P13255 (GNMT_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glycine N-methyltransferase
EC=2.1.1.20

Alternative name(s):
Folate-binding protein

Gene names

Name:

Gnmt

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	293 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the methylation of glycine by using S-adenosylmethionine (AdoMet) to form N-methylglycine (sarcosine) with the concomitant production of S-adenosylhomocysteine (AdoHcy). Possible crucial role in the regulation of tissue concentration of AdoMet and of metabolism of methionine.
Catalytic activity	S-adenosyl-L-methionine + glycine = S-adenosyl-L-homocysteine + sarcosine.
Enzyme regulation	Inhibited by 5-methyltetrahydrofolate pentaglutamate. Two molecules of 5-methyltetrahydrofolate are bound per tetramer. The binding sites are localized between subunits. Inhibitor binding may preclude movements of the polypeptide chain that are necessary for enzyme activity. Ref.6
Subunit structure	Homotetramer.
Subcellular location	Cytoplasm.
Tissue specificity	Abundant in liver.
Sequence similarities	Belongs to the class I-like SAM-binding methyltransferase superfamily. Glycine N-methyltransferase family.

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	Folate-binding S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	S-adenosylhomocysteine metabolic process Inferred from direct assay PubMed 15347642. Source: RGD S-adenosylmethionine metabolic process Inferred from direct assay PubMed 15340920. Source: UniProtKB folic acid metabolic process Traceable author statement PubMed 12054489. Source: RGD protein homotetramerization Inferred from physical interaction PubMed 15340920. Source: UniProtKB
Cellular_component	cytosol Inferred from direct assay PubMed 8278367. Source: RGD nucleus Inferred from direct assay PubMed 8278367. Source: RGD
Molecular_function	folic acid binding Traceable author statement PubMed 8278367. Source: RGD glycine N-methyltransferase activity Inferred from direct assay PubMed 15340920. Source: UniProtKB glycine binding Inferred from direct assay PubMed 15340920. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.1

Chain

2 – 293

292

Glycine N-methyltransferase

PRO_0000087528

Regions

Region

117 – 118

2

S-adenosyl-L-methionine binding

Sites

Binding site

22

1

S-adenosyl-L-methionine

Binding site

31

1

S-adenosyl-L-methionine

Binding site

34

1

Substrate

Binding site

41

1

S-adenosyl-L-methionine

Binding site

65

1

S-adenosyl-L-methionine; via carbonyl oxygen

Binding site

86

1

S-adenosyl-L-methionine

Binding site

137

1

S-adenosyl-L-methionine; via carbonyl oxygen

Binding site

139

1

Substrate

Binding site

176

1

Substrate

Binding site

221

1

Substrate

Amino acid modifications

Modified residue

2

1

N-acetylvaline Ref.1

Experimental info

Mutagenesis

34

1

Y → F: Reduces affinity for glycine. Ref.5

Mutagenesis

176

1

R → K: Strongly reduced affinity for glycine. Ref.5

Mutagenesis

221

1

Y → F: Reduces affinity for glycine. Ref.5

Secondary structure

1

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293

Helix Strand Turn

Details...

Beta strand

5 – 9

5

Beta strand

11 – 13

3

Turn

21 – 24

4

Helix

26 – 35

10

Beta strand

39 – 41

3

Helix

43 – 55

13

Beta strand

60 – 63

4

Helix

70 – 77

8

Beta strand

81 – 87

7

Helix

89 – 101

13

Turn

102 – 104

3

Helix

106 – 109

4

Beta strand

112 – 115

4

Helix

118 – 120

3

Helix

121 – 124

4

Beta strand

131 – 136

6

Turn

137 – 139

3

Helix

141 – 143

3

Beta strand

147 – 151

5

Helix

152 – 163

12

Beta strand

165 – 176

12

Helix

178 – 184

7

Beta strand

193 – 195

3

Beta strand

202 – 210

9

Beta strand

213 – 225

13

Beta strand

229 – 232

4

Beta strand

235 – 243

9

Helix

248 – 257

10

Turn

258 – 261

4

Beta strand

263 – 269

7

Beta strand

283 – 291

9

Sequences

	Sequence		Length	Mass (Da)
	P13255 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 4E98C7512F0228A5	FASTA	293	32,549
	10 20 30 40 50 60 MVDSVYRTRS LGVAAEGIPD QYADGEAARV WQLYIGDTRS RTAEYKAWLL GLLRQHGCHR 70 80 90 100 110 120 VLDVACGTGV DSIMLVEEGF SVTSVDASDK MLKYALKERW NRRKEPAFDK WVIEEANWLT 130 140 150 160 170 180 LDKDVPAGDG FDAVICLGNS FAHLPDSKGD QSEHRLALKN IASMVRPGGL LVIDHRNYDY 190 200 210 220 230 240 ILSTGCAPPG KNIYYKSDLT KDITTSVLTV NNKAHMVTLD YTVQVPGAGR DGAPGFSKFR 250 260 270 280 290 LSYYPHCLAS FTELVQEAFG GRCQHSVLGD FKPYRPGQAY VPCYFIHVLK KTG

