AGT1_HUMAN
ID AGT1_HUMAN Reviewed; 392 AA.
AC P21549; Q53QU6;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 1.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Alanine--glyoxylate aminotransferase {ECO:0000305};
DE Short=AGT;
DE EC=2.6.1.44 {ECO:0000269|PubMed:10960483, ECO:0000269|PubMed:12777626, ECO:0000269|PubMed:23229545, ECO:0000269|PubMed:24055001, ECO:0000269|PubMed:26149463};
DE AltName: Full=Serine--pyruvate aminotransferase {ECO:0000305};
DE Short=SPT;
DE EC=2.6.1.51 {ECO:0000269|PubMed:10347152};
GN Name=AGXT {ECO:0000312|HGNC:HGNC:341}; Synonyms=AGT1, SPAT;
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].
RC TISSUE=Liver;
RX PubMed=2253628; DOI=10.1111/j.1432-1033.1990.tb19420.x;
RA Nishiyama K., Berstein G., Oda T., Ichiyama A.;
RT "Cloning and nucleotide sequence of cDNA encoding human liver serine-
RT pyruvate aminotransferase.";
RL Eur. J. Biochem. 194:9-18(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-11 AND MET-340, VARIANT HP1
RP ARG-170, AND SUBCELLULAR LOCATION.
RX PubMed=1703535; DOI=10.1083/jcb.111.6.2341;
RA Purdue P.E., Takada Y., Danpure C.J.;
RT "Identification of mutations associated with peroxisome-to-mitochondrion
RT mistargeting of alanine/glyoxylate aminotransferase in primary
RT hyperoxaluria type 1.";
RL J. Cell Biol. 111:2341-2351(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2363689; DOI=10.1042/bj2680517;
RA Takada Y., Kaneko N., Esumi H., Purdue P.E., Danpure C.J.;
RT "Human peroxisomal L-alanine: glyoxylate aminotransferase. Evolutionary
RT loss of a mitochondrial targeting signal by point mutation of the
RT initiation codon.";
RL Biochem. J. 268:517-520(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2045108; DOI=10.1016/0888-7543(91)90481-s;
RA Purdue P.E., Lumb M.J., Fox M., Griffo G., Hamon-Benais C., Povey S.,
RA Danpure C.J.;
RT "Characterization and chromosomal mapping of a genomic clone encoding human
RT alanine:glyoxylate aminotransferase.";
RL Genomics 10:34-42(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=10347152; DOI=10.1074/jbc.274.23.16028;
RA Xue H.H., Sakaguchi T., Fujie M., Ogawa H., Ichiyama A.;
RT "Flux of the L-serine metabolism in rabbit, human, and dog livers.
RT Substantial contributions of both mitochondrial and peroxisomal
RT serine:pyruvate/alanine:glyoxylate aminotransferase.";
RL J. Biol. Chem. 274:16028-16033(1999).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-9, AND IDENTIFICATION BY MASS
RP 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 [11]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH PYRIDOXAL PHOSPHATE
RP AND AMINO-OXYACETIC ACID, SUBUNIT, AND PYRIDOXAL PHOSPHATE AT LYS-209.
RX PubMed=12899834; DOI=10.1016/s0022-2836(03)00791-5;
RA Zhang X., Roe S.M., Hou Y., Bartlam M., Rao Z., Pearl L.H., Danpure C.J.;
RT "Crystal structure of alanine:glyoxylate aminotransferase and the
RT relationship between genotype and enzymatic phenotype in primary
RT hyperoxaluria type 1.";
RL J. Mol. Biol. 331:643-652(2003).
RN [12]
RP VARIANT HP1 PRO-205.
RX PubMed=2039493; DOI=10.1016/0006-291x(91)90396-o;
RA Nishiyama K., Funai T., Katafuchi R., Hattori F., Onoyama K., Ichiyama A.;
RT "Primary hyperoxaluria type I due to a point mutation of T to C in the
RT coding region of the serine:pyruvate aminotransferase gene.";
RL Biochem. Biophys. Res. Commun. 176:1093-1099(1991).
RN [13]
RP VARIANT HP1 GLU-82.
RX PubMed=1349575; DOI=10.1016/0888-7543(92)90225-h;
RA Purdue P.E., Lumb M.J., Allsop J., Minatogawa Y., Danpure C.J.;
RT "A glycine-to-glutamate substitution abolishes alanine:glyoxylate
RT aminotransferase catalytic activity in a subset of patients with primary
RT hyperoxaluria type 1.";
RL Genomics 13:215-218(1992).
RN [14]
RP VARIANT HP1 PHE-187.
RX PubMed=1301173; DOI=10.1093/hmg/1.8.643;
RA Minatogawa Y., Tone S., Allsop J., Purdue P.E., Takada Y., Danpure C.J.,
RA Kido R.;
RT "A serine-to-phenylalanine substitution leads to loss of alanine:glyoxylate
RT aminotransferase catalytic activity and immunoreactivity in a patient with
RT primary hyperoxaluria type 1.";
RL Hum. Mol. Genet. 1:643-644(1992).
RN [15]
RP VARIANTS HP1 ARG-41 AND ILE-152.
RX PubMed=8101040;
RA Danpure C.J., Purdue P.E., Fryer P., Griffiths S., Allsop J., Lumb M.J.,
RA Guttridge K.M., Jennings P.R., Scheinman J.I., Mauer S.M., Davidson N.O.;
RT "Enzymological and mutational analysis of a complex primary hyperoxaluria
RT type 1 phenotype involving alanine:glyoxylate aminotransferase peroxisome-
RT to-mitochondrion mistargeting and intraperoxisomal aggregation.";
RL Am. J. Hum. Genet. 53:417-432(1993).
RN [16]
RP REVIEW ON HP1.
RX PubMed=8507692; DOI=10.1016/0300-9084(93)90091-6;
RA Danpure C.J.;
RT "Primary hyperoxaluria type 1 and peroxisome-to-mitochondrion mistargeting
RT of alanine:glyoxylate aminotransferase.";
RL Biochimie 75:309-315(1993).
RN [17]
RP VARIANTS HP1 CYS-233; HIS-233 AND THR-244.
RX PubMed=9192270; DOI=10.1136/jmg.34.6.489;
RA von Schnakenburg C., Rumsby G.;
RT "Primary hyperoxaluria type 1: a cluster of new mutations in exon 7 of the
RT AGXT gene.";
RL J. Med. Genet. 34:489-492(1997).
RN [18]
RP VARIANTS HP1 ARG-108; TYR-173; ARG-190; ALA-296 DEL AND ASP-350.
RX PubMed=9604803;
RA von Schnakenburg C., Rumsby G.;
RT "Identification of new mutations in primary hyperoxaluria type 1 (PH1).";
RL J. Nephrol. 11:15-17(1998).
RN [19]
RP VARIANTS HP1 VAL-41; GLU-95 INS; ARG-116 AND ARG-156.
