Glycine amidinotransferase, mitochondrial

Details

Name
Glycine amidinotransferase, mitochondrial
Synonyms
  • 2.1.4.1
  • AGAT
  • L-arginine:glycine amidinotransferase
  • Transamidinase
Gene Name
GATM
Organism
Humans
Amino acid sequence
>lcl|BSEQ0000691|Glycine amidinotransferase, mitochondrial
MLRVRCLRGGSRGAEAVHYIGSRLGRTLTGWVQRTFQSTQAATASSRNSCAADDKATEPL
PKDCPVSSYNEWDPLEEVIVGRAENACVPPFTIEVKANTYEKYWPFYQKQGGHYFPKDHL
KKAVAEIEEMCNILKTEGVTVRRPDPIDWSLKYKTPDFESTGLYSAMPRDILIVVGNEII
EAPMAWRSRFFEYRAYRSIIKDYFHRGAKWTTAPKPTMADELYNQDYPIHSVEDRHKLAA
QGKFVTTEFEPCFDAADFIRAGRDIFAQRSQVTNYLGIEWMRRHLAPDYRVHIISFKDPN
PMHIDATFNIIGPGIVLSNPDRPCHQIDLFKKAGWTIITPPTPIIPDDHPLWMSSKWLSM
NVLMLDEKRVMVDANEVPIQKMFEKLGITTIKVNIRNANSLGGGFHCWTCDVRRRGTLQS
YLD
Number of residues
423
Molecular Weight
48455.01
Theoretical pI
8.15
GO Classification
Functions
glycine amidinotransferase activity
Processes
cellular nitrogen compound metabolic process / creatine biosynthetic process / creatine metabolic process / embryonic liver development / polyamine metabolic process / response to mercury ion / response to nutrient / response to oxidative stress / response to peptide hormone / small molecule metabolic process / tissue regeneration
Components
extracellular exosome / mitochondrial inner membrane / mitochondrial intermembrane space
General Function
Glycine amidinotransferase activity
Specific Function
Catalyzes the biosynthesis of guanidinoacetate, the immediate precursor of creatine. Creatine plays a vital role in energy metabolism in muscle tissues. May play a role in embryonic and central nervous system development. May be involved in the response to heart failure by elevating local creatine synthesis.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Mitochondrion inner membrane
Gene sequence
>lcl|BSEQ0010101|Glycine amidinotransferase, mitochondrial (GATM)
ATGCTGCGGGTGCGGTGTCTGCGCGGCGGGAGCCGCGGCGCCGAGGCGGTGCACTACATC
GGATCTCGGCTTGGACGAACCTTGACAGGATGGGTGCAGCGAACTTTCCAGAGCACCCAG
GCAGCTACGGCTTCCTCCCGGAACTCCTGTGCAGCTGACGACAAAGCCACTGAGCCTCTG
CCCAAGGACTGCCCTGTCTCTTCTTACAACGAATGGGACCCCTTAGAGGAAGTGATAGTG
GGCAGAGCAGAAAACGCCTGTGTTCCACCGTTCACCATCGAGGTGAAGGCCAACACATAT
GAAAAGTACTGGCCATTTTACCAGAAGCAAGGAGGGCATTATTTTCCCAAAGATCATTTG
AAAAAGGCTGTTGCTGAAATTGAAGAAATGTGCAATATTTTAAAAACGGAAGGAGTGACA
GTAAGGAGGCCTGACCCCATTGACTGGTCATTGAAGTATAAAACTCCTGATTTTGAGTCT
ACGGGTTTATACAGTGCAATGCCTCGAGACATCCTGATAGTTGTGGGCAATGAGATTATC
GAGGCTCCCATGGCATGGCGTTCACGCTTCTTTGAGTACCGAGCGTACAGGTCAATTATC
AAAGACTACTTCCACCGTGGCGCCAAGTGGACAACAGCTCCTAAGCCCACAATGGCTGAT
GAGCTTTATAACCAGGATTATCCCATCCACTCTGTAGAAGACAGACACAAATTGGCTGCT
CAGGGAAAATTTGTGACAACTGAGTTTGAGCCATGCTTTGATGCTGCTGACTTCATTCGA
GCTGGAAGAGATATTTTTGCACAGAGAAGCCAGGTTACAAACTACCTAGGCATTGAATGG
ATGCGTAGGCATCTTGCTCCAGACTACAGAGTGCATATCATCTCCTTTAAAGATCCCAAT
CCCATGCATATTGATGCTACCTTCAACATCATTGGACCTGGTATTGTGCTTTCCAACCCT
GACCGACCATGTCACCAGATTGATCTTTTCAAGAAAGCAGGATGGACTATCATTACTCCT
CCAACACCAATCATCCCAGACGATCATCCACTCTGGATGTCATCCAAATGGCTTTCCATG
AATGTCTTAATGCTAGATGAAAAACGTGTTATGGTGGATGCCAATGAAGTTCCAATTCAA
AAGATGTTTGAAAAGCTGGGTATCACTACCATTAAAGTTAACATTCGTAATGCCAATTCC
CTGGGAGGAGGCTTCCATTGCTGGACCTGCGATGTCCGGCGCCGAGGCACCTTACAGTCC
TACTTGGACTGA
Chromosome Location
15
Locus
15q21.1
External Identifiers
ResourceLink
UniProtKB IDP50440
UniProtKB Entry NameGATM_HUMAN
GenBank Protein ID545385
GenBank Gene IDS68805
GenAtlas IDGATM
HGNC IDHGNC:4175
General References
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  5. Gross MD, Eggen MA, Simon AM, Van Pilsum JF: The purification and characterization of human kidney L-arginine:glycine amidinotransferase. Arch Biochem Biophys. 1986 Dec;251(2):747-55. [Article]
  6. Humm A, Fritsche E, Mann K, Gohl M, Huber R: Recombinant expression and isolation of human L-arginine:glycine amidinotransferase and identification of its active-site cysteine residue. Biochem J. 1997 Mar 15;322 ( Pt 3):771-6. [Article]
  7. Humm A, Fritsche E, Steinbacher S: Structure and reaction mechanism of L-arginine:glycine amidinotransferase. Biol Chem. 1997 Mar-Apr;378(3-4):193-7. [Article]
  8. Cullen ME, Yuen AH, Felkin LE, Smolenski RT, Hall JL, Grindle S, Miller LW, Birks EJ, Yacoub MH, Barton PJ: Myocardial expression of the arginine:glycine amidinotransferase gene is elevated in heart failure and normalized after recovery: potential implications for local creatine synthesis. Circulation. 2006 Jul 4;114(1 Suppl):I16-20. [Article]
  9. McMinn J, Wei M, Schupf N, Cusmai J, Johnson EB, Smith AC, Weksberg R, Thaker HM, Tycko B: Unbalanced placental expression of imprinted genes in human intrauterine growth restriction. Placenta. 2006 Jun-Jul;27(6-7):540-9. Epub 2005 Aug 24. [Article]
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  11. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [Article]
  12. Edvardson S, Korman SH, Livne A, Shaag A, Saada A, Nalbandian R, Allouche-Arnon H, Gomori JM, Katz-Brull R: l-arginine:glycine amidinotransferase (AGAT) deficiency: clinical presentation and response to treatment in two patients with a novel mutation. Mol Genet Metab. 2010 Oct-Nov;101(2-3):228-32. doi: 10.1016/j.ymgme.2010.06.021. Epub 2010 Jul 7. [Article]
  13. Ndika JD, Johnston K, Barkovich JA, Wirt MD, O'Neill P, Betsalel OT, Jakobs C, Salomons GS: Developmental progress and creatine restoration upon long-term creatine supplementation of a patient with arginine:glycine amidinotransferase deficiency. Mol Genet Metab. 2012 May;106(1):48-54. doi: 10.1016/j.ymgme.2012.01.017. Epub 2012 Jan 27. [Article]
  14. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
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  16. Humm A, Fritsche E, Steinbacher S, Huber R: Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis. EMBO J. 1997 Jun 16;16(12):3373-85. [Article]
  17. Fritsche E, Humm A, Huber R: Substrate binding and catalysis by L-arginine:glycine amidinotransferase--a mutagenesis and crystallographic study. Eur J Biochem. 1997 Jul 15;247(2):483-90. [Article]
  18. Fritsche E, Humm A, Huber R: The ligand-induced structural changes of human L-Arginine:Glycine amidinotransferase. A mutational and crystallographic study. J Biol Chem. 1999 Jan 29;274(5):3026-32. [Article]
  19. Item CB, Stockler-Ipsiroglu S, Stromberger C, Muhl A, Alessandri MG, Bianchi MC, Tosetti M, Fornai F, Cioni G: Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. Am J Hum Genet. 2001 Nov;69(5):1127-33. Epub 2001 Sep 10. [Article]
  20. Comeaux MS, Wang J, Wang G, Kleppe S, Zhang VW, Schmitt ES, Craigen WJ, Renaud D, Sun Q, Wong LJ: Biochemical, molecular, and clinical diagnoses of patients with cerebral creatine deficiency syndromes. Mol Genet Metab. 2013 Jul;109(3):260-8. doi: 10.1016/j.ymgme.2013.04.006. Epub 2013 Apr 17. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00145Glycineapproved, nutraceutical, vet_approvedunknownsubstrateDetails
DB02068Delta-Amino Valeric AcidexperimentalunknownDetails
DB02530gamma-Aminobutyric acidapproved, investigationalunknownDetails
DB04185NorvalineexperimentalunknownDetails
DB04454Alpha-Aminobutyric AcidexperimentalunknownDetails
DB00129Ornithineapproved, nutraceuticalunknownDetails