BPS/IUPHAR Guide to Pharmacology | GRAC ENZYME FAMILIES

L-Arginine turnover

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Arginase
Arginine:glycine amidinotransferase
Dimethylarginine dimethylaminohydrolases
Nitric oxide synthases
Protein arginine N-methyltransferases

L-arginine is a basic amino acid with a guanidino sidechain. As an amino acid, metabolism of L-arginine to form L-ornithine, catalysed by arginase, forms the last step of the urea production cycle. L-Ornithine may be utilised as a precursor of polyamines (see Carboxylases and Decarboxylases) or recycled via L-argininosuccinic acid to L-arginine. L-Arginine may itself be decarboxylated to form agmatine, although the prominence of this pathway in human tissues is uncertain. L-Arginine may be used as a precursor for guanidoacetic acid formation in the creatine synthesis pathway under the influence of arginine:glycine amidinotransferase with L-ornithine as a byproduct. Nitric oxide synthase uses L-arginine to generate NO, with L-citrulline also as a byproduct.

L-Arginine in proteins may be subject to post-translational modification through methylation, catalysed by protein arginine methyltransferases. Subsequent proteolysis can liberate asymmetric N^G,N^G-dimethyl-L-arginine (ADMA), which is an endogenous inhibitor of nitric oxide synthase activities. ADMA is hydrolysed by dimethylarginine dimethylhydrolase activities to generate L-citrulline and dimethylamine.

Arginase

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Arginase (EC 3.5.3.1) are manganese-containing isoforms, which appear to show differential distribution, where the ARG1 isoform predominates in the liver and erythrocytes, while ARG2 is associated more with the kidney.

Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Enzymes

Arginase I Show »« Hide

Nomenclature	Arginase I
Common abbreviation	ARG1
Other names	Liver arginase, cytosolic arginase, AI, type I arginase, AI type I arginase, Arginase 1, liver, arginase 1, arginase 1 liver, arginase, liver, arginase-1, liver-type arginase, type I arginase, PGIF, Arg-1, AI
Genes	ARG1 (Hs), Arg1 (Mm), Arg1 (Rn)
Ensembl ID	ENSG00000118520 (Hs), ENSMUSG00000019987 (Mm), ENSRNOG00000013304 (Rn)
EC number	3.5.3.1

Arginase II Show »« Hide

Nomenclature	Arginase II
Common abbreviation	ARG2
Other names	Mitochondrial arginase, AII, type II arginase, AII type II arginase, arginase 2, arginase II, arginase-2, mitochondrial, kidney-type arginase, non-hepatic arginase, type II arginase, AII
Genes	ARG2 (Hs), Arg2 (Mm), Arg2 (Rn)
Ensembl ID	ENSG00000081181 (Hs), ENSMUSG00000021125 (Mm), ENSRNOG00000011139 (Rn)
EC number	3.5.3.1

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Arginine:glycine amidinotransferase

Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Enzymes

Arginine:glycine amidinotransferase Show »« Hide

Nomenclature	Arginine:glycine amidinotransferase
Common abbreviation	AGAT
Other names	glycine amidinotransferase, GATM, AGAT, AT, MGC93388, L-arginine: glycine amidinotransferase, L-arginine:glycine amidinotransferase, glycine amidinotransferase, mitochondrial, transamidinase
Genes	GATM (Hs), Gatm (Mm), Gatm (Rn)
Ensembl ID	ENSG00000171766 (Hs), ENSMUSG00000027199 (Mm), ENSRNOG00000000168 (Rn)
EC number	2.1.4.1

Dimethylarginine dimethylaminohydrolases

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Dimethylarginine dimethylaminohydrolases (DDAH, EC 3.5.3.18) are cytoplasmic enzymes which hydrolyse N^G,N^G-dimethyl-L-arginine to form dimethylamine and L-citrulline.

Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Enzymes

N^G,N^G-Dimethylarginine dimethylaminohydrolase 1 Show »« Hide

Nomenclature

N^G,N^G-Dimethylarginine dimethylaminohydrolase 1

Common abbreviation

DDAH1

Other names

Dimethylarginine dimethylaminohydrolase 1, DDAHI, dimethylargininase-1, DDAH, DDAH-1, N(G),N(G)-dimethylarginine dimethylaminohydrolase 1, NG,NG dimethylarginine dimethylaminohydrolase, NGNG dimethylarginine dimethylaminohydrolase

Genes

DDAH1 (Hs), Ddah1 (Mm), Ddah1 (Rn)

Ensembl ID

ENSG00000153904 (Hs), ENSMUSG00000028194 (Mm), ENSRNOG00000014613 (Rn)

EC number

3.5.3.18

Cofactors

Zn²⁺

N^G,N^G-Dimethylarginine dimethylaminohydrolase 2 Show »« Hide

Nomenclature	N^G,N^G-Dimethylarginine dimethylaminohydrolase 2
Common abbreviation	DDAH2
Other names	Dimethylarginine dimethylaminohydrolase 2, DDAHII, dimethylargininase-2, S-phase protein, protein G6a, MGC105993, DDAH-2, N(G),N(G)-dimethylarginine dimethylaminohydrolase 2, Clone 7u, G6a, NG30, Ddah
Genes	DDAH2 (Hs), Ddah2 (Mm), Ddah2 (Rn)
Ensembl ID	ENSG00000213722 (Hs), ENSMUSG00000007039 (Mm), ENSRNOG00000000842 (Rn)
EC number	3.5.3.18

Nitric oxide synthases

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Nitric oxide synthases (NOS, E.C. 1.14.13.39) utilise L-arginine (not D-arginine) and molecular oxygen to generate NO and L-citrulline. The nomenclature suggested by NC-IUPHAR of NOS I, II and III [11] has not gained wide acceptance. eNOS and nNOS isoforms are activated at concentrations of calcium greater than 100 nM, while iNOS shows higher affinity for Ca²⁺/calmodulin and thus appears to be constitutively active. All the three isoforms are homodimers and require tetrahydrobiopterin, flavin adenine dinucleotide, flavin mononucleotide and NADPH for catalytic activity. L-NAME is an inhibitor of all three isoforms, with an IC₅₀ value in the micromolar range.

Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Enzymes

Endothelial NOS Show »« Hide

Nomenclature	Endothelial NOS
Common abbreviation	eNOS
Other names	NOS III, NOS-3, ecNOS, NOS3, eNOS, endothelial nitric oxide synthase, EC-NOS, NOS type III, NOSIII, cNOS, constitutive NOS, endothelial NOS, endothelial nitric oxide synthase 3, nitric oxide synthase 3, endothelial cell, nitric oxide synthase, endothelial
Genes	NOS3 (Hs), Nos3 (Mm), Nos3 (Rn)
Ensembl ID	ENSG00000164867 (Hs), ENSMUSG00000028978 (Mm), ENSRNOG00000009348 (Rn)
EC number	1.14.13.39

Inducible NOS Show »« Hide

Nomenclature

Inducible NOS

Common abbreviation

iNOS

Other names

NOS II, NOS-2, NOS2, NOS2A, iNOS, NOS, HEP-NOS, nitric oxide synthase 2A (inducible, hepatocytes), NOS type II, Nitric oxide synthase 2 inducible, Nitric oxide synthase 2 inducible macrophage, inducible NO synthase, inducible NOS, nitric oxide synthase 2, inducible, nitric oxide synthase 2, inducible, macrophage, nitric oxide synthase, inducible, peptidyl-cysteine S-nitrosylase NOS2, NOS-II

Genes

NOS2 (Hs), Nos2 (Mm), Nos2 (Rn)

Ensembl ID

ENSG00000007171 (Hs), ENSMUSG00000020826 (Mm), ENSRNOG00000011023 (Rn)

EC number

1.14.13.39

Selective inhibitors
(pIC₅₀)

aminoguanidine [5]

1400W (8.2) [7]

2-amino-4-methylpyridine (7.4) [6]

PIBTU (7.3) [8]

NIL (5.5) [12]

Neuronal NOS Show »« Hide

Nomenclature

Neuronal NOS

Common abbreviation

nNOS

Other names

bNOS, NOS-1, brain NOS, NOS1, NOS, nNOS, N-NOS, NC-NOS, NOS type I, Nitric oxide synthase 1 (neuronal), constitutive NOS, neuronal NOS, nitric oxidase synthase, nitric oxide synthase 1, nitric oxide synthase 1, neuronal, nitric oxide synthase, brain, peptidyl-cysteine S-nitrosylase NOS1, NO