RX PubMed=10394939; DOI=10.1007/s004390050984;
RA Amoroso A., Pirulli D., Puzzer D., Ferri L., Crovella S., Ferrettini C.,
RA Marangella M., Mazzola G., Florian F.;
RT "Gene symbol: AGXT. Disease: primary hyperoxaluria type I.";
RL Hum. Genet. 104:441-441(1999).
RN [20]
RP VARIANTS HP1 VAL-41; GLU-95 INS; ARG-116 AND ARG-156.
RX PubMed=10453743; DOI=10.1007/s004390050998;
RA Pirulli D., Puzzer D., Ferri L., Crovella S., Amoroso A., Ferrettini C.,
RA Marangella M., Mazzola G., Florian F.;
RT "Molecular analysis of hyperoxaluria type 1 in Italian patients reveals
RT eight new mutations in the alanine: glyoxylate aminotransferase gene.";
RL Hum. Genet. 104:523-525(1999).
RN [21]
RP VARIANTS HP1 ARG-41; ARG-156; ARG-190; THR-244; CYS-289 AND PRO-298.
RX PubMed=10541294; DOI=10.1681/asn.v10112352;
RA Rinat C., Wanders R.J.A., Drukker A., Halle D., Frishberg Y.;
RT "Primary hyperoxaluria type I: a model for multiple mutations in a
RT monogenic disease within a distinct ethnic group.";
RL J. Am. Soc. Nephrol. 10:2352-2358(1999).
RN [22]
RP VARIANTS HP1 ILE-152; ARG-170; ASN-183; CYS-233 AND THR-244.
RX PubMed=10862087;
RX DOI=10.1002/1098-1004(200006)15:6<577::aid-humu9>3.0.co;2-#;
RA Basmaison O., Rolland M.-O., Cochat P., Bozon D.;
RT "Identification of 5 novel mutations in the AGXT gene.";
RL Hum. Mutat. 15:577-577(2000).
RN [23]
RP CHARACTERIZATION OF VARIANTS HP1 ARG-41; GLU-82; ILE-152; ARG-170 AND
RP THR-244, CHARACTERIZATION OF VARIANT LEU-11, MUTAGENESIS OF LYS-209,
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, COFACTOR, SUBUNIT,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=10960483; DOI=10.1074/jbc.m006693200;
RA Lumb M.J., Danpure C.J.;
RT "Functional synergism between the most common polymorphism in human
RT alanine:glyoxylate aminotransferase and four of the most common disease-
RT causing mutations.";
RL J. Biol. Chem. 275:36415-36422(2000).
RN [24]
RP VARIANT HP1 ASP-112, AND VARIANT ILE-326.
RX PubMed=12559847; DOI=10.1016/s1096-7192(02)00204-4;
RA Coulter-Mackie M.B., Tung A., Henderson H.E., Toone J.R., Applegarth D.A.;
RT "The AGT gene in Africa: a distinctive minor allele haplotype, a
RT polymorphism (V326I), and a novel PH1 mutation (A112D) in Black Africans.";
RL Mol. Genet. Metab. 78:44-50(2003).
RN [25]
RP CHARACTERIZATION OF VARIANT HP1 THR-244, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=12777626; DOI=10.1073/pnas.1131968100;
RA Santana A., Salido E., Torres A., Shapiro L.J.;
RT "Primary hyperoxaluria type 1 in the Canary Islands: a conformational
RT disease due to I244T mutation in the P11L-containing alanine:glyoxylate
RT aminotransferase.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:7277-7282(2003).
RN [26]
RP VARIANTS HP1 ARG-82; ILE-152; VAL-153; ARG-170 AND ASP-336.
RX PubMed=15253729; DOI=10.1111/j.1523-1755.2004.00796.x;
RA van Woerden C.S., Groothoff J.W., Wijburg F.A., Annink C., Wanders R.J.A.,
RA Waterham H.R.;
RT "Clinical implications of mutation analysis in primary hyperoxaluria type
RT 1.";
RL Kidney Int. 66:746-752(2004).
RN [27]
RP VARIANTS HP1 VAL-139 DEL; ARG-156; LEU-158; ARG-190; GLU-201; LEU-233;
RP THR-244 AND ARG-253, AND VARIANT ASN-9.
RX PubMed=15849466; DOI=10.1159/000085411;
RA Monico C.G., Olson J.B., Milliner D.S.;
RT "Implications of genotype and enzyme phenotype in pyridoxine response of
RT patients with type I primary hyperoxaluria.";
RL Am. J. Nephrol. 25:183-188(2005).
RN [28]
RP VARIANTS HP1 ARG-41; ARG-108; ARG-156; ARG-190; ARG-195; HIS-243; THR-244;
RP MET-279; THR-287; CYS-289 AND PRO-298, AND VARIANT ASN-9.
RX PubMed=15961946; DOI=10.1159/000086357;
RA Frishberg Y., Rinat C., Shalata A., Khatib I., Feinstein S.,
RA Becker-Cohen R., Weismann I., Wanders R.J.A., Rumsby G., Roels F.,
RA Mandel H.;
RT "Intra-familial clinical heterogeneity: absence of genotype-phenotype
RT correlation in primary hyperoxaluria type 1 in Israel.";
RL Am. J. Nephrol. 25:269-275(2005).
RN [29]
RP VARIANTS HP1 ARG-161 AND LEU-218, AND VARIANTS THR-279 AND VAL-280.
RX PubMed=15963748; DOI=10.1016/j.ymgme.2005.05.005;
RA Coulter-Mackie M.B., Lian Q., Applegarth D., Toone J.;
RT "The major allele of the alanine:glyoxylate aminotransferase gene: nine
RT novel mutations and polymorphisms associated with primary hyperoxaluria
RT type 1.";
RL Mol. Genet. Metab. 86:172-178(2005).
RN [30]
RP CHARACTERIZATION OF VARIANTS HP1 ARG-41; VAL-41; GLU-82; ARG-108; ASP-112;
RP ARG-156; ARG-161; ARG-170; TYR-173; ASN-183; PHE-187; PRO-205 AND LEU-218,
RP MUTAGENESIS OF LYS-209, AND SUBUNIT.
RX PubMed=16971151; DOI=10.1016/j.ymgme.2006.07.013;
RA Coulter-Mackie M.B., Lian Q.;
RT "Consequences of missense mutations for dimerization and turnover of
RT alanine:glyoxylate aminotransferase: study of a spectrum of mutations.";
RL Mol. Genet. Metab. 89:349-359(2006).
RN [31]
RP VARIANTS HP1 CYS-36; ARG-41; GLU-41; PRO-150; ILE-152; ARG-156; LEU-158;
RP CYS-161; SER-161; PRO-166; ARG-170; TYR-173; CYS-233; HIS-233; THR-244 AND
RP ARG-253, VARIANT ASN-9, CHARACTERIZATION OF VARIANTS HP1 CYS-36; GLU-41;
RP PRO-150; ARG-156; LEU-158; CYS-161; SER-161; PRO-166; TYR-173; CYS-233;
RP HIS-233 AND ARG-253, AND CHARACTERIZATION OF VARIANT ASN-9.
RX PubMed=17495019; DOI=10.1373/clinchem.2006.084434;
RA Williams E., Rumsby G.;
RT "Selected exonic sequencing of the AGXT gene provides a genetic diagnosis
RT in 50% of patients with primary hyperoxaluria type 1.";
RL Clin. Chem. 53:1216-1221(2007).
RN [32]
RP CHARACTERIZATION OF VARIANTS HP1 ARG-161; CYS-161 AND SER-161, FUNCTION,
RP CATALYTIC ACTIVITY, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=24055001; DOI=10.1016/j.bbadis.2013.09.002;
RA Oppici E., Roncador A., Montioli R., Bianconi S., Cellini B.;
RT "Gly161 mutations associated with primary hyperoxaluria type I induce the
RT cytosolic aggregation and the intracellular degradation of the apo-form of
RT alanine:glyoxylate aminotransferase.";
RL Biochim. Biophys. Acta 1832:2277-2288(2013).
RN [33]
RP CHARACTERIZATION OF VARIANTS HP1 ARG-41; ILE-152; ARG-170 AND THR-244,
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=23229545; DOI=10.1074/jbc.m112.432617;
RA Fargue S., Lewin J., Rumsby G., Danpure C.J.;
RT "Four of the most common mutations in primary hyperoxaluria type 1 unmask
RT the cryptic mitochondrial targeting sequence of alanine:glyoxylate
RT aminotransferase encoded by the polymorphic minor allele.";
RL J. Biol. Chem. 288:2475-2484(2013).
RN [34]
RP VARIANT HP1 ASN-202.
RX PubMed=24934730; DOI=10.1186/1471-2369-15-92;
RA Li G.M., Xu H., Shen Q., Gong Y.N., Fang X.Y., Sun L., Liu H.M., An Y.;
RT "Mutational analysis of AGXT in two Chinese families with primary
RT hyperoxaluria type 1.";
RL BMC Nephrol. 15:92-92(2014).
RN [35]
RP CHARACTERIZATION OF VARIANT HP1 ARG-47, FUNCTION, CATALYTIC ACTIVITY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=26149463; DOI=10.1016/j.bbapap.2015.07.002;
RA Montioli R., Oppici E., Dindo M., Roncador A., Gotte G., Cellini B.,
RA Borri Voltattorni C.;
RT "Misfolding caused by the pathogenic mutation G47R on the minor allele of
RT alanine:glyoxylate aminotransferase and chaperoning activity of
RT pyridoxine.";
RL Biochim. Biophys. Acta 1854:1280-1289(2015).
CC -!- FUNCTION: Peroxisomal aminotransferase that catalyzes the
CC transamination of glyoxylate to glycine and contributes to the
CC glyoxylate detoxification (PubMed:10960483, PubMed:12777626,
CC PubMed:24055001, PubMed:23229545, PubMed:26149463). Also catalyzes the
CC transamination between L-serine and pyruvate and contributes to
CC gluconeogenesis from the L-serine metabolism (PubMed:10347152).
CC {ECO:0000269|PubMed:10347152, ECO:0000269|PubMed:10960483,
CC ECO:0000269|PubMed:12777626, ECO:0000269|PubMed:23229545,
CC ECO:0000269|PubMed:24055001, ECO:0000269|PubMed:26149463}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-serine + pyruvate = 3-hydroxypyruvate + L-alanine;
CC Xref=Rhea:RHEA:22852, ChEBI:CHEBI:15361, ChEBI:CHEBI:17180,
CC ChEBI:CHEBI:33384, ChEBI:CHEBI:57972; EC=2.6.1.51;
CC Evidence={ECO:0000269|PubMed:10347152};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22853;
CC Evidence={ECO:0000305|PubMed:10347152};
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 Evidence={ECO:0000269|PubMed:10960483, ECO:0000269|PubMed:12777626,
CC ECO:0000269|PubMed:23229545, ECO:0000269|PubMed:24055001,
CC ECO:0000269|PubMed:26149463};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24249;
CC Evidence={ECO:0000269|PubMed:24055001, ECO:0000269|PubMed:26149463};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:10960483};
CC -!- ACTIVITY REGULATION: Alanine--glyoxylate aminotransferase activity is
CC inhibited by 1 mM (aminooxy)acetic acid by 97.5%.
CC {ECO:0000269|PubMed:10960483}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9.1 mM for L-alanine (with the His-AGXT construct)
CC {ECO:0000269|PubMed:10960483};
CC KM=9.4 mM for L-alanine (with the AGXT-His construct)
CC {ECO:0000269|PubMed:10960483};
CC KM=0.23 mM for glyoxylate (with the His-AGXT construct)
CC {ECO:0000269|PubMed:10960483};
CC KM=0.39 mM for glyoxylate (with the AGXT-His construct)
CC {ECO:0000269|PubMed:10960483};
CC KM=0.36 mM for glyoxylate {ECO:0000269|PubMed:12777626};
CC KM=14.9 mM for L-alanine {ECO:0000269|PubMed:12777626};
CC pH dependence:
CC Optimum pH is 7.5- 8.5. {ECO:0000269|PubMed:10960483};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10960483,
CC ECO:0000269|PubMed:12777626, ECO:0000269|PubMed:12899834,
CC ECO:0000269|PubMed:16971151, ECO:0000269|PubMed:23229545,
CC ECO:0000269|PubMed:24055001}.
