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Q14749 (GNMT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glycine N-methyltransferase

EC=2.1.1.20
Gene names
Name:GNMT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length295 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ARRB1P494075EBI-744239,EBI-743313

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 295294Glycine N-methyltransferase
PRO_0000087524

Regions

Region117 – 1182S-adenosyl-L-methionine binding By similarity

Sites

Binding site221S-adenosyl-L-methionine By similarity
Binding site311S-adenosyl-L-methionine By similarity
Binding site341Substrate By similarity
Binding site411S-adenosyl-L-methionine By similarity
Binding site651S-adenosyl-L-methionine; via carbonyl oxygen By similarity
Binding site861S-adenosyl-L-methionine By similarity
Binding site1391S-adenosyl-L-methionine; via carbonyl oxygen By similarity
Binding site1411Substrate By similarity
Binding site1781Substrate By similarity
Binding site2231Substrate By similarity

Amino acid modifications

Modified residue21N-acetylvaline By similarity
Modified residue101Phosphoserine By similarity
Modified residue461N6-succinyllysine By similarity
Modified residue1931N6-succinyllysine By similarity
Modified residue1981N6-succinyllysine By similarity
Modified residue2031N6-succinyllysine By similarity

Natural variations

Natural variant501L → P in GNMT deficiency; 10% wild-type activity. Ref.9 Ref.10
VAR_012766
Natural variant1411N → S in GNMT deficiency; 0.5% wild-type activity. Ref.10 Ref.11
VAR_019840
Natural variant1771H → N in GNMT deficiency; 75% wild-type activity, decreases stability of the tetramer. Ref.8 Ref.9 Ref.10
VAR_012767

Experimental info

Sequence conflict1191Missing in CAA44164. Ref.6
Sequence conflict129 – 1302AE → PK in AAF78289. Ref.2
Sequence conflict1751I → S in CAA44164. Ref.6
Sequence conflict256 – 2605LLQAA → SPSS in CAA44164. Ref.6

Secondary structure

................................................. 295
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q14749 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 34F4546136FD27ED

FASTA29532,742
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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.
PIRS42627.
RefSeqNP_061833.1. NM_018960.4.
UniGeneHs.144914.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1R74X-ray2.55A/B2-294[»]
2AZTX-ray2.70A/B1-294[»]
ProteinModelPortalQ14749.
SMRQ14749. Positions 6-294.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118081. 12 interactions.
IntActQ14749. 7 interactions.
MINTMINT-1436683.
STRING9606.ENSP00000361894.

Chemistry

DrugBankDB00145. Glycine.
DB00118. S-Adenosylmethionine.

PTM databases

PhosphoSiteQ14749.

Polymorphism databases

DMDM12644416.

Proteomic databases

PaxDbQ14749.
PRIDEQ14749.

Protocols and materials databases

DNASU27232.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000372808; ENSP00000361894; ENSG00000124713.
GeneID27232.
KEGGhsa:27232.
UCSCuc003otd.3. human.

Organism-specific databases

CTD27232.
GeneCardsGC06P042928.
HGNCHGNC:4415. GNMT.
HPAHPA027501.
MIM606628. gene.
606664. phenotype.
neXtProtNX_Q14749.
Orphanet289891. Hypermethioninemia due to glycine N-methyltransferase deficiency.
PharmGKBPA28794.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG78825.
HOGENOMHOG000276537.
HOVERGENHBG051748.
InParanoidQ14749.
KOK00552.
OMALIIDHRN.
OrthoDBEOG76QFHR.
PhylomeDBQ14749.
TreeFamTF324814.

Enzyme and pathway databases

SABIO-RKQ14749.

Gene expression databases

BgeeQ14749.
CleanExHS_GNMT.
GenevestigatorQ14749.

Family and domain databases

InterProIPR014369. Gly/Sar_N_MeTrfase.
[Graphical view]
PANTHERPTHR16458. PTHR16458. 1 hit.
PIRSFPIRSF000385. Gly_N-mtase. 1 hit.
PROSITEPS51600. SAM_GNMT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ14749.
GeneWikiGNMT.
GenomeRNAi27232.
NextBio50091.
PROQ14749.
SOURCESearch...

Entry information

Entry nameGNMT_HUMAN
AccessionPrimary (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: March 19, 2014
This is version 130 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM