Reviewed, UniProtKB/Swiss-Prot P50440 (GATM_HUMAN)

Names and origin

Protein names

Recommended name:
    Glycine amidinotransferase, mitochondrial
    EC=2.1.4.1
Alternative name(s):
    L-arginine:glycine amidinotransferase
    Transamidinase

Gene names

Name:	GATM
Synonyms:	AGAT

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	423 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	L-arginine + glycine = L-ornithine + guanidinoacetate.
Pathway	Amine and polyamine biosynthesis; creatine biosynthesis; creatine from L-arginine and glycine: step 1/2.
Subunit structure	Homodimer. There is an equilibrium between the monomeric and dimeric forms, shifted towards the side of the monomer.
Subcellular location	Mitochondrion inner membrane; Peripheral membrane protein; Intermembrane side Potential. Cytoplasm. Note: The mitochondrial form is found in the intermembrane space probably attached to the outer side of the inner membrane.
Tissue specificity	Kidney.
Domain	One chain folds into a compact single domain composed of repeating units, five beta-beta-alpha-beta modules, which surround the central active site.
Involvement in disease	Defects in GATM are the cause of arginine:glycine amidinotransferase deficiency (AGAT deficiency) [MIM:612718]. AGAT deficiency is an autosomal recessive disorder characterized by developmental delay/regression, mental retardation, severe disturbance of expressive and cognitive speech, and severe depletion of creatine/phosphocreatine in the brain.
Sequence similarities	Belongs to the amidinotransferase family.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transit peptide
Molecular function	Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	creatine biosynthetic process Ref.8 Inferred from direct assay. Source: MGI
Cellular component	extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrial inner membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial intermembrane space Ref.8 Inferred from direct assay. Source: MGI
Molecular function	glycine amidinotransferase activity Ref.8 Inferred from direct assay. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Mitochondrial (identifier: P50440-1)

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 Cytoplasmic (identifier: P50440-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-37: MLRVRCLRGGSRGAEAVHYIGSRLGRTLTGWVQRTFQ → MNILK

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 37

37

Mitochondrion By similarity

Chain

38 – 423

386

Glycine amidinotransferase, mitochondrial

PRO_0000001206

Sites

Active site

254

1

Active site

303

1

Active site

407

1

Amidino-cysteine intermediate Ref.5

Amino acid modifications

Modified residue

385

1

N6-acetyllysine Ref.7

Modified residue

417

1

Phosphothreonine By similarity

Natural variations

Alternative sequence

1 – 37

37

MLRVR…QRTFQ → MNILK in isoform Cytoplasmic.

VSP_000235

Natural variant

110

1

Q → H: dbSNP rs1288775. Ref.3

VAR_020305

Secondary structure

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423

Helix Strand Turn

Details...

