Details for: RBM15B

Gene ID: 29890

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: RBM15B

Ensembl ID: ENSG00000259956

Description: RNA binding motif protein 15B

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • hematopoietic precursor cell CL0008001
    CSI 4.75
    rCSI 4.89%
    PRS 97.45
  • pancreatic acinar cell CL0002064
    CSI 3.85
    rCSI 5.12%
    PRS 96.02
  • interneuron CL0000099
    CSI 3.6
    rCSI 7.23%
    PRS 90.36
  • interstitial cell of Cajal CL0002088
    CSI 3.58
    rCSI 4.56%
    PRS 96.62
  • precursor B cell CL0000817
    CSI 3.56
    rCSI 3.12%
    PRS 96.62
  • CD4-positive helper T cell CL0000492
    CSI 3.55
    rCSI 2.68%
    PRS 98.77
  • neural crest cell CL0011012
    CSI 3.27
    rCSI 2.59%
    PRS 89.77
  • bronchus fibroblast of lung CL2000093
    CSI 3.11
    rCSI 2.52%
    PRS 94.25
  • group 3 innate lymphoid cell CL0001071
    CSI 2.98
    rCSI 2.24%
    PRS 96.19
  • stem cell CL0000034
    CSI 2.88
    rCSI 2.78%
    PRS 91.87
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.79
    rCSI 4.93%
    PRS 84.98
  • multi-ciliated epithelial cell CL0005012
    CSI 2.65
    rCSI 2.65%
    PRS 89.89
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.54
    rCSI 2.3%
    PRS 93.61
  • nasal mucosa goblet cell CL0002480
    CSI 2.47
    rCSI 2.86%
    PRS 94.23
  • ciliated cell CL0000064
    CSI 2.37
    rCSI 3.84%
    PRS 89.21
  • mesodermal cell CL0000222
    CSI 2.35
    rCSI 2.83%
    PRS 93.77
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.2
    rCSI 1.7%
    PRS 96.6
  • radial glial cell CL0000681
    CSI 2.1
    rCSI 2.92%
    PRS 93.06
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.1
    rCSI 2.69%
    PRS 91.35
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 2.03
    rCSI 6%
    PRS 94.03
  • enteroendocrine cell CL0000164
    CSI 1.9
    rCSI 2.59%
    PRS 92.49
  • club cell CL0000158
    CSI 1.83
    rCSI 2.68%
    PRS 91.43
  • pancreatic ductal cell CL0002079
    CSI 1.51
    rCSI 2.94%
    PRS 95.14
  • progenitor cell CL0011026
    CSI 1.48
    rCSI 3.15%
    PRS 88.89
  • type B pancreatic cell CL0000169
    CSI 1.48
    rCSI 3.27%
    PRS 94.28

