Details for: TAPBPL

Gene ID: 55080

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: TAPBPL

Ensembl ID: ENSG00000139192

Description: TAP binding protein like

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • neural progenitor cell CL0011020
    CSI 6.1
    rCSI 26.85%
    PRS 68.22
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792
    CSI 4.73
    rCSI 4.65%
    PRS 91.92
  • naive T cell CL0000898
    CSI 4.61
    rCSI 3.21%
    PRS 92.56
  • intestinal tuft cell CL0019032
    CSI 4.37
    rCSI 6.68%
    PRS 83.42
  • plasma cell CL0000786
    CSI 4.36
    rCSI 5.72%
    PRS 92.18
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 4.03
    rCSI 3.07%
    PRS 91.36
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 3.88
    rCSI 3.5%
    PRS 77.81
  • goblet cell CL0000160
    CSI 3.14
    rCSI 2.97%
    PRS 78.26
  • double negative thymocyte CL0002489
    CSI 3.13
    rCSI 2.18%
    PRS 90.32
  • nasal mucosa goblet cell CL0002480
    CSI 3.11
    rCSI 3.6%
    PRS 83.52
  • secretory cell CL0000151
    CSI 3.07
    rCSI 3.2%
    PRS 78.98
  • epithelial cell of lung CL0000082
    CSI 3
    rCSI 2.49%
    PRS 80.3
  • group 3 innate lymphoid cell CL0001071
    CSI 2.93
    rCSI 2.2%
    PRS 85.25
  • duct epithelial cell CL0000068
    CSI 2.81
    rCSI 4.11%
    PRS 84.38
  • hematopoietic stem cell CL0000037
    CSI 2.63
    rCSI 1.75%
    PRS 82.39
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 2.57
    rCSI 1.85%
    PRS 91.31
  • class switched memory B cell CL0000972
    CSI 2.49
    rCSI 1.86%
    PRS 91.28
  • dendritic cell, human CL0001056
    CSI 2.49
    rCSI 3.83%
    PRS 87.86
  • CD4-positive, alpha-beta cytotoxic T cell CL0000934
    CSI 2.49
    rCSI 3.42%
    PRS 93.8
  • plasmablast CL0000980
    CSI 2.46
    rCSI 1.93%
    PRS 84.56
  • intestinal epithelial cell CL0002563
    CSI 2.4
    rCSI 2.51%
    PRS 77.27
  • mucus secreting cell CL0000319
    CSI 2.36
    rCSI 3.75%
    PRS 88.05
  • pulmonary ionocyte CL0017000
    CSI 2.31
    rCSI 2.81%
    PRS 86.09
  • intestine goblet cell CL0019031
    CSI 2.25
    rCSI 1.99%
    PRS 77.31
  • colon epithelial cell CL0011108
    CSI 2.25
    rCSI 2.35%
    PRS 77.09
  • ionocyte CL0005006
    CSI 2.19
    rCSI 2.34%
    PRS 80.92
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.15
    rCSI 1.5%
    PRS 82.86
  • ciliated cell CL0000064
    CSI 2.13
    rCSI 3.46%
    PRS 74.69
  • immature B cell CL0000816
    CSI 2.08
    rCSI 1.55%
    PRS 89.79
  • activated type II NK T cell CL0000931
    CSI 1.98
    rCSI 2.22%
    PRS 91.83
  • IgA plasma cell CL0000987
    CSI 1.97
    rCSI 2.02%
    PRS 87.15
  • mature B cell CL0000785
    CSI 1.97
    rCSI 1.71%
    PRS 88.68
  • extravillous trophoblast CL0008036
    CSI 1.89
    rCSI 2.34%
    PRS 77.46
  • IgG plasma cell CL0000985
    CSI 1.86
    rCSI 2.23%
    PRS 89.28
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 1.83
    rCSI 9.18%
    PRS 90.6
  • alveolar macrophage CL0000583
    CSI 1.69
    rCSI 2.78%
    PRS 83.45
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 1.65
    rCSI 1.68%
    PRS 89
  • enterocyte CL0000584
    CSI 1.58
    rCSI 2.55%
    PRS 78.78
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.5
    rCSI 3.36%
    PRS 62.54
  • fallopian tube secretory epithelial cell CL4030006
    CSI 1.49
    rCSI 1.44%
    PRS 78.99
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 1.43
    rCSI 1.11%
    PRS 82.41
  • club cell CL0000158
    CSI 1.36
    rCSI 1.99%
    PRS 74.23

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)

