The Concise Guide to PHARMACOLOGY 2013/14: enzymes.

The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.12444/full. Enzymes are one of the seven major pharmacological targets into which the Guide is divided, with the others being G protein-coupled receptors, ligand-gated ion channels, ion channels, nuclear hormone receptors, catalytic receptors and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. A new landscape format has easy to use tables comparing related targets. It is a condensed version of material contemporary to late 2013, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in previous Guides to Receptors and Channels. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and the Guide to Receptors and Channels, providing a permanent, citable, point-in-time record that will survive database updates.

An Introduction to Enzymes

Enzymes are protein catalysts facilitating the conversion of substrates into products. The Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) classifies enzymes into families, using a four number code, on the basis of the reactions they catalyse. There are six main families:

EC 1.-.-.- Oxidoreductases;

EC 2.-.-.- Transferases;

EC 3.-.-.- Hydrolases;

EC 4.-.-.- Lyases;

EC 5.-.-.- Isomerases;

EC 6.-.-.- Ligases.

Although there are many more enzymes than receptors in biology, and many drugs that target prokaryotic enzymes are effective medicines, overall the number of enzyme drug targets is relatively small 1,2, which is not to say that they are of modest importance. In the Concise Guide to PHARMACOLOGY 2013/14, enzymes are presented as a group involved in metabolic pathways (for example, of the neurotransmitters acetylcholine, GABA and dopamine). An alternative grouping for presentation is epitomized by the cytochrome P450 enzymes, which essentially conduct the same enzymatic function, albeit on a very diverse range of substrates.

The majority of drugs which act on enzymes act as inhibitors; one exception is metformin, which appears to stimulate activity of AMP-activated protein kinase, albeit through an imprecisely-defined mechanism. Kinetic assays allow discrimination of competitive, non-competitive and un-competitive inhibitors. The majority of inhibitors are competitive (acting at the enzyme's ligand recognition site), non-competitive (acting at a distinct site; potentially interfering with co-factor or co-enzyme binding) or of mixed type. One rare example of an uncompetitive inhibitor is lithium ions, which are effective inhibitors at inositol monophosphatase only in the presence of high substrate concentrations. Some inhibitors are irreversible, including a group known as suicide substrates, which bind to the ligand recognition site and then couple covalently to the enzyme. It is beyond the scope of the Concise Guide To PHARMACOLOGY 2013/14 to give mechanistic information about the inhibitors described, although generally this information is available from the indicated literature.

Many enzymes require additional entities for functional activity. Some of these are used in the catalytic steps, while others promote a particular conformational change. Co-factors are tightly bound to the enzyme and include metal ions and heme groups. Co-enzymes are typically small molecules which accept or donate functional groups to assist in the enzymatic reaction. Examples include ATP, NAD, NADP and S-adenosylmethionine, as well as a number of vitamins, such as riboflavin (vitamin B1) and thiamine (vitamin B2). Where co-factors/co-enzymes have been identified, the Guide indicates their involvement.

Nomenclature	Common abbreviation	HGNC, UniProt	EC number: reaction	Comment
choline O-acetyltransferase	ChAT	CHAT, P28329	2.3.1.6: acetyl CoA + choline = acetylcholine + coenzyme A	Splice variants of choline O-acetyltransferase are suggested to be differentially distributed in the periphery and CNS (see 3)

Nomenclature	acetylcholinesterase	butyrylcholinesterase
Common abbreviation	AChE	BChE
HGNC, UniProt	ACHE, P22303	BCHE, P06276
EC number	3.1.1.7: acetylcholine + H2O = acetic acid + choline + H+	3.1.1.7: acetylcholine + H2O = acetic acid + choline + H+
(Sub)family-selective inhibitors (pIC50)	physostigmine (7.6 – 7.8) 6	physostigmine (7.6 – 7.8) 6
Selective inhibitors (pIC50)	donepezil (7.7 – 8.1) 4,6, BW284C51 (7.7) 5	bambuterol (8.5) 5, rivastigmine (7.4) 6

Nomenclature	Adenosine deaminase	Adenosine kinase	Ecto-5′-Nucleotidase	S-Adenosylhomocysteine hydrolase
Common abbreviation	ADA	ADK	NT5E	SAHH
HGNC, UniProt	ADA, P00813	ADK, P55263	NT5E, P21589	AHCY, P23526
EC number	3.5.4.4	2.7.1.20	3.1.3.5	3.3.1.1
Rank order of affinity	2'-deoxyadenosine > adenosine	adenosine	AMP, 5′-GMP, 5′-IMP, 5′-UMP > 5′-dAMP, 5′-dGMP	S-adenosylhomocysteine
Products	2'-deoxyinosine, inosine	AMP	adenosine, guanine, inosine, uridine	adenosine
Selective inhibitors (pIC50)	EHNA (pKi 8.8) 8, pentostatin (10.8) 8	A134974 (10.2) 14, ABT702 (8.8) 11	αβ-methyleneADP (8.7) 9	3-deazaadenosine (8.5) 10

Nomenclature	5′-nucleotidase IA	5′-nucleotidase IB	5′-nucleotidase II	5′-nucleotidase III	Mitochondrial 5′-nucleotidase
HGNC, UniProt	NT5C1A, Q9BXI3	NT5C1B, Q96P26	NT5C2, P49902	NT5C3A, Q9H0P0	NT5M, Q9NPB1
EC number	3.1.3.5	3.1.3.5	3.1.3.5	3.1.3.5	3.1.3.-

Nomenclature	L-Phenylalanine hydroxylase	L-Tyrosine hydroxylase	L-Tryptophan hydroxylase 1	L-Tryptophan hydroxylase 2
Common abbreviation	PH	TH	TPH	TPH
HGNC, UniProt	PAH, P00439	TH, P07101	TPH1, P17752	TPH2, Q8IWU9
EC number	1.14.16.1: L-phenylalanine + O2 -> L-tyrosine	1.14.16.2: L-tyrosine + O2 -> L-DOPA	1.14.16.4	1.14.16.4
Endogenous activator (Rat)	Protein kinase A-mediated phosphorylation 16	Protein kinase A-mediated phosphorylation 19	Protein kinase A-mediated phosphorylation 20	Protein kinase A-mediated phosphorylation 20
Endogenous substrates	L-phenylalanine	L-tyrosine	L-tryptophan	L-tryptophan
Products	L-tyrosine	L-DOPA	5-hydroxy-L-tryptophan	5-hydroxy-L-tryptophan
Cofactors	tetrahydrobiopterin	Fe2+, tetrahydrobiopterin	–	–
Selective inhibitors (pIC50)	α-methylphenylalanine 18, PCPA	–	6-fluorotryptophan 21, α-propyldopacetamide, fenfluramine, PCPA	6-fluorotryptophan 21, α-propyldopacetamide, fenfluramine, PCPA
Inhibitors (pIC50)	–	3-chlorotyrosine, 3-iodotyrosine, α-methyltyrosine, α-propyldopacetamide	–	–
Comment	PAH is an iron bound homodimer or -tetramer from the same structural family as tyrosine 3-monooxygenase and the tryptophan hydroxylases. Deficiency or loss-of-function of PAH is associated with phenylketonuria	TH is a homotetramer, which is inhibited by dopamine and other catecholamines in a physiological negative feedback pathway 17	–	–

Nomenclature	Arginase I	Arginase II
Common abbreviation	ARG1	ARG2
HGNC, UniProt	ARG1, P05089	ARG2, P78540

Nomenclature	Arginine:glycine amidinotransferase
Common abbreviation	AGAT
HGNC, UniProt	GATM, P50440
EC number	2.1.4.1

Nomenclature	NG,NG-Dimethylarginine dimethylaminohydrolase 1	NG,NG-Dimethylarginine dimethylaminohydrolase 2
Common abbreviation	DDAH1	DDAH2
HGNC, UniProt	DDAH1, O94760	DDAH2, O95865
Cofactors	Zn2+	–

Nomenclature	Endothelial NOS	Inducible NOS	Neuronal NOS
Common abbreviation	eNOS	iNOS	nNOS
HGNC, UniProt	NOS3, P29474	NOS2, P35228	NOS1, P29475
Selective inhibitors (pIC50)	–	aminoguanidine 26, 1400W (8.2) 28, 2-amino-4-methylpyridine (7.4) 27, PIBTU (7.3) 29, NIL (5.5) 33	Nωpropyl-L-arginine (pKi 7.2 - Rat) 35, 3-bromo-7NI (6.1 – 6.5) 24, 7NI (5.3) 22

Nomenclature	PRMT1	PRMT2	PRMT3	PRMT4	PRMT5	PRMT6	PRMT7	PRMT8	PRMT9	PRMT10
HGNC, UniProt	PRMT1, Q99873	PRMT2, P55345	PRMT3, O60678	CARM1, Q86X55	PRMT5, O14744	PRMT6, Q96LA8	PRMT7, Q9NVM4	PRMT8, Q9NR22	FBXO11, Q86XK2	PRMT10, Q6P2P2
EC number	–	–	–	2.1.1.125	–	–	2.1.1.125, 2.1.1.126	–	–	–

Nomenclature	Pyruvate carboxylase	Acetyl-CoA carboxylase 1	Acetyl-CoA carboxylase 2	Propionyl-CoA carboxylase	γ-Glutamyl carboxylase
Common abbreviation	PC	ACC1	ACC2	–	GGCX
HGNC, UniProt	PC, P11498	ACACA, Q13085	ACACB, O00763	–	GGCX, P38435
Subunits	–	–	–	Propionyl-CoA carboxylase α subunit, Propionyl-CoA carboxylase β subunit	–
EC number	6.4.1.1	6.4.1.2	6.4.1.2	6.4.1.3	4.1.1.90
Endogenous substrates	ATP, pyruvic acid	ATP, acetyl CoA	ATP, acetyl CoA	ATP, propionyl-CoA	glutamyl peptides
Products	ADP, oxalacetic acid, PO34-	malonyl-CoA, ADP, PO34-	malonyl-CoA, ADP, PO34-	ADP, methylmalonyl-CoA, PO34-	carboxyglutamyl peptides
Cofactors	biotin	biotin	biotin	biotin	NADPH, vitamin K hydroquinone
Selective inhibitors (pIC50)	–	TOFA 38	TOFA 38	–	–
Comment	–	Citrate and other dicarboxylic acids are allosteric activators of acetyl-CoA carboxylase	Citrate and other dicarboxylic acids are allosteric activators of acetyl-CoA carboxylase	Propionyl-CoA carboxylase is able to function in both forward and reverse activity modes, as a ligase (carboxylase) or lyase (decarboxylase), respectively	Loss-of-function mutations in γ-glutamyl carboxylase are associated with clotting disorders

Nomenclature	S-Adenosylmethionine decarboxylase	L-Arginine decarboxylase	L-Aromatic amino-acid decarboxylase	Glutamic acid decarboxylase 1	Glutamic acid decarboxylase 2
Common abbreviation	SAMDC	ADC	AADC	GAD1	GAD2
HGNC, UniProt	AMD1, P17707	ADC, Q96A70	DDC, P20711	GAD1, Q99259	GAD2, Q05329
EC number	4.1.1.50	4.1.1.19	4.1.1.28: L-DOPA -> dopamine + CO2	4.1.1.15: L-glutamic acid + H+ -> GABA + CO2	4.1.1.15: L-glutamic acid + H+ -> GABA + CO2
Endogenous substrates	S-adenosyl methionine	L-arginine	L-tryptophan, L-DOPA, 5-hydroxy-L-tryptophan	L-glutamic acid, L-aspartic acid	L-glutamic acid, L-aspartic acid
Products	5′-deoxyadenosyl-(3-aminopropyl) methylsulfonium	agmatine 43	5-HT, dopamine	GABA	GABA
Cofactors	pyruvic acid	pyridoxal phosphate	pyridoxal phosphate	pyridoxal phosphate	pyridoxal phosphate
Selective inhibitors (pIC50)	SAM486A (8.0) 41	–	3-hydroxybenzylhydrazine, benserazide, carbidopa, L-α-methyldopa	s-allylglycine	s-allylglycine
Comment	s-allylglycine is also an inhibitor of SAMDC 39	The presence of a functional ADC activity in human tissues has been questioned 36	AADC is a homodimer. Reaction 1: L-DOPA -> dopamine + CO2, Reaction 2: 5-hydroxy-L-tryptophan -> 5-HT + CO2, Reaction 3: L-tryptophan -> tryptamine + CO2	L-aspartic acid is a less rapidly metabolised substrate of mouse brain glutamic acid decarboxylase generating β-alanine 42. Autoantibodies against GAD1 and GAD2 are elevated in type 1 diabetes mellitus and neurological disorders (see Further reading)

