STAMBP
Domain
The JAMM motif is essential for the protease activity.
Function
Zinc metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains (PubMed:15314065, PubMed:23542699, PubMed:34425109). Does not cleave 'Lys-48'-linked polyubiquitin chains (PubMed:15314065). Plays a role in signal transduction for cell growth and MYC induction mediated by IL-2 and GM-CSF (PubMed:10383417). Potentiates BMP (bone morphogenetic protein) signaling by antagonizing the inhibitory action of SMAD6 and SMAD7 (PubMed:11483516). Has a key role in regulation of cell surface receptor-mediated endocytosis and ubiquitin-dependent sorting of receptors to lysosomes (PubMed:15314065, PubMed:17261583). Endosomal localization of STAMBP is required for efficient EGFR degradation but not for its internalization (PubMed:15314065, PubMed:17261583). Involved in the negative regulation of PI3K-AKT-mTOR and RAS-MAP signaling pathways (PubMed:23542699).
Involvement in disease
Microcephaly-capillary malformation syndrome
MICCAP
A congenital disorder characterized by severe progressive microcephaly, early-onset refractory epilepsy, profound developmental delay, and multiple small capillary malformations spread diffusely on the body. Additional more variable features include dysmorphic facial features, distal limb abnormalities, and mild heart defects.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated after BMP type I receptor activation.
Ubiquitinated by SMURF2 in the presence of RNF11.
Sequence Similarities
Belongs to the peptidase M67C family.
Tissue Specificity
Ubiquitously expressed.
Cellular localization
- Nucleus
- Membrane
- Peripheral membrane protein
- Cytoplasm
- Early endosome
Alternative names
AMSH, STAMBP, STAM-binding protein, Associated molecule with the SH3 domain of STAM, Endosome-associated ubiquitin isopeptidase