References

[1]	"Rat glycine methyltransferase. Complete amino acid sequence deduced from a cDNA clone and characterization of the genomic DNA." Ogawa H., Konishi K., Takata Y., Nakashima H., Fujioka M. Eur. J. Biochem. 168:141-151(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], PROTEIN SEQUENCE OF 2-7. Strain: Sprague-Dawley.
[2]	"Crystal structure of glycine N-methyltransferase from rat liver." Fu Z., Hu Y., Konishi K., Takata Y., Ogawa H., Gomi T., Fujioka M., Takusagawa F. Biochemistry 35:11985-11993(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS). Tissue: Liver.
[3]	"Crystal structure of apo-glycine N-methyltransferase (GNMT)." Pattanayek R., Newcomer M.E., Wagner C. Protein Sci. 7:1326-1331(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
[4]	"Mechanisms for auto-inhibition and forced product release in glycine N-methyltransferase: crystal structures of wild-type, mutant R175K and S-adenosylhomocysteine-bound R175K enzymes." Huang Y., Komoto J., Konishi K., Takata Y., Ogawa H., Gomi T., Fujioka M., Takusagawa F. J. Mol. Biol. 298:149-162(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
[5]	"Catalytic mechanism of glycine N-methyltransferase." Takata Y., Huang Y., Komoto J., Yamada T., Konishi K., Ogawa H., Gomi T., Fujioka M., Takusagawa F. Biochemistry 42:8394-8402(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 2-292 IN COMPLEXES WITH S-ADENOSYL-L-METHIONINE AND ACETATE, MUTAGENESIS OF TYR-34; ARG-176 AND TYR-221.
[6]	"5-methyltetrahydrofolate is bound in intersubunit areas of rat liver folate-binding protein glycine N-methyltransferase." Luka Z., Pakhomova S., Loukachevitch L.V., Egli M., Newcomer M.E., Wagner C. J. Biol. Chem. 282:4069-4075(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 2-292 IN COMPLEX WITH 5-METHYLTETRAHYDROFOLATE, ENZYME REGULATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X06150 mRNA. Translation: CAA29508.1.
X07833 Genomic DNA. Translation: CAA30686.1.

IPI

IPI00231648.

PIR

S00112.

RefSeq

NP_058780.1. NM_017084.1.

UniGene

Rn.11142.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BHJ	X-ray	2.50	A/B	2-293	[»]
1D2C	X-ray	2.50	A/B	2-293	[»]
1D2G	X-ray	2.50	A/B	2-293	[»]
1D2H	X-ray	3.00	A/B/C/D	2-293	[»]
1KIA	X-ray	2.80	A/B/C/D	2-292	[»]
1NBH	X-ray	2.80	A/B/C/D	2-292	[»]
1NBI	X-ray	3.00	A/B/C/D	2-292	[»]
1XVA	X-ray	2.20	A/B	2-293	[»]
2IDJ	X-ray	2.35	A/B/C/D	2-292	[»]
2IDK	X-ray	2.55	A/B/C/D	2-292	[»]
3THR	X-ray	2.00	A/B/C/D	2-293	[»]
3THS	X-ray	2.50	A/B/C/D	2-293	[»]

DisProt

DP00031.

ProteinModelPortal

P13255.

SMR

P13255. Positions 2-293.

ModBase

Search...

Protein-protein interaction databases

STRING

10116.ENSRNOP00000022307.

PTM databases

PhosphoSite

P13255.

Proteomic databases

PaxDb

P13255.

PRIDE

P13255.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000022307; ENSRNOP00000022307; ENSRNOG00000016349.

GeneID

25134.

KEGG

rno:25134.

UCSC

RGD:2719. rat.

Organism-specific databases

CTD

27232.

RGD

2719. Gnmt.

Phylogenomic databases

eggNOG

NOG78825.

GeneTree

ENSGT00390000006845.

HOGENOM

HOG000276537.

HOVERGEN

HBG051748.

InParanoid

P13255.

KO

K00552.

OMA

LIIDHRN.

OrthoDB

EOG4JM7QD.

Enzyme and pathway databases

SABIO-RK

P13255.

Gene expression databases

Genevestigator

P13255.

GermOnline

ENSRNOG00000016349. Rattus norvegicus.

Family and domain databases

InterPro

IPR014369. Gly/Sar_N_MeTrfase.
[Graphical view]

PANTHER

PTHR16458. PTHR16458. 1 hit.

PIRSF

PIRSF000385. Gly_N-mtase. 1 hit.

PROSITE

PS51600. SAM_GNMT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P13255.

NextBio

605549.

Entry information

Entry name

GNMT_RAT

Accession

Primary (citable) accession number: P13255

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 118 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program