YBX1

Summary

YBX1 (Y-box binding protein 1, HGNC:8014) is a protein-coding gene on chromosome 1p34.2, encoding Y-box-binding protein 1 (P67809). DNA- and RNA-binding protein involved in various processes, such as translational repression, RNA stabilization, mRNA splicing, DNA repair and transcription regulation. It is a common-essential gene (DepMap: required in 98.4% of cancer cell lines).

This gene encodes a highly conserved cold shock domain protein that has broad nucleic acid binding properties. The encoded protein functions as both a DNA and RNA binding protein and has been implicated in numerous cellular processes including regulation of transcription and translation, pre-mRNA splicing, DNA reparation and mRNA packaging. This protein is also a component of messenger ribonucleoprotein (mRNP) complexes and may have a role in microRNA processing. This protein can be secreted through non-classical pathways and functions as an extracellular mitogen. Aberrant expression of the gene is associated with cancer proliferation in numerous tissues. This gene may be a prognostic marker for poor outcome and drug resistance in certain cancers. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on multiple chromosomes.

Source: NCBI Gene 4904 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 36 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 98.4% of screened cell lines (common-essential)
• Transcription factor: yes — 103 downstream targets (CollecTRI)
• MANE Select transcript: NM_004559

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8014
Approved symbol	YBX1
Name	Y-box binding protein 1
Location	1p34.2
Locus type	gene with protein product
Status	Approved
Aliases	YB-1, YB1, DBPB, NSEP-1, MDR-NF1, BP-8, CSDB, CSDA2
Ensembl gene	ENSG00000065978
Ensembl biotype	protein_coding
OMIM	154030
Entrez	4904

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000321358, ENST00000332220, ENST00000436427, ENST00000467957, ENST00000886269, ENST00000886270, ENST00000886271, ENST00000886272, ENST00000886273, ENST00000886274, ENST00000936897, ENST00000953953

RefSeq mRNA: 1 — MANE Select: NM_004559 NM_004559

CCDS: CCDS470

Canonical transcript exons

ENST00000321358 — 8 exons

Exon	Start	End
ENSE00001080452	42683403	42683466
ENSE00001293985	42700781	42701046
ENSE00001458061	42682418	42682731
ENSE00003500335	42693490	42693523
ENSE00003552833	42696199	42696288
ENSE00003572618	42696642	42696944
ENSE00003789081	42697180	42697262
ENSE00003844096	42701981	42703805

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 99.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 83.2089 / max 1263.4890, expressed in 1827 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2465	74.6016	1827
2469	3.6491	1467
2467	1.4390	705
2470	1.2461	447
2466	1.1926	790
2473	0.5504	298
2468	0.5301	263

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	99.86	gold quality
right testis	UBERON:0004534	99.84	gold quality
cortical plate	UBERON:0005343	99.83	gold quality
ganglionic eminence	UBERON:0004023	99.80	gold quality
ventricular zone	UBERON:0003053	99.73	gold quality
calcaneal tendon	UBERON:0003701	99.71	gold quality
muscle of leg	UBERON:0001383	99.70	gold quality
gastrocnemius	UBERON:0001388	99.70	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.60	gold quality
skeletal muscle tissue	UBERON:0001134	99.57	gold quality
heart left ventricle	UBERON:0002084	99.56	gold quality
lower esophagus	UBERON:0013473	99.56	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.56	gold quality
stromal cell of endometrium	CL:0002255	99.55	gold quality
smooth muscle tissue	UBERON:0001135	99.55	gold quality
popliteal artery	UBERON:0002250	99.55	gold quality
tibial artery	UBERON:0007610	99.55	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.55	gold quality
heart	UBERON:0000948	99.54	gold quality
vermiform appendix	UBERON:0001154	99.53	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.53	gold quality
right atrium auricular region	UBERON:0006631	99.52	gold quality
left coronary artery	UBERON:0001626	99.51	gold quality
right coronary artery	UBERON:0001625	99.50	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.49	gold quality
rectum	UBERON:0001052	99.48	gold quality
lymph node	UBERON:0000029	99.46	gold quality
adipose tissue	UBERON:0001013	99.46	gold quality
monocyte	CL:0000576	99.45	gold quality
leukocyte	CL:0000738	99.45	gold quality

Single-cell (SCXA)

Detected in 33 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	8174.98
E-MTAB-9543	yes	3180.87
E-MTAB-8205	yes	1917.31
E-MTAB-11011	yes	1850.15
E-HCAD-4	yes	142.74
E-HCAD-1	yes	83.65
E-CURD-112	yes	60.09
E-CURD-122	yes	54.51
E-GEOD-135922	yes	39.66
E-MTAB-10553	yes	37.03
E-CURD-46	yes	33.23
E-CURD-88	yes	26.14
E-HCAD-9	yes	22.07
E-GEOD-130148	yes	19.31
E-MTAB-9067	yes	16.71

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

103 targets.

Target	Regulation
ABCB1	Activation
ABCC1
ABCC2
ACHE
ACOT11
ACTA2	Unknown
ACTB	Activation
ADAM2
AGT	Activation
AKT2
ANAPC4	Repression
AP1
AR	Unknown
BMI1
BMP7	Repression
CCL5	Unknown
CCNA2	Activation
CCNB1	Repression
CCNC	Repression
CD74
CDC20	Repression
CDC6	Unknown
CDH1	Activation
CDH17
CDKN1A	Activation
CDKN2A	Unknown
CDKN3	Activation
CEL
CFC1
CKS2	Repression

Upstream regulators (CollecTRI, top): EGR1, FOXO3, GATA1, GATA2, MAX, MYC, NEUROD6, TP53, TP63, TP73, TWIST1, YBX1

miRNA regulators (miRDB)

115 targeting YBX1, 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-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-629-3P	99.85	67.99	1875

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• interacts with an upstream element in the alpha1(I) collagen gene (PMID:11731270)
• YB-1 relocates to the nucleus in adenovirus-infected cells and facilitates viral replication (PMID:11788582)
• NMR structure and DNA-binding properties of the cold-shock domain of the human Y-box protein YB-1 (PMID:11851341)
• interacts with JCV agnoprotein to modulate transcriptional activity of JCV promoters (PMID:11907223)
• data suggest that p73 stimulates the transcription of the YB-1 promoter by enhancing recruitment of the c-Myc-Max complex to the E-box (PMID:12080043)
• The central and C-terminal domains of YB-1 are required for specific binding to 8-oxoguanine-containing RNA, a mechanism that involves sequestering oxidatively damaged RNA from normal processes and contributes to the high fidelity of translation in cells. (PMID:12379116)
• Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in human breast carcinoma. (PMID:12565174)
• nuclear YB-1 shuttling and alternative splice site selection is regulated by SRp30c interaction with YB-1 (PMID:12604611)
• YB-1 functions under the regulation of GATA factors in erythroid differentiation and aberrant expression of YB-1 gene may result in dyserythropoiesis (PMID:12646178)
• YB-1 is a cell cycle stage-specific transcription factor important for cell proliferation (PMID:12695516)
• Nuclear localization of this protein requires wild-type p53. (PMID:12743601)
• YB1 interacts directly with Smad3 during TGFbeta signal inhibition by interferon gamma (PMID:12917425)
• findings suggested that YB-1 functions in the early stage of erythropoiesis and that aberrant expression of this protein may induce hematological diseases such as MDS (PMID:14604279)
• YB-1 is involved in base excision and mismatch repair pathways (PMID:14718551)
• autoregulation of YB-1 mRNA translation via the 5’-UTR (PMID:14752049)
• Hepatic nuclear factor 3 and nuclear factor 1 regulate 5-aminolevulinate synthase gene expression and are involved in insulin repression (PMID:15123725)
• 5-HTT VNTR domains differentially respond to YB-1 which binds to the VNTR in a sequence-specific manner– a new mechanism explaining the ability of the distinct VNTR copy numbers to support differential reporter expression based on YB-1 binding sites. (PMID:15229244)
• study demonstrates that NF-1 plays an important role in PMA/IL-1-mediated transactivation of the JC virus early promoter; suggests a possible involvement of NF-1 in JC virus reactivation in immunosuppressive states such as AIDS (PMID:15327898)
• YB-1 mediates DNA polymerase alpha gene expression (PMID:15615704)
• Overexpression of a transfected gene encoding YB-1 in human HeLa cervical carcinoma cells significantly represses the transactivation of a minimal AP-1 reporter construct in response to the tumour promoter PMA. (PMID:15702969)
• YB-1 overexpression can induce EGF independence in human mammary epithelial cells via activation of the EGFR pathway (PMID:15735691)
• activated Akt is positively correlated with the protein expression of the transcription/translation factor Y-box binding protein-1 (YB-1) in primary breast cancer; activated Akt binds to and phosphorylates the YB-1 cold shock domain at Ser102 (PMID:15806160)
• The release of YB-1 from promoter DNA coupled with its ability to bind RNA and shuttle between the nucleus and cytoplasm is suggestive of a regulatory loop for coordinating SMalphaA gene output. (PMID:16093352)
• YB-1 expression is correlated with PCNA expression in NSCLC. The DNA repair pathway and tumor proliferation mediated by YB-1 linking to PCNA may be responsible for controlling the growth of NSCLC. (PMID:16101161)
• FRGY2a and YB1 disassemble nucleoli by sequestering B23, which is associated with pre-ribosomes and other structurally important nucleolar components (PMID:16415342)
• NSEP1 is an authentic selenocysteine insertion sequence binding protein that is structurally associated with the selenoprotein translation complex and functionally involved in the translation of selenoproteins in mammalian cells (PMID:16508950)
• YB-1 colocalized with P-body (messenger RNA processing bodies) (PMID:17339575)
• conclusion, the data demonstrate the utility of the analyzed RNAs as powerful laboratory tools and indicate that YB-1 is not involved in the regulation of the MDR1 gene. (PMID:17418094)
• YB-1 nuclear expression is an important prognostic factor in ovarian carcinoma. (PMID:17459055)
• PP2Cgamma modulates alternative splicing of specific pre-mRNAs coregulated by YB-1. (PMID:17572683)
• OSU-03012 prevents YBX1 from inducing EGFR. (PMID:17595327)
• YB-1 thus appears to have a novel regulatory role in NEIL2-mediated repair under oxidative stress. (PMID:17686777)
• Y-box binding protein-1 (YB-1) as a new repressor of MMP-13 transactivation. (PMID:17822788)
• Radiation mediated increase of nuclear YB-1 in glioma cells enhanced the oncolytic potential of adenovirus dl520 (PMID:17967494)
• TGF-beta1 translation in proximal tubule cells requires YB-1 binding to a high-affinity site in the 5’-untranslated region of its mRNA. (PMID:18075498)
• Both YB-1 and Twist expression could induce tumor progression, promoting cell growth and driving oncogenesis in various cancers. (PMID:18172301)
• that the recruitment of YB1, PURalpha, and H1.2 to the p53 target gene Bax is required for repression of p53-induced transcription. (PMID:18258596)
• YB-1 binds specifically to the auto-inhibitory domain of hNTH1, providing a mechanism by which YB-1 stimulates hNTH1 activity. (PMID:18307537)
• HER2 and estrogen receptor alpha expression depends upon nuclear localization of Y-box binding protein-1 in human breast cancers (PMID:18316615)
• YB-1 nuclear expression support the concept that alveolar and embryonal rhabdomyosarcomas are molecular biologically distinct neoplasms. (PMID:18377424)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	ybx1	ENSDARG00000004757
mus_musculus	Ybx1	ENSMUSG00000028639
rattus_norvegicus	Ybx1	ENSRNOG00000023786
rattus_norvegicus	Ybx1l1	ENSRNOG00000030807
drosophila_melanogaster	lin-28	FBGN0035626
caenorhabditis_elegans	cey-2	WBGENE00000473
caenorhabditis_elegans	cey-3	WBGENE00000474
caenorhabditis_elegans		WBGENE00000475

Paralogs (4): YBX2 (ENSG00000006047), YBX3 (ENSG00000060138), LIN28A (ENSG00000131914), LIN28B (ENSG00000187772)

