Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004838 L-tyrosine:2-oxoglutarate transaminase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assertion of the core molecular function. This is the correct, specific enzymatic activity of TAT (EC 2.6.1.5), directly supported by experimental characterization of the human enzyme. Reason: This is the defining, experimentally validated molecular function of TAT. The IBA is consistent with the IDA on the same term and with the catalytic activity reported in UniProt (RHEA:15093). Core function. Supporting Evidence: PMID:7999802 The expressed protein catalyzed specifically the conversion of L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate.
GO:0006572 L-tyrosine catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic assertion that TAT participates in L-tyrosine catabolism. TAT catalyzes the first, committed step of tyrosine breakdown, so this is the correct biological process. Reason: Consistent with the IDA on the same term and with UniProt FUNCTION ("Transaminase involved in tyrosine breakdown"). Core process. Supporting Evidence: PMID:7999802 The expressed protein catalyzed specifically the conversion of L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate.
GO:0006559 L-phenylalanine catabolic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic assertion of involvement in L-phenylalanine catabolism. Phenylalanine is degraded via conversion to tyrosine, and UniProt places TAT as step 2/6 of the L-phenylalanine degradation pathway (the tyrosine transamination step). TAT itself has only weak, low-affinity activity directly on phenylalanine. Reason: Biologically defensible as pathway membership (Phe -> Tyr -> catabolism), matching the UniProt PATHWAY statement, and it is corroborated by an independent UniPathway mapping annotation. However, TAT's direct catalytic role is on tyrosine; its phenylalanine transaminase activity is much lower. Retain as a non-core, pathway-context process rather than a core function. Supporting Evidence: PMID:16640556 The narrow substrate specificity of human tyrosine aminotransferase -- the enzyme deficient in tyrosinemia type II.
GO:0003824 catalytic activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: InterPro2GO electronic annotation to the root molecular-function catalytic-activity term. TAT is an enzyme, so the term is not wrong, but it is far too general given that the specific activity (GO:0004838) is known experimentally. Reason: GO:0004838 is an entailed subclass of GO:0003824; the specific transaminase activity is experimentally established for the human enzyme, so this uninformative parent should not be treated as a core function. Proposed replacements: L-tyrosine:2-oxoglutarate transaminase activity
GO:0004838 L-tyrosine:2-oxoglutarate transaminase activity	IEA GO_REF:0000120	ACCEPT	Summary: Combined multi-method electronic annotation to the correct, specific molecular function of TAT. Reason: Matches the experimentally supported core molecular function (IDA/IBA on the same term). Correct level of specificity. Supporting Evidence: PMID:7999802 The expressed protein catalyzed specifically the conversion of L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate.
GO:0006520 amino acid metabolic process	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Electronic annotation to a high-level amino-acid metabolic process term. TAT participates in amino-acid metabolism (tyrosine catabolism), so the term is correct but general. Reason: True but subsumed by the more specific and experimentally supported L-tyrosine catabolic process (GO:0006572). Retain as a broad-parent, non-core annotation. Proposed replacements: L-tyrosine catabolic process
GO:0008483 transaminase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: InterPro2GO annotation to the general transaminase-activity term. TAT is a transaminase, so the term is correct but broader than the known specific activity. Reason: GO:0004838 is an entailed subclass of GO:0008483; the specific tyrosine transaminase activity is experimentally known, so the general parent is an over-annotation for core-function purposes. Proposed replacements: L-tyrosine:2-oxoglutarate transaminase activity
GO:0009072 aromatic amino acid metabolic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro2GO annotation to aromatic amino acid metabolic process. Tyrosine and phenylalanine are aromatic amino acids, so the term is correct but broad. Reason: Subsumed by the more specific tyrosine catabolic process (GO:0006572). Correct but general; retain as non-core parent. Proposed replacements: L-tyrosine catabolic process
GO:0009074 aromatic amino acid catabolic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro2GO annotation to aromatic amino acid (family) catabolic process (current ontology primary label: "aromatic amino acid family catabolic process"). TAT catalyzes the first step of catabolism of the aromatic amino acid tyrosine, so the term is correct but broad. Reason: True but subsumed by the more specific and experimentally supported L-tyrosine catabolic process (GO:0006572). Retain as a broad-parent, non-core annotation. Proposed replacements: L-tyrosine catabolic process
GO:0030170 pyridoxal phosphate binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO annotation for PLP cofactor binding. TAT is a PLP-dependent aminotransferase that binds pyridoxal 5'-phosphate as a Schiff base to Lys-280, confirmed by the crystal structure (PDB 3DYD). Reason: Directly supported by the UniProt COFACTOR annotation and the N6-(pyridoxal phosphate)lysine modified residue at Lys-280 seen in the crystal structure. A correct, mechanistically important molecular function.
GO:0005515 protein binding	IPI PMID:24722188 Protein interaction network of alternatively spliced isoform...	MARK AS OVER ANNOTATED	Summary: Interaction reported in a genome-scale interactome map. Bare "protein binding" is uninformative about molecular function and this specific interaction is not discussed for TAT in the body of the paper. Reason: Per curation guidelines, the bare protein-binding term does not convey TAT's function and is derived from a high-throughput screen without a TAT-specific functional interpretation. Not a core function.
GO:0005515 protein binding	IPI PMID:25910212 Widespread macromolecular interaction perturbations in human...	MARK AS OVER ANNOTATED	Summary: High-throughput interactome IPI annotation. Bare "protein binding" is uninformative and the interaction is not functionally characterized for TAT in the paper. Reason: Uninformative molecular-function term from a systematic screen; provides no insight into TAT's function. Not a core function.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	MARK AS OVER ANNOTATED	Summary: High-throughput interactome IPI annotation. Bare "protein binding" is uninformative for molecular function. Reason: Uninformative term derived from a genome-scale binary interaction assay; not functionally characterized for TAT. Not a core function.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Annotation from the HuRI reference human binary protein interactome. Bare "protein binding" does not describe TAT's molecular function. Reason: Uninformative molecular-function term from a systematic Y2H interactome map; no TAT-specific functional interpretation. Not a core function.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: Interaction from a neurodegenerative-disease interactome map. Bare "protein binding" is uninformative for molecular function. Reason: Uninformative term from a high-throughput screen; provides no functional insight for TAT. Not a core function.
GO:0042802 identical protein binding	IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam...	KEEP AS NON CORE	Summary: Self-interaction (homodimerization) annotation. TAT is documented as a homodimer, so self-association is real biology, though it is not the core catalytic function. Reason: Corroborated by the UniProt SUBUNIT statement ("Homodimer.") and the IntAct self-interaction record (P17735-P17735). More informative than bare protein binding, but a structural/quaternary property rather than a core molecular function.
GO:0042802 identical protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	KEEP AS NON CORE	Summary: Self-interaction annotation consistent with TAT being a homodimer. Reason: Corroborated by the UniProt SUBUNIT "Homodimer." statement. A quaternary structural property, not a core molecular function.
GO:0042802 identical protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	KEEP AS NON CORE	Summary: Self-interaction annotation from the HuRI interactome, consistent with the documented homodimer. Reason: Corroborated by the UniProt SUBUNIT "Homodimer." statement. Structural quaternary property, not a core function.
GO:0005829 cytosol	IEA GO_REF:0000107	ACCEPT	Summary: Ensembl-Compara orthology-based location. TAT is a cytosolic enzyme, and this is independently supported by the Reactome TAS annotations to the same term. Reason: Correct subcellular location; TAT is a soluble cytosolic aminotransferase. Core location, corroborated by Reactome. This is a location transfer, not a phenotype-response transfer, so it is reliable regardless of GO_REF source.
GO:0006103 2-oxoglutarate metabolic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology-transferred annotation reflecting that 2-oxoglutarate is a cosubstrate of the transamination reaction. Duplicated by the IDA on the same term. Reason: 2-oxoglutarate is consumed as the amino-group acceptor cosubstrate, so the process is a real consequence of the reaction, but it is a cosubstrate/co-metabolite consequence rather than TAT's core biological role (tyrosine catabolism).
GO:0006536 glutamate metabolic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology-transferred annotation reflecting that L-glutamate is produced as the co-product of the transamination reaction. Duplicated by the IDA on the same term. Reason: L-glutamate is the amino-group-carrying co-product, so the process is a real consequence of the reaction, but it is a co-product consequence rather than TAT's core biological role.
GO:0006572 L-tyrosine catabolic process	IEA GO_REF:0000107	ACCEPT	Summary: Orthology-transferred annotation to the core biological process, tyrosine catabolism. Duplicated by the IDA and IBA on the same term. Reason: Correct core biological process; TAT catalyzes the first step of tyrosine breakdown. Consistent with experimental (IDA) and phylogenetic (IBA) annotations.
GO:0006979 response to oxidative stress	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl-Compara orthology-transferred response term, largely derived from rodent orthologs. Represents a physiological/regulatory response context, not TAT's molecular activity or its direct catabolic role. Reason: Plausible regulatory context transferred by orthology, but not verified for the human protein and not a core function. Retain as non-core.
GO:0016597 amino acid binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Orthology-transferred molecular function reflecting that TAT binds its amino-acid substrate (tyrosine). The term is a general parent; substrate binding is inherent to the specific transaminase activity. Reason: Binding of the amino-acid substrate is subsumed by the specific catalytic activity (GO:0004838); the standalone "amino acid binding" term adds no functional information beyond the enzyme activity. Not a core function. Proposed replacements: L-tyrosine:2-oxoglutarate transaminase activity
GO:0032869 cellular response to insulin stimulus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl-Compara orthology-transferred response term (largely from rodent orthologs). Reflects hormonal regulation of TAT expression rather than the protein's molecular activity. Reason: TAT is a classical hormonally regulated hepatic gene; insulin-response context is plausible but transferred by orthology and unverified for the human protein. Regulatory context, not a core function.
GO:0045471 response to ethanol	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology-transferred response term. Represents a physiological response context of the gene rather than TAT's core molecular or catabolic role. Reason: Regulatory/response context transferred by orthology and unverified for the human protein. Not a core function.
GO:0046689 response to mercury ion	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology-transferred response term. Represents a physiological response context of the gene rather than TAT's core function. Reason: Regulatory/response context transferred by orthology and unverified for the human protein. Not a core function.
GO:0051384 response to glucocorticoid	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology-transferred response term. TAT is the textbook glucocorticoid-inducible hepatic gene, but induction is regulation of expression rather than TAT's molecular activity, and the human promoter GREs are notably degenerate relative to rat. Reason: Well-established regulatory context (glucocorticoid induction) but a response/regulation term, not TAT's core molecular or catabolic function. The human upstream GREs are mutated/replaced by Alu elements, so even the regulatory transfer from rat is imperfect. Retain as non-core. Supporting Evidence: PMID:1973834 Two functional glucocorticoid response elements (GREs) reside 2.5 kb upstream of the rat TAT gene. The DNA sequence of the corresponding region of the human TAT gene shows the distal GRE mutated and the proximal GRE replaced by Alu elements.
GO:0051414 response to cortisol	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology-transferred response term, a specific instance of the glucocorticoid-response context of the gene. Reason: Regulatory/response context transferred by orthology; not a core molecular or catabolic function. Retain as non-core.
GO:0051591 response to cAMP	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology-transferred response term. TAT is a classical cAMP/glucagon- inducible gene, but induction is regulation of expression, not the protein's molecular activity. Reason: Well-known regulatory context but a response/regulation term, not a core function. Retain as non-core.
GO:0071300 cellular response to retinoic acid	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology-transferred response term. Physiological response context rather than TAT's core molecular or catabolic role. Reason: Regulatory/response context transferred by orthology and unverified for the human protein. Not a core function.
GO:0071548 response to dexamethasone	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology-transferred response term; a synthetic-glucocorticoid instance of the well-known hormonal induction of TAT expression. Reason: Regulatory/response context transferred by orthology; not a core molecular or catabolic function. Retain as non-core.
GO:0097421 liver regeneration	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology-transferred process term reflecting hepatic expression dynamics. TAT is a liver-enriched enzyme, but there is no evidence it functions in the regeneration process itself as opposed to being expressed in liver. Reason: Association with liver-expression context, transferred by orthology and unverified mechanistically for the human protein. Not a core function.
GO:0006559 L-phenylalanine catabolic process	IEA GO_REF:0000041	KEEP AS NON CORE	Summary: UniPathway-mapping-based annotation to L-phenylalanine catabolism, matching the UniProt PATHWAY statement (step 2/6 of L-phenylalanine degradation). Phenylalanine is degraded via tyrosine, so TAT participates in the pathway through its tyrosine transamination step. Reason: Defensible as pathway membership (Phe -> Tyr -> catabolism) and consistent with the UniProt PATHWAY annotation, but TAT's direct catalytic role is on tyrosine, with only weak phenylalanine activity. Non-core pathway context. Supporting Evidence: PMID:16640556 The narrow substrate specificity of human tyrosine aminotransferase -- the enzyme deficient in tyrosinemia type II.
GO:0005829 cytosol	TAS Reactome:R-HSA-517444	ACCEPT	Summary: Reactome traceable-author-statement placing TAT in the cytosol, in the context of the reaction "TAT aminates HPP". Correct subcellular location. Reason: TAT is a soluble cytosolic aminotransferase; the location is well established and corroborated by the Ensembl location annotation. Core location.
GO:0005829 cytosol	TAS Reactome:R-HSA-71155	ACCEPT	Summary: Reactome TAS placing TAT in the cytosol in the context of the reaction "TAT deaminates tyrosine" (the forward tyrosine transamination step). Reason: Correct cytosolic location, consistent with the other cytosol annotations. Core location.
GO:0004838 L-tyrosine:2-oxoglutarate transaminase activity	IDA PMID:7999802 Cloning and expression of human tyrosine aminotransferase cD...	ACCEPT	Summary: Direct experimental demonstration that the cloned human TAT protein specifically converts L-tyrosine to 4-hydroxyphenylpyruvate. This is the primary experimental basis for the core molecular function. Reason: Human TAT cDNA expressed in HeLa cells produced a ~50 kDa protein that catalyzed specifically the conversion of L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate. Definitive core molecular function. Supporting Evidence: PMID:7999802 The expressed protein catalyzed specifically the conversion of L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate.
GO:0006103 2-oxoglutarate metabolic process	IDA PMID:7999802 Cloning and expression of human tyrosine aminotransferase cD...	KEEP AS NON CORE	Summary: Annotation reflecting consumption of 2-oxoglutarate as the amino-group acceptor cosubstrate in the demonstrated transamination reaction. Reason: 2-oxoglutarate is the cosubstrate consumed in the transamination; a real but co-metabolite consequence rather than TAT's core biological role of tyrosine catabolism. Supporting Evidence: PMID:7999802 The expressed protein catalyzed specifically the conversion of L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate.
GO:0006536 glutamate metabolic process	IDA PMID:7999802 Cloning and expression of human tyrosine aminotransferase cD...	KEEP AS NON CORE	Summary: Annotation reflecting production of L-glutamate as the co-product of the demonstrated transamination reaction. Reason: L-glutamate is the amino-group-carrying co-product; a real but co-product consequence rather than TAT's core biological role of tyrosine catabolism. Supporting Evidence: PMID:7999802 The expressed protein catalyzed specifically the conversion of L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate.
GO:0006572 L-tyrosine catabolic process	IDA PMID:7999802 Cloning and expression of human tyrosine aminotransferase cD...	ACCEPT	Summary: Direct experimental annotation to tyrosine catabolism, based on the demonstrated conversion of tyrosine to 4-hydroxyphenylpyruvate by the human enzyme (the first, committed step of tyrosine breakdown). Reason: Core biological process, directly supported by expression of functional human TAT that specifically transaminates tyrosine. Supporting Evidence: PMID:7999802 The expressed protein catalyzed specifically the conversion of L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate.
GO:0005575 cellular_component	ND GO_REF:0000015	REMOVE	Summary: Root cellular-component annotation with No Data evidence code, a placeholder indicating no specific component was curated by this source. Superseded by the specific cytosol annotations (TAS and IEA). Reason: This is an uninformative ND root-node placeholder that is superseded by the experimentally/authoritatively supported cytosol location annotations. It conveys no information and should not be retained.
GO:0004838 L-tyrosine:2-oxoglutarate transaminase activity	NAS PMID:1973834 Isolation and characterization of the human tyrosine aminotr...	ACCEPT	Summary: Non-traceable author statement of the core transaminase activity, from the paper characterizing the human TAT gene. Redundant with, and weaker than, the IDA/IBA/IEA support for the same term. Reason: Correct core molecular function; although the evidence code is NAS, the assignment is fully corroborated by the direct experimental (IDA) annotation and UniProt catalytic activity. Supporting Evidence: PMID:1973834 Isolation and characterization of the human tyrosine aminotransferase gene.

Core Functions

L-tyrosine:2-oxoglutarate transaminase (tyrosine aminotransferase), the PLP-dependent enzyme that catalyzes the first, committed step of L-tyrosine catabolism in the liver cytosol.

Molecular Function:

L-tyrosine:2-oxoglutarate transaminase activity

Directly Involved In:

L-tyrosine catabolic process

Cellular Locations:

cytosol

Supporting Evidence:

PMID:7999802
The expressed protein catalyzed specifically the conversion of L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000015

Use of the ND evidence code for Gene Ontology (GO) terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000041

Gene Ontology annotation based on UniPathway vocabulary mapping

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:1973834

Isolation and characterization of the human tyrosine aminotransferase gene.

Characterizes the human TAT gene (12 exons, 454-aa protein, 50,399 Da, 92% protein identity to rat); notes that the functional glucocorticoid response elements present upstream of the rat gene are mutated or Alu-replaced in the human gene.

"The human TAT gene is predicted to code for a 454 amino acid protein of molecular weight 50,399 dalton."

PMID:7999802

Cloning and expression of human tyrosine aminotransferase cDNA.

Human TAT cDNA expressed in HeLa cells produced a ~50 kDa protein that specifically converted L-tyrosine to 4-hydroxyphenylpyruvate, establishing the core molecular function and involvement in tyrosine catabolism.

"The expressed protein catalyzed specifically the conversion of L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate."

PMID:16640556

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

Establishes that human TAT has narrow substrate specificity for tyrosine with only weak activity toward phenylalanine, and that Ile-294 is important for catalytic activity; supports treating phenylalanine/aromatic-amino-acid processes as non-core.

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

PMID:24722188

Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism.

PMID:25502805

A massively parallel pipeline to clone DNA variants and examine molecular phenotypes of human disease mutations.

PMID:25910212

Widespread macromolecular interaction perturbations in human genetic disorders.

PMID:31515488

Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.

PMID:32296183

A reference map of the human binary protein interactome.

PMID:32814053

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

Reactome:R-HSA-517444

TAT aminates HPP

Reactome:R-HSA-71155

TAT deaminates tyrosine

Deep Research

Falcon

(TAT-deep-research-falcon.md)

Comprehensive Research Report: Human Tyrosine Aminotransferase (TAT, P17735) Falcon Edison Scientific Literature 31 citations 2 artifacts 2026-07-05T18:16:37.315676

Edison artifact artifact-00 (text/markdown)

Edison artifact artifact-01 (text/markdown)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Comprehensive Research Report: Human Tyrosine Aminotransferase (TAT, P17735)

1. Gene and Protein Identity

The human TAT gene (Ensembl: ENSG00000198650) encodes tyrosine aminotransferase (UniProt: P17735; EC 2.6.1.5), also known as L-tyrosine:2-oxoglutarate aminotransferase. The gene is located on chromosome 16q22.1–q22.5, contains 12 exons, and encodes a 454-amino acid protein (alsharhan2020disordersofphenylalanine pages 28-29, OpenTargets Search: tyrosinemia-TAT). It is important to note that the gene symbol "TAT" is shared with the HIV-1 transactivator of transcription protein (Tat); this report exclusively addresses the human hepatic tyrosine aminotransferase enzyme.

