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Q14353 (GAMT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Guanidinoacetate N-methyltransferase

EC=2.1.1.2
Gene names
Name:GAMT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length236 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

S-adenosyl-L-methionine + guanidinoacetate = S-adenosyl-L-homocysteine + creatine.

Pathway

Amine and polyamine biosynthesis; creatine biosynthesis; creatine from L-arginine and glycine: step 2/2.

Subunit structure

Monomer By similarity.

Tissue specificity

Expressed in liver. Ref.9

Involvement in disease

Cerebral creatine deficiency syndrome 2 (CCDS2) [MIM:612736]: An autosomal recessive disorder characterized by developmental delay and regression, mental retardation, severe disturbance of expressive and cognitive speech, intractable seizures, movement disturbances, severe depletion of creatine and phosphocreatine in the brain, and accumulation of guanidinoacetic acid in brain and body fluids.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17

Sequence similarities

Belongs to the class I-like SAM-binding methyltransferase superfamily. RMT2 methyltransferase family.

Contains 1 RMT2 (arginine N-methyltransferase 2-like) domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q14353-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q14353-2)

The sequence of this isoform differs from the canonical sequence as follows:
     191-236: ETQVPALLEA...QMITPLVTKG → VRPPEVPHGS...TVEGRGGQIA
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.11
Chain2 – 236235Guanidinoacetate N-methyltransferase
PRO_0000087430

Regions

Domain13 – 236224RMT2
Region69 – 746S-adenosyl-L-methionine binding
Region90 – 923S-adenosyl-L-methionine
Region117 – 1182S-adenosyl-L-methionine binding
Region171 – 1722Substrate binding

Sites

Binding site201S-adenosyl-L-methionine
Binding site421Substrate By similarity
Binding site461Substrate By similarity
Binding site501S-adenosyl-L-methionine
Binding site1351S-adenosyl-L-methionine and substrate By similarity

Amino acid modifications

Modified residue21N-acetylserine Ref.11

Natural variations

Alternative sequence191 – 23646ETQVP…LVTKG → VRPPEVPHGSPGSDLGWGWE GAAGATLLPGEGPFLTPWVG WTVLVHLEIKVLCLAQWLPG AVAQVYNPSTVEGRGGQIA in isoform 2.
VSP_042722
Natural variant201W → S in CCDS2. Ref.14 Ref.15
VAR_058102
Natural variant501M → L in CCDS2. Ref.17
VAR_058103
Natural variant511H → P in CCDS2. Ref.14
VAR_058104
Natural variant541A → P in CCDS2. Ref.14
VAR_058105
Natural variant1691C → Y in CCDS2. Ref.15
VAR_058106
Natural variant1971L → P in CCDS2; unknown pathological significance. Ref.13 Ref.16
VAR_058107
Natural variant2091T → M. Ref.8
Corresponds to variant rs17851582 [ dbSNP | Ensembl ].
VAR_025723

Secondary structure

............................................... 236
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 6B8E845CE56189F5

FASTA23626,318
        10         20         30         40         50         60 
MSAPSATPIF APGENCSPAW GAAPAAYDAA DTHLRILGKP VMERWETPYM HALAAAASSK 

        70         80         90        100        110        120 
GGRVLEVGFG MAIAASKVQE APIDEHWIIE CNDGVFQRLR DWAPRQTHKV IPLKGLWEDV 

       130        140        150        160        170        180 
APTLPDGHFD GILYDTYPLS EETWHTHQFN FIKNHAFRLL KPGGVLTYCN LTSWGELMKS 

       190        200        210        220        230 
KYSDITIMFE ETQVPALLEA GFRRENIRTE VMALVPPADC RYYAFPQMIT PLVTKG 

« Hide

Isoform 2 [UniParc].

Checksum: D04624287AE534A8
Show »

FASTA26929,377

References

« Hide 'large scale' references
[1]"Cloning and sequence analysis of human guanidinoacetate N-methyltransferase cDNA."
Isbrandt D., von Figura K.
Biochim. Biophys. Acta 1264:265-267(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[2]"The human guanidinoacetate methyltransferase (GAMT) gene maps to a syntenic region on 19p13.3, homologous to band C of mouse chromosome 10, but GAMT is not mutated in jittery mice."
Jenne D.E., Olsen A.S., Zimmer M.
Biochem. Biophys. Res. Commun. 238:723-727(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Gene structure of human guanidinoacetate N-methyltransferase."
Isbrandt D., Schmidt A.
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Cerebellum.
[6]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT MET-209.
Tissue: Lymph and Skeletal muscle.
[9]"Guanidinoacetate methyltransferase deficiency: the first inborn error of creatine metabolism in man."
Stoeckler S., Isbrandt D., Hanefeld F., Schmidt B., von Figura K.
Am. J. Hum. Genet. 58:914-922(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INVOLVEMENT IN CCDS2.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[12]"The crystal structure of human guanidinoacetate N-methyltransferase with SAH."
Structural genomics consortium (SGC)
Submitted (MAR-2006) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) IN COMPLEX WITH S-ADENOSYL-L-HOMOCYSTEINE.
[13]"Creatine depletion in a new case with AGAT deficiency: clinical and genetic study in a large pedigree."
Battini R., Leuzzi V., Carducci C., Tosetti M., Bianchi M.C., Item C.B., Stoeckler-Ipsiroglu S., Cioni G.
Mol. Genet. Metab. 77:326-331(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CCDS2 PRO-197.
[14]"Characterization of seven novel mutations in seven patients with GAMT deficiency."
Item C.B., Mercimek-Mahmutoglu S., Battini R., Edlinger-Horvat C., Stromberger C., Bodamer O., Muehl A., Vilaseca M.A., Korall H., Stoeckler-Ipsiroglu S.
Hum. Mutat. 23:524-524(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CCDS2 SER-20; PRO-51 AND PRO-54.
[15]"Guanidinoacetate methyltransferase deficiency identified in adults and a child with mental retardation."
Caldeira Araujo H., Smit W., Verhoeven N.M., Salomons G.S., Silva S., Vasconcelos R., Tomas H., Tavares de Almeida I., Jakobs C., Duran M.
Am. J. Med. Genet. A 133:122-127(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CCDS2 SER-20 AND TYR-169.
[16]"A mutation on exon 6 of guanidinoacetate methyltransferase (GAMT) gene supports a different function for isoform a and b of GAMT enzyme."
Leuzzi V., Carducci C., Carducci C., Matricardi M., Bianchi M.C., Di Sabato M.L., Artiola C., Antonozzi I.
Mol. Genet. Metab. 87:88-90(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CCDS2 PRO-197.
[17]"High frequency of creatine deficiency syndromes in patients with unexplained mental retardation."
Lion-Francois L., Cheillan D., Pitelet G., Acquaviva-Bourdain C., Bussy G., Cotton F., Guibaud L., Gerard D., Rivier C., Vianey-Saban C., Jakobs C., Salomons G.S., des Portes V.
Neurology 67:1713-1714(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CCDS2 LEU-50.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z49878 mRNA. Translation: CAA90035.1.
AF010248, AF010246, AF010247 Genomic DNA. Translation: AAD04781.1.
AF188893 Genomic DNA. Translation: AAF01461.1.
BT007034 mRNA. Translation: AAP35682.1.
AK289465 mRNA. Translation: BAF82154.1.
AC005329 Genomic DNA. Translation: AAC27668.1.
CH471139 Genomic DNA. Translation: EAW69505.1.
BC016760 mRNA. Translation: AAH16760.1.
BC017936 mRNA. Translation: AAH17936.1.
CCDSCCDS12064.1. [Q14353-1]
CCDS45897.1. [Q14353-2]
PIRS62732.
RefSeqNP_000147.1. NM_000156.5. [Q14353-1]
NP_620279.1. NM_138924.2. [Q14353-2]
UniGeneHs.81131.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3ORHX-ray1.86A/B/C/D1-236[»]
ProteinModelPortalQ14353.
SMRQ14353. Positions 7-236.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108865. 6 interactions.
IntActQ14353. 2 interactions.
STRING9606.ENSP00000403536.

Chemistry

DrugBankDB00148. Creatine.

PTM databases

PhosphoSiteQ14353.

Polymorphism databases

DMDM2498404.

2D gel databases

OGPQ14353.

Proteomic databases

MaxQBQ14353.
PaxDbQ14353.
PeptideAtlasQ14353.
PRIDEQ14353.

Protocols and materials databases

DNASU2593.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000252288; ENSP00000252288; ENSG00000130005. [Q14353-1]
ENST00000447102; ENSP00000403536; ENSG00000130005. [Q14353-2]
GeneID2593.
KEGGhsa:2593.
UCSCuc002lsj.4. human. [Q14353-1]
uc002lsk.4. human. [Q14353-2]

Organism-specific databases

CTD2593.
GeneCardsGC19M001397.
GeneReviewsGAMT.
H-InvDBHIX0030201.
HGNCHGNC:4136. GAMT.
HPAHPA051806.
MIM601240. gene.
612736. phenotype.
neXtProtNX_Q14353.
Orphanet382. Guanidinoacetate methyltransferase deficiency.
PharmGKBPA28549.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG235457.
HOGENOMHOG000010290.
HOVERGENHBG005801.
InParanoidQ14353.
KOK00542.
OMARYYAFPQ.
OrthoDBEOG75QR4S.
PhylomeDBQ14353.
TreeFamTF328555.

Enzyme and pathway databases

BioCycMetaCyc:HS05327-MONOMER.
BRENDA2.1.1.2. 2681.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00104; UER00580.

Gene expression databases

BgeeQ14353.
CleanExHS_GAMT.
GenevestigatorQ14353.

Family and domain databases

Gene3D3.40.50.150. 1 hit.
InterProIPR016550. GuanidinoAc_N-MeTrfase.
IPR026480. RMT2_dom.
IPR029063. SAM-dependent_MTases-like.
[Graphical view]
PIRSFPIRSF009285. GAMT. 1 hit.
SUPFAMSSF53335. SSF53335. 1 hit.
PROSITEPS51559. SAM_RMT2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ14353.
GeneWikiGuanidinoacetate_N-methyltransferase.
GenomeRNAi2593.
NextBio10257.
PROQ14353.
SOURCESearch...

Entry information

Entry nameGAMT_HUMAN
AccessionPrimary (citable) accession number: Q14353
Secondary accession number(s): A8K0A0, Q53Y34, Q8WVJ1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM