STAM Binding Protein (STAMBP), also known as AMSH (Associated Molecule with the SH3 domain of STAM), is a protein encoded by the STAMBP gene located on chromosome 2p13.1 . This gene is conserved across various species, including chimpanzees, Rhesus monkeys, dogs, cows, mice, rats, chickens, zebrafish, fruit flies, mosquitoes, and frogs .
STAMBP belongs to the JAMM (JAB1/MPN/Mov34 metalloenzyme) family of deubiquitinating enzymes . It contains a microtubule-interacting/transport domain and a STAM-binding domain . The recombinant human STAMBP protein is typically expressed in baculovirus-infected insect cells and is often tagged with a His-tag for purification purposes .
STAMBP plays a critical role in cytokine-mediated signaling for MYC induction and cell cycle progression . It binds to the SH3 domain of the signal-transducing adaptor molecule (STAM) and is involved in the endosomal sorting complex required for transport (ESCRT) pathway . This pathway is essential for the sorting of ubiquitinated proteins into multivesicular bodies, which are then directed to lysosomes for degradation .
As a deubiquitinating enzyme, STAMBP removes ubiquitin molecules from substrate proteins, thereby regulating their stability and function . This activity is zinc-dependent and is crucial for maintaining cellular homeostasis . Mutations in the STAMBP gene can lead to various disorders, including microcephaly-capillary malformation syndrome, a congenital and neurodevelopmental disorder .
STAMBP is widely expressed in various tissues, including the thyroid and brain . Its expression and activity are tightly regulated to ensure proper cellular function. Dysregulation of STAMBP has been implicated in several diseases, including cancer . For instance, STAMBP has been shown to regulate melanoma metastasis through the stabilization of the transcription factor Slug .