Full text data of GOT1
GOT1
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Aspartate aminotransferase, cytoplasmic; cAspAT; 2.6.1.1; 2.6.1.3 (Cysteine aminotransferase, cytoplasmic; Cysteine transaminase, cytoplasmic; cCAT; Glutamate oxaloacetate transaminase 1; Transaminase A)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Aspartate aminotransferase, cytoplasmic; cAspAT; 2.6.1.1; 2.6.1.3 (Cysteine aminotransferase, cytoplasmic; Cysteine transaminase, cytoplasmic; cCAT; Glutamate oxaloacetate transaminase 1; Transaminase A)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00219029
IPI00219029 Aspartate Aminotransferase 1 aspartate catabolism, L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00219029 Aspartate Aminotransferase 1 aspartate catabolism, L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P17174
ID AATC_HUMAN Reviewed; 413 AA.
AC P17174; B2R6R7; Q5VW80;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 143.
DE RecName: Full=Aspartate aminotransferase, cytoplasmic;
DE Short=cAspAT;
DE EC=2.6.1.1;
DE EC=2.6.1.3;
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;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
RC TISSUE=Liver;
RX PubMed=1974457; DOI=10.1021/bi00474a011;
RA Bousquet-Lemercier B., Pol S., Pave-Preux M., Hanoune J., Barouki R.;
RT "Properties of human liver cytosolic aspartate aminotransferase mRNAs
RT generated by alternative polyadenylation site selection.";
RL Biochemistry 29:5293-5299(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Wang C.Y., Huang Y.Q., Shi J.D., Marron M.P., Ruan Q.G.,
RA Hawkins-Lee B., Ochoa B., She J.X.;
RT "Genomic structure and mutation analysis of GOT1 in the urofacial
RT (Ochoa) syndrome gene critical region on chromosome 10.";
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Yu W., Sarginson J., Gibbs R.A.;
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 2-413.
RC TISSUE=Liver;
RX PubMed=2241899;
RA Doyle J.M., Schinina M.E., Bossa F., Doonan S.;
RT "The amino acid sequence of cytosolic aspartate aminotransferase from
RT human liver.";
RL Biochem. J. 270:651-657(1990).
RN [9]
RP FUNCTION.
RX PubMed=16039064; DOI=10.1016/j.neulet.2005.06.030;
RA D'Aniello A., Fisher G., Migliaccio N., Cammisa G., D'Aniello E.,
RA Spinelli P.;
RT "Amino acids and transaminases activity in ventricular CSF and in
RT brain of normal and Alzheimer patients.";
RL Neurosci. Lett. 388:49-53(2005).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP INVOLVEMENT IN ASTQTL1, VARIANT ASN-389 DEL, AND CHARACTERIZATION OF
RP VARIANT ASN-389 DEL.
RX PubMed=21900944; DOI=10.1038/jhg.2011.105;
RA Shen H., Damcott C., Shuldiner S.R., Chai S., Yang R., Hu H.,
RA Gibson Q., Ryan K.A., Mitchell B.D., Gong D.W.;
RT "Genome-wide association study identifies genetic variants in GOT1
RT determining serum aspartate aminotransferase levels.";
RL J. Hum. Genet. 56:801-805(2011).
RN [12]
RP FETAL BLOOD LEVELS.
RX PubMed=22633534; DOI=10.1016/j.earlhumdev.2012.05.001;
RA Zlotnik A., Tsesis S., Gruenbaum B.F., Ohayon S., Gruenbaum S.E.,
RA Boyko M., Sheiner E., Brotfain E., Shapira Y., Teichberg V.I.;
RT "Relationship between glutamate, GOT and GPT levels in maternal and
RT fetal blood: a potential mechanism for fetal neuroprotection.";
RL Early Hum. Dev. 88:773-778(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 14-412 IN COMPLEX WITH
RP PYRIDOXAL PHOSPHATE AND TARTARIC ACID, SUBUNIT, AND PYRIDOXAL
RP PHOSPHATE AT LYS-259.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human glutamate oxaloacetate transaminase 1
RT (GOT1).";
RL Submitted (AUG-2009) to the PDB data bank.
CC -!- FUNCTION: Biosynthesis of L-glutamate from L-aspartate or L-
CC cysteine. Important regulator of levels of glutamate, the major
CC excitatory neurotransmitter of the vertebrate central nervous
CC system. Acts as a scavenger of glutamate in brain neuroprotection.
CC The aspartate aminotransferase activity is involved in hepatic
CC glucose synthesis during development and in adipocyte
CC glyceroneogenesis. Using L-cysteine as substrate, regulates levels
CC of mercaptopyruvate, an important source of hydrogen sulfide.
CC Mercaptopyruvate is converted into H(2)S via the action of 3-
CC mercaptopyruvate sulfurtransferase (3MST). Hydrogen sulfide is an
CC important synaptic modulator and neuroprotectant in the brain.
CC -!- CATALYTIC ACTIVITY: L-aspartate + 2-oxoglutarate = oxaloacetate +
CC L-glutamate.
CC -!- CATALYTIC ACTIVITY: L-cysteine + 2-oxoglutarate = mercaptopyruvate
CC + L-glutamate.
CC -!- COFACTOR: Pyridoxal phosphate.
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- POLYMORPHISM: Genetic variations in GOT1 are associated with low
CC serum aspartate aminotransferase and define the aspartate
CC aminotransferase serum level quantitative trait locus 1 (ASTQTL1)
CC [MIM:614419].
CC -!- MISCELLANEOUS: In eukaryotes there are cytoplasmic, mitochondrial
CC and chloroplastic isozymes.
CC -!- MISCELLANEOUS: Aspartate aminotransferase activity found to be
CC increased in cerebral spinal fluid (CSF) of patients with
CC Alzheimer disease (PubMed:16039064). Fetal serum levels of the
CC enzyme in the umbilical artery and vein are found to be
CC significantly higher than maternal serum levels (PubMed:22633534).
CC -!- SIMILARITY: Belongs to the class-I pyridoxal-phosphate-dependent
CC aminotransferase family.
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DR EMBL; M37400; AAA35563.1; -; mRNA.
DR EMBL; AF080467; AAC32851.1; -; Genomic_DNA.
DR EMBL; AF080459; AAC32851.1; JOINED; Genomic_DNA.
DR EMBL; AF080460; AAC32851.1; JOINED; Genomic_DNA.
DR EMBL; AF080461; AAC32851.1; JOINED; Genomic_DNA.
DR EMBL; AF080462; AAC32851.1; JOINED; Genomic_DNA.
DR EMBL; AF080463; AAC32851.1; JOINED; Genomic_DNA.
DR EMBL; AF080464; AAC32851.1; JOINED; Genomic_DNA.
DR EMBL; AF080465; AAC32851.1; JOINED; Genomic_DNA.
DR EMBL; AF080466; AAC32851.1; JOINED; Genomic_DNA.
DR EMBL; AF052153; AAC28622.1; -; mRNA.
DR EMBL; AK312684; BAG35564.1; -; mRNA.
DR EMBL; AL391684; CAH73859.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49869.1; -; Genomic_DNA.
DR EMBL; BC000498; AAH00498.1; -; mRNA.
DR PIR; S13035; S13035.
DR PIR; S29027; S29027.
DR RefSeq; NP_002070.1; NM_002079.2.
DR UniGene; Hs.500756; -.
DR PDB; 3II0; X-ray; 2.05 A; A/B/C/D=14-412.
DR PDBsum; 3II0; -.
DR ProteinModelPortal; P17174; -.
DR SMR; P17174; 14-412.
DR IntAct; P17174; 3.
DR MINT; MINT-5002473; -.
DR STRING; 9606.ENSP00000359539; -.
DR ChEMBL; CHEMBL2189139; -.
DR DrugBank; DB00128; L-Aspartic Acid.
DR DrugBank; DB00151; L-Cysteine.
DR DrugBank; DB00142; L-Glutamic Acid.
DR DrugBank; DB00114; Pyridoxal Phosphate.
DR PhosphoSite; P17174; -.
DR DMDM; 5902703; -.
DR REPRODUCTION-2DPAGE; IPI00219029; -.
DR UCD-2DPAGE; P17174; -.
DR PaxDb; P17174; -.
DR PeptideAtlas; P17174; -.
DR PRIDE; P17174; -.
DR Ensembl; ENST00000370508; ENSP00000359539; ENSG00000120053.
DR GeneID; 2805; -.
DR KEGG; hsa:2805; -.
DR UCSC; uc001kpr.3; human.
DR CTD; 2805; -.
DR GeneCards; GC10M101146; -.
DR HGNC; HGNC:4432; GOT1.
DR MIM; 138180; gene.
DR MIM; 614419; phenotype.
DR neXtProt; NX_P17174; -.
DR PharmGKB; PA28817; -.
DR eggNOG; COG1448; -.
DR HOGENOM; HOG000185898; -.
DR HOVERGEN; HBG000951; -.
DR InParanoid; P17174; -.
DR KO; K14454; -.
DR OMA; SWENHRV; -.
DR PhylomeDB; P17174; -.
DR BioCyc; MetaCyc:HS04361-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P17174; -.
DR ChiTaRS; GOT1; human.
DR EvolutionaryTrace; P17174; -.
DR GeneWiki; GOT1; -.
DR GenomeRNAi; 2805; -.
DR NextBio; 11057; -.
DR PRO; PR:P17174; -.
DR ArrayExpress; P17174; -.
DR Bgee; P17174; -.
DR CleanEx; HS_GOT1; -.
DR Genevestigator; P17174; -.
DR GO; GO:0043679; C:axon terminus; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005764; C:lysosome; IEA:Ensembl.
DR GO; GO:0031406; F:carboxylic acid binding; IEA:Ensembl.
DR GO; GO:0004069; F:L-aspartate:2-oxoglutarate aminotransferase activity; IDA:UniProtKB.
DR GO; GO:0047801; F:L-cysteine:2-oxoglutarate aminotransferase activity; ISS:UniProtKB.
DR GO; GO:0080130; F:L-phenylalanine:2-oxoglutarate aminotransferase activity; IEA:UniProtKB-EC.
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; IEA:Ensembl.
DR GO; GO:0006533; P:aspartate catabolic process; IDA:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:UniProtKB.
DR GO; GO:0055089; P:fatty acid homeostasis; IEA:Ensembl.
DR GO; GO:0006094; P:gluconeogenesis; TAS:Reactome.
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:0019509; P:L-methionine salvage from methylthioadenosine; TAS:Reactome.
DR GO; GO:0006107; P:oxaloacetate metabolic process; IEA:Ensembl.
DR GO; GO:0006595; P:polyamine metabolic process; TAS:Reactome.
DR GO; GO:0051384; P:response to glucocorticoid stimulus; IEP:UniProtKB.
DR Gene3D; 3.40.640.10; -; 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_sub1.
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;
KW Complete proteome; Cytoplasm; Direct protein sequencing; Polymorphism;
KW Pyridoxal phosphate; Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 413 Aspartate aminotransferase, cytoplasmic.
FT /FTId=PRO_0000123879.
FT BINDING 39 39 Aspartate; via amide nitrogen.
FT BINDING 141 141 Aspartate.
FT BINDING 195 195 Aspartate.
FT BINDING 387 387 Aspartate.
FT MOD_RES 259 259 N6-(pyridoxal phosphate)lysine (By
FT similarity).
FT VARIANT 389 389 Missing (results in markedly diminished
FT enzymatic activity).
FT /FTId=VAR_067256.
FT CONFLICT 215 215 H -> R (in Ref. 8; AA sequence).
FT HELIX 17 27
FT HELIX 52 62
FT HELIX 78 89
FT HELIX 94 97
FT STRAND 101 107
FT HELIX 108 123
FT STRAND 124 128
FT STRAND 134 139
FT HELIX 143 150
FT STRAND 156 160
FT TURN 164 167
FT HELIX 171 179
FT STRAND 186 190
FT TURN 195 197
FT HELIX 203 216
FT STRAND 219 225
FT TURN 227 231
FT HELIX 234 237
FT HELIX 239 246
FT STRAND 251 256
FT TURN 258 261
FT HELIX 264 266
FT STRAND 268 274
FT HELIX 278 293
FT TURN 294 296
FT HELIX 302 311
FT HELIX 314 344
FT HELIX 352 356
FT STRAND 359 363
FT HELIX 368 378
FT STRAND 387 389
FT HELIX 390 392
FT TURN 395 397
FT HELIX 398 411
SQ SEQUENCE 413 AA; 46248 MW; 69FE68BF0C045219 CRC64;
MAPPSVFAEV PQAQPVLVFK LTADFREDPD PRKVNLGVGA YRTDDCHPWV LPVVKKVEQK
IANDNSLNHE YLPILGLAEF RSCASRLALG DDSPALKEKR VGGVQSLGGT GALRIGADFL
ARWYNGTNNK NTPVYVSSPT WENHNAVFSA AGFKDIRSYR YWDAEKRGLD LQGFLNDLEN
APEFSIVVLH ACAHNPTGID PTPEQWKQIA SVMKHRFLFP FFDSAYQGFA SGNLERDAWA
IRYFVSEGFE FFCAQSFSKN FGLYNERVGN LTVVGKEPES ILQVLSQMEK IVRITWSNPP
AQGARIVAST LSNPELFEEW TGNVKTMADR ILTMRSELRA RLEALKTPGT WNHITDQIGM
FSFTGLNPKQ VEYLVNEKHI YLLPSGRINV SGLTTKNLDY VATSIHEAVT KIQ
//
ID AATC_HUMAN Reviewed; 413 AA.
AC P17174; B2R6R7; Q5VW80;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 143.
