FUBP1

Summary

FUBP1 (far upstream element binding protein 1, HGNC:4004) is a protein-coding gene on chromosome 1p31.1, encoding Far upstream element-binding protein 1 (Q96AE4). Regulates MYC expression by binding to a single-stranded far-upstream element (FUSE) upstream of the MYC promoter.

The protein encoded by this gene is a single stranded DNA-binding protein that binds to multiple DNA elements, including the far upstream element (FUSE) located upstream of c-myc. Binding to FUSE occurs on the non-coding strand, and is important to the regulation of c-myc in undifferentiated cells. This protein contains three domains, an amphipathic helix N-terminal domain, a DNA-binding central domain, and a C-terminal transactivation domain that contains three tyrosine-rich motifs. The N-terminal domain is thought to repress the activity of the C-terminal domain. This protein is also thought to bind RNA, and contains 3’-5’ helicase activity with in vitro activity on both DNA-DNA and RNA-RNA duplexes. Aberrant expression of this gene has been found in malignant tissues, and this gene is important to neural system and lung development. Binding of this protein to viral RNA is thought to play a role in several viral diseases, including hepatitis C and hand, foot and mouth disease. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 8880 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 87 total
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• Transcription factor: yes — 17 downstream targets (CollecTRI)
• MANE Select transcript: NM_003902

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4004
Approved symbol	FUBP1
Name	far upstream element binding protein 1
Location	1p31.1
Locus type	gene with protein product
Status	Approved
Aliases	FBP
Ensembl gene	ENSG00000162613
Ensembl biotype	protein_coding
OMIM	603444
Entrez	8880

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 24 protein_coding, 9 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000294623, ENST00000370767, ENST00000370768, ENST00000421641, ENST00000470287, ENST00000474632, ENST00000480673, ENST00000483894, ENST00000487684, ENST00000488814, ENST00000489495, ENST00000492405, ENST00000492724, ENST00000703586, ENST00000703600, ENST00000867290, ENST00000867291, ENST00000867292, ENST00000867293, ENST00000867294, ENST00000867295, ENST00000867296, ENST00000867297, ENST00000867298, ENST00000867299, ENST00000939330, ENST00000939331, ENST00000939332, ENST00000939333, ENST00000939334, ENST00000957402, ENST00000957403, ENST00000957404, ENST00000957405

RefSeq mRNA: 6 — MANE Select: NM_003902 NM_001303433, NM_001376055, NM_001376056, NM_001376057, NM_001410804, NM_003902

CCDS: CCDS683, CCDS90982, CCDS90984

Canonical transcript exons

ENST00000370768 — 20 exons

Exon	Start	End
ENSE00001066870	77960344	77960495
ENSE00001066871	77969925	77970015
ENSE00001066872	77964646	77964747
ENSE00001066874	77966694	77966751
ENSE00001066879	77967627	77967666
ENSE00001066882	77968165	77968203
ENSE00001066883	77964254	77964356
ENSE00001066884	77964062	77964162
ENSE00001066887	77966884	77966955
ENSE00001066888	77964870	77964968
ENSE00001349606	77967049	77967101
ENSE00001435529	77963574	77963715
ENSE00001435707	77962770	77962930
ENSE00001815368	77978885	77979072
ENSE00001916670	77944055	77948774
ENSE00003535032	77955255	77955329
ENSE00003535266	77949155	77949300
ENSE00003643737	77960184	77960263
ENSE00003676466	77956572	77956700
ENSE00003787203	77965069	77965231

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 98.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 133.4174 / max 1896.6405, expressed in 1825 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12908	111.1538	1824
12909	18.5312	1792
12907	2.3236	1103
12912	0.5596	316
12911	0.3409	136
12910	0.2621	129
12905	0.2461	97

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.51	gold quality
ganglionic eminence	UBERON:0004023	98.33	gold quality
calcaneal tendon	UBERON:0003701	98.20	gold quality
cortical plate	UBERON:0005343	98.06	gold quality
left ovary	UBERON:0002119	97.88	gold quality
right uterine tube	UBERON:0001302	97.75	gold quality
right ovary	UBERON:0002118	97.68	gold quality
body of uterus	UBERON:0009853	97.35	gold quality
left lobe of thyroid gland	UBERON:0001120	97.22	gold quality
right lobe of thyroid gland	UBERON:0001119	97.18	gold quality
endocervix	UBERON:0000458	97.08	gold quality
embryo	UBERON:0000922	97.04	gold quality
lymph node	UBERON:0000029	97.03	gold quality
thyroid gland	UBERON:0002046	97.03	gold quality
nerve	UBERON:0001021	97.00	gold quality
tibial nerve	UBERON:0001323	97.00	gold quality
ovary	UBERON:0000992	96.91	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.84	gold quality
adenohypophysis	UBERON:0002196	96.82	gold quality
cerebellar hemisphere	UBERON:0002245	96.79	gold quality
adrenal tissue	UBERON:0018303	96.78	gold quality
cerebellar cortex	UBERON:0002129	96.70	gold quality
right lung	UBERON:0002167	96.60	gold quality
ectocervix	UBERON:0012249	96.47	gold quality
pituitary gland	UBERON:0000007	96.42	gold quality
rectum	UBERON:0001052	96.39	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.26	gold quality
tibial artery	UBERON:0007610	96.25	gold quality
popliteal artery	UBERON:0002250	96.24	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.16	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-10	no	371.75
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

17 targets.

Target	Regulation
BIK	Repression
CCND2	Activation
CD74
CDKN1A	Unknown
CDKN2B	Repression
ERCC3
ERVW-4
FUSE
GAP43
GNAS
KIT	Activation
MYC	Unknown
NOS2
PMAIP1	Repression
TNF	Repression
TNFSF10	Repression
USP29

Upstream regulators (CollecTRI, top): STAT5A, STAT5B, TAL1

miRNA regulators (miRDB)

69 targeting FUBP1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-579-3P	99.86	71.66	3628
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220

Literature-anchored findings (GeneRIF, showing 40)

• Results describe the roles of the FarUpStream Element (FUSE), FUSE Binding Protein (FBP), FBP Interacting Repressor (FIR), and TFIIH in the regulation of c-myc expression. (PMID:16628215)
• FUBP1 is an authentic substrate of Parkin that might play an important role in development of Parkinson disease pathology along with aminoacyl-tRNA synthetase interacting multifunctional protein type 2 (PMID:16672220)
• The over-expression of a novel protein family, far upstream binding proteins (FUBPs) was identified in both stages of hepatocellular carcinoma and confirmed by western blots. (PMID:19003864)
• investigate the contributions of FBP’s 4 K Homology (KH) domains to sequence selectivity. EMSA and missing contact point analysis revealed that FBP contacts 4 separate patches spanning a large segment of FUSE (PMID:19015535)
• study found that FBP1 as well as FBP3 are more frequently expressed in prostate and bladder cancer than in renal cancer; in addition, a positive correlation between levels of FBP1, FBP3 and c-Myc was exclusively detectable in renal cell carcinomas (PMID:19087307)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• oncogenic potential of c-Myc is ‘switched off’ after apoptosis induction as a consequence of the caspase-mediated cleavage of FBP-1. (PMID:19219071)
• The coordinated activation of FBP-1 and FBP-2 represents a novel and frequent pro-tumorigenic mechanism promoting proliferation (tumor growth) and motility (dissemination) of human liver cancer cells. (PMID:19585652)
• FBP1 is an important oncoprotein overexpressed in hepatocellular carcinoma that induces tumor propagation through direct or indirect repression of cell cycle inhibitors and proapoptotic target genes. (PMID:19637194)
• The noncoding strand FUSE recruits an activator FUSE-binding protein (FBP) and a repressor FBP-interacting repressor (FIR) to fine-tune c-myc transcription. (PMID:20420426)
• Authors propose that FBP1 is a key regulator of cell growth and proliferation through its ability to selectively bind the NPM 3’ UTR and repress NPM translation. (PMID:20802533)
• The authors suggest that FUSE binding protein 1 binds with the Japanese encephalitis virus untranslated RNA and functions as a host anti-virus defense molecule by repressing viral protein expression. (PMID:21367899)
• increased polyubiquitination of FBP1 does not alter its protein stability, but instead modulates the stable recruitment of FBP1 to target loci (PMID:21779003)
• CIC gene was mutated in 6 oligodendrogliomas and FUBP1 gene was mutated in 2; 27 additional oligodendrogliomas showed 12 and 3 more tumors with mutations of CIC and FUBP1; results suggest role of these genes in biology and pathology of oligodendrocytes (PMID:21817013)
• The central domain of FBP1, containing four K homology motifs, was required for p27 5’-UTR RNA binding and the N terminal domain was important for translational activation. (PMID:21855647)
• Found CIC and FUBP1 mutations in oligodendrogliomas and demonstrate the presence of these mutations in oligoastrocytomas. (PMID:22588899)
• Analysis allowed us to define two highly recurrent genetic signatures in gliomas: IDH1/ATRX (I-A) and IDH1/CIC/FUBP1 (I-CF). (PMID:22869205)
• biochemical features of FBP1 (PMID:22926519)
• Far upstream element-binding protein 1 and RNA secondary structure both mediate second-step splicing repression. (PMID:23818605)
• We conclude that absent CIC and FUBP1 expressions are potential markers of shorter time to recurrence in oligodendroglial tumors. (PMID:24030748)
• The data indicates an association between FUBP1 expression and proliferation in gliomas. (PMID:24117486)
• FUBP1 expression differs among gastric tissues; there is a correlation between overall survival rates and age, sex, lymph node metastasis, and distant metastasis. (PMID:24192769)
• High FBP1 expression was observed in glioma. (PMID:24347226)
• These findings are the first report describing the regulation of alternative splicing of MDM2 mediated by the oncogenic factor FUBP1. (PMID:24798327)
• Apoptosis-mediated cleavage of FBP1 and its decreased expression in epithelial cells induces cell cycle arrest, which may play an important role in colonic epithelial disruption in colitis. (PMID:24966911)
• FBP1 promotes hepatitis C virus eplication by inhibiting p53 expression. (PMID:25995247)
• Concomitant overexpression of far upstream element (FUSE) binding protein (FBP) interacting repressor (FIR) and its splice variants induce migration and invasion of non-small cell lung cancer cells. (PMID:26177862)
• FUBP1 may potentially stimulate c-Myc expression in ESCC and its expression may promote esophageal squamous cell carcinoma progression. (PMID:26490982)
• With the advent of large-scale genome sequencing technology, molecular genetic alterations in FUBP1 promoter have now been identified in the majority of oligodendrogliomas (PMID:26545048)
• direct connection between the cellular PI3K/AKT/mTOR signaling pathway, frequently activated in human hepatocarcinogenesis, and the enrichment of oncogenic transcription factors of the FBP family (PMID:26901106)
• we identified cyclin J and far upstream element-binding protein 1 (FUBP1) as novel miR-16 targets, which mediate miR-16 antiproliferative effects. (PMID:27157613)
• FBP1 expression in Bcell lymphoma was also associated with poor survival outcomes. Functionally, small interfering RNAmediated silencing of FBP1 was able to inhibit the proliferation of Bcell lymphoma cells, resulting in G0/G1 phase cell cycle arrest. (PMID:27599538)
• FUBP1 acts as a potential oncogene in clear cell renal cell carcinoma (ccRCC) and may be considered as a novel biomarker or an attractive treatment target of ccRCC. (PMID:28076379)
• High FUBP1 expression is associated with low Chemosensitivity to Adriamycin in Gastric Cancer. (PMID:28667493)
• The findings demonstrate an association between FUBP1 levels and chordoma progression and prognosis, suggesting that FUBP1 can be used as a biomarker and a potential therapeutic target. (PMID:28780352)
• These results suggest that the interference with the FUBP1/FUSE interaction as a further molecular mechanism that, in addition to the inactivation of TOP1, may contribute to the therapeutic potential of camptothecin/SN-38. (PMID:29031818)
• Low FUBP1 expression is associated with adenovirus infection. (PMID:29743362)
• FUBP1 promotes tumor cell proliferation and migration and regulates the cancer cell immunity by increasing the PD-L1 expression mediated by Myc in pancreatic cancer cells. (PMID:30301530)
• FUBP1 regulates the oncogene KIT by binding to its enhancer, and its promoter, and by interacting with RUNX1. (PMID:30500954)
• The results reveal a new mechanism of action of RUNX1 that implicates FUBP1, as a facilitator, to trigger transcriptional regulation of c-KIT and to regulate cell proliferation in precursor B-cell lymphoblastic leukemia. (PMID:30500954)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	fubp1	ENSDARG00000029248
mus_musculus	Fubp1	ENSMUSG00000028034
rattus_norvegicus	Fubp1	ENSRNOG00000043370
drosophila_melanogaster	ps	FBGN0261552
drosophila_melanogaster	mub	FBGN0262737
drosophila_melanogaster	Imp	FBGN0285926
caenorhabditis_elegans		WBGENE00003978
caenorhabditis_elegans		WBGENE00010908
caenorhabditis_elegans		WBGENE00013347
caenorhabditis_elegans		WBGENE00016489
caenorhabditis_elegans	fubl-4	WBGENE00019692

Paralogs (12): IGF2BP2 (ENSG00000073792), KHSRP (ENSG00000088247), PCBP4 (ENSG00000090097), NOVA2 (ENSG00000104967), FUBP3 (ENSG00000107164), IGF2BP3 (ENSG00000136231), NOVA1 (ENSG00000139910), IGF2BP1 (ENSG00000159217), HNRNPK (ENSG00000165119), PCBP1 (ENSG00000169564), PCBP3 (ENSG00000183570), PCBP2 (ENSG00000197111)

Protein

Protein identifiers

Far upstream element-binding protein 1 — Q96AE4 (reviewed: Q96AE4)

Alternative names: DNA helicase V

All UniProt accessions (7): A0A384MDX9, A0A994J3Q8, A0A994J6G7, B4DT31, Q96AE4, C9JSZ1, E9PEB5

UniProt curated annotations — full annotation on UniProt →

Function. Regulates MYC expression by binding to a single-stranded far-upstream element (FUSE) upstream of the MYC promoter. May act both as activator and repressor of transcription.

Subunit / interactions. Found in a complex with PUF60 and far upstream element (FUSE) DNA segment. Interacts with PUF60 and JTV1.

Subcellular location. Nucleus.

Post-translational modifications. Ubiquitinated. This targets the protein for proteasome-mediated degradation.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96AE4-1	1	yes
Q96AE4-2	2

RefSeq proteins (6): NP_001290362, NP_001362984, NP_001362985, NP_001362986, NP_001397733, NP_003893* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004087	KH_dom	Domain
IPR004088	KH_dom_type_1	Domain
IPR015096	FUBP_C	Domain
IPR036612	KH_dom_type_1_sf	Homologous_superfamily
IPR048249	KH-I_FUBP1_dom1	Domain
IPR048250	KH-I_FUBP1_dom2	Domain
IPR048251	KH-I_FUBP1_dom3	Domain
IPR048252	KH-I_FUBP1_dom4	Domain

Pfam: PF00013, PF09005

UniProt features (68 total): helix 22, strand 12, modified residue 11, compositionally biased region 6, region of interest 5, domain 4, turn 3, splice variant 2, initiator methionine 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
4LIJ	X-RAY DIFFRACTION	1.8
6Y24	X-RAY DIFFRACTION	1.86
6Y2D	X-RAY DIFFRACTION	1.9
6Y2C	X-RAY DIFFRACTION	2
1J4W	SOLUTION NMR
2KXH	SOLUTION NMR
8P25	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96AE4-F1	64.63	0.17

Functional residue map

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

Post-translational modifications (11): 2, 52, 55, 140, 153, 321, 359, 361, 363, 432, 630

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 208 (showing top): MORF_RAB5A, DORN_ADENOVIRUS_INFECTION_12HR_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, BROWNE_HCMV_INFECTION_16HR_UP, MORF_PSMC2, PUJANA_CHEK2_PCC_NETWORK, MUELLER_PLURINET, CADWELL_ATG16L1_TARGETS_DN, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, MARTINEZ_RB1_TARGETS_DN, DER_IFN_BETA_RESPONSE_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, MORF_PPP6C, GARY_CD5_TARGETS_DN

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of gene expression (GO:0010628), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (6): single-stranded DNA binding (GO:0003697), RNA binding (GO:0003723), mRNA binding (GO:0003729), nucleic acid binding (GO:0003676), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of gene expression	2
nucleic acid binding	2
binding	2
cellular anatomical structure	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
DNA-templated transcription	1
regulation of RNA biosynthetic process	1
DNA binding	1
RNA binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2356 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FUBP1	PUF60	Q9UHX1	975
FUBP1	FBP1	P09467	881
FUBP1	MYC	P01106	800
FUBP1	HNRNPF	P52597	745
FUBP1	AIMP2	Q13155	726
FUBP1	TP53	P04637	688
FUBP1	ERCC3	P19447	680
FUBP1	ERCC2	P18074	669
FUBP1	ATRX	P46100	666
FUBP1	IMMT	Q16891	666
FUBP1	IDH1	O75874	621
FUBP1	TIA1	P31483	611
FUBP1	UBP1	Q9NZI7	567
FUBP1	TERT	O14746	542
FUBP1	HNRNPA2B1	P22626	531

IntAct

124 interactions, top by confidence:

A	B	Type	Score
AIMP2	FUBP1	psi-mi:“MI:0915”(physical association)	0.670
FUBP1	AIMP2	psi-mi:“MI:0915”(physical association)	0.670
AIMP2	FUBP1	psi-mi:“MI:0403”(colocalization)	0.670
HRAS	RGL2	psi-mi:“MI:0914”(association)	0.660
FUBP1	USP22	psi-mi:“MI:0915”(physical association)	0.580
	FUBP1	psi-mi:“MI:0915”(physical association)	0.460
	FUBP1	psi-mi:“MI:0403”(colocalization)	0.460
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
Bub1	PEX10	psi-mi:“MI:0914”(association)	0.350
Racgap1	DDX3X	psi-mi:“MI:0914”(association)	0.350
Smad3		psi-mi:“MI:0914”(association)	0.350
CEP170P1	PCYT1A	psi-mi:“MI:0914”(association)	0.350
Chmp3	DTL	psi-mi:“MI:0914”(association)	0.350
RAB32	PHF20L1	psi-mi:“MI:0914”(association)	0.350
PDHA1		psi-mi:“MI:0914”(association)	0.350
SOD1	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
SOD1	PGK1	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
DICER1	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
apa	NUDT21	psi-mi:“MI:0914”(association)	0.350
PLEKHG6	PSMA7	psi-mi:“MI:0914”(association)	0.350
ARHGEF39	SEC16A	psi-mi:“MI:0914”(association)	0.350

BioGRID (406): FUBP1 (Affinity Capture-RNA), FUBP1 (Affinity Capture-MS), FUBP1 (Affinity Capture-MS), FUBP1 (Affinity Capture-MS), FUBP1 (Reconstituted Complex), FUBP1 (Affinity Capture-MS), ANXA11 (Co-fractionation), ANXA2 (Co-fractionation), CCDC58 (Co-fractionation), CHORDC1 (Co-fractionation), DUT (Co-fractionation), FUBP1 (Co-fractionation), FUBP1 (Co-fractionation), FUBP1 (Co-fractionation), FUBP1 (Co-fractionation)

ESM2 similar proteins: A0A1W2P872, A1L1C7, A4IIM2, B2RYD2, F1LQ48, O57406, O88532, O95319, P14866, P28659, P51513, P57723, P57724, Q28HE9, Q2PFW9, Q32PX7, Q3U0V1, Q3US41, Q4QQT3, Q4R535, Q58A45, Q5F3T7, Q5NVC8, Q5R8Y8, Q5R995, Q5U231, Q640Q5, Q6DGV1, Q6GPM1, Q6NXG1, Q6P0B1, Q6PF35, Q792H5, Q7T2T1, Q7TSY6, Q7ZXE2, Q80WA4, Q8R081, Q8UVD9, Q91WJ8

Diamond homologs: A0A0B4KGY6, A0A1W2P872, O19048, O19049, O73932, O74919, P51513, P57721, P57722, P60335, P61978, P61979, P61980, Q15365, Q15366, Q2PFW9, Q32PX7, Q3T0D0, Q4R4M6, Q5E9A3, Q5R5H8, Q5RB68, Q5SF07, Q5ZIQ3, Q5ZLP8, Q61990, Q80WA4, Q8UVD9, Q91WJ8, Q96AE4, Q96I24, Q9JKN6, Q9LZ82, Q9SZH4, Q9UNW9, Q9Y6M1, A6ZKR5, B3LNH0, C5DIR2, C7GND0

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
FUBP1	“up-regulates quantity by expression”	MYC	“transcriptional regulation”
FUBP1	“up-regulates quantity by expression”	CCND2	“transcriptional regulation”
FUBP1	“up-regulates quantity by expression”	CDKN1A	“transcriptional regulation”
FUBP1	“down-regulates quantity by repression”	CDKN2B	“transcriptional regulation”
FUBP1	“down-regulates quantity by repression”	BIK	“transcriptional regulation”
FUBP1	“down-regulates quantity by repression”	PMAIP1	“transcriptional regulation”
FUBP1	“down-regulates quantity by repression”	TNFSF10	“transcriptional regulation”
FUBP1	“down-regulates quantity by repression”	TNF	“transcriptional regulation”
TAL1	“up-regulates quantity by expression”	FUBP1	“transcriptional regulation”
FUBP1	“up-regulates quantity by expression”	KIT	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 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
mRNA 3’-end processing	5	12.0×	8e-03
mRNA Polyadenylation	9	9.6×	1e-04
Dengue Virus-Host Interactions	12	6.7×	1e-04
mRNA Splicing - Major Pathway	9	6.0×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
mRNA processing	9	7.0×	6e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — BRCA, CLLSLL, LGGNOS.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2831 predictions. Top by Δscore:

Variant	Effect	Δscore
1:77955250:CATA:C	donor_loss	1.0000
1:77955251:ATAC:A	donor_loss	1.0000
1:77955252:TACCC:T	donor_loss	1.0000
1:77955253:A:T	donor_loss	1.0000
1:77955253:AC:A	donor_gain	1.0000
1:77955254:CC:C	donor_gain	1.0000
1:77955329:CCT:C	acceptor_gain	1.0000
1:77955331:T:C	acceptor_gain	1.0000
1:77955331:T:TC	acceptor_gain	1.0000
1:77955333:G:GC	acceptor_gain	1.0000
1:77955336:C:CT	acceptor_gain	1.0000
1:77955337:A:T	acceptor_gain	1.0000
1:77955340:C:CT	acceptor_gain	1.0000
1:77955341:A:T	acceptor_gain	1.0000
1:77955345:C:CT	acceptor_gain	1.0000
1:77956568:TTACC:T	donor_loss	1.0000
1:77956696:CTTAG:C	acceptor_gain	1.0000
1:77956697:TTAG:T	acceptor_gain	1.0000
1:77956698:TAG:T	acceptor_gain	1.0000
1:77956699:AG:A	acceptor_gain	1.0000
1:77956700:GC:G	acceptor_loss	1.0000
1:77956701:C:CC	acceptor_gain	1.0000
1:77956706:A:AC	acceptor_gain	1.0000
1:77960261:CCA:C	acceptor_gain	1.0000
1:77960262:CAC:C	acceptor_gain	1.0000
1:77960264:C:CC	acceptor_gain	1.0000
1:77960339:CTT:C	donor_loss	1.0000
1:77960339:CTTA:C	donor_gain	1.0000
1:77960340:TTA:T	donor_loss	1.0000
1:77960341:TA:T	donor_loss	1.0000

AlphaMissense

4145 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:77949222:C:A	R620I	1.000
1:77949226:A:C	Y619D	1.000
1:77949228:T:C	Y618C	1.000
1:77949229:A:C	Y618D	1.000
1:77949229:A:G	Y618H	1.000
1:77949236:C:A	W615C	1.000
1:77949236:C:G	W615C	1.000
1:77949238:A:G	W615R	1.000
1:77949238:A:T	W615R	1.000
1:77949246:C:A	S612I	1.000
1:77949253:C:G	D610H	1.000
1:77955277:C:A	W586C	1.000
1:77955277:C:G	W586C	1.000
1:77955279:A:G	W586R	1.000
1:77955279:A:T	W586R	1.000
1:77956666:C:A	W537C	1.000
1:77956666:C:G	W537C	1.000
1:77956668:A:G	W537R	1.000
1:77956668:A:T	W537R	1.000
1:77962789:A:G	L442P	1.000
1:77962795:C:G	R440P	1.000
1:77962798:G:T	A439D	1.000
1:77962799:C:G	A439P	1.000
1:77962822:C:A	G431V	1.000
1:77962822:C:T	G431D	1.000
1:77962823:C:G	G431R	1.000
1:77962828:A:T	I429N	1.000
1:77962833:A:C	F427L	1.000
1:77962833:A:T	F427L	1.000
1:77962834:A:G	F427S	1.000

