GATM_RAT
ID GATM_RAT Reviewed; 423 AA.
AC P50442; Q6ITZ7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Glycine amidinotransferase, mitochondrial;
DE EC=2.1.4.1 {ECO:0000269|PubMed:6766137, ECO:0000269|PubMed:8035648};
DE AltName: Full=L-arginine:glycine amidinotransferase;
DE AltName: Full=Transamidinase;
DE Flags: Precursor;
GN Name=Gatm; Synonyms=Agat;
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 INDUCTION.
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=8021264; DOI=10.1016/s0021-9258(17)32477-8;
RA Guthmiller P., van Pilsum J.F., Boen J.R., McGuire D.M.;
RT "Cloning and sequencing of rat kidney L-arginine:glycine
RT amidinotransferase. Studies on the mechanism of regulation by growth
RT hormone and creatine.";
RL J. Biol. Chem. 269:17556-17560(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [3]
RP PROTEIN SEQUENCE OF 51-64.
RX PubMed=3057136; DOI=10.1093/jn/118.11.1403;
RA Gross M.D., Simon A.M., Jenny R.J., Gray E.D., McGuire D.M.,
RA van Pilsum J.F.;
RT "Multiple forms of rat kidney L-arginine:glycine amidinotransferase.";
RL J. Nutr. 118:1403-1409(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 120-358.
RA Zink R.M., Westberg M.C., Van Pilsum J.F.;
RT "The comparative cDNA sequences of some mammalian kidney L-arginine:glycine
RT amidinotransferase genes and their evolutionary significance.";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PROTEIN SEQUENCE OF 244-260, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (NOV-2006) to UniProtKB.
RN [6]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND INDUCTION.
RX PubMed=6766137; DOI=10.1016/s0021-9258(19)86155-0;
RA McGuire D.M., Tormanen C.D., Segal I.S., Van Pilsum J.F.;
RT "The effect of growth hormone and thyroxine on the amount of L-
RT arginine:glycine amidinotransferase in kidneys of hypophysectomized rats.
RT Purification and some properties of rat kidney transamidinase.";
RL J. Biol. Chem. 255:1152-1159(1980).
RN [7]
RP INDUCTION.
RX PubMed=6384218; DOI=10.1016/s0021-9258(20)71316-5;
RA McGuire D.M., Gross M.D., Van Pilsum J.F., Towle H.C.;
RT "Repression of rat kidney L-arginine:glycine amidinotransferase synthesis
RT by creatine at a pretranslational level.";
RL J. Biol. Chem. 259:12034-12038(1984).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=3512696; DOI=10.1177/34.4.3512696;
RA McGuire D.M., Gross M.D., Elde R.P., van Pilsum J.F.;
RT "Localization of L-arginine-glycine amidinotransferase protein in rat
RT tissues by immunofluorescence microscopy.";
RL J. Histochem. Cytochem. 34:429-435(1986).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=8035648; DOI=10.1016/0024-3205(94)00645-8;
RA Watanabe Y., Van Pilsum J.F., Yokoi I., Mori A.;
RT "Synthesis of neuroactive guanidino compounds by rat kidney L-arginine:
RT glycine amidinotransferase.";
RL Life Sci. 55:351-358(1994).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=9623603; DOI=10.1095/biolreprod58.6.1437;
RA Lee H., Kim J.H., Chae Y.J., Ogawa H., Lee M.H., Gerton G.L.;
RT "Creatine synthesis and transport systems in the male rat reproductive
RT tract.";
RL Biol. Reprod. 58:1437-1444(1998).
RN [11]
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 [12]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
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 [13]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=19826191;
RA Garcia-Miranda P., Garcia-Delgado M., Peral M.J., Calonge M.L.,
RA Ilundain A.A.;
RT "Ontogeny regulates creatine metabolism in rat small and large intestine.";
RL J. Physiol. Pharmacol. 60:127-133(2009).
CC -!- FUNCTION: Catalyzes the biosynthesis of guanidinoacetate, the immediate
CC precursor of creatine. Creatine plays a vital role in energy metabolism
CC in muscle tissues. May play a role in embryonic and central nervous
CC system development. Also capable of catalyzing the synthesis of a range
CC of neuroactive guanidino compounds by utilizing alternative amidine
CC donors and acceptors for the transamidination reaction.