Genes

NOS1 (Hs), Nos1 (Mm), Nos1 (Rn)

Ensembl ID

ENSG00000089250 (Hs), ENSMUSG00000029361 (Mm), ENSRNOG00000001130 (Rn)

EC number

1.14.13.39

Selective inhibitors
(pIC₅₀)

3-bromo-7NI (6.1 – 6.5) [3]

7NI (5.3) [1]

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Protein arginine N-methyltransferases

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Protein arginine N-methyltransferases (PRMT, EC 2.1.1.-) encompass histone arginine N-methyltransferases (PRMT4, PRMT7, EC 2.1.1.125) and myelin basic protein N-methyltransferases (PRMT7, EC 2.1.1.126). They are dimeric or tetrameric enzymes which use S-adenosyl methionine as a methyl donor, generating S-adenosyl-L-homocysteine as a by-product. They generate both mono-methylated and di-methylated products; these may be symmetric (SDMA) or asymmetric (N^G,N^G-dimethyl-L-arginine) versions, where both guanidine nitrogens are monomethylated or one of the two is dimethylated, respectively.

Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Enzymes

PRMT1 Show »« Hide

Nomenclature	PRMT1
Other names	Interferon receptor 1-bound protein 4, ANM1, HCP1, HRMT1L2, HMT1 (hnRNP methyltransferase, S. cerevisiae)-like 2, HMT1 hnRNP methyltransferase-like 2 (S. cerevisiae), heterogeneous nuclear ribonucleoproteins methyltransferase-like 2, heterogeneous nuclear ribonucleoproteins methyltransferase-like 2 (S. cerevisiae) , histone-arginine N-methyltransferase PRMT1, protein arginine N-methyltransferase 1, protein arginine methyltransferase 1
Genes	PRMT1 (Hs), Prmt1 (Mm), Prmt1 (Rn)
Ensembl ID	ENSG00000126457 (Hs), ENSMUSG00000052429 (Mm), ENSRNOG00000026109 (Rn)

PRMT2 Show »« Hide

Nomenclature	PRMT2
Other names	HRMT1L1, MGC111373, HMT1 (hnRNP methyltransferase, S. cerevisiae)-like 1, HMT1 hnRNP methyltransferase-like 1 (S. cerevisiae), HMT1 hnRNP methyltransferase-like 1, protein arginine N-methyltransferase 2, protein arginine methyltransferase 2
Genes	PRMT2 (Hs), Prmt2 (Mm), Prmt2 (Rn)
Ensembl ID	ENSG00000160310 (Hs), ENSMUSG00000020230 (Mm), ENSRNOG00000001297 (Rn)

PRMT3 Show »« Hide

Nomenclature	PRMT3
Other names	Heterogeneous nuclear ribonucleoprotein methyltransferase-like protein 3, HRMT1L3, HMT1 hnRNP methyltransferase-like 3 (S. cerevisiae), heterogeneous nuclear ribonucleoprotein methyltransferase-like 3, heterogeneous nuclear ribonucleoprotein methyltransferase-like 3 (S. cerevisiae), protein arginine N-methyltransferase 3, protein arginine N-methyltransferase 3(hnRNP methyltransferase S. cerevisiae)-like 3, protein arginine methyltransferase 3
Genes	PRMT3 (Hs), Prmt3 (Mm), Prmt3 (Rn)
Ensembl ID	ENSG00000185238 (Hs), ENSMUSG00000030505 (Mm), ENSRNOG00000014829 (Rn)

PRMT4 Show »« Hide

Nomenclature	PRMT4
Other names	Histone-arginine methyltransferase CARM1, coactivator-associated arginine methyltransferase 1, Carm1_predicted, LOC363026, coactivator-associated arginine methyltransferase 1 (predicted), protein arginine N-methyltransferase 4
Genes	CARM1 (Hs), Carm1 (Mm), Carm1 (Rn)
Ensembl ID	ENSG00000142453 (Hs), ENSMUSG00000032185 (Mm), ENSRNOG00000031129 (Rn)
EC number	2.1.1.125