The following table summarizes the key molecular and functional properties of human TAT:

Characteristic	Summary
Gene symbol	TAT (tyrosine aminotransferase) (OpenTargets Search: tyrosinemia-TAT, alsharhan2020disordersofphenylalanine pages 28-29)
UniProt ID	P17735 (from user-provided UniProt target specification)
EC number	EC 2.6.1.5 (tyrosine aminotransferase) (parthasarathy2018athreeringcircus pages 4-5, xu2020generalandspecialized pages 2-5)
Gene location	Chromosome 16q22.1-q22.5 (alsharhan2020disordersofphenylalanine pages 28-29)
Protein size	454 amino acids; gene contains 12 exons (alsharhan2020disordersofphenylalanine pages 28-29)
Cofactor	Pyridoxal 5′-phosphate (PLP) (xu2020generalandspecialized pages 2-5, alsharhan2020disordersofphenylalanine pages 28-29)
Quaternary structure	Homodimer (parthasarathy2018athreeringcircus pages 4-5, jensen1996evolutionaryrecruitmentof pages 2-3)
Subcellular localization	Predominantly cytosolic; human TAT is described as the cytosolic tyrosine aminotransferase (alsharhan2020disordersofphenylalanine pages 28-29, caligiore2022humancytosolictransaminases pages 2-4)
Primary tissue expression	Expressed primarily in liver, especially hepatic parenchymal cells; tyrosine degradation is mainly hepatic with minor kidney contribution (holme2013tyrosinemetabolism pages 1-2, jantzen1987cooperativityofglucocorticoid pages 1-2)
Primary reaction	Reversible transamination of L-tyrosine to 4-hydroxyphenylpyruvate (4-HPP/pHPP) using an amino-group acceptor; first step of tyrosine degradation (xu2020generalandspecialized pages 2-5, scherman2020drugrepositioningfor pages 3-5)
Primary substrates	L-tyrosine and α-ketoglutarate as the canonical substrate pair for tyrosine catabolism (xu2020generalandspecialized pages 2-5, scherman2020drugrepositioningfor pages 3-5)
Products	4-hydroxyphenylpyruvate and L-glutamate (from the canonical tyrosine + α-ketoglutarate reaction) (xu2020generalandspecialized pages 2-5, scherman2020drugrepositioningfor pages 3-5)
Alternative substrates	Accepts phenylalanine; human cytosolic TAT also shows side activity toward L-tryptophan (parthasarathy2018athreeringcircus pages 4-5, caligiore2022humancytosolictransaminases pages 6-8)
Disease association	Tyrosinemia type II / Richner-Hanhart syndrome; autosomal recessive TAT deficiency causing hypertyrosinemia, dendritic keratitis, palmoplantar hyperkeratosis, and sometimes learning disability (OpenTargets Search: tyrosinemia-TAT, alsharhan2020disordersofphenylalanine pages 28-29, alsharhan2020disordersofphenylalanine pages 31-33)
Evolutionary family classification	Class I PLP-dependent aminotransferase; mammalian cytosolic TAT is placed in Family I, subfamily Ig, distinct from bacterial TyrB enzymes of subfamily Ia (jensen1996evolutionaryrecruitmentof pages 4-7, jensen1996evolutionaryrecruitmentof pages 3-4)

Table: This table summarizes the core molecular, biochemical, cellular, and disease-related properties of human tyrosine aminotransferase (TAT, UniProt P17735). It is useful as a compact reference for functional annotation and report writing.

2. Enzymatic Function and Catalytic Mechanism

2.1 Primary Reaction

Human TAT catalyzes the reversible transamination of L-tyrosine to 4-hydroxyphenylpyruvate (4-HPP, also referred to as p-hydroxyphenylpyruvate or pHPP), using α-ketoglutarate (2-oxoglutarate) as the amino group acceptor, with the concomitant production of L-glutamate (xu2020generalandspecialized pages 2-5, scherman2020drugrepositioningfor pages 3-5). This reaction represents the first and rate-limiting step in the tyrosine catabolic pathway (alsharhan2020disordersofphenylalanine pages 28-29, holme2013tyrosinemetabolism pages 1-2). The overall reaction can be written as:

L-tyrosine + 2-oxoglutarate ⇌ 4-hydroxyphenylpyruvate + L-glutamate

2.2 Cofactor and Mechanism

TAT belongs to the class-I pyridoxal-5′-phosphate (PLP)-dependent aminotransferase family (parthasarathy2018athreeringcircus pages 4-5, xu2020generalandspecialized pages 2-5, alsharhan2020disordersofphenylalanine pages 28-29). Like other PLP-dependent aminotransferases, TAT operates via a ping-pong bi-bi mechanism. In the first half-reaction, the PLP cofactor forms an internal aldimine (Schiff base) with a catalytic lysine residue. The amino acid substrate displaces the lysine to form an external aldimine, and following a 1,3-prototropic shift, a ketimine intermediate is formed. Hydrolysis of this intermediate releases the α-keto acid product and leaves the cofactor in the pyridoxamine-5′-phosphate (PMP) form. In the second half-reaction, the amino group is transferred from PMP to the acceptor α-keto acid (α-ketoglutarate), regenerating PLP and releasing glutamate. Structural studies on related family I aminotransferases reveal that upon substrate binding, the smaller domain of the homodimer moves toward the larger domain, closing the active site pocket to properly position substrates for catalysis (parthasarathy2018athreeringcircus pages 4-5).

2.3 Substrate Specificity and Side Activities

While L-tyrosine is the canonical physiological substrate, TAT also efficiently transamines L-phenylalanine (parthasarathy2018athreeringcircus pages 4-5, parthasarathy2018athreeringcircus pages 2-4). A systematic investigation of human cytosolic transaminase side activities by Caligiore et al. (2022) demonstrated that TAT, along with five other human cytosolic transaminases (GOT1, GPT, GTK, PSAT1, BCAT1), was tested against amino acids whose primary degradation pathways do not typically involve transamination. TAT exhibited notable side activity toward L-tryptophan, displaying relatively high apparent k_cat and high apparent K_M values for L-Trp transamination, suggesting it could contribute to a minor pathway for L-Trp degradation (caligiore2022humancytosolictransaminases pages 6-8, caligiore2022humancytosolictransaminases pages 5-6). In contrast, reactions with L-Thr, L-Arg, L-Lys, and L-Asn were consistently very slow across all tested transaminases (caligiore2022humancytosolictransaminases pages 5-6). For recombinant expression studies, the first 40 codons of the human TAT coding sequence were removed to obtain a shortened recombinant protein compatible with soluble expression (caligiore2022humancytosolictransaminases pages 2-4).

3. Subcellular Localization and Tissue Expression

3.1 Subcellular Localization

Human TAT functions predominantly as a cytosolic enzyme (alsharhan2020disordersofphenylalanine pages 28-29, caligiore2022humancytosolictransaminases pages 2-4). The designation of TAT as "cytosolic tyrosine aminotransferase" distinguishes it from the mitochondrial aspartate aminotransferase isoform. Donini et al. (2009) confirmed that the TAT gene encodes the cytosolic tyrosine aminotransferase in humans (caligiore2022humancytosolictransaminases pages 2-4). Although one source mentions possible transport to mitochondria (alsharhan2020disordersofphenylalanine pages 28-29), the predominant body of evidence identifies the cytosol as the primary functional compartment.

3.2 Tissue Expression

TAT is synthesized almost exclusively in hepatic parenchymal cells of the liver (jantzen1987cooperativityofglucocorticoid pages 1-2). Tyrosine degradation occurs primarily in the liver, with minor degradation activity detected in the kidney (holme2013tyrosinemetabolism pages 1-2). Expression of TAT increases rapidly after birth in a developmentally regulated manner, and glucocorticoid hormones and cAMP can prematurely activate TAT gene expression, suggesting a role for these signaling molecules in developmental control of tyrosine catabolism (jantzen1987cooperativityofglucocorticoid pages 1-2).

4. Biochemical Pathway: Tyrosine Catabolism

TAT catalyzes the first step of the five-enzyme tyrosine degradation pathway, which converts L-tyrosine to the tricarboxylic acid (TCA) cycle intermediates fumarate and the ketone body acetoacetate. The complete pathway and its associated inborn errors of metabolism are presented below:

Step Number	Enzyme Name	Gene Symbol	EC Number	Substrate	Product	Associated Disease (when deficient)
1	Tyrosine aminotransferase	TAT	EC 2.6.1.5	L-tyrosine + 2-oxoglutarate	4-hydroxyphenylpyruvate + L-glutamate	Tyrosinemia type II (Richner-Hanhart syndrome) (alsharhan2020disordersofphenylalanine pages 28-29, holme2013tyrosinemetabolism pages 1-2, scherman2020drugrepositioningfor pages 3-5)
2	4-Hydroxyphenylpyruvate dioxygenase	HPD	EC 1.13.11.27	4-hydroxyphenylpyruvate	Homogentisic acid (homogentisate)	Tyrosinemia type III (holme2013tyrosinemetabolism pages 1-2, scherman2020drugrepositioningfor pages 3-5, holme2013tyrosinemetabolism pages 2-4)
3	Homogentisate 1,2-dioxygenase	HGD	EC 1.13.11.5	Homogentisic acid (homogentisate)	Maleylacetoacetate	Alkaptonuria (holme2013tyrosinemetabolism pages 1-2, scherman2020drugrepositioningfor pages 3-5, holme2013tyrosinemetabolism pages 2-4)
4	Maleylacetoacetate isomerase (glutathione S-transferase zeta 1)	GSTZ1	EC 5.2.1.2	Maleylacetoacetate	Fumarylacetoacetate	Maleylacetoacetate isomerase deficiency (MAAID) (scherman2020drugrepositioningfor pages 3-5)
5	Fumarylacetoacetate hydrolase	FAH	EC 3.7.1.2	Fumarylacetoacetate	Fumarate + acetoacetate	Tyrosinemia type I (holme2013tyrosinemetabolism pages 1-2, scherman2020drugrepositioningfor pages 3-5)

Table: This table summarizes the complete five-step human tyrosine catabolic pathway from tyrosine to fumarate and acetoacetate. It also links each enzymatic step to the inherited disorder caused by deficiency of that enzyme, making it useful for functional annotation and clinical interpretation.

The pathway begins with TAT-catalyzed transamination of tyrosine to 4-hydroxyphenylpyruvate. This intermediate is then oxidized by 4-hydroxyphenylpyruvate dioxygenase (HPD) to homogentisic acid (scherman2020drugrepositioningfor pages 3-5, holme2013tyrosinemetabolism pages 2-4). Homogentisate 1,2-dioxygenase (HGD) cleaves the aromatic ring to produce maleylacetoacetate, which is isomerized by maleylacetoacetate isomerase (GSTZ1) to fumarylacetoacetate. Finally, fumarylacetoacetate hydrolase (FAH) cleaves fumarylacetoacetate into fumarate and acetoacetate, completing the catabolic sequence (scherman2020drugrepositioningfor pages 3-5, holme2013tyrosinemetabolism pages 1-2). This pathway connects aromatic amino acid catabolism to central carbon metabolism and energy production. Perturbations at each step result in distinct inherited metabolic diseases, as detailed in the table above.

Beyond this primary catabolic route, alternative biotransformation products arise from the major pathway metabolites. Norman et al. (2022) identified 13 phase 1 and phase 2 biotransformation products from phenylalanine through to homogentisic acid, representing alternative clearance routes that minimize hypertyrosinemia, particularly when the pathway is pharmacologically inhibited by nitisinone (norman2022comprehensivebiotransformationanalysis pages 1-2).

