E3 ubiquitin-protein ligase SH3RF1 (SH3RF1)

E3 ubiquitin-protein ligase SH3RF1 (SH3 domain containing ring finger 1, also known as POSH) is a multidomain protein containing an N-terminal RING-finger, four SH3 domains, and a Rac-binding region[1][3][4][5][7]. SH3RF1 functions as a RING-type E3 ubiquitin ligase, mediating ubiquitination of target proteins, which regulates their degradation or trafficking—particularly in processes like protein sorting at the trans-Golgi network and potassium channel endocytosis[1][3]. It acts as a scaffold protein facilitating the assembly and activation of the c-Jun N-terminal kinase (JNK) signaling complex, thus playing a role in signal transduction cascades involving Rho GTPases (notably Rac1/2), MAPK kinases, and other molecules[1]. SH3RF1 is implicated in the regulation of apoptosis, acting as a pro-apoptotic factor that induces JNK activation and cell death; it is involved in T-cell differentiation, specifically promoting T-helper 1 (Th1) lineage commitment[2]. Additionally, SH3RF1 plays a crucial role in neuronal migration during brain development by supporting cortical neuron migration and F-actin assembly[1][6]. The gene has been associated with several disease processes, including hereditary breast-ovarian cancer syndrome, lissencephaly, and possibly other cancers and neurodevelopmental disorders[1]. In the context of viral infection, SH3RF1 is essential for targeting HIV-1 Gag protein to the plasma membrane through its E3 ligase activity[1].

Other names

SH3 domain containing ring finger 1POSHPOSH1KIAA1494RNF142SH3MD2Protein POSHRING finger protein 142SH3 multiple domains protein 2Plenty of SH3splenty of SH3 domainsSH3 multiple domains 2putative E3 ubiquitin-protein ligase SH3RF1ring finger protein 142