CC -!- INTERACTION:
CC P21549; P21549: AGXT; NbExp=6; IntAct=EBI-727098, EBI-727098;
CC P21549; P0C7T5: ATXN1L; NbExp=3; IntAct=EBI-727098, EBI-8624731;
CC P21549; Q9NR55: BATF3; NbExp=3; IntAct=EBI-727098, EBI-10312707;
CC P21549; Q9H5F2: C11orf1; NbExp=3; IntAct=EBI-727098, EBI-718615;
CC P21549; Q5BKX5-3: C19orf54; NbExp=3; IntAct=EBI-727098, EBI-11976299;
CC P21549; Q9UKJ5: CHIC2; NbExp=3; IntAct=EBI-727098, EBI-741528;
CC P21549; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-727098, EBI-3867333;
CC P21549; O43281-2: EFS; NbExp=3; IntAct=EBI-727098, EBI-11525448;
CC P21549; A1KXE4-2: FAM168B; NbExp=3; IntAct=EBI-727098, EBI-12193763;
CC P21549; Q5TD97: FHL5; NbExp=3; IntAct=EBI-727098, EBI-750641;
CC P21549; P49356: FNTB; NbExp=3; IntAct=EBI-727098, EBI-602349;
CC P21549; P53539: FOSB; NbExp=3; IntAct=EBI-727098, EBI-2806743;
CC P21549; P49639: HOXA1; NbExp=3; IntAct=EBI-727098, EBI-740785;
CC P21549; Q15323: KRT31; NbExp=3; IntAct=EBI-727098, EBI-948001;
CC P21549; O76011: KRT34; NbExp=3; IntAct=EBI-727098, EBI-1047093;
CC P21549; O76014: KRT37; NbExp=3; IntAct=EBI-727098, EBI-1045716;
CC P21549; Q6A162: KRT40; NbExp=3; IntAct=EBI-727098, EBI-10171697;
CC P21549; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-727098, EBI-11959885;
CC P21549; P60328: KRTAP12-3; NbExp=3; IntAct=EBI-727098, EBI-11953334;
CC P21549; Q9BYR8: KRTAP3-1; NbExp=3; IntAct=EBI-727098, EBI-9996449;
CC P21549; Q8IUC2: KRTAP8-1; NbExp=3; IntAct=EBI-727098, EBI-10261141;
CC P21549; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-727098, EBI-1044640;
CC P21549; O60711: LPXN; NbExp=3; IntAct=EBI-727098, EBI-744222;
CC P21549; Q99750: MDFI; NbExp=5; IntAct=EBI-727098, EBI-724076;
CC P21549; Q5VZ52: MORN5; NbExp=3; IntAct=EBI-727098, EBI-12835568;
CC P21549; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-727098, EBI-22310682;
CC P21549; O43482: OIP5; NbExp=3; IntAct=EBI-727098, EBI-536879;
CC P21549; P50542-1: PEX5; NbExp=4; IntAct=EBI-727098, EBI-15982193;
CC P21549; O15496: PLA2G10; NbExp=3; IntAct=EBI-727098, EBI-726466;
CC P21549; Q6ZR37: PLEKHG7; NbExp=3; IntAct=EBI-727098, EBI-12891828;
CC P21549; Q9NQX0: PRDM6; NbExp=3; IntAct=EBI-727098, EBI-11320284;
CC P21549; Q8HWS3: RFX6; NbExp=3; IntAct=EBI-727098, EBI-746118;
CC P21549; Q5W111-2: SPRYD7; NbExp=3; IntAct=EBI-727098, EBI-12408727;
CC P21549; Q8WVR3: TRAPPC14; NbExp=3; IntAct=EBI-727098, EBI-719893;
CC P21549; Q6DKK2: TTC19; NbExp=3; IntAct=EBI-727098, EBI-948354;
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:10960483,
CC ECO:0000269|PubMed:12777626, ECO:0000269|PubMed:1703535,
CC ECO:0000269|PubMed:23229545, ECO:0000269|PubMed:24055001,
CC ECO:0000269|PubMed:26149463}.
CC -!- TISSUE SPECIFICITY: Liver.
CC -!- POLYMORPHISM: Polymorphism at position 11 acts synergistically with
CC different mutations in AGXT producing specific enzymatic phenotypes in
CC HP1 patients. The combined presence of Leu-11 and Met-340 polymorphisms
CC defines the minor AGXT allele, whereas their absence defines the major
CC allele. The minor allele has frequencies of 20% in normal European and
CC North American populations, and 50% in HP1 patients.
CC {ECO:0000269|PubMed:1703535}.
CC -!- DISEASE: Hyperoxaluria primary 1 (HP1) [MIM:259900]: An inborn error of
CC glyoxylate metabolism characterized by increased excretion of oxalate
CC and glycolate, and progressive tissue accumulation of insoluble calcium
CC oxalate. Affected individuals are at risk for nephrolithiasis,
CC nephrocalcinosis and early onset end-stage renal disease.
CC {ECO:0000269|PubMed:10394939, ECO:0000269|PubMed:10453743,
CC ECO:0000269|PubMed:10541294, ECO:0000269|PubMed:10862087,
CC ECO:0000269|PubMed:10960483, ECO:0000269|PubMed:12559847,
CC ECO:0000269|PubMed:12777626, ECO:0000269|PubMed:1301173,
CC ECO:0000269|PubMed:1349575, ECO:0000269|PubMed:15253729,
CC ECO:0000269|PubMed:15849466, ECO:0000269|PubMed:15961946,
CC ECO:0000269|PubMed:15963748, ECO:0000269|PubMed:16971151,
CC ECO:0000269|PubMed:1703535, ECO:0000269|PubMed:17495019,
CC ECO:0000269|PubMed:2039493, ECO:0000269|PubMed:23229545,
CC ECO:0000269|PubMed:24055001, ECO:0000269|PubMed:24934730,
CC ECO:0000269|PubMed:26149463, ECO:0000269|PubMed:8101040,
CC ECO:0000269|PubMed:9192270, ECO:0000269|PubMed:9604803}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the class-V pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000305}.
CC -!- CAUTION: The intracellular compartmentalization of AGTX in mammalian
CC hepatocytes is species dependent. In human and rabbit, AGTX is
CC peroxisomal. In new world monkeys (marmoset) and rodents (rat and
CC mouse), it is distributed approximately evenly between peroxisomes and
CC mitochondria. In carnivores, like cat, the great majority of the enzyme
CC is mitochondrial with only a small proportion being peroxisomal.
CC {ECO:0000305}.
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DR EMBL; X56092; CAA39572.1; -; mRNA.
DR EMBL; X53414; CAA37493.1; -; mRNA.
DR EMBL; D13368; BAA02632.1; -; mRNA.
DR EMBL; M61763; AAA51680.1; -; Genomic_DNA.
DR EMBL; AK292754; BAF85443.1; -; mRNA.
DR EMBL; AC104809; AAY24168.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW71222.1; -; Genomic_DNA.
DR EMBL; BC132819; AAI32820.1; -; mRNA.
DR CCDS; CCDS2543.1; -.
DR PIR; I39419; XNHUSP.
DR RefSeq; NP_000021.1; NM_000030.2.
DR PDB; 1H0C; X-ray; 2.50 A; A=1-392.
DR PDB; 1J04; X-ray; 2.60 A; A=1-392.
DR PDB; 2YOB; X-ray; 1.90 A; A/B=1-388.
DR PDB; 3R9A; X-ray; 2.35 A; A/C=1-392.
DR PDB; 4CBR; X-ray; 2.30 A; A=1-392.
DR PDB; 4CBS; X-ray; 2.30 A; A=1-392.
DR PDB; 4I8A; X-ray; 2.90 A; A/B/C/D=1-392.
DR PDB; 4KXK; X-ray; 2.90 A; A/C=1-392.
DR PDB; 4KYO; X-ray; 2.20 A; A/C=1-392.
DR PDB; 5F9S; X-ray; 1.70 A; A/B=6-391.
DR PDB; 5HHY; X-ray; 1.70 A; A/B=6-391.
DR PDB; 5LUC; X-ray; 1.80 A; A/B/E/G/M/N/S/T=1-392.
DR PDB; 5OFY; X-ray; 2.80 A; A=1-392.
DR PDB; 5OG0; X-ray; 2.50 A; A=1-392.
DR PDB; 6RV0; X-ray; 2.70 A; A=1-392.
DR PDB; 6RV1; X-ray; 3.00 A; A=1-392.
DR PDB; 7NS7; X-ray; 2.20 A; A/B=1-392.
DR PDBsum; 1H0C; -.
DR PDBsum; 1J04; -.
DR PDBsum; 2YOB; -.