Nomenclature	Histidine decarboxylase	Malonyl-CoA decarboxylase	Ornithine decarboxylase	Phosphatidylserine decarboxylase
Common abbreviation	HDC	MLYCD	ODC	PSDC
HGNC, UniProt	HDC, P19113	MLYCD, O95822	ODC1, P11926	PISD, Q9UG56
EC number	4.1.1.22	4.1.1.9	4.1.1.17	4.1.1.65
Endogenous substrates	L-histidine	malonyl-CoA	L-ornithine	phosphatidylserine
Products	histamine	acetyl CoA	putrescine	phosphatidylethanolamine
Cofactors	pyridoxal phosphate	pyridoxal phosphate	pyridoxal phosphate	pyruvic acid
Selective inhibitors (pIC50)	AMA, FMH 37	–	APA, DFMO	–
Comment	–	Inhibited by AMP-activated protein kinase-evoked phosphorylation 40	The activity of ODC is regulated by the presence of an antizyme (ENSG00000104904) and an ODC antizyme inhibitor (ENSG00000155096)	S-allylglycine is also an inhibitor of SAMDC 39

Nomenclature	Common abbreviation	HGNC, UniProt	EC number	Endogenous activator (Rat)	Endogenous substrates	Products	Cofactors	Selective inhibitors (pIC50)	Comment
L-Phenylalanine hydroxylase	PH	PAH, P00439	1.14.16.1: L-phenylalanine + O2 -> L-tyrosine	Protein kinase A-mediated phosphorylation 44	L-phenylalanine	L-tyrosine	tetrahydrobiopterin	α-methylphenylalanine 49, PCPA	PAH is an iron bound homodimer or -tetramer from the same structural family as tyrosine 3-monooxygenase and the tryptophan hydroxylases. Deficiency or loss-of-function of PAH is associated with phenylketonuria

Nomenclature	Common abbreviation	HGNC, UniProt	EC number	Cofactors	Comment
Tyrosine aminotransferase	TAT	TAT, P17735	2.6.1.5: L-tyrosine + α-ketoglutaric acid -> 4-hydroxyphenylpyruvic acid + L-glutamic acid	pyridoxal phosphate	Tyrosine may also be metabolized in the liver by tyrosine transaminase to generate 4-hydroxyphenylpyruvic acid, which can be further metabolized to homogentisic acid., TAT is a homodimer, where loss-of-function mutations are associated with type II tyrosinemia

Nomenclature	Common abbreviation	HGNC, UniProt	EC number	Endogenous substrates	Products	Cofactors	Selective inhibitors (pIC50)	Comment
L-Aromatic amino-acid decarboxylase	AADC	DDC, P20711	4.1.1.28: L-DOPA -> dopamine + CO2	L-tryptophan, L-DOPA, 5-hydroxy-L-tryptophan	5-HT, dopamine	pyridoxal phosphate	3-hydroxybenzylhydrazine, benserazide, carbidopa, L-α-methyldopa	AADC is a homodimer, Reaction 1: L-DOPA -> dopamine + CO2, Reaction 2: 5-hydroxy-L-tryptophan -> 5-HT + CO2, Reaction 3: L-tryptophan -> tryptamine + CO2

Nomenclature	Common abbreviation	HGNC, UniProt	EC number	Endogenous activators	Endogenous substrates	Products	Cofactors	Inhibitors (pIC50)	Comment
L-Tyrosine hydroxylase	TH	TH, P07101	1.14.16.2: L-tyrosine + O2 -> L-DOPA	Protein kinase A-mediated phosphorylation 51	L-tyrosine	L-DOPA	Fe2+, tetrahydrobiopterin	3-chlorotyrosine, 3-iodotyrosine, α-methyltyrosine, α-propyldopacetamide	TH is a homotetramer, which is inhibited by dopamine and other catecholamines in a physiological negative feedback pathway 47

Nomenclature	Common abbreviation	HGNC, UniProt	EC number	Cofactors	Selective inhibitors (pIC50)	Comment
Dopamine beta-hydroxylase (dopamine beta-monooxygenase)	DBH	DBH, P09172	1.14.17.1: dopamine + O2 -> (-)-noradrenaline + H2O	Cu2+, L-ascorbic acid	nepicastat (8.0) 55	DBH is a homotetramer. A protein structurally-related to DBH (MOXD1, Q6UVY6) has been described and for which a function has yet to be identified 45

Nomenclature	Common abbreviation	HGNC, UniProt	EC number	Cofactors	Selective inhibitors (pIC50)
Phenylethanolamine N-methyltransferase	PNMT	PNMT, P11086	2.1.1.28: (-)-noradrenaline -> (-)-adrenaline	S-adenosyl methionine	LY134046 (pKi 7.6) 48

Nomenclature	Monoamine oxidase A	Monoamine oxidase B
Common abbreviation	MAO-A	MAO-B
HGNC, UniProt	MAOA, P21397	MAOB, P27338
EC number	1.4.3.4: dopamine -> 3,4-dihydroxyphenylacetaldehyde + NH3	1.4.3.4: dopamine -> 3,4-dihydroxyphenylacetaldehyde + NH3
Cofactors	flavin adenine dinucleotide	flavin adenine dinucleotide
Selective inhibitors (pIC50)	befloxatone 46, clorgyline, pirlindole 53	lazabemide 50, L-Deprenyl, rasagiline 56
Comment	Reaction 1: dopamine -> 3,4-dihydroxyphenylacetaldehyde + NH3, Reaction 2: (-)-noradrenaline -> 3,4-dihydroxymandelic acid + NH3, Reaction 3: (-)-adrenaline -> 3,4-dihydroxymandelic acid + NH3, Reaction 4: 5-HT -> 5-hydroxyindole acetaldehyde + NH3, Reaction 5: tyramine -> 4-hydroxyphenyl acetaldehyde + NH3	–

Nomenclature	Common abbreviation	HGNC, UniProt	EC number	Cofactors	Selective inhibitors (pIC50)	Comment
Catechol-O-methyltransferase	COMT	COMT, P21964	2.1.1.6: dopamine -> 3-methoxytyramine	S-adenosyl methionine	entacapone 52,54, tolcapone 52,54	COMT appears to exist in both membrane-bound and soluble forms. COMT has also been described to methylate steroids, particularly hydroxyestradiols, Reaction 1: dopamine -> 3-methoxytyramine, Reaction 2: (-)-noradrenaline -> normetanephrine, Reaction 3: (-)-adrenaline -> metanephrine, Reaction 4: 3,4-dihydroxymandelic acid -> vanillylmandelic acid

Nomenclature	serine palmitoyltransferase, long chain base subunit 1	serine palmitoyltransferase, long chain base subunit 2	serine palmitoyltransferase, long chain base subunit 3	serine palmitoyltransferase, small subunit A	serine palmitoyltransferase, small subunit B
Common abbreviation	SPT1	SPT2	SPT3	SPTSSA	SPTSSB
HGNC, UniProt	SPTLC1, O15269	SPTLC2, O15270	SPTLC3, Q9NUV7	SPTSSA, Q969W0	SPTSSB, Q8NFR3
EC number	2.3.1.50: palmitoylCoA + L-serine -> 3-Ketosphinganine + coenzyme A + CO2	–	–
Cofactors	pyridoxal phosphate	pyridoxal phosphate	pyridoxal phosphate	–	–
Selective inhibitors (pIC50)	myriocin 67	myriocin 67	myriocin 67	–	–

Nomenclature	HGNC, UniProt	EC number	Cofactors
3-ketodihydrosphingosine reductase	KDSR, Q06136	1.1.1.102: 3-Ketosphinganine + NADPH -> sphinganine + NADP+	NADPH

Nomenclature	ceramide synthase 1	ceramide synthase 2	ceramide synthase 3
Common abbreviation	CERS1	CERS2	CERS3
HGNC, UniProt	CERS1, P27544	CERS2, Q96G23	CERS3, Q8IU89
EC number	2.3.1.24: sphinganine + acylCoA -> dihydroceramide + coenzyme A, sphingosine + acylCoA -> ceramide + coenzyme A
Substrates	C18-CoA 76	C24- and C26-CoA 65	C26-CoA and longer 69,71

Nomenclature	ceramide synthase 4	ceramide synthase 5	ceramide synthase 6
Common abbreviation	CERS4	CERS5	CERS6
HGNC, UniProt	CERS4, Q9HA82	CERS5, Q8N5B7	CERS6, Q6ZMG9
EC number	2.3.1.24: sphinganine + acylCoA -> dihydroceramide + coenzyme A, sphingosine + acylCoA -> ceramide + coenzyme A
Substrates	C18-, C20- and C22-CoA 72	C16-CoA 64,72	C14- and C16-CoA 68

Nomenclature	delta(4)-desaturase, sphingolipid 1	delta(4)-desaturase, sphingolipid 2
HGNC, UniProt	DEGS1, O15121	DEGS2, Q6QHC5
EC number	1.14.-.-: dihydroceramide + NADH + O2 -> ceramide + H2O + NAD, sphinganine + NADH + O2 -> sphingosine + H2O + NAD
Cofactors	NAD	NAD
Comment	Myristoylation of DEGS1 enhances its activity and targets it to the mitochondria 59	–

Nomenclature	sphingomyelin synthase 1	sphingomyelin synthase 2
HGNC, UniProt	SGMS1, Q86VZ5	SGMS2, Q8NHU3
EC number	2.7.8.27: ceramide + phosphatidylcholine -> sphingomyelin + diacylglycerol
Comment	–	Palmitoylation of sphingomyelin synthase 2 may allow targeting to the plasma membrane 75

Nomenclature	HGNC, UniProt	EC number
sterile alpha motif domain containing 8	SAMD8, Q96LT4	2.7.8.-: ceramide + phosphatidylethanolamine -> ceramide phosphoethanolamine

Nomenclature	sphingomyelin phosphodiesterase 1, acid lysosomal	sphingomyelin phosphodiesterase 2, neutral membrane (neutral sphingomyelinase)	sphingomyelin phosphodiesterase 3, neutral membrane (neutral sphingomyelinase II)	sphingomyelin phosphodiesterase 4, neutral membrane (neutral sphingomyelinase-3)
HGNC, UniProt	SMPD1, P17405	SMPD2, O60906	SMPD3, Q9NY59	SMPD4, Q9NXE4
EC number	3.1.4.12: sphingomyelin -> ceramide + phosphocholine

Nomenclature	sphingomyelin phosphodiesterase, acid-like 3A	sphingomyelin phosphodiesterase, acid-like 3B
HGNC, UniProt	SMPDL3A, Q92484	SMPDL3B, Q92485
EC number	3.1.4.-: sphingomyelin -> ceramide + phosphocholine

