2.A.2.7.3
MFSD12, melanosome and lysosome cysteine transporter, of 480 aas and 12 TMSs. It is associated with skin pigmentation in humans, mice, dogs and horses (Crawford et al. 2017; Adhikari et al. 2019; Hédan et al. 2019; Tanaka et al. 2019). Its upregulated expression is observed in melanomas, and elevated MFSD12 levels promote cell proliferation by promoting cell cycle progression (Wei et al. 2019). MFSD12 interference inhibited tumor growth and lung metastasis in melanoma. It mediates the import of cysteine into melanosomes and lysosomes (Adelmann et al. 2020). MFSD12 is required to maintain normal levels of cystine - the oxidized dimer of cysteine - in melanosomes, and to produce cysteinyldopas, the precursors of pheomelanin synthesis made in melanosomes via cysteine oxidation. MFSD12 is necessary for the import of cysteine into melanosomes and, in non-pigmented cells, lysosomes. Loss of MFSD12 reduced the accumulation of cystine in lysosomes of fibroblasts from patients with cystinosis, a lysosomal-storage disease caused by inactivation of the lysosomal cystine exporter, cystinosin (TC# 2.A.43.1.1). Thus, MFSD12 is an essential component of the cysteine importer for melanosomes and lysosomes (Adelmann et al. 2020).