DR PDBsum; 3R9A; -.
DR PDBsum; 4CBR; -.
DR PDBsum; 4CBS; -.
DR PDBsum; 4I8A; -.
DR PDBsum; 4KXK; -.
DR PDBsum; 4KYO; -.
DR PDBsum; 5F9S; -.
DR PDBsum; 5HHY; -.
DR PDBsum; 5LUC; -.
DR PDBsum; 5OFY; -.
DR PDBsum; 5OG0; -.
DR PDBsum; 6RV0; -.
DR PDBsum; 6RV1; -.
DR PDBsum; 7NS7; -.
DR AlphaFoldDB; P21549; -.
DR SMR; P21549; -.
DR BioGRID; 106694; 43.
DR DIP; DIP-59650N; -.
DR IntAct; P21549; 37.
DR STRING; 9606.ENSP00000302620; -.
DR DrugBank; DB08060; 4-(2-AMINOPHENYL)-4-OXOBUTANOIC ACID.
DR DrugBank; DB00160; Alanine.
DR DrugBank; DB02079; Aminooxyacetic acid.
DR DrugBank; DB00145; Glycine.
DR DrugBank; DB04083; N(6)-(pyridoxal phosphate)-L-lysine.
DR DrugBank; DB00114; Pyridoxal phosphate.
DR DrugBank; DB00133; Serine.
DR iPTMnet; P21549; -.
DR PhosphoSitePlus; P21549; -.
DR BioMuta; AGXT; -.
DR DMDM; 134855; -.
DR MassIVE; P21549; -.
DR MaxQB; P21549; -.
DR PaxDb; P21549; -.
DR PeptideAtlas; P21549; -.
DR PRIDE; P21549; -.
DR ProteomicsDB; 53874; -.
DR Antibodypedia; 34535; 320 antibodies from 30 providers.
DR DNASU; 189; -.
DR Ensembl; ENST00000307503.4; ENSP00000302620.3; ENSG00000172482.5.
DR GeneID; 189; -.
DR KEGG; hsa:189; -.
DR MANE-Select; ENST00000307503.4; ENSP00000302620.3; NM_000030.3; NP_000021.1.
DR UCSC; uc002waa.5; human.
DR CTD; 189; -.
DR DisGeNET; 189; -.
DR GeneCards; AGXT; -.
DR GeneReviews; AGXT; -.
DR HGNC; HGNC:341; AGXT.
DR HPA; ENSG00000172482; Tissue enriched (liver).
DR MalaCards; AGXT; -.
DR MIM; 259900; phenotype.
DR MIM; 604285; gene.
DR neXtProt; NX_P21549; -.
DR OpenTargets; ENSG00000172482; -.
DR Orphanet; 93598; Primary hyperoxaluria type 1.
DR PharmGKB; PA24633; -.
DR VEuPathDB; HostDB:ENSG00000172482; -.
DR eggNOG; KOG2862; Eukaryota.
DR GeneTree; ENSGT00940000153241; -.
DR HOGENOM; CLU_027686_0_0_1; -.
DR InParanoid; P21549; -.
DR OMA; KNWLPIM; -.
DR OrthoDB; 984738at2759; -.
DR PhylomeDB; P21549; -.
DR TreeFam; TF313234; -.
DR BioCyc; MetaCyc:HS10525-MON; -.
DR BRENDA; 2.6.1.44; 2681.
DR BRENDA; 2.6.1.51; 2681.
DR PathwayCommons; P21549; -.
DR Reactome; R-HSA-389661; Glyoxylate metabolism and glycine degradation.
DR Reactome; R-HSA-9033241; Peroxisomal protein import.
DR SignaLink; P21549; -.
DR BioGRID-ORCS; 189; 8 hits in 1070 CRISPR screens.
DR EvolutionaryTrace; P21549; -.
DR GeneWiki; AGXT; -.
DR GenomeRNAi; 189; -.
DR Pharos; P21549; Tbio.
DR PRO; PR:P21549; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P21549; protein.
DR Bgee; ENSG00000172482; Expressed in right lobe of liver and 95 other tissues.
DR Genevisible; P21549; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005782; C:peroxisomal matrix; IDA:UniProtKB.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0008453; F:alanine-glyoxylate transaminase activity; IDA:UniProtKB.
DR GO; GO:0016597; F:amino acid binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0043621; F:protein self-association; IDA:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:UniProtKB.
DR GO; GO:0004760; F:serine-pyruvate transaminase activity; IDA:UniProtKB.
DR GO; GO:0008483; F:transaminase activity; IDA:UniProtKB.
DR GO; GO:0019265; P:glycine biosynthetic process, by transamination of glyoxylate; IDA:UniProtKB.
DR GO; GO:0009436; P:glyoxylate catabolic process; IDA:UniProtKB.
DR GO; GO:0046487; P:glyoxylate metabolic process; IDA:UniProtKB.
DR GO; GO:0042853; P:L-alanine catabolic process; IDA:UniProtKB.
DR GO; GO:0019448; P:L-cysteine catabolic process; IDA:UniProtKB.
DR GO; GO:0006563; P:L-serine metabolic process; IDA:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0046724; P:oxalic acid secretion; IEA:Ensembl.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR000192; Aminotrans_V_dom.
DR InterPro; IPR020578; Aminotrans_V_PyrdxlP_BS.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR InterPro; IPR024169; SP_NH2Trfase/AEP_transaminase.
DR Pfam; PF00266; Aminotran_5; 1.
DR PIRSF; PIRSF000524; SPT; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
DR PROSITE; PS00595; AA_TRANSFER_CLASS_5; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Aminotransferase; Disease variant; Peroxisome;
KW Phosphoprotein; Pyridoxal phosphate; Reference proteome; Transferase.
FT CHAIN 1..392
FT /note="Alanine--glyoxylate aminotransferase"
FT /id="PRO_0000150237"
FT BINDING 360
FT /ligand="substrate"
FT MOD_RES 9
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 209
FT /note="N6-(pyridoxal phosphate)lysine"
FT MOD_RES 225
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O35423"
FT MOD_RES 225
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O35423"
FT MOD_RES 234
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O35423"
FT MOD_RES 312
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O35423"
FT VARIANT 9
FT /note="T -> N (no loss of alanine--glyoxylate
FT aminotransferase activity; dbSNP:rs115014558)"
FT /evidence="ECO:0000269|PubMed:15849466,
FT ECO:0000269|PubMed:15961946, ECO:0000269|PubMed:17495019"
FT /id="VAR_060547"
FT VARIANT 11
FT /note="P -> L (reduction of specific alanine--glyoxylate
FT aminotransferase activity in vitro; causes mitochondrial
FT mistargeting when associated with R-170; dbSNP:rs34116584)"
FT /evidence="ECO:0000269|PubMed:10960483,
FT ECO:0000269|PubMed:1703535"
FT /id="VAR_000587"
FT VARIANT 22
FT /note="N -> S (in dbSNP:rs34885252)"
FT /id="VAR_048236"
FT VARIANT 36
FT /note="R -> C (in HP1; when associated with L-11 and M-340
FT on the minor AGXT allele; results in loss of alanine--
FT glyoxylate aminotransferase activity; dbSNP:rs180177157)"
FT /evidence="ECO:0000269|PubMed:17495019"
FT /id="VAR_074582"
FT VARIANT 41
FT /note="G -> E (in HP1; loss of alanine--glyoxylate
FT aminotransferase activity; dbSNP:rs180177168)"
FT /evidence="ECO:0000269|PubMed:17495019"
FT /id="VAR_074583"
FT VARIANT 41
FT /note="G -> R (in HP1; when associated with L-11 and M-340
FT on the minor AGXT allele; results in loss of protein
FT stability; loss of alanine--glyoxylate aminotransferase
FT activity; loss of dimerization; partial mitochondrial
FT mistargeting; intraperoxisomal protein aggregation seen;
FT dbSNP:rs121908523)"
FT /evidence="ECO:0000269|PubMed:10541294,
FT ECO:0000269|PubMed:10960483, ECO:0000269|PubMed:15961946,
FT ECO:0000269|PubMed:16971151, ECO:0000269|PubMed:17495019,
FT ECO:0000269|PubMed:23229545, ECO:0000269|PubMed:8101040"
FT /id="VAR_000588"
FT VARIANT 41
FT /note="G -> V (in HP1; reduced alanine--glyoxylate
FT aminotransferase activity; no loss of dimerization; no
FT effect on protein stability; dbSNP:rs180177168)"
FT /evidence="ECO:0000269|PubMed:10394939,
FT ECO:0000269|PubMed:10453743, ECO:0000269|PubMed:16971151"
FT /id="VAR_010969"
FT VARIANT 47
FT /note="G -> R (in HP1; when associated with L-11 and M-340
FT on the minor AGXT allele; results in protein misfolding;
FT decreased alanine--glyoxylate aminotransferase activity;
FT reduced expression levels; reduced pyridoxal phosphate
FT binding; reduced dimerization; reduced thermostability;
FT increased propensity to aggregation; increased
FT susceptibility to proteolytic degradation within the N-
FT terminal region; mitochondrial mistargeting; exposure to
FT pyridoxine can rescue the functionality by partially
FT preventing aggregation and degradation and by redirecting
FT all the protein to the peroxisome; dbSNP:rs180177173)"
FT /evidence="ECO:0000269|PubMed:26149463"
FT /id="VAR_074584"
FT VARIANT 82
FT /note="G -> E (in HP1; abolishes alanine--glyoxylate
FT aminotransferase activity by interfering with pyridoxal
FT phosphate binding; dbSNP:rs121908522)"
FT /evidence="ECO:0000269|PubMed:10960483,
FT ECO:0000269|PubMed:1349575, ECO:0000269|PubMed:16971151"
FT /id="VAR_008878"
FT VARIANT 82
FT /note="G -> R (in HP1; dbSNP:rs180177185)"
FT /evidence="ECO:0000269|PubMed:15253729"
FT /id="VAR_060548"
FT VARIANT 95
FT /note="E -> EE (in HP1)"
FT /evidence="ECO:0000269|PubMed:10394939,
FT ECO:0000269|PubMed:10453743"
FT /id="VAR_010970"
FT VARIANT 108
FT /note="W -> R (in HP1; when associated with L-11 and M-340
FT on the minor AGXT allele; results in loss of alanine--
FT glyoxylate aminotransferase activity; loss of dimerization;
FT decreased protein stability; dbSNP:rs180177197)"
FT /evidence="ECO:0000269|PubMed:15961946,
FT ECO:0000269|PubMed:16971151, ECO:0000269|PubMed:9604803"
FT /id="VAR_060549"
FT VARIANT 112
FT /note="A -> D (in HP1; loss of alanine--glyoxylate
FT aminotransferase activity; loss of dimerization; decreased
FT protein stability; causes protein aggregation;
FT dbSNP:rs796052061)"
FT /evidence="ECO:0000269|PubMed:12559847,
FT ECO:0000269|PubMed:16971151"
FT /id="VAR_060550"
FT VARIANT 116
FT /note="G -> R (in HP1; dbSNP:rs180177207)"
FT /evidence="ECO:0000269|PubMed:10394939,
FT ECO:0000269|PubMed:10453743"
FT /id="VAR_010971"
FT VARIANT 139
FT /note="Missing (in HP1)"
FT /evidence="ECO:0000269|PubMed:15849466"
FT /id="VAR_060551"
FT VARIANT 150
FT /note="L -> P (in HP1; when associated with L-11 and M-340
FT on the minor AGXT allele; results in loss of alanine--
FT glyoxylate aminotransferase activity; dbSNP:rs180177222)"
FT /evidence="ECO:0000269|PubMed:17495019"
FT /id="VAR_074585"
FT VARIANT 152
FT /note="F -> I (in HP1; when associated with L-11 and M-340
FT on the minor AGXT allele; results in protein
FT destabilization; decreased alanine--glyoxylate
FT aminotransferase activity; no loss of dimerization;
FT mitochondrial mistargeting; dbSNP:rs121908524)"
FT /evidence="ECO:0000269|PubMed:10862087,
FT ECO:0000269|PubMed:10960483, ECO:0000269|PubMed:15253729,
FT ECO:0000269|PubMed:17495019, ECO:0000269|PubMed:23229545,
FT ECO:0000269|PubMed:8101040"
FT /id="VAR_000589"
FT VARIANT 153
FT /note="L -> V (in HP1; dbSNP:rs180177223)"