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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 [TAPBPL](/details-gene/55080) (TAP binding protein like), also known as Tapasin-related protein (TAPBPR), is a protein-coding gene located on chromosome 12p13.31. Functionally, it is an important component of the antigen presentation pathway, acting as a chaperone and peptide editor for Major Histocompatibility Complex (MHC) class I molecules. It binds to the MHC class I complex within the endoplasmic reticulum and facilitates the loading and exchange of high-affinity peptides, a critical step for immune surveillance ([Link](https://doi.org/10.1073/pnas.1222342110), [Link](https://doi.org/10.1073/pnas.1519894113)). While its highest significance scores are observed in various immune cell populations, including regulatory T cells and plasma cells, consistent with its immunological role, expression data also suggest a notable presence in diverse non-immune cell types such as [neural progenitor cell](/details-cell/CL0011020)s and secretory epithelial cells, indicating potentially broader biological functions. ## Cellular Roles and Expression Landscape The expression profile of [TAPBPL](/details-gene/55080) highlights its dual role in both the immune system and various progenitor and specialized cell populations. **Overall**, the gene shows significant expression in a wide array of cell types. Its prominence in the immune system is demonstrated by high significance in several lymphocyte populations, including [CD4-positive, CD25-positive, alpha-beta regulatory T cell](/details-cell/CL0000792) (CSI: 4.73), [naive T cell](/details-cell/CL0000898) (CSI: 4.61), [plasma cell](/details-cell/CL0000786) (CSI: 4.36), and [effector CD8-positive, alpha-beta T cell](/details-cell/CL0001050) (CSI: 4.03). This pattern is consistent with its established function in MHC class I antigen presentation, a cornerstone of adaptive immunity. Intriguingly, the highest observed significance for [TAPBPL](/details-gene/55080) is in [neural progenitor cell](/details-cell/CL0011020) (CSI: 6.10). Significant expression is also noted in other progenitor lineages, such as [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 3.88) and [hematopoietic stem cell](/details-cell/CL0000037) (CSI: 2.63). This suggests a potential role for [TAPBPL](/details-gene/55080) in regulating the immunopeptidome during cellular differentiation and development, possibly to modulate immune recognition of these critical cell populations. Furthermore, [TAPBPL](/details-gene/55080) is significantly expressed in multiple secretory and epithelial cell types, including [intestinal tuft cell](/details-cell/CL0019032) (CSI: 4.37), [goblet cell](/details-cell/CL0000160) (CSI: 3.14), and [epithelial cell of lung](/details-cell/CL0000082) (CSI: 3.00). This broad expression across mucosal and glandular tissues implies a conserved function in maintaining proper MHC class I-mediated surveillance in diverse physiological contexts. ## Pathways and Molecular Function The functional annotations for [TAPBPL](/details-gene/55080) align closely with its role as an accessory protein in the MHC class I antigen processing and presentation pathway. - **Biological Process:** The gene is primarily involved in modulating antigen presentation. It contributes to the [peptide antigen assembly with mhc class i protein complex](/details-go/GO:0002502) and also participates in the [negative regulation of antigen processing and presentation of peptide antigen via mhc class i](/details-go/GO:0002590). This dual role suggests it acts as a quality control checkpoint, both facilitating the assembly of peptide-MHC complexes and potentially editing the repertoire of presented peptides. - **Molecular Function:** At the molecular level, [TAPBPL](/details-gene/55080) exerts its function through direct physical interactions. It is annotated with [Mhc class i protein complex binding](/details-go/GO:0023024) and [Tap complex binding](/details-go/GO:0062061), placing it at the core of the peptide-loading complex ([Link](https://doi.org/10.1073/pnas.1222342110)). - **Cellular Component:** Consistent with its function in protein trafficking and antigen processing, [TAPBPL](/details-gene/55080) is localized to the [endoplasmic reticulum](/details-go/GO:0005783), the [Golgi membrane](/details-go/GO:0000139), and the [Mhc class i peptide loading complex](/details-go/GO:0042824). Its annotation to the [plasma membrane](/details-go/GO:0005886) suggests that in some contexts, it may also influence MHC-I complexes at the cell surface. ## Research Directions The widespread yet specific expression pattern of [TAPBPL](/details-gene/55080) prompts several avenues for future investigation, particularly regarding its roles outside of canonical immune cells and its potential as a therapeutic target. ### Proposed Hypotheses: 1. **Hypothesis 1:** The high significance of [TAPBPL](/details-gene/55080) in progenitor cells ([neural progenitor cell](/details-cell/CL0011020), [hematopoietic stem cell](/details-cell/CL0000037)) suggests it plays a critical role in modulating MHC class I surface expression during differentiation to protect these cells from premature or inappropriate immune attack. Its activity may shape a unique peptidome that signals cell identity and developmental stage to the immune system. 2. **Hypothesis 2:** Given its function in negatively regulating antigen presentation and its high expression in [CD4-positive, CD25-positive, alpha-beta regulatory T cell](/details-cell/CL0000792)s, [TAPBPL](/details-gene/55080) may be a key factor in establishing the immunosuppressive phenotype of these cells by editing the peptide repertoire on interacting antigen-presenting cells or on the regulatory T cells themselves, thereby promoting immune tolerance. ### Key Experiment: To test Hypothesis 1, one could utilize an *in vitro* differentiation system, such as human induced pluripotent stem cells (iPSCs) directed towards a neural progenitor fate. - **Approach:** Generate a [TAPBPL](/details-gene/55080) knockout iPSC line using CRISPR-Cas9 technology. Differentiate both wild-type and knockout iPSCs into [neural progenitor cell](/details-cell/CL0011020)s. At various stages of differentiation, analyze the cell surface levels of MHC class I molecules (e.g., HLA-A, -B, -C) by flow cytometry. Concurrently, perform immunopeptidomics using mass spectrometry to compare the repertoire of peptides presented by wild-type versus knockout cells. - **Expected Outcome:** A significant alteration in the abundance or composition of presented peptides, or a change in the kinetics of MHC-I surface expression in the knockout line, would provide strong evidence for the role of [TAPBPL](/details-gene/55080) in modulating immune visibility during neurodevelopment. ### Therapeutic Potential: As a key editor of the MHC class I immunopeptidome, [TAPBPL](/details-gene/55080) represents an attractive target for immunomodulation. - **Cancer Immunotherapy:** In oncology, inhibiting [TAPBPL](/details-gene/55080) could be a therapeutic strategy. By blocking its peptide editing function, cancer cells might be forced to present a broader, less optimal repertoire of peptides, including low-affinity neoantigens that would otherwise be removed. This could enhance their recognition and destruction by cytotoxic T lymphocytes, potentially synergizing with checkpoint blockade therapies. - **Autoimmunity:** Conversely, for autoimmune diseases driven by the presentation of self-peptides, enhancing the function or expression of [TAPBPL](/details-gene/55080) could be beneficial. A small molecule agonist could promote more stringent peptide editing, reducing the surface display of autoreactive peptide-MHC class I complexes and thus dampening the autoimmune response.

