AGT2_HUMAN
ID AGT2_HUMAN Reviewed; 514 AA.
AC Q9BYV1; B7ZM47; E9PDL7; Q53FB4; Q53FY7; Q53G03; Q5W7Q1;
DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Alanine--glyoxylate aminotransferase 2, mitochondrial;
DE Short=AGT 2;
DE EC=2.6.1.44;
DE AltName: Full=(R)-3-amino-2-methylpropionate--pyruvate transaminase;
DE EC=2.6.1.40;
DE AltName: Full=Beta-ALAAT II;
DE AltName: Full=Beta-alanine-pyruvate aminotransferase;
DE AltName: Full=D-AIBAT;
DE Flags: Precursor;
GN Name=AGXT2; Synonyms=AGT2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Jenne D.E.;
RT "The human ortholog for rat alanine-glyoxylate aminotransferase 2.";
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ASN-102; ILE-140 AND
RP ILE-212.
RA Matsuda K., Horikawa Y., Kaneko M., Sakata S., Tamaki N.;
RT "Human beta-alanine-pyruvate aminotransferase cDNA.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS ASN-102;
RP ILE-140; ILE-212 AND LEU-498.
RC TISSUE=Kidney;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS ASN-102
RP AND ILE-212.
RC TISSUE=Testis;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, TRANSIT PEPTIDE CLEAVAGE SITE,
RP AND SUBCELLULAR LOCATION.
RX PubMed=20018850; DOI=10.1074/jbc.m109.091280;
RA Rodionov R.N., Murry D.J., Vaulman S.F., Stevens J.W., Lentz S.R.;
RT "Human alanine-glyoxylate aminotransferase 2 lowers asymmetric
RT dimethylarginine and protects from inhibition of nitric oxide production.";
RL J. Biol. Chem. 285:5385-5391(2010).
RN [7]
RP FUNCTION.
RX PubMed=23023372; DOI=10.1161/atvbaha.112.254078;
RA Caplin B., Wang Z., Slaviero A., Tomlinson J., Dowsett L., Delahaye M.,
RA Salama A., Wheeler D.C., Leiper J.;
RT "Alanine-Glyoxylate aminotransferase-2 metabolizes endogenous
RT methylarginines, regulates NO, and controls blood pressure.";
RL Arterioscler. Thromb. Vasc. Biol. 32:2892-2900(2012).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [9]
RP VARIANT ILE-140.
RX PubMed=24834905; DOI=10.5551/jat.23077;
RA Zhou J.P., Bai Y.P., Hu X.L., Kuang D.B., Shi R.Z., Xiong Y., Zhang W.,
RA Xia J., Chen B.L., Yang T.L., Chen X.P.;
RT "Association of the AGXT2 V140I polymorphism with risk for coronary heart
RT disease in a Chinese population.";
RL J. Atheroscler. Thromb. 21:1022-1030(2014).
RN [10]
RP POLYMORPHISM, VARIANTS ILE-140 AND LEU-498, FUNCTION, SUBCELLULAR LOCATION,
RP AND CHARACTERIZATION OF VARIANT ILE-140.
RX PubMed=24586340; DOI=10.1371/journal.pone.0088544;
RA Kittel A., Muller F., Konig J., Mieth M., Sticht H., Zolk O., Kralj A.,
RA Heinrich M.R., Fromm M.F., Maas R.;
RT "Alanine-glyoxylate aminotransferase 2 (AGXT2) polymorphisms have
RT considerable impact on methylarginine and beta-aminoisobutyrate metabolism
RT in healthy volunteers.";
RL PLoS ONE 9:E88544-E88544(2014).
CC -!- FUNCTION: Can metabolize asymmetric dimethylarginine (ADMA) via
CC transamination to alpha-keto-delta-(NN-dimethylguanidino) valeric acid
CC (DMGV). ADMA is a potent inhibitor of nitric-oxide (NO) synthase, and
CC this activity provides mechanism through which the kidney regulates
CC blood pressure. {ECO:0000269|PubMed:20018850,
CC ECO:0000269|PubMed:23023372, ECO:0000269|PubMed:24586340}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glyoxylate + L-alanine = glycine + pyruvate;
CC Xref=Rhea:RHEA:24248, ChEBI:CHEBI:15361, ChEBI:CHEBI:36655,
CC ChEBI:CHEBI:57305, ChEBI:CHEBI:57972; EC=2.6.1.44;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-3-amino-2-methylpropanoate + pyruvate = 2-methyl-3-
CC oxopropanoate + L-alanine; Xref=Rhea:RHEA:18393, ChEBI:CHEBI:15361,
CC ChEBI:CHEBI:57700, ChEBI:CHEBI:57731, ChEBI:CHEBI:57972; EC=2.6.1.40;
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC -!- SUBUNIT: Homotetramer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:20018850,
CC ECO:0000269|PubMed:24586340}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BYV1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BYV1-2; Sequence=VSP_055802;
CC -!- POLYMORPHISM: Genetic variants in AGXT2 are association with beta-
CC aminoisobutyric aciduria (BAIBA)[MIM:210100]. Excretion of beta-
CC aminoisobutyric acid in urine is a common, benign, metabolic trait.
CC {ECO:0000269|PubMed:24586340}.
CC -!- SIMILARITY: Belongs to the class-III pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000305}.
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DR EMBL; AJ292204; CAC24841.1; -; mRNA.
DR EMBL; AB193309; BAD66662.1; -; mRNA.
DR EMBL; AK223128; BAD96848.1; -; mRNA.
DR EMBL; AK223144; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK223375; BAD97095.1; -; mRNA.
DR EMBL; AC010368; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC144268; AAI44269.1; -; mRNA.
DR EMBL; BC150603; AAI50604.1; -; mRNA.
DR CCDS; CCDS3908.1; -. [Q9BYV1-1]
DR CCDS; CCDS78000.1; -. [Q9BYV1-2]
DR RefSeq; NP_001293102.1; NM_001306173.1. [Q9BYV1-2]
DR RefSeq; NP_114106.1; NM_031900.3. [Q9BYV1-1]
DR RefSeq; XP_016865237.1; XM_017009748.1. [Q9BYV1-2]
DR AlphaFoldDB; Q9BYV1; -.
DR SMR; Q9BYV1; -.
DR BioGRID; 122342; 59.
DR IntAct; Q9BYV1; 2.
DR STRING; 9606.ENSP00000231420; -.
DR DrugBank; DB00160; Alanine.
DR DrugBank; DB00145; Glycine.
DR DrugBank; DB00114; Pyridoxal phosphate.
DR DrugBank; DB00119; Pyruvic acid.
DR iPTMnet; Q9BYV1; -.
DR PhosphoSitePlus; Q9BYV1; -.
DR BioMuta; AGXT2; -.
DR DMDM; 17432913; -.
DR MassIVE; Q9BYV1; -.
DR PaxDb; Q9BYV1; -.
DR PeptideAtlas; Q9BYV1; -.
DR PRIDE; Q9BYV1; -.
DR ProteomicsDB; 19698; -.
DR ProteomicsDB; 79711; -. [Q9BYV1-1]
DR Antibodypedia; 43482; 149 antibodies from 26 providers.
DR DNASU; 64902; -.
DR Ensembl; ENST00000231420.11; ENSP00000231420.6; ENSG00000113492.14. [Q9BYV1-1]
DR Ensembl; ENST00000510428.1; ENSP00000422799.1; ENSG00000113492.14. [Q9BYV1-2]
DR Ensembl; ENST00000618015.4; ENSP00000479154.1; ENSG00000113492.14. [Q9BYV1-2]
DR GeneID; 64902; -.
DR KEGG; hsa:64902; -.
DR MANE-Select; ENST00000231420.11; ENSP00000231420.6; NM_031900.4; NP_114106.1.
DR UCSC; uc003jjf.4; human. [Q9BYV1-1]
DR CTD; 64902; -.
DR DisGeNET; 64902; -.
DR GeneCards; AGXT2; -.
DR HGNC; HGNC:14412; AGXT2.
DR HPA; ENSG00000113492; Group enriched (kidney, liver).
DR MalaCards; AGXT2; -.
DR MIM; 210100; phenotype.
DR MIM; 612471; gene.
DR neXtProt; NX_Q9BYV1; -.
DR OpenTargets; ENSG00000113492; -.
DR PharmGKB; PA24634; -.
DR VEuPathDB; HostDB:ENSG00000113492; -.
DR eggNOG; KOG1404; Eukaryota.
DR GeneTree; ENSGT00940000156125; -.
DR HOGENOM; CLU_016922_8_0_1; -.
DR InParanoid; Q9BYV1; -.
DR OMA; PFMVPTY; -.
DR OrthoDB; 145181at2759; -.
DR PhylomeDB; Q9BYV1; -.
DR TreeFam; TF105945; -.
DR BioCyc; MetaCyc:HS03685-MON; -.
DR BRENDA; 2.6.1.44; 2681.
DR PathwayCommons; Q9BYV1; -.
DR Reactome; R-HSA-389661; Glyoxylate metabolism and glycine degradation.
DR Reactome; R-HSA-73621; Pyrimidine catabolism.
DR SignaLink; Q9BYV1; -.
DR BioGRID-ORCS; 64902; 8 hits in 1074 CRISPR screens.
DR ChiTaRS; AGXT2; human.
DR GenomeRNAi; 64902; -.
DR Pharos; Q9BYV1; Tbio.
DR PRO; PR:Q9BYV1; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9BYV1; protein.
DR Bgee; ENSG00000113492; Expressed in kidney epithelium and 41 other tissues.
DR Genevisible; Q9BYV1; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0047305; F:(R)-3-amino-2-methylpropionate-pyruvate transaminase activity; IEA:UniProtKB-EC.
