Details for: PTCRA

Gene ID: 171558

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: PTCRA

Ensembl ID: ENSG00000171611

Description: pre T cell antigen receptor alpha

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • plasmacytoid dendritic cell, human CL0001058
    CSI 14.53
    rCSI 10.15%
    PRS 99.93
  • dendritic cell CL0000451
    CSI 12.38
    rCSI 15.26%
    PRS 99.73
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 7.91
    rCSI 8.06%
    PRS 99.64
  • plasmacytoid dendritic cell CL0000784
    CSI 7.07
    rCSI 7.16%
    PRS 99.78
  • megakaryocyte CL0000556
    CSI 4.79
    rCSI 20.8%
    PRS 99.11
  • platelet CL0000233
    CSI 3.62
    rCSI 15.02%
    PRS 98.75

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.

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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    • 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 [PTCRA](/details-gene/171558), or Pre T-Cell Antigen Receptor Alpha, is a protein-coding gene located on chromosome 6 that is essential for T-lymphocyte development. It encodes the alpha chain of the pre-T-cell receptor (pre-TCR), a critical component for checkpoint control during the early stages of thymocyte maturation. The pre-TCR complex, formed by [PTCRA](/details-gene/171558) and a functionally rearranged TCR beta chain, signals for the survival, proliferation, and differentiation of developing T cells, a process known as beta-selection ([Link](https://doi.org/10.1084/jem.184.2.519)). While its canonical role is firmly established in [double-positive, alpha-beta thymocyte](/details-cell/CL0000809)s, expression data surprisingly reveals its highest significance in dendritic cell populations, particularly [plasmacytoid dendritic cell, human](/details-cell/CL0001058), suggesting potential, less-characterized functions in innate immunity. ## Cellular Roles and Expression Landscape The expression profile of [PTCRA](/details-gene/171558) highlights its specialized role within the hematopoietic system. **Overall**, its significance is most pronounced in key immune cell populations, consistent with its function in lymphocyte development. * **Primary Role in T-Cell Development:** As expected from its name, [PTCRA](/details-gene/171558) is a significant marker in [double-positive, alpha-beta thymocyte](/details-cell/CL0000809)s. In these cells, the pre-TCR complex provides crucial survival signals that prevent apoptosis and drive progression to the next stage of T cell maturation. * **Prominent Expression in Dendritic Cells:** The data unexpectedly indicates the highest significance for [PTCRA](/details-gene/171558) in [plasmacytoid dendritic cell, human](/details-cell/CL0001058) (CSI: 14.53) and the broader [dendritic cell](/details-cell/CL0000451) category (CSI: 12.38). This suggests a potential non-canonical function for [PTCRA](/details-gene/171558) in these professional antigen-presenting cells, which may be independent of its role in the pre-TCR complex. * **Significance in Megakaryocyte-Platelet Lineage:** [PTCRA](/details-gene/171558) also shows notable significance in [megakaryocyte](/details-cell/CL0000556)s and [platelet](/details-cell/CL0000233)s. This expression pattern suggests a previously underappreciated role in megakaryopoiesis or platelet biology, potentially linking developmental signaling pathways across different hematopoietic lineages. ## Pathways and Molecular Function The molecular functions and pathway associations of [PTCRA](/details-gene/171558) are consistent with its role as a key signaling component during thymocyte development. Functionally, the [PTCRA](/details-gene/171558) protein is a [membrane](/details-go/GO0016020) component that engages in [protein binding](/details-go/GO0005515), primarily with the TCR beta chain to form the pre-TCR ([Link](https://doi.org/10.1038/nature09448)). A critical biological process associated with [PTCRA](/details-gene/171558) is the [negative regulation of thymocyte apoptotic process](/details-go/GO0070244), which is central to the beta-selection checkpoint in the thymus. Successful pre-TCR signaling rescues developing thymocytes from programmed cell death. Furthermore, [PTCRA](/details-gene/171558) is linked to broader [signal transduction](/details-reactome/R-HSA-162582) pathways, including [Signaling by notch](/details-reactome/R-HSA-157118) and specifically [Notch3 intracellular domain regulates transcription](/details-reactome/R-HSA-9013508). Notch signaling is fundamental for T-cell lineage commitment and differentiation in the thymus, suggesting a direct molecular crosstalk between the pre-TCR and the Notch pathway to coordinate thymocyte development. Its association with Notch signaling may also provide a mechanistic link to its observed expression in other hematopoietic cells like dendritic cells and megakaryocytes, where Notch pathways are also active. ## Research Directions The established role of [PTCRA](/details-gene/171558) in T-cell development is well-documented, but its high significance in dendritic cells and the megakaryocyte lineage opens new avenues for investigation. **Proposed Hypotheses:** 1. The high expression of [PTCRA](/details-gene/171558) in [plasmacytoid dendritic cell](/details-cell/CL0000784)s suggests it may function as a co-receptor or signaling molecule that modulates their unique ability to produce vast amounts of type I interferon in response to viral nucleic acids. 2. Given its association with Notch signaling and its expression in [megakaryocyte](/details-cell/CL0000556)s, [PTCRA](/details-gene/171558) may play a role in regulating the differentiation or maturation of megakaryocytes from hematopoietic progenitors. **Key Experimental Approach:** To test the hypothesis regarding its role in pDCs, a functional study could be conducted. [PTCRA](/details-gene/171558) could be knocked down in primary human pDCs using siRNA. These modified pDCs, along with control cells, would then be stimulated with a TLR9 agonist like CpG-A. The primary readouts would be the quantification of IFN-alpha secretion via ELISA and the analysis of a broader cytokine panel using multiplex assays. Changes in cell surface activation markers (e.g., CD86, HLA-DR) could be measured by flow cytometry to determine if [PTCRA](/details-gene/171558) is involved in pDC activation. **Therapeutic Potential:** As a surface protein critical for the proliferation and survival of developing T-cells, [PTCRA](/details-gene/171558) represents a potential therapeutic target in diseases characterized by aberrant pre-T-cell expansion, such as T-cell acute lymphoblastic leukemia (T-ALL). A therapeutic strategy would involve **inhibition** of its function or targeted depletion of [PTCRA](/details-gene/171558)-expressing malignant cells. This could be achieved through monoclonal antibodies, antibody-drug conjugates, or CAR-T cell therapies directed against [PTCRA](/details-gene/171558). However, its expression in other hematopoietic cells, such as pDCs and megakaryocytes, would need to be carefully evaluated to predict and mitigate potential on-target, off-tumor toxicities.

