Details for: GCSAM

Gene ID: 257144

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: GCSAM

Ensembl ID: ENSG00000174500

Description: germinal center associated signaling and motility

Cell Significance Landscape

Associated with

Significant Cells

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

  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 29.89
    rCSI 36.22%
    PRS 90.74
  • pro-B cell CL0000826
    CSI 26.11
    rCSI 21.62%
    PRS 99.29
  • chondrocyte CL0000138
    CSI 25.22
    rCSI 40.11%
    PRS 97.94
  • pericyte CL0000669
    CSI 24.95
    rCSI 66.45%
    PRS 89.94
  • precursor B cell CL0000817
    CSI 22.58
    rCSI 19.78%
    PRS 99.49
  • mast cell CL0000097
    CSI 20.04
    rCSI 43.27%
    PRS 94.85
  • regulatory T cell CL0000815
    CSI 19.72
    rCSI 22.86%
    PRS 95.44
  • helper T cell CL0000912
    CSI 19.16
    rCSI 27.09%
    PRS 96.34
  • melanocyte of skin CL1000458
    CSI 17.81
    rCSI 24.27%
    PRS 88.61
  • class switched memory B cell CL0000972
    CSI 17.41
    rCSI 13%
    PRS 99.36
  • basal cell of epidermis CL0002187
    CSI 16.58
    rCSI 29.38%
    PRS 87.32
  • innate lymphoid cell CL0001065
    CSI 14.46
    rCSI 29.86%
    PRS 96.02
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 14.08
    rCSI 14.35%
    PRS 99.45
  • suprabasal keratinocyte CL4033013
    CSI 13.29
    rCSI 21.7%
    PRS 88.98
  • CD4-positive helper T cell CL0000492
    CSI 12.99
    rCSI 9.83%
    PRS 99.79
  • small pre-B-II cell CL0000954
    CSI 12.9
    rCSI 12.41%
    PRS 99.42
  • dendritic cell, human CL0001056
    CSI 10.18
    rCSI 15.63%
    PRS 99.75
  • germinal center B cell CL0000844
    CSI 9.67
    rCSI 28.82%
    PRS 99.59
  • large pre-B-II cell CL0000957
    CSI 8.81
    rCSI 25.16%
    PRS 98.64
  • late pro-B cell CL0002048
    CSI 5.88
    rCSI 14.74%
    PRS 99.54
  • cytotoxic T cell CL0000910
    CSI 5.37
    rCSI 30.75%
    PRS 96.83
  • fraction A pre-pro B cell CL0002045
    CSI 2.69
    rCSI 3.08%
    PRS 99.38

