Zinc-finger proteins contain DNA-binding domains and have a wide variety of functions, most of which encompass some form of transcriptional activation or repression. The RING-type zinc finger motif is present in a number of viral and eukaryotic proteins and is made of a conserved cysteine-rich domain that is able to bind two zinc atoms. Proteins that contain this conserved domain are generally involved in the ubiquitination pathway of protein degradation. ZNRF1 (zinc and ring finger 1), also known as NIN283, is a 227 amino acid protein that contains one RING-type zinc finger and localizes to the lysosome and the endosome, as well as to cytoplasmic vesicles and the peripheral membrane. Expressed primarily in nervous system tissue, but also present in testis and thymus, ZNRF1 functions as an E3 ubiquitin-protein ligase that is thought to play a role in the establishment and maintenance of neuronal plasticity. Multiple isoforms of ZNRF1 exist due to alternative splicing events.
Function:
E3 ubiquitin-protein ligase that mediates the ubiquitination of AKT1 and GLUL, thereby playing a role in neuron cells differentiation. Plays a role in the establishment and maintenance of neuronal transmission and plasticity. Regulates Schwann cells differentiation by mediating ubiquitination of GLUL. Promotes neurodegeneration by mediating 'Lys-48'-linked polyubiquitination and subsequent degradation of AKT1 in axons: degradation of AKT1 prevents AKT1-mediated phosphorylation of GSK3B, leading to GSK3B activation and phosphorylation of DPYSL2/CRMP2 followed by destabilization of microtubule assembly in axons (Probable).
Subunit:
Interacts with AKT1, GLUL and TUBB2A (By similarity).
Subcellular Location:
Endosome. Lysosome. Membrane.
Tissue Specificity:
Expressed primarily in the nervous system, with expression higher in developing brain relative to adult. Expressed at low levels in testis and thymus.
Similarity:
Contains 1 RING-type zinc finger.
SWISS:
Q8ND25
Gene ID:
84937
Database links:
Entrez Gene: 84937 Human
Entrez Gene: 170737 Mouse
Entrez Gene: 690769 Rat
Omim: 612060 Human
SwissProt: Q8ND25 Human
SwissProt: Q91V17 Mouse
Unigene: 427284 Human
Unigene: 271578 Mouse
Unigene: 470106 Mouse
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