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [RBM15B](/details-gene/29890) (RNA Binding Motif Protein 15B) is a protein-coding gene located on chromosome 3. It functions as an RNA-binding protein that plays a central role in multiple stages of RNA metabolism, including mRNA processing, alternative splicing, and nuclear export. Functionally, it is a component of the RNA N6-methyladenosine (m6A) methyltransferase complex, linking it to the field of epitranscriptomics. Expression data indicates that **Overall**, [RBM15B](/details-gene/29890) has the highest significance in [hematopoietic precursor cell](/details-cell/CL0008001), suggesting a critical role in the development and maintenance of the blood and immune systems. Its notable expression in other diverse cell types, such as [pancreatic acinar cell](/details-cell/CL0002064) and [interneuron](/details-cell/CL0000099), points towards a broader, fundamental function in cellular RNA biology. ## Cellular Roles and Expression Landscape The expression profile of [RBM15B](/details-gene/29890) highlights its profound importance in hematopoiesis and immunity. **Overall**, it is most significant in [hematopoietic precursor cell](/details-cell/CL0008001) (CSI: 4.75), a finding strongly supported by its high significance in more committed lineages such as [precursor B cell](/details-cell/CL0000817), [CD4-positive helper T cell](/details-cell/CL0000492), [group 3 innate lymphoid cell](/details-cell/CL0001071), and [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050). This pattern suggests [RBM15B](/details-gene/29890) is a key regulator throughout the hematopoietic differentiation cascade. Beyond the hematopoietic system, [RBM15B](/details-gene/29890) also shows significant expression in several other specialized cell types. Its high CSI in [pancreatic acinar cell](/details-cell/CL0002064) may relate to the high demand for protein synthesis and mRNA processing in these secretory cells. Furthermore, its significance in neuronal populations like [interneuron](/details-cell/CL0000099) and developmental cells such as [neural crest cell](/details-cell/CL0011012) suggests a role in the complex gene regulation required for nervous system development and function. The gene's activity in various progenitor and stem cell populations, including [stem cell](/details-cell/CL0000034), underscores its likely involvement in fundamental processes of cell fate determination and maintenance. ## Pathways and Molecular Function [RBM15B](/details-gene/29890) is primarily localized to the [nucleus](/details-cell/GO:0005634), specifically within the [nucleoplasm](/details-cell/GO:0005654), [nuclear speck](/details-cell/GO:0016607), and [nucleolus](/details-cell/GO:0005730). Its molecular function is defined by its ability to bind RNA ([GO:0003723](https://www.ebi.ac.uk/QuickGO/term/GO:0003723)), particularly mRNA ([GO:0003729](https://www.ebi.ac.uk/QuickGO/term/GO:0003729)), and to interact with other proteins ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)). This binding activity enables its participation in several critical biological processes: * **RNA Splicing and Processing:** [RBM15B](/details-gene/29890) is involved in [mRNA processing](/details-cell/GO:0006397) and [RNA splicing](/details-cell/GO:0008380). It can antagonize the function of serine-arginine (SR) proteins, thereby negatively regulating alternative mRNA splicing events ([Link](https://doi.org/10.1074/jbc.m110.192518)). * **mRNA Export:** The protein facilitates [mRNA export from nucleus](/details-cell/GO:0006406) by acting as a cofactor for the nuclear export receptor NXF1, a key component of the transport machinery ([Link](https://doi.org/10.1074/jbc.m109.040113)). * **Epitranscriptomics:** [RBM15B](/details-gene/29890) is a component of the [RNA n6-methyladenosine methyltransferase complex](/details-cell/GO:0036396), which is responsible for one of the most common internal modifications on mRNA, a process known as [RNA methylation](/details-cell/GO:0001510). This modification influences mRNA stability, splicing, and translation. * **Transcriptional Regulation:** It has also been implicated in the [negative regulation of dna-templated transcription](/details-cell/GO:0045892) and dosage compensation mechanisms ([GO:0009048](https://www.ebi.ac.uk/QuickGO/term/GO:0009048)). ## Research Directions The widespread and fundamental role of [RBM15B](/details-gene/29890) in RNA biology, coupled with its pronounced significance in hematopoietic precursors, provides several avenues for future investigation. **Proposed Hypotheses:** 1. Given its high significance in diverse hematopoietic progenitor populations and its function in alternative splicing, [RBM15B](/details-gene/29890) may act as a critical splicing factor that orchestrates lineage-specific transcript isoforms required for the commitment of hematopoietic stem cells to either myeloid or lymphoid fates. 2. As a component of the m6A methyltransferase complex, RBM15B-mediated m6A deposition on specific transcripts (e.g., those encoding key transcription factors) may be essential for maintaining the self-renewal capacity of [hematopoietic precursor cell](/details-cell/CL0008001). 3. The high expression of [RBM15B](/details-gene/29890) in [pancreatic acinar cell](/details-cell/CL0002064) suggests it is required to facilitate the massive export and processing of mRNAs encoding digestive enzymes, and its dysfunction could contribute to exocrine pancreatic insufficiency. **Experimental Approach:** To test the hypothesis that [RBM15B](/details-gene/29890) governs hematopoietic lineage commitment via splicing, one could utilize an *in vitro* model of human hematopoiesis with CD34+ hematopoietic stem and progenitor cells. A CRISPR-Cas9-mediated knockout of [RBM15B](/details-gene/29890) would be performed. Control and knockout cells would then be cultured under conditions that promote differentiation towards erythroid, myeloid, and lymphoid lineages. The outcome could be assessed by flow cytometry for lineage-specific surface markers. Concurrently, RNA-sequencing combined with bioinformatic analysis of differential splicing events would be performed at key time points to identify the specific transcripts and splicing patterns controlled by [RBM15B](/details-gene/29890) during differentiation. **Therapeutic Potential:** Due to its integral role in fundamental RNA processing, systemic inhibition of [RBM15B](/details-gene/29890) would likely be highly toxic. However, its crucial function in hematopoiesis suggests it could be a context-dependent therapeutic target in hematological malignancies that exhibit dependency on specific splicing events or m6A modifications. A potential strategy would be to develop small molecule inhibitors that selectively disrupt the interaction of [RBM15B](/details-gene/29890) with specific oncogenic partner proteins or RNA targets, rather than blocking its general RNA-binding activity. Such an approach would aim to achieve a therapeutic window by targeting a vulnerability specific to the cancer cells.