Protein

Protein identifiers

Y-box-binding protein 1 — P67809 (reviewed: P67809)

Alternative names: CCAAT-binding transcription factor I subunit A, DNA-binding protein B, Enhancer factor I subunit A, Nuclease-sensitive element-binding protein 1, Y-box transcription factor

All UniProt accessions (3): P67809, C9J5V9, H0Y449

UniProt curated annotations — full annotation on UniProt →

Function. DNA- and RNA-binding protein involved in various processes, such as translational repression, RNA stabilization, mRNA splicing, DNA repair and transcription regulation. Predominantly acts as a RNA-binding protein: binds preferentially to the 5’-[CU]CUGCG-3’ RNA motif and specifically recognizes mRNA transcripts modified by C5-methylcytosine (m5C). Promotes mRNA stabilization: acts by binding to m5C-containing mRNAs and recruiting the mRNA stability maintainer ELAVL1, thereby preventing mRNA decay. Component of the CRD-mediated complex that promotes MYC mRNA stability. Contributes to the regulation of translation by modulating the interaction between the mRNA and eukaryotic initiation factors. Plays a key role in RNA composition of extracellular exosomes by defining the sorting of small non-coding RNAs, such as tRNAs, Y RNAs, Vault RNAs and miRNAs. Probably sorts RNAs in exosomes by recognizing and binding C5-methylcytosine (m5C)-containing RNAs. Acts as a key effector of epidermal progenitors by preventing epidermal progenitor senescence: acts by regulating the translation of a senescence-associated subset of cytokine mRNAs, possibly by binding to m5C-containing mRNAs. Also involved in pre-mRNA alternative splicing regulation: binds to splice sites in pre-mRNA and regulates splice site selection. Binds to TSC22D1 transcripts, thereby inhibiting their translation and negatively regulating TGF-beta-mediated transcription of COL1A2. Also able to bind DNA: regulates transcription of the multidrug resistance gene MDR1 is enhanced in presence of the APEX1 acetylated form at ‘Lys-6’ and ‘Lys-7’. Binds to promoters that contain a Y-box (5’-CTGATTGGCCAA-3’), such as MDR1 and HLA class II genes. Promotes separation of DNA strands that contain mismatches or are modified by cisplatin. Has endonucleolytic activity and can introduce nicks or breaks into double-stranded DNA, suggesting a role in DNA repair. The secreted form acts as an extracellular mitogen and stimulates cell migration and proliferation.

Subunit / interactions. Homodimer in the presence of ATP. Component of the coding region determinant (CRD)-mediated complex, composed of DHX9, HNRNPU, IGF2BP1, SYNCRIP and YBX1. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Component of the U11/U12 snRNPs that are part of the U12-type spliceosome. Identified in a histone pre-mRNA complex, at least composed of ERI1, LSM11, SLBP, SNRPB, SYNCRIP and YBX1. Interacts with IGF2BP1 and RBBP6. Component of cytoplasmic messenger ribonucleoprotein particles (mRNPs). Interacts with AKT1, MBNL1, SFRS9, SFRS12, ALYREF/THOC4, MSH2, XRCC5, WRN and NCL. Interacts (via C-terminus) with APEX1 (via N-terminus); the interaction is increased with APEX1 acetylated at ‘Lys-6’ and ‘Lys-7’. Interacts with AGO1 and AGO2. Interacts with ANKRD2. Interacts with DERA. Interacts with FMR1; this interaction occurs in association with polyribosome. Interacts with ZBTB7B. Interacts with HDGF (isoform 1). Interacts with ELAVL1; leading to ELAVL1 recruitment on C5-methylcytosine (m5C)-containing mRNAs and subsequent mRNA stability. Interacts with PURB.

Subcellular location. Cytoplasm. Nucleus. Cytoplasmic granule. Secreted. Extracellular exosome. P-body.

Post-translational modifications. Ubiquitinated by RBBP6; leading to a decrease of YBX1 transactivational ability. Phosphorylated; increased by TGFB1 treatment (Ref.6). Phosphorylation by PKB/AKT1 reduces interaction with cytoplasmic mRNA. In the absence of phosphorylation the protein is retained in the cytoplasm. Cleaved by a 20S proteasomal protease in response to agents that damage DNA. Cleavage takes place in the absence of ubiquitination and ATP. The resulting N-terminal fragment accumulates in the nucleus.

