GAMT_HUMAN
ID GAMT_HUMAN Reviewed; 236 AA.
AC Q14353; A8K0A0; Q53Y34; Q8WVJ1;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Guanidinoacetate N-methyltransferase;
DE EC=2.1.1.2;
GN Name=GAMT;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=8547310; DOI=10.1016/0167-4781(95)00184-0;
RA Isbrandt D., von Figura K.;
RT "Cloning and sequence analysis of human guanidinoacetate N-
RT methyltransferase cDNA.";
RL Biochim. Biophys. Acta 1264:265-267(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9325156; DOI=10.1006/bbrc.1997.9992;
RA Jenne D.E., Olsen A.S., Zimmer M.;
RT "The human guanidinoacetate methyltransferase (GAMT) gene maps to a
RT syntenic region on 19p13.3, homologous to band C of mouse chromosome 10,
RT but GAMT is not mutated in jittery mice.";
RL Biochem. Biophys. Res. Commun. 238:723-727(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Isbrandt D., Schmidt A.;
RT "Gene structure of human guanidinoacetate N-methyltransferase.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT MET-209.
RC TISSUE=Lymph, and Skeletal muscle;
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 [9]
RP TISSUE SPECIFICITY, AND INVOLVEMENT IN CCDS2.
RX PubMed=8651275;
RA Stoeckler S., Isbrandt D., Hanefeld F., Schmidt B., von Figura K.;
RT "Guanidinoacetate methyltransferase deficiency: the first inborn error of
RT creatine metabolism in man.";
RL Am. J. Hum. Genet. 58:914-922(1996).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE.
RG Structural genomics consortium (SGC);
RT "The crystal structure of human guanidinoacetate N-methyltransferase with
RT SAH.";
RL Submitted (MAR-2006) to the PDB data bank.
RN [13]
RP VARIANT CCDS2 PRO-197.
RX PubMed=12468279; DOI=10.1016/s1096-7192(02)00175-0;
RA Battini R., Leuzzi V., Carducci C., Tosetti M., Bianchi M.C., Item C.B.,
RA Stoeckler-Ipsiroglu S., Cioni G.;
RT "Creatine depletion in a new case with AGAT deficiency: clinical and
RT genetic study in a large pedigree.";
RL Mol. Genet. Metab. 77:326-331(2002).
RN [14]
RP VARIANTS CCDS2 SER-20; PRO-51 AND PRO-54.
RX PubMed=15108290; DOI=10.1002/humu.9238;
RA Item C.B., Mercimek-Mahmutoglu S., Battini R., Edlinger-Horvat C.,
RA Stromberger C., Bodamer O., Muehl A., Vilaseca M.A., Korall H.,
RA Stoeckler-Ipsiroglu S.;
RT "Characterization of seven novel mutations in seven patients with GAMT
RT deficiency.";
RL Hum. Mutat. 23:524-524(2004).
RN [15]
RP VARIANTS CCDS2 SER-20 AND TYR-169.
RX PubMed=15651030; DOI=10.1002/ajmg.a.30226;
RA Caldeira Araujo H., Smit W., Verhoeven N.M., Salomons G.S., Silva S.,
RA Vasconcelos R., Tomas H., Tavares de Almeida I., Jakobs C., Duran M.;
RT "Guanidinoacetate methyltransferase deficiency identified in adults and a
RT child with mental retardation.";
RL Am. J. Med. Genet. A 133:122-127(2005).
RN [16]
RP VARIANT CCDS2 PRO-197.
RX PubMed=16293431; DOI=10.1016/j.ymgme.2005.09.017;
RA Leuzzi V., Carducci C., Carducci C., Matricardi M., Bianchi M.C.,
RA Di Sabato M.L., Artiola C., Antonozzi I.;
RT "A mutation on exon 6 of guanidinoacetate methyltransferase (GAMT) gene
RT supports a different function for isoform a and b of GAMT enzyme.";
RL Mol. Genet. Metab. 87:88-90(2006).
RN [17]
RP VARIANT CCDS2 PRO-51.
RX PubMed=16855203; DOI=10.1212/01.wnl.0000234852.43688.bf;
RA Mercimek-Mahmutoglu S., Stoeckler-Ipsiroglu S., Adami A., Appleton R.,
RA Araujo H.C., Duran M., Ensenauer R., Fernandez-Alvarez E., Garcia P.,
RA Grolik C., Item C.B., Leuzzi V., Marquardt I., Muehl A.,
RA Saelke-Kellermann R.A., Salomons G.S., Schulze A., Surtees R.,
RA van der Knaap M.S., Vasconcelos R., Verhoeven N.M., Vilarinho L.,
RA Wilichowski E., Jakobs C.;
RT "GAMT deficiency: features, treatment, and outcome in an inborn error of
RT creatine synthesis.";
RL Neurology 67:480-484(2006).
RN [18]
RP VARIANT CCDS2 LEU-50.
RX PubMed=17101918; DOI=10.1212/01.wnl.0000239153.39710.81;
RA Lion-Francois L., Cheillan D., Pitelet G., Acquaviva-Bourdain C., Bussy G.,
RA Cotton F., Guibaud L., Gerard D., Rivier C., Vianey-Saban C., Jakobs C.,
RA Salomons G.S., des Portes V.;
RT "High frequency of creatine deficiency syndromes in patients with
RT unexplained mental retardation.";
RL Neurology 67:1713-1714(2006).
RN [19]
RP VARIANT CCDS2 PRO-166.
RX PubMed=17466557; DOI=10.1016/j.ymgme.2007.03.006;
RA Verbruggen K.T., Sijens P.E., Schulze A., Lunsing R.J., Jakobs C.,
RA Salomons G.S., van Spronsen F.J.;
RT "Successful treatment of a guanidinoacetate methyltransferase deficient
RT patient: findings with relevance to treatment strategy and
RT pathophysiology.";
RL Mol. Genet. Metab. 91:294-296(2007).
RN [20]
RP VARIANT CCDS2 ASN-135.
RX PubMed=19388150; DOI=10.1111/j.1469-8749.2008.03227.x;
RA O'Rourke D.J., Ryan S., Salomons G., Jakobs C., Monavari A., King M.D.;
RT "Guanidinoacetate methyltransferase (GAMT) deficiency: late onset of
RT movement disorder and preserved expressive language.";
RL Dev. Med. Child. Neurol. 51:404-407(2009).
RN [21]
RP VARIANTS CCDS2 ARG-45; GLU-78; ASP-164 AND ARG-169.
RX PubMed=23660394; DOI=10.1016/j.ymgme.2013.04.006;
RA Comeaux M.S., Wang J., Wang G., Kleppe S., Zhang V.W., Schmitt E.S.,
RA Craigen W.J., Renaud D., Sun Q., Wong L.J.;
RT "Biochemical, molecular, and clinical diagnoses of patients with cerebral
RT creatine deficiency syndromes.";
RL Mol. Genet. Metab. 109:260-268(2013).
RN [22]
RP VARIANTS CCDS2 CYS-68; VAL-75; PHE-110; TYR-147; PRO-159 AND PRO-208,
RP VARIANTS THR-8 AND HIS-27, CHARACTERIZATION OF VARIANTS CCDS2 ARG-45;
RP LEU-50; PRO-51; PRO-54; CYS-68; VAL-75; PHE-110; TYR-147; PRO-159; PRO-166;
RP TYR-169; PRO-197 AND PRO-208, CHARACTERIZATION OF VARIANTS THR-8 AND
RP HIS-27, AND FUNCTION.
RX PubMed=24415674; DOI=10.1002/humu.22511;
RA Mercimek-Mahmutoglu S., Ndika J., Kanhai W., de Villemeur T.B.,
RA Cheillan D., Christensen E., Dorison N., Hannig V., Hendriks Y.,
RA Hofstede F.C., Lion-Francois L., Lund A.M., Mundy H., Pitelet G.,
RA Raspall-Chaure M., Scott-Schwoerer J.A., Szakszon K., Valayannopoulos V.,
RA Williams M., Salomons G.S.;
RT "Thirteen new patients with guanidinoacetate methyltransferase deficiency
RT and functional characterization of nineteen novel missense variants in the
RT GAMT gene.";
RL Hum. Mutat. 35:462-469(2014).
RN [23]
RP VARIANTS VAL-71; MET-78; ILE-95; GLN-105; PRO-106; ARG-146; ASP-156;
RP LEU-157 AND ILE-167, CHARACTERIZATION OF VARIANTS VAL-71; MET-78; ILE-95;
RP GLN-105; PRO-106; ARG-146; ASP-156; LEU-157 AND ILE-167, AND FUNCTION.
RX PubMed=26003046; DOI=10.1007/s00438-015-1067-x;
RA Desroches C.L., Patel J., Wang P., Minassian B., Marshall C.R.,
RA Salomons G.S., Mercimek-Mahmutoglu S.;
RT "Carrier frequency of guanidinoacetate methyltransferase deficiency in the
RT general population by functional characterization of missense variants in
RT the GAMT gene.";
RL Mol. Genet. Genomics 290:2163-2171(2015).
RN [24]
RP VARIANTS LEU-44; LEU-76; THR-196; VAL-196 AND THR-224, CHARACTERIZATION OF
RP VARIANTS LEU-44; LEU-76; THR-196; VAL-196 AND THR-224, AND FUNCTION.
RX PubMed=26319512; DOI=10.1016/j.gene.2015.08.045;
RA Mercimek-Mahmutoglu S., Pop A., Kanhai W., Fernandez Ojeda M., Holwerda U.,
RA Smith D., Loeber J.G., Schielen P.C., Salomons G.S.;
RT "A pilot study to estimate incidence of guanidinoacetate methyltransferase
RT deficiency in newborns by direct sequencing of the GAMT gene.";
RL Gene 575:127-131(2016).
CC -!- FUNCTION: Converts guanidinoacetate to creatine, using S-
CC adenosylmethionine as the methyl donor (PubMed:26003046,
CC PubMed:24415674, PubMed:26319512). Important in nervous system
CC development (PubMed:24415674). {ECO:0000269|PubMed:24415674,
CC ECO:0000269|PubMed:26003046, ECO:0000269|PubMed:26319512}.
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. {ECO:0000250}.
CC -!- INTERACTION:
CC Q14353; Q969Q5: RAB24; NbExp=3; IntAct=EBI-3909086, EBI-3060998;
CC Q14353; Q9HCM9-2: TRIM39; NbExp=5; IntAct=EBI-3909086, EBI-11523450;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q14353-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14353-2; Sequence=VSP_042722;
CC -!- TISSUE SPECIFICITY: Expressed in liver. {ECO:0000269|PubMed:8651275}.
CC -!- DISEASE: Cerebral creatine deficiency syndrome 2 (CCDS2) [MIM:612736]:
CC An autosomal recessive disorder characterized by developmental delay
CC and regression, intellectual disability, severe disturbance of
CC expressive and cognitive speech, intractable seizures, movement
CC disturbances, severe depletion of creatine and phosphocreatine in the
CC brain, and accumulation of guanidinoacetic acid in brain and body
CC fluids. {ECO:0000269|PubMed:12468279, ECO:0000269|PubMed:15108290,
CC ECO:0000269|PubMed:15651030, ECO:0000269|PubMed:16293431,
CC ECO:0000269|PubMed:16855203, ECO:0000269|PubMed:17101918,
CC ECO:0000269|PubMed:17466557, ECO:0000269|PubMed:19388150,
CC ECO:0000269|PubMed:23660394, ECO:0000269|PubMed:24415674,
CC ECO:0000269|PubMed:8651275}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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; Z49878; CAA90035.1; -; mRNA.
DR EMBL; AF010248; AAD04781.1; -; Genomic_DNA.
DR EMBL; AF010246; AAD04781.1; JOINED; Genomic_DNA.
DR EMBL; AF010247; AAD04781.1; JOINED; Genomic_DNA.
DR EMBL; AF188893; AAF01461.1; -; Genomic_DNA.
DR EMBL; BT007034; AAP35682.1; -; mRNA.
DR EMBL; AK289465; BAF82154.1; -; mRNA.
DR EMBL; AC005329; AAC27668.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW69505.1; -; Genomic_DNA.
DR EMBL; BC016760; AAH16760.1; -; mRNA.
DR EMBL; BC017936; AAH17936.1; -; mRNA.
DR CCDS; CCDS12064.1; -. [Q14353-1]
DR CCDS; CCDS45897.1; -. [Q14353-2]
DR PIR; S62732; S62732.
DR RefSeq; NP_000147.1; NM_000156.5. [Q14353-1]
DR RefSeq; NP_620279.1; NM_138924.2. [Q14353-2]
DR PDB; 3ORH; X-ray; 1.86 A; A/B/C/D=1-236.
DR PDBsum; 3ORH; -.
DR AlphaFoldDB; Q14353; -.
DR SMR; Q14353; -.
DR BioGRID; 108865; 30.
DR IntAct; Q14353; 10.
DR STRING; 9606.ENSP00000403536; -.
DR ChEMBL; CHEMBL4523290; -.
DR DrugBank; DB00148; Creatine.
DR DrugBank; DB02751; Glycocyamine.
DR DrugBank; DB00536; Guanidine.
DR DrugBank; DB13191; Phosphocreatine.
DR DrugBank; DB01752; S-adenosyl-L-homocysteine.
DR iPTMnet; Q14353; -.
DR PhosphoSitePlus; Q14353; -.
DR BioMuta; GAMT; -.
DR DMDM; 2498404; -.
DR OGP; Q14353; -.
DR EPD; Q14353; -.
DR jPOST; Q14353; -.
DR MassIVE; Q14353; -.
DR MaxQB; Q14353; -.
DR PaxDb; Q14353; -.
DR PeptideAtlas; Q14353; -.
DR PRIDE; Q14353; -.
DR ProteomicsDB; 59970; -. [Q14353-1]
DR ProteomicsDB; 59971; -. [Q14353-2]
DR Antibodypedia; 22677; 235 antibodies from 29 providers.
DR DNASU; 2593; -.
DR Ensembl; ENST00000252288.8; ENSP00000252288.1; ENSG00000130005.13. [Q14353-1]
DR Ensembl; ENST00000447102.8; ENSP00000403536.2; ENSG00000130005.13. [Q14353-2]
DR GeneID; 2593; -.
DR KEGG; hsa:2593; -.
DR MANE-Select; ENST00000252288.8; ENSP00000252288.1; NM_000156.6; NP_000147.1.
DR UCSC; uc002lsk.5; human. [Q14353-1]
DR CTD; 2593; -.
DR DisGeNET; 2593; -.
DR GeneCards; GAMT; -.
DR GeneReviews; GAMT; -.
DR HGNC; HGNC:4136; GAMT.
DR HPA; ENSG00000130005; Tissue enhanced (liver, skeletal muscle, tongue).
DR MalaCards; GAMT; -.
DR MIM; 601240; gene.
DR MIM; 612736; phenotype.
DR neXtProt; NX_Q14353; -.
DR OpenTargets; ENSG00000130005; -.
DR Orphanet; 382; Guanidinoacetate methyltransferase deficiency.
DR PharmGKB; PA28549; -.
DR VEuPathDB; HostDB:ENSG00000130005; -.
DR eggNOG; KOG1709; Eukaryota.
DR GeneTree; ENSGT00390000018061; -.
DR HOGENOM; CLU_102800_0_0_1; -.
DR InParanoid; Q14353; -.
DR OMA; FRRENIH; -.
DR OrthoDB; 1297303at2759; -.
DR PhylomeDB; Q14353; -.
DR TreeFam; TF328555; -.
DR BioCyc; MetaCyc:HS05327-MON; -.
DR BRENDA; 2.1.1.2; 2681.
DR PathwayCommons; Q14353; -.
DR Reactome; R-HSA-71288; Creatine metabolism.
DR Reactome; R-HSA-8986944; Transcriptional Regulation by MECP2.
DR SignaLink; Q14353; -.
DR SIGNOR; Q14353; -.
DR UniPathway; UPA00104; UER00580.
DR BioGRID-ORCS; 2593; 14 hits in 1083 CRISPR screens.
DR ChiTaRS; GAMT; human.
DR EvolutionaryTrace; Q14353; -.
DR GeneWiki; Guanidinoacetate_N-methyltransferase; -.
DR GenomeRNAi; 2593; -.
DR Pharos; Q14353; Tbio.
DR PRO; PR:Q14353; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q14353; protein.
DR Bgee; ENSG00000130005; Expressed in hindlimb stylopod muscle and 175 other tissues.
DR ExpressionAtlas; Q14353; baseline and differential.
DR Genevisible; Q14353; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0030731; F:guanidinoacetate N-methyltransferase activity; IMP:UniProtKB.
DR GO; GO:0008168; F:methyltransferase activity; TAS:Reactome.
DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; IBA:GO_Central.
DR GO; GO:0009887; P:animal organ morphogenesis; IEA:Ensembl.
DR GO; GO:0006601; P:creatine biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006600; P:creatine metabolic process; TAS:Reactome.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0006936; P:muscle contraction; TAS:ProtInc.
DR GO; GO:0040014; P:regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
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; Alternative splicing; Disease variant;
KW Methyltransferase; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895"
FT CHAIN 2..236
FT /note="Guanidinoacetate N-methyltransferase"
FT /id="PRO_0000087430"
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:0000250|UniProtKB:P10868,
FT ECO:0000255|PROSITE-ProRule:PRU00892"
FT BINDING 46
FT /ligand="guanidinoacetate"
FT /ligand_id="ChEBI:CHEBI:57742"
FT /evidence="ECO:0000250|UniProtKB:P10868,
FT ECO:0000255|PROSITE-ProRule:PRU00892"
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:0000250|UniProtKB:P10868"
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:0000250|UniProtKB:P10868"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22223895"
FT VAR_SEQ 191..236
FT /note="ETQVPALLEAGFRRENIRTEVMALVPPADCRYYAFPQMITPLVTKG -> VR
FT PPEVPHGSPGSDLGWGWEGAAGATLLPGEGPFLTPWVGWTVLVHLEIKVLCLAQWLPGA
FT VAQVYNPSTVEGRGGQIA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042722"
FT VARIANT 8
FT /note="P -> T (no effect on activity; dbSNP:rs776498025)"
FT /evidence="ECO:0000269|PubMed:24415674"
FT /id="VAR_071775"
FT VARIANT 20
FT /note="W -> S (in CCDS2; dbSNP:rs80338734)"
FT /evidence="ECO:0000269|PubMed:15108290,
FT ECO:0000269|PubMed:15651030"
FT /id="VAR_058102"
FT VARIANT 27
FT /note="Y -> H (no effect on activity; dbSNP:rs200833152)"
FT /evidence="ECO:0000269|PubMed:24415674"
FT /id="VAR_071776"
FT VARIANT 44
FT /note="R -> L (no effect on enzymatic activity;
FT dbSNP:rs200339910)"
FT /evidence="ECO:0000269|PubMed:26319512"
FT /id="VAR_075290"
FT VARIANT 45
FT /note="W -> R (in CCDS2; loss of activity;
FT dbSNP:rs886054247 and dbSNP:rs967404590)"
FT /evidence="ECO:0000269|PubMed:23660394,
FT ECO:0000269|PubMed:24415674"
FT /id="VAR_071777"
FT VARIANT 50
FT /note="M -> L (in CCDS2; retains no significant activity;
FT dbSNP:rs104894694)"
FT /evidence="ECO:0000269|PubMed:17101918,
FT ECO:0000269|PubMed:24415674"
FT /id="VAR_058103"
FT VARIANT 51
FT /note="H -> P (in CCDS2; retains no significant activity)"
FT /evidence="ECO:0000269|PubMed:15108290,
FT ECO:0000269|PubMed:16855203, ECO:0000269|PubMed:24415674"
FT /id="VAR_058104"
FT VARIANT 54
FT /note="A -> P (in CCDS2; loss of activity;
FT dbSNP:rs1220169908)"
FT /evidence="ECO:0000269|PubMed:15108290,
FT ECO:0000269|PubMed:24415674"
FT /id="VAR_058105"
FT VARIANT 68
FT /note="G -> C (in CCDS2; retains no significant activity;
FT dbSNP:rs1447665588)"
FT /evidence="ECO:0000269|PubMed:24415674"
FT /id="VAR_071778"
FT VARIANT 71
FT /note="M -> V (no effect on enzymatic activity;
FT dbSNP:rs372027428)"
FT /evidence="ECO:0000269|PubMed:26003046"
FT /id="VAR_075291"
FT VARIANT 75
FT /note="A -> V (in CCDS2; retains no significant activity;
FT dbSNP:rs1441030187)"
FT /evidence="ECO:0000269|PubMed:24415674"
FT /id="VAR_071779"
FT VARIANT 76
FT /note="S -> L (no effect on enzymatic activity;
FT dbSNP:rs150338273)"
FT /evidence="ECO:0000269|PubMed:26319512"
FT /id="VAR_075292"
FT VARIANT 78
FT /note="V -> E (in CCDS2)"
FT /evidence="ECO:0000269|PubMed:23660394"
FT /id="VAR_071780"
FT VARIANT 78
FT /note="V -> M (no effect on enzymatic activity;
FT dbSNP:rs141358977)"
FT /evidence="ECO:0000269|PubMed:26003046"
FT /id="VAR_075293"
FT VARIANT 95
FT /note="V -> I (no effect on enzymatic activity;
FT dbSNP:rs140778208)"
FT /evidence="ECO:0000269|PubMed:26003046"
FT /id="VAR_075294"
FT VARIANT 105
FT /note="R -> Q (no effect on enzymatic activity;
FT dbSNP:rs148838075)"
FT /evidence="ECO:0000269|PubMed:26003046"
FT /id="VAR_075295"
FT VARIANT 106
FT /note="Q -> P (disrupts enzymatic activity;
FT dbSNP:rs145817990)"
FT /evidence="ECO:0000269|PubMed:26003046"
FT /id="VAR_075296"
FT VARIANT 110
FT /note="V -> F (in CCDS2; retains no significant activity;
FT dbSNP:rs753198836)"
FT /evidence="ECO:0000269|PubMed:24415674"
FT /id="VAR_071781"
FT VARIANT 135
FT /note="D -> N (in CCDS2; dbSNP:rs774144200)"
FT /evidence="ECO:0000269|PubMed:19388150"
FT /id="VAR_071782"
FT VARIANT 146
FT /note="T -> R (no effect on enzymatic activity;
FT dbSNP:rs149821870)"
FT /evidence="ECO:0000269|PubMed:26003046"
FT /id="VAR_075297"
FT VARIANT 147
FT /note="H -> Y (in CCDS2; retains no significant activity;
FT dbSNP:rs1371496558)"
FT /evidence="ECO:0000269|PubMed:24415674"
FT /id="VAR_071783"
FT VARIANT 156
FT /note="A -> D (disrupts enzymatic activity;
FT dbSNP:rs368221789)"
FT /evidence="ECO:0000269|PubMed:26003046"
FT /id="VAR_075298"
FT VARIANT 157
FT /note="F -> L (no effect on enzymatic activity;
FT dbSNP:rs372260609)"
FT /evidence="ECO:0000269|PubMed:26003046"
FT /id="VAR_075299"
FT VARIANT 159
FT /note="L -> P (in CCDS2; loss of activity)"
FT /evidence="ECO:0000269|PubMed:24415674"
FT /id="VAR_071784"
FT VARIANT 164
FT /note="G -> D (in CCDS2; dbSNP:rs760101382)"
FT /evidence="ECO:0000269|PubMed:23660394"
FT /id="VAR_071785"
FT VARIANT 166
FT /note="L -> P (in CCDS2; loss of activity;
FT dbSNP:rs1483148182)"
FT /evidence="ECO:0000269|PubMed:17466557,
FT ECO:0000269|PubMed:24415674"
FT /id="VAR_071786"
FT VARIANT 167
FT /note="T -> I (disrupts enzymatic activity;
FT dbSNP:rs374762419)"
FT /evidence="ECO:0000269|PubMed:26003046"
FT /id="VAR_075300"
FT VARIANT 169
FT /note="C -> R (in CCDS2; dbSNP:rs1600158346)"