DE RecName: Full=Aspartate aminotransferase, cytoplasmic;
DE Short=cAspAT;
DE EC=2.6.1.1;
DE EC=2.6.1.3;
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;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
RC TISSUE=Liver;
RX PubMed=1974457; DOI=10.1021/bi00474a011;
RA Bousquet-Lemercier B., Pol S., Pave-Preux M., Hanoune J., Barouki R.;
RT "Properties of human liver cytosolic aspartate aminotransferase mRNAs
RT generated by alternative polyadenylation site selection.";
RL Biochemistry 29:5293-5299(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Wang C.Y., Huang Y.Q., Shi J.D., Marron M.P., Ruan Q.G.,
RA Hawkins-Lee B., Ochoa B., She J.X.;
RT "Genomic structure and mutation analysis of GOT1 in the urofacial
RT (Ochoa) syndrome gene critical region on chromosome 10.";
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Yu W., Sarginson J., Gibbs R.A.;
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 2-413.
RC TISSUE=Liver;
RX PubMed=2241899;
RA Doyle J.M., Schinina M.E., Bossa F., Doonan S.;
RT "The amino acid sequence of cytosolic aspartate aminotransferase from
RT human liver.";
RL Biochem. J. 270:651-657(1990).
RN [9]
RP FUNCTION.
RX PubMed=16039064; DOI=10.1016/j.neulet.2005.06.030;
RA D'Aniello A., Fisher G., Migliaccio N., Cammisa G., D'Aniello E.,
RA Spinelli P.;
RT "Amino acids and transaminases activity in ventricular CSF and in
RT brain of normal and Alzheimer patients.";
RL Neurosci. Lett. 388:49-53(2005).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP INVOLVEMENT IN ASTQTL1, VARIANT ASN-389 DEL, AND CHARACTERIZATION OF
RP VARIANT ASN-389 DEL.
RX PubMed=21900944; DOI=10.1038/jhg.2011.105;
RA Shen H., Damcott C., Shuldiner S.R., Chai S., Yang R., Hu H.,
RA Gibson Q., Ryan K.A., Mitchell B.D., Gong D.W.;
RT "Genome-wide association study identifies genetic variants in GOT1
RT determining serum aspartate aminotransferase levels.";
RL J. Hum. Genet. 56:801-805(2011).
RN [12]
RP FETAL BLOOD LEVELS.
RX PubMed=22633534; DOI=10.1016/j.earlhumdev.2012.05.001;
RA Zlotnik A., Tsesis S., Gruenbaum B.F., Ohayon S., Gruenbaum S.E.,
RA Boyko M., Sheiner E., Brotfain E., Shapira Y., Teichberg V.I.;
RT "Relationship between glutamate, GOT and GPT levels in maternal and
RT fetal blood: a potential mechanism for fetal neuroprotection.";
RL Early Hum. Dev. 88:773-778(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 14-412 IN COMPLEX WITH
RP PYRIDOXAL PHOSPHATE AND TARTARIC ACID, SUBUNIT, AND PYRIDOXAL
RP PHOSPHATE AT LYS-259.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human glutamate oxaloacetate transaminase 1
RT (GOT1).";
RL Submitted (AUG-2009) to the PDB data bank.
CC -!- FUNCTION: Biosynthesis of L-glutamate from L-aspartate or L-
CC cysteine. Important regulator of levels of glutamate, the major
CC excitatory neurotransmitter of the vertebrate central nervous
CC system. Acts as a scavenger of glutamate in brain neuroprotection.
CC The aspartate aminotransferase activity is involved in hepatic
CC glucose synthesis during development and in adipocyte
CC glyceroneogenesis. Using L-cysteine as substrate, regulates levels
CC of mercaptopyruvate, an important source of hydrogen sulfide.
CC Mercaptopyruvate is converted into H(2)S via the action of 3-
CC mercaptopyruvate sulfurtransferase (3MST). Hydrogen sulfide is an
CC important synaptic modulator and neuroprotectant in the brain.
CC -!- CATALYTIC ACTIVITY: L-aspartate + 2-oxoglutarate = oxaloacetate +
CC L-glutamate.
CC -!- CATALYTIC ACTIVITY: L-cysteine + 2-oxoglutarate = mercaptopyruvate
CC + L-glutamate.
CC -!- COFACTOR: Pyridoxal phosphate.
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- POLYMORPHISM: Genetic variations in GOT1 are associated with low
CC serum aspartate aminotransferase and define the aspartate
CC aminotransferase serum level quantitative trait locus 1 (ASTQTL1)
CC [MIM:614419].
CC -!- MISCELLANEOUS: In eukaryotes there are cytoplasmic, mitochondrial
CC and chloroplastic isozymes.
CC -!- MISCELLANEOUS: Aspartate aminotransferase activity found to be
CC increased in cerebral spinal fluid (CSF) of patients with
CC Alzheimer disease (PubMed:16039064). Fetal serum levels of the
CC enzyme in the umbilical artery and vein are found to be
CC significantly higher than maternal serum levels (PubMed:22633534).
CC -!- SIMILARITY: Belongs to the class-I pyridoxal-phosphate-dependent
CC aminotransferase family.
CC -----------------------------------------------------------------------
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DR EMBL; M37400; AAA35563.1; -; mRNA.
DR EMBL; AF080467; AAC32851.1; -; Genomic_DNA.
DR EMBL; AF080459; AAC32851.1; JOINED; Genomic_DNA.
DR EMBL; AF080460; AAC32851.1; JOINED; Genomic_DNA.
DR EMBL; AF080461; AAC32851.1; JOINED; Genomic_DNA.
DR EMBL; AF080462; AAC32851.1; JOINED; Genomic_DNA.
DR EMBL; AF080463; AAC32851.1; JOINED; Genomic_DNA.
DR EMBL; AF080464; AAC32851.1; JOINED; Genomic_DNA.
DR EMBL; AF080465; AAC32851.1; JOINED; Genomic_DNA.
DR EMBL; AF080466; AAC32851.1; JOINED; Genomic_DNA.
DR EMBL; AF052153; AAC28622.1; -; mRNA.
DR EMBL; AK312684; BAG35564.1; -; mRNA.
DR EMBL; AL391684; CAH73859.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49869.1; -; Genomic_DNA.
DR EMBL; BC000498; AAH00498.1; -; mRNA.
DR PIR; S13035; S13035.
DR PIR; S29027; S29027.
DR RefSeq; NP_002070.1; NM_002079.2.
DR UniGene; Hs.500756; -.
DR PDB; 3II0; X-ray; 2.05 A; A/B/C/D=14-412.
DR PDBsum; 3II0; -.
DR ProteinModelPortal; P17174; -.
DR SMR; P17174; 14-412.
DR IntAct; P17174; 3.
DR MINT; MINT-5002473; -.
DR STRING; 9606.ENSP00000359539; -.
DR ChEMBL; CHEMBL2189139; -.
DR DrugBank; DB00128; L-Aspartic Acid.
DR DrugBank; DB00151; L-Cysteine.
DR DrugBank; DB00142; L-Glutamic Acid.
