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 24-JAN-2024, entry version 205. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 35. DR IntAct; Q14353; 12. 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 GlyGen; Q14353; 1 site, 1 O-linked glycan (1 site). 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; 9606-ENSP00000403536; -. DR PeptideAtlas; Q14353; -. DR ProteomicsDB; 59970; -. [Q14353-1] DR ProteomicsDB; 59971; -. [Q14353-2] DR Pumba; Q14353; -. DR Antibodypedia; 22677; 254 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 AGR; HGNC:4136; -. 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; HKMITPT; -. DR OrthoDB; 275675at2759; -. DR PhylomeDB; Q14353; -. DR TreeFam; TF328555; -. DR BioCyc; MetaCyc:HS05327-MONOMER; -. 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 1169 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 177 other cell types or tissues. DR ExpressionAtlas; Q14353; baseline and differential. 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: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 CDD; cd02440; AdoMet_MTases; 1. DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1. DR InterPro; IPR016550; GuanidinoAc_N-MeTrfase. DR InterPro; IPR026480; RMT2_dom. DR InterPro; IPR029063; SAM-dependent_MTases_sf. DR PANTHER; PTHR32379; GUANIDINOACETATE N-METHYLTRANSFERASE; 1. DR PANTHER; PTHR32379:SF1; GUANIDINOACETATE N-METHYLTRANSFERASE; 1. DR PIRSF; PIRSF009285; GAMT; 1. DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1. DR PROSITE; PS51559; SAM_RMT2; 1. DR Genevisible; Q14353; HS. 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 //