FT /evidence="ECO:0000269|PubMed:23660394"
FT /id="VAR_071787"
FT VARIANT 169
FT /note="C -> Y (in CCDS2; retains no significant activity;
FT dbSNP:rs121909272)"
FT /evidence="ECO:0000269|PubMed:15651030,
FT ECO:0000269|PubMed:24415674"
FT /id="VAR_058106"
FT VARIANT 196
FT /note="A -> T (no effect on enzymatic activity;
FT dbSNP:rs1355291180)"
FT /evidence="ECO:0000269|PubMed:26319512"
FT /id="VAR_075301"
FT VARIANT 196
FT /note="A -> V (no effect on enzymatic activity;
FT dbSNP:rs565109128)"
FT /evidence="ECO:0000269|PubMed:26319512"
FT /id="VAR_075302"
FT VARIANT 197
FT /note="L -> P (in CCDS2; loss of activity)"
FT /evidence="ECO:0000269|PubMed:12468279,
FT ECO:0000269|PubMed:16293431, ECO:0000269|PubMed:24415674"
FT /id="VAR_058107"
FT VARIANT 208
FT /note="R -> P (in CCDS2; retains no significant activity;
FT dbSNP:rs767887772)"
FT /evidence="ECO:0000269|PubMed:24415674"
FT /id="VAR_071788"
FT VARIANT 209
FT /note="T -> M (in dbSNP:rs17851582)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_025723"
FT VARIANT 224
FT /note="A -> T (no effect on enzymatic activity;
FT dbSNP:rs141471799)"
FT /evidence="ECO:0000269|PubMed:26319512"
FT /id="VAR_075303"
FT HELIX 17..20
FT /evidence="ECO:0007829|PDB:3ORH"
FT STRAND 25..27
FT /evidence="ECO:0007829|PDB:3ORH"
FT STRAND 31..36
FT /evidence="ECO:0007829|PDB:3ORH"
FT STRAND 39..43
FT /evidence="ECO:0007829|PDB:3ORH"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:3ORH"
FT HELIX 47..57
FT /evidence="ECO:0007829|PDB:3ORH"
FT TURN 58..60
FT /evidence="ECO:0007829|PDB:3ORH"
FT STRAND 62..67
FT /evidence="ECO:0007829|PDB:3ORH"
FT HELIX 73..78
FT /evidence="ECO:0007829|PDB:3ORH"
FT STRAND 83..90
FT /evidence="ECO:0007829|PDB:3ORH"
FT HELIX 93..102
FT /evidence="ECO:0007829|PDB:3ORH"
FT HELIX 103..105
FT /evidence="ECO:0007829|PDB:3ORH"
FT STRAND 107..115
FT /evidence="ECO:0007829|PDB:3ORH"
FT HELIX 117..120
FT /evidence="ECO:0007829|PDB:3ORH"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:3ORH"
FT STRAND 129..134
FT /evidence="ECO:0007829|PDB:3ORH"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:3ORH"
FT TURN 144..146
FT /evidence="ECO:0007829|PDB:3ORH"
FT HELIX 147..154
FT /evidence="ECO:0007829|PDB:3ORH"
FT HELIX 156..159
FT /evidence="ECO:0007829|PDB:3ORH"
FT STRAND 160..168
FT /evidence="ECO:0007829|PDB:3ORH"
FT HELIX 171..177
FT /evidence="ECO:0007829|PDB:3ORH"
FT TURN 178..181
FT /evidence="ECO:0007829|PDB:3ORH"
FT HELIX 185..192
FT /evidence="ECO:0007829|PDB:3ORH"
FT HELIX 194..200
FT /evidence="ECO:0007829|PDB:3ORH"
FT HELIX 204..206
FT /evidence="ECO:0007829|PDB:3ORH"
FT STRAND 207..213
FT /evidence="ECO:0007829|PDB:3ORH"
FT STRAND 226..234
FT /evidence="ECO:0007829|PDB:3ORH"
SQ SEQUENCE 236 AA; 26318 MW; 6B8E845CE56189F5 CRC64;
MSAPSATPIF APGENCSPAW GAAPAAYDAA DTHLRILGKP VMERWETPYM HALAAAASSK
GGRVLEVGFG MAIAASKVQE APIDEHWIIE CNDGVFQRLR DWAPRQTHKV IPLKGLWEDV
APTLPDGHFD GILYDTYPLS EETWHTHQFN FIKNHAFRLL KPGGVLTYCN LTSWGELMKS
KYSDITIMFE ETQVPALLEA GFRRENIRTE VMALVPPADC RYYAFPQMIT PLVTKG
