PIAS4 (protein inhibitor of activated STAT 4)

Gene

• Entrez ID: 51588
• Gene name: Protein inhibitor of activated STAT 4
• Gene symbol: PIAS4
• Synonyms (NCBI Gene): PIAS-gamma, PIASY, Piasg, ZMIZ6
• Chromosome: 19
• Chromosome location: 19p13.3

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT043227	hsa-miR-324-5p	CLASH	23622248
MIRT719599	hsa-miR-1203	HITS-CLIP	19536157
MIRT719598	hsa-miR-5090	HITS-CLIP	19536157
MIRT719597	hsa-miR-6775-5p	HITS-CLIP	19536157
MIRT501631	hsa-miR-3960	HITS-CLIP	19536157
MIRT501630	hsa-miR-8072	HITS-CLIP	19536157
MIRT719596	hsa-miR-4767	HITS-CLIP	19536157
MIRT719595	hsa-miR-744-5p	HITS-CLIP	19536157
MIRT501629	hsa-miR-4467	HITS-CLIP	19536157
MIRT719594	hsa-miR-1908-5p	HITS-CLIP	19536157
MIRT719593	hsa-miR-663a	HITS-CLIP	19536157
MIRT719592	hsa-miR-6787-5p	HITS-CLIP	19536157
MIRT719599	hsa-miR-1203	HITS-CLIP	19536157
MIRT719598	hsa-miR-5090	HITS-CLIP	19536157
MIRT719597	hsa-miR-6775-5p	HITS-CLIP	19536157
MIRT501631	hsa-miR-3960	HITS-CLIP	19536157
MIRT501630	hsa-miR-8072	HITS-CLIP	19536157
MIRT719596	hsa-miR-4767	HITS-CLIP	19536157
MIRT719595	hsa-miR-744-5p	HITS-CLIP	19536157
MIRT501629	hsa-miR-4467	HITS-CLIP	19536157
MIRT719594	hsa-miR-1908-5p	HITS-CLIP	19536157
MIRT719593	hsa-miR-663a	HITS-CLIP	19536157
MIRT719592	hsa-miR-6787-5p	HITS-CLIP	19536157
MIRT639988	hsa-miR-135b-5p	HITS-CLIP	23824327
MIRT639987	hsa-miR-135a-5p	HITS-CLIP	23824327
MIRT639986	hsa-miR-6793-3p	HITS-CLIP	23824327
MIRT639985	hsa-miR-7108-3p	HITS-CLIP	23824327
MIRT639984	hsa-miR-1307-3p	HITS-CLIP	23824327
MIRT639983	hsa-miR-4638-5p	HITS-CLIP	23824327
MIRT639982	hsa-miR-5699-5p	HITS-CLIP	23824327
MIRT639981	hsa-miR-6815-3p	HITS-CLIP	23824327
MIRT501637	hsa-miR-4758-3p	PAR-CLIP	20371350
MIRT501636	hsa-miR-4707-3p	PAR-CLIP	20371350
MIRT501635	hsa-miR-4632-3p	PAR-CLIP	20371350
MIRT501634	hsa-miR-604	PAR-CLIP	20371350
MIRT501632	hsa-miR-6829-5p	PAR-CLIP	20371350
MIRT501637	hsa-miR-4758-3p	PAR-CLIP	24398324
MIRT501636	hsa-miR-4707-3p	PAR-CLIP	24398324
MIRT501635	hsa-miR-4632-3p	PAR-CLIP	24398324
MIRT501634	hsa-miR-604	PAR-CLIP	24398324
MIRT501632	hsa-miR-6829-5p	PAR-CLIP	24398324
MIRT501633	hsa-miR-185-3p	PAR-CLIP	24398324
MIRT501631	hsa-miR-3960	PAR-CLIP	24398324
MIRT501630	hsa-miR-8072	PAR-CLIP	24398324
MIRT501629	hsa-miR-4467	PAR-CLIP	24398324
MIRT501628	hsa-miR-6770-3p	PAR-CLIP	24398324
MIRT501631	hsa-miR-3960	PAR-CLIP	26701625
MIRT501631	hsa-miR-3960	PAR-CLIP	26701625
MIRT501631	hsa-miR-3960	PAR-CLIP	26701625
MIRT501631	hsa-miR-3960	PAR-CLIP	26701625
MIRT501631	hsa-miR-3960	PAR-CLIP	26701625
MIRT501631	hsa-miR-3960	PAR-CLIP	26701625
MIRT501631	hsa-miR-3960	PAR-CLIP	26701625
MIRT501629	hsa-miR-4467	PAR-CLIP	26701625
MIRT501629	hsa-miR-4467	PAR-CLIP	26701625
MIRT501629	hsa-miR-4467	PAR-CLIP	26701625
MIRT501629	hsa-miR-4467	PAR-CLIP	26701625
MIRT501629	hsa-miR-4467	PAR-CLIP	26701625
MIRT501629	hsa-miR-4467	PAR-CLIP	26701625
MIRT501629	hsa-miR-4467	PAR-CLIP	26701625
MIRT501628	hsa-miR-6770-3p	PAR-CLIP	26701625
MIRT501628	hsa-miR-6770-3p	PAR-CLIP	26701625
MIRT501628	hsa-miR-6770-3p	PAR-CLIP	26701625
MIRT501628	hsa-miR-6770-3p	PAR-CLIP	26701625
MIRT501628	hsa-miR-6770-3p	PAR-CLIP	26701625
MIRT501628	hsa-miR-6770-3p	PAR-CLIP	26701625