Beta strand

70 – 73

4

Beta strand

75 – 80

6

Helix

93 – 96

4

Helix

101 – 103

3

Helix

104 – 110

7

Beta strand

113 – 115

3

Helix

117 – 136

20

Beta strand

140 – 142

3

Beta strand

152 – 154

3

Beta strand

159 – 161

3

Helix

168 – 171

4

Beta strand

172 – 176

5

Beta strand

178 – 181

4

Helix

187 – 189

3

Helix

192 – 195

4

Helix

197 – 205

9

Beta strand

209 – 212

4

Helix

220 – 222

3

Helix

232 – 240

9

Beta strand

248 – 250

3

Helix

255 – 257

3

Beta strand

258 – 261

4

Beta strand

264 – 267

4

Helix

275 – 285

11

Turn

286 – 288

3

Beta strand

290 – 293

4

Beta strand

296 – 298

3

Turn

305 – 307

3

Beta strand

308 – 312

5

Beta strand

315 – 318

4

Helix

327 – 332

6

Beta strand

336 – 338

3

Beta strand

352 – 354

3

Helix

356 – 360

5

Beta strand

363 – 366

4

Beta strand

369 – 373

5

Helix

377 – 385

9

Beta strand

389 – 393

5

Helix

396 – 399

4

Turn

400 – 402

3

Turn

405 – 408

4

Beta strand

409 – 415

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform Mitochondrial [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 5BEF7A8A039B70FB	FASTA	423	48,455
	10 20 30 40 50 60 MLRVRCLRGG SRGAEAVHYI GSRLGRTLTG WVQRTFQSTQ AATASSRNSC AADDKATEPL 70 80 90 100 110 120 PKDCPVSSYN EWDPLEEVIV GRAENACVPP FTIEVKANTY EKYWPFYQKQ GGHYFPKDHL 130 140 150 160 170 180 KKAVAEIEEM CNILKTEGVT VRRPDPIDWS LKYKTPDFES TGLYSAMPRD ILIVVGNEII 190 200 210 220 230 240 EAPMAWRSRF FEYRAYRSII KDYFHRGAKW TTAPKPTMAD ELYNQDYPIH SVEDRHKLAA 250 260 270 280 290 300 QGKFVTTEFE PCFDAADFIR AGRDIFAQRS QVTNYLGIEW MRRHLAPDYR VHIISFKDPN 310 320 330 340 350 360 PMHIDATFNI IGPGIVLSNP DRPCHQIDLF KKAGWTIITP PTPIIPDDHP LWMSSKWLSM 370 380 390 400 410 420 NVLMLDEKRV MVDANEVPIQ KMFEKLGITT IKVNIRNANS LGGGFHCWTC DVRRRGTLQS YLD
	Isoform Cytoplasmic. Checksum: DA7E75BB41D91528	FASTA	391	44,883
	10 20 30 40 50 60 MNILKSTQAA TASSRNSCAA DDKATEPLPK DCPVSSYNEW DPLEEVIVGR AENACVPPFT 70 80 90 100 110 120 IEVKANTYEK YWPFYQKQGG HYFPKDHLKK AVAEIEEMCN ILKTEGVTVR RPDPIDWSLK 130 140 150 160 170 180 YKTPDFESTG LYSAMPRDIL IVVGNEIIEA PMAWRSRFFE YRAYRSIIKD YFHRGAKWTT 190 200 210 220 230 240 APKPTMADEL YNQDYPIHSV EDRHKLAAQG KFVTTEFEPC FDAADFIRAG RDIFAQRSQV 250 260 270 280 290 300 TNYLGIEWMR RHLAPDYRVH IISFKDPNPM HIDATFNIIG PGIVLSNPDR PCHQIDLFKK 310 320 330 340 350 360 AGWTIITPPT PIIPDDHPLW MSSKWLSMNV LMLDEKRVMV DANEVPIQKM FEKLGITTIK 370 380 390 VNIRNANSLG GGFHCWTCDV RRRGTLQSYL D

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The amino acid sequences of human and pig L-arginine:glycine amidinotransferase." Humm A., Huber R., Mann K. FEBS Lett. 339:101-107(1994) [PubMed: 8313955] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MITOCHONDRIAL). Tissue: Kidney.
[2]	"Characterization of the human cDNA with partial homology with the gamma subunit of sodium potassium ATPase of rat, mouse, rabbit and sheep." Austruy E., Belley L., Millasot P., Junien C., Jeanpierre C. Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CYTOPLASMIC). Tissue: Kidney.
[3]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MITOCHONDRIAL), VARIANT HIS-110. Tissue: Kidney.
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MITOCHONDRIAL). Tissue: Muscle.
[5]	"Recombinant expression and isolation of human L-arginine:glycine amidinotransferase and identification of its active-site cysteine residue." Humm A., Fritsche E., Mann K., Goehl U., Huber R. Biochem. J. 322:771-776(1997) [PubMed: 9148748] [Abstract] Cited for: ACTIVE SITE CYS-407.
[6]	"Structure and reaction mechanism of L-arginine:glycine amidinotransferase." Humm A., Fritsche E., Steinbacher S. Biol. Chem. 378:193-197(1997) [PubMed: 9165070] [Abstract] Cited for: REVIEW.
[7]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-385, MASS SPECTROMETRY.
[8]	"Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis." Humm A., Fritsche E., Steinbacher S., Huber R. EMBO J. 16:3373-3385(1997) [PubMed: 9218780] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 38-423. Tissue: Kidney.
[9]	"The ligand-induced structural changes of human L-arginine:glycine amidinotransferase. A mutational and crystallographic study." Fritsche E., Humm A., Huber R. J. Biol. Chem. 274:3026-3032(1999) [PubMed: 9915841] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 38-423.
[10]	"Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans." Item C.B., Stockler-Ipsiroglu S., Stromberger C., Muhl A., Alessandri M.G., Bianchi M.C., Tosetti M., Fornai F., Cioni G. Am. J. Hum. Genet. 69:1127-1133(2001) [PubMed: 11555793] [Abstract] Cited for: INVOLVEMENT IN AGAT DEFICIENCY.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

S68805 mRNA. Translation: AAB29892.1.
X86401 mRNA. Translation: CAA60153.1.
AK223585 mRNA. Translation: BAD97305.1.
BC004141 mRNA. Translation: AAH04141.1.

IPI

IPI00032103.
IPI00216279.

PIR

S41734.
S54161.

RefSeq

NP_001473.1.

UniGene

Hs.75335

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JDW	X-ray	1.90	A	1-423	[»]
1JDX	X-ray	2.40	A	38-423	[»]
2JDW	X-ray	2.10	A	1-423	[»]
2JDX	X-ray	2.90	A	38-423	[»]
3JDW	X-ray	2.40	A	1-423	[»]
4JDW	X-ray	2.50	A	1-423	[»]
5JDW	X-ray	2.60	A	38-423	[»]
6JDW	X-ray	2.50	A	38-423	[»]
7JDW	X-ray	2.37	A	38-423	[»]
8JDW	X-ray	2.30	A	38-423	[»]
9JDW	X-ray	2.50	A	38-423	[»]

DisProt

DP00099.

ModBase

Search...

Protein-protein interaction databases

STRING

P50440.

2-D gel databases

REPRODUCTION-2DPAGE

IPI00032103.

Proteomic databases

PRIDE

P50440.

Genome annotation databases

Ensembl

ENST00000396659; ENSP00000379895; ENSG00000171766; Homo sapiens. [Genome view]
ENST00000432007; ENSP00000388809; ENSG00000171766; Homo sapiens. [Genome view]

GeneID

2628.

KEGG

hsa:2628.

UCSC

uc001zvb.1. human.
uc001zvc.1. human.

Organism-specific databases

CTD

2628.

GeneCards

GC15M043440.

H-InvDB

HIX0012208.

HGNC

HGNC:4175. GATM.

HPA

HPA026077.

MIM

602360. gene.
612718. phenotype.

Orphanet

35704. Arginine:glycine amidinotransferase deficiency.

PharmGKB

PA28590.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13437.

HOVERGEN

P50440.

InParanoid

P50440.

PhylomeDB

P50440.

Enzyme and pathway databases

BRENDA

2.1.4.1. 247.

Reactome

REACT_13. Metabolism of amino acids.

Gene expression databases

ArrayExpress

P50440.

Bgee

P50440.

CleanEx

HS_GATM.

Genevestigator

P50440.

GermOnline

ENSG00000171766. Homo sapiens.

Family and domain databases

ProtoNet

Search...

Other Resources

DrugBank

DB00148. Creatine.
DB00145. Glycine.
DB00129. L-Ornithine.

NextBio

10353.

SOURCE

Search...

Entry information

Entry name

GATM_HUMAN

Accession

Primary (citable) accession number: P50440
Secondary accession number(s): Q53EQ4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	February 9, 2010
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.