFREE	20551174, 31273062		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of esophagus	Esophagus Neoplasm	BEFREE	27109891		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of ovary	Ovarian cancer	BEFREE	24702277		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	14639620		★☆☆☆☆ Found in Text Mining only
MYELODYSPLASTIC SYNDROME	Myelodysplastic Syndrome	BEFREE	28539603		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	24190252, 24296348, 27109891, 28667123		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	17947461, 21908575, 24190252		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	Pubtator	21109931	Associate	★☆☆☆☆ Found in Text Mining only
Neuropathy	Neuropathy	BEFREE	29217679		★☆☆☆☆ Found in Text Mining only
ovarian neoplasm	Ovarian neoplasm	BEFREE	24702277		★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	BEFREE	29180403		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	27672034	Associate	★☆☆☆☆ Found in Text Mining only
Renal Cell Carcinoma	Renal Carcinoma	BEFREE	22159222		★☆☆☆☆ Found in Text Mining only
T-Cell Lymphoma	T-Cell Lymphoma	BEFREE	20551174		★☆☆☆☆ Found in Text Mining only