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.

Involvement in disease

Neurodevelopmental disorder with dysmorphic facies and ischiopubic hypoplasia

NEDFIH

An autosomal recessive disorder characterized by moderate to severe global developmental delay, facial dysmorphism, and ischiopubic synchondrosis hypoplasia. Affected individuals show infection-triggered lymphopenia, and loss of developmental milestones associated with epileptic spasms. Diminished white matter volume, enlarged ventricles, and thin corpus callosum are visible on brain imaging.

None

The disease may be caused by variants affecting the gene represented in this entry.

Pathway

Protein modification; protein neddylation.

Post-translational modifications

Ubiquitinated by TRIP12, leading to its degradation by the proteasome.

Sequence Similarities

Belongs to the ubiquitin-activating E1 family. ULA1 subfamily.

Tissue Specificity

Ubiquitous in fetal tissues. Expressed throughout the adult brain.

Cellular localization

• Cell membrane
• Colocalizes with APP in lipid rafts.

Alternative names

APPBP1, HPP1, NAE1, NEDD8-activating enzyme E1 regulatory subunit, Amyloid protein-binding protein 1, Proto-oncogene protein 1, APP-BP1

Database links

swissprot:Q13564 entrezGene:8883 omim:603385 swissprot:Q8TBC4