5. Transcriptional Regulation

The TAT gene is one of the best-characterized models for hormonal gene regulation. TAT expression is potently induced by glucocorticoids at the transcriptional level. Jantzen et al. (1987) identified two glucocorticoid response elements (GREs) located approximately 2.5 kb upstream of the transcription initiation site that cooperatively mediate hormonal induction. The proximal GRE alone lacks inherent transcriptional stimulatory capacity but synergistically enhances glucocorticoid induction when combined with the distal GRE, resulting in approximately 15-fold increases in TAT mRNA expression upon dexamethasone treatment (jantzen1987cooperativityofglucocorticoid pages 1-2, jantzen1987cooperativityofglucocorticoid pages 2-3). In addition to glucocorticoids, cAMP also directly activates TAT gene transcription (jantzen1987cooperativityofglucocorticoid pages 1-2).

Chromatin remodeling plays a critical role in TAT gene regulation. Upon glucocorticoid treatment, the GR recruits FOXA1/2 transcription factors to the glucocorticoid response unit (GRU), followed by stable recruitment of C/EBP factors. After 2–3 days of dexamethasone treatment, CpG dinucleotides within the GRU are demethylated, providing a form of transcriptional "gene memory" for subsequent glucocorticoid stimulation (chang2026hepaticglucocorticoidreceptor pages 7-7). Insulin can counteract glucocorticoid-induced TAT transcription through mechanisms involving the glucocorticoid receptor's ligand-binding domain (chang2026hepaticglucocorticoidreceptor pages 19-19).

6. Structural and Evolutionary Context

6.1 Protein Structure

Human TAT is a homodimeric enzyme, consistent with other members of the class I aminotransferase superfamily (parthasarathy2018athreeringcircus pages 4-5, jensen1996evolutionaryrecruitmentof pages 2-3). Each subunit contains the PLP cofactor covalently bound to a conserved lysine residue via a Schiff base linkage. The enzyme contains domains characteristic of the aminotransferase I/II superfamily, including the large aminotransferase domain (IPR004839), the pyridoxal-phosphate binding site motif (IPR004838), and the smaller substrate-binding domain (IPR015422). Structural studies on related aminotransferases show that substrate binding triggers a conformational change in which the smaller domain moves toward the larger domain to close the active-site pocket, properly positioning the substrate for catalysis (parthasarathy2018athreeringcircus pages 4-5).

6.2 Evolutionary Classification

TAT belongs to the broader Family I of PLP-dependent aminotransferases, which share a common protein scaffold and catalytic mechanism (jensen1996evolutionaryrecruitmentof pages 4-7, jensen1996evolutionaryrecruitmentof pages 7-8). However, mammalian cytosolic TAT is evolutionarily distinct from bacterial TyrB enzymes. While bacterial TyrB (e.g., from E. coli) is classified in subfamily Ia alongside aspartate aminotransferases, rat cytosolic TAT clusters within subfamily Ig, and Jensen and Gu (1996) suggested it may warrant its own subfamily status due to distinctly different substrate specificities compared to other subfamily Ig members such as kynurenine aminotransferase and glutamine transaminase K (jensen1996evolutionaryrecruitmentof pages 3-4). A homolog of mammalian TAT was identified in Trypanosoma cruzi with 39% sequence identity, though the parasitic version demonstrates broader substrate specificity, accepting all three aromatic amino acids and multiple amino group acceptors (jensen1996evolutionaryrecruitmentof pages 3-4).

The evolution of aromatic amino acid specificity within Family I aminotransferases involved multiple structural modifications rather than simple point mutations. Site-directed mutagenesis studies converting E. coli AspC to TyrB substrate specificity required six simultaneous residue changes, indicating that evolutionary recruitment of aromatic substrate binding involved coordinated rearrangements of the active-site pocket (jensen1996evolutionaryrecruitmentof pages 8-10). The active-site pocket of aromatic aminotransferases is larger and more hydrophobic compared to aspartate-specific enzymes, with a key leucine at position 39 creating hydrophobic interactions critical for aromatic substrate accommodation (jensen1996evolutionaryrecruitmentof pages 8-10).

7. Clinical Significance: Tyrosinemia Type II

Loss-of-function mutations in the TAT gene cause tyrosinemia type II (OMIM #276600), also known as Richner-Hanhart syndrome or oculocutaneous tyrosinemia (alsharhan2020disordersofphenylalanine pages 28-29, OpenTargets Search: tyrosinemia-TAT). This autosomal recessive disorder is characterized by the classic triad of bilateral dendritic (pseudodendritic) keratitis, painful palmoplantar hyperkeratotic lesions, and occasionally mild intellectual disability (alsharhan2020disordersofphenylalanine pages 28-29). The pathogenesis of the ocular and skin manifestations is attributed to an inflammatory response secondary to tyrosine crystal deposition in tissues, resulting from markedly elevated plasma tyrosine levels (alsharhan2020disordersofphenylalanine pages 28-29).

The Open Targets Platform assigns a high disease-target association score of 0.793 between TAT and tyrosinemia type II, with a definitive classification from the ClinGen Aminoacidopathy Gene Curation Expert Panel confirming TAT as the causative gene (OpenTargets Search: tyrosinemia-TAT). No clear genotype-phenotype correlation has been identified among the various reported TAT mutations (alsharhan2020disordersofphenylalanine pages 28-29).

Treatment consists of a low-protein diet supplemented with a medical formula free of phenylalanine and tyrosine, aiming to reduce plasma tyrosine levels below 500 μmol/L (alsharhan2020disordersofphenylalanine pages 31-33). This dietary intervention results in resolution of eye and skin symptoms within days to several weeks. Early dietary management in infancy, maintaining serum tyrosine concentrations between 300–800 μmol/L, is associated with normal psychomotor development (alsharhan2020disordersofphenylalanine pages 31-33). Recent reviews emphasize that newborn screening programs have enabled early detection and reduced morbidity from this and related disorders of tyrosine metabolism (alsharhan2020disordersofphenylalanine pages 31-33).

8. Recent Developments

Recent research on TAT has focused on several areas. Caligiore et al. (2022) provided the most detailed characterization to date of human cytosolic TAT side activities, demonstrating that the enzyme can transaminate L-tryptophan with appreciable efficiency, expanding our understanding of its potential physiological roles beyond tyrosine catabolism (caligiore2022humancytosolictransaminases pages 6-8, caligiore2022humancytosolictransaminases pages 5-6). Norman et al. (2022) identified alternative biotransformation routes in phenylalanine-tyrosine metabolism using comprehensive metabolomic approaches, revealing 13 phase 1 and phase 2 biotransformation products that serve as alternative clearance mechanisms when the canonical pathway is disrupted (norman2022comprehensivebiotransformationanalysis pages 1-2). Shakerdi et al. (2025) reviewed the current therapeutic landscape for inborn errors of amino acid metabolism including TAT deficiency, noting that while dietary management remains the cornerstone of treatment, novel approaches including gene therapy are under preclinical investigation for related disorders. Barretta et al. (2025) highlighted the importance of differential diagnosis between tyrosinemia type II (TAT deficiency) and maleylacetoacetate isomerase deficiency (GSTZ1 mutations), as both can present with elevated succinylacetone on newborn screening.

9. Summary

Human tyrosine aminotransferase (TAT) is a cytosolic, PLP-dependent homodimeric enzyme that catalyzes the first and rate-limiting step of tyrosine catabolism in the liver, converting L-tyrosine and α-ketoglutarate to 4-hydroxyphenylpyruvate and L-glutamate. It belongs to the class I aminotransferase superfamily (subfamily Ig) and functions primarily in hepatic parenchymal cells. Its expression is tightly regulated by glucocorticoids, cAMP, and insulin, and is developmentally activated at birth. Loss-of-function mutations cause tyrosinemia type II (Richner-Hanhart syndrome), an autosomal recessive disorder characterized by oculocutaneous manifestations due to tyrosine crystal deposition. Beyond its canonical tyrosine substrate, TAT also accepts phenylalanine and demonstrates side activity toward L-tryptophan, pointing to a broader metabolic versatility than previously appreciated.

References

(alsharhan2020disordersofphenylalanine pages 28-29): Hind Alsharhan and Can Ficicioglu. Disorders of phenylalanine and tyrosine metabolism. Translational Science of Rare Diseases, 5:3-58, Jul 2020. URL: https://doi.org/10.3233/trd-200049, doi:10.3233/trd-200049. This article has 41 citations.
(OpenTargets Search: tyrosinemia-TAT): Open Targets Query (tyrosinemia-TAT, 8 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(parthasarathy2018athreeringcircus pages 4-5): Anutthaman Parthasarathy, Penelope J. Cross, Renwick C. J. Dobson, Lily E. Adams, Michael A. Savka, and André O. Hudson. A three-ring circus: metabolism of the three proteogenic aromatic amino acids and their role in the health of plants and animals. Frontiers in Molecular Biosciences, Apr 2018. URL: https://doi.org/10.3389/fmolb.2018.00029, doi:10.3389/fmolb.2018.00029. This article has 435 citations.
(xu2020generalandspecialized pages 2-5): Jing-Jing Xu, Xin Fang, Chen-Yi Li, Lei Yang, and Xiao-Ya Chen. General and specialized tyrosine metabolism pathways in plants. aBIOTECH, 1:97-105, Sep 2020. URL: https://doi.org/10.1007/s42994-019-00006-w, doi:10.1007/s42994-019-00006-w. This article has 127 citations.
(jensen1996evolutionaryrecruitmentof pages 2-3): R A Jensen and W Gu. Evolutionary recruitment of biochemically specialized subdivisions of family i within the protein superfamily of aminotransferases. Journal of Bacteriology, 178:2161-2171, Apr 1996. URL: https://doi.org/10.1128/jb.178.8.2161-2171.1996, doi:10.1128/jb.178.8.2161-2171.1996. This article has 197 citations and is from a peer-reviewed journal.
(caligiore2022humancytosolictransaminases pages 2-4): Francesco Caligiore, Erika Zangelmi, Carola Vetro, Takfarinas Kentache, Joseph P. Dewulf, Maria Veiga-da-Cunha, Emile Van Schaftingen, Guido Bommer, and Alessio Peracchi. Human cytosolic transaminases: side activities and patterns of discrimination towards physiologically available alternative substrates. Cellular and Molecular Life Sciences: CMLS, Jul 2022. URL: https://doi.org/10.1007/s00018-022-04439-3, doi:10.1007/s00018-022-04439-3. This article has 19 citations.
(holme2013tyrosinemetabolism pages 1-2): Elisabeth Holme and Grant A. Mitchell. Tyrosine Metabolism, pages 23-31. Springer Berlin Heidelberg, Jan 2013. URL: https://doi.org/10.1007/978-3-642-40337-8_2, doi:10.1007/978-3-642-40337-8_2. This article has 18 citations.
(jantzen1987cooperativityofglucocorticoid pages 1-2): Hans-Michael Jantzen, Uwe Strähle, Bernd Gloss, Francis Stewart, Wolfgang Schmid, Michael Boshart, Richard Miksicek, and Günther Schütz. Cooperativity of glucocorticoid response elements located far upstream of the tyrosine aminotransferase gene. Cell, 49:29-38, Apr 1987. URL: https://doi.org/10.1016/0092-8674(87)90752-5, doi:10.1016/0092-8674(87)90752-5. This article has 855 citations and is from a highest quality peer-reviewed journal.
(scherman2020drugrepositioningfor pages 3-5): Daniel Scherman and Christine Fetro. Drug repositioning for rare diseases: knowledge-based success stories. Therapies, 75:161-167, Apr 2020. URL: https://doi.org/10.1016/j.therap.2020.02.007, doi:10.1016/j.therap.2020.02.007. This article has 74 citations.
(caligiore2022humancytosolictransaminases pages 6-8): Francesco Caligiore, Erika Zangelmi, Carola Vetro, Takfarinas Kentache, Joseph P. Dewulf, Maria Veiga-da-Cunha, Emile Van Schaftingen, Guido Bommer, and Alessio Peracchi. Human cytosolic transaminases: side activities and patterns of discrimination towards physiologically available alternative substrates. Cellular and Molecular Life Sciences: CMLS, Jul 2022. URL: https://doi.org/10.1007/s00018-022-04439-3, doi:10.1007/s00018-022-04439-3. This article has 19 citations.
(alsharhan2020disordersofphenylalanine pages 31-33): Hind Alsharhan and Can Ficicioglu. Disorders of phenylalanine and tyrosine metabolism. Translational Science of Rare Diseases, 5:3-58, Jul 2020. URL: https://doi.org/10.3233/trd-200049, doi:10.3233/trd-200049. This article has 41 citations.
(jensen1996evolutionaryrecruitmentof pages 4-7): R A Jensen and W Gu. Evolutionary recruitment of biochemically specialized subdivisions of family i within the protein superfamily of aminotransferases. Journal of Bacteriology, 178:2161-2171, Apr 1996. URL: https://doi.org/10.1128/jb.178.8.2161-2171.1996, doi:10.1128/jb.178.8.2161-2171.1996. This article has 197 citations and is from a peer-reviewed journal.
(jensen1996evolutionaryrecruitmentof pages 3-4): R A Jensen and W Gu. Evolutionary recruitment of biochemically specialized subdivisions of family i within the protein superfamily of aminotransferases. Journal of Bacteriology, 178:2161-2171, Apr 1996. URL: https://doi.org/10.1128/jb.178.8.2161-2171.1996, doi:10.1128/jb.178.8.2161-2171.1996. This article has 197 citations and is from a peer-reviewed journal.
(parthasarathy2018athreeringcircus pages 2-4): Anutthaman Parthasarathy, Penelope J. Cross, Renwick C. J. Dobson, Lily E. Adams, Michael A. Savka, and André O. Hudson. A three-ring circus: metabolism of the three proteogenic aromatic amino acids and their role in the health of plants and animals. Frontiers in Molecular Biosciences, Apr 2018. URL: https://doi.org/10.3389/fmolb.2018.00029, doi:10.3389/fmolb.2018.00029. This article has 435 citations.
(caligiore2022humancytosolictransaminases pages 5-6): Francesco Caligiore, Erika Zangelmi, Carola Vetro, Takfarinas Kentache, Joseph P. Dewulf, Maria Veiga-da-Cunha, Emile Van Schaftingen, Guido Bommer, and Alessio Peracchi. Human cytosolic transaminases: side activities and patterns of discrimination towards physiologically available alternative substrates. Cellular and Molecular Life Sciences: CMLS, Jul 2022. URL: https://doi.org/10.1007/s00018-022-04439-3, doi:10.1007/s00018-022-04439-3. This article has 19 citations.
(holme2013tyrosinemetabolism pages 2-4): Elisabeth Holme and Grant A. Mitchell. Tyrosine Metabolism, pages 23-31. Springer Berlin Heidelberg, Jan 2013. URL: https://doi.org/10.1007/978-3-642-40337-8_2, doi:10.1007/978-3-642-40337-8_2. This article has 18 citations.
(norman2022comprehensivebiotransformationanalysis pages 1-2): Brendan P. Norman, Andrew S. Davison, Bryony Hickton, Gordon A. Ross, Anna M. Milan, Andrew T. Hughes, Peter J. M. Wilson, Hazel Sutherland, Juliette H. Hughes, Norman B. Roberts, George Bou-Gharios, James A. Gallagher, and Lakshminarayan R. Ranganath. Comprehensive biotransformation analysis of phenylalanine-tyrosine metabolism reveals alternative routes of metabolite clearance in nitisinone-treated alkaptonuria. Metabolites, 12:927, Sep 2022. URL: https://doi.org/10.3390/metabo12100927, doi:10.3390/metabo12100927. This article has 11 citations.
(jantzen1987cooperativityofglucocorticoid pages 2-3): Hans-Michael Jantzen, Uwe Strähle, Bernd Gloss, Francis Stewart, Wolfgang Schmid, Michael Boshart, Richard Miksicek, and Günther Schütz. Cooperativity of glucocorticoid response elements located far upstream of the tyrosine aminotransferase gene. Cell, 49:29-38, Apr 1987. URL: https://doi.org/10.1016/0092-8674(87)90752-5, doi:10.1016/0092-8674(87)90752-5. This article has 855 citations and is from a highest quality peer-reviewed journal.
(chang2026hepaticglucocorticoidreceptor pages 7-7): Maggie Chang and Jen-Chywan Wang. Hepatic glucocorticoid receptor action and glucose homeostasis. Endocrine Reviews, 47:52-74, Sep 2026. URL: https://doi.org/10.1210/endrev/bnaf030, doi:10.1210/endrev/bnaf030. This article has 7 citations and is from a domain leading peer-reviewed journal.
(chang2026hepaticglucocorticoidreceptor pages 19-19): Maggie Chang and Jen-Chywan Wang. Hepatic glucocorticoid receptor action and glucose homeostasis. Endocrine Reviews, 47:52-74, Sep 2026. URL: https://doi.org/10.1210/endrev/bnaf030, doi:10.1210/endrev/bnaf030. This article has 7 citations and is from a domain leading peer-reviewed journal.
(jensen1996evolutionaryrecruitmentof pages 7-8): R A Jensen and W Gu. Evolutionary recruitment of biochemically specialized subdivisions of family i within the protein superfamily of aminotransferases. Journal of Bacteriology, 178:2161-2171, Apr 1996. URL: https://doi.org/10.1128/jb.178.8.2161-2171.1996, doi:10.1128/jb.178.8.2161-2171.1996. This article has 197 citations and is from a peer-reviewed journal.
(jensen1996evolutionaryrecruitmentof pages 8-10): R A Jensen and W Gu. Evolutionary recruitment of biochemically specialized subdivisions of family i within the protein superfamily of aminotransferases. Journal of Bacteriology, 178:2161-2171, Apr 1996. URL: https://doi.org/10.1128/jb.178.8.2161-2171.1996, doi:10.1128/jb.178.8.2161-2171.1996. This article has 197 citations and is from a peer-reviewed journal.

Artifacts

Citations

alsharhan2020disordersofphenylalanine pages 28-29
parthasarathy2018athreeringcircus pages 4-5
caligiore2022humancytosolictransaminases pages 5-6
caligiore2022humancytosolictransaminases pages 2-4
jantzen1987cooperativityofglucocorticoid pages 1-2
holme2013tyrosinemetabolism pages 1-2
scherman2020drugrepositioningfor pages 3-5
norman2022comprehensivebiotransformationanalysis pages 1-2
chang2026hepaticglucocorticoidreceptor pages 7-7
chang2026hepaticglucocorticoidreceptor pages 19-19
jensen1996evolutionaryrecruitmentof pages 3-4
jensen1996evolutionaryrecruitmentof pages 8-10
alsharhan2020disordersofphenylalanine pages 31-33
xu2020generalandspecialized pages 2-5
jensen1996evolutionaryrecruitmentof pages 2-3
caligiore2022humancytosolictransaminases pages 6-8
jensen1996evolutionaryrecruitmentof pages 4-7
parthasarathy2018athreeringcircus pages 2-4
holme2013tyrosinemetabolism pages 2-4
jantzen1987cooperativityofglucocorticoid pages 2-3
jensen1996evolutionaryrecruitmentof pages 7-8
https://doi.org/10.3233/trd-200049,
https://doi.org/10.3389/fmolb.2018.00029,
https://doi.org/10.1007/s42994-019-00006-w,
https://doi.org/10.1128/jb.178.8.2161-2171.1996,
https://doi.org/10.1007/s00018-022-04439-3,
https://doi.org/10.1007/978-3-642-40337-8_2,
https://doi.org/10.1016/0092-8674(87
https://doi.org/10.1016/j.therap.2020.02.007,
https://doi.org/10.3390/metabo12100927,
https://doi.org/10.1210/endrev/bnaf030,

📚 Additional Documentation

Notes

(TAT-notes.md)

TAT (Tyrosine aminotransferase, P17735) — review notes

Core biology (verified from UniProt record + cached pubs)

Cytosolic, liver-expressed, PLP (pyridoxal-5'-phosphate)-dependent aminotransferase; class-I
PLP-dependent aminotransferase family. HPA: "Tissue enriched (liver)".
Catalyzes the FIRST/committed step of L-tyrosine catabolism:
L-tyrosine + 2-oxoglutarate = 3-(4-hydroxyphenyl)pyruvate + L-glutamate. EC 2.6.1.5; RHEA:15093.
[UniProt P17735 CATALYTIC ACTIVITY, "L-tyrosine + 2-oxoglutarate = 3-(4-hydroxyphenyl)pyruvate + L-glutamate"]
FUNCTION (UniProt): "Transaminase involved in tyrosine breakdown. Converts tyrosine to
p-hydroxyphenylpyruvate. Can catalyze the reverse reaction, using glutamic acid, with 2-oxoglutarate
as cosubstrate (in vitro). Has much lower affinity and transaminase activity towards phenylalanine."
Cofactor: pyridoxal 5'-phosphate; PLP-lysine Schiff base at Lys-280 (MOD_RES 280,
"N6-(pyridoxal phosphate)lysine"; PDB 3DYD).
SUBUNIT: Homodimer. {ECO:0000305|Ref.8} — supports GO:0042802 identical protein binding.
PATHWAY (UniProt): "Amino-acid degradation; L-phenylalanine degradation; acetoacetate and
fumarate from L-phenylalanine: step 2/6." (Phe catabolism proceeds via Phe->Tyr then Tyr catabolism;
TAT is the Tyr-catabolism step, hence the phenylalanine-catabolism pathway membership annotation.)

