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Protein

Kynureninase

Gene

KYNU

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the cleavage of L-kynurenine (L-Kyn) and L-3-hydroxykynurenine (L-3OHKyn) into anthranilic acid (AA) and 3-hydroxyanthranilic acid (3-OHAA), respectively. Has a preference for the L-3-hydroxy form. Also has cysteine-conjugate-beta-lyase activity.5 Publications

Caution

It has been reported that this enzyme possesses no measurable activity against L-kynurenine and is subject to inhibition by both L-kynurenine and D-kynurenine at pH 7.9.1 Publication

Catalytic activityi

L-kynurenine + H2O = anthranilate + L-alanine.UniRule annotation4 Publications
L-3-hydroxykynurenine + H2O = 3-hydroxyanthranilate + L-alanine.UniRule annotation5 Publications

Cofactori

pyridoxal 5'-phosphate1 Publication

Activity regulationi

Inhibited by o-methoxybenzoylalanine (OMBA).2 Publications

Kineticsi

  1. KM=493 µM for L-kynurenine (at pH 7.0)4 Publications
  2. KM=28.3 µM for DL-3-hydroxykynurenine (at pH 7.0)4 Publications
  3. KM=3.0 µM for DL-3-hydroxykynurenine (at pH 7.9)4 Publications

    pH dependencei

    Optimum pH is 8.25 with DL-3-hydroxykynurenine as substrate.4 Publications

    Pathwayi: L-kynurenine degradation

    This protein is involved in step 1 of the subpathway that synthesizes L-alanine and anthranilate from L-kynurenine.UniRule annotation
    Proteins known to be involved in this subpathway in this organism are:
    1. Kynureninase (KYNU), Kynureninase (KYNU), Kynureninase (KYNU)
    This subpathway is part of the pathway L-kynurenine degradation, which is itself part of Amino-acid degradation.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-alanine and anthranilate from L-kynurenine, the pathway L-kynurenine degradation and in Amino-acid degradation.

    Pathwayi: NAD(+) biosynthesis

    This protein is involved in step 2 of the subpathway that synthesizes quinolinate from L-kynurenine.UniRule annotation1 Publication
    Proteins known to be involved in the 3 steps of the subpathway in this organism are:
    1. Kynurenine 3-monooxygenase (KMO), Kynurenine 3-monooxygenase (KMO), Kynurenine 3-monooxygenase (KMO), Kynurenine 3-monooxygenase (KMO)
    2. Kynureninase (KYNU), Kynureninase (KYNU), Kynureninase (KYNU)
    3. 3-hydroxyanthranilate 3,4-dioxygenase (HAAO)
    This subpathway is part of the pathway NAD(+) biosynthesis, which is itself part of Cofactor biosynthesis.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes quinolinate from L-kynurenine, the pathway NAD(+) biosynthesis and in Cofactor biosynthesis.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei137Pyridoxal phosphate; via amide nitrogenUniRule annotation1
    Binding sitei138Pyridoxal phosphateUniRule annotation1 Publication1
    Binding sitei221Pyridoxal phosphateUniRule annotation1
    Binding sitei250Pyridoxal phosphateUniRule annotation1 Publication1
    Binding sitei253Pyridoxal phosphateUniRule annotation1 Publication1
    Binding sitei275Pyridoxal phosphateUniRule annotation1 Publication1
    Binding sitei305Pyridoxal phosphateUniRule annotation1 Publication1
    Binding sitei333Pyridoxal phosphateUniRule annotation1 Publication1

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionHydrolase
    Biological processPyridine nucleotide biosynthesis
    LigandPyridoxal phosphate

    Enzyme and pathway databases

    BioCyciMetaCyc:HS03952-MONOMER
    BRENDAi3.7.1.3 2681
    ReactomeiR-HSA-71240 Tryptophan catabolism
    SABIO-RKiQ16719
    UniPathwayi
    UPA00253;UER00329

    UPA00334;UER00455

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    KynureninaseUniRule annotation (EC:3.7.1.3UniRule annotation4 Publications)
    Alternative name(s):
    L-kynurenine hydrolaseUniRule annotation
    Gene namesi
    Name:KYNUUniRule annotationImported
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 2

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000115919.14
    HGNCiHGNC:6469 KYNU
    MIMi605197 gene
    neXtProtiNX_Q16719

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    Hydroxykynureninuria (HYXKY)2 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionAn inborn error of amino acid metabolism characterized by massive urinary excretion of large amounts of kynurenine, 3-hydroxykynurenine and xanthurenic acid. Affected individuals manifest renal tubular dysfunction, metabolic acidosis, psychomotor retardation, non-progressive encephalopathy, and muscular hypertonia.
    See also OMIM:236800
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_054401198T → A in HYXKY; reduced 3-hydroxykynureninase activity. 2 PublicationsCorresponds to variant dbSNP:rs606231307EnsemblClinVar.1
    Vertebral, cardiac, renal, and limb defects syndrome 2 (VCRL2)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionAn autosomal recessive congenital malformation syndrome characterized by vertebral segmentation abnormalities, congenital cardiac defects, renal defects, and distal mild limb defects.
    See also OMIM:617661
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_080254156 – 465Missing in VCRL2; strongly reduced 3-hydroxykynureninase activity. 1 PublicationAdd BLAST310

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi8942
    MalaCardsiKYNU
    MIMi236800 phenotype
    617661 phenotype
    OpenTargetsiENSG00000115919
    Orphaneti79155 Encephalopathy due to hydroxykynureninuria
    PharmGKBiPA30258

    Chemistry databases

    ChEMBLiCHEMBL5100
    DrugBankiDB07069 3-Hydroxyhippuric acid
    DB00160 L-Alanine
    DB00114 Pyridoxal Phosphate

    Polymorphism and mutation databases

    BioMutaiKYNU
    DMDMi3913982

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002186571 – 465KynureninaseAdd BLAST465

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei1N-acetylmethionineCombined sources1
    Modified residuei276N6-(pyridoxal phosphate)lysine1

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiQ16719
    MaxQBiQ16719
    PaxDbiQ16719
    PeptideAtlasiQ16719
    PRIDEiQ16719
    ProteomicsDBi61040
    61041 [Q16719-2]

    PTM databases

    iPTMnetiQ16719
    PhosphoSitePlusiQ16719

    Expressioni

    Tissue specificityi

    Expressed in all tissues tested (heart, brain placenta, lung, liver, skeletal muscle, kidney and pancreas). Highest levels found in placenta, liver and lung. Expressed in all brain regions.2 Publications

    Inductioni

    Increased levels in several cerebral and systemic inflammatory conditions.

    Gene expression databases

    BgeeiENSG00000115919 Expressed in 184 organ(s), highest expression level in palpebral conjunctiva
    CleanExiHS_KYNU
    ExpressionAtlasiQ16719 baseline and differential
    GenevisibleiQ16719 HS

    Organism-specific databases

    HPAiHPA031686

    Interactioni

    Subunit structurei

    Homodimer.UniRule annotation1 Publication

    GO - Molecular functioni

    Protein-protein interaction databases

    BioGridi114454, 45 interactors
    IntActiQ16719, 9 interactors
    STRINGi9606.ENSP00000264170

    Chemistry databases

    BindingDBiQ16719

    Structurei

    Secondary structure

    1465
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliQ16719
    SMRiQ16719
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ16719

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni165 – 168Pyridoxal phosphate binding4

    Sequence similaritiesi

    Belongs to the kynureninase family.UniRule annotation

    Phylogenomic databases

    eggNOGiKOG3846 Eukaryota
    COG3844 LUCA
    GeneTreeiENSGT00390000008033
    HOGENOMiHOG000242438
    HOVERGENiHBG001170
    InParanoidiQ16719
    KOiK01556
    OMAiVCSLHAS
    OrthoDBiEOG091G077R
    PhylomeDBiQ16719
    TreeFamiTF300707

    Family and domain databases

    Gene3Di3.40.640.10, 1 hit
    3.90.1150.10, 2 hits
    HAMAPiMF_01970 Kynureninase, 1 hit
    InterProiView protein in InterPro
    IPR000192 Aminotrans_V_dom
    IPR010111 Kynureninase
    IPR015424 PyrdxlP-dep_Trfase
    IPR015422 PyrdxlP-dep_Trfase_dom1
    IPR015421 PyrdxlP-dep_Trfase_major
    PANTHERiPTHR14084 PTHR14084, 1 hit
    PfamiView protein in Pfam
    PF00266 Aminotran_5, 1 hit
    PIRSFiPIRSF038800 KYNU, 1 hit
    SUPFAMiSSF53383 SSF53383, 1 hit
    TIGRFAMsiTIGR01814 kynureninase, 1 hit

    Sequences (2+)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    This entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

