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 09-DEC-2015, entry version 127. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RP AND 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 RP ASN-102; 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., RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., RA 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 RP ASN-102 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, TRANSIT PEPTIDE CLEAVAGE RP SITE, 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 RT 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., RA Delahaye M., 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [9] RP VARIANT ILE-140. RX PubMed=24834905; RA Zhou J.P., Bai Y.P., Hu X.L., Kuang D.B., Shi R.Z., Xiong Y., RA Zhang W., Xia J., Chen B.L., Yang T.L., Chen X.P.; RT "Association of the AGXT2 V140I polymorphism with risk for coronary RT heart disease in a Chinese population."; RL J. Atheroscler. Thromb. 21:1022-1030(2014). RN [10] RP VARIANTS ILE-140 AND LEU-498, FUNCTION, SUBCELLULAR LOCATION, AND RP CHARACTERIZATION 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., RA Kralj A., Heinrich M.R., Fromm M.F., Maas R.; RT "Alanine-glyoxylate aminotransferase 2 (AGXT2) polymorphisms have RT considerable impact on methylarginine and beta-aminoisobutyrate RT metabolism 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 CC acid (DMGV). ADMA is a potent inhibitor of nitric-oxide (NO) CC synthase, and this activity provides mechanism through which the CC kidney regulates blood pressure. {ECO:0000269|PubMed:20018850, CC ECO:0000269|PubMed:23023372, ECO:0000269|PubMed:24586340}. CC -!- CATALYTIC ACTIVITY: L-alanine + glyoxylate = pyruvate + glycine. CC -!- CATALYTIC ACTIVITY: (R)-3-amino-2-methylpropanoate + pyruvate = 2- CC methyl-3-oxopropanoate + L-alanine. 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 Note=No experimental confirmation available.; CC -!- SIMILARITY: Belongs to the class-III pyridoxal-phosphate-dependent CC aminotransferase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 UniGene; Hs.34494; -. DR ProteinModelPortal; Q9BYV1; -. DR SMR; Q9BYV1; 61-509. DR BioGrid; 122342; 2. DR IntAct; Q9BYV1; 2. DR STRING; 9606.ENSP00000231420; -. DR DrugBank; DB00145; Glycine. DR DrugBank; DB00160; L-Alanine. DR DrugBank; DB00119; Pyruvic acid. DR PhosphoSite; Q9BYV1; -. DR BioMuta; AGXT2; -. DR DMDM; 17432913; -. DR PaxDb; Q9BYV1; -. DR PRIDE; Q9BYV1; -. DR Ensembl; ENST00000231420; ENSP00000231420; ENSG00000113492. [Q9BYV1-1] DR Ensembl; ENST00000510428; ENSP00000422799; ENSG00000113492. [Q9BYV1-2] DR Ensembl; ENST00000618015; ENSP00000479154; ENSG00000113492. [Q9BYV1-2] DR GeneID; 64902; -. DR KEGG; hsa:64902; -. DR UCSC; uc003jjf.3; human. [Q9BYV1-1] DR CTD; 64902; -. DR GeneCards; AGXT2; -. DR HGNC; HGNC:14412; AGXT2. DR HPA; HPA037382; -. DR MIM; 612471; gene. DR neXtProt; NX_Q9BYV1; -. DR PharmGKB; PA24634; -. DR eggNOG; KOG1404; Eukaryota. DR eggNOG; COG0160; LUCA. DR GeneTree; ENSGT00530000062907; -. DR HOGENOM; HOG000020206; -. DR HOVERGEN; HBG004196; -. DR InParanoid; Q9BYV1; -. DR KO; K00827; -. DR OMA; LQVSKRP; -. DR OrthoDB; EOG79KPF2; -. DR PhylomeDB; Q9BYV1; -. DR TreeFam; TF105945; -. DR BioCyc; MetaCyc:HS03685-MONOMER; -. DR Reactome; R-HSA-389661; Glyoxylate metabolism and glycine degradation. DR Reactome; R-HSA-73621; Pyrimidine catabolism. DR ChiTaRS; AGXT2; human. DR GenomeRNAi; 64902; -. DR NextBio; 35481381; -. DR PRO; PR:Q9BYV1; -. DR Proteomes; UP000005640; Chromosome 5. DR Bgee; Q9BYV1; -. DR CleanEx; HS_AGXT2; -. 