USF2

Summary

USF2 (upstream transcription factor 2, c-fos interacting, HGNC:12594) is a protein-coding gene on chromosome 19q13.12, encoding Upstream stimulatory factor 2 (Q15853). Transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5’-CACGTG-3’) that is found in a variety of viral and cellular promoters. It is a selective cancer dependency (DepMap: 20.4% of cell lines).

This gene encodes a member of the basic helix-loop-helix leucine zipper family of transcription factors. The encoded protein can activate transcription through pyrimidine-rich initiator (Inr) elements and E-box motifs and is involved in regulating multiple cellular processes.

Source: NCBI Gene 7392 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 48 total
• Cancer dependency (DepMap): dependent in 20.4% of screened cell lines
• Transcription factor: yes — 124 downstream targets (CollecTRI)
• MANE Select transcript: NM_003367

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12594
Approved symbol	USF2
Name	upstream transcription factor 2, c-fos interacting
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	FIP, bHLHb12
Ensembl gene	ENSG00000105698
Ensembl biotype	protein_coding
OMIM	600390
Entrez	7392

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 10 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000222305, ENST00000343550, ENST00000379134, ENST00000593708, ENST00000594064, ENST00000594264, ENST00000595068, ENST00000596380, ENST00000597671, ENST00000598058, ENST00000599471, ENST00000599625, ENST00000600341, ENST00000600898, ENST00000602164, ENST00000607959, ENST00000886191

RefSeq mRNA: 3 — MANE Select: NM_003367 NM_001321150, NM_003367, NM_207291

CCDS: CCDS12452, CCDS12453, CCDS82329

Canonical transcript exons

ENST00000222305 — 10 exons

Exon	Start	End
ENSE00000700282	35270447	35270597
ENSE00000700284	35269581	35269699
ENSE00003188698	35279167	35279821
ENSE00003468240	35270718	35270805
ENSE00003515656	35269803	35270003
ENSE00003519034	35278698	35278792
ENSE00003557226	35269446	35269492
ENSE00003607749	35271083	35271141
ENSE00003692874	35278946	35279074
ENSE00003849794	35268962	35269163

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 57.7311 / max 443.2297, expressed in 1828 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175268	41.4587	1824
175266	5.2675	1680
175269	5.2585	1712
175267	4.9735	1720
175265	0.3344	136
175270	0.3331	133
175271	0.1055	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.16	gold quality
apex of heart	UBERON:0002098	99.04	gold quality
cerebellar hemisphere	UBERON:0002245	99.03	gold quality
cortical plate	UBERON:0005343	99.03	gold quality
cerebellar cortex	UBERON:0002129	98.99	gold quality
right frontal lobe	UBERON:0002810	98.92	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.85	gold quality
ganglionic eminence	UBERON:0004023	98.83	gold quality
left ovary	UBERON:0002119	98.79	gold quality
adenohypophysis	UBERON:0002196	98.75	gold quality
right ovary	UBERON:0002118	98.70	gold quality
right lobe of thyroid gland	UBERON:0001119	98.64	gold quality
ventricular zone	UBERON:0003053	98.62	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.53	gold quality
tibial nerve	UBERON:0001323	98.51	gold quality
nucleus accumbens	UBERON:0001882	98.51	gold quality
left lobe of thyroid gland	UBERON:0001120	98.50	gold quality
right atrium auricular region	UBERON:0006631	98.49	gold quality
prefrontal cortex	UBERON:0000451	98.46	gold quality
amygdala	UBERON:0001876	98.46	gold quality
type B pancreatic cell	CL:0000169	98.43	gold quality
putamen	UBERON:0001874	98.40	gold quality
skin of leg	UBERON:0001511	98.38	gold quality
granulocyte	CL:0000094	98.37	gold quality
olfactory bulb	UBERON:0002264	98.34	gold quality
gastrocnemius	UBERON:0001388	98.32	gold quality
skin of abdomen	UBERON:0001416	98.30	gold quality
monocyte	CL:0000576	98.27	gold quality
caudate nucleus	UBERON:0001873	98.26	gold quality
body of uterus	UBERON:0009853	98.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.13

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

124 targets.

