Melanoma-derived growth regulatory protein or Melanoma inhibitory activity (MIA) is a 12kDa protein that is secreted from both chondrocytes and malignant melanoma cells. It has effects on cell growth and adhesion and it may play a role in melanoma metastasis and cartilage development. MIA elicits growth inhibition on melanoma cells in vitro. It is possible that secretion of MIA in vivo leads to decreased adhesiveness of melanocytic cells and thereby promotes melanoma progression and invasion []. Crystal structure revealed an Src homology 3 (SH)-like domain with N- and C-terminal extensions of about 20 aa each. It is thefirst structure of a secreted protein that contains an SH3 subdomain. MIA SH3 subdomain shares sequence similarity with canonical SH3 domains, suggesting that they are evolutionary related. It has a protein interaction site and, unlike conventional SH3 domains, MIA does not recognise polyproline helices [].
Otoraplin, also known as MIAL (MIA-like), is specifically expressed in the cochlea and the vestibule of the inner ear and may contribute to inner ear dysfunction in humans []. It is a member of the MIA family. MIA (melanoma inhibitory activity) family members include MIA, MIAL, MIA2, and MIA3 (also called TANGO). MIA was found to be strongly expressed and secreted by malignant melanomas. It contains a domain that adopts a Src Homology 3 (SH3) domain-like fold; however, it contains an additional antiparallel beta sheet and two disulfide bonds compared to classical SH3 domains. Unlike classical SH3 domains, MIA does not bind proline-rich ligands [, ].
Otoraplin, also known as MIAL (MIA-like), is specifically expressed in the cochlea and the vestibule of the inner ear and may contribute to inner ear dysfunction in humans []. It is a member of the MIA family. MIA (melanoma inhibitory activity) family members include MIA, MIAL, MIA2, and MIA3 (also called TANGO). MIA was found to be strongly expressed and secreted by malignant melanomas. It contains a domain that adopts a Src Homology 3 (SH3) domain-like fold; however, it contains an additional antiparallel beta sheet and two disulfide bonds compared to classical SH3 domains. Unlike classical SH3 domains, MIA does not bind proline-rich ligands [, ].
These proteins homolytically cleave the C-alpha--C-beta bond of aromatic amino acids (such as tyrosine in ThiH and HydG or tryptophan in the MIA synthase family) using the 5'-deoxyadenosyl radical formed by the Radical SAM enzymes [, , , ].
MIA2 is expressed specifically in hepatocytes and its expression is controlled by hepatocyte nuclear factor 1 binding sites in the MIA2 promoter [, ]. It inhibits the growth and invasion of hepatocellular carcinomas (HCC) and may act as a tumour suppressor []. A mutation in MIA2 in mice resulted in reduced cholesterol and triglycerides. Since MIA2 localizes to ER exit sites, it may function as an ER-to-Golgi trafficking protein that regulates lipid metabolism []. MIA2 contains an N-terminal SH3-like domain, similar to MIA.MIA (melanoma inhibitory activity) family members include MIA, MIAL, MIA2, and MIA3 (also called TANGO). MIA was found to be strongly expressed and secreted by malignant melanomas. It contains a domain that adopts a Src Homology 3 (SH3) domain-like fold; however, it contains an additional antiparallel beta sheet and two disulfide bonds compared to classical SH3 domains. Unlike classical SH3 domains, MIA does not bind proline-rich ligands [, ].
