YBX1
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. [provided by RefSeq, Sep 2015]
Function
DNA- and RNA-binding protein involved in various processes, such as translational repression, RNA stabilization, mRNA splicing, DNA repair and transcription regulation (PubMed:8188694, PubMed:10817758, PubMed:11698476, PubMed:14718551, PubMed:18809583, PubMed:31358969).
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) (PubMed:19561594, PubMed:31358969).
Promotes mRNA stabilization: acts by binding to m5C-containing mRNAs and recruiting the mRNA stability maintainer ELAVL1, thereby preventing mRNA decay (PubMed:10817758, PubMed:11698476, PubMed:31358969).
Component of the CRD-mediated complex that promotes MYC mRNA stability (PubMed:19029303).
Contributes to the regulation of translation by modulating the interaction between the mRNA and eukaryotic initiation factors (By similarity).
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 (PubMed:27559612, PubMed:29073095).
Probably sorts RNAs in exosomes by recognizing and binding C5-methylcytosine (m5C)-containing RNAs (PubMed:28341602, PubMed:29073095).
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 (PubMed:29712925).
Also involved in pre-mRNA alternative splicing regulation: binds to splice sites in pre-mRNA and regulates splice site selection (PubMed:12604611).
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' (PubMed:18809583).
Binds to promoters that contain a Y-box (5'-CTGATTGGCCAA-3'), such as MDR1 and HLA class II genes (PubMed:8188694, PubMed:18809583).
Promotes separation of DNA strands that contain mismatches or are modified by cisplatin (PubMed:14718551).
Has endonucleolytic activity and can introduce nicks or breaks into double-stranded DNA, suggesting a role in DNA repair (PubMed:14718551).
The secreted form acts as an extracellular mitogen and stimulates cell migration and proliferation (PubMed:19483673).
Biological Process
Cellular response to interleukin-7IEA:Ensembl
CRD-mediated mRNA stabilizationManual Assertion Based On ExperimentIDA:ComplexPortal
Embryonic morphogenesisISS:UniProtKB
Epidermis developmentISS:UniProtKB
In utero embryonic developmentIEA:Ensembl
miRNA transportManual Assertion Based On ExperimentIDA:UniProtKB
mRNA processingIEA:UniProtKB-KW
mRNA stabilizationManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of cellular senescenceISS:UniProtKB
Negative regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decayManual Assertion Based On ExperimentIDA:ComplexPortal
Negative regulation of striated muscle cell differentiationIEA:Ensembl
Negative regulation of transcription by RNA polymerase IIIEA:Ensembl
Negative regulation of translationISS:UniProtKB
Positive regulation of cell divisionIEA:UniProtKB-KW
Positive regulation of cytoplasmic translationManual Assertion Based On ExperimentIDA:ComplexPortal
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:NTNU_SB
Protein localization to cytoplasmic stress granuleManual Assertion Based On ExperimentIMP:AgBase
Regulation of gene expressionManual Assertion Based On ExperimentIBA:GO_Central
Regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
RNA splicingIEA:UniProtKB-KW
RNA transportManual Assertion Based On ExperimentIMP:UniProtKB
tRNA transportManual Assertion Based On ExperimentIMP:UniProtKB
Cellular Location
Cytoplasm
Nucleus
Cytoplasmic granule
Secreted
Secreted, extracellular exosome
Predominantly cytoplasmic in proliferating cells (PubMed:12604611).
Cytotoxic stress and DNA damage enhance translocation to the nucleus (PubMed:14718551).
Localized in cytoplasmic mRNP granules containing untranslated mRNAs (PubMed:25229427).
Shuttles between nucleus and cytoplasm (PubMed:25229427).
Localized with DDX1, MBNL1 and TIAL1 in stress granules upon stress (PubMed:18335541).
Secreted by mesangial and monocytic cells after inflammatory challenges (PubMed:19483673).
PTM
Ubiquitinated by RBBP6; leading to a decrease of YBX1 transcactivational ability.
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 (By similarity).