Target	Regulation
ABCA1	Activation
ACACA
AGT	Unknown
AGTRAP
AIRN
ALB
ALX3	Unknown
APC	Activation
APOA2	Unknown
APOA5	Activation
APOC3
AR
ASCL2	Repression
ASPH	Unknown
ATP5F1A	Activation
AVP	Activation
B2M	Activation
BRCA1	Unknown
BRCA2	Unknown
CALCA	Activation
CBLIF
CCND2	Repression
CD2	Activation
CD40
CD40LG	Activation
CDK4
CEACAM1	Activation
CEACAM5	Activation
CEBPA	Unknown
CFTR	Unknown

JASPAR motifs

Motif	Name	Family
MA0526.1	USF2	bHLH-ZIP
MA0526.2	USF2	bHLH-ZIP
MA0526.3	USF2	bHLH-ZIP
MA0526.4	USF2	bHLH-ZIP
MA0526.5	USF2	bHLH-ZIP

JASPAR matrix evidence (PMIDs): PMID:8943301, PMID:28473536

Upstream regulators (CollecTRI, top): CREB1, EPAS1, HOXB6, NFKB, SP1, USF1, USF2

miRNA regulators (miRDB)

53 targeting USF2, 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-7110-3P	100.00	73.18	2486
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-642A-5P	99.51	65.10	1152

