PIAS2

Summary

PIAS2 (protein inhibitor of activated STAT 2, HGNC:17311) is a protein-coding gene on chromosome 18q21.1, encoding E3 SUMO-protein ligase PIAS2 (O75928). 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.

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.

Source: NCBI Gene 9063 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 82 total
• MANE Select transcript: NM_004671

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17311
Approved symbol	PIAS2
Name	protein inhibitor of activated STAT 2
Location	18q21.1
Locus type	gene with protein product
Status	Approved
Aliases	PIASX-BETA, miz, PIASX-ALPHA, ZMIZ4, ARIP3
Ensembl gene	ENSG00000078043
Ensembl biotype	protein_coding
OMIM	603567
Entrez	9063

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 11 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000324794, ENST00000398654, ENST00000545673, ENST00000585916, ENST00000586170, ENST00000586634, ENST00000586953, ENST00000587810, ENST00000589819, ENST00000589917, ENST00000590127, ENST00000590944, ENST00000591865, ENST00000592011, ENST00000592212, ENST00000592221, ENST00000862885, ENST00000862886, ENST00000862887

RefSeq mRNA: 22 — MANE Select: NM_004671 NM_001324046, NM_001324047, NM_001324048, NM_001324049, NM_001324051, NM_001324052, NM_001324053, NM_001324054, NM_001324055, NM_001324057, NM_001324058, NM_001324059, NM_001324060, NM_001354033, NM_001354034, NM_001354035, NM_001354036, NM_001354037, NM_001354038, NM_001354039, NM_004671, NM_173206

CCDS: CCDS32824, CCDS32825

Canonical transcript exons

ENST00000585916 — 14 exons

Exon	Start	End
ENSE00002813999	46917322	46917507
ENSE00002829802	46803218	46812612
ENSE00003468421	46890580	46891054
ENSE00003476719	46855345	46855435
ENSE00003481104	46844054	46844127
ENSE00003499412	46855565	46855615
ENSE00003513772	46827959	46828130
ENSE00003553767	46844734	46844839
ENSE00003564048	46836357	46836517
ENSE00003572310	46846707	46846841
ENSE00003616826	46820933	46821072
ENSE00003636653	46864164	46864248
ENSE00003649327	46815312	46815349
ENSE00003679166	46829734	46829867

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 98.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.6665 / max 322.0747, expressed in 1810 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171830	20.6451	1810
171832	0.0175	3
171831	0.0038	3

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.12	gold quality
male germ cell	CL:0000015	97.92	gold quality
adult organism	UBERON:0007023	97.25	gold quality
left testis	UBERON:0004533	97.06	gold quality
right testis	UBERON:0004534	96.60	gold quality
testis	UBERON:0000473	95.61	gold quality
colonic epithelium	UBERON:0000397	91.53	gold quality
adrenal tissue	UBERON:0018303	91.48	gold quality
secondary oocyte	CL:0000655	90.21	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.06	gold quality
gastrocnemius	UBERON:0001388	90.04	gold quality
muscle of leg	UBERON:0001383	89.82	gold quality
buccal mucosa cell	CL:0002336	89.20	gold quality
cerebellar vermis	UBERON:0004720	88.93	gold quality
medial globus pallidus	UBERON:0002477	88.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.65	gold quality
oocyte	CL:0000023	88.64	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.32	gold quality
cerebellar cortex	UBERON:0002129	87.94	gold quality
cerebellar hemisphere	UBERON:0002245	87.88	gold quality
muscle organ	UBERON:0001630	87.80	gold quality
calcaneal tendon	UBERON:0003701	87.74	gold quality
globus pallidus	UBERON:0001875	87.42	gold quality
cerebellum	UBERON:0002037	87.22	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.18	gold quality
corpus callosum	UBERON:0002336	86.75	gold quality
tendon	UBERON:0000043	86.37	gold quality
cortical plate	UBERON:0005343	86.19	gold quality
primary visual cortex	UBERON:0002436	85.65	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	85.52	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.94

