AATM_DANRE
ID AATM_DANRE Reviewed; 428 AA.
AC Q7SYK7;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Aspartate aminotransferase, mitochondrial {ECO:0000250|UniProtKB:P00505};
DE Short=mAspAT;
DE EC=2.6.1.1 {ECO:0000250|UniProtKB:P00505};
DE EC=2.6.1.7 {ECO:0000250|UniProtKB:P00505};
DE AltName: Full=Glutamate oxaloacetate transaminase 2a {ECO:0000250|UniProtKB:P00505};
DE AltName: Full=Glutamic-oxaloacetic transaminase 2a, mitochondrial {ECO:0000312|ZFIN:ZDB-GENE-040426-2703};
DE AltName: Full=Kynurenine aminotransferase 4 {ECO:0000250|UniProtKB:P00505};
DE AltName: Full=Kynurenine aminotransferase IV {ECO:0000250|UniProtKB:P00505};
DE AltName: Full=Kynurenine--oxoglutarate transaminase 4 {ECO:0000250|UniProtKB:P00505};
DE AltName: Full=Kynurenine--oxoglutarate transaminase IV {ECO:0000250|UniProtKB:P00505};
DE AltName: Full=Transaminase A {ECO:0000250|UniProtKB:P00505};
DE Flags: Precursor;
GN Name=got2a {ECO:0000312|ZFIN:ZDB-GENE-040426-2703};
GN Synonyms=got2 {ECO:0000312|ZFIN:ZDB-GENE-040426-2703};
GN ORFNames=zgc:66329 {ECO:0000312|ZFIN:ZDB-GENE-040426-2703};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=31422819; DOI=10.1016/j.ajhg.2019.07.015;
RA van Karnebeek C.D.M., Ramos R.J., Wen X.Y., Tarailo-Graovac M.,
RA Gleeson J.G., Skrypnyk C., Brand-Arzamendi K., Karbassi F., Issa M.Y.,
RA van der Lee R., Droegemoeller B.I., Koster J., Rousseau J., Campeau P.M.,
RA Wang Y., Cao F., Li M., Ruiter J., Ciapaite J., Kluijtmans L.A.J.,
RA Willemsen M.A.A.P., Jans J.J., Ross C.J., Wintjes L.T., Rodenburg R.J.,
RA Huigen M.C.D.G., Jia Z., Waterham H.R., Wasserman W.W., Wanders R.J.A.,
RA Verhoeven-Duif N.M., Zaki M.S., Wevers R.A.;
RT "Bi-allelic GOT2 mutations cause a treatable malate-aspartate shuttle-
RT related encephalopathy.";
RL Am. J. Hum. Genet. 105:534-548(2019).
CC -!- FUNCTION: Catalyzes the irreversible transamination of the L-tryptophan
CC metabolite L-kynurenine to form kynurenic acid (KA). As a member of the
CC malate-aspartate shuttle, it has a key role in the intracellular NAD(H)
CC redox balance. Is important for metabolite exchange between
CC mitochondria and cytosol, and for amino acid metabolism.
CC {ECO:0000250|UniProtKB:P00505}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + L-aspartate = L-glutamate + oxaloacetate;
CC Xref=Rhea:RHEA:21824, ChEBI:CHEBI:16452, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:29985, ChEBI:CHEBI:29991; EC=2.6.1.1;
CC Evidence={ECO:0000250|UniProtKB:P00505};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + L-kynurenine = H2O + kynurenate + L-
CC glutamate; Xref=Rhea:RHEA:65560, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:29985, ChEBI:CHEBI:57959,
CC ChEBI:CHEBI:58454; EC=2.6.1.7;
CC Evidence={ECO:0000250|UniProtKB:P00505};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250|UniProtKB:P00505};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P00505}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:P00505}. Cell membrane
CC {ECO:0000250|UniProtKB:P00505}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein results in
CC brain developmental defects. Morphants show a small head and seizure-
CC like electroencephalography spikes. Additional defects include slow
CC circulation, bend body and pericardial edema.
CC {ECO:0000269|PubMed:31422819}.
CC -!- MISCELLANEOUS: In eukaryotes there are cytoplasmic, mitochondrial and
CC chloroplastic isozymes.
CC -!- SIMILARITY: Belongs to the class-I pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000305}.
