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Q14749

- GNMT_HUMAN

UniProt

Q14749 - GNMT_HUMAN

Protein

Glycine N-methyltransferase

Gene

GNMT

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 133 (01 Oct 2014)
      Sequence version 3 (23 Jan 2007)
      Previous versions | rss
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    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

    1. folic acid binding Source: UniProtKB-KW
    2. glycine binding Source: UniProtKB
    3. glycine N-methyltransferase activity Source: UniProtKB
    4. protein binding Source: IntAct

    GO - Biological processi

    1. cellular protein modification process Source: UniProtKB
    2. glycogen metabolic process Source: Ensembl
    3. methionine metabolic process Source: Ensembl
    4. one-carbon metabolic process Source: Ensembl
    5. protein homotetramerization Source: UniProtKB
    6. regulation of gluconeogenesis Source: Ensembl
    7. S-adenosylmethionine metabolic process Source: UniProtKB

    Keywords - Molecular functioni

    Methyltransferase, Transferase

    Keywords - Ligandi

    Folate-binding, S-adenosyl-L-methionine

    Enzyme and pathway databases

    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: Chromosome 6

    Organism-specific databases

    HGNCiHGNC:4415. GNMT.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: HPA

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    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.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti50 – 501L → P in GNMT deficiency; 10% wild-type activity. 1 Publication
    VAR_012766
    Natural varianti141 – 1411N → S in GNMT deficiency; 0.5% wild-type activity. 1 Publication
    VAR_019840
    Natural varianti177 – 1771H → N in GNMT deficiency; 75% wild-type activity, decreases stability of the tetramer. 1 Publication
    VAR_012767

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

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

    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.
    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. 12 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 – 244
    Helixi28 – 347
    Helixi43 – 5513
    Beta strandi60 – 645
    Helixi70 – 789
    Beta strandi81 – 877
    Helixi89 – 10113
    Turni102 – 1043
    Helixi106 – 1094
    Beta strandi112 – 1154
    Helixi118 – 1203
    Helixi121 – 1244
    Beta strandi133 – 1386
    Helixi143 – 1453
    Beta strandi150 – 1534
    Helixi154 – 16512
    Beta strandi167 – 17812
    Helixi180 – 1867
    Beta strandi195 – 1973
    Beta strandi204 – 2129
    Beta strandi215 – 22511
    Beta strandi239 – 2457
    Helixi250 – 26011
    Turni261 – 2633
    Beta strandi265 – 2717
    Beta strandi285 – 2939

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.
    OMAiLIIDHRN.
    OrthoDBiEOG76QFHR.
    PhylomeDBiQ14749.
    TreeFamiTF324814.

    Family and domain databases

    Gene3Di3.40.50.150. 1 hit.
    InterProiIPR014369. Gly/Sar_N_MeTrfase.
    IPR029063. SAM-dependent_MTases-like.
    [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

    MVDSVYRTRS LGVAAEGLPD QYADGEAARV WQLYIGDTRS RTAEYKAWLL    50
    GLLRQHGCQR VLDVACGTGV DSIMLVEEGF SVTSVDASDK MLKYALKERW 100
    NRRHEPAFDK WVIEEANWMT LDKDVPQSAE GGFDAVICLG NSFAHLPDCK 150
    GDQSEHRLAL KNIASMVRAG GLLVIDHRNY DHILSTGCAP PGKNIYYKSD 200
    LTKDVTTSVL IVNNKAHMVT LDYTVQVPGA GQDGSPGLSK FRLSYYPHCL 250
    ASFTELLQAA FGGKCQHSVL GDFKPYKPGQ TYIPCYFIHV LKRTD 295
    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. 1 Publication
    VAR_012766
    Natural varianti141 – 1411N → S in GNMT deficiency; 0.5% wild-type activity. 1 Publication
    VAR_019840
    Natural varianti177 – 1771H → N in GNMT deficiency; 75% wild-type activity, decreases stability of the tetramer. 1 Publication
    VAR_012767

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.

    Polymorphism databases

    DMDMi12644416.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS4876.1.
    PIRi S42627.
    RefSeqi NP_061833.1. NM_018960.4.
    UniGenei Hs.144914.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1R74 X-ray 2.55 A/B 2-295 [» ]
    2AZT X-ray 2.70 A/B 1-295 [» ]
    ProteinModelPortali Q14749.
    SMRi Q14749. Positions 6-294.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 118081. 12 interactions.
    IntActi Q14749. 7 interactions.
    MINTi MINT-1436683.
    STRINGi 9606.ENSP00000361894.

    Chemistry

    DrugBanki DB00145. Glycine.
    DB00118. S-Adenosylmethionine.

    PTM databases

    PhosphoSitei Q14749.

    Polymorphism databases

    DMDMi 12644416.

    Proteomic databases

    PaxDbi Q14749.
    PRIDEi Q14749.

    Protocols and materials databases

    DNASUi 27232.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000372808 ; ENSP00000361894 ; ENSG00000124713 .
    GeneIDi 27232.
    KEGGi hsa:27232.
    UCSCi uc003otd.3. human.

    Organism-specific databases

    CTDi 27232.
    GeneCardsi GC06P042928.
    HGNCi HGNC:4415. GNMT.
    HPAi HPA027501.
    MIMi 606628. gene.
    606664. phenotype.
    neXtProti NX_Q14749.
    Orphaneti 289891. Hypermethioninemia due to glycine N-methyltransferase deficiency.
    PharmGKBi PA28794.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG78825.
    HOGENOMi HOG000276537.
    HOVERGENi HBG051748.
    InParanoidi Q14749.
    KOi K00552.
    OMAi LIIDHRN.
    OrthoDBi EOG76QFHR.
    PhylomeDBi Q14749.
    TreeFami TF324814.

    Enzyme and pathway databases

    SABIO-RK Q14749.

    Miscellaneous databases

    EvolutionaryTracei Q14749.
    GeneWikii GNMT.
    GenomeRNAii 27232.
    NextBioi 50091.
    PROi Q14749.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q14749.
    CleanExi HS_GNMT.
    Genevestigatori Q14749.

    Family and domain databases

    Gene3Di 3.40.50.150. 1 hit.
    InterProi IPR014369. Gly/Sar_N_MeTrfase.
    IPR029063. SAM-dependent_MTases-like.
    [Graphical view ]
    PANTHERi PTHR16458. PTHR16458. 1 hit.
    PIRSFi PIRSF000385. Gly_N-mtase. 1 hit.
    SUPFAMi SSF53335. SSF53335. 1 hit.
    PROSITEi PS51600. SAM_GNMT. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. "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. 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: October 1, 2014
    This is version 133 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