DR DrugBank; DB00114; Pyridoxal Phosphate.
DR PhosphoSite; P17174; -.
DR DMDM; 5902703; -.
DR REPRODUCTION-2DPAGE; IPI00219029; -.
DR UCD-2DPAGE; P17174; -.
DR PaxDb; P17174; -.
DR PeptideAtlas; P17174; -.
DR PRIDE; P17174; -.
DR Ensembl; ENST00000370508; ENSP00000359539; ENSG00000120053.
DR GeneID; 2805; -.
DR KEGG; hsa:2805; -.
DR UCSC; uc001kpr.3; human.
DR CTD; 2805; -.
DR GeneCards; GC10M101146; -.
DR HGNC; HGNC:4432; GOT1.
DR MIM; 138180; gene.
DR MIM; 614419; phenotype.
DR neXtProt; NX_P17174; -.
DR PharmGKB; PA28817; -.
DR eggNOG; COG1448; -.
DR HOGENOM; HOG000185898; -.
DR HOVERGEN; HBG000951; -.
DR InParanoid; P17174; -.
DR KO; K14454; -.
DR OMA; SWENHRV; -.
DR PhylomeDB; P17174; -.
DR BioCyc; MetaCyc:HS04361-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P17174; -.
DR ChiTaRS; GOT1; human.
DR EvolutionaryTrace; P17174; -.
DR GeneWiki; GOT1; -.
DR GenomeRNAi; 2805; -.
DR NextBio; 11057; -.
DR PRO; PR:P17174; -.
DR ArrayExpress; P17174; -.
DR Bgee; P17174; -.
DR CleanEx; HS_GOT1; -.
DR Genevestigator; P17174; -.
DR GO; GO:0043679; C:axon terminus; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005764; C:lysosome; IEA:Ensembl.
DR GO; GO:0031406; F:carboxylic acid binding; IEA:Ensembl.
DR GO; GO:0004069; F:L-aspartate:2-oxoglutarate aminotransferase activity; IDA:UniProtKB.
DR GO; GO:0047801; F:L-cysteine:2-oxoglutarate aminotransferase activity; ISS:UniProtKB.
DR GO; GO:0080130; F:L-phenylalanine:2-oxoglutarate aminotransferase activity; IEA:UniProtKB-EC.
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; IEA:Ensembl.
DR GO; GO:0006533; P:aspartate catabolic process; IDA:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:UniProtKB.
DR GO; GO:0055089; P:fatty acid homeostasis; IEA:Ensembl.
DR GO; GO:0006094; P:gluconeogenesis; TAS:Reactome.
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:0019509; P:L-methionine salvage from methylthioadenosine; TAS:Reactome.
DR GO; GO:0006107; P:oxaloacetate metabolic process; IEA:Ensembl.
DR GO; GO:0006595; P:polyamine metabolic process; TAS:Reactome.
DR GO; GO:0051384; P:response to glucocorticoid stimulus; IEP:UniProtKB.
DR Gene3D; 3.40.640.10; -; 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_sub1.
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;
KW Complete proteome; Cytoplasm; Direct protein sequencing; Polymorphism;
KW Pyridoxal phosphate; Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 413 Aspartate aminotransferase, cytoplasmic.
FT /FTId=PRO_0000123879.
FT BINDING 39 39 Aspartate; via amide nitrogen.
FT BINDING 141 141 Aspartate.
FT BINDING 195 195 Aspartate.
FT BINDING 387 387 Aspartate.
FT MOD_RES 259 259 N6-(pyridoxal phosphate)lysine (By
FT similarity).
FT VARIANT 389 389 Missing (results in markedly diminished
FT enzymatic activity).
FT /FTId=VAR_067256.
FT CONFLICT 215 215 H -> R (in Ref. 8; AA sequence).
FT HELIX 17 27
FT HELIX 52 62
FT HELIX 78 89
FT HELIX 94 97
FT STRAND 101 107
FT HELIX 108 123
FT STRAND 124 128
FT STRAND 134 139
FT HELIX 143 150
FT STRAND 156 160
FT TURN 164 167
FT HELIX 171 179
FT STRAND 186 190
FT TURN 195 197
FT HELIX 203 216
FT STRAND 219 225
FT TURN 227 231
FT HELIX 234 237
FT HELIX 239 246
FT STRAND 251 256
FT TURN 258 261
FT HELIX 264 266
FT STRAND 268 274
FT HELIX 278 293
FT TURN 294 296
FT HELIX 302 311
FT HELIX 314 344
FT HELIX 352 356
FT STRAND 359 363
FT HELIX 368 378
FT STRAND 387 389
FT HELIX 390 392
FT TURN 395 397
FT HELIX 398 411
SQ SEQUENCE 413 AA; 46248 MW; 69FE68BF0C045219 CRC64;
MAPPSVFAEV PQAQPVLVFK LTADFREDPD PRKVNLGVGA YRTDDCHPWV LPVVKKVEQK
IANDNSLNHE YLPILGLAEF RSCASRLALG DDSPALKEKR VGGVQSLGGT GALRIGADFL
ARWYNGTNNK NTPVYVSSPT WENHNAVFSA AGFKDIRSYR YWDAEKRGLD LQGFLNDLEN
APEFSIVVLH ACAHNPTGID PTPEQWKQIA SVMKHRFLFP FFDSAYQGFA SGNLERDAWA
IRYFVSEGFE FFCAQSFSKN FGLYNERVGN LTVVGKEPES ILQVLSQMEK IVRITWSNPP
AQGARIVAST LSNPELFEEW TGNVKTMADR ILTMRSELRA RLEALKTPGT WNHITDQIGM
FSFTGLNPKQ VEYLVNEKHI YLLPSGRINV SGLTTKNLDY VATSIHEAVT KIQ
//
MIM
138180
*RECORD*
*FIELD* NO
138180
*FIELD* TI
*138180 GLUTAMATE OXALOACETATE TRANSAMINASE, SOLUBLE; GOT1
;;ASPARTATE AMINOTRANSFERASE, CYTOSOLIC
read more*FIELD* TX
DESCRIPTION
Glutamate oxaloacetate transaminase (EC 2.6.1.1) is a ubiquitous
pyridoxal phosphate-dependent enzyme which exists in both mitochondrial
(138150) and cytosolic forms. The enzyme plays an important role in
amino acid metabolism and in the urea and tricarboxylic acid cycles. The
2 isoenzymes are homodimeric. In liver about 80% of the enzyme activity
is mitochondrial in origin, whereas in serum the enzyme activity is
largely cytosolic. Although the mitochondrial and soluble forms of GOT
are coded by different chromosomes (according to a rule that has few
exceptions; McKusick, 1986), the 2 show close homology in amino acid
sequence and were presumably derived from a common ancestral gene (Ford
et al., 1980; Doonan et al., 1984).
See ASTQTL1 (614419) for information on a quantitative trait locus
influencing the serum level of cytosolic glutamate oxaloacetate
transaminase.
