GAMT_RAT
ID GAMT_RAT Reviewed; 236 AA.
AC P10868;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Guanidinoacetate N-methyltransferase;
DE EC=2.1.1.2;
GN Name=Gamt;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=3277179; DOI=10.1073/pnas.85.3.694;
RA Ogawa H., Date T., Gomi T., Konishi K., Pitot H.C., Cantoni G.L.,
RA Fujioka M.;
RT "Molecular cloning, sequence analysis, and expression in Escherichia coli
RT of the cDNA for guanidinoacetate methyltransferase from rat liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:694-698(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3419933; DOI=10.1093/nar/16.17.8715;
RA Ogawa H., Fujioka M.;
RT "Nucleotide sequence of the rat guanidinoacetate methyltransferase gene.";
RL Nucleic Acids Res. 16:8715-8716(1988).
RN [3]
RP PROTEIN SEQUENCE OF 22-29, FUNCTION, AND SUBUNIT STRUCTURE.
RX PubMed=1990977; DOI=10.1016/0003-9861(91)90347-l;
RA Fujioka M., Takata Y., Gomi T.;
RT "Recombinant rat guanidinoacetate methyltransferase: structure and function
RT of the NH2-terminal region as deduced by limited proteolysis.";
RL Arch. Biochem. Biophys. 285:181-186(1991).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=11165387; DOI=10.1016/s0169-328x(00)00269-2;
RA Braissant O., Henry H., Loup M., Eilers B., Bachmann C.;
RT "Endogenous synthesis and transport of creatine in the rat brain: an in
RT situ hybridization study.";
RL Brain Res. Mol. Brain Res. 86:193-201(2001).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=15918910; DOI=10.1186/1471-213x-5-9;
RA Braissant O., Henry H., Villard A.M., Speer O., Wallimann T., Bachmann C.;
RT "Creatine synthesis and transport during rat embryogenesis: spatiotemporal
RT expression of AGAT, GAMT and CT1.";
RL BMC Dev. Biol. 5:9-9(2005).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [7] {ECO:0007744|PDB:1KHH}
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 39-236 IN COMPLEX WITH
RP S-ADENOSYLHOMOCYSTEINE, AND SUBUNIT.
RC TISSUE=Liver;
RX PubMed=12079381; DOI=10.1016/s0022-2836(02)00448-5;
RA Komoto J., Huang Y., Takata Y., Yamada T., Konishi K., Ogawa H., Gomi T.,
RA Fujioka M., Takusagawa F.;
RT "Crystal structure of guanidinoacetate methyltransferase from rat liver: a
RT model structure of protein arginine methyltransferase.";
RL J. Mol. Biol. 320:223-235(2002).
RN [8] {ECO:0007744|PDB:1P1B, ECO:0007744|PDB:1P1C}
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 38-236 IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE, AND SUBUNIT.
RX PubMed=12925789; DOI=10.1107/s0907444903014719;
RA Komoto J., Takata Y., Yamada T., Konishi K., Ogawa H., Gomi T., Fujioka M.,
RA Takusagawa F.;
RT "Monoclinic guanidinoacetate methyltransferase and gadolinium ion-binding
RT characteristics.";
RL Acta Crystallogr. D 59:1589-1596(2003).
RN [9] {ECO:0007744|PDB:1XCJ, ECO:0007744|PDB:1XCL}
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE AND GUANIDINOACETATE, AND MUTAGENESIS OF GLU-46;
RP ASP-135 AND TYR-222.
RX PubMed=15533043; DOI=10.1021/bi0486785;
RA Komoto J., Yamada T., Takata Y., Konishi K., Ogawa H., Gomi T., Fujioka M.,
RA Takusagawa F.;
RT "Catalytic mechanism of guanidinoacetate methyltransferase: crystal
RT structures of guanidinoacetate methyltransferase ternary complexes.";
RL Biochemistry 43:14385-14394(2004).
CC -!- FUNCTION: Converts guanidinoacetate to creatine, using S-
CC adenosylmethionine as the methyl donor. Important in nervous system
CC development. {ECO:0000250|UniProtKB:Q14353}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=guanidinoacetate + S-adenosyl-L-methionine = creatine + H(+) +
CC S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:10656, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57742, ChEBI:CHEBI:57856, ChEBI:CHEBI:57947,
CC ChEBI:CHEBI:59789; EC=2.1.1.2; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU00892};
CC -!- PATHWAY: Amine and polyamine biosynthesis; creatine biosynthesis;
CC creatine from L-arginine and glycine: step 2/2.
