KYNU

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005737 cytoplasm	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic (IBA) inference that kynureninase is active in the cytoplasm. Consistent with the UniProt authoritative subcellular location call (Cytoplasm, cytosol) and with the more specific cytosol annotations. The generic parent "cytoplasm" is acceptable but the more precise cytosol term is preferred; kept as non-core in favour of GO:0005829. Supporting Evidence: file:human/KYNU/KYNU-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0006569 L-tryptophan catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) inference of involvement in L-tryptophan catabolism. Kynureninase is a committed enzyme of the tryptophan/kynurenine catabolic pathway, directly supported by experimental biochemistry. Accept as a core biological process. Supporting Evidence: PMID:8706755 catalyses the cleavage of L-kynurenine and L-3-hydroxykynurenine into anthranilic and 3-hydroxyanthranilic
GO:0030429 kynureninase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) inference of kynureninase activity, the defining molecular function of this gene. Redundant with multiple experimental EXP/IDA annotations to the same term. Accept as the core molecular function. Supporting Evidence: file:human/KYNU/KYNU-uniprot.txt Catalyzes the cleavage of L-kynurenine (L-Kyn) and L-3-
GO:0005739 mitochondrion	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Phylogenetic (IBA) inference of mitochondrial localization (from PANTHER subfamily PTN001019478). The UniProt authoritative call is cytosol only, and the enzyme has no mitochondrial targeting sequence. Older fractionation work did detect activity in a mitochondrial fraction of human liver (PMID:6468727), but the current consensus places human kynureninase in the cytosol. This broad phylogenetic mitochondrion call is an over-annotation for the human protein. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN001019478 · Kynureninase subfamily node SUPPORTS SOURCE BUT NOT TARGET Mitochondrial localization from the PANTHER subfamily node does not transfer to human KYNU, which lacks a mitochondrial targeting sequence and is placed in the cytosol by UniProt; the primary/core location is cytosol. Supporting Evidence: file:human/KYNU/KYNU-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005737 cytoplasm	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Electronic (InterPro/UniRule) annotation of cytoplasmic localization. Consistent with the UniProt cytosol call. The more specific cytosol term is preferred; kept as non-core. Supporting Evidence: file:human/KYNU/KYNU-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation of cytosol from the UniProt Subcellular Location vocabulary mapping (SL-0091). This matches the authoritative UniProt call and the experimental IDA/HPA cytosol annotations. Accept as the core location. Supporting Evidence: file:human/KYNU/KYNU-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0006569 L-tryptophan catabolic process	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (InterPro/UniRule) annotation of involvement in L-tryptophan catabolism, redundant with the IBA and IMP annotations to the same term. Accept as a core biological process. Supporting Evidence: PMID:8706755 catalyses the cleavage of L-kynurenine and L-3-hydroxykynurenine into anthranilic and 3-hydroxyanthranilic
GO:0009435 NAD+ biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (InterPro/UniPathway) annotation of involvement in NAD+ biosynthesis. Kynureninase feeds the de novo (tryptophan) NAD+ biosynthetic route via quinolinate. Redundant with the IMP annotation to the same term. Accept as core process context. Supporting Evidence: file:human/KYNU/KYNU-uniprot.txt Cofactor biosynthesis; NAD(+) biosynthesis; quinolinate from
GO:0019805 quinolinate biosynthetic process	IEA GO_REF:0000104	ACCEPT	Summary: Electronic annotation (transfer of manual annotation) of involvement in quinolinate biosynthesis. Kynureninase produces 3-hydroxyanthranilate, the immediate precursor of quinolinate; UniProt records the pathway "quinolinate from L-kynurenine: step 2/3". Redundant with the experimental IDA to the same term. Accept. Supporting Evidence: file:human/KYNU/KYNU-uniprot.txt NAD(+) biosynthesis; quinolinate from
GO:0030170 pyridoxal phosphate binding	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (InterPro/UniRule) annotation of pyridoxal 5'-phosphate binding. PLP is the obligate cofactor of kynureninase, established by the PLP-bound crystal structure and by the internal Schiff base to Lys276. Accept as a core molecular function. Supporting Evidence: PMID:17300176 the atomic structure of the PLP-bound holoenzyme was determined