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
AR	Activation
LRRN3	Repression
MUC1	Repression
MYCN	Repression

Upstream regulators (CollecTRI, top): MYC, NFATC1, NFATC3, ZBTB17

miRNA regulators (miRDB)

295 targeting PIAS2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4775	99.98	75.00	6394

Literature-anchored findings (GeneRIF, showing 19)

• PIASx may function as a co-repressor of Stat4 (PMID:12716907)
• Required for upregulation of a large group of genes in response to DNA damage, a function that is regulated by c-Myc, but not by 14-3-3eta and represses the expression of many genes (PMID:15580267)
• the repressive properties of PIASxalpha/ARIP3 require its physical interaction with FLI-1, identifying PIASxalpha as a novel corepressor of FLI-1 (PMID:16148010)
• findings show that Epstein-Barr virus Rta interacts and colocalizes with PIASxalpha and PIASxbeta in the nucleus; these interactions seem to enhance Rta sumoylation (PMID:16460827)
• PIASxalpha acts as a key signal integrator that permits different responses from the same transcription factor, depending on the signaling pathway that is activated. (PMID:16713578)
• These findings suggest that SUMO-1 modification of MDA5 possibly via PIAS2beta may play a role in the MDA5-mediated interferon response to viral infections. (PMID:21156324)
• PIASxalpha is a novel SUMO E3 ligase for PTEN, and it positively regulates PTEN protein level in tumor suppression. (PMID:24344134)
• UXT is a binding protein of PIAS2, and interaction between PIAS2 and UXT may be important for the transcriptional activation of AR. (PMID:25434787)
• the expression of SENP8, SAE1, PIAS1, PIAS2 and ZMIZ1 is deregulated in the majority of PTC tissues, likely contributing to the PTC phenotype. (PMID:26403403)
• results indicated that PIAS2-mediated SUMOylation constrained HCV replication (PMID:28973998)
• the results presented demonstrate that in heat-stressed HeLa cells, p38 MAPK pathway-dependent SUMOylation of Elk-1 and phosphorylation of PIAS2 correlate with the downregulation of transactivation by Elk-1. (PMID:30783905)
• PIAS genes as disease markers in bipolar disorder. (PMID:30861611)
• PIAS1expression of PIAS1 gene was increased in patients with MS compared to healthy subjects; also, there was a significant correlation between the expression of PIAS1 and PIAS2 genes with disease severity of multiple sclerosis (PMID:31084243)
• We are the first to reveal that mutations of rs644731 in the PIAS2 gene were significantly correlated with the progression of interstitial fibrosis and tubular atrophy in kidney transplant recipients. (PMID:31582715)
• SUMOylation of the transcription factor ZFHX3 at Lys-2806 requires SAE1, UBC9, and PIAS2 and enhances its stability and function in cell proliferation. (PMID:32249212)
• Expression of PIAS Genes in Migraine Patients. (PMID:33763841)
• PIAS2-mediated blockade of IFN-beta signaling: a basis for sporadic Parkinson disease dementia. (PMID:34234281)
• Integrative transcriptome analysis reveals TEKT2 and PIAS2 involvement in diabetic nephropathy. (PMID:36251411)
• dsRNAi-mediated silencing of PIAS2beta specifically kills anaplastic carcinomas by mitotic catastrophe. (PMID:38744818)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pias2	ENSDARG00000092979
mus_musculus	Pias2	ENSMUSG00000025423
rattus_norvegicus	Pias2	ENSRNOG00000017493
drosophila_melanogaster	Su(var)2-10	FBGN0003612

Paralogs (5): PIAS1 (ENSG00000033800), PIAS4 (ENSG00000105229), ZMIZ1 (ENSG00000108175), ZMIZ2 (ENSG00000122515), PIAS3 (ENSG00000131788)

Protein

Protein identifiers

E3 SUMO-protein ligase PIAS2 — O75928 (reviewed: O75928)

Alternative names: Androgen receptor-interacting protein 3, DAB2-interacting protein, E3 SUMO-protein transferase PIAS2, Msx-interacting zinc finger protein, PIAS-NY protein, Protein inhibitor of activated STAT x, Protein inhibitor of activated STAT2

All UniProt accessions (8): O75928, A0A087WUY7, A0A0A0MS92, B4DGW0, K7EJT4, K7EMP6, K7EQX5, K7ER97

UniProt curated annotations — full annotation on UniProt →

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. Isoform PIAS2-alpha sumoylates PML at’Lys-65’ and ‘Lys-160’.