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 20.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Unregulated activation of STAT-5, ERK1/2 and c-Fos may contribute to the phenotypic transformation from myelodysplastic syndrome to acute leukaemia. Impaired ERK1/2 signalling pathways were activated only by GM-CSF but not by Epo. (PMID:11583024)
• requirement of carboxy ester lipase gene E-box for activation binds upstream regulatory factor 1 and 2 (PMID:11945176)
• Cooperative E-box regulation of human GLI1 by TWIST and this protein (PMID:11948912)
• transfection of expression vectors containing USF-1 or USF-2 cDNAs activated CYP1A2 reporter gene activity, while a dominant-negative USF-2 expression vector blocked such activity. (PMID:12663044)
• defect in USF function may contribute to down-regulation of IGF2R expression in cancer cells. (PMID:12857727)
• These findings suggest that increased protein levels and DNA binding of USF1 and USF2 mediate the inhibitory effects of hypoxia and of Mash-2 on CYP19 gene expression in human placenta (PMID:12917334)
• USF1/2 activates the hTERT promoter exclusively in hTERT-positive cells in a manner that is enhanced by the coactivator p300 and attenuated upon inhibiting p38-MAP kinase, a known modulator of USF activity. (PMID:12970752)
• USF1 and 2 transactivate rat and human PF4 promoters and may play an important role in megakaryocytic gene expression (PMID:15187018)
• results demonstrate for the first time that USF proteins bind to the human HO-1 promoter in vivo and are required for high-level expression of HO-1 by haem and cadmium in human renal epithelial cells (PMID:15242350)
• Cotransfection experiments demonstrated that overexpression of upstream stimulatory factor 2 increases cyclic GMP-dependent protein kinase I promoter activity in human vascular smooth muscle cells. (PMID:15741164)
• These results demonstrate that USF1/USF2 and TFII-I interact cooperatively at the upstream RBEIII element and are necessary for the induction of latent HIV-1 in response to T-cell activation signals. (PMID:15767439)
• USF1 and USF2 mRNA levels were reduced in non-small cell lung carcinoma; AP2-alpha levels were elevated; regression analysis demonstrated that reduced USF2 mRNA & increased AP2-alpha mRNA levels were predictive of downregulated PIGR mRNA expressions (PMID:15864740)
• early in gestation when the placenta is relatively hypoxic, increased USF1/2 may block trophoblast differentiation and CYP19 gene expression (PMID:16199862)
• USF transcription factors have thus been involved as key regulators of a wide number of gene regulation network including stress and immune response, cell cycle and proliferation. (review) (PMID:16386222)
• Overexpression of USF-1 and USF-2 significantly suppressed TSH-stimulated thymidine uptake while maintaining TSH-stimulated cAMP production in FRTL-5 cells. Significantly suppressed BrdU uptake in carcinoma cells. (PMID:17379962)
• study reports a methylation-dependent upstream stimulatory factor (USF) binding site influencing the basal and insulin-stimulated transcriptional activity of the IGFBP3 promoter (PMID:17823260)
• Data show that the elevated levels of USF2 in endometriosis account for, in part, the aberrant expression of SF-1 and its target gene StAR and aromatase. (PMID:18165439)
• USF1 and USF2 are important contributors to neuronal-specific and mitogen-activated protein kinase regulation of the CGRP gene in trigeminal ganglion neurons (PMID:18167349)
• both USF1 and USF2 bind to an E-box sequence located in the OCT1 core promoter region and are required for the basal gene expression of this transporter. (PMID:18845576)
• down-regulation of hsa-miR-10a may increase USF2 and contribute to the increase in cell proliferation of chronic myeloid leukemia implicating a miRNA in its abnormal behavior (PMID:19074828)
• USF1 and USF2 positively regulate the core of P1 promoter od AAH. (PMID:19087304)
• decreased expression of the Hint1 gene through epigenetic silencing may play a role in enhancing the growth of a subset of human hepatoma by increasing the expression of genes controlled by the transcription factors beta-catenin, USF2, and NFkappaB (PMID:19089909)
• USF1 and USF2 regulate transcriptional activity of the FOXE1 promoter. (PMID:19730683)
• Ddata indicate that USF2 is one of the components of the FoxA1/androgen receptor transcriptional protein complex that contributes to the expression of androgen-regulated and prostate-specific genes. (PMID:19846536)
• This study demonstrated the involvement of USF1 and USF2 as molecular targets of Helicobacter pylori and the key role of DNA methylation in their regulation. (PMID:20180799)
• Usf2 mediates quercetin-induced suppression of PAI-1 gene expression in human endothelial cells (PMID:20626032)
• data established that high glucose stimulated USF2 expression in HK-2 cells, at least in part, through angiotensin II-AT1-dependent activation of CREB, which can contribute to diabetic tubulointerstitial fibrosis (PMID:20814220)
• These data indicate that an E-box motif (RBE1) within the core promoter in the long terminal repeat of HIV-1 is a bona fide binding site for the RBF-2 transcription factor complex USF1, USF2, and TFII-I. (PMID:21813151)
• Bone morphogenetic proteins and ID1 exerted an anti-apoptotic effect in mesangial cells by inhibition of USF2 transcriptional activity. (PMID:21921026)
• Transcription factors upstream stimulatory factor 1 (USF-1) and USF-2 are indispensable for the transcription of RORgammaT in human lymphocytes. (PMID:22891280)
• USF2 and hypoxia-inducible factor 2alpha (HIF2alpha) cooperatively activate HIF2 target genes during hypoxia. (PMID:22966206)
• USF2 functionally interacts with YY1 blocking its inhibitory activity, in favor of CEBPB transactivation. (PMID:23560079)
• RNA Pol II on HIF1 or HIF2 target genes is primarily associated with HIF1alpha or HIF2alpha in a STAT3 or USF2 dependent manner (PMID:23991099)
• USF2, and its target gene PAI-1, regulate serum-stimulated keratinocyte growth, and likely the cadence of cell cycle progression in replicatively competent cells as part of the injury repair program. (PMID:24905330)
• Increased upstream stimulatory factor in HCC is associated with heparanase expression. USF might be an important factor in regulating HPSE expression and act as a novel marker of metastatic recurrence of HCC patients (PMID:25149140)
• PLAG1 and USF2 cooperation is thus an important contributor to stem cell-specific expression of MSI2 and hematopoietic stem and progenitor cell-specific transcriptional circuitry. (PMID:29641991)
• TCF21 modulates Steroidogenic factor-1 and estrogen receptor beta expression through the recruitment of USF2 in endometriotic stromal cells. (PMID:30018006)
• This study reported that USF2 (upstream stimulatory factor 2), a basic helix-loop-helix-leucine-zip transcription factor, is necessary for the transcriptional activity of Smurf1 and Smurf2. (PMID:30244169)
• USF2 and ATF4 were upregulated in the osteogenic differentiation of periodontal ligament cells (PMID:31448831)
• Irrelevance of USF2 rs916145 polymorphism with the risk of biliary atresia susceptibility in Southern Chinese children. (PMID:32109289)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	usf2	ENSDARG00000020228
mus_musculus	Usf2	ENSMUSG00000058239
rattus_norvegicus	Usf2	ENSRNOG00000053725

Paralogs (3): SREBF1 (ENSG00000072310), USF1 (ENSG00000158773), SREBF2 (ENSG00000198911)

Protein

Protein identifiers

Upstream stimulatory factor 2 — Q15853 (reviewed: Q15853)

Alternative names: Class B basic helix-loop-helix protein 12, FOS-interacting protein, Major late transcription factor 2, Upstream transcription factor 2

All UniProt accessions (8): Q15853, B4DLJ1, M0QXT0, M0QY46, M0QYU7, M0QZ39, M0R1C6, V9GYR5

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5’-CACGTG-3’) that is found in a variety of viral and cellular promoters.

