PROSITE documentation PDOC50197

BEACH domain profile

The BEACH (for BEIge And CHS) domain is a region of about 300 residues that is highly conserved in a large family of eukaryotic proteins. Many of the proteins that contain a BEACH domain are very large (with >2000 residues) and have putative functions in vesicular transport, membrane dynamics and receptor signaling. The BEACH domain is crucial for the normal function of these proteins. In all known BEACH-containing proteins, the BEACH domain is located just prior to a WD-40 domain (see <PDOC00574>) in the primary sequence, which is located at the extreme C-terminus of most of these proteins. In addition, structural analysis revealed that BEACH domain has intimate contacts with a fold identical to that of PH domains (see <PDOC50003>) just prior to it in the primary sequence. Consistent with the structural analysis, biochemical studies show that the PH and BEACH domains have strong interactions, suggesting they may function as a single unit. The function of the BEACH domain is unknown [1,2,3].

The resolution of the crystal structure of the BEACH domain of human Nbea (see <PDB:1MI1>) as shown that it has a new and unusual polypeptide backbone fold, as the peptide segments in its core do not assume regular secondary structures (α-helix or β-sheet). In addition, only a few main-chain hydrogen-bonds are made among these segments. The structure of the BEACH domain also contains 11 α-helices that are arranged on the periphery of the structure, but help to enclose the core of the domain [3].

Proteins known to contain a BEACH domain are listed below:

• Human lysosomal trafficking regulator or Chediak-Higashi Syndrome (CHS) protein. Defects in the CHS protein are the cause of Chediak-Higashi Syndrome, a rare autosomal disorder characterized by hypopigmentation, severe immunologic deficiency, a bleeding tendency and neurologic abnormalities. As an important hallmark of several tissues derived from CHS patients is the occurrence of giant inclusion bodies and organelles and protein sorting defects in these organelles, the CHS protein is thought to be involved in vesicle fusion or fission. The CHS protein contains 7 WD- repeats. The mouse ortholog of CHS is called 'beige'.
• Mammalian FAN (Factor Associated with Neutral-sphingomyelinase activation). It binds to the N-SMase activation domain (NSD) of the p55 TNF-receptor and mediates the activation of N-SMase after ligand binding. FAN contains five WD-repeats.
• Human lipopolysaccharide-responsive and beige-like anchor protein (LBA) (also known as Beige like protein or CDC4-like protein). It may have a function in in polarized vesicle trafficking, and is localized to vesicles after stimulation by lipopolysaccharide (LPS).
• Vertebrate neurobeachin (Nbea). It has been implicated in membrane traffic in neuronal cells.
• Caenorhabditis elegans hypothetical proteins F52C9.2 and F52C9.3.
• Yeast hypothetical protein YCR032W.