Q14749 (GNMT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glycine N-methyltransferase
EC=2.1.1.20

Gene names

Name:

GNMT

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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. Ref.7 Ref.8
Catalytic activity	S-adenosyl-L-methionine + glycine = S-adenosyl-L-homocysteine + sarcosine.
Subunit structure	Homotetramer. Ref.7 Ref.8
Subcellular location	Cytoplasm.
Tissue specificity	Abundant in liver.
Involvement in disease	Glycine N-methyltransferase deficiency (GNMT deficiency) [MIM:606664]: The only clinical abnormalities in patients with this deficiency are mild hepatomegaly and chronic elevation of serum transaminases. Note: The disease is caused by mutations affecting the gene represented in this entry.
Sequence similarities	Belongs to the class I-like SAM-binding methyltransferase superfamily. Glycine N-methyltransferase family.

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 Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	S-adenosylmethionine metabolic process Inferred from direct assay Ref.7. Source: UniProtKB cellular protein modification process Non-traceable author statement Ref.2. Source: UniProtKB glycogen metabolic process Inferred from electronic annotation. Source: Compara methionine metabolic process Inferred from electronic annotation. Source: Compara one-carbon metabolic process Inferred from electronic annotation. Source: Compara protein homotetramerization Inferred from physical interaction Ref.7. Source: UniProtKB regulation of gluconeogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA
Molecular_function	folic acid binding Inferred from electronic annotation. Source: UniProtKB-KW glycine N-methyltransferase activity Inferred from direct assay Ref.7. Source: UniProtKB glycine binding Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARRB1	P49407	5	EBI-744239,EBI-743313

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

Regions

Region

117 – 118

2

S-adenosyl-L-methionine binding By similarity

Sites

Binding site

22

1

S-adenosyl-L-methionine By similarity

Binding site

31

1

S-adenosyl-L-methionine By similarity

Binding site

34

1

Substrate By similarity

Binding site

41

1

S-adenosyl-L-methionine By similarity

Binding site

65

1

S-adenosyl-L-methionine; via carbonyl oxygen By similarity

Binding site

86

1

S-adenosyl-L-methionine By similarity

Binding site

139

1

S-adenosyl-L-methionine; via carbonyl oxygen By similarity

Binding site

141

1

Substrate By similarity

Binding site

178

1

Substrate By similarity

Binding site

223

1

Substrate By similarity

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. Ref.9 Ref.10

VAR_012766

Natural variant

141

1

N → S in GNMT deficiency; 0.5% wild-type activity. Ref.10 Ref.11

VAR_019840

Natural variant

177

1

H → N in GNMT deficiency; 75% wild-type activity, decreases stability of the tetramer. Ref.8 Ref.9 Ref.10

VAR_012767

Experimental info

Sequence conflict

119

1

Missing in CAA44164. Ref.6

Sequence conflict

129 – 130

2

AE → PK in AAF78289. Ref.2

Sequence conflict

175

1

I → S in CAA44164. Ref.6

Sequence conflict

256 – 260

5

LLQAA → SPSS in CAA44164. Ref.6

Secondary structure

1

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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 [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[3]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas.
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 31-295.
[7]	"Glycine N-methyltransferases: a comparison of the crystal structures and kinetic properties of recombinant human, mouse and rat enzymes." Pakhomova S., Luka Z., Grohmann S., Wagner C., Newcomer M.E. Proteins 57:331-337(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 2-294, SUBUNIT, FUNCTION.
[8]	"Destabilization of human glycine N-methyltransferase by H176N mutation." Luka Z., Pakhomova S., Luka Y., Newcomer M.E., Wagner C. Protein Sci. 16:1957-1964(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1-294, SUBUNIT, FUNCTION, CHARACTERIZATION OF VARIANT GNMT DEFICIENCY ASN-177.
[9]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS GNMT DEFICIENCY PRO-50 AND ASN-177.
[10]	"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] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS GNMT DEFICIENCY PRO-50; SER-141 AND ASN-177.
[11]	"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] [Europe PMC] [Abstract] Cited for: VARIANT GNMT DEFICIENCY SER-141.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF101477 mRNA. Translation: AAF78290.1.
AF101475 Genomic DNA. Translation: AAF78289.1.
AL158815 Genomic DNA. Translation: CAI19462.1.
CH471081 Genomic DNA. Translation: EAX04124.1.
BC032627 mRNA. Translation: AAH32627.1.
X62250 mRNA. Translation: CAA44164.1.

IPI

IPI00215925.

PIR

S42627.

RefSeq

NP_061833.1. NM_018960.4.

UniGene

Hs.144914.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1R74	X-ray	2.55	A/B	2-294	[»]
2AZT	X-ray	2.70	A/B	1-294	[»]

ProteinModelPortal

Q14749.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q14749. 6 interactions.

MINT

MINT-1436683.

STRING

9606.ENSP00000361894.

PTM databases

PhosphoSite

Q14749.

Polymorphism databases

DMDM

12644416.

Proteomic databases

PaxDb

Q14749.

PRIDE

Q14749.

Protocols and materials databases

DNASU

27232.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000372808; ENSP00000361894; ENSG00000124713.

GeneID

27232.

KEGG

hsa:27232.

UCSC

uc003otd.3. human.

Organism-specific databases

CTD

27232.

GeneCards

GC06P042928.

HGNC

HGNC:4415. GNMT.

HPA

HPA027501.

MIM

606628. gene.
606664. phenotype.

neXtProt

NX_Q14749.

Orphanet

289891. Hypermethioninemia due to glycine N-methyltransferase deficiency.

PharmGKB

PA28794.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG78825.

HOGENOM

HOG000276537.

HOVERGEN

HBG051748.

InParanoid

Q14749.

KO

K00552.

OMA

LIIDHRN.

OrthoDB

EOG4JM7QD.

PhylomeDB

Q14749.

Enzyme and pathway databases

SABIO-RK

Q14749.

Gene expression databases

Bgee

Q14749.

CleanEx

HS_GNMT.

Genevestigator

Q14749.

GermOnline

ENSG00000124713. Homo sapiens.

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

DrugBank

DB00145. Glycine.
DB00118. S-Adenosylmethionine.

EvolutionaryTrace

Q14749.

GenomeRNAi

27232.

NextBio

50091.

SOURCE

Search...

Entry information

Entry name

GNMT_HUMAN

Accession

Primary (citable) accession number: Q14749
Secondary accession number(s): Q5T8W2, Q9NNZ1, Q9NS24

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 123 of the entry and version 3 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.