Subunit / interactions. Interacts with MAF. Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a homodimer or a heterodimer (USF1/USF2). In vivo, the USF1/USF2A heterodimer represents over 66% of the usf binding activity whereas the USF1 and USF2A homodimers represent less than 10%. The USF1/USF2B heterodimer accounted for almost 15% in some cell.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous.

Miscellaneous. Can bind as a homodimer to the E-box of the cathepsin B (CTSB) promoter.

Isoforms (4)

UniProt ID	Names	Canonical?
Q15853-1	USF2A	yes
Q15853-2	USF2A-delta-H
Q15853-3	USF2B
Q15853-4	USF2c

RefSeq proteins (3): NP_001308079, NP_003358, NP_997174 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR051732	USF	Family

Pfam: PF00010

UniProt features (21 total): sequence conflict 4, turn 4, helix 3, region of interest 3, splice variant 3, compositionally biased region 2, chain 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8IA3	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15853-F1	60.69	0.29

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9018519	Estrogen-dependent gene expression

MSigDB gene sets: 176 (showing top): TGCGCANK_UNKNOWN, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GGGTGGRR_PAX4_03, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, TANG_SENESCENCE_TP53_TARGETS_UP, NKX61_01, GOBP_LIPID_HOMEOSTASIS, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_SECRETION, HOSHIDA_LIVER_CANCER_LATE_RECURRENCE_DN, GOBP_MAMMARY_GLAND_DEVELOPMENT, GGCKCATGS_UNKNOWN, HIF1_Q3, GOBP_INTRACELLULAR_GLUCOSE_HOMEOSTASIS

GO Biological Process (10): positive regulation of transcription from RNA polymerase II promoter by glucose (GO:0000432), regulation of transcription by RNA polymerase II (GO:0006357), lactation (GO:0007595), glucose mediated signaling pathway (GO:0010255), late viral transcription (GO:0019086), positive regulation of transcription by RNA polymerase II (GO:0045944), lipid homeostasis (GO:0055088), cellular response to glucose stimulus (GO:0071333), regulation of transcription from RNA polymerase II promoter by glucose (GO:0000430), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (13): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), protein homodimerization activity (GO:0042803), bHLH transcription factor binding (GO:0043425), protein heterodimerization activity (GO:0046982), E-box binding (GO:0070888), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), protein dimerization activity (GO:0046983)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
ESR-mediated signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	3
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
protein dimerization activity	2
cellular anatomical structure	2
regulation of transcription from RNA polymerase II promoter by glucose	1
carbon catabolite activation of transcription from RNA polymerase II promoter	1
positive regulation of transcription by glucose	1
body fluid secretion	1
mammary gland development	1
milk ejection reflex	1
hexose mediated signaling	1
cellular response to glucose stimulus	1
viral transcription	1
positive regulation of DNA-templated transcription	1
chemical homeostasis	1
intracellular glucose homeostasis	1
response to glucose	1
cellular response to hexose stimulus	1
carbon catabolite regulation of transcription from RNA polymerase II promoter	1
regulation of transcription by glucose	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	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
transcription cis-regulatory region binding	1
transcription regulator activity	1
identical protein binding	1
DNA-binding transcription factor binding	1
RNA polymerase II cis-regulatory region sequence-specific DNA binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
DNA binding	1

Protein interactions and networks

STRING

1390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USF2	USF1	P22415	982
USF2	BRCA1	P38398	703
USF2	CDC5L	Q99459	689
USF2	FASN	P49327	685
USF2	MYC	P01106	671
USF2	RFX5	P48382	670
USF2	NFYB	P25208	634
USF2	GTF2I	P78347	632
USF2	TBP	P20226	629
USF2	E2F1	Q01094	588
USF2	KARS1	Q15046	587
USF2	STAT3	P40763	579
USF2	FOSL1	P15407	562
USF2	TERT	O14746	560
USF2	EPC1	Q9H2F5	549

IntAct

60 interactions, top by confidence:

