NEDD8-activating enzyme E1 regulatory subunit

UniProt Q13564 Organism Homo sapiens Gene APPBP1, NAE1

Also known as: APPBP1, NAE1

Function

Regulatory 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. Necessary for cell cycle progression through the S-M checkpoint. Overexpression of NAE1 causes apoptosis through deregulation of NEDD8 conjugation. The covalent attachment of NEDD8 to target proteins is known as 'neddylation' and the process is involved in the regulation of cell growth, viability and development.

Classification

Family (Pfam): PF00899 ThiF
InterPro: APP-BP1, ThiF/MoeB/HesA, ThiF_NAD_FAD-bd, Ubiquitin-activating_enz
Functional cluster: Zinc-Finger Nucleic-Acid-Binding & Methyltransferases

Experimental structures · PDB · 9

1R4M X-ray 3.00A
1R4N X-ray 3.60A
1TT5 X-ray 2.60A
1YOV X-ray 2.60A
2NVU X-ray 2.80A
3DBH X-ray 2.85A
3DBL X-ray 2.90A
3DBR X-ray 3.05A
3GZN X-ray 3.00A

A predicted model is available from AlphaFold.

Gene Ontology · 15

Disease associations

neurodevelopmental disorder with dysmorphic facies and ischiopubic hypoplasia MONDO:0859361

Drugs targeting this protein · 1

PEVONEDISTAT inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

NEDD8-activating enzyme E1 catalytic subunit 5 shared papers
NEDD8-activating enzyme E1 regulatory subunit 2 shared papers
E3 ubiquitin-protein ligase TRIP12 1 shared papers
Apoptosis-stimulating of p53 protein 2 1 shared papers
NEDD8-conjugating enzyme Ubc12 2 shared papers
NEDD8-activating enzyme E1 catalytic subunit 1 shared papers
Ubiquitin-like protein NEDD8 1 shared papers
Amyloid-beta precursor protein 1 shared papers

Literature · 19 cited papers

Bi-allelic variants in NAE1 cause intellectual disability, ischiopubic hypoplasia, stress-mediated lymphopenia and neurodegeneration. Am. J. Hum. Genet. · 2023
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
Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science · 2009
TRIP12 functions as an E3 ubiquitin ligase of APP-BP1. Biochem. Biophys. Res. Commun. · 2008
The sequence and analysis of duplication-rich human chromosome 16. Nature · 2004
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
APP-BP1 mediates APP-induced apoptosis and DNA synthesis and is increased in Alzheimer's disease brain. J. Cell Biol. · 2003
Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer. J. Biol. Chem. · 2003
… and 7 more in the literature graph

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