MIRT501630	hsa-miR-8072	PAR-CLIP	26701625
MIRT501630	hsa-miR-8072	PAR-CLIP	26701625
MIRT501630	hsa-miR-8072	PAR-CLIP	26701625
MIRT501630	hsa-miR-8072	PAR-CLIP	26701625
MIRT501630	hsa-miR-8072	PAR-CLIP	26701625
MIRT501630	hsa-miR-8072	PAR-CLIP	26701625
MIRT501630	hsa-miR-8072	PAR-CLIP	26701625
MIRT719599	hsa-miR-1203	HITS-CLIP	19536157
MIRT719598	hsa-miR-5090	HITS-CLIP	19536157
MIRT719597	hsa-miR-6775-5p	HITS-CLIP	19536157
MIRT501631	hsa-miR-3960	HITS-CLIP	19536157
MIRT501630	hsa-miR-8072	HITS-CLIP	19536157
MIRT719596	hsa-miR-4767	HITS-CLIP	19536157
MIRT719595	hsa-miR-744-5p	HITS-CLIP	19536157
MIRT501629	hsa-miR-4467	HITS-CLIP	19536157
MIRT719594	hsa-miR-1908-5p	HITS-CLIP	19536157
MIRT719593	hsa-miR-663a	HITS-CLIP	19536157
MIRT719592	hsa-miR-6787-5p	HITS-CLIP	19536157
MIRT719599	hsa-miR-1203	HITS-CLIP	19536157
MIRT719598	hsa-miR-5090	HITS-CLIP	19536157
MIRT719597	hsa-miR-6775-5p	HITS-CLIP	19536157
MIRT501631	hsa-miR-3960	HITS-CLIP	19536157
MIRT501630	hsa-miR-8072	HITS-CLIP	19536157
MIRT719596	hsa-miR-4767	HITS-CLIP	19536157
MIRT719595	hsa-miR-744-5p	HITS-CLIP	19536157
MIRT501629	hsa-miR-4467	HITS-CLIP	19536157
MIRT719594	hsa-miR-1908-5p	HITS-CLIP	19536157
MIRT719593	hsa-miR-663a	HITS-CLIP	19536157
MIRT719592	hsa-miR-6787-5p	HITS-CLIP	19536157
MIRT639988	hsa-miR-135b-5p	HITS-CLIP	23824327
MIRT639987	hsa-miR-135a-5p	HITS-CLIP	23824327
MIRT639986	hsa-miR-6793-3p	HITS-CLIP	23824327
MIRT639985	hsa-miR-7108-3p	HITS-CLIP	23824327
MIRT639984	hsa-miR-1307-3p	HITS-CLIP	23824327
MIRT639983	hsa-miR-4638-5p	HITS-CLIP	23824327
MIRT639982	hsa-miR-5699-5p	HITS-CLIP	23824327
MIRT639981	hsa-miR-6815-3p	HITS-CLIP	23824327
MIRT501637	hsa-miR-4758-3p	PAR-CLIP	20371350
MIRT501636	hsa-miR-4707-3p	PAR-CLIP	20371350
MIRT501635	hsa-miR-4632-3p	PAR-CLIP	20371350
MIRT501634	hsa-miR-604	PAR-CLIP	20371350
MIRT501632	hsa-miR-6829-5p	PAR-CLIP	20371350
MIRT501637	hsa-miR-4758-3p	PAR-CLIP	24398324
MIRT501636	hsa-miR-4707-3p	PAR-CLIP	24398324
MIRT501635	hsa-miR-4632-3p	PAR-CLIP	24398324
MIRT501634	hsa-miR-604	PAR-CLIP	24398324
MIRT501632	hsa-miR-6829-5p	PAR-CLIP	24398324
MIRT501633	hsa-miR-185-3p	PAR-CLIP	24398324
MIRT501631	hsa-miR-3960	PAR-CLIP	24398324
MIRT501630	hsa-miR-8072	PAR-CLIP	24398324
MIRT501629	hsa-miR-4467	PAR-CLIP	24398324
MIRT501628	hsa-miR-6770-3p	PAR-CLIP	24398324
MIRT1232953	hsa-miR-29a	CLIP-seq
MIRT1232954	hsa-miR-29b	CLIP-seq
MIRT1232955	hsa-miR-29c	CLIP-seq
MIRT1232956	hsa-miR-3663-3p	CLIP-seq
MIRT1232957	hsa-miR-4520a-5p	CLIP-seq
MIRT1232958	hsa-miR-4520b-5p	CLIP-seq
MIRT1232959	hsa-miR-4710	CLIP-seq
MIRT1232960	hsa-miR-4733-3p	CLIP-seq
MIRT1232961	hsa-miR-4792	CLIP-seq
MIRT2295681	hsa-miR-198	CLIP-seq
MIRT2295682	hsa-miR-4257	CLIP-seq
MIRT2295683	hsa-miR-520a-5p	CLIP-seq
MIRT2295684	hsa-miR-525-5p	CLIP-seq
MIRT2295685	hsa-miR-552	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IEA
GO:0000785	Component	Chromatin	IBA
GO:0001942	Process	Hair follicle development	IEA
GO:0003677	Function	DNA binding	IEA
GO:0003712	Function	Transcription coregulator activity	IBA
GO:0003714	Function	Transcription corepressor activity	IEA
GO:0005515	Function	Protein binding	IPI	11388671, 15383276, 17606919, 17696781, 18063693, 19779455, 20661221, 21965678, 21988832, 28842558, 32296183, 32814053, 33961781