A	B	Type	Score
USF2	TEAD2	psi-mi:“MI:0915”(physical association)	0.560
USF2	FOS	psi-mi:“MI:0915”(physical association)	0.560
USF2	LZTS2	psi-mi:“MI:0915”(physical association)	0.560
TEAD2	USF2	psi-mi:“MI:0915”(physical association)	0.560
FOS	USF2	psi-mi:“MI:0915”(physical association)	0.560
LZTS2	USF2	psi-mi:“MI:0915”(physical association)	0.560
USF1	PARP1	psi-mi:“MI:0914”(association)	0.560
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
FOSL2	ZZEF1	psi-mi:“MI:0914”(association)	0.530
USF1	FHL2	psi-mi:“MI:0914”(association)	0.530
	USF1	psi-mi:“MI:0915”(physical association)	0.520
USF2		psi-mi:“MI:0915”(physical association)	0.400
	USF2	psi-mi:“MI:0915”(physical association)	0.400
USF2	CDC42	psi-mi:“MI:0915”(physical association)	0.370
USF2		psi-mi:“MI:0915”(physical association)	0.370
CCL3L1	USF2	psi-mi:“MI:0915”(physical association)	0.370
XCL1	USF2	psi-mi:“MI:0915”(physical association)	0.370
USF2	ENTREP1	psi-mi:“MI:0915”(physical association)	0.370
	USF2	psi-mi:“MI:0914”(association)	0.350
FOXJ2	TCERG1	psi-mi:“MI:0914”(association)	0.350
	ARID1A	psi-mi:“MI:0914”(association)	0.350
PHAX	FLNB	psi-mi:“MI:0914”(association)	0.350
CALML3	MYO1C	psi-mi:“MI:0914”(association)	0.350

BioGRID (75): USF2 (Two-hybrid), TEAD2 (Two-hybrid), LZTS2 (Two-hybrid), USF2 (Affinity Capture-MS), USF2 (Affinity Capture-MS), USF2 (Reconstituted Complex), PPARGC1A (Affinity Capture-Western), USF2 (Affinity Capture-MS), USF2 (Affinity Capture-MS), USF2 (Affinity Capture-MS), USF2 (Affinity Capture-MS), USF2 (Affinity Capture-MS), USF2 (Affinity Capture-MS), USF2 (Affinity Capture-MS), USF1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I6G705, A6QNT8, B5DFF2, D4A055, O00305, O14639, O16011, O19048, O95319, O95486, P56223, P60335, P60762, Q08DJ0, Q12800, Q13330, Q15365, Q15853, Q16514, Q3T174, Q4V860, Q5E9A3, Q5R8Y8, Q62599, Q63665, Q64705, Q68G74, Q6DH13, Q6NZH6, Q6P0B1, Q6ZRY4, Q792H5, Q7T2T1, Q7T2U9, Q86SE5, Q8K4B0, Q8K4G5, Q8K4Q0, Q8N122, Q8R0S4

Diamond homologs: A0A286LEZ9, A3KNA7, G5EEH5, H2KZZ2, O02818, O75030, O88368, O97676, P0DPB0, P22415, P28574, P36956, P49379, P52161, P52162, P52164, P56720, P61244, P61245, P91664, Q07016, Q07956, Q07957, Q08874, Q10186, Q15853, Q3T1I5, Q3U1N2, Q60416, Q60429, Q61069, Q63665, Q64705, Q6GQ26, Q6XBT4, Q9WTN3, Q12772, A1YG22, A2T7L5, B0XU60

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
USF2	“up-regulates quantity by expression”	MYH9	“transcriptional regulation”
USF2	“up-regulates quantity by expression”	B2M	“transcriptional regulation”
USF2	“up-regulates quantity by expression”	FMR1	“transcriptional regulation”
USF2	“up-regulates quantity by expression”	CTSD	“transcriptional regulation”
GTF2I	“up-regulates activity”	USF2	binding
GSK3B	“up-regulates activity”	USF2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1292 predictions. Top by Δscore:

Variant	Effect	Δscore
19:35269163:GGTA:G	donor_loss	1.0000
19:35269164:GT:G	donor_loss	1.0000
19:35269165:T:A	donor_loss	1.0000
19:35269434:T:TA	acceptor_gain	1.0000
19:35269440:T:A	acceptor_gain	1.0000
19:35269441:G:A	acceptor_gain	1.0000
19:35269444:A:AG	acceptor_gain	1.0000
19:35269445:G:GG	acceptor_gain	1.0000
19:35269488:GGAAG:G	donor_gain	1.0000
19:35269489:G:GT	donor_gain	1.0000
19:35269489:GAAG:G	donor_gain	1.0000
19:35269489:GAAGG:G	donor_loss	1.0000
19:35269490:A:T	donor_gain	1.0000
19:35269490:AAGGT:A	donor_loss	1.0000
19:35269491:AGGT:A	donor_loss	1.0000
19:35269492:GGT:G	donor_loss	1.0000
19:35269493:G:GG	donor_gain	1.0000
19:35269572:C:CA	acceptor_gain	1.0000
19:35269573:G:A	acceptor_gain	1.0000
19:35269577:CCAGG:C	acceptor_loss	1.0000
19:35269578:CAGGC:C	acceptor_loss	1.0000
19:35269579:A:AG	acceptor_gain	1.0000
19:35269579:AGGC:A	acceptor_gain	1.0000
19:35269579:AGGCG:A	acceptor_gain	1.0000
19:35269580:G:GT	acceptor_gain	1.0000
19:35269580:GGC:G	acceptor_gain	1.0000
19:35269580:GGCG:G	acceptor_gain	1.0000
19:35269580:GGCGG:G	acceptor_gain	1.0000
19:35269695:GACAG:G	donor_gain	1.0000
19:35269698:AGGTG:A	donor_loss	1.0000

