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ZNRF2

Domain

The RING-type zinc finger domain is required for E3 ligase activity.

Function

E3 ubiquitin-protein ligase that plays a role in the establishment and maintenance of neuronal transmission and plasticity. Ubiquitinates the Na(+)/K(+) ATPase alpha-1 subunit/ATP1A1 and thereby influences its endocytosis and/or degradation (PubMed:22797923). Acts also as a positive regulator of mTORC1 activation by amino acids, which functions upstream of the V-ATPase and of Rag-GTPases (PubMed:27244671). In turn, phosphorylation by mTOR leads to its inhibition via targeting to the cytosol allowing a self-regulating feedback mechanism (PubMed:27244671).

Pathway

Protein modification; protein ubiquitination.

Post-translational modifications

Phosphorylated; leading to binding to YWHAE (PubMed:22797923). Phosphorylated by MTOR at Ser-145 and dephosphorylated by PP6C. Ser-145 phosphorylation stimulates vesicle-to-cytosol translocation (PubMed:27244671).

Tissue Specificity

Highly expressed in the brain, with higher expression during development than in adult. Expressed also in mammary glands, testis, colon and kidney.

Cellular localization

Alternative names

RNF202, ZNRF2, E3 ubiquitin-protein ligase ZNRF2, Protein Ells2, RING finger protein 202, RING-type E3 ubiquitin transferase ZNRF2, Zinc/RING finger protein 2

swissprot:Q8NHG8 omim:612061 entrezGene:223082