Domain organisation. In the CSD domain, Trp-65 specifically recognizes C5-methylcytosine (m5C) modification through its indole ring.

Similarity. Belongs to the YBX1 family.

RefSeq proteins (1): NP_004550* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002059	CSP_DNA-bd	Domain
IPR011129	CSD	Domain
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR019844	CSD_CS	Conserved_site
IPR050181	Cold_shock_domain	Family

Pfam: PF00313

UniProt features (44 total): modified residue 10, compositionally biased region 7, strand 6, mutagenesis site 5, region of interest 4, site 2, cross-link 2, turn 2, helix 2, initiator methionine 1, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
6KUG	X-RAY DIFFRACTION	1.4
5YTX	X-RAY DIFFRACTION	1.55
5YTT	X-RAY DIFFRACTION	1.6
5YTV	X-RAY DIFFRACTION	1.7
5YTS	X-RAY DIFFRACTION	1.77
6A6L	X-RAY DIFFRACTION	1.78
6KTC	X-RAY DIFFRACTION	2.01
6A6J	X-RAY DIFFRACTION	2.25
1H95	SOLUTION NMR
6LMR	SOLUTION NMR
6LMS	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P67809-F1	61.16	0.23

Functional residue map

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

Catalytic / active sites (2): 65 (important for c5-methylcytosine-recognition); 219–220 (cleavage; by 20s proteasomal protease)

Post-translational modifications (12): 2, 102, 162, 165, 167, 174, 176, 301, 304, 314, 26, 137

Mutagenesis-validated functional residues (5):

Position	Phenotype
65	abolished binding to c5-methylcytosine (m5c)-containing mrnas.
65	decreased binding to c5-methylcytosine (m5c)-containing mrnas. decreased ability to discriminate between m5c-containing
102	loss of phosphorylation by pkb/akt1. inhibits translocation to the nucleus and tumor cell growth.
301	abrogates unconventional secretion.
304	abrogates unconventional secretion.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-2173796	SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72165	mRNA Splicing - Minor Pathway
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-877300	Interferon gamma signaling
R-HSA-9017802	Noncanonical activation of NOTCH3
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918476	Assembly and Release of Dengue Virus Virions
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9918487	Dengue Virus Genome Translation and Replication

MSigDB gene sets: 383 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, REACTOME_SIGNALING_BY_NOTCH, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, CCAWYNNGAAR_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, MORF_UBE2I, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION

GO Biological Process (22): negative regulation of transcription by RNA polymerase II (GO:0000122), in utero embryonic development (GO:0001701), regulation of DNA-templated transcription (GO:0006355), mRNA processing (GO:0006397), RNA splicing (GO:0008380), epidermis development (GO:0008544), regulation of gene expression (GO:0010468), negative regulation of translation (GO:0017148), positive regulation of transcription by RNA polymerase II (GO:0045944), mRNA stabilization (GO:0048255), embryonic morphogenesis (GO:0048598), RNA transport (GO:0050658), tRNA transport (GO:0051031), negative regulation of striated muscle cell differentiation (GO:0051154), positive regulation of cell division (GO:0051781), CRD-mediated mRNA stabilization (GO:0070934), cellular response to interleukin-7 (GO:0098761), negative regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:1900152), protein localization to cytoplasmic stress granule (GO:1903608), miRNA transport (GO:1990428), positive regulation of cytoplasmic translation (GO:2000767), negative regulation of cellular senescence (GO:2000773)

GO Molecular Function (12): nucleic acid binding (GO:0003676), DNA binding (GO:0003677), chromatin binding (GO:0003682), double-stranded DNA binding (GO:0003690), single-stranded DNA binding (GO:0003697), RNA binding (GO:0003723), mRNA binding (GO:0003729), miRNA binding (GO:0035198), GTPase binding (GO:0051020), C5-methylcytidine-containing RNA reader activity (GO:0062153), sequence-specific double-stranded DNA binding (GO:1990837), protein binding (GO:0005515)