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DR EMBL; BX548052; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX571884; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC054684; AAH54684.1; -; mRNA.
DR EMBL; BC165803; AAI65803.1; -; mRNA.
DR RefSeq; NP_998544.1; NM_213379.1.
DR AlphaFoldDB; Q7SYK7; -.
DR SMR; Q7SYK7; -.
DR STRING; 7955.ENSDARP00000060165; -.
DR PaxDb; Q7SYK7; -.
DR PRIDE; Q7SYK7; -.
DR Ensembl; ENSDART00000060166; ENSDARP00000060165; ENSDARG00000041068.
DR Ensembl; ENSDART00000180639; ENSDARP00000149137; ENSDARG00000114282.
DR GeneID; 406688; -.
DR KEGG; dre:406688; -.
DR CTD; 406688; -.
DR ZFIN; ZDB-GENE-040426-2703; got2a.
DR eggNOG; KOG1411; Eukaryota.
DR GeneTree; ENSGT00950000183082; -.
DR HOGENOM; CLU_032440_1_0_1; -.
DR InParanoid; Q7SYK7; -.
DR OMA; QLKKQWY; -.
DR OrthoDB; 1104596at2759; -.
DR PhylomeDB; Q7SYK7; -.
DR TreeFam; TF300641; -.
DR Reactome; R-DRE-389661; Glyoxylate metabolism and glycine degradation.
DR Reactome; R-DRE-70263; Gluconeogenesis.
DR Reactome; R-DRE-8963693; Aspartate and asparagine metabolism.
DR Reactome; R-DRE-8964539; Glutamate and glutamine metabolism.
DR PRO; PR:Q7SYK7; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 18.
DR Bgee; ENSDARG00000041068; Expressed in cardiac ventricle and 26 other tissues.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016212; F:kynurenine-oxoglutarate transaminase activity; IEA:UniProtKB-EC.
DR GO; GO:0004069; F:L-aspartate:2-oxoglutarate aminotransferase activity; IBA:GO_Central.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0006533; P:aspartate catabolic process; IBA:GO_Central.
DR GO; GO:0009058; P:biosynthetic process; IEA:InterPro.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR004839; Aminotransferase_I/II.
DR InterPro; IPR000796; Asp_trans.
DR InterPro; IPR004838; NHTrfase_class1_PyrdxlP-BS.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR PANTHER; PTHR11879; PTHR11879; 1.
DR Pfam; PF00155; Aminotran_1_2; 1.
DR PRINTS; PR00799; TRANSAMINASE.
DR SUPFAM; SSF53383; SSF53383; 1.
DR PROSITE; PS00105; AA_TRANSFER_CLASS_1; 1.
PE 2: Evidence at transcript level;
KW Aminotransferase; Cell membrane; Membrane; Mitochondrion;
KW Pyridoxal phosphate; Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..27
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P00505"
FT CHAIN 28..428
FT /note="Aspartate aminotransferase, mitochondrial"
FT /id="PRO_0000450123"
FT BINDING 63
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q28F67"
FT BINDING 160
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q28F67"
FT BINDING 213
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q28F67"
FT BINDING 405
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q28F67"
FT MOD_RES 277
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:Q28F67"
SQ SEQUENCE 428 AA; 47587 MW; 7C5F9553620B4278 CRC64;
MALFKSSKIL SSVGSQTPVL AVLQLRASSW WTEVQMGPPD PILGVTEAFK RDTNPKKMNL
GVGAYRDDQG KPFVLSSVRK AEAQIAAKKL DKEYLPIGGL ADFSKACVQL ALGPDNEVLK
SGRSITVQTI SGTGSLRIGA NFVSRFHNAS RDVYLPKPSW GNHTPVFRDA GMQLKAYTYY
EPKTCGFNLK GALDDISKIP EKSVILLHAC AHNPTGVDPR PEQWKEMAAL IKKRNLLVFF
DMAYQGFASG DIDRDAWAVR YFIEQGHNIL LSQSFAKNMG LYGERVGGFT VVCKDAEEAK
RVESQLKILI RPIYSNPPMN GARIAATILN TPELYKEWLQ EVKGMADRII RMREMLVSNL
KKEGSTHNWQ HVTDQIGMFC FTGLKPEQVE RLINEFSIYM TKDGRISVAG VTSANVEYLA
HAIHAVTK
