Vhl
Developmental stage
Expressed throughout fetal nephrogenesis, abdominal and thoracic organogenesis, and nervous system development between day 10.5 and day 16.5. In the developing lung, differential expression within the endodermally derived cuboidal epithelial lining of the terminal and respiratory bronchioles. In the developing eye, high expression in both the inner and outer neuroblastic layers of the retina and lens.
Domain
The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV].
Function
Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Seems to act as a target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions. Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases. Ubiquitinates, in an oxygen-responsive manner, ADRB2. Acts as a negative regulator of mTORC1 by promoting ubiquitination and degradation of RPTOR.
Pathway
Protein modification; protein ubiquitination.
Sequence Similarities
Belongs to the VHL family.
Cellular localization
- Cytoplasm
- Cell membrane
- Peripheral membrane protein
- Endoplasmic reticulum
- Nucleus
- Found predominantly in the cytoplasm and with less amounts nuclear or membrane-associated. Colocalizes with ADRB2 at the cell membrane.
Alternative names
Vhlh, von Hippel-Lindau disease tumor suppressor, pVHL