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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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 [GCSAM](/details-gene/257144), or Germinal Center Associated Signaling and Motility protein, is a cytoplasmic adapter protein primarily recognized for its role in the immune system. It is critically involved in the regulation of the [B cell receptor signaling pathway](/details-cell/GO:0050855) and the [negative regulation of lymphocyte migration](/details-cell/GO:2000402). As its name suggests, it is highly significant in B cell lineages, including [pro-B cell](/details-cell/CL0000826) and [precursor B cell](/details-cell/CL0000817), where it modulates signaling and motility ([Link](https://doi.org/10.1182/blood-2010-04-281568)). However, expression data also reveals its significance in various T cell subsets, such as [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203), and even in non-hematopoietic cells like [chondrocyte](/details-cell/CL0000138), suggesting a broader functional scope beyond its established role in germinal center biology. ## Cellular Roles and Expression Landscape The expression profile of [GCSAM](/details-gene/257144) highlights its multifaceted role, with a strong footprint in the adaptive immune system alongside notable significance in several non-immune cell types. **Overall**, the gene shows the highest significance in lymphocytes. It is a key marker in the B cell lineage, with high Cell Significance Index (CSI) scores in [pro-B cell](/details-cell/CL0000826) (CSI: 26.11), [precursor B cell](/details-cell/CL0000817) (CSI: 22.58), and [class switched memory B cell](/details-cell/CL0000972) (CSI: 17.41). This pattern is consistent with its established function as a crucial signaling component in B cell development and germinal center reactions ([Link](https://doi.org/10.1016/s0002-9440(10)63637-1), [Link](https://doi.org/10.1182/blood-2004-08-3112)). Beyond B cells, [GCSAM](/details-gene/257144) demonstrates substantial importance across the T cell compartment. It is the top-ranked cell marker in [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) (CSI: 29.89) and also shows high significance in [regulatory T cell](/details-cell/CL0000815) (CSI: 19.72), [helper T cell](/details-cell/CL0000912) (CSI: 19.16), and [double-positive, alpha-beta thymocyte](/details-cell/CL0000809) (CSI: 14.08). This broad expression across both B and T lymphocytes suggests it may play a conserved role in antigen receptor signaling and cytoskeletal organization in adaptive immune cells. Interestingly, the expression landscape is not confined to the immune system. [GCSAM](/details-gene/257144) shows high significance in structural and stromal cells such as [chondrocyte](/details-cell/CL0000138) (CSI: 25.22) and [pericyte](/details-cell/CL0000669) (CSI: 24.95), as well as in various skin cells including [melanocyte of skin](/details-cell/CL1000458) and [basal cell of epidermis](/details-cell/CL0002187). This suggests that its function in modulating the cytoskeleton and cell signaling may be utilized in diverse biological contexts beyond immunity, potentially related to cell adhesion, mechanotransduction, or tissue homeostasis. ## Pathways and Molecular Function The functions of [GCSAM](/details-gene/257144) are tightly linked to its role as a signaling scaffold protein that bridges membrane-proximal events with the intracellular actin cytoskeleton. Its localization to the [cytoplasm](/details-cell/GO:0005737) and [plasma membrane](/details-cell/GO:0005886) facilitates this role. The gene's most well-characterized function is the [regulation of B cell receptor signaling pathway](/details-cell/GO:0050855). Studies have shown that [GCSAM](/details-gene/257144) (also known as HGAL) promotes B-cell receptor-mediated Syk activation, a critical step in B cell activation, which can drive lymphoid hyperplasia ([Link](https://doi.org/10.1038/ncomms2334)). Its involvement in a negative feedback loop further underscores its importance in tightly controlling B cell responses ([Link](https://doi.org/10.1038/s41375-019-0579-5)). Consistent with its high expression in multiple lymphocyte populations, [GCSAM](/details-gene/257144) is annotated for the [negative regulation of lymphocyte migration](/details-cell/GO:2000402). This function is mediated by its molecular interactions with core cytoskeletal components, as evidenced by its capacity for [actin binding](/details-cell/GO:0003779) and [myosin II binding](/details-cell/GO:0045159). Research indicates that [GCSAM](/details-gene/257144) can decrease lymphoma cell motility by modulating the RhoA signaling pathway, a key regulator of the actin cytoskeleton ([Link](https://doi.org/10.1182/blood-2010-04-281568)). Its general capacity for [protein kinase binding](/details-cell/GO:0019901) likely underpins its function as an adapter in multiple signaling cascades. ## Research Directions The widespread significance of [GCSAM](/details-gene/257144) in both immune and non-immune cells, combined with its known function as a cytoskeletal-linked signaling adapter, opens several avenues for future research. **Proposed Hypotheses:** 1. Given its high significance in both B and T cell lineages and its known interactions with actin, [GCSAM](/details-gene/257144) may function as a master regulator of immunological synapse assembly. It could act as a scaffold to coordinate actin remodeling and signalosome formation downstream of both B-cell and T-cell receptor engagement, thereby controlling the quality and duration of the adaptive immune response. 2. The unexpectedly high CSI of [GCSAM](/details-gene/257144) in [chondrocyte](/details-cell/CL0000138) and [pericyte](/details-cell/CL0000669) suggests a novel role in mechanobiology. In these cells, [GCSAM](/details-gene/257144) may link the extracellular matrix to the actin cytoskeleton, enabling cells to sense and respond to mechanical forces by modulating RhoA-dependent contractility and gene expression. **Experimental Approach:** To test the second hypothesis regarding its role in mechanobiology, a targeted experiment could be designed. CRISPR-Cas9 could be used to generate [GCSAM](/details-gene/257144)-knockout and control human primary chondrocytes. These cells could then be cultured on flexible substrates and subjected to defined mechanical strain using a cell-stretching device. The impact of [GCSAM](/details-gene/257144) deletion on cellular response could be quantified by measuring changes in cell alignment, focal adhesion formation via immunofluorescence staining for vinculin, and the expression of key cartilage matrix genes (e.g., *COL2A1*, *ACAN*) and mechanosensitive transcription factors (e.g., *YAP/TAZ*) using RT-qPCR and Western blotting. **Therapeutic Potential:** [GCSAM](/details-gene/257144) is a well-established prognostic biomarker in diffuse large B-cell lymphoma, where high expression is associated with a germinal center origin and better survival outcomes ([Link](https://doi.org/10.1182/blood-2002-06-1931)). However, it also promotes lymphoid hyperplasia ([Link](https://doi.org/10.1038/ncomms2334)) and influences cell motility, making it a context-dependent therapeutic target. As an intracellular protein, it is not amenable to antibody-based therapies. A more promising strategy would be the development of small molecule inhibitors designed to disrupt its key protein-protein interactions, such as its binding to Syk or components of the RhoA pathway. Such an approach, aimed at **inhibition**, could potentially reduce the proliferation and dissemination of certain B-cell malignancies.