Genular Protein ID: 1803540351

Symbol: PTCRA_HUMAN

Name: Pre T-cell antigen receptor alpha

UniProtKB Accession Codes:

Q6ISU1 Q5TFZ7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 12 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 2 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MINT 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 Reactome 1 RefSeq 4 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 8618853

Title: Cloning and comparative analysis of the human pre-T-cell receptor alpha-chain gene.

PubMed ID: 8618853

DOI: 10.1073/pnas.92.26.12105

PubMed ID: 9842925

Title: Genomic structure of the human pre-T cell receptor alpha chain and expression of two mRNA isoforms.

PubMed ID: 9842925

DOI: 10.1002/(sici)1521-4141(199811)28:11<3824::aid-immu3824>3.0.co;2-9

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

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: 8760805

Title: Regulation of pre-T cell receptor (pT alpha-TCR beta) gene expression during human thymic development.

PubMed ID: 8760805

DOI: 10.1084/jem.184.2.519

PubMed ID: 22795130

Title: Ubiquitin-dependent intramembrane rhomboid protease promotes ERAD of membrane proteins.

PubMed ID: 22795130

DOI: 10.1016/j.molcel.2012.06.008

PubMed ID: 20944746

Title: The structural basis for autonomous dimerization of the pre-T-cell antigen receptor.

PubMed ID: 20944746

DOI: 10.1038/nature09448

Sequence Information:

  • Length: 281
  • Mass: 29266
  • Checksum: A49B86A151619B9F
  • Sequence:
    • MAGTWLLLLL ALGCPALPTG VGGTPFPSLA PPIMLLVDGK QQMVVVCLVL DVAPPGLDSP 
IWFSAGNGSA LDAFTYGPSP ATDGTWTNLA HLSLPSEELA SWEPLVCHTG PGAEGHSRST 
QPMHLSGEAS TARTCPQEPL RGTPGGALWL GVLRLLLFKL LLFDLLLTCS CLCDPAGPLP 
SPATTTRLRA LGSHRLHPAT ETGGREATSS PRPQPRDRRW GDTPPGRKPG SPVWGEGSYL 
SSYPTCPAQA WCSRSALRAP SSSLGAFFAG DLPPPLQAGA A

Genular Protein ID: 1119250107

Symbol: Q6ZNR1_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q6ZNR1

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 Gene3D 1 InterPro 3 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 1 RefSeq 1 SAM 2 SUPFAM 1

Sequence Information:

  • Length: 328
  • Mass: 34298
  • Checksum: C1E458D0BAE9838C
  • Sequence:
    • MAGTWLLLLL ALGCPALPTG VGGTPFPSLA PPIMLLVDGK QQMVVVCLVL DVAPPGLDSP 
IWFSAGNGSA LDAFTYGPSP ATDGTWTNLA HLSLPSEELA SWEPLVCHTG PGAEGHSRST 
QPMHLSGEAS TARTCPQEPL RGGCGLLRAP ERFLLAGTPG GALWLGVLRL LLFKLLLLTC 
SCLCDPAGPL PSPATTTRLR ALGSHRLHPA TESGGREATS SPRPQPRDRR WGDTPPGRKP 
GSPVWGEGSY LSSYPTCPAT WHVTREPDAH GWLAGGTPCW LPIWCSSSAS TWHATHHDGS 
IPKTPACAPG AASHACPAPG VKEEEDGR

Genular Protein ID: 3345925353

Symbol: A0A087WTE9_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A087WTE9

Database IDs:

AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 2 ExpressionAtlas 1 Gene3D 1 GeneTree 1 HGNC 1 InterPro 3 MassIVE 1 NCBI Taxonomy 1 OMA 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 1 Proteomes 2 RefSeq 1 SAM 2 SMR 1 SUPFAM 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

Sequence Information:

  • Length: 296
  • Mass: 30820
  • Checksum: F8A4DC22F09A3D3E
  • Sequence:
    • MAGTWLLLLL ALGCPALPTG VGGTPFPSLA PPIMLLVDGK QQMVVVCLVL DVAPPGLDSP 
IWFSAGNGSA LDAFTYGPSP ATDGTWTNLA HLSLPSEELA SWEPLVCHTG PGAEGHSRST 
QPMHLSGEAS TARTCPQEPL RGGCGLLRAP ERFLLAGTPG GALWLGVLRL LLFKLLLFDL 
LLTCSCLCDP AGPLPSPATT TRLRALGSHR LHPATETGGR EATSSPRPQP RDRRWGDTPP 
GRKPGSPVWG EGSYLSSYPT CPAQAWCSRS ALRAPSSSLG AFFAGDLPPP LQAGAA