Q8N5Z0 (AADAT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial
Short name=KAT/AadAT

Alternative name(s):
2-aminoadipate aminotransferase
2-aminoadipate transaminase
EC=2.6.1.39
Alpha-aminoadipate aminotransferase
Short name=AadAT
Kynurenine aminotransferase II
Kynurenine--oxoglutarate aminotransferase II
Kynurenine--oxoglutarate transaminase 2
EC=2.6.1.7
Kynurenine--oxoglutarate transaminase II

Gene names

Name:	AADAT
Synonyms:	KAT2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	425 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transaminase with broad substrate specificity. Has transaminase activity towards aminoadipate, kynurenine, methionine and glutamate. Shows activity also towards tryptophan, aspartate and hydroxykynurenine. Accepts a variety of oxo-acids as amino-group acceptors, with a preference for 2-oxoglutarate, 2-oxocaproic acid, phenylpyruvate and alpha-oxo-gamma-methiol butyric acid. Can also use glyoxylate as amino-group acceptor (in vitro). Ref.5
Catalytic activity	L-kynurenine + 2-oxoglutarate = 4-(2-aminophenyl)-2,4-dioxobutanoate + L-glutamate. Ref.2 Ref.5 Ref.6 L-2-aminoadipate + 2-oxoglutarate = 2-oxoadipate + L-glutamate. Ref.2 Ref.5 Ref.6
Cofactor	Pyridoxal phosphate. Ref.2 Ref.6 Ref.7
Enzyme regulation	Kynurenine transaminase activity is competitively inhibited by aminoadipate, asparagine, glutamate, histidine, cysteine, lysine, 3-hydroxy-kynurenine and phenylalanine. Ref.5
Pathway	Amino-acid degradation; L-lysine degradation via saccharopine pathway; glutaryl-CoA from L-lysine: step 4/6.
Subunit structure	Homodimer. Ref.5 Ref.6 Ref.7
Subcellular location	Mitochondrion Potential.
Tissue specificity	Higher expression in the liver. Also found in heart, brain, kidney, pancreas, prostate, testis and ovary.
Sequence similarities	Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.
Biophysicochemical properties	Kinetic parameters: KM=0.9 mM for aminoadipate Ref.5 KM=4.7 mM for kynurenine KM=1.7 mM for methionine KM=1.6 mM for glutamate KM=1.8 mM for tyrosine KM=1.2 mM for 2-oxoglutarate KM=1.5 mM for 2-oxocaproic acid KM=1.8 mM for phenylpyruvate KM=1.4 mM for ino-3-pyruvate pH dependence: Optimum pH is 7-9. Temperature dependence: Optimum temperature is 50 degrees Celsius.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transit peptide
Ligand	Pyridoxal phosphate
Molecular function	Aminotransferase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	2-oxoglutarate metabolic process Inferred from direct assay Ref.5. Source: UniProtKB L-lysine catabolic process to acetyl-CoA via saccharopine Inferred from electronic annotation. Source: UniProtKB-UniPathway biosynthetic process Inferred from electronic annotation. Source: InterPro glutamate metabolic process Inferred from direct assay Ref.5. Source: UniProtKB lysine catabolic process Traceable author statement. Source: Reactome tryptophan catabolic process Traceable author statement. Source: Reactome tryptophan catabolic process to kynurenine Inferred from electronic annotation. Source: Compara
Cellular_component	mitochondrial matrix Traceable author statement. Source: Reactome
Molecular_function	2-aminoadipate transaminase activity Inferred from direct assay Ref.5. Source: UniProtKB kynurenine-oxoglutarate transaminase activity Inferred from direct assay Ref.5. Source: UniProtKB pyridoxal phosphate binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8N5Z0-1)

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.

Note: May be due to a competing donor splice site.

Isoform 2 (identifier: Q8N5Z0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     23-23: T → SEKRA

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 29

29

Mitochondrion Potential

Chain

30 – 425

396

Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial

PRO_0000020602

Sites

Binding site

20

1

Substrate

Binding site

74

1

Substrate

Binding site

142

1

Substrate

Binding site

202

1

Substrate

Binding site

399

1

Substrate

Amino acid modifications

Modified residue

263

1

N6-(pyridoxal phosphate)lysine

Natural variations

Alternative sequence

23

1

T → SEKRA in isoform 2.

VSP_009874

Natural variant

243

1

V → I.
Corresponds to variant rs56350236 [ dbSNP | Ensembl ].

VAR_061005

Experimental info

Sequence conflict

103

1

P → Q in AAH31068. Ref.4

Sequence conflict

380

1

L → S in BAG51596. Ref.3

Secondary structure

1

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425

Helix Strand Turn

Details...

Helix

3 – 6

4

Helix

9 – 12

4

Helix

19 – 21

3

Helix

22 – 28

7

Helix

43 – 45

3

Beta strand

47 – 55

9

Beta strand

61 – 63

3

Helix

65 – 71

7

Helix

81 – 95

15

Turn

98 – 101

4

Helix

104 – 106

3

Beta strand

109 – 116

8

Helix

117 – 128

12

Beta strand

134 – 140

7

Helix

143 – 149

7

Helix

150 – 152

3

Beta strand

155 – 159

5

Helix

168 – 175

8

Helix

180 – 182

3

Beta strand

183 – 185

3

Helix

186 – 188

3

Beta strand

192 – 196

5

Turn

202 – 204

3

Helix

210 – 222

13

Beta strand

226 – 230

5

Helix

234 – 236

3

Beta strand

237 – 241

5

Helix

247 – 249

3

Beta strand

251 – 253

3

Beta strand

255 – 261

7

Turn

262 – 265

4

Turn

267 – 270

4

Beta strand

272 – 277

6

Helix

278 – 289

12

Turn

290 – 292

3

Beta strand

293 – 295

3

Helix

297 – 340

44

Beta strand

342 – 347

6

Beta strand

351 – 360

10

Helix

367 – 371

5

Helix

373 – 376

4

Beta strand

381 – 383

3

Helix

384 – 387

4

Beta strand

388 – 390

3

Beta strand

391 – 393

3

Beta strand

397 – 401

5

Turn

402 – 404

3

Helix

407 – 424

18

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 13, 2004. Version 2. Checksum: 448CCAAB2173A7BA	FASTA	425	47,352
	10 20 30 40 50 60 MNYARFITAA SAARNPSPIR TMTDILSRGP KSMISLAGGL PNPNMFPFKT AVITVENGKT 70 80 90 100 110 120 IQFGEEMMKR ALQYSPSAGI PELLSWLKQL QIKLHNPPTI HYPPSQGQMD LCVTSGSQQG 130 140 150 160 170 180 LCKVFEMIIN PGDNVLLDEP AYSGTLQSLH PLGCNIINVA SDESGIVPDS LRDILSRWKP 190 200 210 220 230 240 EDAKNPQKNT PKFLYTVPNG NNPTGNSLTS ERKKEIYELA RKYDFLIIED DPYYFLQFNK 250 260 270 280 290 300 FRVPTFLSMD VDGRVIRADS FSKIISSGLR IGFLTGPKPL IERVILHIQV STLHPSTFNQ 310 320 330 340 350 360 LMISQLLHEW GEEGFMAHVD RVIDFYSNQK DAILAAADKW LTGLAEWHVP AAGMFLWIKV 370 380 390 400 410 420 KGINDVKELI EEKAVKMGVL MLPGNAFYVD SSAPSPYLRA SFSSASPEQM DVAFQVLAQL IKESL
	Isoform 2 [UniParc]. Checksum: 0C5A6E51F1BD6F53	FASTA	429	47,822
	10 20 30 40 50 60 MNYARFITAA SAARNPSPIR TMSEKRADIL SRGPKSMISL AGGLPNPNMF PFKTAVITVE 70 80 90 100 110 120 NGKTIQFGEE MMKRALQYSP SAGIPELLSW LKQLQIKLHN PPTIHYPPSQ GQMDLCVTSG 130 140 150 160 170 180 SQQGLCKVFE MIINPGDNVL LDEPAYSGTL QSLHPLGCNI INVASDESGI VPDSLRDILS 190 200 210 220 230 240 RWKPEDAKNP QKNTPKFLYT VPNGNNPTGN SLTSERKKEI YELARKYDFL IIEDDPYYFL 250 260 270 280 290 300 QFNKFRVPTF LSMDVDGRVI RADSFSKIIS SGLRIGFLTG PKPLIERVIL HIQVSTLHPS 310 320 330 340 350 360 TFNQLMISQL LHEWGEEGFM AHVDRVIDFY SNQKDAILAA ADKWLTGLAE WHVPAAGMFL 370 380 390 400 410 420 WIKVKGINDV KELIEEKAVK MGVLMLPGNA FYVDSSAPSP YLRASFSSAS PEQMDVAFQV LAQLIKESL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of human L-kynurenine/alpha-aminoadipate aminotransferase cDNA from brain tissue." Gatti S., Breton J., Mostardini M., Mosca M., Tarroni P., Schwarcz R., Speciale C., Okuno E., Toma S., Benatti L. Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Characterization of the human gene encoding alpha-aminoadipate aminotransferase (AADAT)." Goh D.L.M., Patel A., Thomas G.H., Salomons G.S., Schor D.S.M., Jakobs C., Geraghty M.T. Mol. Genet. Metab. 76:172-180(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY, COFACTOR.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[5]	"Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II." Han Q., Cai T., Tagle D.A., Robinson H., Li J. Biosci. Rep. 28:205-215(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH 2-OXOGLUTARATE, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, SUBUNIT, FUNCTION.
[6]	"Crystal structure of human kynurenine aminotransferase II." Han Q., Robinson H., Li J. J. Biol. Chem. 283:3567-3573(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH PYRIDOXAL PHOSPHATE AND KYRUNENINE, CATALYTIC ACTIVITY, COFACTOR, SUBUNIT.
[7]	"Crystal structure of human kynurenine aminotransferase II, a drug target for the treatment of schizophrenia." Rossi F., Garavaglia S., Montalbano V., Walsh M.A., Rizzi M. J. Biol. Chem. 283:3559-3566(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH PYRIDOXAL PHOSPHATE, SUBUNIT, COFACTOR.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF097994 mRNA. Translation: AAF04623.1.
AF481738 mRNA. Translation: AAM09683.1.
AK055952 mRNA. Translation: BAG51596.1.
BC031068 mRNA. Translation: AAH31068.1.

