ALK (anaplastic lymphoma receptor tyrosine kinase)

2p23.2

ALK is composed of an extracellular region (containing two MAM (meprin, A-5 protein, and receptor protein-tyrosine phosphatase mu) and one LDLa (low-density lipoprotein receptor) domains, and one glycin-rich region), a transmembrane domain, and an intracellular region (composed of a tyrosine kinase domain. Membrane receptor tyrosine kinase.

In familial neuroblastoma.

Fusion proteins in anaplastic large cell lymphoma, some diffuse large B-cell lymphomas, inflammatory myofibroblastic tumours, and some non-small cell lung cancers. Somatic mutations in sporadic neuroblastoma (review in Allouche, 2010).

SQSTM1 (sequestosome 1)

5q35.3

SQSTM1 (sequestosome1), also called p62, is a scaffolding protein with several interaction domains; it is composed of an OPR domain (octicosapeptide repeat (PB1 dimerization domain)), a Zn finger, a LIM protein-binding region, a TRAF6-binding motif, a PEST sequence (proline, glutamic acid, serine, and threonine rich), a LIR motif (LC3 interaction region, SGGDDDWTHLSS), a second PEST sequence, a KIR (keap1 interacting region), and an UBA (ubiquitin-associated) domain. Interacts with Caspase-8 and the apoptosis, machinery, MAPK kinases such as MAP2K5 (15q23), LCK (1p34), NBR1 (17q21), PRKCI (3q26), PAWR (12q21), RIPK1 (6p25), TRAF6 (11p12) and NTRK1 (1q23) and the NF-kappaB pathway, KEAP1 (19p13), GABARAPL1 (12p13), MAP1LC3A/LC3 (20q11), and ubiquitin. Mediates the interaction between TRAF6 and CYLD (16q12). Implicated in the activation of the transcription factor NF-kappaB. Involved in the autophagy-lysosome pathway. Plays a role in the formation of cytoplasmic proteinaceous inclusions in various pathologic situations where autophagy is inactivated (Geetha and Wooten, 2002; Lamark et al., 2009; Moscat and Diaz-Meco, 2009; Moscat et al., 2009; Ichimura and Komatsu, 2010; Komatsu and Ichimura, 2010; Moscat and Diaz-Meco, 2011).

Mutated in Pagets disease of bone.