NEDD8-activating enzyme E1 catalytic subunit

Function

Catalytic subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Down-regulates steroid receptor activity. Necessary for cell cycle progression.

Classification

Family (Pfam)

PF08825 E2_bind, PF00899 ThiF

InterPro

E2-binding, ThiF/MoeB/HesA, ThiF_NAD_FAD-bd, Ub_act_enz_dom_a_sf, Uba3_N, Ubiquitin-activating_enz, UBQ-activ_enz_E1_Cys_AS

Functional cluster

Mixed Regulatory & Membrane Proteins

Experimental structures · PDB · 13

• 1R4M X-ray 3.00A
• 1R4N X-ray 3.60A
• 1TT5 X-ray 2.60A
• 1Y8X X-ray 2.40A
• 1YOV X-ray 2.60A
• 2LQ7 NMR
• 2NVU X-ray 2.80A
• 3DBH X-ray 2.85A
• 3DBL X-ray 2.90A
• 3DBR X-ray 3.05A
• 3FN1 X-ray 2.50A
• 3GZN X-ray 3.00A
• … and 1 more

A predicted model is available from AlphaFold.

Gene Ontology · 13

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005634 nucleus
• GO:0032991 protein-containing complex
• GO:0005524 ATP binding
• GO:0042802 identical protein binding
• GO:0019781 NEDD8 activating enzyme activity
• GO:0019788 NEDD8 transferase activity
• GO:0046982 protein heterodimerization activity
• GO:0043687 post-translational protein modification
• GO:0036211 protein modification process
• GO:0045116 protein neddylation
• GO:0006508 proteolysis

Drugs targeting this protein · 1

• PEVONEDISTAT inhibitor

Related proteins · sequence + function similarity

• NEDD8-activating enzyme E1 catalytic subunit 1.00
• NEDD8-activating enzyme E1 catalytic subunit 1.00
• NEDD8-activating enzyme E1 catalytic subunit 1.00
• NEDD8-activating enzyme E1 catalytic subunit 0.98
• Nedd8-activating enzyme E1 catalytic subunit 0.84
• SUMO-activating enzyme subunit 2 0.81
• NEDD8-activating enzyme E1 catalytic subunit 0.80
• SUMO-activating enzyme subunit 2 0.79
• SUMO-activating enzyme subunit 2 0.78
• SUMO-activating enzyme subunit 2 0.77
• SUMO-activating enzyme subunit 2-A 0.77
• SUMO-activating enzyme subunit 2-B 0.77

Co-cited proteins · studied together in the literature

• NEDD8-activating enzyme E1 regulatory subunit 5 shared papers
• NEDD8-conjugating enzyme Ubc12 5 shared papers
• NEDD8-activating enzyme E1 catalytic subunit 1 shared papers
• Ubiquitin-like protein NEDD8 2 shared papers
• NEDD8-conjugating enzyme UBE2F 1 shared papers
• NEDD8-conjugating enzyme UBE2F 1 shared papers
• Cullin-4A 1 shared papers
• RING-box protein 2 1 shared papers
• E3 ubiquitin-protein ligase RBX1 1 shared papers

Literature · 14 cited papers

• N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification. Mol. Cell · 2009
• The DNA sequence, annotation and analysis of human chromosome 3. Nature · 2006
• Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1. Mol. Cell · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8. Nat. Struct. Mol. Biol. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1. Mol. Cell · 2003
• Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer. J. Biol. Chem. · 2003
• Insights into the ubiquitin transfer cascade from the structure of the activating enzyme for NEDD8. Nature · 2003
• Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome Res. · 2001
• … and 2 more in the literature graph