DR GO; GO:0008453; F:alanine-glyoxylate transaminase activity; IDA:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0019265; P:glycine biosynthetic process, by transamination of glyoxylate; IDA:BHF-UCL.
DR GO; GO:0009436; P:glyoxylate catabolic process; IDA:BHF-UCL.
DR GO; GO:0019481; P:L-alanine catabolic process, by transamination; IDA:BHF-UCL.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:BHF-UCL.
DR CDD; cd00610; OAT_like; 1.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR005814; Aminotrans_3.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR Pfam; PF00202; Aminotran_3; 1.
DR PIRSF; PIRSF000521; Transaminase_4ab_Lys_Orn; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
DR PROSITE; PS00600; AA_TRANSFER_CLASS_3; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Aminotransferase;
KW Direct protein sequencing; Mitochondrion; Pyridoxal phosphate;
KW Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..41
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:20018850"
FT CHAIN 42..514
FT /note="Alanine--glyoxylate aminotransferase 2,
FT mitochondrial"
FT /id="PRO_0000001269"
FT MOD_RES 71
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q3UEG6"
FT MOD_RES 71
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q3UEG6"
FT MOD_RES 84
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q3UEG6"
FT MOD_RES 262
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q3UEG6"
FT MOD_RES 262
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q3UEG6"
FT MOD_RES 304
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q3UEG6"
FT MOD_RES 350
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250"
FT MOD_RES 417
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q3UEG6"
FT MOD_RES 417
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q3UEG6"
FT MOD_RES 420
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q3UEG6"
FT MOD_RES 420
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q3UEG6"
FT VAR_SEQ 321..395
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055802"
FT VARIANT 102
FT /note="S -> I (in dbSNP:rs37370)"
FT /id="VAR_061006"
FT VARIANT 102
FT /note="S -> N (in dbSNP:rs37370)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2,
FT ECO:0000269|Ref.3"
FT /id="VAR_023483"
FT VARIANT 102
FT /note="S -> T (in dbSNP:rs37370)"
FT /id="VAR_061007"
FT VARIANT 132
FT /note="G -> R (in dbSNP:rs16870794)"
FT /id="VAR_048231"
FT VARIANT 140
FT /note="V -> I (associated with an increased risk for
FT coronary heart disease (CHD) in smoker and diabetic
FT mellitus (DM) patients in a Chinese population; higher
FT plasma symmetric (SDMA) dimethylarginine as well as plasma
FT and urinary beta-aminoisobutyrate (BAIB) concentrations;
FT localized to the mitochondrion as the wild-type; reduces
FT alanine-glyoxylate aminotransferase activity;
FT dbSNP:rs37369)"
FT /evidence="ECO:0000269|PubMed:24586340,
FT ECO:0000269|PubMed:24834905, ECO:0000269|Ref.2,
FT ECO:0000269|Ref.3"
FT /id="VAR_022140"
FT VARIANT 212
FT /note="T -> I (in dbSNP:rs180749)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2,
FT ECO:0000269|Ref.3"
FT /id="VAR_022141"
FT VARIANT 492
FT /note="P -> R (in dbSNP:rs17245714)"
FT /id="VAR_048232"
FT VARIANT 498
FT /note="V -> L (higher plasma and urinary beta-
FT aminoisobutyrate (BAIB) concentrations; dbSNP:rs16899974)"
FT /evidence="ECO:0000269|PubMed:24586340, ECO:0000269|Ref.3"
FT /id="VAR_029513"
SQ SEQUENCE 514 AA; 57156 MW; CA562F84FF39B5AC CRC64;
MTLIWRHLLR PLCLVTSAPR ILEMHPFLSL GTSRTSVTKL SLHTKPRMPP CDFMPERYQS
LGYNRVLEIH KEHLSPVVTA YFQKPLLLHQ GHMEWLFDAE GSRYLDFFSG IVTVSVGHCH
PKVNAVAQKQ LGRLWHTSTV FFHPPMHEYA EKLAALLPEP LKVIFLVNSG SEANELAMLM
ARAHSNNIDI ISFRGAYHGC SPYTLGLTNV GTYKMELPGG TGCQPTMCPD VFRGPWGGSH
CRDSPVQTIR KCSCAPDCCQ AKDQYIEQFK DTLSTSVAKS IAGFFAEPIQ GVNGVVQYPK
GFLKEAFELV RARGGVCIAD EVQTGFGRLG SHFWGFQTHD VLPDIVTMAK GIGNGFPMAA
VITTPEIAKS LAKCLQHFNT FGGNPMACAI GSAVLEVIKE ENLQENSQEV GTYMLLKFAK
LRDEFEIVGD VRGKGLMIGI EMVQDKISCR PLPREEVNQI HEDCKHMGLL VGRGSIFSQT
FRIAPSMCIT KPEVDFAVEV FRSALTQHME RRAK
