YY2

Summary

YY2 (YY2 transcription factor, HGNC:31684) is a protein-coding gene on chromosome Xp22.12, encoding Transcription factor YY2 (O15391). Functions as a multifunctional transcription factor that may exhibit positive and negative control on a large number of genes.

The protein encoded by this gene is a transcription factor that includes several Kruppel-like zinc fingers in its C-terminal region. It possesses both activation and repression domains, and it can therefore have both positive and negative effects on the transcription of target genes. This gene has an intronless coding region, and it appears to have arisen by retrotransposition of the related YY1 transcription factor gene, which is located on chromosome 14.

Source: NCBI Gene 404281 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_206923

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31684
Approved symbol	YY2
Name	YY2 transcription factor
Location	Xp22.12
Locus type	gene with protein product
Status	Approved
Aliases	ZNF631
Ensembl gene	ENSG00000230797
Ensembl biotype	protein_coding
OMIM	300570
Entrez	404281

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000429584

RefSeq mRNA: 1 — MANE Select: NM_206923 NM_206923

CCDS: CCDS14202

Canonical transcript exons

ENST00000429584 — 1 exons

Exon	Start	End
ENSE00001797926	21855987	21858740

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 84.01.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.01	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.38	gold quality
stromal cell of endometrium	CL:0002255	72.49	gold quality
endometrium	UBERON:0001295	68.46	gold quality
islet of Langerhans	UBERON:0000006	68.13	gold quality
descending thoracic aorta	UBERON:0002345	67.66	gold quality
thoracic aorta	UBERON:0001515	66.91	gold quality
ascending aorta	UBERON:0001496	66.79	gold quality
smooth muscle tissue	UBERON:0001135	66.61	gold quality
popliteal artery	UBERON:0002250	66.56	gold quality
tibial artery	UBERON:0007610	66.55	gold quality
right coronary artery	UBERON:0001625	66.36	gold quality
left coronary artery	UBERON:0001626	65.87	gold quality
placenta	UBERON:0001987	65.81	gold quality
cortical plate	UBERON:0005343	65.42	gold quality
left ovary	UBERON:0002119	64.63	gold quality
ovary	UBERON:0000992	64.42	gold quality
myometrium	UBERON:0001296	64.29	gold quality
ventricular zone	UBERON:0003053	64.00	gold quality
testis	UBERON:0000473	63.28	gold quality
body of uterus	UBERON:0009853	63.25	gold quality
right lobe of liver	UBERON:0001114	63.17	gold quality
right ovary	UBERON:0002118	63.05	gold quality
mucosa of stomach	UBERON:0001199	62.32	gold quality
muscle tissue	UBERON:0002385	62.22	gold quality
adenohypophysis	UBERON:0002196	62.16	gold quality
vermiform appendix	UBERON:0001154	62.15	gold quality
right adrenal gland cortex	UBERON:0035827	62.11	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	61.86	gold quality
right adrenal gland	UBERON:0001233	61.84	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-CURD-10	no	91.71
E-ANND-3	no	1.69

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
FOS	Activation
IFNB1	Activation
TP53	Activation

JASPAR motifs

Motif	Name	Family
MA0748.1	YY2	More than 3 adjacent zinc fingers
MA0748.2	YY2	More than 3 adjacent zinc fingers
MA0748.3	YY2	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:17478514, PMID:23332764

miRNA regulators (miRDB)

63 targeting YY2, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349

Literature-anchored findings (GeneRIF, showing 12)

• YY2 can bind to and regulate some promoters known to be controlled by YY1. Similar to YY1, YY2 contains both transcriptional activation and repression functions. (PMID:15087442)
• the novel factor YY2 antagonizes the negative actions exerted by YY1 (PMID:16260628)
• yy2 expression is mediated by its own methylation-sensitive promoter. (PMID:19026728)
• Results show that human YY2 is not redundant to YY1, and YY2 is a significant regulator of genes previously identified as uniquely responding to YY1. (PMID:20215434)
• article summarizes all critical aspects that are (or will be) relevant for a better understanding of YY1- and/or YY2-mediated cellular control mechanisms (PMID:22248057)
• In human colorectal cancer metastases to the liver, the levels of AES protein are correlated with those of YY2 (PMID:27561171)
• A summary is of the published studies on the expression levels of YY1 in human cancers and their potential cross-reactivities with YY2 is also provided. Well-documented monospecific antibodies to both YY1 and YY2 have to be developed and used when examining the expression levels of YY1 and YY2 in human cancers to elucidate the accurate relationship between them and clinical significance of each. (PMID:29604937)
• different effects of YY1 and YY2 on gene expression patterns (PMID:31131888)
• Biological roles of Yin Yang 2: Its implications in physiological and pathological events. (PMID:32969187)
• Homeostasis Imbalance of YY2 and YY1 Promotes Tumor Growth by Manipulating Ferroptosis. (PMID:35246964)
• YY2-DRP1 Axis Regulates Mitochondrial Fission and Determines Cancer Stem Cell Asymmetric Division. (PMID:37300334)
• Integrative high-throughput enhancer surveying and functional verification divulges a YY2-condensed regulatory axis conferring risk for osteoporosis. (PMID:38335956)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
rattus_norvegicus		ENSRNOG00000076532
drosophila_melanogaster	phol	FBGN0035997
caenorhabditis_elegans		WBGENE00011639