FT /evidence="ECO:0000269|PubMed:15253729"
FT /id="VAR_060552"
FT VARIANT 156
FT /note="G -> R (in HP1; loss of alanine--glyoxylate
FT aminotransferase activity; loss of dimerization; decreased
FT protein stability; dbSNP:rs121908530)"
FT /evidence="ECO:0000269|PubMed:10394939,
FT ECO:0000269|PubMed:10453743, ECO:0000269|PubMed:10541294,
FT ECO:0000269|PubMed:15849466, ECO:0000269|PubMed:15961946,
FT ECO:0000269|PubMed:16971151, ECO:0000269|PubMed:17495019"
FT /id="VAR_010972"
FT VARIANT 158
FT /note="S -> L (in HP1; loss of alanine--glyoxylate
FT aminotransferase activity; dbSNP:rs180177225)"
FT /evidence="ECO:0000269|PubMed:15849466,
FT ECO:0000269|PubMed:17495019"
FT /id="VAR_060553"
FT VARIANT 161
FT /note="G -> C (in HP1; when associated with L-11 and M-340
FT on the minor AGXT allele; results in loss of alanine--
FT glyoxylate aminotransferase activity; reduced expression
FT levels; decreased protein stability; protein aggregation
FT seen in the cytosol with a decreased aggregation propensity
FT in the presence of pyridoxal phosphate; reduced peroxisomal
FT localization; dbSNP:rs180177227)"
FT /evidence="ECO:0000269|PubMed:17495019,
FT ECO:0000269|PubMed:24055001"
FT /id="VAR_074586"
FT VARIANT 161
FT /note="G -> R (in HP1; loss of alanine--glyoxylate
FT aminotransferase activity; reduced expression levels;
FT decreased protein stability; protein aggregation seen in
FT the cytosol with a decreased aggregation propensity in the
FT presence of pyridoxal phosphate; loss of dimerization;
FT dbSNP:rs180177227)"
FT /evidence="ECO:0000269|PubMed:15963748,
FT ECO:0000269|PubMed:16971151, ECO:0000269|PubMed:24055001"
FT /id="VAR_060554"
FT VARIANT 161
FT /note="G -> S (in HP1; when associated with L-11 and M-340
FT on the minor AGXT allele; results in loss of alanine--
FT glyoxylate aminotransferase activity; reduced expression
FT levels; decreased protein stability; protein aggregation
FT seen in the cytosol with a decreased aggregation propensity
FT in the presence of pyridoxal phosphate; reduced peroxisomal
FT localization; dbSNP:rs180177227)"
FT /evidence="ECO:0000269|PubMed:17495019,
FT ECO:0000269|PubMed:24055001"
FT /id="VAR_074587"
FT VARIANT 166
FT /note="L -> P (in HP1; when associated with L-11 and M-340
FT on the minor AGXT allele; results in loss of alanine--
FT glyoxylate aminotransferase activity; dbSNP:rs180177230)"
FT /evidence="ECO:0000269|PubMed:17495019"
FT /id="VAR_074588"
FT VARIANT 170
FT /note="G -> R (in HP1; when associated with L-11 and M-340
FT on the minor AGXT allele; results in mitochondrial
FT mistargeting; slight decrease in alanine--glyoxylate
FT aminotransferase activity; loss of dimerization; partial
FT loss of protein stability but protein stability increases
FT in the presence of pyridoxal phosphate; causes protein
FT aggregation; dbSNP:rs121908529)"
FT /evidence="ECO:0000269|PubMed:10862087,
FT ECO:0000269|PubMed:10960483, ECO:0000269|PubMed:15253729,
FT ECO:0000269|PubMed:16971151, ECO:0000269|PubMed:1703535,
FT ECO:0000269|PubMed:17495019, ECO:0000269|PubMed:23229545"
FT /id="VAR_000590"
FT VARIANT 173
FT /note="C -> Y (in HP1; loss of alanine--glyoxylate
FT aminotransferase activity; loss of dimerization; decreased
FT protein stability; causes protein aggregation;
FT dbSNP:rs180177231)"
FT /evidence="ECO:0000269|PubMed:16971151,
FT ECO:0000269|PubMed:17495019, ECO:0000269|PubMed:9604803"
FT /id="VAR_060555"
FT VARIANT 183
FT /note="D -> N (in HP1; loss of alanine--glyoxylate
FT aminotransferase activity; no loss of dimerization; no
FT effect on protein stability; dbSNP:rs180177236)"
FT /evidence="ECO:0000269|PubMed:10862087,
FT ECO:0000269|PubMed:16971151"
FT /id="VAR_010973"
FT VARIANT 187
FT /note="S -> F (in HP1; loss of alanine--glyoxylate
FT aminotransferase activity; loss of dimerization but
FT improved dimerization in the presence of pyridoxal
FT phosphate; decreased protein stability; dbSNP:rs180177238)"
FT /evidence="ECO:0000269|PubMed:1301173,
FT ECO:0000269|PubMed:16971151"
FT /id="VAR_000591"
FT VARIANT 190
FT /note="G -> R (in HP1; dbSNP:rs180177239)"
FT /evidence="ECO:0000269|PubMed:10541294,
FT ECO:0000269|PubMed:15849466, ECO:0000269|PubMed:15961946,
FT ECO:0000269|PubMed:9604803"
FT /id="VAR_060556"
FT VARIANT 195
FT /note="M -> R (in HP1; dbSNP:rs180177244)"
FT /evidence="ECO:0000269|PubMed:15961946"
FT /id="VAR_060557"
FT VARIANT 201
FT /note="D -> E (in HP1; dbSNP:rs180177246)"
FT /evidence="ECO:0000269|PubMed:15849466"
FT /id="VAR_060558"
FT VARIANT 202
FT /note="I -> N (in HP1; unknown pathological significance;
FT dbSNP:rs536352238)"
FT /evidence="ECO:0000269|PubMed:24934730"
FT /id="VAR_074589"
FT VARIANT 205
FT /note="S -> P (in HP1; loss of alanine--glyoxylate
FT aminotransferase activity; decreased protein stability;
FT dbSNP:rs121908520)"
FT /evidence="ECO:0000269|PubMed:16971151,
FT ECO:0000269|PubMed:2039493"
FT /id="VAR_000592"
FT VARIANT 218
FT /note="S -> L (in HP1; loss of alanine--glyoxylate
FT aminotransferase activity; loss of dimerization; no effect
FT on protein stability; dbSNP:rs180177253)"
FT /evidence="ECO:0000269|PubMed:15963748,
FT ECO:0000269|PubMed:16971151"
FT /id="VAR_060559"
FT VARIANT 233
FT /note="R -> C (in HP1; when associated with L-11 and M-340
FT on the minor AGXT allele; results in loss of alanine--
FT glyoxylate aminotransferase activity; dbSNP:rs121908526)"
FT /evidence="ECO:0000269|PubMed:10862087,
FT ECO:0000269|PubMed:17495019, ECO:0000269|PubMed:9192270"