GO Cellular Component (15): P-body (GO:0000932), extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), U12-type spliceosomal complex (GO:0005689), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasmic stress granule (GO:0010494), synapse (GO:0045202), extracellular exosome (GO:0070062), CRD-mediated mRNA stability complex (GO:0070937), histone pre-mRNA 3’end processing complex (GO:0071204), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Dengue Virus Infection	3
mRNA Splicing	2
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1
Metabolism of RNA	1
Interferon Signaling	1
NOTCH3 Activation and Transmission of Signal to the Nucleus	1
mRNA 3’-end processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
RNA processing	2
negative regulation of mRNA catabolic process	2
RNA transport	2
nucleic acid binding	2
DNA binding	2
RNA binding	2
cytoplasmic ribonucleoprotein granule	2
intracellular membrane-bounded organelle	2
cytoplasm	2
negative regulation of DNA-templated transcription	1
chordate embryonic development	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
mRNA metabolic process	1
tissue development	1
gene expression	1
regulation of macromolecule biosynthetic process	1
translation	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
positive regulation of DNA-templated transcription	1
regulation of mRNA stability	1
RNA stabilization	1
anatomical structure morphogenesis	1
embryo development	1
nucleic acid transport	1
establishment of RNA localization	1
striated muscle cell differentiation	1
negative regulation of muscle cell differentiation	1
regulation of striated muscle cell differentiation	1
positive regulation of cellular process	1
cell division	1
regulation of cell division	1
mRNA stabilization	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

579 interactions, top by confidence:

A	B	Type	Score
C1QBP	YBX1	psi-mi:“MI:0915”(physical association)	0.920
IFIT1	IFIT3	psi-mi:“MI:0914”(association)	0.920
DDX6	YBX1	psi-mi:“MI:0915”(physical association)	0.820
IFIT2	IFIT3	psi-mi:“MI:0914”(association)	0.780
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
EP300	APEX1	psi-mi:“MI:0915”(physical association)	0.720
TPT1	XRCC6	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
YBX1	SSB	psi-mi:“MI:0914”(association)	0.710
DDX6	RPS3	psi-mi:“MI:0915”(physical association)	0.690
IGF2BP1	YBX1	psi-mi:“MI:0403”(colocalization)	0.680
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
C1QBP	DDX6	psi-mi:“MI:0915”(physical association)	0.620
DDX6	RPLP0	psi-mi:“MI:0915”(physical association)	0.620
YBX1	DDX3X	psi-mi:“MI:0403”(colocalization)	0.610
YBX1		psi-mi:“MI:0403”(colocalization)	0.600
YBX1		psi-mi:“MI:0915”(physical association)	0.600
IGF2BP1	SYNCRIP	psi-mi:“MI:0914”(association)	0.580
TPT1	YBX1	psi-mi:“MI:0915”(physical association)	0.570

BioGRID (1022): YBX1 (Affinity Capture-Western), YBX1 (Reconstituted Complex), YBX1 (Biochemical Activity), YBX1 (Co-localization), YBX1 (Affinity Capture-MS), YBX1 (Affinity Capture-MS), YBX1 (Affinity Capture-MS), YBX1 (Affinity Capture-MS), YBX1 (Biochemical Activity), AKT1 (Affinity Capture-Western), AKT1 (Reconstituted Complex), YBX1 (Affinity Capture-MS), YBX1 (Affinity Capture-MS), YBX1 (Affinity Capture-MS), YBX1 (Affinity Capture-MS)

ESM2 similar proteins: A1L1K8, B5DE31, D5MCN2, O94432, O95817, P14199, P16989, P21573, P21574, P25567, P41073, P41824, P45441, P45978, P46553, P62960, P62961, P67808, P67809, Q00436, Q06066, Q09801, Q10193, Q10422, Q10475, Q21351, Q24629, Q28618, Q3TLH4, Q57UZ7, Q5JVS0, Q5UR41, Q5XJD3, Q62764, Q69Z08, Q6CVS3, Q6NRY1, Q6NYG6, Q6PB22, Q75A59

Diamond homologs: B5DE31, E0J1Q3, E0J500, E1WGN1, O30875, O54310, O65639, O67327, P0A355, P0A356, P0A357, P0A358, P0A361, P0A362, P0A363, P0A972, P0A973, P0A974, P0A975, P0A978, P0A979, P0A980, P0A981, P0A986, P0A987, P0A9X9, P0A9Y0, P0A9Y1, P0A9Y2, P0A9Y3, P0A9Y4, P0A9Y5, P0A9Y6, P0A9Y7, P0A9Y8, P0A9Y9, P0A9Z0, P0C0F1, P0CL01, P0DA48

SIGNOR signaling

22 interactions.