Nomenclature	embryonic ectoderm development	neutral sphingomyelinase (N-SMase) activation associated factor
HGNC, UniProt	EED, O75530	NSMAF, Q92636

Nomenclature	HGNC, UniProt	EC number	Selective inhibitors	Comment
UDP-glucose ceramide glucosyltransferase	UGCG, Q16739	2.4.1.80: UDP-glucose + ceramide = UDP + glucosylceramide	miglustat 57	Glycoceramides are an extended family of sphingolipids, differing in the content and organization of the sugar moieties, as well as the acyl sidechains

Nomenclature	HGNC, UniProt	EC number	Comment
N-acylsphingosine amidohydrolase (acid ceramidase) 1	ASAH1, Q13510	3.5.1.23: ceramide -> sphingosine + a fatty acid	This lysosomal enzyme is proteolysed to form the mature protein made up of two chains from the same gene product 63

Nomenclature	N-acylsphingosine amidohydrolase (non-lysosomal ceramidase) 2	N-acylsphingosine amidohydrolase (non-lysosomal ceramidase) 2B	N-acylsphingosine amidohydrolase (non-lysosomal ceramidase) 2C
HGNC, UniProt	ASAH2, Q9NR71	ASAH2B, P0C7U1	ASAH2C, P0C7U2
EC number	3.5.1.23: ceramide -> sphingosine + a fatty acid	–	–
Comment	The enzyme is associated with the plasma membrane 74	–	–

Nomenclature	alkaline ceramidase 1	alkaline ceramidase 2	alkaline ceramidase 3
HGNC, UniProt	ACER1, Q8TDN7	ACER2, Q5QJU3	ACER3, Q9NUN7
EC number	3.5.1.23: ceramide -> sphingosine + a fatty acid	3.5.1.23: ceramide -> sphingosine + a fatty acid	3.5.1.-
Comment	ACER1 is associated with the ER 73	ACER2 is associated with the Golgi apparatus 77	ACER3 is associated with the ER and Golgi apparatus 66

Nomenclature	HGNC, UniProt	EC number	Selective inhibitors (pIC50)
ceramide kinase	CERK, Q8TCT0	2.7.1.138: ceramide + ATP -> ceramide 1-phosphate + ADP	NVP 231 (7.9) 61

Nomenclature	AC1	AC3	AC8
HGNC, UniProt	ADCY1, Q08828	ADCY3, O60266	ADCY8, P40145
Endogenous activators	calmodulin (CALM2, CALM3, CALM1, P62158), PKC-evoked phosphorylation 110,132	calmodulin (CALM2, CALM3, CALM1, P62158), PKC-evoked phosphorylation 88,110	–
Endogenous inhibitors	Gαi, Gαo, Gβγ 133,134	Gαi, RGS2 (RGS2, P41220), CaM kinase II-evoked phosphorylation 127,134,140	Ca2+ 82

Nomenclature	AC5	AC6	AC9
HGNC, UniProt	ADCY5, O95622	ADCY6, O43306	ADCY9, O60503
Endogenous activators	PKC-evoked phophorylation 111	–	–
Endogenous inhibitors	Gαi, Ca2+, PKA-evoked phosphorylation 108,109,134	Gαi, Ca2+, PKA-evoked phosphorylation, PKC-evoked phosphorylation 87,112,134,141	Ca2+/calcineurin 120
Selective inhibitors (pIC50)	NKY80 119	–	–

Nomenclature	AC2	AC4	AC7
HGNC, UniProt	ADCY2, Q08462	ADCY4, Q8NFM4	ADCY7, P51828
Endogenous activators	Gβγ, PKC-evoked phosphorylation 85,114,133	Gβγ 99	PKC-evoked phosphorylation 139
Endogenous inhibitors	–	PKC-evoked phophorylation 143	–

Nomenclature	Soluble guanylyl cyclase
Common abbreviation	sGC
Subunits	Soluble guanylyl cyclase α 1 subunit, Soluble guanylyl cyclase β 1 subunit
EC number	4.6.1.2
Selective activators	ataciguat 125, BAY412272 129, cinaciguat 130, NO, riociguat 130, YC1 96
Selective inhibitors (pIC50)	NS 2028 (8.1 - Bovine) 118, ODQ (7.5) 101

Nomenclature	Epac1	Epac2
HGNC, UniProt	RAPGEF3, O95398	RAPGEF4, Q8WZA2
Selective inhibitors (pIC50)	–	HJC 0350 (6.5) 84

Nomenclature	PDE1A	PDE1B	PDE1C
HGNC, UniProt	PDE1A, P54750	PDE1B, Q01064	PDE1C, Q14123
Rank order of affinity	cGMP > cAMP	cGMP > cAMP	cGMP = cAMP
Endogenous activators	calmodulin (CALM2, CALM3, CALM1, P62158)	calmodulin (CALM2, CALM3, CALM1, P62158)	calmodulin (CALM2, CALM3, CALM1, P62158)
Selective inhibitors (pIC50)	SCH51866 (7.2) 137, vinpocetine (5.1) 113	SCH51866 (7.2) 137	SCH51866 (7.2) 137, vinpocetine (4.3) 113

Nomenclature	PDE2A	PDE3A	PDE3B
HGNC, UniProt	PDE2A, O00408	PDE3A, Q14432	PDE3B, Q13370
Rank order of affinity	cAMP >> cGMP	–	–
Endogenous activators	cGMP	–	–
Endogenous inhibitors (pIC50)	–	cGMP (Selective)	cGMP (Selective)
Selective inhibitors (pIC50)	BAY607550 (8.3 – 8.8) 80, EHNA (5.3) 116	cilostamide (7.5) 131, milrinone (6.3) 131	cilostamide (7.3) 131, milrinone (6.0) 131
Comment	EHNA is also an inhibitor of adenosine deaminase (E.C. 3.5.4.4)	–	–

Nomenclature	PDE4A	PDE4B	PDE4C	PDE4D
HGNC, UniProt	PDE4A, P27815	PDE4B, Q07343	PDE4C, Q08493	PDE4D, Q08499
Activator	–	–	–	PKA-mediated phosphorylation 107
Rank order of affinity	cAMP >> cGMP	cAMP >> cGMP	cAMP >> cGMP	cAMP >> cGMP
Selective inhibitors (pIC50)	rolipram (9.0) 138, YM976 (8.3) 79, RS-25344 (7.2) 123, Ro201724 (6.5) 138	rolipram (9.0) 138, RS-25344 (6.5) 123, Ro201724 (6.4) 138	RS-25344 (8.1) 123, rolipram (6.5) 138, Ro201724 (5.4) 138	RS-25344 (8.4) 123, rolipram (7.2) 138, Ro201724 (6.2) 138

Nomenclature	PDE5A
HGNC, UniProt	PDE5A, O76074
EC number	3.1.4.17
Activators	Protein kinase A, protein kinase G 89
Rank order of affinity	cGMP > cAMP
Selective inhibitors (pIC50)	T0156 (9.5) 117, sildenafil (9.0) 136, gisadenafil (8.9) 122, SCH51866 (7.2) 137, zaprinast (6.8) 136

Nomenclature	PDE6A	PDE6B	PDE6C	PDE6D	PDE6G	PDE6H
HGNC, UniProt	PDE6A, P16499	PDE6B, P35913	PDE6C, P51160	PDE6D, O43924	PDE6G, P18545	PDE6H, Q13956

Nomenclature	PDE7A	PDE7B	PDE8A	PDE8B
HGNC, UniProt	PDE7A, Q13946	PDE7B, Q9NP56	PDE8A, O60658	PDE8B, O95263
EC number	3.1.4.17	3.1.4.17	3.1.4.17	3.1.4.17
Rank order of affinity	cAMP >> cGMP 115	cAMP >> cGMP 100	cAMP >> cGMP 93	cAMP >> cGMP 102
Selective inhibitors (pIC50)	BRL50481 (6.7 – 6.8) 78,128	dipyridamole (5.7 – 6.0) 100,124, SCH51866 (5.8) 124, BRL50481 (4.9) 78	dipyridamole (5.1) 93	dipyridamole (4.3) 102
Comment	PDE7A appears to be membrane-bound or soluble for PDE7A1 and 7A2 splice variants, respectively	–	–	–

Nomenclature	PDE9A	PDE10A	PDE11A
HGNC, UniProt	PDE9A, O76083	PDE10A, Q9Y233	PDE11A, Q9HCR9
EC number	3.1.4.17	3.1.4.17	3.1.4.17
Rank order of affinity	cGMP >> cAMP 94	cAMP, cGMP 97	cAMP, cGMP 91
Selective inhibitors (pIC50)	SCH51866 (5.8) 94, zaprinast (4.5) 94	–	BC11-38 (6.5) 83

Nomenclature	HGNC, UniProt	EC number	Comment
CYP1A1	CYP1A1, P04798	1.14.1.1	–
CYP1A2	CYP1A2, P05177	1.14.1.1	–
CYP1B1	CYP1B1, Q16678	1.14.1.1	Mutations have been associated with primary congenitial glucoma 165

Nomenclature	HGNC, UniProt	EC number	Comment
CYP2A6	CYP2A6, P11509	1.14.14.1	Metabolises nicotine
CYP2A7	CYP2A7, P20853	1.14.14.1	CYP2A7 does not incorporate haem and is functionally inactive 148
CYP2A13	CYP2A13, Q16696	1.14.14.1	–
CYP2B6	CYP2B6, P20813	1.14.14.1	–
CYP2C8	CYP2C8, P10632	1.14.14.1	Converts arachidonic acid to 11(R)-12(S)-epoxyeicosatrienoic acid or 14(R)-15(S)-epoxyeicosatrienoic acid 168
CYP2C9	CYP2C9, P11712	1.14.13.80, 1.14.13.48, 1.14.13.49	–
CYP2C18	CYP2C18, P33260	1.14.14.1	–
CYP2C19	CYP2C19, P33261	1.14.13.80, 1.14.13.48, 1.14.13.49	–
CYP2D6	CYP2D6, P10635	1.14.14.1	–
CYP2E1	CYP2E1, P05181	1.14.14.1	–
CYP2F1	CYP2F1, P24903	1.14.14.1	–
CYP2J2	CYP2J2, P51589	1.14.14.1	Converts arachidonic acid to 14(R)-15(S)-epoxyeicosatrienoic acid 167
CYP2R1	CYP2R1, Q6VVX0	1.14.13.15	Converts vitamin D3 to 25-hydroxyvitamin D3 146
CYP2S1	CYP2S1, Q96SQ9	1.14.14.1	–
CYP2U1	CYP2U1, Q7Z449	1.14.14.1	–
CYP2W1	CYP2W1, Q8TAV3	1.14.14.-	–

Nomenclature	HGNC, UniProt	EC number	Comment
CYP3A4	CYP3A4, P08684	1.14.13.67, 1.14.13.97, 1.14.13.32	Metabolises a vast range of xenobiotics, including antidepressants, benzodiazepines, calcium channel blockers, and chemotherapeutic agents
CYP3A5	CYP3A5, P20815	1.14.14.1	–
CYP3A7	CYP3A7, P24462	1.14.14.1	–
CYP3A43	CYP3A43, Q9HB55	1.14.14.1	–