Enzyme substrate specificity — narrow, with weak Phe activity

PMID:16640556 (Sivaraman & Kirsch 2006) title: "The narrow substrate specificity of human tyrosine
aminotransferase -- the enzyme deficient in tyrosinemia type II." (abstract-only in cache; full text
not available). Supports narrow Tyr specificity, plus weak phenylalanine transamination; mutagenesis
of Ile-294 reduced activity. This underpins treating aromatic-AA / phenylalanine activities as
secondary (KEEP_AS_NON_CORE / broad-parent) rather than core.

Expression cloning / functional demonstration

PMID:7999802 — human TAT cDNA expressed in HeLa; IDA basis for GO:0004838 MF and
the tyrosine catabolic process / 2-oxoglutarate + glutamate metabolic annotations (products/cosubstrates).
PMID:1973834 — gene structure; also documents glucocorticoid response elements (GRE) context:
"Two functional glucocorticoid response elements (GREs) reside 2.5 kb upstream of the rat TAT gene."
NAS basis for GO:0004838.

Disease

Tyrosinemia type II (TYRSN2, Richner-Hanhart syndrome), MIM:276600: oculocutaneous tyrosinemia —
palmoplantar keratosis, painful corneal ulcers, intellectual disability, from elevated plasma/urine
tyrosine. [UniProt DISEASE, "palmoplantar keratosis, painful corneal ulcers, and intellectual disability"]
Variant G362V (VAR_000560) in TYRSN2 PMID:1357662.

Regulation (classic glucocorticoid/glucagon/cAMP-inducible gene)

TAT is a textbook glucocorticoid- and cAMP-inducible hepatic gene. The Ensembl-Compara IEA
(GO_REF:0000107) response terms (glucocorticoid, cortisol, cAMP, dexamethasone, insulin, retinoic acid,
ethanol, mercury, oxidative stress, liver regeneration) are transferred largely from rat/mouse orthologs
(P04694 rat, Q8QZR1 mouse). These are hormonal-regulation responses of the gene, biologically plausible
for the rodent orthologs but are regulatory/physiological context, not TAT's core molecular activity or
its direct catabolic process. Treat as KEEP_AS_NON_CORE (regulation/response context transferred by
orthology), not core function.

Interactions (IPI, IntAct high-throughput)

IntAct/interactome IPI annotations (protein binding GO:0005515) with UBE3A (Q05086), GLUL (P15104),
GRN (P28799) and self (P17735) come from systematic interactome maps
(PMID:24722188, 25910212, 31515488, 32296183, 32814053, 25502805). TAT appears in these as one node in
genome-scale Y2H/AP-MS screens; body text of the papers does not discuss TAT specifically. Bare
"protein binding" is uninformative for MF (curation guideline) -> MARK_AS_OVER_ANNOTATED.
GO:0042802 identical protein binding is corroborated by the documented homodimer
[UniProt SUBUNIT "Homodimer."] -> ACCEPT (self-association is real biology), though non-core.

Deep research provenance

Falcon deep research (TAT-deep-research-falcon.md) did NOT land within the 8-minute poll
window (2026-07-05). Review grounded in UniProt P17735, seeded GOA, cached publications
(PMID_7999802, PMID_1973834, interactome PMIDs), and local go.db term labels/definitions.

Term-label notes (current ontology, from local go.db)

GO:0004838 = "L-tyrosine:2-oxoglutarate transaminase activity" (def matches RHEA:15093 reaction). CORE MF.
GO:0006572 = "L-tyrosine catabolic process". CORE BP.
GO:0005829 = "cytosol". CORE location.
GO:0030170 = "pyridoxal phosphate binding" (cofactor binding). ACCEPT.
GO:0009074 current primary label = "aromatic amino acid family catabolic process" (GOA seed label is
"aromatic amino acid catabolic process" — GOA label retained in existing_annotations as trusted).

📄 View Raw YAML

id: P17735
gene_symbol: TAT
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  TAT encodes tyrosine aminotransferase (EC 2.6.1.5), a cytosolic, pyridoxal
  5'-phosphate (PLP)-dependent aminotransferase of the class-I PLP-dependent
  aminotransferase family that is strongly enriched in the liver. It catalyzes
  the first and committed step of L-tyrosine catabolism, transamination of
  L-tyrosine with 2-oxoglutarate to yield 4-hydroxyphenylpyruvate and
  L-glutamate. The reaction is reversible in vitro, and the enzyme has much
  lower affinity and activity toward L-phenylalanine; PLP is bound as a Schiff
  base to Lys-280, and the active protein is a homodimer. Because phenylalanine
  is catabolized via conversion to tyrosine, TAT also functions within the
  overall L-phenylalanine degradation pathway. Expression of the gene is a
  classical target of hormonal induction by glucocorticoids, glucagon and cAMP.
  Loss-of-function variants cause tyrosinemia type II (Richner-Hanhart syndrome),
  an oculocutaneous disorder with elevated plasma and urinary tyrosine,
  palmoplantar keratosis, painful corneal ulcers and intellectual disability.
existing_annotations:
- term:
    id: GO:0004838
    label: L-tyrosine:2-oxoglutarate transaminase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Phylogenetic (IBA) assertion of the core molecular function. This is the
      correct, specific enzymatic activity of TAT (EC 2.6.1.5), directly
      supported by experimental characterization of the human enzyme.
    action: ACCEPT
    reason: >-
      This is the defining, experimentally validated molecular function of TAT.
      The IBA is consistent with the IDA on the same term and with the catalytic
      activity reported in UniProt (RHEA:15093). Core function.
    supported_by:
    - reference_id: PMID:7999802
      supporting_text: >-
        The expressed protein catalyzed specifically the conversion of
        L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate.
- term:
    id: GO:0006572
    label: L-tyrosine catabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Phylogenetic assertion that TAT participates in L-tyrosine catabolism.
      TAT catalyzes the first, committed step of tyrosine breakdown, so this is
      the correct biological process.
    action: ACCEPT
    reason: >-
      Consistent with the IDA on the same term and with UniProt FUNCTION
      ("Transaminase involved in tyrosine breakdown"). Core process.
    supported_by:
    - reference_id: PMID:7999802
      supporting_text: >-
        The expressed protein catalyzed specifically the conversion of
        L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate.
- term:
    id: GO:0006559
    label: L-phenylalanine catabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Phylogenetic assertion of involvement in L-phenylalanine catabolism.
      Phenylalanine is degraded via conversion to tyrosine, and UniProt places
      TAT as step 2/6 of the L-phenylalanine degradation pathway (the tyrosine
      transamination step). TAT itself has only weak, low-affinity activity
      directly on phenylalanine.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biologically defensible as pathway membership (Phe -> Tyr -> catabolism),
      matching the UniProt PATHWAY statement, and it is corroborated by an
      independent UniPathway mapping annotation. However, TAT's direct catalytic
      role is on tyrosine; its phenylalanine transaminase activity is much lower.
      Retain as a non-core, pathway-context process rather than a core function.
    supported_by:
    - reference_id: PMID:16640556
      supporting_text: >-
        The narrow substrate specificity of human tyrosine aminotransferase --
        the enzyme deficient in tyrosinemia type II.
- term:
    id: GO:0003824
    label: catalytic activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro2GO electronic annotation to the root molecular-function
      catalytic-activity term. TAT is an enzyme, so the term is not wrong, but
      it is far too general given that the specific activity (GO:0004838) is
      known experimentally.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      GO:0004838 is an entailed subclass of GO:0003824; the specific
      transaminase activity is experimentally established for the human enzyme,
      so this uninformative parent should not be treated as a core function.
    proposed_replacement_terms:
    - id: GO:0004838
      label: L-tyrosine:2-oxoglutarate transaminase activity
- term:
    id: GO:0004838
    label: L-tyrosine:2-oxoglutarate transaminase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Combined multi-method electronic annotation to the correct, specific
      molecular function of TAT.
    action: ACCEPT
    reason: >-
      Matches the experimentally supported core molecular function (IDA/IBA on
      the same term). Correct level of specificity.
    supported_by:
    - reference_id: PMID:7999802
      supporting_text: >-
        The expressed protein catalyzed specifically the conversion of
        L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate.
- term:
    id: GO:0006520
    label: amino acid metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: >-
      Electronic annotation to a high-level amino-acid metabolic process term.
      TAT participates in amino-acid metabolism (tyrosine catabolism), so the
      term is correct but general.
    action: KEEP_AS_NON_CORE
    reason: >-
      True but subsumed by the more specific and experimentally supported
      L-tyrosine catabolic process (GO:0006572). Retain as a broad-parent,
      non-core annotation.
    proposed_replacement_terms:
    - id: GO:0006572
      label: L-tyrosine catabolic process
- term:
    id: GO:0008483
    label: transaminase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro2GO annotation to the general transaminase-activity term. TAT is a
      transaminase, so the term is correct but broader than the known specific
      activity.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      GO:0004838 is an entailed subclass of GO:0008483; the specific tyrosine
      transaminase activity is experimentally known, so the general parent is an
      over-annotation for core-function purposes.
    proposed_replacement_terms:
    - id: GO:0004838
      label: L-tyrosine:2-oxoglutarate transaminase activity
- term:
    id: GO:0009072
    label: aromatic amino acid metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      InterPro2GO annotation to aromatic amino acid metabolic process. Tyrosine
      and phenylalanine are aromatic amino acids, so the term is correct but
      broad.
    action: KEEP_AS_NON_CORE
    reason: >-
      Subsumed by the more specific tyrosine catabolic process (GO:0006572).
      Correct but general; retain as non-core parent.
    proposed_replacement_terms:
    - id: GO:0006572
      label: L-tyrosine catabolic process
- term:
    id: GO:0009074
    label: aromatic amino acid catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      InterPro2GO annotation to aromatic amino acid (family) catabolic process
      (current ontology primary label: "aromatic amino acid family catabolic
      process"). TAT catalyzes the first step of catabolism of the aromatic
      amino acid tyrosine, so the term is correct but broad.
    action: KEEP_AS_NON_CORE
    reason: >-
      True but subsumed by the more specific and experimentally supported
      L-tyrosine catabolic process (GO:0006572). Retain as a broad-parent,
      non-core annotation.
    proposed_replacement_terms:
    - id: GO:0006572
      label: L-tyrosine catabolic process
- term:
    id: GO:0030170
    label: pyridoxal phosphate binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro2GO annotation for PLP cofactor binding. TAT is a PLP-dependent
      aminotransferase that binds pyridoxal 5'-phosphate as a Schiff base to
      Lys-280, confirmed by the crystal structure (PDB 3DYD).
    action: ACCEPT
    reason: >-
      Directly supported by the UniProt COFACTOR annotation and the
      N6-(pyridoxal phosphate)lysine modified residue at Lys-280 seen in the
      crystal structure. A correct, mechanistically important molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24722188
  qualifier: enables
  review:
    summary: >-
      Interaction reported in a genome-scale interactome map. Bare "protein
      binding" is uninformative about molecular function and this specific
      interaction is not discussed for TAT in the body of the paper.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Per curation guidelines, the bare protein-binding term does not convey
      TAT's function and is derived from a high-throughput screen without a
      TAT-specific functional interpretation. Not a core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25910212
  qualifier: enables
  review:
    summary: >-
      High-throughput interactome IPI annotation. Bare "protein binding" is
      uninformative and the interaction is not functionally characterized for
      TAT in the paper.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative molecular-function term from a systematic screen; provides
      no insight into TAT's function. Not a core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: >-
      High-throughput interactome IPI annotation. Bare "protein binding" is
      uninformative for molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative term derived from a genome-scale binary interaction assay;
      not functionally characterized for TAT. Not a core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: >-
      Annotation from the HuRI reference human binary protein interactome. Bare
      "protein binding" does not describe TAT's molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative molecular-function term from a systematic Y2H interactome
      map; no TAT-specific functional interpretation. Not a core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: >-
      Interaction from a neurodegenerative-disease interactome map. Bare
      "protein binding" is uninformative for molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative term from a high-throughput screen; provides no functional
      insight for TAT. Not a core function.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:25502805
  qualifier: enables
  review:
    summary: >-
      Self-interaction (homodimerization) annotation. TAT is documented as a
      homodimer, so self-association is real biology, though it is not the core
      catalytic function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Corroborated by the UniProt SUBUNIT statement ("Homodimer.") and the
      IntAct self-interaction record (P17735-P17735). More informative than bare
      protein binding, but a structural/quaternary property rather than a core
      molecular function.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: >-
      Self-interaction annotation consistent with TAT being a homodimer.
    action: KEEP_AS_NON_CORE
    reason: >-
      Corroborated by the UniProt SUBUNIT "Homodimer." statement. A quaternary
      structural property, not a core molecular function.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: >-
      Self-interaction annotation from the HuRI interactome, consistent with the
      documented homodimer.
    action: KEEP_AS_NON_CORE
    reason: >-
      Corroborated by the UniProt SUBUNIT "Homodimer." statement. Structural
      quaternary property, not a core function.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: >-
      Ensembl-Compara orthology-based location. TAT is a cytosolic enzyme, and
      this is independently supported by the Reactome TAS annotations to the
      same term.
    action: ACCEPT
    reason: >-
      Correct subcellular location; TAT is a soluble cytosolic aminotransferase.
      Core location, corroborated by Reactome. This is a location transfer, not
      a phenotype-response transfer, so it is reliable regardless of GO_REF
      source.
- term:
    id: GO:0006103
    label: 2-oxoglutarate metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Orthology-transferred annotation reflecting that 2-oxoglutarate is a
      cosubstrate of the transamination reaction. Duplicated by the IDA on the
      same term.
    action: KEEP_AS_NON_CORE
    reason: >-
      2-oxoglutarate is consumed as the amino-group acceptor cosubstrate, so the
      process is a real consequence of the reaction, but it is a
      cosubstrate/co-metabolite consequence rather than TAT's core biological
      role (tyrosine catabolism).
- term:
    id: GO:0006536
    label: glutamate metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Orthology-transferred annotation reflecting that L-glutamate is produced
      as the co-product of the transamination reaction. Duplicated by the IDA on
      the same term.
    action: KEEP_AS_NON_CORE
    reason: >-
      L-glutamate is the amino-group-carrying co-product, so the process is a
      real consequence of the reaction, but it is a co-product consequence
      rather than TAT's core biological role.
- term:
    id: GO:0006572
    label: L-tyrosine catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Orthology-transferred annotation to the core biological process, tyrosine
      catabolism. Duplicated by the IDA and IBA on the same term.
    action: ACCEPT
    reason: >-
      Correct core biological process; TAT catalyzes the first step of tyrosine
      breakdown. Consistent with experimental (IDA) and phylogenetic (IBA)
      annotations.
- term:
    id: GO:0006979
    label: response to oxidative stress
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Ensembl-Compara orthology-transferred response term, largely derived from
      rodent orthologs. Represents a physiological/regulatory response context,
      not TAT's molecular activity or its direct catabolic role.
    action: KEEP_AS_NON_CORE
    reason: >-
      Plausible regulatory context transferred by orthology, but not verified
      for the human protein and not a core function. Retain as non-core.
- term:
    id: GO:0016597
    label: amino acid binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: >-
      Orthology-transferred molecular function reflecting that TAT binds its
      amino-acid substrate (tyrosine). The term is a general parent; substrate
      binding is inherent to the specific transaminase activity.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Binding of the amino-acid substrate is subsumed by the specific catalytic
      activity (GO:0004838); the standalone "amino acid binding" term adds no
      functional information beyond the enzyme activity. Not a core function.
    proposed_replacement_terms:
    - id: GO:0004838
      label: L-tyrosine:2-oxoglutarate transaminase activity
- term:
    id: GO:0032869
    label: cellular response to insulin stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Ensembl-Compara orthology-transferred response term (largely from rodent
      orthologs). Reflects hormonal regulation of TAT expression rather than the
      protein's molecular activity.
    action: KEEP_AS_NON_CORE
    reason: >-
      TAT is a classical hormonally regulated hepatic gene; insulin-response
      context is plausible but transferred by orthology and unverified for the
      human protein. Regulatory context, not a core function.
- term:
    id: GO:0045471
    label: response to ethanol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Orthology-transferred response term. Represents a physiological response
      context of the gene rather than TAT's core molecular or catabolic role.
    action: KEEP_AS_NON_CORE
    reason: >-
      Regulatory/response context transferred by orthology and unverified for
      the human protein. Not a core function.
- term:
    id: GO:0046689
    label: response to mercury ion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Orthology-transferred response term. Represents a physiological response
      context of the gene rather than TAT's core function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Regulatory/response context transferred by orthology and unverified for
      the human protein. Not a core function.
- term:
    id: GO:0051384
    label: response to glucocorticoid
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Orthology-transferred response term. TAT is the textbook
      glucocorticoid-inducible hepatic gene, but induction is regulation of
      expression rather than TAT's molecular activity, and the human promoter
      GREs are notably degenerate relative to rat.
    action: KEEP_AS_NON_CORE
    reason: >-
      Well-established regulatory context (glucocorticoid induction) but a
      response/regulation term, not TAT's core molecular or catabolic function.
      The human upstream GREs are mutated/replaced by Alu elements, so even the
      regulatory transfer from rat is imperfect. Retain as non-core.
    supported_by:
    - reference_id: PMID:1973834
      supporting_text: >-
        Two functional glucocorticoid response elements (GREs) reside 2.5 kb
        upstream of the rat TAT gene. The DNA sequence of the corresponding
        region of the human TAT gene shows the distal GRE mutated and the
        proximal GRE replaced by Alu elements.
- term:
    id: GO:0051414
    label: response to cortisol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Orthology-transferred response term, a specific instance of the
      glucocorticoid-response context of the gene.
    action: KEEP_AS_NON_CORE
    reason: >-
      Regulatory/response context transferred by orthology; not a core molecular
      or catabolic function. Retain as non-core.
- term:
    id: GO:0051591
    label: response to cAMP
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Orthology-transferred response term. TAT is a classical cAMP/glucagon-
      inducible gene, but induction is regulation of expression, not the
      protein's molecular activity.
    action: KEEP_AS_NON_CORE
    reason: >-
      Well-known regulatory context but a response/regulation term, not a core
      function. Retain as non-core.
- term:
    id: GO:0071300
    label: cellular response to retinoic acid
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Orthology-transferred response term. Physiological response context rather
      than TAT's core molecular or catabolic role.
    action: KEEP_AS_NON_CORE
    reason: >-
      Regulatory/response context transferred by orthology and unverified for
      the human protein. Not a core function.
- term:
    id: GO:0071548
    label: response to dexamethasone
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Orthology-transferred response term; a synthetic-glucocorticoid instance
      of the well-known hormonal induction of TAT expression.
    action: KEEP_AS_NON_CORE
    reason: >-
      Regulatory/response context transferred by orthology; not a core molecular
      or catabolic function. Retain as non-core.
- term:
    id: GO:0097421
    label: liver regeneration
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Orthology-transferred process term reflecting hepatic expression dynamics.
      TAT is a liver-enriched enzyme, but there is no evidence it functions in
      the regeneration process itself as opposed to being expressed in liver.
    action: KEEP_AS_NON_CORE
    reason: >-
      Association with liver-expression context, transferred by orthology and
      unverified mechanistically for the human protein. Not a core function.
- term:
    id: GO:0006559
    label: L-phenylalanine catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  qualifier: involved_in
  review:
    summary: >-
      UniPathway-mapping-based annotation to L-phenylalanine catabolism, matching
      the UniProt PATHWAY statement (step 2/6 of L-phenylalanine degradation).
      Phenylalanine is degraded via tyrosine, so TAT participates in the pathway
      through its tyrosine transamination step.
    action: KEEP_AS_NON_CORE
    reason: >-
      Defensible as pathway membership (Phe -> Tyr -> catabolism) and consistent
      with the UniProt PATHWAY annotation, but TAT's direct catalytic role is on
      tyrosine, with only weak phenylalanine activity. Non-core pathway context.
    supported_by:
    - reference_id: PMID:16640556
      supporting_text: >-
        The narrow substrate specificity of human tyrosine aminotransferase --
        the enzyme deficient in tyrosinemia type II.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-517444
  qualifier: located_in
  review:
    summary: >-
      Reactome traceable-author-statement placing TAT in the cytosol, in the
      context of the reaction "TAT aminates HPP". Correct subcellular location.
    action: ACCEPT
    reason: >-
      TAT is a soluble cytosolic aminotransferase; the location is well
      established and corroborated by the Ensembl location annotation. Core
      location.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-71155
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS placing TAT in the cytosol in the context of the reaction
      "TAT deaminates tyrosine" (the forward tyrosine transamination step).
    action: ACCEPT
    reason: >-
      Correct cytosolic location, consistent with the other cytosol annotations.
      Core location.
- term:
    id: GO:0004838
    label: L-tyrosine:2-oxoglutarate transaminase activity
  evidence_type: IDA
  original_reference_id: PMID:7999802
  qualifier: enables
  review:
    summary: >-
      Direct experimental demonstration that the cloned human TAT protein
      specifically converts L-tyrosine to 4-hydroxyphenylpyruvate. This is the
      primary experimental basis for the core molecular function.
    action: ACCEPT
    reason: >-
      Human TAT cDNA expressed in HeLa cells produced a ~50 kDa protein that
      catalyzed specifically the conversion of L-[14C]tyrosine into
      p-[14C]hydroxyphenylpyruvate. Definitive core molecular function.
    supported_by:
    - reference_id: PMID:7999802
      supporting_text: >-
        The expressed protein catalyzed specifically the conversion of
        L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate.
- term:
    id: GO:0006103
    label: 2-oxoglutarate metabolic process
  evidence_type: IDA
  original_reference_id: PMID:7999802
  qualifier: involved_in
  review:
    summary: >-
      Annotation reflecting consumption of 2-oxoglutarate as the amino-group
      acceptor cosubstrate in the demonstrated transamination reaction.
    action: KEEP_AS_NON_CORE
    reason: >-
      2-oxoglutarate is the cosubstrate consumed in the transamination; a real
      but co-metabolite consequence rather than TAT's core biological role of
      tyrosine catabolism.
    supported_by:
    - reference_id: PMID:7999802
      supporting_text: >-
        The expressed protein catalyzed specifically the conversion of
        L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate.
- term:
    id: GO:0006536
    label: glutamate metabolic process
  evidence_type: IDA
  original_reference_id: PMID:7999802
  qualifier: involved_in
  review:
    summary: >-
      Annotation reflecting production of L-glutamate as the co-product of the
      demonstrated transamination reaction.
    action: KEEP_AS_NON_CORE
    reason: >-
      L-glutamate is the amino-group-carrying co-product; a real but co-product
      consequence rather than TAT's core biological role of tyrosine catabolism.
    supported_by:
    - reference_id: PMID:7999802
      supporting_text: >-
        The expressed protein catalyzed specifically the conversion of
        L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate.
- term:
    id: GO:0006572
    label: L-tyrosine catabolic process
  evidence_type: IDA
  original_reference_id: PMID:7999802
  qualifier: involved_in
  review:
    summary: >-
      Direct experimental annotation to tyrosine catabolism, based on the
      demonstrated conversion of tyrosine to 4-hydroxyphenylpyruvate by the
      human enzyme (the first, committed step of tyrosine breakdown).
    action: ACCEPT
    reason: >-
      Core biological process, directly supported by expression of functional
      human TAT that specifically transaminates tyrosine.
    supported_by:
    - reference_id: PMID:7999802
      supporting_text: >-
        The expressed protein catalyzed specifically the conversion of
        L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate.
- term:
    id: GO:0005575
    label: cellular_component
  evidence_type: ND
  original_reference_id: GO_REF:0000015
  qualifier: is_active_in
  review:
    summary: >-
      Root cellular-component annotation with No Data evidence code, a
      placeholder indicating no specific component was curated by this source.
      Superseded by the specific cytosol annotations (TAS and IEA).
    action: REMOVE
    reason: >-
      This is an uninformative ND root-node placeholder that is superseded by
      the experimentally/authoritatively supported cytosol location annotations.
      It conveys no information and should not be retained.
- term:
    id: GO:0004838
    label: L-tyrosine:2-oxoglutarate transaminase activity
  evidence_type: NAS
  original_reference_id: PMID:1973834
  qualifier: enables
  review:
    summary: >-
      Non-traceable author statement of the core transaminase activity, from the
      paper characterizing the human TAT gene. Redundant with, and weaker than,
      the IDA/IBA/IEA support for the same term.
    action: ACCEPT
    reason: >-
      Correct core molecular function; although the evidence code is NAS, the
      assignment is fully corroborated by the direct experimental (IDA)
      annotation and UniProt catalytic activity.
    supported_by:
    - reference_id: PMID:1973834
      supporting_text: >-
        Isolation and characterization of the human tyrosine aminotransferase
        gene.
core_functions:
- description: >-
    L-tyrosine:2-oxoglutarate transaminase (tyrosine aminotransferase), the
    PLP-dependent enzyme that catalyzes the first, committed step of L-tyrosine
    catabolism in the liver cytosol.
  molecular_function:
    id: GO:0004838
    label: L-tyrosine:2-oxoglutarate transaminase activity
  directly_involved_in:
  - id: GO:0006572
    label: L-tyrosine catabolic process
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:7999802
    supporting_text: >-
      The expressed protein catalyzed specifically the conversion of
      L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000015
  title: Use of the ND evidence code for Gene Ontology (GO) terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000041
  title: Gene Ontology annotation based on UniPathway vocabulary mapping
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:1973834
  title: Isolation and characterization of the human tyrosine aminotransferase gene.
  findings:
  - statement: >-
      Characterizes the human TAT gene (12 exons, 454-aa protein, 50,399 Da,
      92% protein identity to rat); notes that the functional glucocorticoid
      response elements present upstream of the rat gene are mutated or
      Alu-replaced in the human gene.
    supporting_text: >-
      The human TAT gene is predicted to code for a 454 amino acid protein of
      molecular weight 50,399 dalton.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified as the human TAT gene characterization paper; abstract in
      cache. Supports gene structure, size, and the caveat that human upstream
      GREs are degenerate relative to rat.
- id: PMID:7999802
  title: Cloning and expression of human tyrosine aminotransferase cDNA.
  findings:
  - statement: >-
      Human TAT cDNA expressed in HeLa cells produced a ~50 kDa protein that
      specifically converted L-tyrosine to 4-hydroxyphenylpyruvate, establishing
      the core molecular function and involvement in tyrosine catabolism.
    supporting_text: >-
      The expressed protein catalyzed specifically the conversion of
      L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified primary paper demonstrating the human TAT enzymatic
      activity by expression cloning; direct basis for the IDA core-function
      annotations.
- id: PMID:16640556
  title: The narrow substrate specificity of human tyrosine aminotransferase -- the
    enzyme deficient in tyrosinemia type II.
  findings:
  - statement: >-
      Establishes that human TAT has narrow substrate specificity for tyrosine
      with only weak activity toward phenylalanine, and that Ile-294 is important
      for catalytic activity; supports treating phenylalanine/aromatic-amino-acid
      processes as non-core.
    supporting_text: >-
      The narrow substrate specificity of human tyrosine aminotransferase --
      the enzyme deficient in tyrosinemia type II.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Cited in UniProt for FUNCTION and CATALYTIC ACTIVITY; abstract-only in
      cache. Underpins the narrow tyrosine specificity and weak phenylalanine
      activity used to rank Phe/aromatic processes as non-core.
- id: PMID:24722188
  title: Protein interaction network of alternatively spliced isoforms from brain
    links genetic risk factors for autism.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Genome-scale interactome map; TAT appears only as a node, not discussed
      specifically. Basis of an uninformative protein-binding IPI.
- id: PMID:25502805
  title: A massively parallel pipeline to clone DNA variants and examine molecular
    phenotypes of human disease mutations.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      High-throughput variant/interaction pipeline; source of an identical
      protein binding (self-interaction) IPI, consistent with the documented
      homodimer but not TAT-specific in the text.
- id: PMID:25910212
  title: Widespread macromolecular interaction perturbations in human genetic disorders.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Systematic interactome-perturbation study; TAT is only a node. Basis of an
      uninformative protein-binding IPI.
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the
    allele frequency spectrum in human populations.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Genome-scale binary-interaction screen; source of protein-binding and
      identical protein binding IPIs, not functionally interpreted for TAT.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      HuRI reference interactome; TAT is a node. Source of protein-binding and
      identical protein binding IPIs.
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Neurodegenerative-disease interactome map (abstract-only in cache); TAT is
      only a node. Basis of an uninformative protein-binding IPI.
- id: Reactome:R-HSA-517444
  title: TAT aminates HPP
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Reactome reaction placing TAT in the cytosol (reverse direction, aminating
      4-hydroxyphenylpyruvate). Supports cytosolic location.
- id: Reactome:R-HSA-71155
  title: TAT deaminates tyrosine
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Reactome reaction for the forward tyrosine transamination step, in the
      cytosol. Supports the core activity and cytosolic location.