IPI

IPI00395929.
IPI00410702.

RefSeq

NP_057312.1. NM_016228.3.
NP_872603.1. NM_182662.1.

UniGene

Hs.529735.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2QLR	X-ray	2.30	A/B/C/D	1-425	[»]
2R2N	X-ray	1.95	A/B/C/D	1-425	[»]
2VGZ	X-ray	2.30	A/B	2-425	[»]
2XH1	X-ray	2.10	A/B	2-425	[»]
3DC1	X-ray	2.50	A/B/C/D	1-425	[»]
3UE8	X-ray	3.22	A/B	1-425	[»]
4GDY	X-ray	2.89	A/B	1-425	[»]
4GE4	X-ray	2.41	A/B	1-425	[»]
4GE7	X-ray	2.10	A/B	1-425	[»]
4GE9	X-ray	2.43	A/B/C/D	1-425	[»]

ProteinModelPortal

Q8N5Z0.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000226840.

PTM databases

PhosphoSite

Q8N5Z0.

Polymorphism databases

DMDM

46395904.

Proteomic databases

PaxDb

Q8N5Z0.

PRIDE

Q8N5Z0.

Protocols and materials databases

DNASU

51166.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000337664; ENSP00000336808; ENSG00000109576.
ENST00000353187; ENSP00000226840; ENSG00000109576.
ENST00000509167; ENSP00000423190; ENSG00000109576.
ENST00000515480; ENSP00000423341; ENSG00000109576.

GeneID

51166.

KEGG

hsa:51166.

UCSC

uc003isr.3. human.
uc003ist.3. human.

Organism-specific databases

CTD

51166.

GeneCards

GC04M170981.

HGNC

HGNC:17929. AADAT.

HPA

HPA037502.

MIM

611754. gene.

neXtProt

NX_Q8N5Z0.

PharmGKB

PA24364.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1167.

HOGENOM

HOG000223057.

HOVERGEN

HBG050429.

InParanoid

Q8N5Z0.

KO

K00825.

OMA

PFQSASI.

OrthoDB

EOG480HWQ.

PhylomeDB

Q8N5Z0.

Enzyme and pathway databases

BioCyc

MetaCyc:HS03239-MONOMER.

BRENDA

2.6.1.7. 2681.

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00868; UER00838.

Gene expression databases

ArrayExpress

Q8N5Z0.

Bgee

Q8N5Z0.

CleanEx

HS_AADAT.

Genevestigator

Q8N5Z0.

GermOnline

ENSG00000109576. Homo sapiens.

Family and domain databases

Gene3D

3.40.640.10. 1 hit.
3.90.1150.10. 1 hit.

InterPro

IPR004839. Aminotransferase_I/II.
IPR015424. PyrdxlP-dep_Trfase.
IPR015421. PyrdxlP-dep_Trfase_major_sub1.
IPR015422. PyrdxlP-dep_Trfase_major_sub2.
[Graphical view]

Pfam

PF00155. Aminotran_1_2. 1 hit.
[Graphical view]

SUPFAM

SSF53383. PyrdxlP-dep_Trfase_major. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

AADAT. human.

DrugBank

DB00142. L-Glutamic Acid.
DB00114. Pyridoxal Phosphate.

EvolutionaryTrace

Q8N5Z0.

GenomeRNAi

51166.

NextBio

54097.

SOURCE

Search...

Entry information

Entry name

AADAT_HUMAN

Accession

Primary (citable) accession number: Q8N5Z0
Secondary accession number(s): B3KP84, Q9UL02

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 13, 2004
Last sequence update:	April 13, 2004
Last modified:	May 1, 2013
This is version 99 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.