Nomenclature	HGNC, UniProt	EC number	Comment
CYP4A11	CYP4A11, Q02928	1.14.15.3	Converts lauric acid to 12-hydroxylauric acid
CYP4A22	CYP4A22, Q5TCH4	1.14.15.3	–
CYP4B1	CYP4B1, P13584	1.14.14.1	–
CYP4F2	CYP4F2, P78329	1.14.13.30	Responsible for ω-hydroxylation of LTB4, LXB4 155, and tocopherols, including vitamin E 163
CYP4F3	CYP4F3, Q08477	1.14.13.30	Responsible for ω-hydroxylation of LTB4, LXB4 155, and polyunsaturated fatty acids 147,151
CYP4F8	CYP4F8, P98187	1.14.14.1	Converts PGH2 to 19-hydroxyPGH2 145 and 8,9-EET or 11,12-EET to 18-hydroxy-8,9-EET or 18-hydroxy-11,12-EET 157
CYP4F11	CYP4F11, Q9HBI6	1.14.14.1	–
CYP4F12	CYP4F12, Q9HCS2	1.14.14.1	AC004597.1 (ENSG00000225607) is described as being highly similar to CYP4F12
CYP4F22	CYP4F22, Q6NT55	1.14.14.-	Converts arachidonic acid to 16-HETE and 18-HETE 157
CYP4V2	CYP4V2, Q6ZWL3	1.14.-.-	Converts myristic acid to 14-hydroxymyristic acid 156
CYP4X1	CYP4X1, Q8N118	1.14.14.1	Converts anandamide to 14,15-epoxyeicosatrienoic ethanolamide 164
CYP4Z1	CYP4Z1, Q86W10	1.14.14.1	Converts lauric acid to 12-hydroxylauric acid

Nomenclature	Common name	HGNC, UniProt	EC number	Comment
CYP5A1	–	TBXAS1, P24557	5.3.99.5	Converts PGH2 to thromboxane A2. Inhibited by dazoxiben 161 and camonagrel 150
CYP8A1	Prostacyclin synthase	PTGIS, Q16647	5.3.99.4	Converts prostaglandin H2 to prostaglandin I2 152. Inhibited by tranylcypromine 149
CYP7A1	–	CYP7A1, P22680	1.14.13.17	Converts cholesterol to 7α-hydroxycholesterol 158
CYP7B1	–	CYP7B1, O75881	1.14.13.100	Converts DHEA to 7α-DHEA 162
CYP8B1	–	CYP8B1, Q9UNU6	1.14.13.95	Converts 7α-hydroxycholest-4-en-3-one to 7-alpha,12α-dihydroxycholest-4-en-3-one (in rabbit) 153 in the biosynthesis of bile acids

Nomenclature	Common name	HGNC, UniProt	EC number	Comment
CYP11A1	–	CYP11A1, P05108	1.14.15.6	Converts cholesterol to pregnenolone plus 4-methylpentanal
CYP11B1	–	CYP11B1, P15538	1.14.15.4	Converts deoxycortisone and 11-deoxycortisol to cortisone and cortisol, respectively Loss-of-function mutations are associated with familial adrenal hyperplasia and hypertension Inhibited by metyrapone 166
CYP11B2	Aldosterone synthase	CYP11B2, P19099	1.14.15.4, 1.14.15.5	Converts corticosterone to aldosterone
CYP17A1	–	CYP17A1, P05093	1.14.99.9	Converts pregnenolone and progesterone to 17α-hydroxypregnenolone and 17α-hydroxyprogesterone, respectively. Converts 17α-hydroxypregnenolone and 17α-hydroxyprogesterone to dehydroepiandrosterone and androstenedione, respectively Converts corticosterone to cortisol. Inhibited by abiraterone (pIC50 8.4) 160
CYP19A1	Aromatase	CYP19A1, P11511	1.14.14.1	Converts androstenedione and testosterone to estrone and 17β-estradiol, respectively Inhibited by anastrazole 159, and letrozole 144
CYP20A1	–	CYP20A1, Q6UW02	1.14.-.-	–
CYP21A2	–	CYP21A2, P08686	1.14.99.10	Converts progesterone and 17α-hydroxyprogesterone to deoxycortisone and 11-deoxycortisol, respectively

Nomenclature	Common name	HGNC, UniProt	EC number	Comment
CYP24A1	–	CYP24A1, Q07973	1.14.13.126	Converts 1α,25-dihydroxyvitamin D3 (calcitriol) to 1α,24R,25-trihydroxyvitamin D3
CYP26A1	–	CYP26A1, O43174	1.14.-.-	Converts retinoic acid to 4-hydroxyretinoic acid. Inhibited by liarozole
CYP26B1	–	CYP26B1, Q9NR63	1.14.-.-	Converts retinoic acid to 4-hydroxyretinoic acid
CYP26C1	–	CYP26C1, Q6V0L0	1.14.-.-	–
CYP27A1	Sterol 27-hydroxylase	CYP27A1, Q02318	1.14.13.15	Converts cholesterol to 27-hydroxyxcholesterol
CYP27B1	–	CYP27B1, O15528	1.14.13.13	Converts 25-hydroxyvitamin D3 to 1α,25-dihydroxyvitamin D3 (calcitriol)
CYP27C1	–	CYP27C1, Q4G0S4	1.14.-.-	–

Nomenclature	Common name	HGNC, UniProt	EC number	Comment
CYP39A1	–	CYP39A1, Q9NYL5	1.14.13.99	Converts 24-hydroxycholesterol to 7α,24-dihydroxycholesterol 154
CYP46A1	Cholesterol 24-hydroxylase	CYP46A1, Q9Y6A2	1.14.13.98	Converts cholesterol to 24(S)-hydroxycholesterol
CYP51A1	Lanosterol 14-α-demethylase	CYP51A1, Q16850	–	Converts lanosterol to 4,4-dimethylcholesta-8.14.24-trienol

Nomenclature	COX-1	COX-2
HGNC, UniProt	PTGS1, P23219	PTGS2, P35354
EC number	1.14.99.1	1.14.99.1
Reaction 1:	arachidonic acid => PGG2 => PGH2	arachidonic acid => PGG2 => PGH2
Reaction 2:	–	docosahexaenoic acid => PGH3
Selective inhibitors (pIC50)	ketorolac (9.72) 190, FR122047 (7.5) 183, flurbiprofen (7.12) 190	etoricoxib, lumiracoxib, valdecoxib (8.3) 189, rofecoxib (6.1 – 6.5) 190

Nomenclature	HGNC, UniProt	EC number	Reaction:	Cofactors	Selective inhibitors (pIC50)	Comment
mPGES1	PTGES, O14684	5.3.99.3	PGH2 => PGE2	glutathione 175	–	–
mPGES2	PTGES2, Q9H7Z7	5.3.99.3	PGH2 => PGE2	Thiols, including dihydrolipoic acid 191	–	–
cPGES	PTGES3, Q15185	5.3.99.3	PGH2 => PGE2	–	–	Phosphorylated and activated by casein kinase 2 (CK2) 177. Appears to regulate steroid hormone function by interaction with dimeric hsp90 170,176.
L-PGDS	PTGDS, P41222	5.3.99.2	PGH2 => PGD2	–	–	–
H-PGDS	HPGDS, O60760	5.3.99.2	PGH2 => PGD2	–	HQL-79 (5.3 – 5.5) 169	–

Nomenclature	AKR1C3	CBR1	HPGD
HGNC, UniProt	AKR1C3, P42330	CBR1, P16152	HPGD, P15428
EC number	1.1.1.188, 1.3.1.20, 1.1.1.213, 1.1.1.63, 1.1.1.64	1.1.1.197, 1.1.1.184, 1.1.1.189	1.1.1.141
Inhibitors	flufenamic acid, indomethacin, flavonoids 182,188	–	–
Reaction 1:	PGD2 + NADP+ => PGF2α + NADPH + H+	PGE2 + NADP+ => PGF2α + NADPH + H+	15-hydroxyprostaglandins => 15-ketoprostaglandins
Reaction 2:	–	–	Lipoxin A4 => 15-keto-lipoxin A4 181
Cofactors	NADP	NADP	–
Comment	Also acts as a hydroxysteroid dehydrogenase activity.	–	–

Nomenclature	5-LOX	12R-LOX	12S-LOX
HGNC, UniProt	ALOX5, P09917	ALOX12B, O75342	ALOX12, P18054
EC number	1.13.11.34	1.13.11.-	1.13.11.31
Endogenous inhibitor	Protein kinase A-mediated phosphorylation 180	–	–
Reaction:	arachidonic acid + O2 => LTA4 + H22O	arachidonic acid + O2 => 12R-HPETE	arachidonic acid + O2 => 12S-HPETE
Endogenous substrates	arachidonic acid	–	–
Endogenous activators	FLAP (ALOX5AP, P20292)	–	–
Selective inhibitors (pIC50)	CJ13610 172, zileuton	–	–
Substrates	–	methyl arachidonate	–
Comment	FLAP activity can be inhibited by MK-886 171 and BAY-X1005 174 leading to a selective inhibition of 5-LOX activity	–	–

Nomenclature	15-LOX-1	15-LOX-2	E-LOX
HGNC, UniProt	ALOX15, P16050	ALOX15B, O15296	ALOXE3, Q9BYJ1
EC number	1.13.11.33	1.13.11.33	1.13.11.-
Endogenous substrates	–	–	12R-HPETE
Reaction 1:	arachidonic acid + O2 => 15S-HPETE	arachidonic acid + O2 => 15S-HPETE	–
Reaction 2:	linoleic acid + O2 => 13S-HPODE	–	–
Comment	–	–	E-LOX metabolises the product from the 12R-lipoxygenase (12R-HPETE) to a specific epoxyalcohol compound 192

Nomenclature	Leukotriene C4 synthase	γ-Glutamyltransferase	Dipeptidase 1	Dipeptidase 2	Leukotriene A4 hydrolase
HGNC, UniProt	LTC4S, Q16873	GGCT, O75223	DPEP1, P16444	DPEP2, Q9H4A9	LTA4H, P09960
EC number	4.4.1.20	2.3.2.2	3.4.13.19	3.4.13.19	3.3.2.6
Reaction:	LTA4 +glutathione => LTC4	LTC4 + H2O => LTD4 + L-glutamate	LTD4 + H2O = LTE4 + glycine	LTD4 + H2O = LTE4 + glycine	LTA4 + H2O = LTB4
Inhibitors	–	–	cilastatin 179	–	bestatin 185

Nomenclature	Diacylglycerol lipase α	Diacylglycerol lipase β	N-Acylphosphatidylethanolamine-phospholipase D
Common abbreviation	DGLα	DGLβ	NAPE-PLD
HGNC, UniProt	DAGLA, Q9Y4D2	DAGLB, Q8NCG7	NAPEPLD, Q6IQ20
EC number	3.1.1.-	3.1.1.-	–
Selective inhibitors (pIC50)	RHC80267, orlistat (7.2) 196	RHC80267, orlistat (7.0) 196	–
Comment	–	–	NAPE-PLD activity appears to be enhanced by polyamines in the physiological range 202, but fails to transphosphatidylate with alcohols 205 unlike phosphatidylcholine-specific phospholipase D

Nomenclature	Monoacylglycerol lipase	Fatty acid amide hydrolase	Fatty acid amide hydrolase-2	N-Acylethanolamine acid amidase
Common abbreviation	MGL	FAAH	FAAH2	NAAA
HGNC, UniProt	MGLL, Q99685	FAAH, O00519	FAAH2, Q6GMR7	NAAA, Q02083
EC number	3.1.1.23	3.5.1.-	3.5.1.-	3.5.1.-
Rank order of affinity	2-oleoyl glycerol = 2-arachidonoylglycerol >> anandamide 199	anandamide > oleamide > N-oleoylethanolamide > N-palmitoylethanolamine 211	oleamide > N-oleoylethanolamide > anandamide > N-palmitoylethanolamine 211	N-palmitoylethanolamine > MEA > SEA ≥ N-oleoylethanolamide > anandamide 210
Selective inhibitors (pIC50)	JZL184 (8.1) 203	JNJ1661010 (7.8) 200, OL135 (7.4) 211, PF750 (6.3 – 7.8) 193, URB597 (6.3 – 7.0) 211, PF3845 (6.6) 194	OL135 (7.9) 211, URB597 (7.5 – 8.3) 211	S-OOPP (6.4 - Rat) 208, CCP (5.3) 209