FT /id="VAR_008879"
FT VARIANT 233
FT /note="R -> H (in HP1; when associated with L-11 and M-340
FT on the minor AGXT allele; results in loss of alanine--
FT glyoxylate aminotransferase activity; dbSNP:rs121908527)"
FT /evidence="ECO:0000269|PubMed:17495019,
FT ECO:0000269|PubMed:9192270"
FT /id="VAR_008880"
FT VARIANT 233
FT /note="R -> L (in HP1; dbSNP:rs121908527)"
FT /evidence="ECO:0000269|PubMed:15849466"
FT /id="VAR_060560"
FT VARIANT 243
FT /note="D -> H (in HP1; dbSNP:rs180177258)"
FT /evidence="ECO:0000269|PubMed:15961946"
FT /id="VAR_060561"
FT VARIANT 244
FT /note="I -> T (in HP1; prevalent mutation in the Canary
FT islands; when associated with L-11 and M-340 on the minor
FT AGXT allele; results in protein misfolding; decreased
FT alanine--glyoxylate aminotransferase activity; no loss of
FT dimerization; partial mitochondrial mistargeting;
FT dbSNP:rs121908525)"
FT /evidence="ECO:0000269|PubMed:10541294,
FT ECO:0000269|PubMed:10862087, ECO:0000269|PubMed:10960483,
FT ECO:0000269|PubMed:12777626, ECO:0000269|PubMed:15849466,
FT ECO:0000269|PubMed:15961946, ECO:0000269|PubMed:17495019,
FT ECO:0000269|PubMed:23229545, ECO:0000269|PubMed:9192270"
FT /id="VAR_008881"
FT VARIANT 253
FT /note="C -> R (in HP1; when associated with L-11 and M-340
FT on the minor AGXT allele; results in loss of alanine--
FT glyoxylate aminotransferase activity; dbSNP:rs180177264)"
FT /evidence="ECO:0000269|PubMed:15849466,
FT ECO:0000269|PubMed:17495019"
FT /id="VAR_060562"
FT VARIANT 279
FT /note="I -> M (in HP1; dbSNP:rs180177277)"
FT /evidence="ECO:0000269|PubMed:15961946"
FT /id="VAR_060563"
FT VARIANT 279
FT /note="I -> T (in dbSNP:rs140992177)"
FT /evidence="ECO:0000269|PubMed:15963748"
FT /id="VAR_060564"
FT VARIANT 280
FT /note="A -> V (in dbSNP:rs73106685)"
FT /evidence="ECO:0000269|PubMed:15963748"
FT /id="VAR_060565"
FT VARIANT 287
FT /note="S -> T (in HP1; dbSNP:rs180177289)"
FT /evidence="ECO:0000269|PubMed:15961946"
FT /id="VAR_060566"
FT VARIANT 289
FT /note="R -> C (in HP1; dbSNP:rs180177290)"
FT /evidence="ECO:0000269|PubMed:10541294,
FT ECO:0000269|PubMed:15961946"
FT /id="VAR_060567"
FT VARIANT 295
FT /note="A -> T (in dbSNP:rs13408961)"
FT /id="VAR_048237"
FT VARIANT 296
FT /note="Missing (in HP1; dbSNP:rs180177291)"
FT /evidence="ECO:0000269|PubMed:9604803"
FT /id="VAR_060568"
FT VARIANT 298
FT /note="L -> P (in HP1; dbSNP:rs180177293)"
FT /evidence="ECO:0000269|PubMed:10541294,
FT ECO:0000269|PubMed:15961946"
FT /id="VAR_060569"
FT VARIANT 326
FT /note="V -> I (in dbSNP:rs115057148)"
FT /evidence="ECO:0000269|PubMed:12559847"
FT /id="VAR_060570"
FT VARIANT 336
FT /note="V -> D (in HP1; dbSNP:rs180177155)"
FT /evidence="ECO:0000269|PubMed:15253729"
FT /id="VAR_060571"
FT VARIANT 340
FT /note="I -> M (associated with hyperoxaluria;
FT dbSNP:rs4426527)"
FT /evidence="ECO:0000269|PubMed:1703535"
FT /id="VAR_000593"
FT VARIANT 350
FT /note="G -> D (in HP1; dbSNP:rs180177156)"
FT /evidence="ECO:0000269|PubMed:9604803"
FT /id="VAR_060572"
FT MUTAGEN 209
FT /note="K->R: Affects pyridoxal phosphate binding; loss of
FT alanine--glyoxylate aminotransferase activity."
FT /evidence="ECO:0000269|PubMed:10960483,
FT ECO:0000269|PubMed:16971151"
FT HELIX 13..15
FT /evidence="ECO:0007829|PDB:5F9S"
FT STRAND 27..29
FT /evidence="ECO:0007829|PDB:5F9S"
FT HELIX 35..41
FT /evidence="ECO:0007829|PDB:5F9S"
FT HELIX 51..68
FT /evidence="ECO:0007829|PDB:5F9S"
FT STRAND 73..80
FT /evidence="ECO:0007829|PDB:5F9S"
FT HELIX 82..93
FT /evidence="ECO:0007829|PDB:5F9S"
FT STRAND 99..106
FT /evidence="ECO:0007829|PDB:5F9S"
FT HELIX 107..118
FT /evidence="ECO:0007829|PDB:5F9S"
FT STRAND 122..127
FT /evidence="ECO:0007829|PDB:5F9S"
FT HELIX 136..146
FT /evidence="ECO:0007829|PDB:5F9S"
FT STRAND 149..156
FT /evidence="ECO:0007829|PDB:5F9S"
FT TURN 158..160
FT /evidence="ECO:0007829|PDB:5F9S"
FT HELIX 169..175
FT /evidence="ECO:0007829|PDB:5F9S"
FT STRAND 179..183
FT /evidence="ECO:0007829|PDB:5F9S"
FT TURN 185..190
FT /evidence="ECO:0007829|PDB:5F9S"
FT TURN 195..199
FT /evidence="ECO:0007829|PDB:5F9S"
FT STRAND 201..209
FT /evidence="ECO:0007829|PDB:5F9S"
FT STRAND 218..222
FT /evidence="ECO:0007829|PDB:5F9S"
FT HELIX 224..231
FT /evidence="ECO:0007829|PDB:5F9S"
FT HELIX 244..250
FT /evidence="ECO:0007829|PDB:5F9S"
FT STRAND 254..256
FT /evidence="ECO:0007829|PDB:5F9S"
FT HELIX 266..282
FT /evidence="ECO:0007829|PDB:5F9S"
FT HELIX 284..304
FT /evidence="ECO:0007829|PDB:5F9S"
FT STRAND 308..311
FT /evidence="ECO:0007829|PDB:5F9S"
FT HELIX 314..316
FT /evidence="ECO:0007829|PDB:5F9S"
FT STRAND 321..325
FT /evidence="ECO:0007829|PDB:5F9S"
FT HELIX 332..343
FT /evidence="ECO:0007829|PDB:5F9S"
FT STRAND 344..346
FT /evidence="ECO:0007829|PDB:4KYO"
FT HELIX 352..354
FT /evidence="ECO:0007829|PDB:5F9S"
FT TURN 355..357
FT /evidence="ECO:0007829|PDB:5F9S"
FT STRAND 358..362
FT /evidence="ECO:0007829|PDB:5F9S"
FT HELIX 365..367
FT /evidence="ECO:0007829|PDB:5F9S"
FT HELIX 370..386
FT /evidence="ECO:0007829|PDB:5F9S"
SQ SEQUENCE 392 AA; 43010 MW; 2987DDE85B2470B4 CRC64;
MASHKLLVTP PKALLKPLSI PNQLLLGPGP SNLPPRIMAA GGLQMIGSMS KDMYQIMDEI
KEGIQYVFQT RNPLTLVISG SGHCALEAAL VNVLEPGDSF LVGANGIWGQ RAVDIGERIG
ARVHPMTKDP GGHYTLQEVE EGLAQHKPVL LFLTHGESST GVLQPLDGFG ELCHRYKCLL
LVDSVASLGG TPLYMDRQGI DILYSGSQKA LNAPPGTSLI SFSDKAKKKM YSRKTKPFSF
YLDIKWLANF WGCDDQPRMY HHTIPVISLY SLRESLALIA EQGLENSWRQ HREAAAYLHG
RLQALGLQLF VKDPALRLPT VTTVAVPAGY DWRDIVSYVI DHFDIEIMGG LGPSTGKVLR
IGLLGCNATR ENVDRVTEAL RAALQHCPKK KL
