GNMT_MOUSE
ID GNMT_MOUSE Reviewed; 293 AA.
AC Q9QXF8; Q91WN7;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Glycine N-methyltransferase;
DE EC=2.1.1.20 {ECO:0000269|PubMed:15340920};
GN Name=Gnmt;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=9497905; DOI=10.1055/s-2007-978982;
RA Aida K., Tawata M., Negishi M., Onaya T.;
RT "Mouse glycine N-methyltransferase is sexually dimorphic and regulated by
RT growth hormone.";
RL Horm. Metab. Res. 29:646-649(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/SvJ;
RA Luka Z.A., Wagner C.;
RT "Mouse glycine methyltransferase gene.";
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/SvEv;
RA Chen Y.-M.A., Wang Y.-C., Liu S.-P., Lee C.-M., Tsai T.-F.;
RT "Identification of the mouse GNMT and PEX6 genes.";
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10 AND TYR-34, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-46; LYS-191; LYS-196 AND
RP LYS-201, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 2-293, SUBUNIT, FUNCTION,
RP CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15340920; DOI=10.1002/prot.20209;
RA Pakhomova S., Luka Z., Grohmann S., Wagner C., Newcomer M.E.;
RT "Glycine N-methyltransferases: a comparison of the crystal structures and
RT kinetic properties of recombinant human, mouse and rat enzymes.";
RL Proteins 57:331-337(2004).
RN [9]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=16779654; DOI=10.1007/s11248-006-0008-1;
RA Luka Z., Capdevila A., Mato J.M., Wagner C.;
RT "A glycine N-methyltransferase knockout mouse model for humans with
RT deficiency of this enzyme.";
RL Transgenic Res. 15:393-397(2006).
CC -!- FUNCTION: Catalyzes the methylation of glycine by using S-
CC adenosylmethionine (AdoMet) to form N-methylglycine (sarcosine) with
CC the concomitant production of S-adenosylhomocysteine (AdoHcy), a
CC reaction regulated by the binding of 5-methyltetrahydrofolate
CC (PubMed:15340920). Plays an important role in the regulation of methyl
CC group metabolism by regulating the ratio between S-adenosyl-L-
CC methionine and S-adenosyl-L-homocysteine (PubMed:16779654).
CC {ECO:0000269|PubMed:15340920, ECO:0000269|PubMed:16779654}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycine + S-adenosyl-L-methionine = H(+) + S-adenosyl-L-
CC homocysteine + sarcosine; Xref=Rhea:RHEA:19937, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57305, ChEBI:CHEBI:57433, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789; EC=2.1.1.20;
CC Evidence={ECO:0000269|PubMed:15340920};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19938;
CC Evidence={ECO:0000305|PubMed:15340920};
CC -!- ACTIVITY REGULATION: Inhibited by 5-methyltetrahydrofolate
CC monoglutamate and by 5-methyltetrahydrofolate pentaglutamate,
CC inhibition is much more effective by the pentaglutamate form than by
CC the monoglutamate form. Two molecules of 5-methyltetrahydrofolate are
CC bound per tetramer. The binding sites are localized between subunits.
CC Inhibitor binding may preclude movements of the polypeptide chain that
CC are necessary for enzyme activity. {ECO:0000250|UniProtKB:P13255}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=180 uM for S-adenosyl-L-methionine {ECO:0000269|PubMed:15340920};
CC KM=3.6 mM for glycine {ECO:0000269|PubMed:15340920};
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:15340920}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P13255}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice are fertile and display elevated
CC levels of methionine and S-adenosylmethionine in the liver. At 3 and 8
CC months of age, the livers at 3 and 8 months of age show evidence of
CC fatty accumulation and fibrosis that worsen progressively.
CC {ECO:0000269|PubMed:16779654}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Glycine N-methyltransferase family. {ECO:0000255|PROSITE-
CC ProRule:PRU00932}.
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DR EMBL; D89664; BAA88218.1; -; mRNA.
DR EMBL; AF325352; AAK00338.1; -; Genomic_DNA.
DR EMBL; AY054408; AAL06142.1; -; Genomic_DNA.
DR EMBL; BC014283; AAH14283.1; -; mRNA.
DR CCDS; CCDS28838.1; -.
DR RefSeq; NP_034451.1; NM_010321.1.
DR PDB; 1R8X; X-ray; 2.95 A; A/B=2-293.
DR PDB; 1R8Y; X-ray; 3.00 A; A/B/C/D/E/F/G/H=2-293.
DR PDBsum; 1R8X; -.
DR PDBsum; 1R8Y; -.
DR AlphaFoldDB; Q9QXF8; -.
DR SMR; Q9QXF8; -.
DR BioGRID; 199995; 1.
DR STRING; 10090.ENSMUSP00000002846; -.
DR iPTMnet; Q9QXF8; -.
DR PhosphoSitePlus; Q9QXF8; -.
DR SwissPalm; Q9QXF8; -.
DR jPOST; Q9QXF8; -.
DR MaxQB; Q9QXF8; -.
DR PaxDb; Q9QXF8; -.
DR PeptideAtlas; Q9QXF8; -.
DR PRIDE; Q9QXF8; -.
DR ProteomicsDB; 267738; -.
DR Antibodypedia; 16133; 352 antibodies from 30 providers.
DR DNASU; 14711; -.
DR Ensembl; ENSMUST00000002846; ENSMUSP00000002846; ENSMUSG00000002769.
DR GeneID; 14711; -.
DR KEGG; mmu:14711; -.
DR UCSC; uc008cue.1; mouse.
DR CTD; 27232; -.
DR MGI; MGI:1202304; Gnmt.
DR VEuPathDB; HostDB:ENSMUSG00000002769; -.
DR eggNOG; ENOG502QRN6; Eukaryota.
DR GeneTree; ENSGT00390000006845; -.
DR HOGENOM; CLU_069129_0_0_1; -.
DR InParanoid; Q9QXF8; -.
DR OMA; YALKSRW; -.
DR OrthoDB; 1049906at2759; -.
DR PhylomeDB; Q9QXF8; -.
DR TreeFam; TF324814; -.
DR BRENDA; 2.1.1.20; 3474.
DR Reactome; R-MMU-389661; Glyoxylate metabolism and glycine degradation.
DR BioGRID-ORCS; 14711; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Gnmt; mouse.
DR EvolutionaryTrace; Q9QXF8; -.
DR PRO; PR:Q9QXF8; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q9QXF8; protein.
DR Bgee; ENSMUSG00000002769; Expressed in left lobe of liver and 118 other tissues.
DR Genevisible; Q9QXF8; MM.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0034708; C:methyltransferase complex; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005542; F:folic acid binding; ISO:MGI.
DR GO; GO:0016594; F:glycine binding; IDA:UniProtKB.
DR GO; GO:0017174; F:glycine N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:1904047; F:S-adenosyl-L-methionine binding; ISO:MGI.
DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; ISO:MGI.
DR GO; GO:0006544; P:glycine metabolic process; ISO:MGI.
DR GO; GO:0005977; P:glycogen metabolic process; IMP:MGI.
DR GO; GO:0006555; P:methionine metabolic process; IMP:MGI.
DR GO; GO:0032259; P:methylation; ISO:MGI.
DR GO; GO:0006730; P:one-carbon metabolic process; IMP:MGI.
DR GO; GO:0051289; P:protein homotetramerization; IPI:UniProtKB.
DR GO; GO:0006111; P:regulation of gluconeogenesis; IMP:MGI.
DR GO; GO:0046498; P:S-adenosylhomocysteine metabolic process; ISO:MGI.
DR GO; GO:0046500; P:S-adenosylmethionine metabolic process; IDA:UniProtKB.
DR GO; GO:1901052; P:sarcosine metabolic process; ISO:MGI.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR014369; Gly/Sar_N_MeTrfase.
DR InterPro; IPR025714; Methyltranfer_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR16458; PTHR16458; 1.
DR Pfam; PF13847; Methyltransf_31; 1.
DR PIRSF; PIRSF000385; Gly_N-mtase; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51600; SAM_GNMT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Folate-binding; Methyltransferase;
KW Phosphoprotein; Reference proteome; S-adenosyl-L-methionine; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT CHAIN 2..293
FT /note="Glycine N-methyltransferase"
FT /id="PRO_0000087525"
FT BINDING 4
FT /ligand="(6S)-5-methyl-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:18608"
FT /ligand_label="1"
FT /ligand_note="ligand shared between tetrameric partners"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT BINDING 6
FT /ligand="(6S)-5-methyl-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:18608"
FT /ligand_label="1"
FT /ligand_note="ligand shared between tetrameric partners"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT BINDING 6
FT /ligand="(6S)-5-methyl-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:18608"
FT /ligand_label="2"
FT /ligand_note="ligand shared between tetrameric partners"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT BINDING 22
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT BINDING 31
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT BINDING 34
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT BINDING 41
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT BINDING 65
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT BINDING 86..88
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT BINDING 117..118
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT BINDING 137..140
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT BINDING 137
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT BINDING 176
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT BINDING 215
FT /ligand="(6S)-5-methyl-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:18608"
FT /ligand_label="2"
FT /ligand_note="ligand shared between tetrameric partners"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT BINDING 221
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT BINDING 240
FT /ligand="(6S)-5-methyl-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:18608"
FT /ligand_label="1"
FT /ligand_note="ligand shared between tetrameric partners"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT BINDING 240
FT /ligand="(6S)-5-methyl-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:18608"
FT /ligand_label="2"
FT /ligand_note="ligand shared between tetrameric partners"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT MOD_RES 2
FT /note="N-acetylvaline"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 34
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 46
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 191
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 196
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 201
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 157
FT /note="A -> E (in Ref. 4; AAH14283)"
FT /evidence="ECO:0000305"
FT STRAND 16..18
FT /evidence="ECO:0007829|PDB:1R8Y"
FT TURN 21..24
FT /evidence="ECO:0007829|PDB:1R8X"
FT HELIX 26..35
FT /evidence="ECO:0007829|PDB:1R8X"
FT STRAND 39..41
FT /evidence="ECO:0007829|PDB:1R8X"
FT HELIX 43..55
FT /evidence="ECO:0007829|PDB:1R8X"
FT STRAND 60..65
FT /evidence="ECO:0007829|PDB:1R8X"
FT HELIX 70..77
FT /evidence="ECO:0007829|PDB:1R8X"
FT STRAND 81..87
FT /evidence="ECO:0007829|PDB:1R8X"
FT HELIX 89..101
FT /evidence="ECO:0007829|PDB:1R8X"
FT TURN 102..104
FT /evidence="ECO:0007829|PDB:1R8X"
FT HELIX 106..109
FT /evidence="ECO:0007829|PDB:1R8X"
FT STRAND 112..115
FT /evidence="ECO:0007829|PDB:1R8X"
FT HELIX 118..120
FT /evidence="ECO:0007829|PDB:1R8X"
FT HELIX 122..124
FT /evidence="ECO:0007829|PDB:1R8X"
FT STRAND 131..136
FT /evidence="ECO:0007829|PDB:1R8X"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:1R8X"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:1R8X"
FT HELIX 152..162
FT /evidence="ECO:0007829|PDB:1R8X"
FT STRAND 165..176
FT /evidence="ECO:0007829|PDB:1R8X"
FT HELIX 178..184
FT /evidence="ECO:0007829|PDB:1R8X"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:1R8X"
FT STRAND 201..210
FT /evidence="ECO:0007829|PDB:1R8X"
FT STRAND 213..224
FT /evidence="ECO:0007829|PDB:1R8X"
FT STRAND 236..243
FT /evidence="ECO:0007829|PDB:1R8X"
FT HELIX 248..257
FT /evidence="ECO:0007829|PDB:1R8X"
FT TURN 258..261
FT /evidence="ECO:0007829|PDB:1R8X"
FT STRAND 263..273
FT /evidence="ECO:0007829|PDB:1R8X"
FT STRAND 283..291
FT /evidence="ECO:0007829|PDB:1R8X"
SQ SEQUENCE 293 AA; 32675 MW; 264F0ACB6BBF3CDA CRC64;
MVDSVYRTRS LGVAAEGLPD QYADGEAARV WQLYIGDTRS RTAEYKAWLL GLLRQHGCHR
VLDVACGTGV DSIMLVEEGF SVMSVDASDK MLKYALKERW NRRKEPSFDN WVIEEANWLT
LDKDVLSGDG FDAVICLGNS FAHLPDCKGD QSEHRLALKN IASMVRPGGL LVIDHRNYDY
ILSTGCAPPG KNIYYKSDLT KDITTSVLTV NNKAHMVTLD YTVQVPGTGR DGSPGFSKFR
LSYYPHCLAS FTELVRAAFG GRCQHSVLGD FKPYKPGQAY VPCYFIHVLK KTD
