AATC_PIG
ID AATC_PIG Reviewed; 413 AA.
AC P00503;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Aspartate aminotransferase, cytoplasmic {ECO:0000250|UniProtKB:P17174};
DE Short=cAspAT;
DE EC=2.6.1.1 {ECO:0000269|PubMed:4634443};
DE EC=2.6.1.3 {ECO:0000269|PubMed:4634443};
DE AltName: Full=Cysteine aminotransferase, cytoplasmic;
DE AltName: Full=Cysteine transaminase, cytoplasmic;
DE Short=cCAT;
DE AltName: Full=Glutamate oxaloacetate transaminase 1;
DE AltName: Full=Transaminase A;
GN Name=GOT1 {ECO:0000250|UniProtKB:P17174};
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2653435; DOI=10.1021/bi00429a033;
RA Nagashima F., Tanase S., Fukumoto Y., Joh T., Nomiyama H., Tsuzuki T.,
RA Shimada K., Kuramitsu S., Kagamiyama H., Morino Y.;
RT "cDNA cloning and expression of pig cytosolic aspartate aminotransferase in
RT Escherichia coli: amino-terminal heterogeneity of expressed products and
RT lack of its correlation with enzyme function.";
RL Biochemistry 28:1153-1160(1989).
RN [2]
RP PROTEIN SEQUENCE OF 2-413.
RC TISSUE=Heart muscle;
RX PubMed=11946901; DOI=10.1016/0014-5793(73)80008-0;
RA Ovchinnikov Y.A., Egorov T.A., Aldanova N.A., Feigina M.Y., Lipkin V.M.,
RA Abdulaev N.G., Grishin E.V., Kiselev A.P., Modyanov N.N., Braunstein A.E.,
RA Polyanovsky O.L., Nosikov V.V.;
RT "The complete amino acid sequence of cytoplasmic aspartate aminotransferase
RT from pig heart.";
RL FEBS Lett. 29:31-34(1973).
RN [3]
RP PROTEIN SEQUENCE OF 2-413.
RA Ovchinnikov Y.A., Egorov T.A., Aldanova N.A., Feigina M.Y., Lipkin V.M.,
RA Abdulaev N.G., Grishin E.V., Kiselev A.P., Modyanov N.N., Braunstein A.E.,
RA Polyanovsky O.L., Nosikov V.V.;
RT "The complete primary structure of cytoplasmic aspartate amino-transferase
RT from pig heart muscle.";
RL Izv. Akad. Nauk SSSR, Ser. Khim. 1974:1189-1196(1974).
RN [4]
RP PROTEIN SEQUENCE OF 2-413.
RX PubMed=1239277; DOI=10.1042/bj1490497d;
RA Doonan S., Doonan H.J., Hanford R., Vernon C.A., Walker J.M., Airoldi L.P.,
RA Da S., Bossa F., Barra D., Carloni M., Fasella P., Riva F.;
RT "The primary structure of aspartate aminotransferase from pig heart muscle.
RT Digestion with a proteinase having specificity for lysine residues.";
RL Biochem. J. 149:497-506(1975).
RN [5]
RP CATALYTIC ACTIVITY.
RX PubMed=4634443; DOI=10.1016/0014-5793(72)80356-9;
RA Polyanovsky O.L., Demidkina T.V., Egorov C.A.;
RT "The position of an essential tyrosine residue in the polypeptide chain of
RT aspartate transaminase.";
RL FEBS Lett. 23:262-264(1972).
RN [6]
RP COFACTOR.
RX PubMed=5809231; DOI=10.1021/bi00836a041;
RA Morino Y., Watanabe T.;
RT "Primary structure of pyridoxal phosphate binding site in the mitochondrial
RT and extramitochondrial aspartate aminotransferases from pig heart muscle.
RT Chymotryptic peptides.";
RL Biochemistry 8:3412-3417(1969).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.74 ANGSTROMS) IN COMPLEX WITH PYRIDOXAL PHOSPHATE
RP AND 2-METHYLASPARTATE, COFACTOR, PYRIDOXAL PHOSPHATE AT LYS-259, AND
RP SUBUNIT.
