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Q8N5Z0 (AADAT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length425 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 componentMitochondrion
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransit peptide
   LigandPyridoxal phosphate
   Molecular functionAminotransferase
Transferase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_process2-oxoglutarate metabolic process

Inferred from direct assay Ref.5. Source: UniProtKB

L-kynurenine metabolic process

Inferred from direct assay Ref.5. Source: GOC

L-lysine catabolic process to acetyl-CoA via saccharopine

Inferred from electronic annotation. Source: UniProtKB-UniPathway

biosynthetic process

Inferred from electronic annotation. Source: InterPro

cellular nitrogen compound metabolic process

Traceable author statement. Source: Reactome

glutamate metabolic process

Inferred from direct assay Ref.5. Source: UniProtKB

kynurenine metabolic process

Inferred from direct assay Ref.5. Source: UniProtKB

lysine catabolic process

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

tryptophan catabolic process

Traceable author statement. Source: Reactome

tryptophan catabolic process to kynurenine

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentmitochondrial matrix

Traceable author statement. Source: Reactome

   Molecular_function2-aminoadipate transaminase activity

Inferred from direct assay Ref.5. Source: UniProtKB

kynurenine-oxoglutarate transaminase activity

Inferred from direct assay Ref.5. Source: UniProtKB

protein homodimerization activity

Inferred from physical interaction Ref.5. Source: UniProtKB

pyridoxal phosphate binding

Inferred from electronic annotation. Source: Ensembl

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2929Mitochondrion Potential
Chain30 – 425396Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial
PRO_0000020602

Sites

Binding site201Substrate
Binding site741Substrate
Binding site1421Substrate
Binding site2021Substrate
Binding site3991Substrate

Amino acid modifications

Modified residue691N6-acetyllysine By similarity
Modified residue1791N6-acetyllysine By similarity
Modified residue2631N6-(pyridoxal phosphate)lysine; alternate
Modified residue2631N6-acetyllysine; alternate By similarity
Modified residue2631N6-succinyllysine; alternate By similarity
Modified residue3391N6-acetyllysine; alternate By similarity
Modified residue3391N6-succinyllysine; alternate By similarity
Modified residue3671N6-acetyllysine; alternate By similarity
Modified residue3671N6-succinyllysine; alternate By similarity
Modified residue4221N6-acetyllysine By similarity

Natural variations

Alternative sequence231T → SEKRA in isoform 2.
VSP_009874
Natural variant2431V → I.
Corresponds to variant rs56350236 [ dbSNP | Ensembl ].
VAR_061005

Experimental info

Sequence conflict1031P → Q in AAH31068. Ref.4
Sequence conflict3801L → S in BAG51596. Ref.3

Secondary structure

.................................................................................... 425
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 13, 2004. Version 2.
Checksum: 448CCAAB2173A7BA

FASTA42547,352
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 0C5A6E51F1BD6F53
Show »

FASTA42947,822

References

« Hide '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. expand/collapse author list , 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.
RefSeqNP_001273611.1. NM_001286682.1.
NP_001273612.1. NM_001286683.1.
NP_057312.1. NM_016228.3.
NP_872603.1. NM_182662.1.
UniGeneHs.529735.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2QLRX-ray2.30A/B/C/D1-425[»]
2R2NX-ray1.95A/B/C/D1-425[»]
2VGZX-ray2.30A/B2-425[»]
2XH1X-ray2.10A/B2-425[»]
3DC1X-ray2.50A/B/C/D1-425[»]
3UE8X-ray3.22A/B1-425[»]
4GDYX-ray2.89A/B1-425[»]
4GE4X-ray2.41A/B1-425[»]
4GE7X-ray2.10A/B1-425[»]
4GE9X-ray2.43A/B/C/D1-425[»]
4GEBX-ray2.15A/B1-425[»]
ProteinModelPortalQ8N5Z0.
SMRQ8N5Z0. Positions 1-425.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000226840.

Chemistry

ChEMBLCHEMBL2046259.
DrugBankDB00142. L-Glutamic Acid.
DB00114. Pyridoxal Phosphate.

PTM databases

PhosphoSiteQ8N5Z0.

Polymorphism databases

DMDM46395904.

Proteomic databases

PaxDbQ8N5Z0.
PRIDEQ8N5Z0.

Protocols and materials databases

DNASU51166.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000337664; ENSP00000336808; ENSG00000109576. [Q8N5Z0-1]
ENST00000353187; ENSP00000226840; ENSG00000109576. [Q8N5Z0-1]
ENST00000509167; ENSP00000423190; ENSG00000109576. [Q8N5Z0-2]
ENST00000515480; ENSP00000423341; ENSG00000109576. [Q8N5Z0-1]
GeneID51166.
KEGGhsa:51166.
UCSCuc003isr.3. human. [Q8N5Z0-1]
uc003ist.3. human. [Q8N5Z0-2]

Organism-specific databases

CTD51166.
GeneCardsGC04M170981.
HGNCHGNC:17929. AADAT.
HPAHPA037502.
MIM611754. gene.
neXtProtNX_Q8N5Z0.
PharmGKBPA24364.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1167.
HOGENOMHOG000223057.
HOVERGENHBG050429.
InParanoidQ8N5Z0.
KOK00825.
OMANTFPFQS.
OrthoDBEOG7ZKSBF.
PhylomeDBQ8N5Z0.
TreeFamTF328598.

Enzyme and pathway databases

BioCycMetaCyc:HS03239-MONOMER.
BRENDA2.6.1.7. 2681.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00868; UER00838.

Gene expression databases

ArrayExpressQ8N5Z0.
BgeeQ8N5Z0.
CleanExHS_AADAT.
GenevestigatorQ8N5Z0.

Family and domain databases

Gene3D3.40.640.10. 1 hit.
3.90.1150.10. 1 hit.
InterProIPR004839. Aminotransferase_I/II.
IPR015424. PyrdxlP-dep_Trfase.
IPR015421. PyrdxlP-dep_Trfase_major_sub1.
IPR015422. PyrdxlP-dep_Trfase_major_sub2.
[Graphical view]
PfamPF00155. Aminotran_1_2. 1 hit.
[Graphical view]
SUPFAMSSF53383. SSF53383. 1 hit.
ProtoNetSearch...

Other

ChiTaRSAADAT. human.
EvolutionaryTraceQ8N5Z0.
GenomeRNAi51166.
NextBio54097.
PROQ8N5Z0.
SOURCESearch...

Entry information

Entry nameAADAT_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM