GNMT_RABIT
ID GNMT_RABIT Reviewed; 295 AA.
AC Q29513; G1SKJ7;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 2.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=Glycine N-methyltransferase;
DE EC=2.1.1.20 {ECO:0000269|PubMed:4692843, ECO:0000269|PubMed:8281755};
GN Name=GNMT;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=21993624; DOI=10.1038/nature10530;
RA Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J., Washietl S.,
RA Kheradpour P., Ernst J., Jordan G., Mauceli E., Ward L.D., Lowe C.B.,
RA Holloway A.K., Clamp M., Gnerre S., Alfoldi J., Beal K., Chang J.,
RA Clawson H., Cuff J., Di Palma F., Fitzgerald S., Flicek P., Guttman M.,
RA Hubisz M.J., Jaffe D.B., Jungreis I., Kent W.J., Kostka D., Lara M.,
RA Martins A.L., Massingham T., Moltke I., Raney B.J., Rasmussen M.D.,
RA Robinson J., Stark A., Vilella A.J., Wen J., Xie X., Zody M.C., Baldwin J.,
RA Bloom T., Chin C.W., Heiman D., Nicol R., Nusbaum C., Young S.,
RA Wilkinson J., Worley K.C., Kovar C.L., Muzny D.M., Gibbs R.A., Cree A.,
RA Dihn H.H., Fowler G., Jhangiani S., Joshi V., Lee S., Lewis L.R.,
RA Nazareth L.V., Okwuonu G., Santibanez J., Warren W.C., Mardis E.R.,
RA Weinstock G.M., Wilson R.K., Delehaunty K., Dooling D., Fronik C.,
RA Fulton L., Fulton B., Graves T., Minx P., Sodergren E., Birney E.,
RA Margulies E.H., Herrero J., Green E.D., Haussler D., Siepel A., Goldman N.,
RA Pollard K.S., Pedersen J.S., Lander E.S., Kellis M.;
RT "A high-resolution map of human evolutionary constraint using 29 mammals.";
RL Nature 478:476-482(2011).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-295, CATALYTIC ACTIVITY, AND FUNCTION.
RC TISSUE=Liver;
RX PubMed=8281755; DOI=10.1016/0305-0491(93)90137-t;
RA Ogawa H., Gomi T., Fujioka M.;
RT "Mammalian glycine N-methyltransferases. Comparative kinetic and structural
RT properties of the enzymes from human, rat, rabbit and pig livers.";
RL Comp. Biochem. Physiol. 106B:601-611(1993).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=4692843; DOI=10.1016/s0021-9258(19)44446-3;
RA Heady J.E., Kerr S.J.;
RT "Purification and characterization of glycine N-methyltransferase.";
RL J. Biol. Chem. 248:69-72(1973).
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:4692843, PubMed:8281755). Plays an important role in the
CC regulation of methyl group metabolism by regulating the ratio between
CC S-adenosyl-L-methionine and S-adenosyl-L-homocysteine (By similarity).
CC {ECO:0000250|UniProtKB:P13255, ECO:0000269|PubMed:4692843,
CC ECO:0000269|PubMed:8281755}.
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; Evidence={ECO:0000269|PubMed:4692843,
CC ECO:0000269|PubMed:8281755};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19938;
CC Evidence={ECO:0000305|PubMed:4692843};
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=0.1 mM for S-adenosyl-L-methionine {ECO:0000269|PubMed:4692843};
CC KM=2.2 mM for glycine {ECO:0000269|PubMed:4692843};
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P13255}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P13255}.
CC -!- TISSUE SPECIFICITY: Abundant in liver.
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; AAGW02017997; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; D13307; BAA02567.1; -; mRNA.
DR RefSeq; XP_002714459.1; XM_002714413.3.
DR AlphaFoldDB; Q29513; -.
DR SMR; Q29513; -.
DR STRING; 9986.ENSOCUP00000003341; -.
DR Ensembl; ENSOCUT00000003855; ENSOCUP00000003341; ENSOCUG00000003858.
DR GeneID; 100009512; -.
DR KEGG; ocu:100009512; -.
DR CTD; 27232; -.
DR eggNOG; ENOG502QRN6; Eukaryota.
DR GeneTree; ENSGT00390000006845; -.
DR HOGENOM; CLU_069129_0_0_1; -.
DR InParanoid; Q29513; -.
DR OMA; YALKSRW; -.
DR OrthoDB; 1049906at2759; -.
DR TreeFam; TF324814; -.
DR SABIO-RK; Q29513; -.
DR Proteomes; UP000001811; Chromosome 12.
DR Bgee; ENSOCUG00000003858; Expressed in liver and 16 other tissues.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005542; F:folic acid binding; IEA:UniProtKB-KW.
DR GO; GO:0016594; F:glycine binding; ISS:UniProtKB.
DR GO; GO:0017174; F:glycine N-methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0046500; P:S-adenosylmethionine metabolic process; ISS:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR014369; Gly/Sar_N_MeTrfase.
DR InterPro; IPR041698; Methyltransf_25.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR16458; PTHR16458; 1.
DR Pfam; PF13649; Methyltransf_25; 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 Cytoplasm; Folate-binding; Methyltransferase; Phosphoprotein;
KW Reference proteome; S-adenosyl-L-methionine; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT CHAIN 2..295
FT /note="Glycine N-methyltransferase"
FT /id="PRO_0000087527"
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 139..142
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT BINDING 178
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT BINDING 217
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 223
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13255"
FT BINDING 242
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 242
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 10
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXF8"
FT MOD_RES 34
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXF8"
FT MOD_RES 46
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXF8"
FT MOD_RES 193
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXF8"
FT MOD_RES 198
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXF8"
FT MOD_RES 203
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXF8"
FT CONFLICT 187
FT /note="G -> L (in Ref. 2; AAGW02017997)"
FT /evidence="ECO:0000305"
FT CONFLICT 191
FT /note="Missing (in Ref. 2; AAGW02017997)"
FT /evidence="ECO:0000305"
FT CONFLICT 256
FT /note="L -> F (in Ref. 2; AAGW02017997)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 295 AA; 32863 MW; 5A89D990A35A6E33 CRC64;
MVDSVYRTRS LGVAAEGLPD QYADGEAARV WQLYIGDTRS RTSEYKTWLL GLLRQHGCRR
VLDVACGTGV DSIMLVEEGF SVTSVDASDK MLKYALKERW NRRHEPAFDK WVIEEANWMT
LDKDVPQPAG GGFDAVICLG NSFAHLPDCK GDQSEHRQAL KNIASMVRTG GLLVIDHRNY
DHILSTGCAP PGKNIYYKSD LTKDVTTSVL TVNNKAHMVT LDYTVQVPAA GQDGPPSLSK
FRLSYYPHCL APFTELLRAA FEGKCQHSVL GDFKPYQPGQ AYVPCYFIHV LKRTA