CLONING
Pol et al. (1988) cloned cDNAs corresponding to human liver cytosolic
and mitochondrial aspartate aminotransferase mRNAs.
GENE STRUCTURE
Wang et al. (1999) determined the genomic structure of the GOT1 gene.
The gene contains 9 exons and all of its intron/exon junctions follow
the GT-AG rule.
GENE FUNCTION
Son et al. (2013) reported the identification of a noncanonical pathway
of glutamine use in human pancreatic ductal adenocarcinoma (PDAC; see
260350) cells that is required for tumor growth. Whereas most cells use
glutamate dehydrogenase (GLUD1; 138130) to convert glutamine-derived
glutamate into alpha-ketoglutarate in the mitochondria to fuel the
tricarboxylic acid cycle, PDAC relies on a distinct pathway in which
glutamine-derived aspartate is transported into the cytoplasm where it
can be converted into oxaloacetate by aspartate transaminase (GOT1).
Subsequently, this oxaloacetate is converted into malate and then
pyruvate, ostensibly increasing the NADPH/NADP+ ratio which can
potentially maintain the cellular redox state. Importantly, PDAC cells
are strongly dependent on this series of reactions, as glutamine
deprivation or genetic inhibition of any enzyme in this pathway leads to
an increase in reactive oxygen species and a reduction in reduced
glutathione. Moreover, knockdown of any component enzyme in this series
of reactions also results in a pronounced suppression of PDAC growth in
vitro and in vivo. Furthermore, Son et al. (2013) established that the
reprogramming of glutamine metabolism is mediated by oncogenic KRAS
(190070), the signature genetic alteration in PDAC, through the
transcriptional upregulation and repression of key metabolic enzymes in
this pathway.
MAPPING
By analysis of mouse-human somatic cell hybrids, Creagan et al. (1973)
concluded that the structural locus for cytoplasmic glutamate
oxaloacetate transaminase is on chromosome 10.
Spritz et al. (1979) studied soluble GOT activity in fibroblasts of 2
persons with duplications of the long arm of chromosome 10. Since the 2
differed by only half a band, the authors concluded that the structural
locus is on band 10q24.
Junien et al. (1982) assigned GOT1 and PGAMA (172250) to 10q26.1 (or
10q25.3) by dosage studies.
Pol et al. (1989) used human liver cytosolic and mitochondrial aspartate
aminotransferase cDNA probes to locate the GOT1 gene in the region
10q24.1-q25.1 by in situ hybridization. Wang et al. (1999) located the
GOT1 gene within the critical region for the urofacial syndrome
(236730), between markers D10S198 and D10S2494, but excluded it as a
candidate for that disorder by mutation analysis.
Koch et al. (1981) pointed out that GOT1 and LIPA (278000) are also
syntenic on chromosome 19 of the mouse.
OTHER FEATURES
Panteghini (1990) reviewed the clinical usefulness of assays for
aspartate aminotransferase (AST) isoenzymes in serum.
MOLECULAR GENETICS
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
*FIELD* AV
.0001
ASPARTATE AMINOTRANSFERASE, REDUCED SERUM LEVEL OF
GOT1, ASN389 DEL
In 10 Amish individuals, Shen et al. (2011) identified a 3-nucleotide
deletion in the GOT1 gene, 1165_1167delAAC, resulting in a deletion of
asparagine at position 389. Deletion carriers had significantly lower
AST activity levels (614419) compared with homozygous deletion
noncarriers (mean +/- SD: 10.0 +/- 2.8 vs 18.8 +/- 5.2 microliter; p =
2.80 x 10(-14)). Mutant cAST protein was barely detectable in cells in
in vitro transient transfection assays of wildtype and mutant cAST. This
mutation had a minor allele frequency of 0.0052 among the Old Order
Amish but was not detected in 647 outbred Caucasians. All deletion
carriers could be traced back to one most likely founder who was born in
the mid-18th century. Shen et al. (2011) found no association between
deletion and metabolic traits including serum fasting glucose or
insulin, fasting and postmeal lipids, inflammatory markers, or
subclinical markers of cardiovascular disease.
*FIELD* SA
Aitken and Ferguson-Smith (1978); Gitelman et al. (1980); Scott and
Wright (1981); Tomkins et al. (1983); Wurzinger and Mohrenweiser (1982)
*FIELD* RF
1. Aitken, D. A.; Ferguson-Smith, M. A.: Gene dosage evidence for
the regional assignment of the GOT-S structural gene locus to 10q24-10q25. Cytogenet.
Cell Genet. 22: 468-471, 1978.
2. Creagan, R.; Tischfield, J.; McMorris, F. A.; Chen, S.-H.; Hirschi,
M.; Chen, T.-T.; Ricciuti, F.; Ruddle, F. H.: Assignment of the genes
for human peptidase A to chromosome 18 and cytoplasmic glutamic oxaloacetate
transaminase to chromosome 10 using somatic-cell hybrids. Cytogenet.
Cell Genet. 12: 187-198, 1973.
3. Doonan, S.; Barra, D.; Bossa, F.: Structural and genetic relationships
between cytosolic and mitochondrial isoenzymes. Int. J. Biochem. 16:
1193-1199, 1984.
4. Ford, G. C.; Eichele, G.; Jansonius, J. N.: Three-dimensional
structure of a pyridoxal-phosphate-dependent enzyme, mitochondrial
aspartate aminotransferase. Proc. Nat. Acad. Sci. 77: 2559-2563,
1980.
5. Gitelman, B. J.; Tomkins, D. J.; Partington, M. W.; Roberts, M.
H.; Simpson, N. E.: Gene dosage studies of glutamic oxaloacetic transaminase
(GOT) and hexokinase (HK) in two patients with possible partial trisomy
10q. (Abstract) Am. J. Hum. Genet. 32: 41A only, 1980.
6. Junien, C.; Despoisse, S.; Turleau, C.; de Grouchy, J.; Bucher,
T.; Fundele, R.: Assignment of phosphoglycerate mutase (PGAMA) to
human chromosome 10: regional mapping of GOT1 and PGAMA to subbands
10q26.1 (or q25.3). Ann. Genet. 25: 25-27, 1982.
7. Koch, G.; Lalley, P. A.; McAvoy, M.; Shows, T. B.: Assignment
of LIPA, associated with human acid lipase deficiency, to human chromosome
10 and comparative assignment to mouse chromosome 19. Somat. Cell
Genet. 7: 345-358, 1981.
8. McKusick, V. A.: The morbid anatomy of the human genome: a review
of gene mapping in clinical medicine (part 1). Medicine 65: 1-33,
1986.
9. Panteghini, M.: Aspartate aminotransferase isoenzymes. Clin.
Biochem. 23: 311-319, 1990.
10. Pol, S.; Bousquet-Lemercier, B.; Pave-Preux, M.; Bulle, F.; Passage,
E.; Hanoune, J.; Mattei, M. G.; Barouki, R.: Chromosomal localization
of human aspartate aminotransferase genes by in situ hybridization. Hum.