    Isoform 1 (identifier: Q16719-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide
            10         20         30         40         50
    MEPSSLELPA DTVQRIAAEL KCHPTDERVA LHLDEEDKLR HFRECFYIPK
    60 70 80 90 100
    IQDLPPVDLS LVNKDENAIY FLGNSLGLQP KMVKTYLEEE LDKWAKIAAY
    110 120 130 140 150
    GHEVGKRPWI TGDESIVGLM KDIVGANEKE IALMNALTVN LHLLMLSFFK
    160 170 180 190 200
    PTPKRYKILL EAKAFPSDHY AIESQLQLHG LNIEESMRMI KPREGEETLR
    210 220 230 240 250
    IEDILEVIEK EGDSIAVILF SGVHFYTGQH FNIPAITKAG QAKGCYVGFD
    260 270 280 290 300
    LAHAVGNVEL YLHDWGVDFA CWCSYKYLNA GAGGIAGAFI HEKHAHTIKP
    310 320 330 340 350
    ALVGWFGHEL STRFKMDNKL QLIPGVCGFR ISNPPILLVC SLHASLEIFK
    360 370 380 390 400
    QATMKALRKK SVLLTGYLEY LIKHNYGKDK AATKKPVVNI ITPSHVEERG
    410 420 430 440 450
    CQLTITFSVP NKDVFQELEK RGVVCDKRNP NGIRVAPVPL YNSFHDVYKF
    460
    TNLLTSILDS AETKN
    Length:465
    Mass (Da):52,352
    Last modified:November 1, 1996 - v1
    Checksum:iBDD136BE18C79EBB
    GO
    Isoform 2 (identifier: Q16719-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         302-307: LVGWFG → RSEFFN
         308-465: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:307
    Mass (Da):34,635
    Checksum:i9219F37B19D2163E
    GO

    Computationally mapped potential isoform sequencesi

    There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    A0A087X297A0A087X297_HUMAN
    Kynureninase
    KYNU
    236Annotation score:
    B8ZZA3B8ZZA3_HUMAN
    Kynureninase
    KYNU
    148Annotation score:
    A0A087WYQ7A0A087WYQ7_HUMAN
    Kynureninase
    KYNU
    157Annotation score:
    A0A087WYM2A0A087WYM2_HUMAN
    Kynureninase
    KYNU
    168Annotation score:
    F8WEP1F8WEP1_HUMAN
    Kynureninase
    KYNU
    76Annotation score:

    Mass spectrometryi

    Molecular mass is 52400 Da from positions 1 - 465. Determined by MALDI. The reported mass is given to only three significant figures.1 Publication

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_080254156 – 465Missing in VCRL2; strongly reduced 3-hydroxykynureninase activity. 1 PublicationAdd BLAST310
    Natural variantiVAR_049724188R → Q. Corresponds to variant dbSNP:rs2304705EnsemblClinVar.1
    Natural variantiVAR_054401198T → A in HYXKY; reduced 3-hydroxykynureninase activity. 2 PublicationsCorresponds to variant dbSNP:rs606231307EnsemblClinVar.1
    Natural variantiVAR_022092412K → E1 PublicationCorresponds to variant dbSNP:rs9013Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_042739302 – 307LVGWFG → RSEFFN in isoform 2. Curated6
    Alternative sequenceiVSP_042740308 – 465Missing in isoform 2. CuratedAdd BLAST158

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U57721 mRNA Translation: AAC50650.1
    AK315343 mRNA Translation: BAG37742.1
    CR457423 mRNA Translation: CAG33704.1
    AC013437 Genomic DNA No translation available.
    AC013444 Genomic DNA No translation available.
    CH471058 Genomic DNA Translation: EAX11599.1
    CH471058 Genomic DNA Translation: EAX11600.1
    CH471058 Genomic DNA Translation: EAX11601.1
    BC000879 mRNA Translation: AAH00879.1
    CCDSiCCDS2183.1 [Q16719-1]
    CCDS33299.1 [Q16719-2]
    PIRiG02652
    RefSeqiNP_001028170.1, NM_001032998.1 [Q16719-2]
    NP_001186170.1, NM_001199241.1 [Q16719-1]
    NP_003928.1, NM_003937.2 [Q16719-1]
    XP_016860706.1, XM_017005217.1 [Q16719-2]
    UniGeneiHs.470126

    Genome annotation databases

    EnsembliENST00000264170; ENSP00000264170; ENSG00000115919 [Q16719-1]
    ENST00000375773; ENSP00000364928; ENSG00000115919 [Q16719-2]
    ENST00000409512; ENSP00000386731; ENSG00000115919 [Q16719-1]
    GeneIDi8942
    KEGGihsa:8942
    UCSCiuc002tvk.4 human [Q16719-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U57721 mRNA Translation: AAC50650.1
    AK315343 mRNA Translation: BAG37742.1
    CR457423 mRNA Translation: CAG33704.1
    AC013437 Genomic DNA No translation available.
    AC013444 Genomic DNA No translation available.
    CH471058 Genomic DNA Translation: EAX11599.1
    CH471058 Genomic DNA Translation: EAX11600.1
    CH471058 Genomic DNA Translation: EAX11601.1
    BC000879 mRNA Translation: AAH00879.1
    CCDSiCCDS2183.1 [Q16719-1]
    CCDS33299.1 [Q16719-2]
    PIRiG02652
    RefSeqiNP_001028170.1, NM_001032998.1 [Q16719-2]
    NP_001186170.1, NM_001199241.1 [Q16719-1]
    NP_003928.1, NM_003937.2 [Q16719-1]
    XP_016860706.1, XM_017005217.1 [Q16719-2]
    UniGeneiHs.470126