RX PubMed=9211866; DOI=10.1074/jbc.272.28.17293;
RA Rhee S., Silva M.M., Hyde C.C., Rogers P.H., Metzler C.M., Metzler D.E.,
RA Arnone A.;
RT "Refinement and comparisons of the crystal structures of pig cytosolic
RT aspartate aminotransferase and its complex with 2-methylaspartate.";
RL J. Biol. Chem. 272:17293-17302(1997).
CC -!- FUNCTION: Biosynthesis of L-glutamate from L-aspartate or L-cysteine
CC (PubMed:4634443). Important regulator of levels of glutamate, the major
CC excitatory neurotransmitter of the vertebrate central nervous system.
CC Acts as a scavenger of glutamate in brain neuroprotection. The
CC aspartate aminotransferase activity is involved in hepatic glucose
CC synthesis during development and in adipocyte glyceroneogenesis. Using
CC L-cysteine as substrate, regulates levels of mercaptopyruvate, an
CC important source of hydrogen sulfide. Mercaptopyruvate is converted
CC into H(2)S via the action of 3-mercaptopyruvate sulfurtransferase
CC (3MST). Hydrogen sulfide is an important synaptic modulator and
CC neuroprotectant in the brain (By similarity).
CC {ECO:0000250|UniProtKB:P13221, ECO:0000269|PubMed:4634443}.
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:0000269|PubMed:4634443};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21825;
CC Evidence={ECO:0000250|UniProtKB:P13221};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + L-cysteine = 2-oxo-3-sulfanylpropanoate + L-
CC glutamate; Xref=Rhea:RHEA:17441, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:29985, ChEBI:CHEBI:35235, ChEBI:CHEBI:57678; EC=2.6.1.3;
CC Evidence={ECO:0000269|PubMed:4634443};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17442;
CC Evidence={ECO:0000250|UniProtKB:P13221};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2S)-2-aminobutanoate + 2-oxoglutarate = 2-oxobutanoate + L-
CC glutamate; Xref=Rhea:RHEA:70223, ChEBI:CHEBI:16763,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:29985, ChEBI:CHEBI:74359;
CC Evidence={ECO:0000250|UniProtKB:P17174};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70225;
CC Evidence={ECO:0000250|UniProtKB:P17174};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + 3-sulfino-L-alanine = 3-sulfinopyruvate + L-
CC glutamate; Xref=Rhea:RHEA:70295, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:29985, ChEBI:CHEBI:61085, ChEBI:CHEBI:140699;
CC Evidence={ECO:0000250|UniProtKB:P13221};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70297;
CC Evidence={ECO:0000250|UniProtKB:P13221};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:5809231, ECO:0000269|PubMed:9211866};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:9211866}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
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}.
CC -!- WEB RESOURCE: Name=Worthington enzyme manual;
CC URL="https://www.worthington-biochem.com/CGOT/";
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DR EMBL; M24088; AAA53531.1; -; mRNA.
DR PIR; A30138; XNPGDC.
DR RefSeq; NP_999092.1; NM_213927.1.
DR PDB; 1AJR; X-ray; 1.74 A; A/B=2-413.
DR PDB; 1AJS; X-ray; 1.60 A; A/B=2-413.
DR PDB; 5TON; X-ray; 1.40 A; A/B=1-413.
DR PDB; 5TOQ; X-ray; 1.20 A; A/B=1-413.
DR PDB; 5TOR; X-ray; 1.35 A; A/B=1-413.
DR PDB; 5TOT; X-ray; 1.40 A; A/B=1-413.
DR PDB; 5VJZ; Other; 2.00 A; A/B=2-413.
DR PDB; 5VK7; X-ray; 1.90 A; A/B=1-413.
DR PDBsum; 1AJR; -.
DR PDBsum; 1AJS; -.
DR PDBsum; 5TON; -.
DR PDBsum; 5TOQ; -.
DR PDBsum; 5TOR; -.
DR PDBsum; 5TOT; -.
DR PDBsum; 5VJZ; -.
DR PDBsum; 5VK7; -.
DR AlphaFoldDB; P00503; -.
DR SMR; P00503; -.
DR STRING; 9823.ENSSSCP00000011226; -.
DR PaxDb; P00503; -.
DR PeptideAtlas; P00503; -.
DR PRIDE; P00503; -.
DR Ensembl; ENSSSCT00000011527; ENSSSCP00000011226; ENSSSCG00000010537.
DR Ensembl; ENSSSCT00005040048; ENSSSCP00005024514; ENSSSCG00005025160.
DR Ensembl; ENSSSCT00015097909; ENSSSCP00015040239; ENSSSCG00015072790.
DR Ensembl; ENSSSCT00025106177; ENSSSCP00025047612; ENSSSCG00025076609.
DR Ensembl; ENSSSCT00035082758; ENSSSCP00035034354; ENSSSCG00035061591.
DR Ensembl; ENSSSCT00040089752; ENSSSCP00040039448; ENSSSCG00040065637.
DR Ensembl; ENSSSCT00045036363; ENSSSCP00045025297; ENSSSCG00045021280.
DR Ensembl; ENSSSCT00050071860; ENSSSCP00050030901; ENSSSCG00050052766.
DR Ensembl; ENSSSCT00055003685; ENSSSCP00055002814; ENSSSCG00055001970.
DR Ensembl; ENSSSCT00060059202; ENSSSCP00060025356; ENSSSCG00060043652.
DR Ensembl; ENSSSCT00065098926; ENSSSCP00065043393; ENSSSCG00065071886.
DR Ensembl; ENSSSCT00070028254; ENSSSCP00070023534; ENSSSCG00070014407.
DR GeneID; 396967; -.
DR KEGG; ssc:396967; -.
DR CTD; 2805; -.
DR VGNC; VGNC:88561; GOT1.
DR eggNOG; KOG1412; Eukaryota.
DR GeneTree; ENSGT00950000183082; -.
DR HOGENOM; CLU_032440_1_2_1; -.
DR InParanoid; P00503; -.
DR OMA; WDQNKRQ; -.
DR OrthoDB; 1104596at2759; -.
DR TreeFam; TF314089; -.
DR BioCyc; MetaCyc:MON-13031; -.
DR BRENDA; 2.6.1.1; 6170.
DR Reactome; R-SSC-70263; Gluconeogenesis.
DR Reactome; R-SSC-8963693; Aspartate and asparagine metabolism.
DR SABIO-RK; P00503; -.
DR EvolutionaryTrace; P00503; -.
DR Proteomes; UP000008227; Chromosome 14.
DR Proteomes; UP000314985; Chromosome 14.
DR Bgee; ENSSSCG00000010537; Expressed in psoas major muscle and 44 other tissues.
DR ExpressionAtlas; P00503; baseline.
DR Genevisible; P00503; SS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0004069; F:L-aspartate:2-oxoglutarate aminotransferase activity; ISS:UniProtKB.
DR GO; GO:0047801; F:L-cysteine transaminase activity; ISS:UniProtKB.
DR GO; GO:0004609; F:phosphatidylserine decarboxylase activity; IEA:Ensembl.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0006103; P:2-oxoglutarate metabolic process; ISS:UniProtKB.
DR GO; GO:0006532; P:aspartate biosynthetic process; IBA:GO_Central.
DR GO; GO:0006533; P:aspartate catabolic process; IEA:Ensembl.
DR GO; GO:0006531; P:aspartate metabolic process; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0055089; P:fatty acid homeostasis; IEA:Ensembl.
DR GO; GO:0019551; P:glutamate catabolic process to 2-oxoglutarate; IEA:Ensembl.
DR GO; GO:0019550; P:glutamate catabolic process to aspartate; IEA:Ensembl.
DR GO; GO:0006536; P:glutamate metabolic process; ISS:UniProtKB.