Nomenclature	Glutamic acid decarboxylase 1	Glutamic acid decarboxylase 2
Common abbreviation	GAD1	GAD2
HGNC, UniProt	GAD1, Q99259	GAD2, Q05329
EC number	4.1.1.15: L-glutamic acid + H+ -> GABA + CO2
Endogenous substrates	L-glutamic acid, L-aspartic acid
Products	GABA
Cofactors	pyridoxal phosphate
Selective inhibitors (pIC50)	s-allylglycine
Comment	L-aspartic acid is a less rapidly metabolised substrate of mouse brain glutamic acid decarboxylase generating β-alanine 215. Autoantibodies against GAD1 and GAD2 are elevated in type 1 diabetes mellitus and neurological disorders (see Further reading)

Nomenclature	aldehyde dehydrogenase 9 family, member A1 (γ-aminobutyraldehyde dehydrogenase)
HGNC, UniProt	ALDH9A1, P49189
EC number	1.2.1.47: 4-trimethylammoniobutanal + NAD + H2O = 4-trimethylammoniobutanoate + NADPH + 2 H+, 1.2.1.3: an aldehyde + H2O + NAD = a carboxylate + 2 H+ + NADH, 1.2.1.19: 4-aminobutanal + NAD + H2O = GABA + NADH + H+
Cofactors	NAD

Nomenclature	4-aminobutyrate aminotransferase (GABA transaminase)
Common abbreviation	GABA-T
HGNC, UniProt	ABAT, P80404
EC number	2.6.1.19: GABA + α-ketoglutaric acid = L-glutamic acid + 4-oxobutanoate, 2.6.1.22: (S)-3-amino-2-methylpropanoate + α-ketoglutaric acid = 2-methyl-3-oxopropanoate + L-glutamic acid
Cofactors	pyridoxal phosphate
Selective inhibitors (pIC50)	vigabatrin 214
Comment	vigabatrin is an irreversible inhibitor of GABA-T 214

Nomenclature	aldehyde dehydrogenase 5 family, member A1 (succinic semialdehyde dehydrogenase)
Common abbreviation	SSADH
HGNC, UniProt	ALDH5A1, P51649
EC number	1.2.1.24: 4-oxobutanoate + NAD + H2O = succinic acid + NADH + 2 H+, 4-hydroxy-trans-2-nonenal + NAD + H2O = 4-hydroxy-trans-2-nonenoate + NADH + 2 H+
Cofactors	NAD

Nomenclature	PLCβ1	PLCβ2	PLCβ3	PLCβ4
HGNC, UniProt	PLCB1, Q9NQ66	PLCB2, Q00722	PLCB3, Q01970	PLCB4, Q15147
Endogenous activators	Gαq, Gα11, Gβγ 228,248,258	Gα16, Gβγ, Rac2 (RAC2, P15153) 221,231,232,237,248	Gαq, Gβγ 222,237,248	Gαq 233

Nomenclature	PLCγ1	PLCγ2	PLCδ1	PLCδ3	PLCδ4
HGNC, UniProt	PLCG1, P19174	PLCG2, P16885	PLCD1, P51178	PLCD3, Q8N3E9	PLCD4, Q9BRC7
Endogenous activators	PIP3 217	PIP3, Rac1 (RAC1, P63000), Rac2 (RAC2, P15153), Rac3 (RAC3, P60763) 217,251,263	Transglutaminase II, p122-RhoGAP, spermine, Gβγ 225,229,244,248	–	–
Endogenous inhibitors	–	–	Sphingomyelin 249	–	–

Nomenclature	PLCε1	PLCζ1	PLCη1	PLCη2
HGNC, UniProt	PLCE1, Q9P212	PLCZ1, Q86YW0	PLCH1, Q4KWH8	PLCH2, O75038
Endogenous activators	Ras, rho 259,264	–	–	Gβγ 266

Nomenclature	sPLA2-1B	sPLA2-2A	sPLA2-2D	sPLA2-2E	sPLA2-2F	sPLA2-3	sPLA2-10	sPLA2-12A
HGNC, UniProt	PLA2G1B, P04054	PLA2G2A, P14555	PLA2G2D, Q9UNK4	PLA2G2E, Q9NZK7	PLA2G2F, Q9BZM2	PLA2G3, Q9NZ20	PLA2G10, O15496	PLA2G12A, Q9BZM1

Nomenclature	cPLA2-4A	cPLA2-4B	cPLA2-4C	cPLA2-4D	cPLA2-4E	cPLA2-4F
HGNC, UniProt	PLA2G4A, P47712	PLA2G4B, P0C869	PLA2G4C, Q9UP65	PLA2G4D, Q86XP0	PLA2G4E, Q3MJ16	PLA2G4F, Q68DD2
Comment	cPLA2-4A also expresses lysophospholipase (EC 3.1.1.5) activity 256.	–	–	–	–	–

Nomenclature	PLA2-G5	iPLA2-G6	PLA2-G7	platelet-activating factor acetylhydrolase 2, 40kDa
HGNC, UniProt	PLA2G5, P39877	PLA2G6, O60733	PLA2G7, Q13093	PAFAH2, Q99487
Comment	–	–	–	PAFAH2 also expresses PAF hydrolase activity (EC 3.1.1.47)

Nomenclature	PLD1	PLD2
HGNC, UniProt	PLD1, Q13393	PLD2, O14939
Endogenous activators	Arf1 (ARF1, P84077), PIP2, RhoA, PKC evoked phosphorylation, RalA 226,241	Arf1 (ARF1, P84077), oleic acid 255, PIP2 240
Endogenous inhibitor	Gβγ 252	Gβγ 252
Selective inhibitors (pIC50)	–	VU0364739 (7.7) 236

Nomenclature	Lipin1	Lipin2	Lipin3	PPA2A	PPA2B	PPA3A	phosphatase and tensin homolog
HGNC, UniProt	LPIN1, Q14693	LPIN2, Q92539	LPIN3, Q9BQK8	PPAP2A, O14494	PPAP2B, O14495	PPAP2C, O43688	PTEN, P60484
EC number	3.1.3.4	3.1.3.4	3.1.3.4	3.1.3.4	3.1.3.4	3.1.3.4	3.1.3.16, 3.1.3.48, 3.1.3.67
Substrates	–	phosphatidic acid	–	–	phosphatidic acid	–	phosphatidylinositol (3,4,5)-trisphosphate

Nomenclature	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta	phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma
Common abbreviation	p110α/PIK3CA	p110β/PIK3CB	p110δ/PIK3CD	p110γ/PIK3CG
HGNC, UniProt	PIK3CA, P42336	PIK3CB, P42338	PIK3CD, O00329	PIK3CG, P48736
EC number	2.7.1.153, 2.7.11.1	2.7.1.153	2.7.1.153	2.7.1.153
Selective inhibitors (pIC50)	–	–	–	CZC 24832 (pKd 7.7) 220

Nomenclature	phosphoinositide-3-kinase, regulatory subunit 1 (alpha)	phosphoinositide-3-kinase, regulatory subunit 2 (beta)	phosphoinositide-3-kinase, regulatory subunit 3 (gamma)	phosphoinositide-3-kinase, regulatory subunit 4	phosphoinositide-3-kinase, regulatory subunit 5	phosphoinositide-3-kinase, regulatory subunit 6
Common abbreviation	p85α/PIK3R1	p85β/PIK3R2	p55γ/PIK3R3	p150/VPS15/PIK3R4	p101/PIK3R5	p87/PIK3R6
HGNC, UniProt	PIK3R1, P27986	PIK3R2, O00459	PIK3R3, Q92569	PIK3R4, Q99570	PIK3R5, Q8WYR1	PIK3R6, Q5UE93
EC number	–	–	–	2.7.11.1	–	–

Nomenclature	phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 alpha	phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 beta	phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 gamma
Common abbreviation	C2α/PIK3C2A	C2β/PIK3C2B	C2γ/PIK3C2G
HGNC, UniProt	PIK3C2A, O00443	PIK3C2B, O00750	PIK3C2G, O75747
EC number	2.7.1.154	2.7.1.154	2.7.1.154

Nomenclature	phosphatidylinositol 3-kinase, catalytic subunit type 3	phosphoinositide-3-kinase, regulatory subunit 4
Common abbreviation	VPS34/PIK3C3	p150/VPS15/PIK3R4
HGNC, UniProt	PIK3C3, Q8NEB9	PIK3R4, Q99570

Nomenclature	phosphatidylinositol 4-kinase, catalytic, alpha	phosphatidylinositol 4-kinase, catalytic, beta	phosphatidylinositol 4-kinase type 2 alpha	phosphatidylinositol 4-kinase type 2 beta
Common abbreviation	PI4KIIIα/PIK4CA	PI4KIIIβ/PIK4CB	PI4KIIα/PI4K2A	PI4KIIβ/PI4K2B
HGNC, UniProt	PI4KA, P42356	PI4KB, Q9UBF8	PI4K2A, Q9BTU6	PI4K2B, Q8TCG2
Endogenous activation	–	PKD-mediated phosphorylation 227	–	–
(Sub)family-selective inhibitors (pIC50)	wortmannin (6.7 – 6.8) 223,243	wortmannin (6.7 – 6.8) 223,243	adenosine (4.5 – 5.0) 261	adenosine (4.5 – 5.0) 261
Selective inhibitors (pIC50)	–	PIK-93 234	–	–

Nomenclature	phosphatidylinositol-4-phosphate 5-kinase, type I, alpha	phosphatidylinositol-4-phosphate 5-kinase, type I, beta	phosphatidylinositol-4-phosphate 5-kinase, type I, gamma
Common abbreviation	PIP5K1A	PIP5K1B	PIP5K1C
HGNC, UniProt	PIP5K1A, Q99755	PIP5K1B, O14986	PIP5K1C, O60331
EC number	2.7.1.68	2.7.1.68	2.7.1.68

Nomenclature	phosphatidylinositol-5-phosphate 4-kinase, type II, alpha	phosphatidylinositol-5-phosphate 4-kinase, type II, beta	phosphatidylinositol-5-phosphate 4-kinase, type II, gamma
Common abbreviation	PIP4K2A	PIP4K2B	PIP4K2G
HGNC, UniProt	PIP4K2A, P48426	PIP4K2B, P78356	PIP4K2C, Q8TBX8
EC number	2.7.1.149	2.7.1.149	2.7.1.149

Nomenclature	Haem oxygenase 1	Haem oxygenase 2
Common abbreviation	HO1	HO2
HGNC, UniProt	HMOX1, P09601	HMOX2, P30519
EC number	1.14.99.3	1.14.99.3

Nomenclature	Cystathionine β-synthase	Cystathionine γ-lyase	L-Cysteine:2-oxoglutarate aminotransferase	3-Mercaptopyruvate sulfurtransferase
Common abbreviation	CBS	CSE	CAT	MPST
HGNC, UniProt	CBS, P35520	CTH, P32929	CCBL1, Q16773	MPST, P25325
EC number	4.2.1.22	4.4.1.1	4.4.1.13	2.8.1.2
Endogenous substrates	L-homocysteine, L-cysteine (Km 6x10-3 M) 269	L-cysteine	L-cysteine	3-mercaptopyruvic acid (Km 1.2x10-3 M) 270
Products	cystathionine	NH3, pyruvic acid	NH3, pyruvic acid	pyruvic acid
Cofactors	pyridoxal phosphate	pyridoxal phosphate	pyridoxal phosphate	Zn2+
Inhibitors (pIC50)	aminooxyacetic acid	propargylglycine	–	–