TAT

Gene Description

Existing Annotations Review

Core Functions

L-tyrosine:2-oxoglutarate transaminase (tyrosine aminotransferase), the PLP-dependent enzyme that catalyzes the first, committed step of L-tyrosine catabolism in the liver cytosol.

References

Deep Research

Falcon

Comprehensive Research Report: Human Tyrosine Aminotransferase (TAT, P17735)

1. Gene and Protein Identity

2. Enzymatic Function and Catalytic Mechanism

2.1 Primary Reaction

2.2 Cofactor and Mechanism

2.3 Substrate Specificity and Side Activities

3. Subcellular Localization and Tissue Expression

3.1 Subcellular Localization

3.2 Tissue Expression

4. Biochemical Pathway: Tyrosine Catabolism

5. Transcriptional Regulation

6. Structural and Evolutionary Context

6.1 Protein Structure

6.2 Evolutionary Classification

7. Clinical Significance: Tyrosinemia Type II

8. Recent Developments

9. Summary

Artifacts

Citations

📚 Additional Documentation

Notes

TAT (Tyrosine aminotransferase, P17735) — review notes

Core biology (verified from UniProt record + cached pubs)

Enzyme substrate specificity — narrow, with weak Phe activity

Expression cloning / functional demonstration

Disease

Regulation (classic glucocorticoid/glucagon/cAMP-inducible gene)

Interactions (IPI, IntAct high-throughput)

Deep research provenance

Term-label notes (current ontology, from local go.db)

📄 View Raw YAML