UniProt functional annotation for Q13564

UniProt code: Q13564.

Organism: Homo sapiens (Human).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
 
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. {ECO:0000269|PubMed:10207026, ECO:0000269|PubMed:10722740, ECO:0000269|PubMed:12740388}.
 
Activity regulation: Binding of TP53BP2 to the regulatory subunit NAE1 decreases neddylation activity.
Pathway: Protein modification; protein neddylation.
Subunit: Heterodimer of UBA3 and NAE1. The complex binds NEDD8 and UBE2M. Binds APP and TP53BP2. {ECO:0000269|PubMed:12646924, ECO:0000269|PubMed:14690597, ECO:0000269|PubMed:15361859}.
Subcellular location: Cell membrane {ECO:0000269|PubMed:14557245}. Note=Colocalizes with APP in lipid rafts.
Tissue specificity: Ubiquitous in fetal tissues. Expressed throughout the adult brain. {ECO:0000269|PubMed:8626687}.
Ptm: Ubiquitinated by TRIP12, leading to its degradation by the proteasome. {ECO:0000269|PubMed:18627766}.
Miscellaneous: NAE1 and UBA3 correspond to the N-terminal and the C- terminal part of yeast UBA3. In yeast the two subunits form a single polypeptide chain.
Similarity: Belongs to the ubiquitin-activating E1 family. ULA1 subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.