Q14353 (GAMT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Guanidinoacetate N-methyltransferase
EC=2.1.1.2

Gene names

Name:

GAMT

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	236 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	S-adenosyl-L-methionine + guanidinoacetate = S-adenosyl-L-homocysteine + creatine.
Pathway	Amine and polyamine biosynthesis; creatine biosynthesis; creatine from L-arginine and glycine: step 2/2.
Subunit structure	Monomer By similarity.
Tissue specificity	Expressed in liver. Ref.7
Involvement in disease	Defects in GAMT are the cause of guanidinoacetate methyltransferase deficiency (GAMT deficiency) [MIM:612736]. GAMT deficiency is an autosomal recessive disorder characterized by developmental delay/regression, mental retardation, severe disturbance of expressive and cognitive speech, intractable seizures and movement disturbances, severe depletion of creatine/phosphocreatine in the brain, and accumulation of guanidinoacetic acid (GAA) in brain and body fluids.
Sequence similarities	Belongs to the RMT2 methyltransferase family.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	creatine biosynthetic process Inferred from direct assay Ref.7. Source: UniProtKB muscle contraction Traceable author statement. Source: ProtInc
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	guanidinoacetate N-methyltransferase activity Inferred from mutant phenotype Ref.7. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 236

236

Guanidinoacetate N-methyltransferase

PRO_0000087430

Regions

Region

69 – 74

6

S-adenosyl-L-methionine binding

Region

117 – 118

2

S-adenosyl-L-methionine binding

Region

171 – 172

2

Substrate binding

Sites

Binding site

20

1

S-adenosyl-L-methionine

Binding site

42

1

Substrate By similarity

Binding site

46

1

Substrate By similarity

Binding site

50

1

S-adenosyl-L-methionine

Binding site

90

1

S-adenosyl-L-methionine

Binding site

135

1

Substrate By similarity

Amino acid modifications

Modified residue

222

1

Phosphotyrosine Ref.8

Modified residue

223

1

Phosphotyrosine Ref.8

Natural variations

Natural variant

20

1

W → S in GAMT deficiency. Ref.12 Ref.13

VAR_058102

Natural variant

50

1

M → L in GAMT deficiency. Ref.15

VAR_058103

Natural variant

51

1

H → P in GAMT deficiency. Ref.12

VAR_058104

Natural variant

54

1

A → P in GAMT deficiency. Ref.12

VAR_058105

Natural variant

169

1

C → Y in GAMT deficiency. Ref.13

VAR_058106

Natural variant

197

1

L → P in GAMT deficiency; uncertain pathogenicity. Ref.11 Ref.14

VAR_058107

Natural variant

209

1

T → M. Ref.6
Corresponds to variant rs17851582 [ dbSNP | Ensembl ].

VAR_025723

Secondary structure

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236

Helix Strand Turn

Details...

Helix

17 – 20

4

Beta strand

25 – 27

3

Beta strand

33 – 36

4

Beta strand

39 – 43

5

Helix

44 – 46

3

Helix

47 – 57

11

Turn

58 – 60

3

Beta strand

62 – 67

6

Helix

73 – 79

7

Beta strand

83 – 90

8

Helix

93 – 102

10

Helix

103 – 105

3

Beta strand

107 – 115

9

Helix

117 – 120

4

Helix

121 – 123

3

Beta strand

129 – 134

6

Helix

141 – 143

3

Turn

144 – 146

3

Helix

147 – 154

8

Helix

156 – 159

4

Beta strand

160 – 168

9

Helix

171 – 177

7

Turn

178 – 181

4

Helix

185 – 192

8

Helix

194 – 199

6

Helix

204 – 206

3

Beta strand

207 – 213

7

Beta strand

226 – 234

9

Sequences

	Sequence		Length	Mass (Da)
	Q14353 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 6B8E845CE56189F5	FASTA	236	26,318
	10 20 30 40 50 60 MSAPSATPIF APGENCSPAW GAAPAAYDAA DTHLRILGKP VMERWETPYM HALAAAASSK 70 80 90 100 110 120 GGRVLEVGFG MAIAASKVQE APIDEHWIIE CNDGVFQRLR DWAPRQTHKV IPLKGLWEDV 130 140 150 160 170 180 APTLPDGHFD GILYDTYPLS EETWHTHQFN FIKNHAFRLL KPGGVLTYCN LTSWGELMKS 190 200 210 220 230 KYSDITIMFE ETQVPALLEA GFRRENIRTE VMALVPPADC RYYAFPQMIT PLVTKG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequence analysis of human guanidinoacetate N-methyltransferase cDNA." Isbrandt D., von Figura K. Biochim. Biophys. Acta 1264:265-267(1995) [PubMed: 8547310] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"The human guanidinoacetate methyltransferase (GAMT) gene maps to a syntenic region on 19p13.3, homologous to band C of mouse chromosome 10, but GAMT is not mutated in jittery mice." Jenne D.E., Olsen A.S., Zimmer M. Biochem. Biophys. Res. Commun. 238:723-727(1997) [PubMed: 9325156] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Gene structure of human guanidinoacetate N-methyltransferase." Isbrandt D., Schmidt A. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-209. Tissue: Lymph and Skeletal muscle.
[7]	"Guanidinoacetate methyltransferase deficiency: the first inborn error of creatine metabolism in man." Stoeckler S., Isbrandt D., Hanefeld F., Schmidt B., von Figura K. Am. J. Hum. Genet. 58:914-922(1996) [PubMed: 8651275] [Abstract] Cited for: TISSUE SPECIFICITY, INVOLVEMENT IN GAMT DEFICIENCY.
[8]	"Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling." Wang Y., Du D., Fang L., Yang G., Zhang C., Zeng R., Ullrich A., Lottspeich F., Chen Z. EMBO J. 25:5058-5070(2006) [PubMed: 17053785] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-222 AND TYR-223, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[9]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"The crystal structure of human guanidinoacetate N-methyltransferase with SAH." Structural genomics consortium (SGC) Submitted (MAR-2006) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) IN COMPLEX WITH S-ADENOSYL-L-HOMOCYSTEINE.
[11]	"Creatine depletion in a new case with AGAT deficiency: clinical and genetic study in a large pedigree." Battini R., Leuzzi V., Carducci C., Tosetti M., Bianchi M.C., Item C.B., Stoeckler-Ipsiroglu S., Cioni G. Mol. Genet. Metab. 77:326-331(2002) [PubMed: 12468279] [Abstract] Cited for: VARIANT GAMT DEFICIENCY PRO-197.
[12]	"Characterization of seven novel mutations in seven patients with GAMT deficiency." Item C.B., Mercimek-Mahmutoglu S., Battini R., Edlinger-Horvat C., Stromberger C., Bodamer O., Muehl A., Vilaseca M.A., Korall H., Stoeckler-Ipsiroglu S. Hum. Mutat. 23:524-524(2004) [PubMed: 15108290] [Abstract] Cited for: VARIANTS GAMT DEFICIENCY SER-20; PRO-51 AND PRO-54.
[13]	"Guanidinoacetate methyltransferase deficiency identified in adults and a child with mental retardation." Caldeira Araujo H., Smit W., Verhoeven N.M., Salomons G.S., Silva S., Vasconcelos R., Tomas H., Tavares de Almeida I., Jakobs C., Duran M. Am. J. Med. Genet. A 133:122-127(2005) [PubMed: 15651030] [Abstract] Cited for: VARIANTS GAMT DEFICIENCY SER-20 AND TYR-169.
[14]	"A mutation on exon 6 of guanidinoacetate methyltransferase (GAMT) gene supports a different function for isoform a and b of GAMT enzyme." Leuzzi V., Carducci C., Carducci C., Matricardi M., Bianchi M.C., Di Sabato M.L., Artiola C., Antonozzi I. Mol. Genet. Metab. 87:88-90(2006) [PubMed: 16293431] [Abstract] Cited for: VARIANT GAMT DEFICIENCY PRO-197.
[15]	"High frequency of creatine deficiency syndromes in patients with unexplained mental retardation." Lion-Francois L., Cheillan D., Pitelet G., Acquaviva-Bourdain C., Bussy G., Cotton F., Guibaud L., Gerard D., Rivier C., Vianey-Saban C., Jakobs C., Salomons G.S., des Portes V. Neurology 67:1713-1714(2006) [PubMed: 17101918] [Abstract] Cited for: VARIANT GAMT DEFICIENCY LEU-50.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z49878 mRNA. Translation: CAA90035.1.
AF010248, AF010246, AF010247 Genomic DNA. Translation: AAD04781.1.
AF188893 Genomic DNA. Translation: AAF01461.1.
BT007034 mRNA. Translation: AAP35682.1.
AC005329 Genomic DNA. Translation: AAC27668.1.
BC016760 mRNA. Translation: AAH16760.1.
BC017936 mRNA. Translation: AAH17936.1.

IPI

IPI00030182.

PIR

S62732.

RefSeq

NP_000147.1. NM_000156.4.
NP_620279.1. NM_138924.1.

UniGene

Hs.81131.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3ORH	X-ray	1.86	A/B/C/D	1-236	[»]

ProteinModelPortal

Q14353.

SMR

Q14353. Positions 7-236.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q14353. 2 interactions.

STRING

Q14353.

PTM databases

PhosphoSite

Q14353.

Polymorphism databases

DMDM

2498404.

2D gel databases

OGP

Q14353.

Proteomic databases

PeptideAtlas

Q14353.

PRIDE

Q14353.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000252288; ENSP00000252288; ENSG00000130005.

GeneID

2593.

KEGG

hsa:2593.

UCSC

uc002lsj.1. human.

Organism-specific databases

CTD

2593.

GeneCards

GC19M001397.

H-InvDB

HIX0014583.

HGNC

HGNC:4136. GAMT.

MIM

601240. gene.
612736. phenotype.

neXtProt

NX_Q14353.

Orphanet

382. Guanidinoacetate methyltransferase deficiency.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08477.

GeneTree

ENSGT00390000018061.

HOVERGEN

HBG005801.

InParanoid

Q14353.

OMA

FEETQVP.

OrthoDB

EOG4XSKQP.

PhylomeDB

Q14353.

Enzyme and pathway databases

BRENDA

2.1.1.2. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q14353.

Bgee

Q14353.

CleanEx

HS_GAMT.

Genevestigator

Q14353.

GermOnline

ENSG00000130005. Homo sapiens.

Family and domain databases

InterPro

IPR016550. GuanidinoAc_N-MeTrfase.
[Graphical view]

KO

K00542.

PIRSF

PIRSF009285. GAMT. 1 hit.

ProtoNet

Search...

Other

DrugBank

DB00148. Creatine.

NextBio

10257.

SOURCE

Search...

Entry information

Entry name

GAMT_HUMAN

Accession

Primary (citable) accession number: Q14353
Secondary accession number(s): Q53Y34, Q8WVJ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.