Reviewed, UniProtKB/Swiss-Prot Q16719 (KYNU_HUMAN)

Names and origin

Protein names

Recommended name:
    Kynureninase
    EC=3.7.1.3
Alternative name(s):
    L-kynurenine hydrolase

Gene names

Name:

KYNU

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	465 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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.
Catalytic activity	L-kynurenine + H2O = anthranilate + L-alanine. Ref.1 Ref.2 Ref.4 Ref.5 L-3-hydroxykynurenine + H2O = 3-hydroxyanthranilate + L-alanine. Ref.1 Ref.2 Ref.4 Ref.5
Cofactor	Pyridoxal phosphate.
Enzyme regulation	Inhibited by o-methoxybenzoylalanine (OMBA). Ref.1 Ref.2
Pathway	Amino-acid degradation; L-kynurenine degradation; L-alanine and anthranilate from L-kynurenine: step 1/1. Cofactor biosynthesis; NAD(+) biosynthesis; quinolinate from L-kynurenine: step 2/3.
Subunit structure	Homodimer. Ref.5
Subcellular location	Cytoplasm. Ref.1
Tissue specificity	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. Ref.1 Ref.2
Induction	Increased levels in several cerebral and systemic inflammatory conditions.
Involvement in disease	Defects in KYNU may be a cause of hydroxykynureninuria [MIM:236800]; also known as kynureninase deficiency. Hydroxykynureninuria is characterized by urinary excretion of large amounts of kynurenine, 3-hydroxykynurenine and xanthurenic acid. This suggests a block in the conversion of kynurenine and 3-hydroxykynurenine to anthranilate and 3-hydroxyanthranilate, respectively, which leads to impaired niacin biosynthesis. Hydroxykynureninuria can be associated with psychomotor retardation and non-progressive encephalopathy. Ref.6
Sequence similarities	Belongs to the kynureninase family.
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 (Ref.4).
Biophysicochemical properties	Kinetic parameters: KM=493 µM for L-kynurenine (at pH 7.0) KM=28.3 µM for DL-3-hydroxykynurenine (at pH 7.0) KM=3.0 µM for DL-3-hydroxykynurenine (at pH 7.9) pH dependence: Optimum pH is 8.25 with DL-3-hydroxykynurenine as substrate.
Mass spectrometry	Molecular mass is 52400 Da from positions 1 - 465. Determined by MALDI. The reported mass is given to only three significant figures. Ref.4

Ontologies

Keywords
Biological process	Pyridine nucleotide biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	Pyridoxal phosphate
Molecular function	Hydrolase
PTM	Acetylation
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	NAD biosynthetic process Inferred from electronic annotation. Source: InterPro anthranilate metabolic process Ref.4 Inferred from direct assay. Source: UniProtKB quinolinate biosynthetic process Inferred from direct assay. Source: UniProtKB response to interferon-gamma Inferred from direct assay. Source: UniProtKB response to vitamin B6 Inferred from mutant phenotype. Source: UniProtKB tryptophan catabolic process Ref.6 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cytosol Ref.2 Inferred from direct assay. Source: UniProtKB mitochondrion Inferred from direct assay. Source: UniProtKB soluble fraction Ref.4 Inferred from direct assay. Source: UniProtKB
Molecular function	kynureninase activity Ref.2 Ref.4 Ref.6 Inferred from direct assay. Source: UniProtKB protein homodimerization activity Ref.4 Inferred from direct assay. Source: UniProtKB pyridoxal phosphate binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 465

465

Kynureninase

PRO_0000218657

Regions

Region

165 – 168

4

Pyridoxal phosphate binding

Sites

Binding site

137

1

Pyridoxal phosphate; via amide nitrogen By similarity

Binding site

138

1

Pyridoxal phosphate

Binding site

250

1

Pyridoxal phosphate

Binding site

253

1

Pyridoxal phosphate

Binding site

275

1

Pyridoxal phosphate

Binding site

305

1

Pyridoxal phosphate

Binding site

333

1

Pyridoxal phosphate

Amino acid modifications

Modified residue

1

1

N-acetylmethionine By similarity

Modified residue

276

1

N6-(pyridoxal phosphate)lysine

Natural variations

Natural variant

188

1

R → Q: dbSNP rs2304705.

VAR_049724

Natural variant

198

1

T → A in hydroxykynureninuria. Ref.6

VAR_054401

Natural variant

412

1

K → E: dbSNP rs9013. Ref.3

VAR_022092

Secondary structure

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465

Helix Strand Turn

Details...

Helix

9 – 20

12

Helix

27 – 36

10

Helix

40 – 45

6

Helix

51 – 53

3

Helix

59 – 61

3

Turn

73 – 75

3

Helix

83 – 97

15

Helix

98 – 102

5

Beta strand

104 – 107

4

Helix

109 – 111

3

Turn

112 – 116

5

Helix

117 – 120

4

Helix

121 – 124

4

Helix

128 – 130

3

Beta strand

131 – 133

3

Helix

137 – 148

12

Beta strand

153 – 155

3

Beta strand

157 – 161

5

Helix

166 – 178

13

Helix

183 – 186

4

Beta strand

187 – 190

4

Helix

201 – 211

11

Helix

212 – 214

3

Beta strand

215 – 223

9

Turn

225 – 227

3

Helix

233 – 242

10

Beta strand

246 – 250

5

Turn

252 – 257

6

Helix

262 – 265

4

Beta strand

269 – 272

4

Beta strand

274 – 276

3

Beta strand

287 – 290

4

Helix

292 – 294

3

Turn

295 – 297

3

Helix

305 – 307

3

Helix

310 – 313

4

Helix

326 – 329

4

Helix

336 – 352

17

Helix

354 – 375

22

Beta strand

388 – 390

3

Helix

396 – 398

3

Beta strand

403 – 407

5

Helix

414 – 419

6

Turn

420 – 422

3

Beta strand

426 – 428

3

Turn

429 – 431

3

Beta strand

432 – 436

5

Turn

439 – 441

3

Helix

444 – 458

15

Sequences

	Sequence		Length	Mass (Da)
	Q16719-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: BDD136BE18C79EBB	FASTA	465	52,352
	10 20 30 40 50 60 MEPSSLELPA DTVQRIAAEL KCHPTDERVA LHLDEEDKLR HFRECFYIPK IQDLPPVDLS 70 80 90 100 110 120 LVNKDENAIY FLGNSLGLQP KMVKTYLEEE LDKWAKIAAY GHEVGKRPWI TGDESIVGLM 130 140 150 160 170 180 KDIVGANEKE IALMNALTVN LHLLMLSFFK PTPKRYKILL EAKAFPSDHY AIESQLQLHG 190 200 210 220 230 240 LNIEESMRMI KPREGEETLR IEDILEVIEK EGDSIAVILF SGVHFYTGQH FNIPAITKAG 250 260 270 280 290 300 QAKGCYVGFD LAHAVGNVEL YLHDWGVDFA CWCSYKYLNA GAGGIAGAFI HEKHAHTIKP 310 320 330 340 350 360 ALVGWFGHEL STRFKMDNKL QLIPGVCGFR ISNPPILLVC SLHASLEIFK QATMKALRKK 370 380 390 400 410 420 SVLLTGYLEY LIKHNYGKDK AATKKPVVNI ITPSHVEERG CQLTITFSVP NKDVFQELEK 430 440 450 460 RGVVCDKRNP NGIRVAPVPL YNSFHDVYKF TNLLTSILDS AETKN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and expression of a cDNA clone encoding human kynureninase." Alberati-Giani D., Buchli R., Malherbe P., Broger C., Lang G., Koehler C., Lahm H.-W., Cesura A.M. Eur. J. Biochem. 239:460-468(1996) [PubMed: 8706755] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, CATALYTIC ACTIVITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES. Tissue: Hepatoma.
[2]	"Cloning and recombinant expression of rat and human kynureninase." Toma S., Nakamura M., Tone S., Okuno E., Kido R., Breton J., Avanzi N., Cozzi L., Speciale C., Mostardini M., Gatti S., Benatti L. FEBS Lett. 408:5-10(1997) [PubMed: 9180257] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, CATALYTIC ACTIVITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES. Tissue: Liver.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLU-412. Tissue: Synovium.
[4]	"Purification and biochemical characterization of some of the properties of recombinant human kynureninase." Walsh H.A., Botting N.P. Eur. J. Biochem. 269:2069-2074(2002) [PubMed: 11985583] [Abstract] Cited for: MASS SPECTROMETRY, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
[5]	"Crystal structure of Homo sapiens kynureninase." Lima S., Khristoforov R., Momany C., Phillips R.S. Biochemistry 46:2735-2744(2007) [PubMed: 17300176] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH PYRIDOXAL PHOSPHATE, HOMODIMERIZATION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
[6]	"Xanthurenic aciduria due to a mutation in KYNU encoding kynureninase." Christensen M., Duno M., Lund A.M., Skovby F., Christensen E. J. Inherit. Metab. Dis. 30:248-255(2007) [PubMed: 17334708] [Abstract] Cited for: VARIANT HYDROXYKYNURENINURIA ALA-198.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

U57721 mRNA. Translation: AAC50650.1.
AK315343 mRNA. Translation: BAG37742.1.

IPI

IPI00003818.

PIR

G02652.

RefSeq

NP_003928.1.

UniGene

Hs.470126

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2HZP	X-ray	2.00	A	1-465	[»]
3E9K	X-ray	1.70	A	1-465	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

Q16719.

Proteomic databases

PeptideAtlas

Q16719.

PRIDE

Q16719.

Genome annotation databases

Ensembl

ENST00000264170; ENSP00000264170; ENSG00000115919; Homo sapiens. [Genome view]
ENST00000375773; ENSP00000364928; ENSG00000115919; Homo sapiens. [Genome view]
ENST00000392874; ENSP00000376613; ENSG00000115919; Homo sapiens. [Genome view]
ENST00000409512; ENSP00000386731; ENSG00000115919; Homo sapiens. [Genome view]
ENST00000410015; ENSP00000387296; ENSG00000115919; Homo sapiens. [Genome view]
ENST00000424385; ENSP00000401190; ENSG00000115919; Homo sapiens. [Genome view]

GeneID

8942.

UCSC

uc002tvl.1. human.

Organism-specific databases

CTD

8942.

GeneCards

GC02P143351.

H-InvDB

HIX0002487.

HGNC

HGNC:6469. KYNU.

MIM

236800. phenotype.
605197. gene.

Orphanet

79155. Encephalopathy due to hydroxykynureninuria.

PharmGKB

PA30258.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q16719.

HOVERGEN

Q16719.

OMA

WQPLSGW.

Enzyme and pathway databases

BRENDA

3.7.1.3. 247.

Reactome

REACT_11193. Metabolism of vitamins and cofactors.
REACT_13. Metabolism of amino acids.

Gene expression databases

ArrayExpress

Q16719.

Bgee

Q16719.

CleanEx

HS_KYNU.

Genevestigator

Q16719.

GermOnline

ENSG00000115919. Homo sapiens.

Family and domain databases

InterPro

IPR000192. Aminotrans_V/Cys_dSase.
IPR010111. Kynureninase.
IPR015421. PyrdxlP-dep_Trfase_major_sub1.
[Graphical view]

Gene3D

G3DSA:3.40.640.10. PyrdxlP-dep_Trfase_major_sub1. 1 hit.

PANTHER

PTHR14084. Kynureninase. 1 hit.

Pfam

PF00266. Aminotran_5. 1 hit.
[Graphical view]

TIGRFAMs

TIGR01814. kynureninase. 1 hit.

ProtoNet

Search...

Other Resources

DrugBank

DB00160. L-Alanine.
DB00114. Pyridoxal Phosphate.

NextBio

33630.

SOURCE

Search...

Entry information

Entry name

KYNU_HUMAN

Accession

Primary (citable) accession number: Q16719
Secondary accession number(s): B2RCZ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	November 1, 1996
Last modified:	November 3, 2009
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.