CC -!- SUBUNIT: Monomer. May form homodimers upon proteolytic removal of the
CC first 36 amino acid residues. {ECO:0000269|PubMed:12079381,
CC ECO:0000269|PubMed:12925789, ECO:0000269|PubMed:15533043,
CC ECO:0000269|PubMed:1990977}.
CC -!- TISSUE SPECIFICITY: Expressed in hepatic primordium in the embryo as
CC soon as 12.5 days. In the adult, high levels of expression are found in
CC liver and pancreas. Ubiquitously expressed in neuronal and glial cells
CC in the brain. {ECO:0000269|PubMed:11165387,
CC ECO:0000269|PubMed:15918910}.
CC -!- MISCELLANEOUS: The N-terminal first 36 amino acid residues are
CC susceptible to proteolytic cleavage, leading to loss of activity.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. RMT2 methyltransferase family. {ECO:0000255|PROSITE-
CC ProRule:PRU00892}.
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DR EMBL; J03588; AAA41258.1; -; mRNA.
DR EMBL; X08056; CAA30845.1; -; Genomic_DNA.
DR PIR; S01395; S01395.
DR PDB; 1KHH; X-ray; 2.50 A; A/B=39-236.
DR PDB; 1P1B; X-ray; 2.80 A; A/B/C/D=38-236.
DR PDB; 1P1C; X-ray; 2.50 A; A/B=38-236.
DR PDB; 1XCJ; X-ray; 2.00 A; A=2-236.
DR PDB; 1XCL; X-ray; 2.00 A; A=2-236.
DR PDBsum; 1KHH; -.
DR PDBsum; 1P1B; -.
DR PDBsum; 1P1C; -.
DR PDBsum; 1XCJ; -.
DR PDBsum; 1XCL; -.
DR AlphaFoldDB; P10868; -.
DR SMR; P10868; -.
DR STRING; 10116.ENSRNOP00000036927; -.
DR iPTMnet; P10868; -.
DR PaxDb; P10868; -.
DR UCSC; RGD:2659; rat.
DR RGD; 2659; Gamt.
DR eggNOG; KOG1709; Eukaryota.
DR InParanoid; P10868; -.
DR BioCyc; MetaCyc:MON-7641; -.
DR BRENDA; 2.1.1.2; 5301.
DR Reactome; R-RNO-71288; Creatine metabolism.
DR SABIO-RK; P10868; -.
DR UniPathway; UPA00104; UER00580.
DR EvolutionaryTrace; P10868; -.
DR PRO; PR:P10868; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0030731; F:guanidinoacetate N-methyltransferase activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; IDA:RGD.
DR GO; GO:0009887; P:animal organ morphogenesis; ISO:RGD.
DR GO; GO:0006601; P:creatine biosynthetic process; IDA:RGD.
DR GO; GO:1990402; P:embryonic liver development; IEP:RGD.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0040014; P:regulation of multicellular organism growth; ISO:RGD.
DR GO; GO:0046498; P:S-adenosylhomocysteine metabolic process; IDA:RGD.
DR GO; GO:0046500; P:S-adenosylmethionine metabolic process; IDA:RGD.
DR GO; GO:0007283; P:spermatogenesis; ISO:RGD.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR016550; GuanidinoAc_N-MeTrfase.
DR InterPro; IPR026480; RMT2_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PIRSF; PIRSF009285; GAMT; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51559; SAM_RMT2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing; Methyltransferase;
KW Phosphoprotein; Reference proteome; S-adenosyl-L-methionine; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q14353"
FT CHAIN 2..236
FT /note="Guanidinoacetate N-methyltransferase"
FT /id="PRO_0000087432"
FT DOMAIN 13..236
FT /note="RMT2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00892"
FT REGION 90..92
FT /note="S-adenosyl-L-methionine"
FT BINDING 20
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 42
FT /ligand="guanidinoacetate"
FT /ligand_id="ChEBI:CHEBI:57742"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00892,
FT ECO:0000269|PubMed:15533043, ECO:0007744|PDB:1XCJ"
FT BINDING 46
FT /ligand="guanidinoacetate"
FT /ligand_id="ChEBI:CHEBI:57742"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00892,
FT ECO:0000269|PubMed:15533043, ECO:0007744|PDB:1XCJ"
FT BINDING 50
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 69..74
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 117..118
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 135
FT /ligand="guanidinoacetate"
FT /ligand_id="ChEBI:CHEBI:57742"
FT /evidence="ECO:0000269|PubMed:15533043,
FT ECO:0007744|PDB:1XCJ"
FT BINDING 135
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 171..172
FT /ligand="guanidinoacetate"
FT /ligand_id="ChEBI:CHEBI:57742"
FT /evidence="ECO:0000269|PubMed:15533043,
FT ECO:0007744|PDB:1XCJ"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q14353"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MUTAGEN 46
FT /note="E->D: Reduces affinity for substrate and S-adenosyl-
FT L-methionine about 2-fold."
FT /evidence="ECO:0000269|PubMed:15533043"
FT MUTAGEN 46
FT /note="E->Q: Reduces affinity for substrate and S-adenosyl-
FT L-methionine about 4-fold."
FT /evidence="ECO:0000269|PubMed:15533043"
FT MUTAGEN 46
FT /note="E->S: Loss of activity."
FT /evidence="ECO:0000269|PubMed:15533043"
FT MUTAGEN 135
FT /note="D->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:15533043"
FT MUTAGEN 135
FT /note="D->E: Reduces affinity for S-adenosyl-L-methionine
FT 500-fold. Reduces affinity for substrate about 40-fold."
FT /evidence="ECO:0000269|PubMed:15533043"
FT MUTAGEN 135
FT /note="D->N: Reduces affinity for S-adenosyl-L-methionine
FT 2000-fold. Reduces affinity for substrate about 40-fold."
FT /evidence="ECO:0000269|PubMed:15533043"
FT MUTAGEN 222
FT /note="Y->F: Reduces affinity for S-adenosyl-L-methionine
FT about 5-fold. Reduces affinity for substrate about 40-
FT fold."
FT /evidence="ECO:0000269|PubMed:15533043"
FT HELIX 17..20
FT /evidence="ECO:0007829|PDB:1XCJ"
FT STRAND 33..36
FT /evidence="ECO:0007829|PDB:1XCJ"
FT STRAND 39..43
FT /evidence="ECO:0007829|PDB:1XCJ"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:1XCJ"
FT HELIX 47..57
FT /evidence="ECO:0007829|PDB:1XCJ"
FT TURN 58..60
FT /evidence="ECO:0007829|PDB:1XCJ"
FT STRAND 62..67
FT /evidence="ECO:0007829|PDB:1XCJ"
FT HELIX 73..80
FT /evidence="ECO:0007829|PDB:1XCJ"
FT STRAND 84..90
FT /evidence="ECO:0007829|PDB:1XCJ"
FT HELIX 93..103
FT /evidence="ECO:0007829|PDB:1XCJ"
FT STRAND 107..115
FT /evidence="ECO:0007829|PDB:1XCJ"
FT HELIX 117..120
FT /evidence="ECO:0007829|PDB:1XCJ"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:1XCJ"
FT STRAND 129..134
FT /evidence="ECO:0007829|PDB:1XCJ"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:1XCJ"
FT TURN 144..146
FT /evidence="ECO:0007829|PDB:1XCJ"
FT HELIX 147..154
FT /evidence="ECO:0007829|PDB:1XCJ"
FT HELIX 156..159
FT /evidence="ECO:0007829|PDB:1XCJ"
FT STRAND 160..168
FT /evidence="ECO:0007829|PDB:1XCJ"
FT HELIX 171..180
FT /evidence="ECO:0007829|PDB:1XCJ"
FT HELIX 185..192
FT /evidence="ECO:0007829|PDB:1XCJ"
FT HELIX 194..200
FT /evidence="ECO:0007829|PDB:1XCJ"
FT HELIX 204..206
FT /evidence="ECO:0007829|PDB:1XCJ"
FT STRAND 207..213
FT /evidence="ECO:0007829|PDB:1XCJ"
FT STRAND 226..234
FT /evidence="ECO:0007829|PDB:1XCJ"
SQ SEQUENCE 236 AA; 26407 MW; 738D6F0BC86DB1C3 CRC64;
MSSSAASPLF APGEDCGPAW RAAPAAYDTS DTHLQILGKP VMERWETPYM HSLAAAAASR
GGRVLEVGFG MAIAASRVQQ APIKEHWIIE CNDGVFQRLQ NWALKQPHKV VPLKGLWEEE
APTLPDGHFD GILYDTYPLS EETWHTHQFN FIKTHAFRLL KPGGILTYCN LTSWGELMKS
KYTDITAMFE ETQVPALLEA GFQRENICTE VMALVPPADC RYYAFPQMIT PLVTKH