Genular Protein ID: 293110097

Symbol: TPSNR_HUMAN

Name: Tapasin-related protein

UniProtKB Accession Codes:

Q9BX59 Q9NWB8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 ExpressionAtlas 1 GO 8 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 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 RNAct 1 RefSeq 1 SMART 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11920573

Title: A human TAPBP (TAPASIN)-related gene, TAPBP-R.

PubMed ID: 11920573

DOI: 10.1002/1521-4141(200204)32:4<1059::aid-immu1059>3.0.co;2-g

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

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: 15340161

Title: Signal peptide prediction based on analysis of experimentally verified cleavage sites.

PubMed ID: 15340161

DOI: 10.1110/ps.04682504

PubMed ID: 23401559

Title: Tapasin-related protein TAPBPR is an additional component of the MHC class I presentation pathway.

PubMed ID: 23401559

DOI: 10.1073/pnas.1222342110

PubMed ID: 24444341

Title: TAPBPR isoforms exhibit altered association with MHC class I.

PubMed ID: 24444341

DOI: 10.1111/imm.12253

PubMed ID: 26869717

Title: Interaction of TAPBPR, a tapasin homolog, with MHC-I molecules promotes peptide editing.

PubMed ID: 26869717

DOI: 10.1073/pnas.1519894113

Sequence Information:

  • Length: 468
  • Mass: 50183
  • Checksum: FA39C335FC22960E
  • Sequence:
    • MGTQEGWCLL LCLALSGAAE TKPHPAEGQW RAVDVVLDCF LAKDGAHRGA LASSEDRARA 
SLVLKQVPVL DDGSLEDFTD FQGGTLAQDD PPIIFEASVD LVQIPQAEAL LHADCSGKEV 
TCEISRYFLQ MTETTVKTAA WFMANMQVSG GGPSISLVMK TPRVTKNEAL WHPTLNLPLS 
PQGTVRTAVE FQVMTQTQSL SFLLGSSASL DCGFSMAPGL DLISVEWRLQ HKGRGQLVYS 
WTAGQGQAVR KGATLEPAQL GMARDASLTL PGLTIQDEGT YICQITTSLY RAQQIIQLNI 
QASPKVRLSL ANEALLPTLI CDIAGYYPLD VVVTWTREEL GGSPAQVSGA SFSSLRQSVA 
GTYSISSSLT AEPGSAGATY TCQVTHISLE EPLGASTQVV PPERRTALGV IFASSLFLLA 
LMFLGLQRRQ APTGLGLLQA ERWETTSCAD TQSSHLHEDR TARVSQPS