The Dan (Differential screening-selected gene aberrative in neuroblastoma , also known as N03) gene was first identified as the putative rat tumor suppressor gene and encodes a protein structurally related to Cerberus and Gremlin in the vertebrates. It is a founding member of the DAN family of secreted proteins , acts as an inhibitor of cell cycle progression , and is closely involved in retinoic acid-induced neuroblastoma differentiation. There are at least five mammalian protein members in the evolutionarily conserved Dan family including DAN , Gremlin/DRM , Cer1 (Cerberus-related) , Dante , and PRDC (protein related to DAN and Cerberus) , and share the C-terminal cystine-knot motif. As a secreted glycoprotein , DAN is a member of a class of glycoproteins shown to be secreted inhibitors of the transforming growth factor-beta (TGF-beta) and bone morphogenic protein pathways. It binds to BMPs and preventing their interactions with signaling receptor complexes , and accordingly regulates the processes of embryonic development and tissue differentiation. DAN gene product may have an important role in the regulation of the entry of cells into the S phase. Besides , the DAN gene product possesses an ability to revert phenotypes of transformed rat fibroblasts and represents a candidate tumor suppressor gene for neuroblastoma.
NCAM1, also known as CD56, is a neural adhesion protein (NCAM) which belongs to the immunoglobulin superfamily. NCAM is involved in neural development and in plasticity in the adult brain. UCHL1 is a novel interaction partner of both NCAM isoforms that regulates their ubiquitination and intracellular trafficking. NCAM1 is a cell adhesion molecule involved in neuron-neuron adhesion, neurite fasciculation, outgrowth of neurites, etc. NCAM1 has also been shown to be involved in the expansion of T cells and dendritic cells which play an important role in immune surveillance.
Neural cell adhesion molecule 1 (NCAM-1) is a single-pass type I membrane protein, it belongs to a family of membrane-bound glycoproteins that are involved in Ca2+ independent cell matrix and homophilic or heterophilic cell-cell interactions. NCAM-1 is synthesized as a 761 aa preproprecursor that contains a 19 aa signal sequence, a 722 aa GPI-linked mature region, and a 20 aa C-terminal prosegment. The molecule contains five C-2 type Ig-like domains and two fibronectin type-III domains. NCAM-1 is a cell adhesion molecule involved in neuron-neuron adhesion, neurite fasciculation, outgrowth of neurites, etc. Acting as a receptor for rabies virus, NCAM-1 in the adult brain shows a decline of sialylation relative to earlier developmental periods.
NCF2, also known as NCF-2 and p67phox, is a subunit of the multi-protein NADPH oxidase complex. NCF2, NCF1, and a membrane bound cytochrome b558 are required for activation of the latent NADPH oxidase. This oxidase produces a burst of superoxide which is delivered to the lumen of the neutrophil phagosome. Mutations in NCF2 gene, as well as in other NADPH oxidase subunits, can result in chronic granulomatous disease, a disease that causes recurrent infections by catalase-positive organisms.
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