A	Effect	B	Mechanism
RPS6KA3	up-regulates	YBX1	phosphorylation
AKT	up-regulates	YBX1	phosphorylation
RPS6KA1	up-regulates	YBX1	phosphorylation
AKT1	up-regulates	YBX1	phosphorylation
RPS6K	up-regulates	YBX1	phosphorylation
YBX1	“up-regulates quantity by expression”	ABCB1	“transcriptional regulation”
YBX1	“up-regulates quantity by expression”	CDH1	“transcriptional regulation”
YBX1	“up-regulates quantity by expression”	CXCR4	“transcriptional regulation”
YBX1	“up-regulates quantity by expression”	NDRG1	“transcriptional regulation”
YBX1	“down-regulates quantity by repression”	TYMS	“transcriptional regulation”
YBX1	“down-regulates quantity by repression”	ABCB1	“transcriptional regulation”
YBX1	“down-regulates quantity by repression”	MMP13	“transcriptional regulation”
FBXO33	“down-regulates quantity by destabilization”	YBX1	binding
SCF-betaTRCP	“down-regulates quantity by destabilization”	YBX1	polyubiquitination
RBBP6	“down-regulates quantity by destabilization”	YBX1	ubiquitination
PRKDC	“up-regulates activity”	YBX1	phosphorylation
SIAH1	“down-regulates quantity by destabilization”	YBX1	ubiquitination
MAPK1	“up-regulates activity”	YBX1	phosphorylation
PLK1	“up-regulates quantity”	YBX1	phosphorylation
MECP2	“up-regulates activity”	YBX1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 175 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.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytoplasmic translation	6	38.1×	4e-06
stress granule assembly	5	19.3×	5e-04
negative regulation of translation	12	15.1×	3e-08
mRNA stabilization	6	14.1×	4e-04
stem cell population maintenance	5	13.5×	2e-03
regulation of alternative mRNA splicing, via spliceosome	7	11.0×	4e-04
mRNA export from nucleus	5	9.5×	8e-03
positive regulation of translation	6	8.8×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1079 predictions. Top by Δscore:

Variant	Effect	Δscore
1:42683401:A:AG	acceptor_gain	1.0000
1:42683402:G:GG	acceptor_gain	1.0000
1:42683464:CAGGT:C	donor_loss	1.0000
1:42683467:GTGAG:G	donor_loss	1.0000
1:42683468:T:A	donor_loss	1.0000
1:42693484:TTGCA:T	acceptor_loss	1.0000
1:42693485:TGCA:T	acceptor_loss	1.0000
1:42693486:GCAGG:G	acceptor_loss	1.0000
1:42693487:CA:C	acceptor_loss	1.0000
1:42693488:A:AG	acceptor_gain	1.0000
1:42693488:A:G	acceptor_loss	1.0000
1:42693488:AG:A	acceptor_gain	1.0000
1:42693489:G:GT	acceptor_gain	1.0000
1:42693489:GG:G	acceptor_gain	1.0000
1:42693489:GGA:G	acceptor_gain	1.0000
1:42693489:GGAAT:G	acceptor_gain	1.0000
1:42693521:CAGG:C	donor_loss	1.0000
1:42693522:AGGTG:A	donor_loss	1.0000
1:42693523:GGT:G	donor_loss	1.0000
1:42693524:G:A	donor_loss	1.0000
1:42693525:T:G	donor_loss	1.0000
1:42696170:A:AG	acceptor_gain	1.0000
1:42696181:G:A	acceptor_gain	1.0000
1:42696187:T:TA	acceptor_gain	1.0000
1:42696197:A:AG	acceptor_gain	1.0000
1:42696198:G:GG	acceptor_gain	1.0000
1:42696198:GACT:G	acceptor_gain	1.0000
1:42697174:TTTCA:T	acceptor_loss	1.0000
1:42697177:CAGG:C	acceptor_loss	1.0000
1:42697178:AG:A	acceptor_gain	1.0000

AlphaMissense

2107 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:42682731:G:C	A56P	1.000
1:42683411:G:C	V59L	1.000
1:42683412:T:A	V59D	1.000
1:42683412:T:C	V59A	1.000
1:42683417:G:A	G61R	1.000
1:42683417:G:C	G61R	1.000
1:42683418:G:A	G61E	1.000
1:42683418:G:C	G61A	1.000
1:42683418:G:T	G61V	1.000
1:42683423:G:C	V63L	1.000
1:42683423:G:T	V63L	1.000
1:42683424:T:A	V63E	1.000
1:42683424:T:C	V63A	1.000
1:42683426:A:C	K64Q	1.000
1:42683426:A:G	K64E	1.000
1:42683427:A:T	K64I	1.000
1:42683428:A:C	K64N	1.000
1:42683428:A:T	K64N	1.000
1:42683429:T:A	W65R	1.000
1:42683429:T:C	W65R	1.000
1:42683429:T:G	W65G	1.000
1:42683430:G:C	W65S	1.000
1:42683430:G:T	W65L	1.000
1:42683431:G:C	W65C	1.000
1:42683431:G:T	W65C	1.000
1:42683432:T:A	F66I	1.000
1:42683432:T:C	F66L	1.000
1:42683432:T:G	F66V	1.000
1:42683433:T:C	F66S	1.000
1:42683433:T:G	F66C	1.000

dbSNP variants (sampled 300 via entrez): RS1000182910 (1:42685326 C>T), RS1000260090 (1:42684828 G>C), RS1000291167 (1:42685137 G>A), RS1000303284 (1:42701914 G>A,C), RS1000312485 (1:42696511 G>A,C,T), RS1000422870 (1:42690296 CAT>C), RS1000594343 (1:42686039 C>T), RS1000603337 (1:42690466 A>G), RS1000625337 (1:42686343 A>G), RS1000625701 (1:42689393 G>A), RS1000789876 (1:42684098 C>T), RS1001139483 (1:42682085 T>C), RS1001219925 (1:42684751 G>C), RS1001375760 (1:42703373 G>A,C), RS1001604221 (1:42681504 T>C,G)

Disease associations

OMIM: gene MIM:154030 | 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: yes

ChEMBL targets (1): CHEMBL4296006 (SINGLE PROTEIN)

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

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs323719	YBX1		0.00	0
rs323720	YBX1		0.00	0
rs10493112	YBX1		0.00	0

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.25	Kd	56.44	nM	CHEMBL5653589
7.25	ED50	56.44	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 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	2149795: Binding affinity to human YBX1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0564	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, affects cotreatment	3
sodium arsenite	affects binding, increases reaction, affects cotreatment, decreases expression, increases abundance (+1 more)	3
arsenite	affects localization, affects binding, increases reaction	2
bisphenol S	affects expression, affects cotreatment, decreases expression	2
Cisplatin	affects binding, increases reaction, decreases response to substance	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	decreases sumoylation	1
ZCL-082	decreases phosphorylation, decreases reaction	1
beauvericin	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
beta-lapachone	increases expression	1
sodium bichromate	increases activity	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
butylidenephthalide	decreases expression	1
gossypol acetic acid	increases expression	1
coumarin	decreases phosphorylation	1
cupric oxide	increases expression	1
quinoline	decreases expression	1
nivalenol	increases expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
CD 437	decreases expression	1
chloropicrin	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118550	Binding	Binding affinity to YBX1 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

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A7Z0	SEES3-1V human YBX1, clone1	Embryonic stem cell	Male
CVCL_A7Z1	SEES3-1V human YBX1, clone2	Embryonic stem cell	Male
CVCL_A7Z2	SEES3-1V human YBX1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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