GO:0030429 kynureninase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (ARBA/InterPro/Rhea/EC 3.7.1.3) annotation of kynureninase activity, redundant with the multiple experimental annotations to the same term. Accept as the core molecular function. Supporting Evidence: file:human/KYNU/KYNU-uniprot.txt L-kynurenine + H2O = anthranilate + L-alanine
GO:0034354 'de novo' NAD+ biosynthetic process from L-tryptophan	IEA GO_REF:0000104	ACCEPT	Summary: Electronic annotation of involvement in de novo NAD+ biosynthesis from L-tryptophan. This is the precise process term for kynureninase's role: its reaction is on the tryptophan-to-quinolinate-to-NAD route, and KYNU loss-of-function causes NAD deficiency in patients. Accept as core. Supporting Evidence: PMID:28792876 Nicotinamide adenine dinucleotide (NAD) is synthesized de novo from tryptophan through the kynurenine pathway.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: Direct (IDA, Human Protein Atlas immunofluorescence) annotation of cytosolic localization. Matches the authoritative UniProt call. Accept as the core location. Supporting Evidence: file:human/KYNU/KYNU-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0030429 kynureninase activity	EXP PMID:17300176 Crystal structure of Homo sapiens kynureninase.	ACCEPT	Summary: Experimental (EXP) annotation of kynureninase activity from the crystal structure and kinetic characterization of recombinant human kynureninase. The enzyme catalyses hydrolytic cleavage of 3-hydroxy-L-kynurenine to 3-hydroxyanthranilate and L-alanine. This is the core molecular function. Accept. Supporting Evidence: PMID:17300176 preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine
GO:0030429 kynureninase activity	EXP PMID:8706755 Isolation and expression of a cDNA clone encoding human kynu...	ACCEPT	Summary: Experimental (EXP) annotation of kynureninase activity from the cloning and functional expression of human kynureninase, which catalyses cleavage of L-kynurenine and L-3-hydroxykynurenine to anthranilate and 3-hydroxyanthranilate. Core molecular function. Accept. Supporting Evidence: PMID:8706755 catalyses the cleavage of L-kynurenine and L-3-hydroxykynurenine into anthranilic and 3-hydroxyanthranilic acids
GO:0009435 NAD+ biosynthetic process	IMP PMID:28792876 NAD Deficiency, Congenital Malformations, and Niacin Supplem...	ACCEPT	Summary: Experimental (IMP) annotation of involvement in NAD+ biosynthesis. Patients with loss-of-function KYNU variants had reduced circulating NAD, and mutant enzymes had greatly reduced activity; NAD is synthesized de novo from tryptophan through the kynurenine pathway in which KYNU acts. Accept as core process. Supporting Evidence: PMID:28792876 The patients had reduced levels of circulating NAD.
GO:0030429 kynureninase activity	IDA PMID:28792876 NAD Deficiency, Congenital Malformations, and Niacin Supplem...	ACCEPT	Summary: Direct (IDA) annotation of kynureninase activity, based on in vitro enzyme assays of wild-type and patient-derived mutant KYNU; the mutant enzymes had greatly reduced activity, confirming the kynureninase function of the gene product. Core molecular function. Accept. Supporting Evidence: PMID:28792876 The mutant enzymes had greatly reduced activity in vitro.
GO:0005829 cytosol	TAS Reactome:R-HSA-71217	ACCEPT	Summary: Reactome traceable (TAS) annotation placing the kynureninase reaction (3-hydroxykynurenine to 3-hydroxyanthranilate) in the cytosol. Matches the authoritative UniProt location. Accept as core. Supporting Evidence: Reactome:R-HSA-71217 Cytosolic kynureninase catalyzes the hydrolysis of 3-hydroxy-L-kynurenine to form L-alanine and 3-hydroxyanthranilate.
GO:0034516 response to vitamin B6	IMP PMID:1939450 High-performance liquid chromatographic assay of human lymph...	KEEP AS NON CORE	Summary: Annotation of "response to vitamin B6" based on the observation that human lymphocyte kynureninase activity is depressed in vitamin-B6-deficient men. This reflects the enzyme's obligate dependence on the PLP cofactor (the active form of vitamin B6) rather than KYNU mediating a regulated cellular response to vitamin B6. It is a genuine but peripheral, cofactor-dependency observation; keep as non-core. Supporting Evidence: PMID:1939450 lymphocyte kynureninase activity is depressed during a vitamin B6 deficiency
GO:0005739 mitochondrion	IDA PMID:6468727 Intracellular localization and characterization of 3-hydroxy...	KEEP AS NON CORE	Summary: Direct (IDA) annotation of mitochondrial localization from early subcellular fractionation of human liver, which found 3-hydroxykynureninase activity in both cytosol and mitochondria with identical properties. This is an experimental observation and is not removed. However, the authoritative UniProt call and later data place human kynureninase in the cytosol (no mitochondrial targeting sequence). The mitochondrial pool is therefore kept as a non-core localization. Supporting Evidence: PMID:6468727 3-hydroxykynureninase in human liver was present in cytosol and mitochondria.
GO:0005829 cytosol	IDA PMID:6468727 Intracellular localization and characterization of 3-hydroxy...	ACCEPT	Summary: Direct (IDA) annotation of cytosolic localization from subcellular fractionation of human liver. Consistent with the authoritative UniProt call and the other cytosol annotations. Accept as the core location. Supporting Evidence: PMID:6468727 3-hydroxykynureninase in human liver was present in cytosol and mitochondria.
GO:0006569 L-tryptophan catabolic process	IMP PMID:17334708 Xanthurenic aciduria due to a mutation in KYNU encoding kynu...	ACCEPT	Summary: Experimental (IMP) annotation of involvement in L-tryptophan catabolism, based on a KYNU-deficient patient (homozygous T198A) with hydroxykynureninuria showing accumulation of upstream kynurenine-pathway metabolites (kynurenine, 3-hydroxykynurenine, xanthurenic acid). Accept as core process. Supporting Evidence: PMID:17334708 Massive urinary excretion of xanthurenic acid, 3-hydroxykynurenine and kynurenine
GO:0019805 quinolinate biosynthetic process	IDA PMID:9291104 Different kynurenine pathway enzymes limit quinolinic acid f...	ACCEPT	Summary: Direct (IDA) annotation of involvement in quinolinate biosynthesis. Cell-type comparisons showed that kynureninase activity is one of the determinants of whether a human cell can convert kynurenine-pathway intermediates to quinolinate. Accept as a core process (quinolinate is the precursor to de novo NAD+). Supporting Evidence: PMID:9291104 Kynurenine 3-hydroxylase and, in some cells, kynureninase and 3-hydroxyanthranilate 3,4-dioxygenase are important determinants of whether a cell can make quinolinate.
GO:0030429 kynureninase activity	IDA PMID:11985583 Purification and biochemical characterization of some of the...	ACCEPT	Summary: Direct (IDA) annotation of kynureninase activity from purification and biochemical characterization of recombinant human kynureninase, which was highly specific for 3-hydroxykynurenine. Core molecular function. Accept. Supporting Evidence: PMID:11985583 This cloned enzyme was highly specific for 3-hydroxykynurenine
GO:0030429 kynureninase activity	IMP PMID:17334708 Xanthurenic aciduria due to a mutation in KYNU encoding kynu...	ACCEPT	Summary: IMP annotation of kynureninase activity, inferred from the KYNU-deficient patient (homozygous T198A) with reduced 3-hydroxykynureninase activity and hydroxykynureninuria. This is an experimental (patient-based) annotation to the core molecular function. Accept. Supporting Evidence: PMID:17334708 a mutation in KYNU encoding kynureninase
GO:0030429 kynureninase activity	IDA PMID:9180257 Cloning and recombinant expression of rat and human kynureni...	ACCEPT	Summary: Direct (IDA) annotation of kynureninase activity from cloning and recombinant expression of human (and rat) kynureninase, with measured Km values for L-kynurenine and DL-3-hydroxykynurenine. Core molecular function. Accept. Supporting Evidence: PMID:9180257 A cDNA encoding human liver kynureninase was also isolated.
GO:0034341 response to type II interferon	IDA PMID:9291104 Different kynurenine pathway enzymes limit quinolinic acid f...	KEEP AS NON CORE	Summary: Annotation of "response to type II interferon" from the observation that kynureninase activity (and quinolinate production) is high in interferon-gamma-stimulated cells. This reflects inducibility/context of the kynurenine pathway under immune activation rather than the enzyme's core catalytic role. Keep as non-core. Supporting Evidence: PMID:9291104 High activities of kynurenine 3-hydroxylase, kynureninase or 3-hydroxyanthranilate 3,4-dioxygenase were found in interferon-gamma-stimulated macrophages
GO:0042803 protein homodimerization activity	IDA PMID:11985583 Purification and biochemical characterization of some of the...	KEEP AS NON CORE	Summary: Direct (IDA) annotation of protein homodimerization activity. Human kynureninase is a homodimer (confirmed by the crystal structure). This is a real structural property but describes the enzyme's quaternary assembly rather than its catalytic function; keep as non-core. Supporting Evidence: file:human/KYNU/KYNU-uniprot.txt Homodimer.

Gene Description

Existing Annotations Review

Core Functions

Kynureninase activity: PLP-dependent hydrolytic cleavage of 3-hydroxy-L-kynurenine to 3-hydroxyanthranilate and L-alanine (and of L-kynurenine to anthranilate and L-alanine), the committed step directing tryptophan-derived carbon toward quinolinate.

Pyridoxal 5'-phosphate binding: PLP is the obligate cofactor of kynureninase, bound as an internal Schiff base to the active-site lysine (Lys276) in this fold-type I (aspartate aminotransferase superfamily) enzyme.

References

📚 Additional Documentation

Notes

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