Nomenclature	IP3 kinase A	IP3 kinase B	IP3 kinase C
HGNC, UniProt	ITPKA, P23677	ITPKB, P27987	ITPKC, Q96DU7

Nomenclature	INPP1	INPP4A, INPP4B	INPP5A, INPP5B, INPP5D, INPP5E, INPP5J, INPP5K, INPPL1, OCRL, SYNJ1, SYNJ2
HGNC, UniProt	INPP1, P49441	INPP4A, Q96PE3; INPP4B, O15327	INPP5A, Q14642; INPP5B, P32019; INPP5D, Q92835; INPP5E, Q9NRR6; INPP5J, Q15735; INPP5K, Q9BT40; INPPL1, O15357; OCRL, Q01968; SYNJ1, O43426; SYNJ2, O15056
EC number	3.1.3.57	3.1.3.36, 3.1.3.36	3.1.3.56, 3.1.3.56, 3.1.3.86, 3.1.3.36, 3.1.3.56, 3.1.3.56, 3.1.3.86, 3.1.3.36, 3.1.3.36, 3.1.3.36

Nomenclature	IMPase 1	IMPase 2
HGNC, UniProt	IMPA1, P29218	IMPA2, O14732
EC number	3.1.3.25	3.1.3.25
Rank order of affinity	inositol 4-phosphate > inositol 3-phosphate > inositol 1-phosphate 274	–

Nomenclature	acetyl-CoA acetyltransferase 1	acetyl-CoA acetyltransferase 2
HGNC, UniProt	ACAT1, P24752	ACAT2, Q9BWD1
EC number	2.3.1.9: acetyl CoA + acetyl CoA = acetoacetyl CoA + coenzyme A	2.3.1.9: acetyl CoA + acetyl CoA = acetoacetyl CoA + coenzyme A

Nomenclature	hydroxymethylglutaryl-CoA synthase 1	hydroxymethylglutaryl-CoA synthase 2
HGNC, UniProt	HMGCS1, Q01581	HMGCS2, P54868
EC number	2.3.3.10: acetyl CoA + H2O + acetoacetyl CoA -> (S)-3-hydroxy-3-methylglutaryl-CoA + coenzyme A	2.3.3.10: acetyl CoA + H2O + acetoacetyl CoA -> (S)-3-hydroxy-3-methylglutaryl-CoA + coenzyme A
Comment	HMGCoA synthase is found in cytosolic and mitochondrial versions; the former associated with (R)-mevalonate synthesis and the latter with ketogenesis.	–

Nomenclature	hydroxymethylglutaryl-CoA reductase
HGNC, UniProt	HMGCR, P04035
EC number	1.1.1.34: (S)-3-hydroxy-3-methylglutaryl-CoA + NADPH -> (R)-mevalonate + coenzyme A + NADP+
Selective inhibitors (pIC50)	lovastatin (Competitive) (pKi 9.22) 280, rosuvastatin (Competitive) (8.3) 283, atorvastatin (Competitive) (8.1) 283, simvastatin (Competitive) (7.96) 283, fluvastatin (Competitive) (7.55) 283
Comment	HMGCoA reductase is associated with intracellular membranes; enzymatic activity is inhibited by phosphorylation by AMP-activated kinase. The enzymatic reaction is a three-step reaction involving the intermediate generation of mevaldehyde-CoA and mevaldehyde.

Nomenclature	mevalonate kinase
HGNC, UniProt	MVK, Q03426
EC number	2.7.1.36: ATP + (R)-mevalonate -> ADP + (R)-5-phosphomevalonate
Comment	Mevalonate kinase activity is regulated by the downstream products farnesyl diphosphate and geranyl diphosphate as an example of feedback inhibition.

Nomenclature	phosphomevalonate kinase
HGNC, UniProt	PMVK, Q15126
EC number	2.7.4.2: ATP + (R)-5-phosphomevalonate = ADP + (R)-5-diphosphomevalonate

Nomenclature	diphosphomevalonate decarboxylase
HGNC, UniProt	MVD, P53602
EC number	4.1.1.33: ATP + (R)-5-diphosphomevalonate -> ADP + isopentenyl diphosphate + PO34- + CO2

Nomenclature	isopentenyl-diphosphate Δ-isomerase 1	isopentenyl-diphosphate Δ-isomerase 2
HGNC, UniProt	IDI1, Q13907	IDI2, Q9BXS1
EC number	5.3.3.2: isopentenyl diphosphate = dimethylallyl diphosphate	5.3.3.2: isopentenyl diphosphate = dimethylallyl diphosphate

Nomenclature	geranylgeranyl diphosphate synthase
HGNC, UniProt	GGPS1, O95749
EC number	2.5.1.1: dimethylallyl diphosphate + isopentenyl diphosphate = geranyl diphosphate + diphosphate ion, 2.5.1.10: geranyl diphosphate + isopentenyl diphosphate -> trans,trans-farnesyl diphosphate + diphosphate ion, 2.5.1.29: trans,trans-farnesyl diphosphate + isopentenyl diphosphate -> geranylgeranyl diphosphate + diphosphate ion

Nomenclature	farnesyl diphosphate synthase
HGNC, UniProt	FDPS, P14324
EC number	2.5.1.1: dimethylallyl diphosphate + isopentenyl diphosphate = geranyl diphosphate + diphosphate ion, 2.5.1.10: geranyl diphosphate + isopentenyl diphosphate -> trans,trans-farnesyl diphosphate + diphosphate ion
Selective inhibitors (pIC50)	risedronate (8.4) 281, alendronate (6.34) 281

Nomenclature	squalene synthase
HGNC, UniProt	FDFT1, P37268
EC number	2.5.1.21: 2 trans,trans-farnesyl diphosphate -> presqualene diphosphate + diphosphate ion, presqualene diphosphate + NAD(P)H + H+ -> squalene + diphosphate + NAD(P)+
Cofactors	NADPH 285
Selective inhibitors (pIC50)	zaragozic acid A (pKi 10.1 - Rat) 282, FTI 276 (9.3) 284, zaragozic acid A (9.15) 286

Nomenclature	Caspase 1	Caspase 2	Caspase 3	Caspase 4
HGNC, UniProt	CASP1, P29466	CASP2, P42575	CASP3, P42574	CASP4, P49662
EC number	3.4.22.36	3.4.22.55	3.4.22.56	3.4.22.57
Endogenous activators	–	–	Caspase 8, caspase 9, caspase 10, GrB	–
Endogenous substrates	Rho GDP dissociation inhibitor beta, parkin, pro-caspase 4, pro-interleukin-1β	–	huntingtin, retinoblastoma-associated protein, caspase 3, ICAD, PARP, PKCδ, pro-caspase 7	pro-caspase 1
Activators	–	–	PAC1 301, PETCM 295	–
Selective inhibitors (pIC50)	Z-YVAD-FMK 287	Z-VDVAD-FMK 291	AZ10417808 303, Z-DEVD-FMK 288, Z-DQMD-FMK 294	–
Comment	Consists of caspase-1 subunit p20 and caspase-1 subunit p10 (see Uniprot entry)	Consists of caspase-2 subunit p18, caspase-2 subunit p13, and caspase-2 subunit p12 (see Uniprot entry)	Consists of caspase-3 subunit p17 and caspase-3 subunit p12 (see Uniprot entry)	Consists of caspase-4 subunit 1 and caspase-4 subunit 2 (see Uniprot entry)

Nomenclature	Caspase 5	Caspase 6	Caspase 7	Caspase 8
HGNC, UniProt	CASP5, P51878	CASP6, P55212	CASP7, P55210	CASP8, Q14790
EC number	3.4.22.58	3.4.22.59	3.4.22.60	3.4.22.61
Endogenous activators	–	Caspase 8, caspase 9, caspase 10, GrB	Caspase 8, caspase 9, caspase 10, GrB	DISC
Endogenous substrates	–	–	huntingtin, retinoblastoma-associated protein, caspase 3, ICAD, PARP, PKCδ, Pro-caspase 7	BH3 interacting-domain death agonist, FLICE-like inhibitory protein, caspase 8, pro-caspase 3, pro-caspase 6, pro-caspase 7
Selective inhibitors (pIC50)	Z-WEHD-FMK 299	Z-VEID-FMK 302	–	Z-IETD-FMK 293
Comment	Consists of caspase-5 subunit p20 and caspase-5 subunit p10 (see Uniprot entry)	Consists of caspase-6 subunit p18 and caspase-6 subunit p11 (see Uniprot entry)	Consists of caspase-7 subunit p20 and caspase-7 subunit p11 (see Uniprot entry)	Consists of caspase-8 subunit p18 and caspase-8 subunit p10 (see Uniprot entry)

Nomenclature	Caspase 9	Caspase 10	Caspase 14
HGNC, UniProt	CASP9, P55211	CASP10, Q92851	CASP14, P31944
EC number	3.4.22.62	3.4.22.63	3.4.22.-
Endogenous activators	–	DISC	–
Endogenous substrates	caspase 9, PARP, pro-caspase 3, pro-caspase 6, pro-caspase 7	caspase 10, pro-caspase 3, pro-caspase 6, pro-caspase 7	–
Selective inhibitors (pIC50)	Z-LEHD-FMK 298	–	–
Comment	Consists of caspase-9 subunit p35 and caspase-9 subunit p10 (see Uniprot entry)	Consists of caspase-10 subunit p23/17 and caspase-10 subunit p12 (see Uniprot entry)	Consists of caspase-14 subunit p19 and caspase-14 subunit p10 (see Uniprot entry)

Nomenclature	Aminopeptidase A	Leucyl-cysteinyl aminopeptidase	Leukotriene A4 hydrolase	Neutral endopeptidase
HGNC, UniProt	DNPEP, Q9ULA0	LNPEP, Q9UIQ6	LTA4H, P09960	MME, P08473
EC number	3.4.11.21	3.4.11.3	3.3.2.6	3.4.24.11
Endogenous substrates	–	–	LTA4	enkephalins
Selective inhibitors (pIC50)	–	–	–	thiorphan
Inhibitors (pIC50)	–	–	bestatin 300	–
Comment	Hydrolyses CCK-8 (CCK, P06307) 297, angiotensin II (AGT, P01019) 307, neurokinin B (TAC3, Q9UHF0), chromogranin A (CHGA, P10645), kallidin (KNG1, P01042) 292	Hydrolyses AVP (AVP, P01178), oxytocin (OXT, P01178), kallidin (KNG1, P01042), [Met]enkephalin (PENK, P01210), dynorphin A (PDYN, P01213)	–	–

Nomenclature	Angiotensin-converting enzyme	Angiotensin-converting enzyme 2	Endothelin-converting enzyme 1	Endothelin-converting enzyme 2
Common abbreviation	ACE1	ACE2	ECE1	ECE2
HGNC, UniProt	ACE, P12821	ACE2, Q9BYF1	ECE1, P42892	ECE2, O60344
EC number	3.4.15.1	3.4.15.1	3.4.24.71	3.4.24.71
Endogenous substrates	angiotensin I (AGT, P01019) > angiotensin II (AGT, P01019)	angiotensin I (AGT, P01019) > angiotensin-(1-9) (AGT, P01019) 290	ET-1 (EDN1, P05305), ET-2 (EDN2, P20800), ET-3 (EDN3, P14138)	ET-1 (EDN1, P05305), ET-2 (EDN2, P20800), ET-3 (EDN3, P14138)
Selective inhibitors (pIC50)	captopril	captopril	SM19712 305	–
Comment	Hip-His Leu has been used experimentally as a probe for ACE1. ACE1 appears to express a distinct GPI hydrolase activity 296.	Abz-Ser-Pro-Tyr(NO2)-OH has been used experimentally as a probe for ACE2	–	–

Nomenclature	Aminopeptidase N	Aminopeptidase O	Aminopeptidase Q	Arginyl aminopeptidase	Arginyl aminopeptidase-like 1	Aminopeptidase-like 1
HGNC, UniProt	ANPEP, P15144	C9orf3, Q8N6M6	–, Q6Q4G3	RNPEP, Q9H4A4	RNPEPL1, Q9HAU8	NPEPL1, Q8NDH3
EC number	3.4.11.2	3.4.11.-	3.4.11.-	3.4.11.6	3.4.11.-	3.4.11.-

Nomenclature	Endoplasmic reticulum aminopeptidase 1	Endoplasmic reticulum aminopeptidase 2	Glutamyl aminopeptidase	Leucine aminopeptidase 3	Methionyl aminopeptidase 1	Methionyl aminopeptidase 2
HGNC, UniProt	ERAP1, Q9NZ08	ERAP2, Q6P179	ENPEP, Q07075	LAP3, P28838	METAP1, P53582	METAP2, P50579
EC number	3.4.11.-	3.4.11.-	3.4.11.7	3.4.11.1	3.4.11.3, 3.4.11.18	3.4.11.18

Nomenclature	Methionyl aminopeptidase type 1D (mitochondrial)	Puromycin-sensitive aminopeptidase	Puromycin-sensitive aminopeptidase-like protein	TRH-specific aminopeptidase	X-prolyl aminopeptidase 1	X-prolyl aminopeptidase 2
HGNC, UniProt	METAP1D, Q6UB28	NPEPPS, P55786	–	TRHDE, Q9UKU6	XPNPEP1, Q9NQW7	XPNPEP2, O43895
EC number	3.4.11.18	3.4.11.14	–	3.4.19.6	3.4.11.9	3.4.11.9

Nomenclature	X-prolyl aminopeptidase 3	Carboxypeptidase D	AE binding protein 1	Carboxypeptidase A1 (pancreatic)	Carboxypeptidase A2 (pancreatic)	Carboxypeptidase A3 (mast cell)
HGNC, UniProt	XPNPEP3, Q9NQH7	CPD, O75976	AEBP1, Q8IUX7	CPA1, P15085	CPA2, P48052	CPA3, P15088
EC number	3.4.11.9	3.4.17.22	–	3.4.17.1	3.4.17.15	3.4.17.1

Nomenclature	Carboxypeptidase A4	Carboxypeptidase A5	Carboxypeptidase A6	Carboxypeptidase B1 (tissue)	Carboxypeptidase B2 (plasma)	Carboxypeptidase E
HGNC, UniProt	CPA4, Q9UI42	CPA5, Q8WXQ8	CPA6, Q8N4T0	CPB1, P15086	CPB2, Q96IY4	CPE, P16870
EC number	3.4.17.-	3.4.17.1	3.4.17.1	3.4.17.2	3.4.17.20	3.4.17.10

Nomenclature	Carboxypeptidase M	Carboxypeptidase N, polypeptide 1	Carboxypeptidase N, polypeptide 2	Carboxypeptidase O	Carboxypeptidase Q	Carboxypeptidase X (M14 family), member 1
HGNC, UniProt	CPM, P14384	CPN1, P15169	CPN2, P22792	CPO, Q8IVL8	CPQ, –	CPXM1, Q96SM3
EC number	3.4.17.12	3.4.17.3	–	3.4.17.-	–	3.4.17.-

Nomenclature	Carboxypeptidase X (M14 family), member 2	Carboxypeptidase Z	Carnosine dipeptidase 1 (metallopeptidase M20 family)	Carnosine dipeptidase 2	Folate hydrolase (prostate-specific membrane antigen) 1	Folate hydrolase 1B
HGNC, UniProt	CPXM2, Q8N436	CPZ, Q66K79	CNDP1, Q96KN2	CNDP2, Q96KP4	FOLH1, Q04609	FOLH1B, Q9HBA9
EC number	–	3.4.17.-	3.4.13.20	3.4.13.18	3.4.17.21	–

Nomenclature	N-Acetylated α-linked acidic dipeptidase-like 1	N-Acetylated α-linked acidic dipeptidase 2
HGNC, UniProt	NAALADL1, Q9UQQ1	NAALAD2, Q9Y3Q0
EC number	3.4.17.21	3.4.17.21

Nomenclature	MMP1	MMP2	MMP3	MMP7	MMP8	MMP9
HGNC, UniProt	MMP1, P03956	MMP2, P08253	MMP3, P08254	MMP7, P09237	MMP8, P22894	MMP9, P14780
EC number	3.4.24.7	3.4.24.24	3.4.24.17	3.4.24.23	3.4.24.34	3.4.24.35
Selective inhibitors (pIC50)	–	ARP100 304	–	–	–	–

Nomenclature	MMP10	MMP11	MMP12	MMP13	MMP14	MMP15
HGNC, UniProt	MMP10, P09238	MMP11, P24347	MMP12, P39900	MMP13, P45452	MMP14, P50281	MMP15, P51511
EC number	3.4.24.22	3.4.24.-	3.4.24.65	3.4.24.-	3.4.24.80	3.4.24.-
Selective inhibitors (pIC50)	–	–	–	CL82198 289, WAY170523 289	–	–

Nomenclature	MMP16	MMP17	MMP19	MMP20	MMP21	MMP23	MMP24
HGNC, UniProt	MMP16, P51512	MMP17, Q9ULZ9	MMP19, Q99542	MMP20, O60882	MMP21, Q8N119	MMP23B, O75900	MMP24, Q9Y5R2
EC number	3.4.24.-	3.4.24.-	3.4.24.-	3.4.24.-	3.4.24.-	3.4.24.-	3.4.24.-

Nomenclature	MMP25	MMP26	MMP27	MMP28
HGNC, UniProt	MMP25, Q9NPA2	MMP26, Q9NRE1	MMP27, Q9H306	MMP28, Q9H239
EC number	3.4.24.-	3.4.24.-	3.4.24.-	3.4.24.-

Nomenclature	ADAM2	ADAM7	ADAM8	ADAM9	ADAM10	ADAM11	ADAM12	ADAM15	ADAM17
HGNC, UniProt	ADAM2, Q99965	ADAM7, Q9H2U9	ADAM8, P78325	ADAM9, Q13443	ADAM10, O14672	ADAM11, O75078	ADAM12, O43184	ADAM15, Q13444	ADAM17, P78536
EC number	–	–	3.4.24.-	3.4.24.-	3.4.24.81	–	3.4.24.-	–	3.4.24.86

Nomenclature	ADAM18	ADAM19	ADAM20	ADAM21	ADAM22	ADAM23	ADAM28	ADAM29	ADAM30	ADAM32	ADAM33
HGNC, UniProt	ADAM18, Q9Y3Q7	ADAM19, Q9H013	ADAM20, O43506	ADAM21, Q9UKJ8	ADAM22, Q9P0K1	ADAM23, O75077	ADAM28, Q9UKQ2	ADAM29, Q9UKF5	ADAM30, Q9UKF2	ADAM32, Q8TC27	ADAM33, Q9BZ11
EC number	–	–	–	–	–	–	–	–	–	–	3.4.24.-

Nomenclature	ADAMTS1	ADAMTS2	ADAMTS3	ADAMTS4	ADAMTS5	ADAMTS6	ADAMTS7	ADAMTS8	ADAMTS9	ADAMTS10
HGNC, UniProt	ADAMTS1, Q9UHI8	ADAMTS2, O95450	ADAMTS3, O15072	ADAMTS4, O75173	ADAMTS5, Q9UNA0	ADAMTS6, Q9UKP5	ADAMTS7, Q9UKP4	ADAMTS8, Q9UP79	ADAMTS9, Q9P2N4	ADAMTS10, Q9H324
EC number	3.4.24.-	3.4.24.14	–	3.4.24.82	3.4.24.-	–	–	–	–	–

Nomenclature	ADAMTS12	ADAMTS13	ADAMTS14	ADAMTS15	ADAMTS16	ADAMTS17	ADAMTS18	ADAMTS19	ADAMTS20
HGNC, UniProt	ADAMTS12, P58397	ADAMTS13, Q76LX8	ADAMTS14, Q8WXS8	ADAMTS15, Q8TE58	ADAMTS16, Q8TE57	ADAMTS17, Q8TE56	ADAMTS18, Q8TE60	ADAMTS19, Q8TE59	ADAMTS20, P59510
Comment	–	Loss-of-function mutations of autoimmune antibodies are associated with thrombotic thrombocytopenic purpura	–	–	–	–	–	–	–

Nomenclature	Cathepsin A	Vitellogenic carboxypeptidase-like protein	Prolylcarboxypeptidase	Serine carboxypeptidase 1	Dipeptidyl peptidase 4	Dipeptidyl-peptidase 7
HGNC, UniProt	CTSA, P10619	CPVL, Q9H3G5	PRCP, P42785	SCPEP1, Q9HB40	DPP4, P27487	DPP7, Q9UHL4
EC number	3.4.16.5	3.4.16.-	3.4.16.2	3.4.16.-	3.4.14.5	3.4.14.2
Endogenous substrates	–	–	–	–	glucagon-like peptide 1	–

Nomenclature	Common abbreviation	HGNC, UniProt	EC number	Comment
G protein-coupled receptor kinase 1	GRK1	GRK1, Q15835	2.7.11.14	–
beta adrenergic receptor kinase 1	GRK2	ADRBK1, P25098	2.7.11.15	Protein kinase C-mediated phosphorylation increases membrane association 316,353
beta adrenergic receptor kinase 2	GRK3	ADRBK2, P35626	2.7.11.15	–
G protein-coupled receptor kinase 4	GRK4	GRK4, P32298	2.7.11.16	Inhibited by Ca2+/calmodulin (CALM2, CALM3, CALM1, P62158) 345
G protein-coupled receptor kinase 5	GRK5	GRK5, P34947	2.7.11.16	Phosphorylated and inhibited by protein kinase C 344
G protein-coupled receptor kinase 6	GRK6	GRK6, P43250	2.7.11.16	–
G protein-coupled receptor kinase 7	GRK7	GRK7, Q8WTQ7	2.7.11.14, 2.7.11.16	–

Nomenclature	protein kinase A
UniProtKB AC	–
EC number	2.7.11.11
Activators	N6 benzyl-cAMP 315
Inhibitors (pIC50)	Rp-cAMPS
Radioligands (Kd)	[3H]cAMP (Activator)

Nomenclature	v-akt murine thymoma viral oncogene homolog 1	v-akt murine thymoma viral oncogene homolog 2	v-akt murine thymoma viral oncogene homolog 3
Common abbreviation	Akt1	Akt2	AKT3
HGNC, UniProt	AKT1, P31749	AKT2, P31751	AKT3, Q9Y243
Selective inhibitors (pIC50)	GSK690693 330	–	–

Nomenclature	protein kinase C, alpha	protein kinase C, beta	protein kinase C, gamma
Common abbreviation	PKCα	PKCβ	PKCγ
HGNC, UniProt	PRKCA, P17252	PRKCB, P05771	PRKCG, P05129
Selective inhibitors (pIC50)	–	ruboxistaurin (8.3) 334, CGP53353 (6.4) 313	–

Nomenclature	protein kinase C, delta	protein kinase C, epsilon	protein kinase C, eta	protein kinase C, theta	protein kinase D1
Common abbreviation	PKCδ	PKCε	PKCη	PKCθ	PKD1
HGNC, UniProt	PRKCD, Q05655	PRKCE, Q02156	PRKCH, P24723	PRKCQ, Q04759	PRKD1, Q15139

Nomenclature	protein kinase C, iota	protein kinase C, zeta
Common abbreviation	PKCι	PKCζ
HGNC, UniProt	PRKCI, P41743	PRKCZ, Q05513
Endogenous activators	–	arachidonic acid 343
Comment	Known as PKCλ in rodents	–

Nomenclature	Protein kinase G (PKG) 1	Protein kinase G (PKG) 2
Common abbreviation	PKG1	PKG2
HGNC, UniProt	PRKG1, Q13976	PRKG2, Q13237
EC number	2.7.11.12	2.7.11.12
Selective inhibitors (pIC50)	Rp-8-CPT-cGMPS 312	–

Nomenclature	mitogen-activated protein kinase 1	mitogen-activated protein kinase 3
Common abbreviation	ERK2	ERK1
HGNC, UniProt	MAPK1, P28482	MAPK3, P27361

Nomenclature	mitogen-activated protein kinase 8	mitogen-activated protein kinase 9	mitogen-activated protein kinase 10
Common abbreviation	JNK1	JNK2	JNK3
HGNC, UniProt	MAPK8, P45983	MAPK9, P45984	MAPK10, P53779
Selective inhibitors (pIC50)	SP600125 (7.4) 311	SP600125 (7.4) 311	SP600125 (7.05) 311

Nomenclature	mitogen-activated protein kinase 11	mitogen-activated protein kinase 12	mitogen-activated protein kinase 13	mitogen-activated protein kinase 14
Common abbreviation	p38β	p38γ	p38δ	p38α
HGNC, UniProt	MAPK11, Q15759	MAPK12, P53778	MAPK13, O15264	MAPK14, Q16539
Selective inhibitors (pIC50)	SB202190 341, SB203580 (pKi 7.0) 324	–	–	SB203580 (pKi 8.0) 324

Nomenclature	Systematic nomenclature	Common abbreviation	HGNC, UniProt	EC number	Selective inhibitors (pIC50)
Rho-associated, coiled-coil containing protein kinase 1	ROCK1	Rho kinase 1	ROCK1, Q13464	2.7.11.1	fasudil (Rabbit) 310, Y27632 (pKi 6.9) 351
Rho-associated, coiled-coil containing protein kinase 2	ROCK2	Rho kinase 2	ROCK2, O75116	2.7.11.1	fasudil (Rabbit) 310, Y27632 (pKi 6.9) 351

Nomenclature	Common abbreviation	HGNC, UniProt	EC number	Comment
dystrophia myotonica-protein kinase	DMPK1	DMPK, Q09013	2.7.11.1	Reduced expression of DMPK is associated with myotonic dystrophy 1 336
CDC42 binding protein kinase gamma (DMPK-like)	DMPK2	CDC42BPG, Q6DT37	2.7.11.1	–
CDC42 binding protein kinase alpha (DMPK-like)	MRCKα	CDC42BPA, Q5VT25	2.7.11.1	Reported to have a role in cellular iron regulation 317
CDC42 binding protein kinase beta (DMPK-like)	MRCKβ	CDC42BPB, Q9Y5S2	2.7.11.1	Reported to be involved in cell migration 332
citron (rho-interacting, serine/threonine kinase 21)	CRIK	CIT, O14578	2.7.11.1	Shares structural homology with the Rho kinases
Microtubule associated serine/threonine kinase 1	MAST1	MAST1, Q9Y2H9	2.7.11.1	Members of the microtubule-associated serine/threonine kinase family appear to have a role in platelet production 335 and inflammatory bowel disease 340
Microtubule associated serine/threonine kinase 2	MAST2	MAST2, Q6P0Q8	2.7.11.1	See comment for MAST1
Microtubule associated serine/threonine kinase 3	MAST3	MAST3, O60307	2.7.11.1	See comment for MAST1
Microtubule associated serine/threonine kinase 4	MAST4	MAST4, O15021	2.7.11.1	See comment for MAST1
Microtubule associated serine/threonine kinase-like	MASTL	MASTL, Q96GX5	2.7.11.1	See comment for MAST1
large tumor suppressor kinase 1	LATS1	LATS1, O95835	2.7.11.1	The large tumour suppressor protein kinases are phosphorylated and activated by MST2 kinase (serine/threonine kinase 3, STK3, Q13188, 314)
large tumor suppressor kinase 2	LATS2	LATS2, Q9NRM7	2.7.11.1	See comment for LATS1
Serine/threonine kinase 38	NDR1	STK38, Q15208	2.7.11.1	–
Serine/threonine kinase 38 like	NDR2	STK38L, Q9Y2H1	2.7.11.1	–
3-phosphoinositide dependent protein kinase-1	PDK1	PDPK1, O15530	2.7.11.1	–
protein kinase N1	PKN1	PKN1, Q16512	2.7.11.13	PKN family members are activated by Rho, PIP3 and PDK1 321
protein kinase N2	PKN2	PKN2, Q16513	2.7.11.13	See comment for PKN1
protein kinase N3	PKN3	PKN3, Q6P5Z2	2.7.11.13	See comment for PKN1
ribosomal protein S6 kinase, 90kDa, polypeptide 5	MSK1	RPS6KA5, O75582	2.7.11.1	The mitogen- and stress-acted protein kinases are activated by phosphorylation evoked by MAP kinases and appear to be central to that pathway of cAMP response element-binding protein phosphorylation 352
ribosomal protein S6 kinase, 90kDa, polypeptide 4	MSK2	RPS6KA4, O75676	2.7.11.1	See comment for MSK1
ribosomal protein S6 kinase, 70kDa, polypeptide 1	p70S6K	RPS6KB1, P23443	2.7.11.1	Ribosomal S6 kinases 70 kDa, also known as p70rsk, are activated by MAP kinase-mediated phosphorylation
ribosomal protein S6 kinase, 70kDa, polypeptide 2	p70S6Kβ	RPS6KB2, Q9UBS0	2.7.11.1	See comment for p70S6K
ribosomal protein S6 kinase, 90kDa, polypeptide 1	p90RSK	RPS6KA1, Q15418	2.7.11.1	Ribosomal S6 kinase 90 kDa serine/threonine kinases, also known as p90rsk or MAPK-activated protein kinase-1 (MAPKAP-K1), are activated by MAP kinase -mediated phosphorylation. RSK protein kinases are also activated by phosphorylation by TORC1 327,338 and PDK1 333. Substrates include ribosomal S6 protein (RPS6, P62753), GS3β (P49841) 349) and the 5HT2A receptor 348
ribosomal protein S6 kinase, 90kDa, polypeptide 3	RSK2	RPS6KA3, P51812	2.7.11.1	see comment for p90RSK
ribosomal protein S6 kinase, 90kDa, polypeptide 2	RSK3	RPS6KA2, Q15349	2.7.11.1	see comment for p90RSK
ribosomal protein S6 kinase, 90kDa, polypeptide 6	RSK4	RPS6KA6, Q9UK32	2.7.11.1	see comment for p90RSK
SGK494	–	SGK494, Q96LW2	2.7.11.1	see comment for p90RSK
ribosomal protein S6 kinase, 52kDa, polypeptide 1	RSKL1	RPS6KC1, Q96S38	2.7.11.1	–
ribosomal protein S6 kinase-like 1	RSKL2	RPS6KL1, Q9Y6S9	2.7.11.1	–
serum/glucocorticoid regulated kinase 1	SGK1	SGK1, O00141	2.7.11.1	Serum- and glucocorticoid-inducible kinases are regulated at the transcriptional level by serum and glucocorticoids. SGK1 has been reported to be phosphorylated and activated by mouse TORC2 (Q3U182) 326
serum/glucocorticoid regulated kinase 2	SGK2	SGK2, Q9HBY8	2.7.11.1	see comment for SGK1
serum/glucocorticoid regulated kinase family, member 3	SGK3	SGK3, Q96BR1	2.7.11.1	see comment for SGK1
serine/threonine kinase 32A	YANK1	STK32A, Q8WU08	2.7.11.1	–
serine/threonine kinase 32B	YANK2	STK32B, Q9NY57	2.7.11.1	–
serine/threonine kinase 32C	YANK3	STK32C, Q86UX6	2.7.11.1	–

Nomenclature	AMP kinase	Casein kinase 2	myosin light chain kinase	myosin light chain kinase 2	Calmodulin-dependent kinase II
Common abbreviation	AMPK	CK2	smMLCK	skMLCK	CaMKII
HGNC, UniProt	–	–	MYLK, Q15746	MYLK2, Q9H1R3	–
EC number	2.7.11.1	2.7.11.1	2.7.11.18	2.7.11.18	2.7.11.17
Endogenous activators	AMP	–	calmodulin (CALM2, CALM3, CALM1, P62158) 329	calmodulin (CALM2, CALM3, CALM1, P62158) 329	calmodulin (CALM2, CALM3, CALM1, P62158)
Selective activators	AICA-riboside 318	–	–	–	–
Selective inhibitors (pIC50)	dorsomorphin 355	DRB 354	–	–	K-252a 328

Nomenclature	sphingosine kinase 1	sphingosine kinase 2
Common abbreviation	SPHK1	SPHK2
HGNC, UniProt	SPHK1, Q9NYA1	SPHK2, Q9NRA0
EC number	2.7.1.91: sphingosine + ATP = sphingosine 1-phosphate + ADP, sphinganine + ATP = sphinganine 1-phosphate + ADP
Cofactors	Mg2+
(Sub)family-selective inhibitors	sphingosine kinase inhibitor 356
Selective inhibitors	PF-543 361, SK1-I 360	ABC294640 357, ROMe 358

Nomenclature	sphingosine-1-phosphate phosphatase 1	sphingosine-1-phosphate phosphatase 2
Common abbreviation	SGPP1	SGPP2
HGNC, UniProt	SGPP1, Q9BX95	SGPP2, Q8IWX5
EC number	3.1.3.-: sphingosine 1-phosphate -> sphingosine + inorganic phosphate
Comment	Depletion of S1P phosphohydrolase-1 (SPP1), which degrades intracellular S1P, induces the unfolded protein response and endoplasmic reticulum stress-induced autophagy 359	–

Nomenclature	HGNC, UniProt	EC number	Cofactors	Comment
sphingosine-1-phosphate lyase 1	SGPL1, O95470	4.1.2.27: sphinganine 1-phosphate -> phosphoethanolamine + hexadecanal	pyridoxal phosphate	THI (2-Acetyl-5-tetrahydroxybutyl imidazole) inhibits the enzyme activity in intact cell preparations 362

Nomenclature	thyroid peroxidase
Common abbreviation	TPO
HGNC, UniProt	TPO, P07202
EC number	1.11.1.8: [Thyroglobulin]-L-tyrosine + I- + H2O2 + H+ -> [Thyroglobulin]-3,5,3′-triiodo-L-thyronine + [thyroglobulin]-aminoacrylate + H2O
Cofactors	Ca2+
Selective inhibitors (pIC50)	methimazole 363, propylthiouracil 363
Comment	Carbimazole is a pro-drug for methimazole

Nomenclature	deiodinase, iodothyronine, type I	deiodinase, iodothyronine, type II	deiodinase, iodothyronine, type III
Common abbreviation	DIO1	DIO2	DIO3
HGNC, UniProt	DIO1, P49895	DIO2, Q92813	DIO3, P55073
EC number	1.97.1.10: T4 -> T3, rT3 -> T2	1.97.1.10: T4 -> T3, rT3 -> T2	1.97.1.11: T4 -> T3, rT3 -> T2

Nomenclature	iodotyrosine deiodinase
Common abbreviation	IYD
HGNC, UniProt	IYD, Q6PHW0
EC number	1.22.1.1: 3-iodotyrosine -> L-tyrosine + I-, 3,5-diiodo-L-tyrosine -> 3-iodotyrosine + I-
Cofactors	NADPH, flavin adenine dinucleotide