Group XI - Attractin Family
The attractin group of CTLD-containing type 1 transmembrane proteins has two widely-expressed members in both human and mouse: attractin and attractin-like protein (ATRNL1). Both have large extracellular regions consisting of a membrane-distal epidermal growth factor (EGF) domain followed by a CUB domain; two EGF domains; five Kelch domains; a cysteine-rich/plexin domain; a CTLD; a second cysteine-rich/plexin domain; and two laminin EGF domains.
Attractin is found in both membrane-bound and secreted forms as a result of alternative splicing. Membrane-bound attractin is a co-receptor for Agouti, a paracrine signalling molecule in the skin which regulates hair pigmentation by antagonizing the melanocortin-1 receptor. Attractin also has effects on basal metabolic rate and appetite and was considered as a drug target to combat obesity. Both the secreted and membrane-bound forms of attractin may be involved in the development and maintenance of the central nervous system. In addition to changes in pigmentation and metabolic rate, mouse attractin mutations cause spongiform neurodegeneration, with abnormal myelination and vacuolation in the central nervous system. Secreted attractin is released into serum, in part by activated T lymphocytes, and modulates interactions between T cells and monocytes/macrophages. Attractin may be a component of a pathway for regulated protein turnover that also involves mahogunin, a widely-expressed E3 ubiquitin ligase found at particularly high levels in the brain. Attractin has dipeptidyl peptidase IV-like protease activity. The cytoplasmic region of ATRNL1 interacts with the cytoplasmic tail of the melanocortin-4 receptor, a G-protein-coupled receptor in the brain which regulates appetite and metabolism, but the function of ATRNL1 is not understood.
The CTLDs in attractin and ATRNL1 contain some of the residues which in other CTLDs are involved in binding mannose-type sugars. It is not known if carbohydrate recognition by the CTLDs is involved in the functions of these proteins.
Protein Data Bank structure ID: 1ZGK.