GO:0005634	Component	Nucleus	IDA	11248056, 16816390
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	NAS	9724754
GO:0005654	Component	Nucleoplasm	IEA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IDA	16816390
GO:0006302	Process	Double-strand break repair	TAS
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0006974	Process	DNA damage response	IDA	35013556
GO:0007417	Process	Central nervous system development	IEA
GO:0008270	Function	Zinc ion binding	IEA
GO:0008270	Function	Zinc ion binding	NAS	9724754
GO:0010468	Process	Regulation of gene expression	IEA
GO:0010558	Process	Negative regulation of macromolecule biosynthetic process	IEA
GO:0010804	Process	Negative regulation of tumor necrosis factor-mediated signaling pathway	IEA
GO:0016055	Process	Wnt signaling pathway	IEA
GO:0016363	Component	Nuclear matrix	IEA
GO:0016605	Component	PML body	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0016925	Process	Protein sumoylation	IBA
GO:0016925	Process	Protein sumoylation	IDA	18579533
GO:0016925	Process	Protein sumoylation	IEA
GO:0016925	Process	Protein sumoylation	IEA
GO:0016925	Process	Protein sumoylation	IMP	22508508
GO:0016925	Process	Protein sumoylation	TAS
GO:0019789	Function	SUMO transferase activity	EXP	11731474, 19041634, 21965678
GO:0019789	Function	SUMO transferase activity	IEA
GO:0019789	Function	SUMO transferase activity	IMP	22508508
GO:0019789	Function	SUMO transferase activity	TAS
GO:0031625	Function	Ubiquitin protein ligase binding	IEA
GO:0031625	Function	Ubiquitin protein ligase binding	IPI	16816390
GO:0033235	Process	Positive regulation of protein sumoylation	IDA	17696781, 21965678
GO:0042359	Process	Vitamin D metabolic process	TAS
GO:0043124	Process	Negative regulation of canonical NF-kappaB signal transduction	IEA
GO:0043488	Process	Regulation of mRNA stability	IDA	34048572
GO:0045892	Process	Negative regulation of DNA-templated transcription	IDA	11248056
GO:0045892	Process	Negative regulation of DNA-templated transcription	NAS	9724754
GO:0046872	Function	Metal ion binding	IEA
GO:0060887	Process	Limb epidermis development	IEA
GO:0061157	Process	MRNA destabilization	IDA	34048572
GO:0061630	Function	Ubiquitin protein ligase activity	IEA
GO:0061665	Function	SUMO ligase activity	IBA
GO:0061665	Function	SUMO ligase activity	IDA	18579533, 32832608, 34048572, 35013556
GO:0061665	Function	SUMO ligase activity	IEA
GO:0080135	Process	Regulation of cellular response to stress	IEA
GO:0120186	Process	Negative regulation of protein localization to chromatin	IDA	35013556
GO:0120186	Process	Negative regulation of protein localization to chromatin	IDA	35013556
GO:1902174	Process	Positive regulation of keratinocyte apoptotic process	IEA
GO:1902174	Process	Positive regulation of keratinocyte apoptotic process	ISS
GO:1902231	Process	Positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage	IEA
GO:1905168	Process	Positive regulation of double-strand break repair via homologous recombination	IDA	32832608
GO:1990234	Component	Transferase complex	IEA
GO:2000042	Process	Negative regulation of double-strand break repair via homologous recombination	IDA	32832608

