YBX1 (Y box binding protein 1)

2010-11-01   Valentina Evdokimova , Alexey Sorokin 

Institute of Protein Research, Pushchino, Moscow Region 142290, Russian Federation




Atlas Image
Genomic organization of YBX1. Box = exon (blue = 5UTR, yellow = CDS, light red = 3UTR). Line = intron.


The human YBX1 gene consists of 8 exons and 7 introns spanning a 19.2-kb genomic region. Intron number 1 is phase 1 (between 1st and 2nd base of codon). Introns number 2 and 6 are phase 2 (between 2nd and 3rd base of codon). Introns number 3, 4, 5 are phase 0 (between codons). According to the SNP source (dbSNP NCBI), non-synonymous polymorphism has been reported for the codons 30 (rs11558135), 237 (rs3887881), 251 (rs55676223), and 261 (rs3887879). The YBX1 promoter region contains no typical TATA or CCAAT box, but has multiple E-boxes located between -1855 and -422 nucleotides (relative to the start of exon 1) and several GT and GC boxes. The gene also contains a large and highly conserved CpG island at the immediate 5 promoter region which extends to the first exon encoding 5 UTR of YBX1 mRNA. The region between nucleotides -119 to +127 was shown to be essential for transcriptional activity in the reporter assays (Makino et al., 1996). YBX1 is constitutively expressed in multiple human tissues and its expression can be further induced by the E-box-binding transcription factors such as c-myc (Uramoto et al., 2002), Twist (Shiota et al., 2008) and Math2 (Ohashi et al., 2009).


The main processed mRNA is 1514 bp. It encompasses exons 1-8. The 70-amino acid cold-shock domain (CSD) is encoded separately by exons 2-5. Four additional splice variants in human were predicted (Ensembl), two of which (YBX1-004 and YBX1-201) preserve exons 2 and 3 coding for core elements of the CSD, the RNP1 and RNP2 motifs, respectively. An alternative transcript for ctYB-1, the YBX1 homologous gene in C. tentans, has been reported (Nashchekin et al., 2007).


DescriptionSymbolNCBI gene IDPositionIntrons/exonsORFIdentity with YBX1Gaps
nuclease sensitive element binding protein 1 pseudogenebA327L3.41583739p13.1IntronlessStops after E881477/1515 (97%)2/1515 (0%)
Y box binding protein 1 pseudogene 1YBX1P1506314q23.3Intronless 1496 bp-1488/1531 (97%)20/1511 (1%)
Y box binding protein 1 pseudogene 2YBX1P26465317q22.32 exons, 1 intron, 1553 bpStops after E881431/1529 (93%)43/1529 (2%)
Y box binding protein 1 pseudogeneLOC1001310121001310127q36.1Intronless, 820 bp-287/353 (81%)26/353 (7%)


Atlas Image
Structural and functional organization of YB-1. YB-1 is composed by three domains: N-terminal Ala/Pro rich (AP) domain, cold shock domain (CSD) and the C-terminal domain (CTD) containing clusters of positively and negatively charged amino acids. Indicated are some known molecular partners of YB-1 and sites of their interactions (from Sorokin et al., 2005). The arrow indicates proteasomal cleavage sites.