Paralogs (2): YY1 (ENSG00000100811), ZFP42 (ENSG00000179059)

Protein

Protein identifiers

Transcription factor YY2 — O15391 (reviewed: O15391)

Alternative names: Yin and yang 2, Zinc finger protein 631

All UniProt accessions (1): O15391

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a multifunctional transcription factor that may exhibit positive and negative control on a large number of genes. May antagonize YY1 and function in development and differentiation.

Subcellular location. Nucleus.

Tissue specificity. Expressed in kidney, liver, spleen and testis but not in colon.

Miscellaneous. The gene encoding this protein appears to have arisen by retrotransposition of the YY1 gene in placental mammals. It is encoded by a single exon found in an intron of the gene MBTPS2.

Similarity. Belongs to the YY transcription factor family.

RefSeq proteins (1): NP_996806* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR017114	YY1-like	Family
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (16 total): zinc finger region 4, compositionally biased region 4, region of interest 4, sequence conflict 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15391-F1	57.33	0.14

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 38 (showing top): GOCC_PCG_PROTEIN_COMPLEX, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, chrXp22, GOBP_POSITIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOMF_DNA_BINDING_TRANSCRIPTION_ACTIVATOR_ACTIVITY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, MIR153_5P, MIR3662, MIR30B_5P_MIR30C_5P, MIR30D_5P, MIR30E_5P, MIR30A_5P, MIR130A_5P, MIR6868_3P

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (9): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), cis-regulatory region sequence-specific DNA binding (GO:0000987), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), metal ion binding (GO:0046872)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), transcription regulator complex (GO:0005667), PcG protein complex (GO:0031519)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
regulation of DNA-templated transcription	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
transcription cis-regulatory region binding	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transition metal ion binding	1
DNA binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
cation binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
protein-containing complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

570 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
YY2	CXCR4	P30991	438
YY2	CSF3	P09919	430
YY2	FOS	P01100	416
YY2	MBTPS2	O43462	394
YY2	MYC	P01106	366
YY2	EBLN2	Q6P2I7	339
YY2	SPDYE3	A6NKU9	323
YY2	SAP30	O75446	321
YY2	RYBP	Q8N488	320
YY2	RAX2	Q96IS3	313
YY2	YAF2	Q8IY57	309
YY2	GTSE1	Q9NYZ3	304
YY2	STAU1	O95793	290
YY2	PPARGC1A	Q9UBK2	289
YY2	CIMIP2A	Q6J272	284

IntAct

13 interactions, top by confidence:

A	B	Type	Score
YY1	YY2	psi-mi:“MI:0914”(association)	0.570
TP53	YY2	psi-mi:“MI:0915”(physical association)	0.400
TWIST1	YY2	psi-mi:“MI:0915”(physical association)	0.400
RRP1B	YY2	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
DHX9	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
YY1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (20): YY2 (Reconstituted Complex), YY2 (Reconstituted Complex), YY2 (Affinity Capture-MS), YY2 (Proximity Label-MS), YY2 (Proximity Label-MS), YY2 (Affinity Capture-MS), YY2 (Affinity Capture-MS), YY2 (Affinity Capture-MS), YY2 (Affinity Capture-MS), YY2 (Affinity Capture-MS), YY2 (Affinity Capture-MS), YY2 (Affinity Capture-MS), YY2 (Affinity Capture-MS), YY2 (Affinity Capture-MS), YY2 (Affinity Capture-MS)

ESM2 similar proteins: A6QQW0, B4F7E9, O15391, O43167, O62836, O70230, O70494, P08048, P15337, P17010, P17012, P18846, P20385, P25490, P27699, P36508, P52747, P79145, P81069, P81269, Q00420, Q00899, Q01147, Q01611, Q02447, Q03060, Q03061, Q06547, Q08DA8, Q0V8G2, Q1LYE3, Q1LZH5, Q1RMI3, Q4V8R6, Q52KB5, Q52V16, Q58DZ6, Q5XIU2, Q66K89, Q6B4Z5

Diamond homologs: A1L2U9, A2A884, A2ANX9, A7Y7X5, B0X9H6, B0YDH7, B1WAZ8, B1WBU4, E9PW05, E9PZZ1, G5EBU4, O15391, O60315, O62836, O75362, O77459, O95863, P08048, P0CS62, P0CS63, P10925, P15822, P17010, P17012, P20662, P22227, P25490, P28166, P31509, P31629, P36197, P52739, P52746, P56270, P56670, P56671, P60319, P80944, Q00899, Q00900

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
YY2	“up-regulates quantity by expression”	FOS	“transcriptional regulation”
YY2	“up-regulates quantity by expression”	TP53	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

230 predictions. Top by Δscore:

Variant	Effect	Δscore
X:21856446:C:CA	acceptor_gain	0.9700
X:21856496:CGA:C	acceptor_gain	0.9200
X:21856517:A:G	acceptor_gain	0.8600
X:21857534:G:GT	donor_gain	0.8600
X:21857677:GCTTT:G	donor_gain	0.8300
X:21857652:G:GG	donor_gain	0.7400
X:21857645:G:GT	donor_gain	0.7000
X:21856295:A:AG	acceptor_gain	0.6900
X:21856296:G:GG	acceptor_gain	0.6900
X:21857678:C:G	donor_gain	0.6900
X:21856498:A:C	acceptor_gain	0.6800
X:21856445:AC:A	acceptor_gain	0.6600
X:21856461:C:A	acceptor_gain	0.6400
X:21857656:GGAA:G	donor_gain	0.6200
X:21857631:G:T	donor_gain	0.6100
X:21857631:G:GT	donor_gain	0.5900
X:21857944:G:GT	donor_gain	0.5800
X:21856296:GCTC:G	acceptor_gain	0.5600
X:21857647:CTGCG:C	donor_loss	0.5600
X:21857648:TGCG:T	donor_loss	0.5600
X:21857650:CG:C	donor_loss	0.5600
X:21857651:GGT:G	donor_loss	0.5600
X:21857652:GTAGG:G	donor_loss	0.5600
X:21857653:TAG:T	donor_loss	0.5600
X:21857654:A:C	donor_loss	0.5600
X:21856293:G:GA	acceptor_gain	0.5500
X:21856331:G:GA	acceptor_gain	0.5500
X:21857655:G:GC	donor_loss	0.5500
X:21857656:G:C	donor_loss	0.5500
X:21856019:G:T	acceptor_gain	0.5400

AlphaMissense

2487 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:21857250:T:C	C256R	1.000
X:21857252:C:G	C256W	1.000
X:21857337:T:C	C285R	1.000
X:21857339:T:G	C285W	1.000
X:21857346:T:C	C288R	1.000
X:21857358:T:C	F292L	1.000
X:21857359:T:C	F292S	1.000
X:21857360:T:A	F292L	1.000
X:21857360:T:G	F292L	1.000
X:21857385:C:G	H301D	1.000
X:21857421:T:A	C313S	1.000
X:21857421:T:C	C313R	1.000
X:21857422:G:C	C313S	1.000
X:21857423:C:G	C313W	1.000
X:21857436:T:A	C318S	1.000
X:21857436:T:C	C318R	1.000
X:21857437:G:C	C318S	1.000
X:21857448:T:C	F322L	1.000
X:21857449:T:C	F322S	1.000
X:21857450:T:A	F322L	1.000
X:21857450:T:G	F322L	1.000
X:21857475:C:G	H331D	1.000
X:21857477:C:A	H331Q	1.000
X:21857477:C:G	H331Q	1.000
X:21857481:C:A	R333S	1.000
X:21857482:G:C	R333P	1.000
X:21857487:C:G	H335D	1.000
X:21857511:T:A	C343S	1.000
X:21857511:T:C	C343R	1.000
X:21857512:G:C	C343S	1.000

dbSNP variants (sampled 300 via entrez): RS1000154465 (X:21854777 G>A), RS1001196669 (X:21854646 C>A), RS1001731512 (X:21854090 A>C,T), RS1001966104 (X:21858429 T>G), RS1003815910 (X:21858521 G>A), RS1003866943 (X:21859179 T>A), RS1004045434 (X:21856137 A>C), RS1004823064 (X:21855535 G>A,C,T), RS1007833251 (X:21856556 C>T), RS1009951025 (X:21855154 C>G,T), RS1010501166 (X:21854716 A>G), RS1011735189 (X:21857570 A>G), RS1011789012 (X:21858146 T>G), RS1012122388 (X:21856104 T>C), RS1012506181 (X:21857675 A>G)

Disease associations

OMIM: gene MIM:300570 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
homosalate	affects cotreatment, increases expression	1
Decitabine	decreases methylation, increases expression	1
Paraoxon	increases expression	1
Polystyrenes	affects cotreatment, increases expression	1
Urethane	decreases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_XV84	HEK293 eGFP-YY2	Transformed cell line	Female

Clinical trials (associated diseases)

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