Human Gene GATM (uc001zvc.3)
  Description: Homo sapiens glycine amidinotransferase (L-arginine:glycine amidinotransferase) (GATM), nuclear gene encoding mitochondrial protein, mRNA.
RefSeq Summary (NM_001482): This gene encodes a mitochondrial enzyme that belongs to the amidinotransferase family. This enzyme is involved in creatine biosynthesis, whereby it catalyzes the transfer of a guanido group from L-arginine to glycine, resulting in guanidinoacetic acid, the immediate precursor of creatine. Mutations in this gene cause arginine:glycine amidinotransferase deficiency, an inborn error of creatine synthesis characterized by cognitive disability, language impairment, and behavioral disorders. [provided by RefSeq, Jul 2008].
Transcript (Including UTRs)
   Position: hg19 chr15:45,653,322-45,670,980 Size: 17,659 Total Exon Count: 9 Strand: -
Coding Region
   Position: hg19 chr15:45,654,307-45,670,651 Size: 16,345 Coding Exon Count: 9 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr15:45,653,322-45,670,980)mRNA (may differ from genome)Protein (423 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSCGAPEnsemblEntrez GeneExonPrimer
GeneCardsGeneNetworkH-INVHGNCHPRDLynx
MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: GATM_HUMAN
DESCRIPTION: RecName: Full=Glycine amidinotransferase, mitochondrial; EC=2.1.4.1; AltName: Full=L-arginine:glycine amidinotransferase; AltName: Full=Transamidinase; Flags: Precursor;
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.
CATALYTIC ACTIVITY: L-arginine + glycine = L-ornithine + guanidinoacetate.
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=2.0 uM for arginine; KM=3.0 uM for glycine; Vmax=0.44 umol/min/mg enzyme;
PATHWAY: Amine and polyamine biosynthesis; creatine biosynthesis; creatine from L-arginine and glycine: step 1/2.
SUBUNIT: Homodimer. There is an equilibrium between the monomeric and dimeric forms, shifted towards the side of the monomer.
INTERACTION: Q9D964:Gatm (xeno); NbExp=1; IntAct=EBI-2552594, EBI-2552599;
SUBCELLULAR LOCATION: Isoform 1: Mitochondrion inner membrane; Peripheral membrane protein; Intermembrane side. Note=Probably attached to the outer side of the inner membrane.
SUBCELLULAR LOCATION: Isoform 2: Cytoplasm.
TISSUE SPECIFICITY: Expressed in brain, heart, kidney, liver, lung, salivary gland and skeletal muscle tissue, with the highest expression in kidney. Biallelically expressed in placenta and fetal tissues.
INDUCTION: Expression is elevated in the myocardium during heart failure, and decreased in inter-uterine growth restriction (IUGR)- associated placenta.
DOMAIN: One chain folds into a compact single domain composed of repeating units, five beta-beta-alpha-beta modules, which surround the central active site.
DISEASE: Defects in GATM are the cause of arginine:glycine amidinotransferase deficiency (AGAT deficiency) [MIM:612718]. AGAT deficiency is an autosomal recessive disorder characterized by developmental delay/regression, mental retardation, severe disturbance of expressive and cognitive speech, and severe depletion of creatine/phosphocreatine in the brain.
SIMILARITY: Belongs to the amidinotransferase family.
SEQUENCE CAUTION: Sequence=BAG60595.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/GATM";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): GATM
CDC HuGE Published Literature: GATM
Positive Disease Associations: renal function and chronic kidney disease
Related Studies:
  1. renal function and chronic kidney disease
    Kottgen ,et al. 2009, Multiple loci associated with indices of renal function and chronic kidney disease, Nature genetics 2009 . [PubMed 19430482]

-  MalaCards Disease Associations
  MalaCards Gene Search: GATM
Diseases sorted by gene-association score: cerebral creatine deficiency syndrome 3* (1590), l-arginine:glycine amidinotransferase deficiency* (519), cerebral creatine deficiency syndrome (23), cerebral creatine deficiency syndrome 2 (13), creatine deficiency syndromes (12), radiation cystitis (11), cerebral creatine deficiency syndrome 1 (10), uterine corpus cancer (6)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D000082 Acetaminophen
  • D003401 Creatine
  • C523799 MRK 003
  • D014635 Valproic Acid
  • C111118 2',3,3',4',5-pentachloro-4-hydroxybiphenyl
  • C023514 2,6-dinitrotoluene
  • C532162 2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine
  • C030370 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone
  • C472791 3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid
  • C009505 4,4'-diaminodiphenylmethane
          more ... click here to view the complete list

+  Common Gene Haplotype Alleles
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-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 355.35 RPKM in Pancreas
Total median expression: 1458.72 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -179.60329-0.546 Picture PostScript Text
3' UTR -197.73985-0.201 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003198 - Amidino_trans

SCOP Domains:
55909 - Pentein

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1JDW - X-ray MuPIT 1JDX - X-ray MuPIT 2JDW - X-ray MuPIT 2JDX - X-ray MuPIT 3JDW - X-ray MuPIT 4JDW - X-ray MuPIT 5JDW - X-ray MuPIT 6JDW - X-ray MuPIT 7JDW - X-ray MuPIT 8JDW - X-ray MuPIT 9JDW - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P50440
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGDEnsembl   
 Protein SequenceProtein Sequence   
 AlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0015067 amidinotransferase activity
GO:0015068 glycine amidinotransferase activity
GO:0016740 transferase activity

Biological Process:
GO:0006600 creatine metabolic process
GO:0006601 creatine biosynthetic process
GO:0007275 multicellular organism development
GO:0007611 learning or memory
GO:0014889 muscle atrophy

Cellular Component:
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005743 mitochondrial inner membrane
GO:0005758 mitochondrial intermembrane space
GO:0016020 membrane
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  S68805 - L-arginine:glycine amidinotransferase [human, kidney carcinoma cells, mRNA, 2330 nt].
HM005559 - Homo sapiens clone HTL-S-19 testicular secretory protein Li 19 mRNA, complete cds.
AK098055 - Homo sapiens cDNA FLJ40736 fis, clone TKIDN2003597, highly similar to GLYCINE AMIDINOTRANSFERASE PRECURSOR (EC 2.1.4.1).
AK098393 - Homo sapiens cDNA FLJ25527 fis, clone CBR07379, highly similar to GLYCINE AMIDINOTRANSFERASE PRECURSOR (EC 2.1.4.1).
FW340076 - Screening.
BC004141 - Homo sapiens glycine amidinotransferase (L-arginine:glycine amidinotransferase), mRNA (cDNA clone MGC:1744 IMAGE:3010128), complete cds.
JD083471 - Sequence 64495 from Patent EP1572962.
JD037142 - Sequence 18166 from Patent EP1572962.
JD246177 - Sequence 227201 from Patent EP1572962.
X86401 - H.sapiens mRNA for L-arginine:glycine amidinotransferase.
JD410803 - Sequence 391827 from Patent EP1572962.
JD044364 - Sequence 25388 from Patent EP1572962.
JD061532 - Sequence 42556 from Patent EP1572962.
AK298350 - Homo sapiens cDNA FLJ56372 complete cds, highly similar to Glycine amidinotransferase, mitochondrial precursor (EC 2.1.4.1).
AK223585 - Homo sapiens mRNA for glycine amidinotransferase (L-arginine:glycine amidinotransferase) variant, clone: FCC130D06.
JD262704 - Sequence 243728 from Patent EP1572962.
JD305792 - Sequence 286816 from Patent EP1572962.
JD325633 - Sequence 306657 from Patent EP1572962.
JD486115 - Sequence 467139 from Patent EP1572962.
JD076063 - Sequence 57087 from Patent EP1572962.
JD059200 - Sequence 40224 from Patent EP1572962.
KJ891222 - Synthetic construct Homo sapiens clone ccsbBroadEn_00616 GATM gene, encodes complete protein.
AK294995 - Homo sapiens cDNA FLJ58313 complete cds, highly similar to Glycine amidinotransferase, mitochondrial precursor (EC 2.1.4.1).
CU678590 - Synthetic construct Homo sapiens gateway clone IMAGE:100018254 5' read GATM mRNA.
KM576744 - Homo sapiens clone BC039389-GATM_B3-G3 mRNA sequence.
KM576745 - Homo sapiens clone BC039389-GATM_B3-G2 mRNA sequence.
JD196509 - Sequence 177533 from Patent EP1572962.
JD460635 - Sequence 441659 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00260 - Glycine, serine and threonine metabolism
hsa00330 - Arginine and proline metabolism
hsa01100 - Metabolic pathways

BioCyc Knowledge Library
GLYCGREAT-PWY - glycine degradation (creatine biosynthesis)
PWY3DJ-35588 - creatine biosynthesis

Reactome (by CSHL, EBI, and GO)

Protein P50440 (Reactome details) participates in the following event(s):

R-HSA-71275 arginine + glycine => ornithine + guanidoacetate
R-HSA-71288 Creatine metabolism
R-HSA-351202 Metabolism of polyamines
R-HSA-71291 Metabolism of nitrogenous molecules
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: AGAT, B4DH99, B4DPI3, GATM_HUMAN, NM_001482, NP_001473, P50440, Q53EQ4
UCSC ID: uc001zvc.3
RefSeq Accession: NM_001482
Protein: P50440 (aka GATM_HUMAN)
CCDS: CCDS10122.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene GATM:
creatine (Creatine Deficiency Disorders)
dystonia-ov (Hereditary Dystonia Overview)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001482.2
exon count: 9CDS single in 3' UTR: no RNA size: 2602
ORF size: 1272CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3060.00frame shift in genome: no % Coverage: 99.39
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.