Other IDs

• MIM: 605989
• HGNC: 17002
• e!Ensembl: ENSG00000105229

Protein

• UniProt ID: Q8N2W9
• Protein name: E3 SUMO-protein ligase PIAS4 (EC 2.3.2.27) (PIASy) (Protein inhibitor of activated STAT protein 4) (Protein inhibitor of activated STAT protein gamma) (PIAS-gamma)
• 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 (PubMed:12511558, PubMed:12631292, PubMed:12727872, PubMed:15831457, PubMed:15976810
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF14324	PINIT	130 → 277	PINIT domain	Domain
  PF02891	zf-MIZ	322 → 371	MIZ/SP-RING zinc finger	Domain

• Tissue specificity: TISSUE SPECIFICITY: Highly expressed in testis and, at lower levels, in spleen, prostate, ovary, colon and peripheral blood leukocytes. {ECO:0000269|PubMed:11439351}.
• Sequence:

  MAAELVEAKNMVMSFRVSDLQMLLGFVGRSKSGLKHELVTRALQLVQFDCSPELFKKIKE
  LYETRYAKKNSEPAPQPHRPLDPLTMHSTYDRAGAVPRTPLAGPNIDYPVLYGKYLNGLG
  RLPAKTLKPEVRLVKLPFFNMLDELLKPTELVPQNNEKLQESPCIFALTPRQVELIRNSR
  ELQPGVKAVQVVLRICYSDTSCPQEDQYPPNIAVKVNHSYCSVPGYYPSNKPGVEPKRPC
  RPINLTHLMYLSSATNRITVTWGNYGKSYSVALYLVRQLTSSELLQRLKTIGVKHPELCK
  ALVKEKLRLDPDSEIATTGVRVSLICPLVKMRLSVPCRAETCAHLQCFDAVFYLQMNEKK
  PTWMCPVCDKPAPYDQLIIDGLLSKILSECEDADEIEYLVDGSWCPIRAEKERSCSPQGA
  ILVLGPSDANGLLPAPSVNGSGALGSTGGGGPVGSMENGKPGADVVDLTLDSSSSSEDEE
  EEEEEEEDEDEEGPRPKRRCPFQKGLVPAC

