Details for: GCAT

Gene ID: 23464

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: GCAT

Ensembl ID: ENSG00000100116

Description: glycine C-acetyltransferase

Cell Significance Landscape

Associated with

Significant Cells

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

  • goblet cell CL0000160
    CSI 3.26
    rCSI 3.08%
    PRS 97.18
  • hematopoietic stem cell CL0000037
    CSI 3.22
    rCSI 2.14%
    PRS 98.52
  • stem cell CL0000034
    CSI 3.18
    rCSI 3.07%
    PRS 97.27
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 3.16
    rCSI 2.85%
    PRS 97.88
  • erythrocyte CL0000232
    CSI 3.11
    rCSI 7.06%
    PRS 96.82
  • common myeloid progenitor CL0000049
    CSI 3.1
    rCSI 2.5%
    PRS 98.88
  • intestine goblet cell CL0019031
    CSI 2.99
    rCSI 2.66%
    PRS 97.19
  • hepatocyte CL0000182
    CSI 2.87
    rCSI 5.14%
    PRS 96.68
  • acinar cell CL0000622
    CSI 2.73
    rCSI 4%
    PRS 98.99
  • transit amplifying cell of colon CL0009011
    CSI 2.63
    rCSI 3.09%
    PRS 98.28
  • club cell CL0000158
    CSI 2.48
    rCSI 3.63%
    PRS 96.96
  • pancreatic acinar cell CL0002064
    CSI 2.31
    rCSI 3.07%
    PRS 98.33
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.78
    rCSI 4%
    PRS 93.95
  • tracheobronchial serous cell CL0019001
    CSI 0.87
    rCSI 3.74%
    PRS 98.36
  • primitive red blood cell CL0002355
    CSI 0.81
    rCSI 4.35%
    PRS 98.12
  • erythroid progenitor cell CL0000038
    CSI 0.61
    rCSI 3.49%
    PRS 98.45

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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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 [GCAT](/details-gene/23464) (glycine C-acetyltransferase) is a protein-coding gene located on chromosome 22q13.1. It encodes a mitochondrial enzyme, 2-amino-3-ketobutyrate coenzyme A ligase, which plays a key role in amino acid metabolism, specifically in the catabolism of threonine. Expression data indicates that [GCAT](/details-gene/23464) is highly significant in a diverse range of metabolically active cells and hematopoietic lineages. **Overall**, it shows high significance in secretory cells like [goblet cells](/details-cell/CL0000160) and [acinar cells](/details-cell/CL0000622), metabolic powerhouses such as [hepatocytes](/details-cell/CL0000182), and a spectrum of hematopoietic cells including [hematopoietic stem cells](/details-cell/CL0000037) and [erythrocytes](/details-cell/CL0000232), suggesting a fundamental role in cellular energy and biosynthesis. ## Cellular Roles and Expression Landscape The expression profile of [GCAT](/details-gene/23464) suggests it is a crucial metabolic enzyme in cells with high biosynthetic and proliferative demands. An **Overall** analysis of its expression reveals two primary functional clusters where it is most significant. First, [GCAT](/details-gene/23464) is a prominent marker throughout the hematopoietic system. Its high significance in primitive cell types, including [hematopoietic stem cells](/details-cell/CL0000037) (CSI: 3.22), [common myeloid progenitors](/details-cell/CL0000049) (CSI: 3.10), and [megakaryocyte-erythroid progenitor cells](/details-cell/CL0000050) (CSI: 3.16), points to a foundational role in the maintenance and differentiation of blood cell lineages. This importance extends to mature cells, with a high CSI in [erythrocytes](/details-cell/CL0000232) (CSI: 3.11), which may be related to metabolic pathways supporting heme synthesis or cell integrity. Second, the gene is highly active in secretory and metabolically demanding epithelial and parenchymal cells. It is the top marker in [goblet cells](/details-cell/CL0000160) (CSI: 3.26) and shows high significance in other secretory cells like [acinar cells](/details-cell/CL0000622) (CSI: 2.73) and [club cells](/details-cell/CL0000158) (CSI: 2.48). Its strong signal in [hepatocytes](/details-cell/CL0000182) (CSI: 2.87), the primary site of systemic metabolism, further underscores its importance in processing amino acids. This pattern is consistent with a role in providing metabolic intermediates for the high-energy demands of protein synthesis, modification, and secretion. ## Pathways and Molecular Function [GCAT](/details-gene/23464) encodes an enzyme with [glycine c-acetyltransferase activity (GO:0008890)](https://www.ebi.ac.uk/QuickGO/term/GO:0008890), which requires [pyridoxal phosphate binding (GO:0030170)](https://www.ebi.ac.uk/QuickGO/term/GO:0030170) as a cofactor. This activity is a central step in the [threonine catabolic process (GO:0006567)](https://www.ebi.ac.uk/QuickGO/term/GO:0006567), a pathway detailed in Reactome as [Threonine catabolism (R-HSA-8849175)](https://reactome.org/content/detail/R-HSA-8849175). This function places [GCAT](/details-gene/23464) within the broader context of [Metabolism of amino acids and derivatives (R-HSA-71291)](https://reactome.org/content/detail/R-HSA-71291), aligning with its high expression in metabolically active cells. Interestingly, while its primary localization is the [mitochondrion (GO:0005739)](https://www.ebi.ac.uk/QuickGO/term/GO:0005739), functional annotation also indicates its presence in the [nucleus (GO:0005634)](https://www.ebi.ac.uk/QuickGO/term/GO:0005634) and [nuclear specks (GO:0016607)](https://www.ebi.ac.uk/QuickGO/term/GO:0016607). This dual localization is supported by research demonstrating its nuclear translocation in response to cellular stress, suggesting it may possess non-canonical functions beyond its established metabolic role ([Link](https://doi.org/10.1379/csc-264r.1)). ## Research Directions The diverse expression pattern and dual subcellular localization of [GCAT](/details-gene/23464) suggest several avenues for future investigation. **Proposed Hypotheses:** 1. Given its high significance in hematopoietic progenitors and mature [erythrocytes](/details-cell/CL0000232), [GCAT](/details-gene/23464) may be essential for erythropoiesis by providing glycine or other metabolites crucial for heme synthesis, a process heavily reliant on intermediates from amino acid catabolism. 2. The reported stress-induced nuclear translocation of the GCAT protein suggests a role as a metabolic sensor. Under conditions like osmotic stress, [GCAT](/details-gene/23464) may relocate to the [nucleus](/details-cell/GO:0005634) to directly or indirectly regulate gene expression programs involved in cellular adaptation, thus linking metabolic state to transcriptional responses. **Suggested Experimental Approach:** To test the hypothesis of a non-canonical nuclear function (Hypothesis 2), a multi-faceted approach could be employed. First, using a cell line with high endogenous expression, such as the HepG2 hepatoma line, the stress-induced nuclear translocation of GCAT protein could be validated via immunofluorescence and subcellular fractionation followed by Western blot. To elucidate its nuclear function, techniques like chromatin immunoprecipitation sequencing (ChIP-seq) could determine if GCAT directly binds to chromatin. Alternatively, proximity-dependent biotinylation (BioID) could be used to identify its nuclear protein-protein interaction partners under stressed versus non-stressed conditions, revealing the pathways it may regulate. **Therapeutic Potential:** As an intracellular metabolic enzyme with a broad expression profile in healthy tissues, [GCAT](/details-gene/23464) presents a challenging therapeutic target. Systemic **inhibition** would likely carry a high risk of on-target toxicity, affecting essential cell types like hematopoietic stem cells and hepatocytes. However, its potential could be re-evaluated in specific pathological contexts. For instance, certain cancers exhibit strong addictions to particular amino acid metabolic pathways. If a subset of tumors relies heavily on the threonine catabolism pathway, targeted inhibition of [GCAT](/details-gene/23464) could represent a viable context-specific therapeutic strategy.