PRMT5 Show »« Hide

Nomenclature	PRMT5
Other names	Histone-arginine N-methyltransferase, Shk1 kinase-binding protein 1 homolog, SKB1Hs, Jak-binding protein 1, 72 kDa ICln-binding protein, HRMT1L5, SKB1, skb1 (S. pombe) homolog, SKB1 homolog (S. pombe), LOC364382, Prmt5_predicted, Skb1_predicted, SKB1 homolog, SKB1 homolog (S. pombe) (predicted), protein arginine N-methyltransferase 5, protein arginine N-methyltransferase 5 (predicted), protein arginine methyltransferase 5, Jbp1
Genes	PRMT5 (Hs), Prmt5 (Mm), Prmt5 (Rn)
Ensembl ID	ENSG00000100462 (Hs), ENSMUSG00000023110 (Mm), ENSRNOG00000012046 (Rn)

PRMT6 Show »« Hide

Nomenclature	PRMT6
Other names	Heterogeneous nuclear ribonucleoprotein methyltransferase-like protein 6, HRMT1L6, FLJ10559, HMT1 hnRNP methyltransferase-like 6 (S. cerevisiae), Hrmt1l6_predicted, LOC295384, Prmt6_predicted, HMT1 hnRNP methyltransferase-like 6, HMT1 hnRNP methyltransferase-like 6 (S. cerevisiae) (predicted), protein arginine N-methyltransferase 6, protein arginine N-methyltransferase 6 (predicted), protein arginine methyltransferase 6
Genes	PRMT6 (Hs), Prmt6 (Mm), Prmt6 (Rn)
Ensembl ID	ENSG00000198890 (Hs), ENSMUSG00000049300 (Mm), ENSRNOG00000017187 (Rn)

PRMT7 Show »« Hide

Nomenclature	PRMT7
Other names	Histone-arginine N-methyltransferase, myelin basic protein-arginine N-methyltransferase, FLJ10640, KIAA1933, LOC292116_predicted, RGD1304869, RGD1304869_predicted, [Myelin basic protein]-arginine N-methyltransferase PRMT7, histone-arginine N-methyltransferase PRMT7, protein arginine N-methyltransferase 7, protein arginine methyltransferase 7, similar to arginine N-methyltransferase p82 isoform (predicted)
Genes	PRMT7 (Hs), Prmt7 (Mm), Prmt7 (Rn)
Ensembl ID	ENSG00000132600 (Hs), ENSMUSG00000060098 (Mm), ENSRNOG00000000258 (Rn)
EC number	2.1.1.125 2.1.1.126

PRMT8 Show »« Hide

Nomenclature	PRMT8
Other names	Heterogeneous nuclear ribonucleoprotein methyltransferase-like protein 4, HRMT1L3, HRMT1L4, HMT1 hnRNP methyltransferase-like 3 (S. cerevisiae), HMT1 hnRNP methyltransferase-like 4 (S. cerevisiae), LOC688502, protein arginine N-methyltransferase 8, protein arginine methyltransferase 8, similar to Protein arginine N-methyltransferase 4 (Heterogeneous nuclear ribonucleoprotein methyltransferase-like protein 4)
Genes	PRMT8 (Hs), Prmt8 (Mm), Prmt8 (Rn)
Ensembl ID	ENSG00000111218 (Hs), ENSMUSG00000030350 (Mm), ENSRNOG00000005140 (Rn)

PRMT9 Show »« Hide

Nomenclature	PRMT9
Other names	FBXO11, F-box only protein 11, vitiligo-associated protein 1, VIT-1, FBX11, UBR6, ubiquitin protein ligase E3 component n-recognin 6, Vit1, F-box protein 11, GENA 104, Jf
Genes	FBXO11 (Hs), Fbxo11 (Mm), Fbxo11 (Rn)
Ensembl ID	ENSG00000138081 (Hs), ENSMUSG00000005371 (Mm), ENSRNOG00000016396 (Rn)

PRMT10 Show »« Hide

Nomenclature	PRMT10
Other names	TPR repeat-containing protein LOC90826, FLJ46629, LOC291947_predicted, RGD1306157, RGD1306157_predicted, protein arginine methyltransferase 10 (putative), putative protein arginine N-methyltransferase 10, similar to CG9882-PA , similar to CG9882-PA (predicted)
Genes	PRMT10 (Hs), Prmt10 (Mm), Prmt10 (Rn)
Ensembl ID	ENSG00000164169 (Hs), ENSMUSG00000037134 (Mm), ENSRNOG00000012928 (Rn)

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