Literature summary for 6.2.1.64 extracted from

Xu, G.W.; Toth, J.I.; da Silva, S.R.; Paiva, S.L.; Lukkarila, J.L.; Hurren, R.; Maclean, N.; Sukhai, M.A.; Bhattacharjee, R.N.; Goard, C.A.; Medeiros, B.; Gunning, P.T.; Dhe-Paganon, S.; Petroski, M.D.; Schimmer, A.D.
Mutations in UBA3 confer resistance to the NEDD8-activating enzyme inhibitor MLN4924 in human leukemic cells (2014), PLoS ONE, 9, e93530 .

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Protein Variants

Protein Variants	Comment	Organism
I310N	the mutations in the catalytic subunit UBA3 increases the enzyme's affinity for ATP while decreasing its affinity for NEDD8. This mutation effectively contributes to decreased MLN4924 potency in vitro while providing for sufficient enzyme function for leukemia cell survival	Homo sapiens
Y352H	the mutations in the catalytic subunit UBA3 increases the enzyme's affinity for ATP while decreasing its affinity for NEDD8. This mutation effectively contributes to decreased MLN4924 potency in vitro while providing for sufficient enzyme function for leukemia cell survival	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
MLN4924	selective inhibitor	Homo sapiens

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism	Structure
0.005	-	diphosphate	wild type enzyme, pH and temperature not specified in the publication	Homo sapiens
0.0109	-	diphosphate	mutant enzyme Y352H, pH and temperature not specified in the publication	Homo sapiens
0.02	-	ATP	mutant enzyme I310N, pH and temperature not specified in the publication	Homo sapiens
0.027	-	ATP	mutant enzyme Y352H, pH and temperature not specified in the publication	Homo sapiens
0.0511	-	diphosphate	mutant enzyme I310N, pH and temperature not specified in the publication	Homo sapiens
0.08	-	ATP	wild type enzyme, pH and temperature not specified in the publication	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine	Homo sapiens	-	AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q8TBC4	catalytic subunit UBA3	-

Purification (Commentary)

Purification (Comment)	Organism
Ni-NTA column chromatography	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
K-562 cell	-	Homo sapiens	-
leukemia cell	-	Homo sapiens	-
U-937 cell	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine	-	Homo sapiens	AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine	-	?

Synonyms

Synonyms	Comment	Organism
NAE	-	Homo sapiens
NEDD8-activating enzyme	-	Homo sapiens
Uba3	catalytic subunit	Homo sapiens

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Release 2023.1 (January 2023)