Details for: TAT

Gene ID: 6898

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: TAT

Ensembl ID: ENSG00000198650

Description: tyrosine aminotransferase

Cell Significance Landscape

Associated with

Significant Cells

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

  • midzonal region hepatocyte CL0019028
    CSI 16.69
    rCSI 39.16%
    PRS 96.95
  • hepatocyte CL0000182
    CSI 14.67
    rCSI 26.26%
    PRS 97.36
  • centrilobular region hepatocyte CL0019029
    CSI 14.57
    rCSI 38.01%
    PRS 96.47
  • endothelial cell of periportal hepatic sinusoid CL0019021
    CSI 14.04
    rCSI 64.43%
    PRS 98.62
  • periportal region hepatocyte CL0019026
    CSI 9.4
    rCSI 36.56%
    PRS 96.78
  • hepatic stellate cell CL0000632
    CSI 8.61
    rCSI 32.24%
    PRS 97.9
  • Kupffer cell CL0000091
    CSI 7.75
    rCSI 17.73%
    PRS 98.77
  • cholangiocyte CL1000488
    CSI 5.23
    rCSI 31.36%
    PRS 97.38
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 4.67
    rCSI 14.38%
    PRS 98.84
  • luminal epithelial cell of mammary gland CL0002326
    CSI 3.79
    rCSI 6.88%
    PRS 99.11
  • intrahepatic cholangiocyte CL0002538
    CSI 3.16
    rCSI 7.58%
    PRS 98.37

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
    • Medium
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    • 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 Tyrosine aminotransferase, encoded by the gene **[TAT](/details-gene/6898)**, is a key cytosolic enzyme that catalyzes the first and rate-limiting step in the catabolism of the amino acid tyrosine. Functionally, it is essential for the `Tyrosine catabolic process` ([GO:0006572](https://www.ebi.ac.uk/QuickGO/term/GO:0006572)). Expression data reveals that **[TAT](/details-gene/6898)** is a highly specific marker for liver tissue, with its most significant expression observed in various subpopulations of [hepatocytes](/details-cell/CL0000182). Clinically, mutations in the **[TAT](/details-gene/6898)** gene are the underlying cause of tyrosinemia type II (Richner-Hanhart syndrome), an autosomal recessive metabolic disorder characterized by elevated tyrosine levels ([Link](https://doi.org/10.1073/pnas.89.19.9297)). ## Cellular Roles and Expression Landscape The expression profile of **[TAT](/details-gene/6898)** demonstrates a profound and specific enrichment within the liver, establishing it as a central player in hepatic metabolism. **Overall**, the gene shows its highest significance in [midzonal region hepatocytes](/details-cell/CL0019028) (CSI: 16.69), followed closely by the general [hepatocyte](/details-cell/CL0000182) population (CSI: 14.67) and [centrilobular region hepatocytes](/details-cell/CL0019029) (CSI: 14.57). This high level of expression across different functional zones of the liver lobule underscores its fundamental role in the core metabolic duties of these cells. The significance of **[TAT](/details-gene/6898)** also extends to other non-parenchymal cells of the liver microenvironment, including [endothelial cells of periportal hepatic sinusoids](/details-cell/CL0019021) (CSI: 14.04), [hepatic stellate cells](/details-cell/CL0000632) (CSI: 8.61), and [Kupffer cells](/details-cell/CL0000091) (CSI: 7.75). While its role in these cells is likely secondary to its function in [hepatocytes](/details-cell/CL0000182), this pattern suggests its involvement in the broader network of amino acid handling and metabolic homeostasis within the liver. The highly restricted expression pattern strongly indicates that systemic tyrosine degradation is a specialized function predominantly confined to hepatic tissue. ## Pathways and Molecular Function The **[TAT](/details-gene/6898)** gene product is an enzyme with `L-tyrosine-2-oxoglutarate transaminase activity` ([GO:0004838](https://www.ebi.ac.uk/QuickGO/term/GO:0004838)). It requires pyridoxal phosphate as a cofactor, which is reflected in its `Pyridoxal phosphate binding` function ([GO:0030170](https://www.ebi.ac.uk/QuickGO/term/GO:0030170)). This enzymatic action is the initial step in the `Tyrosine catabolism` ([R-HSA-8963684](https://reactome.org/content/detail/R-HSA-8963684)) pathway, which also intersects with the `Metabolism of amino acids and derivatives` ([R-HSA-71291](https://reactome.org/content/detail/R-HSA-71291)). Research has confirmed the narrow substrate specificity of this enzyme, highlighting its dedicated role in processing tyrosine ([Link](https://doi.org/10.1111/j.1742-4658.2006.05202.x)). Its function is integral to preventing the accumulation of tyrosine, which can be toxic. This molecular function is directly consistent with its high expression in [hepatocytes](/details-cell/CL0000182), the primary site for amino acid metabolism and detoxification in the body. ## Research Directions The highly specific expression of **[TAT](/details-gene/6898)** in the liver and its critical role in amino acid metabolism present several avenues for future investigation. Its association with a monogenic metabolic disease, tyrosinemia type II ([276600](https://omim.org/entry/276600)), provides a strong clinical anchor for further studies. **Proposed Hypotheses:** 1. Given its high expression across different functional zones of the liver, the activity and expression of **[TAT](/details-gene/6898)** may be dynamically regulated across the liver lobule in response to varying metabolic demands, such as circadian rhythms or changes in dietary protein intake. 2. Beyond the rare, penetrant mutations causing tyrosinemia, common genetic variants within the regulatory regions of **[TAT](/details-gene/6898)** may contribute to subclinical variations in tyrosine metabolism, potentially influencing susceptibility to metabolic stress or liver injury in the general population. **Experimental Approach:** To test the hypothesis of zonal regulation (Hypothesis 1), a powerful approach would be to use spatial transcriptomics on liver tissue from animal models subjected to different dietary conditions (e.g., high-protein vs. low-protein diets). By mapping the transcriptome onto the physical structure of the liver lobule, this experiment would precisely quantify **[TAT](/details-gene/6898)** mRNA levels in periportal, midzonal, and pericentral [hepatocytes](/details-cell/CL0000182). This would reveal whether its expression is uniform or dynamically patterned to optimize metabolic efficiency under different physiological states. **Therapeutic Potential:** As the direct cause of a metabolic deficiency disorder, **[TAT](/details-gene/6898)** is a prime candidate for therapeutic intervention based on functional restoration. The primary goal is not inhibition but rather activation or replacement. Gene therapy represents a promising strategy, where a functional copy of the **[TAT](/details-gene/6898)** gene could be delivered specifically to the [hepatocytes](/details-cell/CL0000182) of affected patients using liver-tropic adeno-associated virus (AAV) vectors. This would aim to restore enzymatic activity and correct the underlying metabolic defect of tyrosinemia type II.

Genular Protein ID: 3754986553

Symbol: ATTY_HUMAN

Name: Tyrosine aminotransferase

UniProtKB Accession Codes:

P17735 B2R8I1 D3DWS2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 5 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 4 EC 2 EMBL 16 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 13 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 2 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 PIRSF 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 1 Rhea 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 1973834

Title: Isolation and characterization of the human tyrosine aminotransferase gene.

PubMed ID: 1973834

DOI: 10.1093/nar/18.13.3853

PubMed ID: 7908801

Title: Nucleotide sequence of the human tyrosine aminotransferase gene.

PubMed ID: 7908801

PubMed ID: 7999802

Title: Cloning and expression of human tyrosine aminotransferase cDNA.

PubMed ID: 7999802

DOI: 10.1016/0167-4781(94)00191-5

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16640556

Title: The narrow substrate specificity of human tyrosine aminotransferase -- the enzyme deficient in tyrosinemia type II.

PubMed ID: 16640556

DOI: 10.1111/j.1742-4658.2006.05202.x

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: 1357662

Title: Point mutations in the tyrosine aminotransferase gene in tyrosinemia type II.

PubMed ID: 1357662

DOI: 10.1073/pnas.89.19.9297

Sequence Information:

  • Length: 454
  • Mass: 50399
  • Checksum: 82B5B24F3B2CE489
  • Sequence:
    • MDPYMIQMSS KGNLPSILDV HVNVGGRSSV PGKMKGRKAR WSVRPSDMAK KTFNPIRAIV 
DNMKVKPNPN KTMISLSIGD PTVFGNLPTD PEVTQAMKDA LDSGKYNGYA PSIGFLSSRE 
EIASYYHCPE APLEAKDVIL TSGCSQAIDL CLAVLANPGQ NILVPRPGFS LYKTLAESMG 
IEVKLYNLLP EKSWEIDLKQ LEYLIDEKTA CLIVNNPSNP CGSVFSKRHL QKILAVAARQ 
CVPILADEIY GDMVFSDCKY EPLATLSTDV PILSCGGLAK RWLVPGWRLG WILIHDRRDI 
FGNEIRDGLV KLSQRILGPC TIVQGALKSI LCRTPGEFYH NTLSFLKSNA DLCYGALAAI 
PGLRPVRPSG AMYLMVGIEM EHFPEFENDV EFTERLVAEQ SVHCLPATCF EYPNFIRVVI 
TVPEVMMLEA CSRIQEFCEQ HYHCAEGSQE ECDK