The YBX1 gene encodes the Y-box protein 1 (YB-1) which consists of 324 amino acid residues and has the isoelectric point 10.3. Theoretical MW is 35924, however YB-1 is known to migrate as a ~45-50 kDa protein in SDS-polyacrylamide gels due to its anomalous electrophoretic mobility. YB-1 belongs to the family of multifunctional DNA/RNA binding proteins that are highly conserved throughout evolution and found in eukaryotes, prokaryotes and archaea. The most conserved region in YB-1 is the 80 amino acid CSD which exhibits >40% identity and >60% similarity to the major E. coli cold shock protein CspA (Matsumoto and Wolffe, 1998; Sommerville, 1999). The CSD possesses RNP1 and RNP2-like consensus motifs and is represented by a five-stranded beta-barrel structure which creates a surface rich in aromatic and basic amino acids that may act as a large nucleic acid-binding site (Wolffe et al., 1992; Wolffe, 1994). The CSD has a preference for binding single-stranded pyrimidine-rich sequences. The N-terminal AP domain of YB-1 is similar to that found in several other transcription factors and may thus be important for its transcriptional activity. This region is also essential for interaction with p53 and modulation of p53-mediated transcription (Okamoto et al., 2000), and for association with actin microfilaments and mRNA compartmentalization (Ruzanov et al., 1999). The C-terminal region of YB-1 is responsible for sequence-nonspecific binding to DNA and RNA and mediation of protein-protein interactions (Wolffe, 1994; Sommerville and Ladomery, 1996). An inverted CCAAT-box found in HLA class II gene promoters, a so-called Y-box, was originally determined as the YB-1 binding motif (Didier et al., 1988). Later studies have concluded that YB-1 rather recognizes the DNA structure than a defined nucleotide sequence, making prediction of its target genes not feasible with conventional in silico analyses (Swamynathan et al., 1998). YB-1 is also capable of unwinding DNA and RNA duplexes, especially those containing mismatches, thereby promoting strand exchange and formation of perfectly matched duplex structures (Skabkin et al., 2001; Gaudreault et al., 2004).


According to Human Protein Atlas, YB-1 is variably expressed in most normal human tissues. Its expression is elevated in multiple cancer types (Kohno et al., 2003).


Mostly cytosolic. Shuttles between cytoplasm and nucleus. Localized in cytoplasmic stress granules and processing bodies containing untranslated mRNAs (Kedersha and Anderson, 2007). Nuclear translocation is induced in response to various stresses, including adenoviral infection (Holm et al., 2002), hyperthermia (Stein et al., 2001), DNA damage (Kohno et al., 2003) and activation of PI3K-Akt signaling (Sutherland et al., 2005).


The diverse biological functions of YB-1 appear to arise from its broad nucleic acid binding properties. YB-1 has been implicated in pre-mRNA splicing, transcriptional regulation, mRNA translation and stability as well as in chromatin remodelling, DNA repair and environmental stress responses (Kohno et al., 2003; Matsumoto and Bay, 2005).
Splicing. YB-1 regulates splice site selection via direct binding to splicing recognition motifs in pre-mRNA, including A/C-rich exon enhancers (Stickeler et al., 2001) or via interaction with splicing factors from the SR family (Li et al., 2003; Raffetseder et al., 2003).
Transcription. YB-1 is capable of binding to promoters of many genes, many of which lack the Y-box, and either activates or represses transcription. Among the genes activated by YB-1 are thymidine kinase, proliferating cell nuclear antigen (PCNA), cyclin A and cyclin B1, DNA topoisomerase II alpha, gelatinase A, matrix metalloproteinase 2, multidrug resistance 1 (MDR1), EGFR and protein tyrosine phosphatase 1B. Genes that are transcriptionally repressed by YB-1 include MHC class II, collagen alpha1, granulocyte-macrophage colony-stimulating factor (GM-CSF), etc (reviewed in Ladomery and Sommerville, 1995; Kohno et al., 2003; Kuwano et al., 2003). Overall, YB-1 is considered as an important regulator of growth- and stress-associated genes.
mRNA translation and stability. YB-1 (p50) is known as a major structural component of messenger ribonucleoprotein particles (mRNPs) which exerts positive or negative effects on translation, depending on the amount bound to mRNA (Evdokimova and Ovchinnikov, 1999). YB-1 regulates translational activity of many growth- and differentiation-associated mRNAs, including Snail1, and selectively protects capped mRNAs against degradation (Evdokimova et al., 2001; Evdokimova et al., 2006; Evdokimova et al., 2009). YB-1 appears to play a role in stabilization of short-lived mRNAs, including IL-2 (Chen et al., 2000), GM-CSF (Capowski et al., 2001) and VEGF (Coles et al., 2004).
DNA repair and stress response. YB-1 is involved in base excision and mismatch repair pathways via interaction with multiple DNA repair proteins including glycosylase NEIL2, DNA polymerase beta and delta, DNA ligase III, APE1, MSH2, Ku80, WRN, endonuclease III, etc (Marenstein et al., 2001; Gaudreault et al., 2004; Das et al., 2007). YB-1 also directly binds and promotes separation of DNA strands that contain mismatches or are modified by cisplatin (Ise et al., 1999; Skabkin et al., 2001; Gaudreault et al., 2004). Various stresses, including DNA damage, adenovirus infection and hyperthermia, induce nuclear translocation of YB-1 (Ohga et al., 1996; Kohno et al., 2003) and its proteasomal cleavage (Sorokin et al., 2005). Accumulation of the full-length and/or truncated YB-1 proteins in the nucleus is associated with increased survival and multidrug resistance (Kohno et al., 2003; Sorokin et al., 2005). YB-1 knock-out in mice is lethal (Lu et al., 2005; Lu et al., 2006). Fibroblasts derived from YB-1(-/-) embryos exhibit a reduced ability to respond to oxidative, genotoxic and oncogene-induced stresses, further implicating YB-1 in stress responses and embryonic development.
Tumorigenesis. YB-1 is frequently overexpressed in multiple human cancers (reviewed in Kohno et al., 2003; Kuwano et al., 2003). In many cases, YB-1 levels are elevated in the nucleus, positively correlating with multiple drug resistance and poor patient outcome (Bargou et al., 1997; Janz et al., 2002). Ectopic expression of YB-1 in breast cancer cells and mouse models stimulated tumor growth (Bergmann et al., 2005; Sutherland et al., 2005). Yet, the role of YB-1 in tumorigenesis is controversial. YB-1 overexpression blocked oncogenic transformation caused by PI3K or Akt (Bader et al., 2003). These apparently contradictory results were proposed to be due to differential localization of YB-1; its interference with oncogenic transformation is associated with cytosolic localization and a consequent function in translational control (Bader and Vogt, 2004; Bader and Vogt, 2005).


YB-1 is highly homologous to human DbpA (12p13; expressed predominantly in heart and muscle) and DbpC/contrin (17p11; expressed exclusively in germ cells). They share greater than 90% identity within the CSD and a high degree of similarity in the N- and C-terminal domains, including C-terminal clusters of basic and acidic amino acids. Mouse orthologues are YB-1 (encoded by Ybx1; 99% overall aminoacid identity with human YB-1), MSY2 (Ybx2; ~93% identity with contrin) and MSY4 (~86% identity with DbpA).



Mutations in YBX1 are not reported.

Implicated in

Entity name
Breast cancer
Elevated expression and nuclear localization of YB-1 is associated with increased proliferation, multidrug resistance and tumor aggressiveness across all tumor subtypes. Nuclear localization positively correlates with increased expression of MDR1/P-gp and HER2/ErbB2 (Bargou et al., 1997; Saji et al., 2003; Fujii et al., 2008; Habibi et al., 2008). Enforced YB-1 expression in mammary glands of transgenic mice induced chromosomal instability and tumorigenesis (Bergmann et al., 2005). YB-1 effects on tumorigenesis are likely dependent on cellular signaling. It blocks oncogenic transformation induced by Akt or PI3K but not by Src, Jun or Qin oncoproteins (Bader et al., 2003), and decreases proliferation of tumor cells with activated MAPK-Ras signaling, while inducing their metastatic ability (Evdokimova et al., 2009).
Nuclear YB-1 is considered as a marker of poor clinical outcome. Patients with high YB-1 levels are likely to benefit from dose-intensified chemotherapy regimens (Gluz et al., 2009).
Entity name
Prostate cancer
YB-1 is upregulated during prostate cancer tumor progression and is reported to increase P-glycoprotein activity (Giménez-Bonafé et al., 2004).
Entity name
Lung cancer
Nuclear YB-1 is associated with poor survival and expression of HER2/ErbB2 and HER3/ErbB3 in non-small cell lung cancer (Kashihara et al., 2009).
Patients with nuclear YB-1 expression and p53 mutations appear to have the worst prognosis (median survival 3 months), while best outcome was found in patients with no nuclear YB-1 and wild-type p53 (Gessner et al., 2004).
Entity name
Colon cancer
YB-1 expression levels are elevated in colorectal carcinoma and positively correlate with DNA topoisomerase II alpha and PCNA expression but not with P-gp (Shibao et al., 1999). In colon cancer cells, YB-1 accumulates in the nuclei in response to vinblastin and is associated with development of vinblastin resistance and elevated expression of P-gp (Vaiman et al., 2007).
Entity name
Ovarian cancer
YB-1 levels are elevated in the nuclei of cisplatin-resistant cancer cell lines and cancer patients, indicating that nuclear YB-1 may be associated with acquired cisplatin resistance in ovarian cancers (Yahata et al., 2002).
Co-expression of YB-1 and P-gp is indicative of unfavourable prognosis in ovarian cancer (Huang et al., 2004).
Entity name
Haematopoietic malignancies
Large B-cell lymphoma, multiple myeloma.
Nuclear expression of YB-1 is associated with P-gp expression and poor response to chemotherapy in large B-cell lymphoma (Xu et al., 2009). YB-1 is strongly expressed in normal plasma cell precursor blasts as well as in a multiple myeloma tumor specimens and cell lines but not in normal bone marrow or plasma cells. Its expression is associated with an immature morphology, a highly proliferative phenotype and doxorubicin resistance, indicating its involvement in drug resistance and disease progression in multiple myeloma (Chatterjee et al., 2008).
Entity name
Bone and soft tissue tumors
Rhabdomyosarcoma, synovial sarcoma and osteosarcoma.
Nuclear expression of YB-1 protein positively correlates with P-gp expression and a higher proliferative index in embryonal (ERMS) but not in alveolar rhabdomyosarcoma (ARMS) (Oda et al., 2008), synovial sarcoma (Oda et al., 2003) and osteosarcoma (Oda et al., 1998).
Entity name
YB-1 expression is increased in melanoma cells compared to benign melanocytes, and nuclear YB-1 is found in invasive and metastatic melanoma cells. YB-1 expression is associated with increased proliferation, tumor invasion and chemoresistance (Schittek et al., 2007).
Entity name
Nervous system tumors
Glioblastoma, neuroblastoma.
YB-1 levels are elevated in pediatric glioblastoma (Faury et al., 2007) and neuroblastoma (Wachowiak et al., 2010).
In neuroblastoma, no correlation of YB-1 expression with survival, risk factors or stage of the disease was found.