AlphaMissense

2254 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:35269667:T:G	Y66D	1.000
19:35269674:T:C	F68S	1.000
19:35269809:T:G	Y79D	1.000
19:35270730:T:A	V198D	1.000
19:35271111:G:C	D233H	1.000
19:35271121:G:C	R236T	1.000
19:35271121:G:T	R236I	1.000
19:35271122:A:C	R236S	1.000
19:35271122:A:T	R236S	1.000
19:35271123:A:G	R237G	1.000
19:35271124:G:C	R237T	1.000
19:35271124:G:T	R237I	1.000
19:35271125:A:C	R237S	1.000
19:35271125:A:T	R237S	1.000
19:35271126:G:C	A238P	1.000
19:35271127:C:A	A238D	1.000
19:35271132:C:A	H240N	1.000
19:35271132:C:G	H240D	1.000
19:35271132:C:T	H240Y	1.000
19:35271133:A:C	H240P	1.000
19:35271133:A:G	H240R	1.000
19:35271133:A:T	H240L	1.000
19:35271134:C:A	H240Q	1.000
19:35271134:C:G	H240Q	1.000
19:35271135:A:C	N241H	1.000
19:35271135:A:G	N241D	1.000
19:35271136:A:T	N241I	1.000
19:35271137:C:A	N241K	1.000
19:35271137:C:G	N241K	1.000
19:35271138:G:A	E242K	1.000

dbSNP variants (sampled 300 via entrez): RS1000119262 (19:35271558 C>T), RS1000208206 (19:35274573 G>A), RS1000429501 (19:35279626 C>T), RS1001129625 (19:35275780 C>T), RS1001157102 (19:35273812 A>T), RS1001248262 (19:35275459 T>C), RS1001293409 (19:35275361 T>C), RS1001836306 (19:35278346 A>G), RS1002419471 (19:35277161 C>T), RS1002755376 (19:35275179 T>C), RS1002796857 (19:35277358 C>G,T), RS1003262252 (19:35277788 G>A), RS1003366245 (19:35274020 C>T), RS1003845902 (19:35276041 C>G,T), RS1004285241 (19:35272997 C>G)

Disease associations

OMIM: gene MIM:600390 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004602_275	Mean corpuscular volume	5.000000e-09
GCST004621_164	Red cell distribution width	4.000000e-09
GCST004630_68	Mean corpuscular hemoglobin	2.000000e-12
GCST006804_186	Red cell distribution width	2.000000e-08
GCST009028_2	Adverse response to drug	2.000000e-07
GCST90002392_72	Mean corpuscular volume	3.000000e-15
GCST90002404_527	Red cell distribution width	2.000000e-18

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0004527	mean corpuscular hemoglobin
EFO:0009658	adverse effect

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	3
Arsenic Trioxide	decreases expression, increases methylation	2
FR900359	decreases phosphorylation	1
PF-06840003	decreases expression, decreases reaction	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
potassium perchlorate	decreases expression	1
trichostatin A	affects expression	1
cobaltous chloride	affects binding, affects reaction, increases expression	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Arsenic	increases abundance, increases expression	1
Oxygen	affects binding, increases expression, increases reaction	1
Plant Extracts	decreases expression, affects cotreatment	1
Selenium	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases expression, increases methylation	1
Vitamin E	affects cotreatment, increases expression	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A7S7	SEES3-1V human USF2, clone1	Embryonic stem cell	Male
CVCL_A7S8	SEES3-1V human USF2, clone2	Embryonic stem cell	Male
CVCL_A7S9	SEES3-1V human USF2, clone3	Embryonic stem cell	Male
CVCL_GZ95	K562 eGFP-USF2	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer