Reviewed, UniProtKB/Swiss-Prot Q14749 (GNMT_HUMAN)

Names and origin

Protein names

Recommended name:
    Glycine N-methyltransferase
    EC=2.1.1.20

Gene names

Name:

GNMT

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	295 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.
Subunit structure	Homotetramer.
Subcellular location	Cytoplasm.
Tissue specificity	Abundant in liver.
Involvement in disease	Defects in GNMT are the cause of GNMT deficiency (also known as hypermethioninemia) [MIM:606664]. The only clinical abnormalities in patients with this deficiency are mild hepatomegaly and chronic elevation of serum transaminases.

Ontologies

Keywords
Cellular component	Cytoplasm
Disease	Disease mutation
Ligand	Folate-binding S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	protein modification process Ref.2 Non-traceable author statement. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	folic acid binding Inferred from electronic annotation. Source: UniProtKB-KW glycine N-methyltransferase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 295

294

Glycine N-methyltransferase

PRO_0000087524

Amino acid modifications

Modified residue

2

1

N-acetylvaline By similarity

Modified residue

235

1

Phosphoserine By similarity

Natural variations

Natural variant

50

1

L → P in GNMT deficiency; 10% wild-type activity.

VAR_012766

Natural variant

141

1

N → S in GNMT deficiency; 0.5% wild-type activity.

VAR_019840

Natural variant

177

1

H → N in GNMT deficiency; 75% wild-type activity.

VAR_012767

Experimental info

Sequence conflict

119

1

Missing in CAA44164. Ref.4

Sequence conflict

129 – 130

2

AE → PK in AAF78289. Ref.2

Sequence conflict

175

1

I → S in CAA44164. Ref.4

Sequence conflict

256 – 260

5

LLQAA → SPSS in CAA44164. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

295

Helix Strand Turn

Details...

Turn

21 – 24

4

Helix

28 – 34

7

Helix

43 – 55

13

Beta strand

60 – 64

5

Helix

70 – 78

9

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

133 – 138

6

Helix

143 – 145

3

Beta strand

150 – 153

4

Helix

154 – 165

12

Beta strand

167 – 178

12

Helix

180 – 186

7

Beta strand

195 – 197

3

Beta strand

204 – 212

9

Beta strand

215 – 225

11

Beta strand

239 – 245

7

Helix

250 – 260

11

Turn

261 – 263

3

Beta strand

265 – 271

7

Beta strand

285 – 293

9

Sequences

	Sequence		Length	Mass (Da)
	Q14749-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 34F4546136FD27ED	FASTA	295	32,742
	10 20 30 40 50 60 MVDSVYRTRS LGVAAEGLPD QYADGEAARV WQLYIGDTRS RTAEYKAWLL GLLRQHGCQR 70 80 90 100 110 120 VLDVACGTGV DSIMLVEEGF SVTSVDASDK MLKYALKERW NRRHEPAFDK WVIEEANWMT 130 140 150 160 170 180 LDKDVPQSAE GGFDAVICLG NSFAHLPDCK GDQSEHRLAL KNIASMVRAG GLLVIDHRNY 190 200 210 220 230 240 DHILSTGCAP PGKNIYYKSD LTKDVTTSVL IVNNKAHMVT LDYTVQVPGA GQDGSPGLSK 250 260 270 280 290 FRLSYYPHCL ASFTELLQAA FGGKCQHSVL GDFKPYKPGQ TYIPCYFIHV LKRTD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of glycine-N-methyltransferase-gene expression in human hepatocellular carcinoma." Chen Y.-M.A., Shiu J.Y., Tzeng S.J., Shih L.S., Chen Y.J., Lui W.Y., Chen P.H. Int. J. Cancer 75:787-793(1998) [PubMed: 9495250] [Abstract] Cited for: NUCLEOTIDE SEQUENCE.
[2]	"Genomic structure, expression, and chromosomal localization of the human glycine N-methyltransferase gene." Chen Y.-M.A., Chen L.-Y., Wong F.H., Lee C.M., Chang T.J., Yang-Feng T.L. Genomics 66:43-47(2000) [PubMed: 10843803] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[3]	"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]. Tissue: Pancreas.
[4]	"Mammalian glycine N-methyltransferases. Comparative kinetic and structural properties of the enzymes from human, rat, rabbit and pig livers." Ogawa H., Gomi T., Fujioka M. Comp. Biochem. Physiol. 106B:601-611(1993) [PubMed: 8281755] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 31-295.
[5]	"Mutations in human glycine N-methyltransferase give insights into its role in methionine metabolism." Luka Z., Cerone R., Phillips J.A. III, Mudd S.H., Wagner C. Hum. Genet. 110:68-74(2002) [PubMed: 11810299] [Abstract] Cited for: VARIANTS GNMT DEFICIENCY PRO-50 AND ASN-177.
[6]	"Effect of naturally occurring mutations in human glycine N-methyltransferase on activity and conformation." Luka Z., Wagner C. Biochem. Biophys. Res. Commun. 312:1067-1072(2003) [PubMed: 14651980] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS GNMT DEFICIENCY PRO-50; SER-141 AND ASN-177.
[7]	"Glycine N-methyltransferase deficiency: a new patient with a novel mutation." Augoustides-Savvopoulou P., Luka Z., Karyda S., Stabler S.P., Allen R.H., Patsiaoura K., Wagner C., Mudd S.H. J. Inherit. Metab. Dis. 26:745-759(2003) [PubMed: 14739680] [Abstract] Cited for: VARIANT GNMT DEFICIENCY SER-141.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF101477 mRNA. Translation: AAF78290.1.
AF101475 Genomic DNA. Translation: AAF78289.1.
BC032627 mRNA. Translation: AAH32627.1.
X62250 mRNA. Translation: CAA44164.1.

PIR

S42627.

RefSeq

NP_061833.1.

UniGene

Hs.144914

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1R74	X-ray	2.55	A/B	1-295	[»]
2AZT	X-ray	2.70	A/B	1-295	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q14749.

PTM databases

PhosphoSite

Q14749.

Genome annotation databases

Ensembl

ENSG00000124713. Homo sapiens. [Contig view]

GeneID

27232.

KEGG

hsa:27232.

Organism-specific databases

H-InvDB

HIX0005888.

HGNC

HGNC:4415. GNMT.

MIM

606628. gene.
606664. phenotype.

PharmGKB

PA28794.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

Q14749.

HOVERGEN

Q14749.

Gene expression databases

CleanEx

HS_GNMT.

GermOnline

ENSG00000124713. Homo sapiens.

Family and domain databases

InterPro

IPR014369. Gly_N_MeTrfase.
IPR013217. Methyltransf_12.
[Graphical view]

Pfam

PF08242. Methyltransf_12. 1 hit.
[Graphical view]

PIRSF

PIRSF000385. Gly_N-mtase. 1 hit.

ProtoNet

Search...

Other Resources

DrugBank

DB00145. Glycine.
DB00118. S-Adenosylmethionine.

NextBio

50091.

SOURCE

Search...

Entry information

Entry name

GNMT_HUMAN

Accession

Primary (citable) accession number: Q14749
Secondary accession number(s): Q9NNZ1, Q9NS24

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	January 23, 2007
Last modified:	November 25, 2008
This is version 76 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)