dbSNP variants (sampled 300 via entrez): RS1000044642 (1:77957287 C>T), RS1000049512 (1:77970234 C>A,T), RS1000075779 (1:77957667 G>A), RS1000089868 (1:77975390 G>C), RS1000137024 (1:77953612 A>G), RS1000332796 (1:77944830 T>C), RS1000353718 (1:77950705 C>T), RS1000459303 (1:77944372 C>T), RS1000463946 (1:77957139 C>T), RS1000508634 (1:77944717 A>C,G), RS1000528860 (1:77968648 A>C), RS1000595776 (1:77962051 T>A,G), RS1000693829 (1:77974115 ACGT>A), RS1000737716 (1:77952461 C>G), RS1000815024 (1:77956876 G>A)

Disease associations

OMIM: gene MIM:603444 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST002783_16	Body mass index	6.000000e-10
GCST002783_362	Body mass index	2.000000e-10
GCST002783_497	Body mass index	1.000000e-10
GCST004346_23	Psoriasis	4.000000e-09
GCST004495_46	BMI (adjusted for smoking behaviour)	9.000000e-08
GCST004495_47	BMI (adjusted for smoking behaviour)	4.000000e-06
GCST004497_94	Body mass index (joint analysis main effects and smoking interaction)	3.000000e-07
GCST004497_95	Body mass index (joint analysis main effects and smoking interaction)	6.000000e-06
GCST004499_57	BMI in non-smokers	8.000000e-08
GCST004499_58	BMI in non-smokers	2.000000e-06
GCST004747_15	Lung cancer in never smokers	4.000000e-06
GCST90000047_8	Age at first sexual intercourse	7.000000e-10
GCST90002392_171	Mean corpuscular volume	3.000000e-12
GCST90002397_635	Mean spheric corpuscular volume	5.000000e-17
GCST90020024_13	A body shape index	7.000000e-13
GCST90020025_248	Waist-to-hip ratio adjusted for BMI	3.000000e-12
GCST90020027_1784	Waist-hip index	2.000000e-11
GCST90020028_571	Hip circumference adjusted for BMI	1.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004318	smoking behavior
EFO:0009749	age at first sexual intercourse measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295922 (SINGLE PROTEIN)

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 9 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.31	Kd	49.48	nM	CHEMBL5653589
7.31	ED50	49.48	nM	CHEMBL5653589
5.12	IC50	7600	nM	CHEMBL4779552

PubChem BioAssay actives

2 with measured affinity, of 65 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148402: Binding affinity to human FUBP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0495	uM
2-(5-bromothiophen-2-yl)-5-(3,4-dimethoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine	1714046: Inhibition of 6xHis-tagged human FUBP1 expressed in HEK293T cells assessed as reduction in FUBP1 interaction with biotinylated NLC chip immobilized FUSE p21 oligonucleotide incubated for 21 hrs by SPR analysis	ic50	7.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	9
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Arsenic Trioxide	decreases expression, increases response to substance	3
Doxorubicin	affects expression, decreases expression, decreases response to substance	3
bisphenol A	decreases expression	2
trichostatin A	affects cotreatment, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
bisphenol S	increases expression, affects cotreatment	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
1-Methyl-4-phenylpyridinium	decreases expression, increases expression	2
Cadmium Chloride	increases expression, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
geraniol	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
beta-lapachone	decreases expression	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
ochratoxin A	decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
coumarin	increases phosphorylation	1
quinoline	decreases expression	1
diallyl trisulfide	increases expression	1

ChEMBL screening assays

22 unique, capped per target: 22 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118552	Binding	Binding affinity to FUBP1 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

6 cell lines: 3 embryonic stem cell, 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A2D9	SEES3-1V human FUBP1, clone1	Embryonic stem cell	Male
CVCL_A2E0	SEES3-1V human FUBP1, clone2	Embryonic stem cell	Male
CVCL_A2E1	SEES3-1V human FUBP1, clone3	Embryonic stem cell	Male
CVCL_D1MN	Abcam K-562 FUBP1 KO	Cancer cell line	Female
CVCL_D2J8	Abcam Raji FUBP1 KO	Cancer cell line	Male
CVCL_UQ55	Abcam Jurkat FUBP1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery