InterPro domain: IPR019498

The following proteins share a conserved region called the MENTAL (MLN64 N-terminal) domain, composed of four transmembrane helices with three shortintervening loops [ 1 , 2 , 3 ]:

• Animal MLN64 (metastatic lymph node 64), a late endosomal membrane protein containing a carboxyl-terminal cholesterol binding START domain ( IPR002913 ). It is probably involved in intracellular cholesterol transport.
• Mammalian MENTHO (MLN64 N-terminal domain homologue), a late endosomal protein containing only the MENTAL domain. It is probably involved in cellular cholesterol homoeostasis.

The ~170-amino acid MENTAL domain mediates MLN64 and MENTHO homo- and hetero-interactions, targets both proteins to late endosomes and binds cholesterol.The MENTAL domain might serve to maintain cholesterol at the membrane of lateendosomes prior to its shuttle to cytoplasmic acceptor(s) through the STARTdomain.

1. MENTHO, a MLN64 homologue devoid of the START domain. J. Biol. Chem. 277, 50780-7
2. Functional characterization of the MENTAL domain. J. Biol. Chem. 280, 17945-52
3. MLN64 and MENTHO, two mediators of endosomal cholesterol transport. Biochem. Soc. Trans. 34, 343-5