CC {ECO:0000269|PubMed:8035648}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycine + L-arginine = guanidinoacetate + L-ornithine;
CC Xref=Rhea:RHEA:13201, ChEBI:CHEBI:32682, ChEBI:CHEBI:46911,
CC ChEBI:CHEBI:57305, ChEBI:CHEBI:57742; EC=2.1.4.1;
CC Evidence={ECO:0000269|PubMed:6766137, ECO:0000269|PubMed:8035648};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.8 mM for arginine (alpha-transamidinase form)
CC {ECO:0000269|PubMed:6766137, ECO:0000269|PubMed:8035648};
CC KM=2.4 mM for arginine (beta-transamidinase form)
CC {ECO:0000269|PubMed:6766137, ECO:0000269|PubMed:8035648};
CC KM=3.0 mM for glycine (alpha-transamidinase form)
CC {ECO:0000269|PubMed:6766137, ECO:0000269|PubMed:8035648};
CC KM=3.1 mM for glycine (beta-transamidinase form)
CC {ECO:0000269|PubMed:6766137, ECO:0000269|PubMed:8035648};
CC KM=27.2 mM for 4-amino-butyrate (alpha-transamidinase form)
CC {ECO:0000269|PubMed:6766137, ECO:0000269|PubMed:8035648};
CC KM=24.9 mM for 4-amino-butyrate (beta-transamidinase form)
CC {ECO:0000269|PubMed:6766137, ECO:0000269|PubMed:8035648};
CC KM=23.0 mM for lysine (alpha-transamidinase form)
CC {ECO:0000269|PubMed:6766137, ECO:0000269|PubMed:8035648};
CC KM=23.5 mM for lysine (beta-transamidinase form)
CC {ECO:0000269|PubMed:6766137, ECO:0000269|PubMed:8035648};
CC KM=23.9 mM for 5-amino-valerate (alpha-transamidinase form)
CC {ECO:0000269|PubMed:6766137, ECO:0000269|PubMed:8035648};
CC KM=23.5 mM for 5-amino-valerate (beta-transamidinase form)
CC {ECO:0000269|PubMed:6766137, ECO:0000269|PubMed:8035648};
CC KM=57.4 mM for 3-amino-propanoate (alpha-transamidinase form)
CC {ECO:0000269|PubMed:6766137, ECO:0000269|PubMed:8035648};
CC KM=57.5 mM for 3-amino-propanoate (beta-transamidinase form)
CC {ECO:0000269|PubMed:6766137, ECO:0000269|PubMed:8035648};
CC KM=174 mM for ethanolamine (alpha-transamidinase form)
CC {ECO:0000269|PubMed:6766137, ECO:0000269|PubMed:8035648};
CC KM=171 mM for ethanolamine (beta-transamidinase form)
CC {ECO:0000269|PubMed:6766137, ECO:0000269|PubMed:8035648};
CC KM=392 mM for taurine (alpha-transamidinase form)
CC {ECO:0000269|PubMed:6766137, ECO:0000269|PubMed:8035648};
CC KM=450 mM for taurine (beta-transamidinase form)
CC {ECO:0000269|PubMed:6766137, ECO:0000269|PubMed:8035648};
CC Vmax=0.39 umol/min/mg enzyme with L-arginine and glycine as
CC substrates (alpha-transamidinase form) {ECO:0000269|PubMed:6766137,
CC ECO:0000269|PubMed:8035648};
CC Vmax=0.37 umol/min/mg enzyme with L-arginine and glycine as
CC substrates (beta-transamidinase form) {ECO:0000269|PubMed:6766137,
CC ECO:0000269|PubMed:8035648};
CC Vmax=39.8 umol/h/mg enzyme with L-arginine and glycine as substrates
CC (alpha-transamidinase form) {ECO:0000269|PubMed:6766137,
CC ECO:0000269|PubMed:8035648};
CC Vmax=27.0 umol/h/mg enzyme with L-arginine and glycine as substrates
CC (beta-transamidinase form) {ECO:0000269|PubMed:6766137,
CC ECO:0000269|PubMed:8035648};
CC Vmax=16.8 umol/h/mg enzyme with L-arginine and 4-amino-butyrate as
CC substrates (alpha-transamidinase form) {ECO:0000269|PubMed:6766137,
CC ECO:0000269|PubMed:8035648};
CC Vmax=11.8 umol/h/mg enzyme with L-arginine and 4-amino-butyrate as
CC substrates (beta-transamidinase form) {ECO:0000269|PubMed:6766137,
CC ECO:0000269|PubMed:8035648};
CC Vmax=12.0 umol/h/ug enzyme with L-arginine and lysine as substrates
CC (alpha-transamidinase form) {ECO:0000269|PubMed:6766137,
CC ECO:0000269|PubMed:8035648};
CC Vmax=10.1 umol/h/ug enzyme with L-arginine and lysine as substrates
CC (beta-transamidinase form) {ECO:0000269|PubMed:6766137,
CC ECO:0000269|PubMed:8035648};
CC Vmax=13.9 umol/h/ug enzyme with L-arginine and 5-amino-valerate as
CC substrates (alpha-transamidinase form) {ECO:0000269|PubMed:6766137,
CC ECO:0000269|PubMed:8035648};
CC Vmax=9.7 umol/h/ug enzyme with L-arginine and 5-amino-valerate as
CC substrates (beta-transamidinase form) {ECO:0000269|PubMed:6766137,
CC ECO:0000269|PubMed:8035648};
CC Vmax=10.8 umol/h/ug enzyme with L-arginine and 3-amino-proponoate as
CC substrates (alpha-transamidinase form) {ECO:0000269|PubMed:6766137,
CC ECO:0000269|PubMed:8035648};
CC Vmax=7.7 umol/h/ug enzyme with L-arginine and 3-amino-proponoate as
CC substrates (beta-transamidinase form) {ECO:0000269|PubMed:6766137,
CC ECO:0000269|PubMed:8035648};
CC Vmax=12.4 umol/h/ug enzyme with L-arginine and ethanolamine as
CC substrates (alpha-transamidinase form) {ECO:0000269|PubMed:6766137,
CC ECO:0000269|PubMed:8035648};
CC Vmax=9.4 umol/h/ug enzyme with L-arginine and ethanolamine as
CC substrates (beta-transamidinase form) {ECO:0000269|PubMed:6766137,
CC ECO:0000269|PubMed:8035648};
CC Vmax=2.8 umol/h/ug enzyme with L-arginine and taurine as substrates
CC (alpha-transamidinase form) {ECO:0000269|PubMed:6766137,
CC ECO:0000269|PubMed:8035648};
CC Vmax=2.1 umol/h/ug enzyme with L-arginine and taurine as substrates
CC (beta-transamidinase form) {ECO:0000269|PubMed:6766137,
CC ECO:0000269|PubMed:8035648};
CC Note=Two forms of the enzyme (denoted alpha and beta) with slightly
CC different kinetic properties are present in cellular extracts. The
CC molecular basis of the differences is unclear.;
CC -!- PATHWAY: Amine and polyamine biosynthesis; creatine biosynthesis;
CC creatine from L-arginine and glycine: step 1/2.
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the kidney and pancreas,
CC especially in the proximal tubules of the kidney, and alpha cells of
CC the pancreatic islets (at protein level). Moderately expressed in liver
CC hepatocytes (at protein level). Expressed in the kidney, pancreas,
CC liver, colon, ileum, jejunum, heart and skeletal muscle. In
CC reproductive tissues, expressed in the testis, epididymis, ovary,
CC oviduct and uterus. Expressed throughout the brain in neurons,
CC astrocytes and oligodendrocytes. In E12.5 embryos, it is expressed in
CC the middle part of the somites, hepatic primordium and wall of the
CC dorsal aorta. Expressed in E15.5 embryos in isolated cells throughout
CC the central nervous system, skeletal muscles, gonad primordia, caudal
CC somites, liver and pancreas, but not in the choroid plexus, root
CC ganglia or kidney. Expressed in skeletal muscle, kidney, pancreas,
CC central nervous system, liver and intestine epithelial cells, but not
CC in epidermis, dermis, olfactory epithelium, trachea, lung, stomach or
CC heart in E18.5 embryos. {ECO:0000269|PubMed:11165387,
CC ECO:0000269|PubMed:15918910, ECO:0000269|PubMed:19826191,
CC ECO:0000269|PubMed:3512696, ECO:0000269|PubMed:9623603}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout embryogenesis. Expression in
CC the colon and small intestine is highest in newborns and declines with
CC age. Expression in the kidney increases with age.
CC {ECO:0000269|PubMed:15918910, ECO:0000269|PubMed:19826191}.
CC -!- INDUCTION: Expression is induced by growth hormone and repressed by
CC dietary intake of creatine. {ECO:0000269|PubMed:6384218,
CC ECO:0000269|PubMed:6766137, ECO:0000269|PubMed:8021264}.
CC -!- SIMILARITY: Belongs to the amidinotransferase family. {ECO:0000305}.
