P10868 (GAMT_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Guanidinoacetate N-methyltransferase
EC=2.1.1.2

Gene names

Name:

Gamt

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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. May form homodimers upon proteolytic removal of the first 36 amino acid residues. Ref.3 Ref.6 Ref.7
Tissue specificity	Expressed in hepatic primordium in the embryo as soon as 12.5 days. In the adult, high levels of expression are found in liver and pancreas. Ubiquitously expressed in neuronal and glial cells in the brain. Ref.4 Ref.5
Miscellaneous	The N-terminal first 36 amino acid residues are susceptible to proteolytic cleavage, leading to loss of activity.
Sequence similarities	Belongs to the class I-like SAM-binding methyltransferase superfamily. RMT2 methyltransferase family. Contains 1 RMT2 (arginine N-methyltransferase 2-like) domain.

Ontologies

Keywords
Ligand	S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	S-adenosylhomocysteine metabolic process Inferred from direct assay Ref.8. Source: RGD S-adenosylmethionine metabolic process Inferred from direct assay Ref.8. Source: RGD creatine biosynthetic process Inferred from direct assay Ref.8. Source: RGD
Molecular_function	guanidinoacetate N-methyltransferase activity Inferred from sequence or structural similarity. Source: UniProtKB protein homodimerization activity Inferred from direct assay Ref.6. Source: RGD
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_0000087432

Regions

Domain

13 – 236

224

RMT2

Region

69 – 74

6

S-adenosyl-L-methionine binding

Region

90 – 92

3

S-adenosyl-L-methionine

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

Binding site

46

1

Substrate

Binding site

50

1

S-adenosyl-L-methionine

Binding site

135

1

S-adenosyl-L-methionine and substrate

Experimental info

Mutagenesis

46

1

E → D: Reduces affinitiy for substrate and S-adenosyl-L-methionine about 2-fold. Ref.8

Mutagenesis

46

1

E → Q: Reduces affinitiy for substrate and S-adenosyl-L-methionine about 4-fold. Ref.8

Mutagenesis

46

1

E → S: Loss of activity. Ref.8

Mutagenesis

135

1

D → A: Loss of activity. Ref.8

Mutagenesis

135

1

D → E: Reduces affinity for S-adenosyl-L-methionine 500-fold. Reduces affinity for substrate about 40-fold. Ref.8

Mutagenesis

135

1

D → N: Reduces affinity for S-adenosyl-L-methionine 2000-fold. Reduces affinity for substrate about 40-fold. Ref.8

Mutagenesis

222

1

Y → F: Reduces affinity for S-adenosyl-L-methionine about 5-fold. Reduces affinity for substrate about 40-fold. Ref.8

Secondary structure

1

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236

Helix Strand Turn

Details...

Helix

17 – 20

4

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 – 80

8

Beta strand

84 – 90

7

Helix

93 – 103

11

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 – 180

10

Helix

185 – 192

8

Helix

194 – 200

7

Helix

204 – 206

3

Beta strand

207 – 213

7

Beta strand

226 – 234

9

Sequences

	Sequence		Length	Mass (Da)
	P10868 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 738D6F0BC86DB1C3	FASTA	236	26,407
	10 20 30 40 50 60 MSSSAASPLF APGEDCGPAW RAAPAAYDTS DTHLQILGKP VMERWETPYM HSLAAAAASR 70 80 90 100 110 120 GGRVLEVGFG MAIAASRVQQ APIKEHWIIE CNDGVFQRLQ NWALKQPHKV VPLKGLWEEE 130 140 150 160 170 180 APTLPDGHFD GILYDTYPLS EETWHTHQFN FIKTHAFRLL KPGGILTYCN LTSWGELMKS 190 200 210 220 230 KYTDITAMFE ETQVPALLEA GFQRENICTE VMALVPPADC RYYAFPQMIT PLVTKH

References

[1]	"Molecular cloning, sequence analysis, and expression in Escherichia coli of the cDNA for guanidinoacetate methyltransferase from rat liver." Ogawa H., Date T., Gomi T., Konishi K., Pitot H.C., Cantoni G.L., Fujioka M. Proc. Natl. Acad. Sci. U.S.A. 85:694-698(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Liver.
[2]	"Nucleotide sequence of the rat guanidinoacetate methyltransferase gene." Ogawa H., Fujioka M. Nucleic Acids Res. 16:8715-8716(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Recombinant rat guanidinoacetate methyltransferase: structure and function of the NH2-terminal region as deduced by limited proteolysis." Fujioka M., Takata Y., Gomi T. Arch. Biochem. Biophys. 285:181-186(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 22-29, FUNCTION, SUBUNIT STRUCTURE.
[4]	"Endogenous synthesis and transport of creatine in the rat brain: an in situ hybridization study." Braissant O., Henry H., Loup M., Eilers B., Bachmann C. Brain Res. Mol. Brain Res. 86:193-201(2001) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[5]	"Creatine synthesis and transport during rat embryogenesis: spatiotemporal expression of AGAT, GAMT and CT1." Braissant O., Henry H., Villard A.M., Speer O., Wallimann T., Bachmann C. BMC Dev. Biol. 5:9-9(2005) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[6]	"Crystal structure of guanidinoacetate methyltransferase from rat liver: a model structure of protein arginine methyltransferase." Komoto J., Huang Y., Takata Y., Yamada T., Konishi K., Ogawa H., Gomi T., Fujioka M., Takusagawa F. J. Mol. Biol. 320:223-235(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 39-236 IN COMPLEX WITH S-ADENOSYLHOMOCYSTEINE, SUBUNIT. Tissue: Liver.
[7]	"Monoclinic guanidinoacetate methyltransferase and gadolinium ion-binding characteristics." Komoto J., Takata Y., Yamada T., Konishi K., Ogawa H., Gomi T., Fujioka M., Takusagawa F. Acta Crystallogr. D 59:1589-1596(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 38-236 IN COMPLEX WITH S-ADENOSYL-L-HOMOCYSTEINE, SUBUNIT.
[8]	"Catalytic mechanism of guanidinoacetate methyltransferase: crystal structures of guanidinoacetate methyltransferase ternary complexes." Komoto J., Yamada T., Takata Y., Konishi K., Ogawa H., Gomi T., Fujioka M., Takusagawa F. Biochemistry 43:14385-14394(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH S-ADENOSYL-L-HOMOCYSTEINE AND SUBSTRATE, MUTAGENESIS OF GLU-46; ASP-135 AND TYR-222.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J03588 mRNA. Translation: AAA41258.1.
X08056 Genomic DNA. Translation: CAA30845.1.

IPI

IPI00231857.

PIR

S01395.

UniGene

Rn.33890.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KHH	X-ray	2.50	A/B	39-236	[»]
1P1B	X-ray	2.80	A/B/C/D	38-236	[»]
1P1C	X-ray	2.50	A/B	38-236	[»]
1XCJ	X-ray	2.00	A	2-236	[»]
1XCL	X-ray	2.00	A	2-236	[»]

ProteinModelPortal

P10868.

SMR

P10868. Positions 8-236.

ModBase

Search...

Protein-protein interaction databases

STRING

10116.ENSRNOP00000057452.

Proteomic databases

PaxDb

P10868.

PRIDE

P10868.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

UCSC

RGD:2659. rat.

Organism-specific databases

RGD

2659. Gamt.

Phylogenomic databases

eggNOG

NOG235457.

HOGENOM

HOG000010290.

HOVERGEN

HBG005801.

OrthoDB

EOG4XSKQP.

Enzyme and pathway databases

BioCyc

MetaCyc:MONOMER-7641.

BRENDA

2.1.1.2. 5301.

SABIO-RK

P10868.

UniPathway

UPA00104; UER00580.

Gene expression databases

ArrayExpress

P10868.

Genevestigator

P10868.

GermOnline

ENSRNOG00000024577. Rattus norvegicus.

Family and domain databases

InterPro

IPR016550. GuanidinoAc_N-MeTrfase.
IPR026480. RMT2_dom.
[Graphical view]

PIRSF

PIRSF009285. GAMT. 1 hit.

PROSITE

PS51559. SAM_RMT2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00536. Guanidine.

EvolutionaryTrace

P10868.

NextBio

605895.

Entry information

Entry name

GAMT_RAT

Accession

Primary (citable) accession number: P10868

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 105 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program