DR GO; GO:0006114; P:glycerol biosynthetic process; ISS:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0006107; P:oxaloacetate metabolic process; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
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 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis; Aminotransferase; Cytoplasm;
KW Direct protein sequencing; Pyridoxal phosphate; Reference proteome;
KW Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:11946901,
FT ECO:0000269|PubMed:1239277, ECO:0000269|Ref.3"
FT CHAIN 2..413
FT /note="Aspartate aminotransferase, cytoplasmic"
FT /id="PRO_0000123881"
FT BINDING 39
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT BINDING 141
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT BINDING 195
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT BINDING 387
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT MOD_RES 259
FT /note="N6-(pyridoxal phosphate)lysine"
FT CONFLICT 145
FT /note="N -> D (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT TURN 6..9
FT /evidence="ECO:0007829|PDB:5TOQ"
FT HELIX 17..27
FT /evidence="ECO:0007829|PDB:5TOQ"
FT HELIX 52..62
FT /evidence="ECO:0007829|PDB:5TOQ"
FT HELIX 78..89
FT /evidence="ECO:0007829|PDB:5TOQ"
FT HELIX 94..97
FT /evidence="ECO:0007829|PDB:5TOQ"
FT STRAND 101..107
FT /evidence="ECO:0007829|PDB:5TOQ"
FT HELIX 108..123
FT /evidence="ECO:0007829|PDB:5TOQ"
FT STRAND 124..128
FT /evidence="ECO:0007829|PDB:5TOQ"
FT STRAND 134..139
FT /evidence="ECO:0007829|PDB:5TOQ"
FT HELIX 144..150
FT /evidence="ECO:0007829|PDB:5TOQ"
FT STRAND 156..160
FT /evidence="ECO:0007829|PDB:5TOQ"
FT TURN 164..167
FT /evidence="ECO:0007829|PDB:5TOQ"
FT HELIX 171..179
FT /evidence="ECO:0007829|PDB:5TOQ"
FT STRAND 186..190
FT /evidence="ECO:0007829|PDB:5TOQ"
FT TURN 195..197
FT /evidence="ECO:0007829|PDB:5TOQ"
FT HELIX 203..216
FT /evidence="ECO:0007829|PDB:5TOQ"
FT STRAND 219..225
FT /evidence="ECO:0007829|PDB:5TOQ"
FT TURN 227..231
FT /evidence="ECO:0007829|PDB:5TOQ"
FT HELIX 234..237
FT /evidence="ECO:0007829|PDB:5TOQ"
FT HELIX 239..246
FT /evidence="ECO:0007829|PDB:5TOQ"
FT STRAND 251..256
FT /evidence="ECO:0007829|PDB:5TOQ"
FT TURN 258..260
FT /evidence="ECO:0007829|PDB:1AJS"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:5TOQ"
FT STRAND 268..274
FT /evidence="ECO:0007829|PDB:5TOQ"
FT HELIX 278..293
FT /evidence="ECO:0007829|PDB:5TOQ"
FT TURN 294..296
FT /evidence="ECO:0007829|PDB:5TOQ"
FT HELIX 302..311
FT /evidence="ECO:0007829|PDB:5TOQ"
FT HELIX 314..344
FT /evidence="ECO:0007829|PDB:5TOQ"
FT HELIX 353..356
FT /evidence="ECO:0007829|PDB:5TOQ"
FT STRAND 359..363
FT /evidence="ECO:0007829|PDB:5TOQ"
FT HELIX 368..378
FT /evidence="ECO:0007829|PDB:5TOQ"
FT STRAND 387..389
FT /evidence="ECO:0007829|PDB:5TOQ"
FT HELIX 390..392
FT /evidence="ECO:0007829|PDB:5TOQ"
FT TURN 395..397
FT /evidence="ECO:0007829|PDB:5TOQ"
FT HELIX 398..411
FT /evidence="ECO:0007829|PDB:5TOQ"
SQ SEQUENCE 413 AA; 46475 MW; E466EDAD9446EF25 CRC64;
MAPPSVFAEV PQAQPVLVFK LIADFREDPD PRKVNLGVGA YRTDDCQPWV LPVVRKVEQR
IANDSSLNHE YLPILGLAEF RTCASRLALG DDSPALQEKR VGGVQSLGGT GALRIGAEFL
ARWYNGTNNK DTPVYVSSPT WENHNGVFTT AGFKDIRSYR YWDTEKRGLD LQGFLSDLEN
APEFSIFVLH ACAHNPTGTD PTPEQWKQIA SVMKRRFLFP FFDSAYQGFA SGNLEKDAWA
IRYFVSEGFE LFCAQSFSKN FGLYNERVGN LTVVAKEPDS ILRVLSQMEK IVRVTWSNPP
AQGARIVART LSDPELFHEW TGNVKTMADR ILSMRSELRA RLEALKTPGT WNHITDQIGM
FSFTGLNPKQ VEYLINEKHI YLLPSGRINM CGLTTKNLDY VATSIHEAVT KIQ