Genular Protein ID: 4122186282

Symbol: RB15B_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q8NDT2 A4QPG7 Q6QE19 Q9BV96

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 4 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 1 GO 13 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 9 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 16641997

Title: The DNA sequence, annotation and analysis of human chromosome 3.

PubMed ID: 16641997

DOI: 10.1038/nature04728

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 16129689

Title: Interaction of the Epstein-Barr virus mRNA export factor EB2 with human Spen proteins SHARP, OTT1, and a novel member of the family, OTT3, links Spen proteins with splicing regulation and mRNA export.

PubMed ID: 16129689

DOI: 10.1074/jbc.m501725200

PubMed ID: 17081983

Title: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.

PubMed ID: 17081983

DOI: 10.1016/j.cell.2006.09.026

PubMed ID: 16964243

Title: A probability-based approach for high-throughput protein phosphorylation analysis and site localization.

PubMed ID: 16964243

DOI: 10.1038/nbt1240

PubMed ID: 18220336

Title: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.

PubMed ID: 18220336

DOI: 10.1021/pr0705441

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19586903

Title: The RNA-binding motif protein 15B (RBM15B/OTT3) acts as cofactor of the nuclear export receptor NXF1.

PubMed ID: 19586903

DOI: 10.1074/jbc.m109.040113

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21044963

Title: The RNA binding motif protein 15B (RBM15B/OTT3) is a functional competitor of serine-arginine (SR) proteins and antagonizes the positive effect of the CDK11p110-cyclin L2alpha complex on splicing.

PubMed ID: 21044963

DOI: 10.1074/jbc.m110.192518

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 28112733

Title: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.

PubMed ID: 28112733

DOI: 10.1038/nsmb.3366

PubMed ID: 27602518

Title: m(6)A RNA methylation promotes XIST-mediated transcriptional repression.

PubMed ID: 27602518

DOI: 10.1038/nature19342

Sequence Information:

  • Length: 890
  • Mass: 97205
  • Checksum: 276C94252F036C83
  • Sequence:
    • MKRQSERDSS PSGRGSSSSA KRPREREREA EAGGRRAAHK ASGGAKHPVP ARARDKPRGS 
GSGGGGHRDG RGTGDANHRA SSGRSSGSGA GGGGRGGKAS GDPGASGMSP RASPLPPPPP 
PPGAEPACPG SSAAAPEYKT LLISSLSPAL PAEHLEDRLF HQFKRFGEIS LRLSHTPELG 
RVAYVNFRHP QDAREARQHA LARQLLLYDR PLKVEPVYLR GGGGSSRRSS SSSAAASTPP 
PGPPAPADPL GYLPLHGGYQ YKQRSLSPVA APPLREPRAR HAAAAFALDA AAAAAVGLSR 
ERALDYYGLY DDRGRPYGYP AVCEEDLMPE DDQRATRNLF IGNLDHSVSE VELRRAFEKY 
GIIEEVVIKR PARGQGGAYA FLKFQNLDMA HRAKVAMSGR VIGRNPIKIG YGKANPTTRL 
WVGGLGPNTS LAALAREFDR FGSIRTIDHV KGDSFAYIQY ESLDAAQAAC AKMRGFPLGG 
PDRRLRVDFA KAEETRYPQQ YQPSPLPVHY ELLTDGYTRH RNLDADLVRD RTPPHLLYSD 
RDRTFLEGDW TSPSKSSDRR NSLEGYSRSV RSRSGERWGA DGDRGLPKPW EERRKRRSLS 
SDRGRTTHSP YEERSRTKGS GQQSERGSDR TPERSRKENH SSEGTKESSS NSLSNSRHGA 
EERGHHHHHH EAADSSHGKK ARDSERNHRT TEAEPKPLEE PKHETKKLKN LSEYAQTLQL 
GWNGLLVLKN SCFPTSMHIL EGDQGVISSL LKDHTSGSKL TQLKIAQRLR LDQPKLDEVT 
RRIKQGSPNG YAVLLATQAT PSGLGTEGMP TVEPGLQRRL LRNLVSYLKQ KQAAGVISLP 
VGGSKGRDGT GMLYAFPPCD FSQQYLQSAL RTLGKLEEEH MVIVIVRDTA