Genular Protein ID: 350879688

Symbol: GCSAM_HUMAN

Name: Germinal center-associated signaling and motility protein

UniProtKB Accession Codes:

Q8N6F7 C9JD17 C9JUG6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CTD 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 6 ExpressionAtlas 1 GO 7 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 RefSeq 3 SIGNOR 1 STRING 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 12819018

Title: Two newly characterized germinal center B-cell-associated genes, GCET1 and GCET2, have differential expression in normal and neoplastic B cells.

PubMed ID: 12819018

DOI: 10.1016/s0002-9440(10)63637-1

PubMed ID: 12509382

Title: HGAL is a novel interleukin-4-inducible gene that strongly predicts survival in diffuse large B-cell lymphoma.

PubMed ID: 12509382

DOI: 10.1182/blood-2002-06-1931

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: 15677569

Title: Expression of the human germinal center-associated lymphoma (HGAL) protein, a new marker of germinal center B-cell derivation.

PubMed ID: 15677569

DOI: 10.1182/blood-2004-08-3112

PubMed ID: 17823310

Title: HGAL, a lymphoma prognostic biomarker, interacts with the cytoskeleton and mediates the effects of IL-6 on cell migration.

PubMed ID: 17823310

DOI: 10.1182/blood-2007-04-087775

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: 20844236

Title: HGAL, a germinal center specific protein, decreases lymphoma cell motility by modulation of the RhoA signaling pathway.

PubMed ID: 20844236

DOI: 10.1182/blood-2010-04-281568

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 23299888

Title: Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation.

PubMed ID: 23299888

DOI: 10.1038/ncomms2334

PubMed ID: 31570756

Title: Recent BCR stimulation induces a negative autoregulatory loop via FBXO10 mediated degradation of HGAL.

PubMed ID: 31570756

DOI: 10.1038/s41375-019-0579-5

Sequence Information:

  • Length: 178
  • Mass: 21005
  • Checksum: B7C91F3D4B78CD03
  • Sequence:
    • MGNSLLRENR RQQNTQEMPW NVRMQSPKQR TSRCWDHHIA EGCFCLPWKK ILIFEKRQDS 
QNENERMSST PIQDNVDQTY SEELCYTLIN HRVLCTRPSG NSAEEYYENV PCKAERPRES 
LGGTETEYSL LHMPSTDPRH ARSPEDEYEL LMPHRISSHF LQQPRPLMAP SETQFSHL