?cl14649: BRO1_Alix_like Superfamily (this model, PSSM-Id:387372 is obsolete and has been replaced by 472700)
 
Protein-interacting Bro1-like domain of mammalian Alix and related domains This superfamily includes the Bro1-like domains of mammalian Alix (apoptosis-linked gene-2 interacting protein X), His-Domain type N23 protein tyrosine phosphatase (HD-PTP, also known as PTPN23), RhoA-binding proteins Rhophilin-1 and Rhophilin-2, Brox, Bro1 and Rim20 (also known as PalA) from Saccharomyces cerevisiae, and related domains. Alix, HD-PTP, Brox, Bro1 and Rim20 interact with the ESCRT (Endosomal Sorting Complexes Required for Transport) system. Alix, also known as apoptosis-linked gene-2 interacting protein 1 (AIP1), participates in membrane remodeling processes during the budding of enveloped viruses, vesicle budding inside late endosomal multivesicular bodies (MVBs), and the abscission reactions of mammalian cell division. It also functions in apoptosis. HD-PTP functions in cell migration and endosomal trafficking, Bro1 in endosomal trafficking, and Rim20 in the response to the external pH via the Rim101 pathway. Bro1-like domains are boomerang-shaped, and part of the domain is a tetratricopeptide repeat (TPR)-like structure. Bro1-like domains bind components of the ESCRT-III complex: CHMP4 (in the case of Alix, HD-PTP, and Brox) and Snf7 (in the case of yeast Bro1, and Rim20). The single domain protein human Brox, and the isolated Bro1-like domains of Alix, HD-PTP and Rhophilin can bind human immunodeficiency virus type 1 (HIV-1) nucleocapsid. Alix, HD-PTP, Bro1, and Rim20 also have a V-shaped (V) domain, which in the case of Alix, has been shown to be a dimerization domain and to contain a binding site for the retroviral late assembly (L) domain YPXnL motif, which is partially conserved in this superfamily. Alix, HD-PTP and Bro1 also have a proline-rich region (PRR); the Alix PRR binds multiple partners. Rhophilin-1, and -2, in addition to this Bro1-like domain, have an N-terminal Rho-binding domain and a C-terminal PDZ (PS.D.-95, Disc-large, ZO-1) domain. HD-PTP is encoded by the PTPN23 gene, a tumor suppressor gene candidate frequently absent in human kidney, breast, lung, and cervical tumors. This protein has a C-terminal, catalytically inactive tyrosine phosphatase domain. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",