Ubiquitination is an important mechanism through which three classes of enzymes act in concert to target short-lived or abnormal proteins for destruction. The three classes of enzymes involved in ubiquitination are the ubiquitin-activating enzymes (E1s), the ubiquitin-conjugating enzymes (E2s) and the ubiquitin-protein ligases (E3s). ZNRF2 (zinc and ring finger 2), also known as RNF202, is a 242 amino acid peripheral membrane protein that contains one RING-type zinc finger and localizes to the lysosome, as well as the endosome and the cell junction. Expressed at high levels in brain tissue, ZNRF2 is thought to function as an E3 ubiquitin-protein ligase that may be involved in the establishment and maintenance of neuronal transmission and plasticity. Upon DNA damage, ZNRF2 is subject to phosphorylation, probably by ATR or ATM.
Function:
May play a role in the establishment and maintenance of neuronal transmission and plasticity via its ubiquitin ligase activity. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates.
Subunit:
Interacts with UBE2N.
Subcellular Location:
Endosome membrane. Lysosome membrane. Cell junction > synapse > presynaptic cell membrane. Present in presynaptic plasma membranes in neurons.
Tissue Specificity:
Highly expressed in the brain, with higher expression during development than in adult. Expressed also in mammary glands, testis, colon and kidney.
Post-translational modifications:
Phosphorylated upon DNA damage, probably by ATM or ATR.
Similarity:
Contains 1 RING-type zinc finger.
SWISS:
Q8NHG8
Gene ID:
223082
Database links:
Entrez Gene: 223082 Human
Entrez Gene: 387524 Mouse
Entrez Gene: 362367 Rat
Omim: 612061 Human
SwissProt: Q8NHG8 Human
SwissProt: Q71FD5 Mouse
Unigene: 487869 Human
Unigene: 286149 Mouse
Unigene: 392146 Mouse
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