Pubmed IDLast YearTitleAuthors
145303932003Y box-binding protein 1 induces resistance to oncogenic transformation by the phosphatidylinositol 3-kinase pathway.Bader AG et al
157438082005Inhibition of protein synthesis by Y box-binding protein 1 blocks oncogenic cell transformation.Bader AG et al
90951801997Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene expression.Bargou RC et al
158997972005YB-1 provokes breast cancer through the induction of chromosomal instability that emerges from mitotic failure and centrosome amplification.Bergmann S et al
116984762001Y box-binding factor promotes eosinophil survival by stabilizing granulocyte-macrophage colony-stimulating factor mRNA.Capowski EE et al
180067042008The Y-box binding protein YB-1 is associated with progressive disease and mediates survival and drug resistance in multiple myeloma.Chatterjee M et al
108177582000Nucleolin and YB-1 are required for JNK-mediated interleukin-2 mRNA stabilization during T-cell activation.Chen CY et al
147286922004A multi-protein complex containing cold shock domain (Y-box) and polypyrimidine tract binding proteins forms on the vascular endothelial growth factor mRNA. Potential role in mRNA stabilization.Coles LS et al
176867772007Stimulation of NEIL2-mediated oxidized base excision repair via YB-1 interaction during oxidative stress.Das S et al
31746361988Characterization of the cDNA encoding a protein binding to the major histocompatibility complex class II Y box.Didier DK et al
194110692009Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial-mesenchymal transition.Evdokimova V et al
174010092007Molecular profiling identifies prognostic subgroups of pediatric glioblastoma and shows increased YB-1 expression in tumors.Faury D et al
183166152008Expression of HER2 and estrogen receptor alpha depends upon nuclear localization of Y-box binding protein-1 in human breast cancers.Fujii T et al
147185512004YB-1 promotes strand separation in vitro of duplex DNA containing either mispaired bases or cisplatin modifications, exhibits endonucleolytic activities and binds several DNA repair proteins.Gaudreault I et al
147382252004Nuclear YB-1 expression as a negative prognostic marker in nonsmall cell lung cancer.Gessner C et al
150426102004YB-1 is upregulated during prostate cancer tumor progression and increases P-glycoprotein activity.Giménez-Bonafé P et al
199011222009Y-box-binding protein YB-1 identifies high-risk patients with primary breast cancer benefiting from rapidly cycled tandem high-dose adjuvant chemotherapy.Gluz O et al
189259502008Redefining prognostic factors for breast cancer: YB-1 is a stronger predictor of relapse and disease-specific survival than estrogen receptor or HER-2 across all tumor subtypes.Habibi G et al
117885822002YB-1 relocates to the nucleus in adenovirus-infected cells and facilitates viral replication by inducing E2 gene expression through the E2 late promoter.Holm PS et al
150999352004Co-expression of Y box-binding protein-1 and P-glycoprotein as a prognostic marker for survival in epithelial ovarian cancer.Huang X et al
99270441999Transcription factor Y-box binding protein 1 binds preferentially to cisplatin-modified DNA and interacts with proliferating cell nuclear antigen.Ise T et al
117742772002Y-box factor YB-1 predicts drug resistance and patient outcome in breast cancer independent of clinically relevant tumor biologic factors HER2, uPA and PAI-1.Janz M et al
196488252009Nuclear Y-box binding protein-1, a predictive marker of prognosis, is correlated with expression of HER2/ErbB2 and HER3/ErbB3 in non-small cell lung cancer.Kashihara M et al
179232312007Mammalian stress granules and processing bodies.Kedersha N et al
128157242003The pleiotropic functions of the Y-box-binding protein, YB-1.Kohno K et al
127084672003The basic and clinical implications of ABC transporters, Y-box-binding protein-1 (YB-1) and angiogenesis-related factors in human malignancies.Kuwano M et al
77025981995A role for Y-box proteins in cell proliferation.Ladomery M et al
145599932003Regulation of alternative splicing by SRrp86 and its interacting proteins.Li J et al
169543782006Cold shock domain family members YB-1 and MSY4 share essential functions during murine embryogenesis.Lu ZH et al
86575681996Structural and functional analysis of the human Y-box binding protein (YB-1) gene promoter.Makino Y et al
112874252001Stimulation of human endonuclease III by Y box-binding protein 1 (DNA-binding protein B). Interaction between a base excision repair enzyme and a transcription factor.Marenstein DR et al
195650082005Significance of the Y-box proteins in human cancers.Matsumoto K et al
172221822007Two splicing isoforms of the Y-box protein ctYB-1 appear on the same mRNA molecule.Nashchekin D et al
183774242008Different expression profiles of Y-box-binding protein-1 and multidrug resistance-associated proteins between alveolar and embryonal rhabdomyosarcoma.Oda Y et al
125338392003Nuclear expression of Y-box-binding protein-1 correlates with P-glycoprotein and topoisomerase II alpha expression, and with poor prognosis in synovial sarcoma.Oda Y et al
97481491998Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in human osteosarcoma.Oda Y et al
192258662009YB-1 transcription in the postnatal brain is regulated by a bHLH transcription factor Math2 through an E-box sequence in the 5'-UTR of the gene.Ohashi S et al
87975961996Role of the human Y box-binding protein YB-1 in cellular sensitivity to the DNA-damaging agents cisplatin, mitomycin C, and ultraviolet light.Ohga T et al
111753332000Direct interaction of p53 with the Y-box binding protein, YB-1: a mechanism for regulation of human gene expression.Okamoto T et al
126046112003Splicing factor SRp30c interaction with Y-box protein-1 confers nuclear YB-1 shuttling and alternative splice site selection.Raffetseder U et al
105042971999Interaction of the universal mRNA-binding protein, p50, with actin: a possible link between mRNA and microfilaments.Ruzanov PV et al
125651742003Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in human breast carcinoma.Saji H et al
172660412007The increased expression of Y box-binding protein 1 in melanoma stimulates proliferation and tumor invasion, antagonizes apoptosis and enhances chemoresistance.Schittek B et al
105971871999Enhanced coexpression of YB-1 and DNA topoisomerase II alpha genes in human colorectal carcinomas.Shibao K et al
181723012008Twist promotes tumor cell growth through YB-1 expression.Shiota M et al
115858332001The major messenger ribonucleoprotein particle protein p50 (YB-1) promotes nucleic acid strand annealing.Skabkin MA et al
103778941999Activities of cold-shock domain proteins in translation control.Sommerville J et al
161930612005Proteasome-mediated cleavage of the Y-box-binding protein 1 is linked to DNA-damage stress response.Sorokin AV et al
113697622001Hyperthermia-induced nuclear translocation of transcription factor YB-1 leads to enhanced expression of multidrug resistance-related ABC transporters.Stein U et al
114471232001The RNA binding protein YB-1 binds A/C-rich exon enhancers and stimulates splicing of the CD44 alternative exon v4.Stickeler E et al
158061602005Akt phosphorylates the Y-box binding protein 1 at Ser102 located in the cold shock domain and affects the anchorage-independent growth of breast cancer cells.Sutherland BW et al
95764781998Role of single-stranded DNA regions and Y-box proteins in transcriptional regulation of viral and cellular genes.Swamynathan SK et al
120800432002p73 Interacts with c-Myc to regulate Y-box-binding protein-1 expression.Uramoto H et al
182143012007Development of drug resistance in the population of colon cancer cells under the effect of multifunctional protein YB-1.Vaiman AV et al
205304342010Y-box-binding protein-1 is a potential novel tumour marker for neuroblastoma.Wachowiak R et al
16229271992The Y-box factors: a family of nucleic acid binding proteins conserved from Escherichia coli to man.Wolffe AP et al
80313011994Structural and functional properties of the evolutionarily ancient Y-box family of nucleic acid binding proteins.Wolffe AP et al
195001332009Nuclear expression of YB-1 in diffuse large B-cell lymphoma: correlation with disease activity and patient outcome.Xu W et al
124583432002Increased nuclear localization of transcription factor YB-1 in acquired cisplatin-resistant ovarian cancer.Yahata H et al

Other Information

Locus ID:

NCBI: 4904
MIM: 154030
HGNC: 8014
Ensembl: ENSG00000065978


dbSNP: 4904
ClinVar: 4904
TCGA: ENSG00000065978


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Gene ExpressionREACTOMER-HSA-74160
Processing of Capped Intron-Containing Pre-mRNAREACTOMER-HSA-72203
mRNA SplicingREACTOMER-HSA-72172
mRNA Splicing - Major PathwayREACTOMER-HSA-72163
mRNA Splicing - Minor PathwayREACTOMER-HSA-72165

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
259576862015Endogenous tRNA-Derived Fragments Suppress Breast Cancer Progression via YBX1 Displacement.155
194110692009Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial-mesenchymal transition.144
223395962011Y-box-binding protein 1 (YB-1) and its functions.106
158061602005Akt phosphorylates the Y-box binding protein 1 at Ser102 located in the cold shock domain and affects the anchorage-independent growth of breast cancer cells.86
242179782014YB-1 protein: functions and regulation.76
259594982015lncRNA GAS5 enhances G1 cell cycle arrest via binding to YBX1 to regulate p21 expression in stomach cancer.71
259655732015Translational Activation of HIF1α by YB-1 Promotes Sarcoma Metastasis.70
126955162003YB-1 as a cell cycle-regulated transcription factor facilitating cyclin A and cyclin B1 gene expression.68
203322342010Y-box binding protein-1 induces the expression of CD44 and CD49f leading to enhanced self-renewal, mammosphere growth, and drug resistance.65
225199562013Protein Ser/Thr phosphatases--the ugly ducklings of cell signalling.63


Valentina Evdokimova ; Alexey Sorokin

YBX1 (Y box binding protein 1)

Atlas Genet Cytogenet Oncol Haematol. 2010-11-01

Online version: http://atlasgeneticsoncology.org/gene/46554/ybx1-(y-box-binding-protein-1)