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DR EMBL; U07971; AAA21250.1; -; mRNA.
DR EMBL; BC081785; AAH81785.1; -; mRNA.
DR EMBL; AY625271; AAT39897.1; -; mRNA.
DR PIR; A54140; A54140.
DR RefSeq; NP_112293.1; NM_031031.2.
DR AlphaFoldDB; P50442; -.
DR SMR; P50442; -.
DR STRING; 10116.ENSRNOP00000000181; -.
DR BindingDB; P50442; -.
DR iPTMnet; P50442; -.
DR PhosphoSitePlus; P50442; -.
DR jPOST; P50442; -.
DR PaxDb; P50442; -.
DR PRIDE; P50442; -.
DR GeneID; 81660; -.
DR KEGG; rno:81660; -.
DR UCSC; RGD:71090; rat.
DR CTD; 2628; -.
DR RGD; 71090; Gatm.
DR eggNOG; ENOG502QVCA; Eukaryota.
DR HOGENOM; CLU_047415_1_0_1; -.
DR InParanoid; P50442; -.
DR OrthoDB; 636718at2759; -.
DR PhylomeDB; P50442; -.
DR BioCyc; MetaCyc:MON-7583; -.
DR BRENDA; 2.1.4.1; 5301.
DR Reactome; R-RNO-71288; Creatine metabolism.
DR UniPathway; UPA00104; UER00579.
DR PRO; PR:P50442; -.
DR Proteomes; UP000002494; Unplaced.
DR Genevisible; P50442; RN.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0015067; F:amidinotransferase activity; IDA:RGD.
DR GO; GO:0015068; F:glycine amidinotransferase activity; ISS:UniProtKB.
DR GO; GO:0006601; P:creatine biosynthetic process; ISO:RGD.
DR GO; GO:0006600; P:creatine metabolic process; ISO:RGD.
DR GO; GO:1990402; P:embryonic liver development; IEP:RGD.
DR GO; GO:0007611; P:learning or memory; ISO:RGD.
DR GO; GO:0014889; P:muscle atrophy; ISO:RGD.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0046689; P:response to mercury ion; IDA:RGD.
DR GO; GO:0007584; P:response to nutrient; IDA:RGD.
DR GO; GO:0010033; P:response to organic substance; IDA:RGD.
DR GO; GO:0006979; P:response to oxidative stress; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IDA:RGD.
DR GO; GO:0042246; P:tissue regeneration; IEP:RGD.
DR InterPro; IPR033195; AmidinoTrfase.
DR PANTHER; PTHR10488; PTHR10488; 1.
PE 1: Evidence at protein level;
KW Acetylation; Direct protein sequencing; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Phosphoprotein; Reference proteome;
KW Transferase; Transit peptide.
FT TRANSIT 1..37
FT /note="Mitochondrion"
FT CHAIN 38..423
FT /note="Glycine amidinotransferase, mitochondrial"
FT /id="PRO_0000001208"
FT ACT_SITE 254
FT /evidence="ECO:0000250"
FT ACT_SITE 303
FT /evidence="ECO:0000250"
FT ACT_SITE 407
FT /note="Amidino-cysteine intermediate"
FT /evidence="ECO:0000250"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P50440"
FT MOD_RES 49
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P50440"
FT MOD_RES 385
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50440"
SQ SEQUENCE 423 AA; 48242 MW; 442D7FBA4984DEA0 CRC64;
MLRVRCLRGG SRGAEAVHYI GSRLGGSLTG WVQRTFQSTQ AATASSQNSC AAEDKATHPL
PKDCPVSSYN EWDPLEEVIV GRAENACVPP FTVEVKANTY EKYWPFYQKN GGLYFPKDHL
KKAVAEVEEM CNILSMEGVT VKRPDPIDWS LKYKTPDFES TGLYSAMPRD ILMVVGNEII
EAPMAWRSRF FEYRAYRSII KDYFHRGAKW TTAPKPTMAD ELYDQDYPIH SVEDRHKLAA
QGKFVTTEFE PCFDAADFIR AGRDIFAQRS QVTNYLGIEW MRRHLAPDYR VHIISFKDPN
PMHIDATFNI IGPGLVLSNP DRPCHQIDLF KKAGWTIVTP PTPVIPDDHP LWMSSKWLSM
NVLMLDEKRV MVDANEVPIQ KMFEKLGIST IKVNIRNANS LGGGFHCWTC DVRRRGTLQS
YFD