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2HZPX-ray2.00A1-465[»]
    3E9KX-ray1.70A1-465[»]
    ProteinModelPortaliQ16719
    SMRiQ16719
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi114454, 45 interactors
    IntActiQ16719, 9 interactors
    STRINGi9606.ENSP00000264170

    Chemistry databases

    BindingDBiQ16719
    ChEMBLiCHEMBL5100
    DrugBankiDB07069 3-Hydroxyhippuric acid
    DB00160 L-Alanine
    DB00114 Pyridoxal Phosphate

    PTM databases

    iPTMnetiQ16719
    PhosphoSitePlusiQ16719

    Polymorphism and mutation databases

    BioMutaiKYNU
    DMDMi3913982

    Proteomic databases

    EPDiQ16719
    MaxQBiQ16719
    PaxDbiQ16719
    PeptideAtlasiQ16719
    PRIDEiQ16719
    ProteomicsDBi61040
    61041 [Q16719-2]

    Protocols and materials databases

    DNASUi8942
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000264170; ENSP00000264170; ENSG00000115919 [Q16719-1]
    ENST00000375773; ENSP00000364928; ENSG00000115919 [Q16719-2]
    ENST00000409512; ENSP00000386731; ENSG00000115919 [Q16719-1]
    GeneIDi8942
    KEGGihsa:8942
    UCSCiuc002tvk.4 human [Q16719-1]

    Organism-specific databases

    CTDi8942
    DisGeNETi8942
    EuPathDBiHostDB:ENSG00000115919.14
    GeneCardsiKYNU
    HGNCiHGNC:6469 KYNU
    HPAiHPA031686
    MalaCardsiKYNU
    MIMi236800 phenotype
    605197 gene
    617661 phenotype
    neXtProtiNX_Q16719
    OpenTargetsiENSG00000115919
    Orphaneti79155 Encephalopathy due to hydroxykynureninuria
    PharmGKBiPA30258
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG3846 Eukaryota
    COG3844 LUCA
    GeneTreeiENSGT00390000008033
    HOGENOMiHOG000242438
    HOVERGENiHBG001170
    InParanoidiQ16719
    KOiK01556
    OMAiVCSLHAS
    OrthoDBiEOG091G077R
    PhylomeDBiQ16719
    TreeFamiTF300707

    Enzyme and pathway databases

    UniPathwayi
    UPA00253;UER00329

    UPA00334;UER00455

    BioCyciMetaCyc:HS03952-MONOMER
    BRENDAi3.7.1.3 2681
    ReactomeiR-HSA-71240 Tryptophan catabolism
    SABIO-RKiQ16719

    Miscellaneous databases

    ChiTaRSiKYNU human
    EvolutionaryTraceiQ16719
    GeneWikiiKynureninase
    GenomeRNAii8942
    PROiPR:Q16719
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000115919 Expressed in 184 organ(s), highest expression level in palpebral conjunctiva
    CleanExiHS_KYNU
    ExpressionAtlasiQ16719 baseline and differential
    GenevisibleiQ16719 HS

    Family and domain databases

    Gene3Di3.40.640.10, 1 hit
    3.90.1150.10, 2 hits
    HAMAPiMF_01970 Kynureninase, 1 hit
    InterProiView protein in InterPro
    IPR000192 Aminotrans_V_dom
    IPR010111 Kynureninase
    IPR015424 PyrdxlP-dep_Trfase
    IPR015422 PyrdxlP-dep_Trfase_dom1
    IPR015421 PyrdxlP-dep_Trfase_major
    PANTHERiPTHR14084 PTHR14084, 1 hit
    PfamiView protein in Pfam
    PF00266 Aminotran_5, 1 hit
    PIRSFiPIRSF038800 KYNU, 1 hit
    SUPFAMiSSF53383 SSF53383, 1 hit
    TIGRFAMsiTIGR01814 kynureninase, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiKYNU_HUMAN
    AccessioniPrimary (citable) accession number: Q16719
    Secondary accession number(s): B2RCZ5
    , D3DP79, Q6I9T2, Q9BVW3
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
    Last sequence update: November 1, 1996
    Last modified: October 10, 2018
    This is version 169 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families
    4. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    5. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    6. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    7. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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