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Protein

Glycine N-methyltransferase

Gene

GNMT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

S-adenosyl-L-methionine + glycine = S-adenosyl-L-homocysteine + sarcosine.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei22 – 221S-adenosyl-L-methioninePROSITE-ProRule annotation
Binding sitei31 – 311S-adenosyl-L-methioninePROSITE-ProRule annotation
Binding sitei34 – 341SubstratePROSITE-ProRule annotation
Binding sitei41 – 411S-adenosyl-L-methioninePROSITE-ProRule annotation
Binding sitei65 – 651S-adenosyl-L-methionine; via carbonyl oxygenPROSITE-ProRule annotation
Binding sitei86 – 861S-adenosyl-L-methioninePROSITE-ProRule annotation
Binding sitei139 – 1391S-adenosyl-L-methionine; via carbonyl oxygenPROSITE-ProRule annotation
Binding sitei141 – 1411SubstratePROSITE-ProRule annotation
Binding sitei178 – 1781SubstratePROSITE-ProRule annotation
Binding sitei223 – 2231SubstratePROSITE-ProRule annotation

GO - Molecular functioni

  • folic acid binding Source: UniProtKB-KW
  • glycine binding Source: UniProtKB
  • glycine N-methyltransferase activity Source: UniProtKB

GO - Biological processi

  • cellular protein modification process Source: UniProtKB
  • glycogen metabolic process Source: Ensembl
  • methionine metabolic process Source: Ensembl
  • one-carbon metabolic process Source: Ensembl
  • protein homotetramerization Source: UniProtKB
  • regulation of gluconeogenesis Source: Ensembl
  • S-adenosylmethionine metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Methyltransferase, Transferase

Keywords - Ligandi

Folate-binding, S-adenosyl-L-methionine

Enzyme and pathway databases

BRENDAi2.1.1.20. 2681.
SABIO-RKQ14749.

Names & Taxonomyi

Protein namesi
Recommended name:
Glycine N-methyltransferase (EC:2.1.1.20)
Gene namesi
Name:GNMT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:4415. GNMT.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Glycine N-methyltransferase deficiency (GNMT deficiency)2 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionThe only clinical abnormalities in patients with this deficiency are mild hepatomegaly and chronic elevation of serum transaminases.

See also OMIM:606664
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti50 – 501L → P in GNMT deficiency; 10% wild-type activity. 2 Publications
VAR_012766
Natural varianti141 – 1411N → S in GNMT deficiency; 0.5% wild-type activity. 2 Publications
VAR_019840
Natural varianti177 – 1771H → N in GNMT deficiency; 75% wild-type activity, decreases stability of the tetramer. 3 Publications
VAR_012767

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi606664. phenotype.
Orphaneti289891. Hypermethioninemia due to glycine N-methyltransferase deficiency.
PharmGKBiPA28794.

Chemistry

DrugBankiDB00145. Glycine.
DB00118. S-Adenosylmethionine.

Polymorphism and mutation databases

BioMutaiGNMT.
DMDMi12644416.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 295294Glycine N-methyltransferasePRO_0000087524Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylvalineBy similarity
Modified residuei10 – 101PhosphoserineBy similarity
Modified residuei46 – 461N6-succinyllysineBy similarity
Modified residuei193 – 1931N6-succinyllysineBy similarity
Modified residuei198 – 1981N6-succinyllysineBy similarity
Modified residuei203 – 2031N6-succinyllysineBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ14749.
PRIDEiQ14749.

PTM databases

PhosphoSiteiQ14749.

Expressioni

Tissue specificityi

Abundant in liver.

Gene expression databases

BgeeiQ14749.
CleanExiHS_GNMT.
ExpressionAtlasiQ14749. baseline and differential.
GenevestigatoriQ14749.

Organism-specific databases

HPAiHPA027501.

Interactioni

Subunit structurei

Homotetramer.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ARRB1P494075EBI-744239,EBI-743313

Protein-protein interaction databases

BioGridi118081. 18 interactions.
IntActiQ14749. 7 interactions.
MINTiMINT-1436683.
STRINGi9606.ENSP00000361894.

Structurei

Secondary structure

1
295
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni21 – 244Combined sources
Helixi28 – 347Combined sources
Helixi43 – 5513Combined sources
Beta strandi60 – 645Combined sources
Helixi70 – 789Combined sources
Beta strandi81 – 877Combined sources
Helixi89 – 10113Combined sources
Turni102 – 1043Combined sources
Helixi106 – 1094Combined sources
Beta strandi112 – 1154Combined sources
Helixi118 – 1203Combined sources
Helixi121 – 1244Combined sources
Beta strandi133 – 1386Combined sources
Helixi143 – 1453Combined sources
Beta strandi150 – 1534Combined sources
Helixi154 – 16512Combined sources
Beta strandi167 – 17812Combined sources
Helixi180 – 1867Combined sources
Beta strandi195 – 1973Combined sources
Beta strandi204 – 2129Combined sources
Beta strandi215 – 22511Combined sources
Beta strandi239 – 2457Combined sources
Helixi250 – 26011Combined sources
Turni261 – 2633Combined sources
Beta strandi265 – 2717Combined sources
Beta strandi285 – 2939Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1R74X-ray2.55A/B2-295[»]
2AZTX-ray2.70A/B1-295[»]
ProteinModelPortaliQ14749.
SMRiQ14749. Positions 6-294.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ14749.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni117 – 1182S-adenosyl-L-methionine bindingPROSITE-ProRule annotation