Genet. 83: 159-164, 1989.
11. Pol, S.; Bousquet-Lemercier, B.; Pave-Preux, M.; Pawlak, A.; Nalpas,
B.; Berthelot, P.; Hanoune, J.; Barouki, R.: Nucleotide sequence
and tissue distribution of the human mitochondrial aspartate aminotransferase
mRNA. Biochem. Biophys. Res. Commun. 157: 1309-1315, 1988.
12. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
13. Scott, E. M.; Wright, R. C.: An alternate method for demonstration
of erythrocytic aminotransferases on starch gels. Am. J. Hum. Genet. 33:
561-563, 1981.
14. Shen, H.; Damcott, C.; Shuldiner, S. R.; Chai, S.; Yang, R.; Hu,
H.; Gibson, Q.; Ryan, K. A.; Mitchell, B. D.; Gong, D.-W.: Genome-wide
association study identifies genetic variants in GOT1 determining
serum aspartate aminotransferase levels. J. Hum. Genet. 56: 801-805,
2011.
15. Son, J.; Lyssiotis, C. A.; Ying, H.; Wang, X.; Hua, S.; Ligorio,
M.; Perera, R. M.; Ferrone, C. R.; Mullarky, E.; Shyh-Chang, N.; Kang,
Y.; Fleming, J. B.; Bardeesy, N.; Asara, J. M.; Haigis, M. C.; DePinho,
R. A.; Cantley, L. C.; Kimmelman, A. C.: Glutamine supports pancreatic
cancer growth through a KRAS-regulated metabolic pathway. Nature 496:
101-105, 2013. Note: Erratum: Nature 499: 504 only, 2013.
16. Spritz, R. A.; Emanuel, B. S.; Chern, C. J.; Mellman, W. J.:
Gene dosage effect: intraband mapping of human soluble glutamic oxaloacetic
transaminase. Cytogenet. Cell Genet. 23: 149-156, 1979.
17. Tomkins, D. J.; Gitelman, B. J.; Roberts, M. H.: Confirmation
of a de novo duplication, dup(10)(q24-q26), by GOT1 gene dosage studies. Hum.
Genet. 63: 369-373, 1983.
18. Wang, C.-Y.; Huang, Y.-Q.; Shi, J.-O.; Marron, M. P.; Ruan, Q.-G.;
Hawkins-Lee, B.; Ochoa, B.; She, J.-X.: Genetic homogeneity, high-resolution
mapping, and mutation analysis of the urofacial (Ochoa) syndrome and
exclusion of the glutamate oxaloacetate transaminase gene (GOT1) in
the critical region as the disease gene. Am. J. Med. Genet. 84:
454-459, 1999.
19. Wurzinger, K. H.; Mohrenweiser, H. W.: Studies on the genetic
and non-genetic (physiological) variation of human erythrocyte glutamic
oxaloacetic transaminase. Ann. Hum. Genet. 46: 191-201, 1982.
*FIELD* CN
Ada Hamosh - updated: 5/30/2013
Ada Hamosh - updated: 1/3/2012
Sonja A. Rasmussen - updated: 6/30/1999
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
alopez: 10/01/2013
alopez: 5/30/2013
joanna: 1/18/2012
alopez: 1/9/2012
terry: 1/3/2012
carol: 6/30/1999
pfoster: 2/18/1994
supermim: 3/16/1992
carol: 3/26/1991
carol: 3/14/1991
carol: 10/29/1990
supermim: 3/20/1990
*RECORD*
*FIELD* NO
138180
*FIELD* TI
*138180 GLUTAMATE OXALOACETATE TRANSAMINASE, SOLUBLE; GOT1
;;ASPARTATE AMINOTRANSFERASE, CYTOSOLIC
read more*FIELD* TX
DESCRIPTION
Glutamate oxaloacetate transaminase (EC 2.6.1.1) is a ubiquitous
pyridoxal phosphate-dependent enzyme which exists in both mitochondrial
(138150) and cytosolic forms. The enzyme plays an important role in
amino acid metabolism and in the urea and tricarboxylic acid cycles. The
2 isoenzymes are homodimeric. In liver about 80% of the enzyme activity
is mitochondrial in origin, whereas in serum the enzyme activity is
largely cytosolic. Although the mitochondrial and soluble forms of GOT
are coded by different chromosomes (according to a rule that has few
exceptions; McKusick, 1986), the 2 show close homology in amino acid
sequence and were presumably derived from a common ancestral gene (Ford
et al., 1980; Doonan et al., 1984).
See ASTQTL1 (614419) for information on a quantitative trait locus
influencing the serum level of cytosolic glutamate oxaloacetate
transaminase.
CLONING
Pol et al. (1988) cloned cDNAs corresponding to human liver cytosolic
and mitochondrial aspartate aminotransferase mRNAs.
GENE STRUCTURE
Wang et al. (1999) determined the genomic structure of the GOT1 gene.
The gene contains 9 exons and all of its intron/exon junctions follow
the GT-AG rule.
GENE FUNCTION
Son et al. (2013) reported the identification of a noncanonical pathway
of glutamine use in human pancreatic ductal adenocarcinoma (PDAC; see
260350) cells that is required for tumor growth. Whereas most cells use
glutamate dehydrogenase (GLUD1; 138130) to convert glutamine-derived
glutamate into alpha-ketoglutarate in the mitochondria to fuel the
tricarboxylic acid cycle, PDAC relies on a distinct pathway in which
glutamine-derived aspartate is transported into the cytoplasm where it
can be converted into oxaloacetate by aspartate transaminase (GOT1).
Subsequently, this oxaloacetate is converted into malate and then
pyruvate, ostensibly increasing the NADPH/NADP+ ratio which can
potentially maintain the cellular redox state. Importantly, PDAC cells
are strongly dependent on this series of reactions, as glutamine
deprivation or genetic inhibition of any enzyme in this pathway leads to
an increase in reactive oxygen species and a reduction in reduced
glutathione. Moreover, knockdown of any component enzyme in this series
of reactions also results in a pronounced suppression of PDAC growth in
vitro and in vivo. Furthermore, Son et al. (2013) established that the
reprogramming of glutamine metabolism is mediated by oncogenic KRAS
(190070), the signature genetic alteration in PDAC, through the
transcriptional upregulation and repression of key metabolic enzymes in
this pathway.
MAPPING
By analysis of mouse-human somatic cell hybrids, Creagan et al. (1973)
concluded that the structural locus for cytoplasmic glutamate
oxaloacetate transaminase is on chromosome 10.
Spritz et al. (1979) studied soluble GOT activity in fibroblasts of 2
persons with duplications of the long arm of chromosome 10. Since the 2
differed by only half a band, the authors concluded that the structural
locus is on band 10q24.
Junien et al. (1982) assigned GOT1 and PGAMA (172250) to 10q26.1 (or
10q25.3) by dosage studies.