• Sequence length: 510

Pathways

KEGG:

NF-kappa B signaling pathway
Ubiquitin mediated proteolysis
JAK-STAT signaling pathway
Fluid shear stress and atherosclerosis

Reactome:

Vitamin D (calciferol) metabolism
SUMOylation of DNA damage response and repair proteins
SUMOylation of transcription factors
SUMOylation of ubiquitinylation proteins
SUMOylation of transcription cofactors
SUMOylation of SUMOylation proteins
SUMOylation of intracellular receptors
SUMOylation of DNA replication proteins
SUMOylation of immune response proteins
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
Nonhomologous End-Joining (NHEJ)
Processing of DNA double-strand break ends
G2/M DNA damage checkpoint

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
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PIAS4-related disorder	Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RHABDOMYOLYSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Breast Neoplasms	Breast neoplasm	Pubtator	26616021	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	39245738	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	30612578		★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	20661221		★☆☆☆☆ Found in Text Mining only
Congenital Abnormalities	Congenital abnormalities	Pubtator	25853300	Associate	★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	25853300	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	30143652		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	30143652		★☆☆☆☆ Found in Text Mining only
Diabetic Nephropathy	Diabetic Nephropathy	BEFREE	29038616		★☆☆☆☆ Found in Text Mining only
Fatty Liver Disease	Fatty Liver	BEFREE	27285989		★☆☆☆☆ Found in Text Mining only
Hypoxia	Hypoxia	Pubtator	20300531, 24002598	Stimulate	★☆☆☆☆ Found in Text Mining only
Hypoxia	Hypoxia	Pubtator	30612578	Associate	★☆☆☆☆ Found in Text Mining only
Idiopathic Pulmonary Fibrosis	Pulmonary Fibrosis	BEFREE	27162139		★☆☆☆☆ Found in Text Mining only
Language Development Disorders	Language development disorders	Pubtator	25853300	Associate	★☆☆☆☆ Found in Text Mining only
leukemia	Leukemia	LHGDN	16219678		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	30612578	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	23704280, 30612578		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	24002598		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	23843607		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	20661221		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	23624367		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	BEFREE	25853300		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	25853300	Associate	★☆☆☆☆ Found in Text Mining only
Mouth Neoplasms	Mouth neoplasm	Pubtator	39245738	Associate	★☆☆☆☆ Found in Text Mining only
MYELODYSPLASTIC SYNDROME	Myelodysplastic Syndrome	BEFREE	14531911		★☆☆☆☆ Found in Text Mining only
Myelodysplastic Syndromes	Myelodysplastic syndrome	Pubtator	14531911	Associate	★☆☆☆☆ Found in Text Mining only
Myeloid Leukemia, Chronic	Myeloid Leukemia	BEFREE	11781839		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	16793547, 20300531, 24002598, 24457965		★☆☆☆☆ Found in Text Mining only
Nephroblastoma	Nephroblastoma	BEFREE	26317783		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	29760808, 30612578		★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	24002598		★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	24002598	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatitis	Pancreatitis	Pubtator	24002598	Associate	★☆☆☆☆ Found in Text Mining only
Psoriasis	Psoriasis	BEFREE	20054338		★☆☆☆☆ Found in Text Mining only
Retinoblastoma	Retinoblastoma	BEFREE	16793547		★☆☆☆☆ Found in Text Mining only
synovial sarcoma	Synovial sarcoma	BEFREE	21454665		★☆☆☆☆ Found in Text Mining only
Von Hippel-Lindau Syndrome	Von Hippel-Lindau Syndrome	BEFREE	20300531		★☆☆☆☆ Found in Text Mining only
Wilms Tumor	Wilms tumor	Pubtator	26317783	Associate	★☆☆☆☆ Found in Text Mining only