STAMBP gene

The STAMBP gene (STAMBP stands for: STAM Binding Protein) is a protein-coding gene localized on chromosome 2p13.1. An important paralog of this gene is STAMBPL1.

Cytokine-mediated signal transduction in the JAK-STAT signaling pathway requires the involvement of adaptor molecules. One of these signal-transducing adaptor molecules contains an SH3 domain that is required for MYC induction and cell growth. The protein encoded by this gene binds to the SH3 domain of the signal-transducing adaptor molecule and plays a critical role in cytokine-mediated signaling for MYC induction and cell cycle progression. Several alternatively spliced transcript variants encoding the same protein isoform have been found for this gene.

The STAMBP gene codes for a zinc metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains (McCullough J et al. (2004). The zinc protease does not cleave 'Lys-48'-linked polyubiquitin chains. It plays a role in signal transduction for cell growth and MYC induction mediated by IL-2 and GM-CSF (Tanaka N et al. 1999). Enhances BMP (bone morphogenetic protein) signaling by antagonizing the inhibitory effect of SMAD6 and SMAD7 (Itoh F et al. 2001). Plays a key role in the regulation of receptor-mediated endocytosis at the cell surface and ubiquitin-dependent sorting of receptors in lysosomes. Endosomal localization of STAMBP is required for efficient EGFR degradation. The enzyme is involved in the negative regulation of the PI3KAKT-mTOR and RAS-MAP signaling pathways (Itoh F et al. (2001).

1. Itoh F et al. (2001) Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads. EMBO J 20:4132-4142.
2. McCullough J et al. (2004) AMSH is an endosome-associated ubiquitin isopeptidase. J Cell Biol 166:487-492.
3. Tanaka N et al. (1999) Possible involvement of a novel STAM-associated molecule "AMSH" in intracellular signal transduction mediated by cytokines. J Biol Chem 274:19129-19135.