Pol et al. (1989) used human liver cytosolic and mitochondrial aspartate
aminotransferase cDNA probes to locate the GOT1 gene in the region
10q24.1-q25.1 by in situ hybridization. Wang et al. (1999) located the
GOT1 gene within the critical region for the urofacial syndrome
(236730), between markers D10S198 and D10S2494, but excluded it as a
candidate for that disorder by mutation analysis.
Koch et al. (1981) pointed out that GOT1 and LIPA (278000) are also
syntenic on chromosome 19 of the mouse.
OTHER FEATURES
Panteghini (1990) reviewed the clinical usefulness of assays for
aspartate aminotransferase (AST) isoenzymes in serum.
MOLECULAR GENETICS
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
*FIELD* AV
.0001
ASPARTATE AMINOTRANSFERASE, REDUCED SERUM LEVEL OF
GOT1, ASN389 DEL
In 10 Amish individuals, Shen et al. (2011) identified a 3-nucleotide
deletion in the GOT1 gene, 1165_1167delAAC, resulting in a deletion of
asparagine at position 389. Deletion carriers had significantly lower
AST activity levels (614419) compared with homozygous deletion
noncarriers (mean +/- SD: 10.0 +/- 2.8 vs 18.8 +/- 5.2 microliter; p =
2.80 x 10(-14)). Mutant cAST protein was barely detectable in cells in
in vitro transient transfection assays of wildtype and mutant cAST. This
mutation had a minor allele frequency of 0.0052 among the Old Order
Amish but was not detected in 647 outbred Caucasians. All deletion
carriers could be traced back to one most likely founder who was born in
the mid-18th century. Shen et al. (2011) found no association between
deletion and metabolic traits including serum fasting glucose or
insulin, fasting and postmeal lipids, inflammatory markers, or
subclinical markers of cardiovascular disease.
*FIELD* SA
Aitken and Ferguson-Smith (1978); Gitelman et al. (1980); Scott and
Wright (1981); Tomkins et al. (1983); Wurzinger and Mohrenweiser (1982)
*FIELD* RF
1. Aitken, D. A.; Ferguson-Smith, M. A.: Gene dosage evidence for
the regional assignment of the GOT-S structural gene locus to 10q24-10q25. Cytogenet.
Cell Genet. 22: 468-471, 1978.
2. Creagan, R.; Tischfield, J.; McMorris, F. A.; Chen, S.-H.; Hirschi,
M.; Chen, T.-T.; Ricciuti, F.; Ruddle, F. H.: Assignment of the genes
for human peptidase A to chromosome 18 and cytoplasmic glutamic oxaloacetate
transaminase to chromosome 10 using somatic-cell hybrids. Cytogenet.
Cell Genet. 12: 187-198, 1973.
3. Doonan, S.; Barra, D.; Bossa, F.: Structural and genetic relationships
between cytosolic and mitochondrial isoenzymes. Int. J. Biochem. 16:
1193-1199, 1984.
4. Ford, G. C.; Eichele, G.; Jansonius, J. N.: Three-dimensional
structure of a pyridoxal-phosphate-dependent enzyme, mitochondrial
aspartate aminotransferase. Proc. Nat. Acad. Sci. 77: 2559-2563,
1980.
5. Gitelman, B. J.; Tomkins, D. J.; Partington, M. W.; Roberts, M.
H.; Simpson, N. E.: Gene dosage studies of glutamic oxaloacetic transaminase
(GOT) and hexokinase (HK) in two patients with possible partial trisomy
10q. (Abstract) Am. J. Hum. Genet. 32: 41A only, 1980.
6. Junien, C.; Despoisse, S.; Turleau, C.; de Grouchy, J.; Bucher,
T.; Fundele, R.: Assignment of phosphoglycerate mutase (PGAMA) to
human chromosome 10: regional mapping of GOT1 and PGAMA to subbands
10q26.1 (or q25.3). Ann. Genet. 25: 25-27, 1982.
7. Koch, G.; Lalley, P. A.; McAvoy, M.; Shows, T. B.: Assignment
of LIPA, associated with human acid lipase deficiency, to human chromosome
10 and comparative assignment to mouse chromosome 19. Somat. Cell
Genet. 7: 345-358, 1981.
8. McKusick, V. A.: The morbid anatomy of the human genome: a review
of gene mapping in clinical medicine (part 1). Medicine 65: 1-33,
1986.
9. Panteghini, M.: Aspartate aminotransferase isoenzymes. Clin.
Biochem. 23: 311-319, 1990.
10. Pol, S.; Bousquet-Lemercier, B.; Pave-Preux, M.; Bulle, F.; Passage,
E.; Hanoune, J.; Mattei, M. G.; Barouki, R.: Chromosomal localization
of human aspartate aminotransferase genes by in situ hybridization. Hum.
Genet. 83: 159-164, 1989.
11. Pol, S.; Bousquet-Lemercier, B.; Pave-Preux, M.; Pawlak, A.; Nalpas,
B.; Berthelot, P.; Hanoune, J.; Barouki, R.: Nucleotide sequence
and tissue distribution of the human mitochondrial aspartate aminotransferase
mRNA. Biochem. Biophys. Res. Commun. 157: 1309-1315, 1988.
12. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
13. Scott, E. M.; Wright, R. C.: An alternate method for demonstration
of erythrocytic aminotransferases on starch gels. Am. J. Hum. Genet. 33:
561-563, 1981.
14. Shen, H.; Damcott, C.; Shuldiner, S. R.; Chai, S.; Yang, R.; Hu,
H.; Gibson, Q.; Ryan, K. A.; Mitchell, B. D.; Gong, D.-W.: Genome-wide
association study identifies genetic variants in GOT1 determining
serum aspartate aminotransferase levels. J. Hum. Genet. 56: 801-805,
2011.
15. Son, J.; Lyssiotis, C. A.; Ying, H.; Wang, X.; Hua, S.; Ligorio,
M.; Perera, R. M.; Ferrone, C. R.; Mullarky, E.; Shyh-Chang, N.; Kang,
Y.; Fleming, J. B.; Bardeesy, N.; Asara, J. M.; Haigis, M. C.; DePinho,
R. A.; Cantley, L. C.; Kimmelman, A. C.: Glutamine supports pancreatic
cancer growth through a KRAS-regulated metabolic pathway. Nature 496:
101-105, 2013. Note: Erratum: Nature 499: 504 only, 2013.
16. Spritz, R. A.; Emanuel, B. S.; Chern, C. J.; Mellman, W. J.:
Gene dosage effect: intraband mapping of human soluble glutamic oxaloacetic
transaminase. Cytogenet. Cell Genet. 23: 149-156, 1979.
17. Tomkins, D. J.; Gitelman, B. J.; Roberts, M. H.: Confirmation
of a de novo duplication, dup(10)(q24-q26), by GOT1 gene dosage studies. Hum.
Genet. 63: 369-373, 1983.