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:0016223; F:beta-alanine-pyruvate transaminase activity; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IBA:GO_Central. DR GO; GO:0030170; F:pyridoxal phosphate binding; IBA:GO_Central. DR GO; GO:0034641; P:cellular nitrogen compound metabolic process; TAS:Reactome. 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:0046487; P:glyoxylate metabolic process; TAS:Reactome. DR GO; GO:0019481; P:L-alanine catabolic process, by transamination; IDA:BHF-UCL. DR GO; GO:0055086; P:nucleobase-containing small molecule metabolic process; TAS:Reactome. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:BHF-UCL. DR GO; GO:0006206; P:pyrimidine nucleobase metabolic process; TAS:Reactome. DR GO; GO:0046135; P:pyrimidine nucleoside catabolic process; TAS:Reactome. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. 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_sub1. DR InterPro; IPR015422; PyrdxlP-dep_Trfase_major_sub2. DR PANTHER; PTHR11986; PTHR11986; 2. DR Pfam; PF00202; Aminotran_3; 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 Complete proteome; Direct protein sequencing; Mitochondrion; KW Polymorphism; Pyridoxal phosphate; Reference proteome; Transferase; KW Transit peptide. FT TRANSIT 1 41 Mitochondrion. FT {ECO:0000269|PubMed:20018850}. FT CHAIN 42 514 Alanine--glyoxylate aminotransferase 2, FT mitochondrial. FT /FTId=PRO_0000001269. FT MOD_RES 71 71 N6-acetyllysine; alternate. FT {ECO:0000250|UniProtKB:Q3UEG6}. FT MOD_RES 71 71 N6-succinyllysine; alternate. FT {ECO:0000250|UniProtKB:Q3UEG6}. FT MOD_RES 84 84 N6-acetyllysine. FT {ECO:0000250|UniProtKB:Q3UEG6}. FT MOD_RES 262 262 N6-acetyllysine; alternate. FT {ECO:0000250|UniProtKB:Q3UEG6}. FT MOD_RES 262 262 N6-succinyllysine; alternate. FT {ECO:0000250|UniProtKB:Q3UEG6}. FT MOD_RES 304 304 N6-succinyllysine. FT {ECO:0000250|UniProtKB:Q3UEG6}. FT MOD_RES 350 350 N6-(pyridoxal phosphate)lysine. FT {ECO:0000250}. FT MOD_RES 417 417 N6-acetyllysine; alternate. FT {ECO:0000250|UniProtKB:Q3UEG6}. FT MOD_RES 417 417 N6-succinyllysine; alternate. FT {ECO:0000250|UniProtKB:Q3UEG6}. FT MOD_RES 420 420 N6-acetyllysine; alternate. FT {ECO:0000250|UniProtKB:Q3UEG6}. FT MOD_RES 420 420 N6-succinyllysine; alternate. FT {ECO:0000250|UniProtKB:Q3UEG6}. FT VAR_SEQ 321 395 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_055802. FT VARIANT 102 102 S -> I (in dbSNP:rs37370). FT /FTId=VAR_061006. FT VARIANT 102 102 S -> N (in dbSNP:rs37370). FT {ECO:0000269|PubMed:15489334, FT ECO:0000269|Ref.2, ECO:0000269|Ref.3}. FT /FTId=VAR_023483. FT VARIANT 102 102 S -> T (in dbSNP:rs37370). FT /FTId=VAR_061007. FT VARIANT 132 132 G -> R (in dbSNP:rs16870794). FT /FTId=VAR_048231. FT VARIANT 140 140 V -> I (polymorphism; associated with an FT increased risk for coronary heart disease FT (CHD) in smoker and diabetic mellitus FT (DM) patients in a Chinese population; FT higher plasma symmetric (SDMA) FT dimethylarginine as well as plasma and FT urinary beta-aminoisobutyrate (BAIB) FT concentrations; localized to the FT mitochondrion as the wild-type; reduces FT alanine-glyoxylate aminotransferase FT activity; dbSNP:rs37369). FT {ECO:0000269|PubMed:24586340, FT ECO:0000269|PubMed:24834905, FT ECO:0000269|Ref.2, ECO:0000269|Ref.3}. FT /FTId=VAR_022140. FT VARIANT 212 212 T -> I (in dbSNP:rs180749). FT {ECO:0000269|PubMed:15489334, FT ECO:0000269|Ref.2, ECO:0000269|Ref.3}. FT /FTId=VAR_022141. FT VARIANT 492 492 P -> R (in dbSNP:rs17245714). FT /FTId=VAR_048232. FT VARIANT 498 498 V -> L (polymorphism; higher plasma and FT urinary beta-aminoisobutyrate (BAIB) FT concentrations; dbSNP:rs16899974). FT {ECO:0000269|PubMed:24586340, FT ECO:0000269|Ref.3}. FT /FTId=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 //