Subunit / interactions. 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. 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. Isoform PIAS2-alpha interacts with PML (isoform PML-12). Interacts with PRDM1/Blimp-1.

Subcellular location. Nucleus speckle. Nucleus. PML body.

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.

Post-translational modifications. Sumoylated.

Domain organisation. The LXXLL motif is a transcriptional coregulator signature.

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.

Pathway. Protein modification; protein sumoylation.

Similarity. Belongs to the PIAS family.

Isoforms (3)

UniProt ID	Names	Canonical?
O75928-1	PIAS2-beta, PIASx-beta, Miz1	yes
O75928-2	PIAS2-alpha, PIASx-alpha, ARIP3
O75928-3	3

RefSeq proteins (22): NP_001310975, NP_001310976, NP_001310977, NP_001310978, NP_001310980, NP_001310981, NP_001310982, NP_001310983, NP_001310984, NP_001310986, NP_001310987, NP_001310988, NP_001310989, NP_001340962, NP_001340963, NP_001340964, NP_001340965, NP_001340966, NP_001340967, NP_001340968, NP_004662, NP_775298 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003034	SAP_dom	Domain
IPR004181	Znf_MIZ	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR023321	PINIT	Domain
IPR036361	SAP_dom_sf	Homologous_superfamily
IPR038654	PINIT_sf	Homologous_superfamily

Pfam: PF02037, PF02891, PF14324

UniProt features (62 total): strand 14, cross-link 9, helix 7, mutagenesis site 6, binding site 4, modified residue 4, splice variant 4, domain 2, sequence conflict 2, region of interest 2, turn 2, short sequence motif 2, chain 1, sequence variant 1, zinc finger region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4FO9	X-RAY DIFFRACTION	2.39
2ASQ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75928-F1	71.74	0.47

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 364; 385; 388; 362

Post-translational modifications (13): 476, 477, 478, 499, 46, 249, 430, 435, 443, 452, 489, 502, 562

Mutagenesis-validated functional residues (6):

Position	Phenotype
362	loss of mdm2 and tp53 sumoylation and of autosumoylation; no loss of jun- and tp53-binding.
467	reduces affinity for sumo1.
469	abolishes binding to sumo1.
470	abolishes binding to sumo1.
472	abolishes binding to sumo1.
473	reduces affinity for sumo1.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins
R-HSA-3232118	SUMOylation of transcription factors
R-HSA-3232142	SUMOylation of ubiquitinylation proteins
R-HSA-3899300	SUMOylation of transcription cofactors
R-HSA-4090294	SUMOylation of intracellular receptors
R-HSA-4551638	SUMOylation of chromatin organization proteins

MSigDB gene sets: 303 (showing top): GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, MORF_MSH3, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, MORF_BRCA1, MORF_ATRX, RIZ_ERYTHROID_DIFFERENTIATION_CCNE1, GOBP_REGULATION_OF_INTRACELLULAR_STEROID_HORMONE_RECEPTOR_SIGNALING_PATHWAY, MORF_ESR1, IWANAGA_E2F1_TARGETS_INDUCED_BY_SERUM, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, PUJANA_CHEK2_PCC_NETWORK, GOBP_REGULATION_OF_ANDROGEN_RECEPTOR_SIGNALING_PATHWAY, GOBP_PEPTIDYL_LYSINE_MODIFICATION

GO Biological Process (7): DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase II (GO:0006357), protein sumoylation (GO:0016925), endoplasmic reticulum unfolded protein response (GO:0030968), negative regulation of androgen receptor signaling pathway (GO:0060766), negative regulation of DNA-templated transcription (GO:0045892), regulation of macromolecule metabolic process (GO:0060255)

GO Molecular Function (11): DNA binding (GO:0003677), transcription coregulator activity (GO:0003712), transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), SUMO transferase activity (GO:0019789), ubiquitin protein ligase binding (GO:0031625), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), SUMO ligase activity (GO:0061665), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), PML body (GO:0016605), nuclear speck (GO:0016607), nuclear body (GO:0016604)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	6
Activation of HOX genes during differentiation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
cellular anatomical structure	2
gene expression	1
RNA biosynthetic process	1
transcription by RNA polymerase II	1
peptidyl-lysine modification	1
protein modification by small protein conjugation	1
cellular response to unfolded protein	1
response to endoplasmic reticulum stress	1
intracellular signal transduction	1
androgen receptor signaling pathway	1
negative regulation of intracellular steroid hormone receptor signaling pathway	1
regulation of androgen receptor signaling pathway	1
DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
regulation of metabolic process	1
macromolecule metabolic process	1
nucleic acid binding	1
transcription regulator activity	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
transition metal ion binding	1
ubiquitin-like protein transferase activity	1
ubiquitin-like protein ligase binding	1
DNA-binding transcription factor binding	1
SUMO transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear body	1
nuclear ribonucleoprotein granule	1
nucleoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1588 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIAS2	SUMO1	P55856	988
PIAS2	UBE2I	P50550	941
PIAS2	SUMO2	P55855	880
PIAS2	NSMCE2	Q96MF7	795
PIAS2	UBA2	Q9UBT2	772
PIAS2	CHMP5	Q9NZZ3	762
PIAS2	STAT3	P40763	728
PIAS2	SAE1	Q9UBE0	715
PIAS2	CHMP1A	Q9HD42	711
PIAS2	PARK7	Q99497	700
PIAS2	SENP1	Q9P0U3	687
PIAS2	HIPK2	Q9H2X6	676
PIAS2	SENP3	Q9H4L4	666
PIAS2	RANBP2	P49792	649
PIAS2	RNF4	P78317	646

IntAct

140 interactions, top by confidence:

A	B	Type	Score
PIAS2	UBE2I	psi-mi:“MI:0915”(physical association)	0.850
UBE2I	PIAS2	psi-mi:“MI:0915”(physical association)	0.850
PIAS2	UBE2I	psi-mi:“MI:0403”(colocalization)	0.850
PIAS2	SUMO1	psi-mi:“MI:0915”(physical association)	0.780
SUMO1	PIAS2	psi-mi:“MI:0915”(physical association)	0.780
SUMO1	PIAS2	psi-mi:“MI:0407”(direct interaction)	0.780
PIAS2	SUMO1	psi-mi:“MI:0407”(direct interaction)	0.780
PIAS2	CCNDBP1	psi-mi:“MI:0915”(physical association)	0.670
PIAS2	NAV2	psi-mi:“MI:0915”(physical association)	0.670
CCNDBP1	PIAS2	psi-mi:“MI:0915”(physical association)	0.670
NAV2	PIAS2	psi-mi:“MI:0915”(physical association)	0.670
PIAS2	RUFY1	psi-mi:“MI:0915”(physical association)	0.580
RUFY1	PIAS2	psi-mi:“MI:0915”(physical association)	0.580
SUMO1P1	PIAS2	psi-mi:“MI:0915”(physical association)	0.560
PRKAB2	PIAS2	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	PIAS2	psi-mi:“MI:0915”(physical association)	0.560
ZBED1	PIAS2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (265): PIAS2 (Two-hybrid), PIAS2 (Two-hybrid), PIAS2 (Biochemical Activity), HIC1 (Co-localization), TP53 (Biochemical Activity), PIAS2 (Two-hybrid), PIAS2 (Two-hybrid), PIAS2 (Two-hybrid), PIAS2 (Two-hybrid), PIAS2 (Two-hybrid), PIAS2 (Two-hybrid), PIAS2 (Two-hybrid), PIAS2 (Two-hybrid), PIAS2 (Two-hybrid), ZBED1 (Two-hybrid)

ESM2 similar proteins: A6QR55, B2GUZ1, F1R4C4, F7BJB9, M9MRI4, O00750, O14976, O70260, O75061, O75925, O75928, O88907, P19838, P23881, P25799, P35123, P97874, Q03601, Q13107, Q27974, Q29RQ5, Q505D9, Q5RCD3, Q61010, Q63369, Q66J69, Q6ASW7, Q6AZ28, Q6F3J0, Q6ZPS6, Q6ZTA4, Q7ZWM8, Q80TZ3, Q80U87, Q86Y01, Q8AW93, Q8C5D8, Q8C7M3, Q8N2W9, Q8R4H2

Diamond homologs: F1R4C4, F4JYG0, O54714, O70260, O75925, O75928, O88907, Q04195, Q12216, Q680Q4, Q6ASW7, Q6AZ28, Q6L4L4, Q6P1E1, Q8C5D8, Q8CIE2, Q8N2W9, Q8NF64, Q94361, Q9JM05, Q9ULJ6, Q9Y6X2, A0A0A7EPL0, O94451

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MAPK11	“up-regulates activity”	PIAS2	phosphorylation
MAPK14	“up-regulates activity”	PIAS2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 94 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SUMOylation of transcription factors	6	49.6×	7e-07
SUMOylation of intracellular receptors	5	24.3×	2e-04
SUMOylation of transcription cofactors	6	21.1×	7e-05
SUMOylation of chromatin organization proteins	5	11.5×	4e-03
SUMOylation of DNA damage response and repair proteins	5	10.6×	4e-03
PKR-mediated signaling	5	10.2×	4e-03
mRNA Polyadenylation	7	8.9×	8e-04
mRNA Splicing - Major Pathway	10	7.9×	7e-05

GO biological processes:

GO term	Partners	Fold	FDR
protein sumoylation	6	23.1×	1e-04
mRNA transport	6	18.8×	2e-04
positive regulation of miRNA transcription	5	17.3×	1e-03
negative regulation of translation	7	16.3×	1e-04
mRNA splicing, via spliceosome	8	8.7×	9e-04
mRNA processing	8	7.5×	1e-03
RNA splicing	7	7.3×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

82 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3343 predictions. Top by Δscore:

Variant	Effect	Δscore
18:46822391:AAG:A	donor_gain	1.0000
18:46827957:AC:A	donor_gain	1.0000
18:46827958:CC:C	donor_gain	1.0000
18:46828002:T:TA	donor_gain	1.0000
18:46828022:T:TA	donor_gain	1.0000
18:46828131:C:CA	acceptor_loss	1.0000
18:46828131:C:CC	acceptor_gain	1.0000
18:46828132:T:A	acceptor_loss	1.0000
18:46828134:CA:C	acceptor_gain	1.0000
18:46828135:A:C	acceptor_gain	1.0000
18:46828137:G:C	acceptor_gain	1.0000
18:46829732:A:AC	donor_gain	1.0000
18:46829733:C:CC	donor_gain	1.0000
18:46829733:CTTT:C	donor_gain	1.0000
18:46829736:T:A	donor_gain	1.0000
18:46829767:T:A	donor_gain	1.0000
18:46829772:G:C	donor_gain	1.0000
18:46836514:CTAA:C	acceptor_gain	1.0000
18:46836518:C:CC	acceptor_gain	1.0000
18:46838074:G:C	donor_gain	1.0000
18:46844048:A:AC	donor_gain	1.0000
18:46844049:C:CC	donor_gain	1.0000
18:46844052:A:AC	donor_gain	1.0000
18:46844053:C:CC	donor_gain	1.0000
18:46844053:CAGGG:C	donor_gain	1.0000
18:46844125:TAA:T	acceptor_gain	1.0000
18:46844125:TAAC:T	acceptor_loss	1.0000
18:46844126:AAC:A	acceptor_loss	1.0000
18:46844127:ACTT:A	acceptor_loss	1.0000
18:46844128:C:CC	acceptor_gain	1.0000

AlphaMissense

4066 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:46828052:A:G	L472P	1.000
18:46829798:C:A	W424C	1.000
18:46829798:C:G	W424C	1.000
18:46829800:A:G	W424R	1.000
18:46829800:A:T	W424R	1.000
18:46829805:C:T	G422D	1.000
18:46829806:C:G	G422R	1.000
18:46829816:G:C	F418L	1.000
18:46829816:G:T	F418L	1.000
18:46829817:A:C	F418C	1.000
18:46829817:A:G	F418S	1.000
18:46829818:A:G	F418L	1.000
18:46829823:A:C	I416S	1.000
18:46829823:A:G	I416T	1.000
18:46829823:A:T	I416N	1.000
18:46829850:A:G	L407P	1.000
18:46829853:A:C	I406S	1.000
18:46829853:A:G	I406T	1.000
18:46829853:A:T	I406N	1.000
18:46829865:A:G	L402P	1.000
18:46836358:C:A	G401W	1.000
18:46836360:T:A	D400V	1.000
18:46836361:C:A	D400Y	1.000
18:46836361:C:G	D400H	1.000
18:46836369:A:C	L397R	1.000
18:46836369:A:G	L397P	1.000
18:46836369:A:T	L397Q	1.000
18:46836384:G:T	A392D	1.000
18:46836395:A:C	C388W	1.000
18:46836396:C:A	C388F	1.000

dbSNP variants (sampled 300 via entrez): RS1000024963 (18:46915121 C>A), RS1000056184 (18:46867943 A>G,T), RS1000086008 (18:46823980 G>A), RS1000087896 (18:46847392 T>A,C), RS1000150620 (18:46833949 G>GTTCC), RS1000191399 (18:46917516 C>A,G,T), RS1000193215 (18:46879486 G>A), RS1000196938 (18:46883218 C>T), RS1000244370 (18:46914838 A>C,G,T), RS1000260274 (18:46830679 C>G,T), RS1000293422 (18:46843981 C>T), RS1000311709 (18:46873419 T>C), RS1000334184 (18:46871255 A>C), RS1000352491 (18:46911521 T>C), RS1000362747 (18:46861591 G>A)

Disease associations

OMIM: gene MIM:603567 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010136_31	Fruit consumption	2.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
sodium arsenite	increases expression	1
pentabromodiphenyl ether	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
eprenetapopt	affects expression, affects reaction	1
bisphenol AF	affects binding, affects folding, increases reaction	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Glyphosate	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cannabinoids	affects methylation, increases abundance	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Gallic Acid	increases expression	1
Hydrogen Peroxide	affects cotreatment, increases expression	1
Mercuric Chloride	affects cotreatment, increases expression	1
Mercury	affects expression	1
Methylmercury Compounds	affects expression	1
Tetrachlorodibenzodioxin	increases expression	1
Theophylline	affects cotreatment, increases expression	1
Thimerosal	affects cotreatment, increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases expression	1

Cellosaurus cell lines

9 cell lines: 5 cancer cell line, 3 embryonic stem cell, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A5I6	SEES3-1V human PIAS2, clone1	Embryonic stem cell	Male
CVCL_A5I7	SEES3-1V human PIAS2, clone2	Embryonic stem cell	Male
CVCL_A5I8	SEES3-1V human PIAS2, clone3	Embryonic stem cell	Male
CVCL_D7X3	Ubigene A-549 PIAS2 KO	Cancer cell line	Male
CVCL_D8SH	Ubigene HCT 116 PIAS2 KO	Cancer cell line	Male
CVCL_D9MZ	Ubigene HEK293 PIAS2 KO	Transformed cell line	Female
CVCL_E0KC	Ubigene HeLa PIAS2 KO	Cancer cell line	Female
CVCL_TD43	HAP1 PIAS2 (-) 1	Cancer cell line	Male
CVCL_TD44	HAP1 PIAS2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.