Genular Protein ID: 2781961871

Symbol: KBL_HUMAN

Name: 2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial

UniProtKB Accession Codes:

O75600 E2QC23 Q6ZWF1 Q96CA9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEBI 9 ChiTaRS 1 DNASU 1 DisGeNET 1 DrugBank 2 EC 1 EMBL 4 Ensembl 2 ExpressionAtlas 1 GO 10 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HAMAP 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 1 RefSeq 4 Rhea 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10712613

Title: Molecular cloning of the human and murine 2-amino-3-ketobutyrate coenzyme A ligase cDNAs.

PubMed ID: 10712613

DOI: 10.1046/j.1432-1327.2000.01175.x

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 10591208

Title: The DNA sequence of human chromosome 22.

PubMed ID: 10591208

DOI: 10.1038/990031

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: 17688197

Title: Nuclear translocation of 2-amino-3-ketobutyrate coenzyme A ligase by cold and osmotic stress.

PubMed ID: 17688197

DOI: 10.1379/csc-264r.1

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

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: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

Sequence Information:

  • Length: 419
  • Mass: 45285
  • Checksum: C7760699E0474821
  • Sequence:
    • MWPGNAWRAA LFWVPRGRRA QSALAQLRGI LEGELEGIRG AGTWKSERVI TSRQGPHIRV 
DGVSGGILNF CANNYLGLSS HPEVIQAGLQ ALEEFGAGLS SVRFICGTQS IHKNLEAKIA 
RFHQREDAIL YPSCYDANAG LFEALLTPED AVLSDELNHA SIIDGIRLCK AHKYRYRHLD 
MADLEAKLQE AQKHRLRLVA TDGAFSMDGD IAPLQEICCL ASRYGALVFM DECHATGFLG 
PTGRGTDELL GVMDQVTIIN STLGKALGGA SGGYTTGPGP LVSLLRQRAR PYLFSNSLPP 
AVVGCASKAL DLLMGSNTIV QSMAAKTQRF RSKMEAAGFT ISGASHPICP VMLGDARLAS 
RMADDMLKRG IFVIGFSYPV VPKGKARIRV QISAVHSEED IDRCVEAFVE VGRLHGALP

Genular Protein ID: 280032000

Symbol: A8K228_HUMAN

Name: N/A

UniProtKB Accession Codes:

A8K228

Database IDs:

ARBA 4 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChEBI 1 DNASU 1 DisGeNET 1 EMBL 2 GO 5 Gene3D 2 HAMAP 1 InterPro 7 KEGG 1 NCBI Taxonomy 1 NCBIfam 1 OrthoDB 1 PANTHER 2 PROSITE 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 RefSeq 1 SUPFAM 1

Sequence Information:

  • Length: 419
  • Mass: 45220
  • Checksum: C1AA7FFC43433391
  • Sequence:
    • MWPGNAWRAA LFWVPRGRRA QSALAQLRGI LEGELEGICG AGTWKSERVI TSRQGPHIRV 
DGVSGGILNF CANNYLGLSS HPEVIQAGLQ ALEEFGAGLS SVRFICGTQS IHKNLEAKIA 
RFHQREDAIL YPSCYDANAG LFEALLTPED AVLSDELNHA SIIDGIRLCK AHKYRYRHLD 
MADLEAKLQE AQKHRLRLVA TDGAFSMDGD IAPLQEICCL ASRYGALVFM DECHATGFLG 
PTGRGTDELL GVMDQVTIIN STLGKALGGA SGGYTTGPGP LVSLLRQRAR PYLFSNSLPP 
AVVGCASKAL DLLMGSNTIV QSMAAKTQRF RSKMEAAGFT ISGASHPICP VMLGDARLAS 
RMADDMLKRG IFVIGFSYPV VPKGKARIRV QTSAVHSEED IDRCVEAFVE VGRLHGALP