18. Wang, C.-Y.; Huang, Y.-Q.; Shi, J.-O.; Marron, M. P.; Ruan, Q.-G.;
Hawkins-Lee, B.; Ochoa, B.; She, J.-X.: Genetic homogeneity, high-resolution
mapping, and mutation analysis of the urofacial (Ochoa) syndrome and
exclusion of the glutamate oxaloacetate transaminase gene (GOT1) in
the critical region as the disease gene. Am. J. Med. Genet. 84:
454-459, 1999.
19. Wurzinger, K. H.; Mohrenweiser, H. W.: Studies on the genetic
and non-genetic (physiological) variation of human erythrocyte glutamic
oxaloacetic transaminase. Ann. Hum. Genet. 46: 191-201, 1982.
*FIELD* CN
Ada Hamosh - updated: 5/30/2013
Ada Hamosh - updated: 1/3/2012
Sonja A. Rasmussen - updated: 6/30/1999
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
alopez: 10/01/2013
alopez: 5/30/2013
joanna: 1/18/2012
alopez: 1/9/2012
terry: 1/3/2012
carol: 6/30/1999
pfoster: 2/18/1994
supermim: 3/16/1992
carol: 3/26/1991
carol: 3/14/1991
carol: 10/29/1990
supermim: 3/20/1990
MIM
614419
*RECORD*
*FIELD* NO
614419
*FIELD* TI
#614419 ASPARTATE AMINOTRANSFERASE, SERUM LEVEL OF, QUANTITATIVE TRAIT LOCUS
1
;;ASTQTL1
read more*FIELD* TX
A number sign (#) is used with this entry because variation in the GOT1
gene (138180) results in low serum glutamate oxaloacetate transaminase,
also known as aspartate aminotransferase (AST).
MAPPING
Shen et al. (2011) carried out a genomewide association study of serum
AST (EC 2.6.1.1) activity in 866 Amish participants of the Heredity and
Phenotype Intervention Heart Study and identified a significant
association of AST activity with a cluster of SNPs located on chromosome
10q24 (peak association was dbSNP rs17109512; p = 2.80 x 10(-14)), in
the vicinity of the GOT1 gene, which encodes cytosolic AST. The 10
subjects heterozygous for the associated SNP had significantly lower AST
levels compared with the 856 homozygotes for the wildtype allele.
MOLECULAR GENETICS
Given the low frequency of the associated SNP, its proximity to GOT1,
and the very large effect size of the association, Shen et al. (2011)
hypothesized that dbSNP rs17109512 might tag a functional SNP in GOT1.
Sequencing of GOT1 revealed an in-frame deletion of 3 nucleic acids
encoding asparagine at position 389 (138180.0001). The deletion was in
complete linkage with dbSNP rs17109512. Deletion carriers had
significantly lower AST activity levels compared with homozygotes for
deletion noncarriers (mean +/- SD: 10.0 +/- 2.8 vs 18.8 +/- 5.2
microliter; p = 2.80 x 10(-14)). Further genotyping of the deletion in
1,932 other Amish samples identified an additional 20 carriers (minor
allele frequency = 0.0052). The deletion was not detected in 647 outbred
Caucasians. Asparagine at codon 389 is conserved among known mammalian
cytoplasmic ASTs (cASTs). In vitro transient transfection assays of
wildtype and mutant cAST indicated that mutant cAST protein was barely
detectable in the cells. Furthermore, even after correction for cAST
expression, mutant cAST had markedly diminished enzymatic activity.
Remarkably, there was no association between the deletion and metabolic
traits including serum fasting glucose or insulin, fasting and postmeal
lipids, inflammatory markers, or subclinical markers of cardiovascular
disease.
*FIELD* RF
1. Shen, H.; Damcott, C.; Shuldiner, S. R.; Chai, S.; Yang, R.; Hu,
H.; Gibson, Q.; Ryan, K. A.; Mitchell, B. D.; Gong, D.-W.: Genome-wide
association study identifies genetic variants in GOT1 determining
serum aspartate aminotransferase levels. J. Hum. Genet. 56: 801-805,
2011.
*FIELD* CD
Ada Hamosh: 1/9/2012
*FIELD* ED
alopez: 01/18/2012
alopez: 1/9/2012
*RECORD*
*FIELD* NO
614419
*FIELD* TI
#614419 ASPARTATE AMINOTRANSFERASE, SERUM LEVEL OF, QUANTITATIVE TRAIT LOCUS
1
;;ASTQTL1
read more*FIELD* TX
A number sign (#) is used with this entry because variation in the GOT1
gene (138180) results in low serum glutamate oxaloacetate transaminase,
also known as aspartate aminotransferase (AST).
MAPPING
Shen et al. (2011) carried out a genomewide association study of serum
AST (EC 2.6.1.1) activity in 866 Amish participants of the Heredity and
Phenotype Intervention Heart Study and identified a significant
association of AST activity with a cluster of SNPs located on chromosome
10q24 (peak association was dbSNP rs17109512; p = 2.80 x 10(-14)), in
the vicinity of the GOT1 gene, which encodes cytosolic AST. The 10
subjects heterozygous for the associated SNP had significantly lower AST
levels compared with the 856 homozygotes for the wildtype allele.
MOLECULAR GENETICS
Given the low frequency of the associated SNP, its proximity to GOT1,
and the very large effect size of the association, Shen et al. (2011)
hypothesized that dbSNP rs17109512 might tag a functional SNP in GOT1.
Sequencing of GOT1 revealed an in-frame deletion of 3 nucleic acids
encoding asparagine at position 389 (138180.0001). The deletion was in
complete linkage with dbSNP rs17109512. Deletion carriers had
significantly lower AST activity levels compared with homozygotes for
deletion noncarriers (mean +/- SD: 10.0 +/- 2.8 vs 18.8 +/- 5.2
microliter; p = 2.80 x 10(-14)). Further genotyping of the deletion in
1,932 other Amish samples identified an additional 20 carriers (minor
allele frequency = 0.0052). The deletion was not detected in 647 outbred
Caucasians. Asparagine at codon 389 is conserved among known mammalian
cytoplasmic ASTs (cASTs). In vitro transient transfection assays of
wildtype and mutant cAST indicated that mutant cAST protein was barely
detectable in the cells. Furthermore, even after correction for cAST
expression, mutant cAST had markedly diminished enzymatic activity.
Remarkably, there was no association between the deletion and metabolic
traits including serum fasting glucose or insulin, fasting and postmeal
lipids, inflammatory markers, or subclinical markers of cardiovascular
disease.
*FIELD* RF
1. Shen, H.; Damcott, C.; Shuldiner, S. R.; Chai, S.; Yang, R.; Hu,
H.; Gibson, Q.; Ryan, K. A.; Mitchell, B. D.; Gong, D.-W.: Genome-wide
association study identifies genetic variants in GOT1 determining
serum aspartate aminotransferase levels. J. Hum. Genet. 56: 801-805,
2011.
*FIELD* CD
Ada Hamosh: 1/9/2012
*FIELD* ED
alopez: 01/18/2012
alopez: 1/9/2012