Sequence similaritiesi

Belongs to the class I-like SAM-binding methyltransferase superfamily. Glycine N-methyltransferase family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG78825.
HOGENOMiHOG000276537.
HOVERGENiHBG051748.
InParanoidiQ14749.
KOiK00552.
OMAiGQAYIPC.
OrthoDBiEOG76QFHR.
PhylomeDBiQ14749.
TreeFamiTF324814.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR014369. Gly/Sar_N_MeTrfase.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR16458. PTHR16458. 1 hit.
PIRSFiPIRSF000385. Gly_N-mtase. 1 hit.
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51600. SAM_GNMT. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q14749-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVDSVYRTRS LGVAAEGLPD QYADGEAARV WQLYIGDTRS RTAEYKAWLL
60 70 80 90 100
GLLRQHGCQR VLDVACGTGV DSIMLVEEGF SVTSVDASDK MLKYALKERW
110 120 130 140 150
NRRHEPAFDK WVIEEANWMT LDKDVPQSAE GGFDAVICLG NSFAHLPDCK
160 170 180 190 200
GDQSEHRLAL KNIASMVRAG GLLVIDHRNY DHILSTGCAP PGKNIYYKSD
210 220 230 240 250
LTKDVTTSVL IVNNKAHMVT LDYTVQVPGA GQDGSPGLSK FRLSYYPHCL
260 270 280 290
ASFTELLQAA FGGKCQHSVL GDFKPYKPGQ TYIPCYFIHV LKRTD
Length:295
Mass (Da):32,742
Last modified:January 23, 2007 - v3
Checksum:i34F4546136FD27ED
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti119 – 1191Missing in CAA44164 (PubMed:8281755).Curated
Sequence conflicti129 – 1302AE → PK in AAF78289 (PubMed:10843803).Curated
Sequence conflicti175 – 1751I → S in CAA44164 (PubMed:8281755).Curated
Sequence conflicti256 – 2605LLQAA → SPSS in CAA44164 (PubMed:8281755).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti50 – 501L → P in GNMT deficiency; 10% wild-type activity. 2 Publications
VAR_012766
Natural varianti141 – 1411N → S in GNMT deficiency; 0.5% wild-type activity. 2 Publications
VAR_019840
Natural varianti177 – 1771H → N in GNMT deficiency; 75% wild-type activity, decreases stability of the tetramer. 3 Publications
VAR_012767

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS4876.1.
PIRiS42627.
RefSeqiNP_061833.1. NM_018960.4.
UniGeneiHs.144914.

Genome annotation databases

EnsembliENST00000372808; ENSP00000361894; ENSG00000124713.
GeneIDi27232.
KEGGihsa:27232.
UCSCiuc003otd.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS4876.1.
PIRiS42627.
RefSeqiNP_061833.1. NM_018960.4.
UniGeneiHs.144914.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1R74X-ray2.55A/B2-295[»]
2AZTX-ray2.70A/B1-295[»]
ProteinModelPortaliQ14749.
SMRiQ14749. Positions 6-294.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118081. 18 interactions.
IntActiQ14749. 7 interactions.
MINTiMINT-1436683.
STRINGi9606.ENSP00000361894.

Chemistry

DrugBankiDB00145. Glycine.
DB00118. S-Adenosylmethionine.

PTM databases

PhosphoSiteiQ14749.

Polymorphism and mutation databases

BioMutaiGNMT.
DMDMi12644416.

Proteomic databases

PaxDbiQ14749.
PRIDEiQ14749.

Protocols and materials databases

DNASUi27232.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000372808; ENSP00000361894; ENSG00000124713.
GeneIDi27232.
KEGGihsa:27232.
UCSCiuc003otd.3. human.

Organism-specific databases

CTDi27232.
GeneCardsiGC06P042928.
HGNCiHGNC:4415. GNMT.
HPAiHPA027501.
MIMi606628. gene.
606664. phenotype.
neXtProtiNX_Q14749.
Orphaneti289891. Hypermethioninemia due to glycine N-methyltransferase deficiency.
PharmGKBiPA28794.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG78825.
HOGENOMiHOG000276537.
HOVERGENiHBG051748.
InParanoidiQ14749.
KOiK00552.
OMAiGQAYIPC.
OrthoDBiEOG76QFHR.
PhylomeDBiQ14749.
TreeFamiTF324814.

Enzyme and pathway databases

BRENDAi2.1.1.20. 2681.
SABIO-RKQ14749.

Miscellaneous databases

EvolutionaryTraceiQ14749.
GeneWikiiGNMT.
GenomeRNAii27232.
NextBioi50091.
PROiQ14749.
SOURCEiSearch...

Gene expression databases

BgeeiQ14749.
CleanExiHS_GNMT.
ExpressionAtlasiQ14749. baseline and differential.
GenevestigatoriQ14749.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR014369. Gly/Sar_N_MeTrfase.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR16458. PTHR16458. 1 hit.
PIRSFiPIRSF000385. Gly_N-mtase. 1 hit.
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51600. SAM_GNMT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  8. "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.
  9. "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.
  10. "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.
  11. "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.
  12. Cited for: VARIANT GNMT DEFICIENCY SER-141.

Entry informationi

Entry nameiGNMT_HUMAN
AccessioniPrimary (citable) accession number: Q14749
Secondary accession number(s): Q5T8W2, Q9NNZ1, Q9NS24
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 23, 2007
Last modified: April 29, 2015
This is version 140 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.