Contactins are a subgroup of molecules belonging to the immunoglobulin superfamily that are expressed exclusively in the nervous system. The subgroup consists of six members: Contactin-1; Contactin-2(TAG-1); Contactin-3(BIG-1); BIG-2; Contactin-5(NB-2) and NB-3. Since their identification in the late 1980s; Contactin-1 and Contactin-2 have been studied extensively. Axonal expression and the neurite extension activity of Contactin-1 and Contactin-2 attracted researchers to study the function of these molecules in axon guidance during development. Contactin-1 and Contactin-2 have come to be known as the principal molecules in the function and maintenance of myelinated neurons. In contrast; the function of the other four members of this subgroup remained unknown until recently. Contactin-3; also known as CNTN3 ( BIG-1 in rat and PANG in mouse ); is a GPI-linked glycoprotein that is expressed on cerebellar Purkinje cells; amygdaloid and thalamic neurons and olfactory granule cells. In the brain; Contactin-3 is expressed in frontal lobe; occipital lobe; cerebellum and amygdala. Contactin-3 contains 4 fibronectin type-III domains and 6 Ig-like C2-type (immunoglobulin-like) domains. Human Contactin-3 shares 92% aa identity with mouse Contactin-3.The exact function of Contactin-3 is unclear. Contactin-3 may mediate cell-cell interaction and may promote neurite outgrowth.
Contactin-4, abbreviated as CNTN4, is a brain-derived protein belonging to the immunoglobulin superfamily. It has been found high expression in testes, thyroid, small intestine, uterus and brain. This protein is an neuronal membrane protein that functions as an glycosylphosphatidylinositol- anchored cell adhesion molecule. Contactin-4 is considered as a candidate protein responsible for the differentiation potential of human neuroblastoma cells and it has been implicated in some cases of autism and spinocerebellar ataxia type 16. Studies of the cantactin family have revealed a complex pattern of hemophilic and heterophilic interactions that are required for axon growth and pathfinding. Such studies demonstrate that these essential functions are mediated by the combination and juxtaposition of multiple Ig and FNIII domains. Second, these neuronal adhesion molecules demonstrate highly regulated temporal and spatial expression patterns in the CNS. For this reason, the disruption of the regulatory region of the predominant brain-expressed isoform reasonable would be expected to have significant functional consequences.
Contactins are a subgroup of molecules belonging to the immunoglobulin superfamily that are expressed mainly in the nervous system. The subgroup consists of six members: Contactin-1, Contactin-2(TAG-1), Contactin-3(BIG-1), BIG-2, Contactin-5(NB-2) and NB-3. Since their identification in the late 1980s, Contactin-1 and Contactin-2 have been studied extensively. Axonal expression and the neurite extension activity of Contactin-1 and Contactin-2 attracted researchers to study the function of these molecules in axon guidance during development. Contactin-1 and Contactin-2 have come to be known as the principal molecules in the function and maintenance of myelinated neurons. In contrast, the function of the other four members of this subgroup remained unknown until recently. Contactin-5, also known as NB-2, is one of the neural recognition molecules in the contactin subgroup. Contactin-5 is expressed in brain and kidney and at very low level in placenta. In brain, Contactin-5 is highly expressed in the occipital lobe, amygdala, cerebral cortex, frontal lobe, thalamus and temporal lobe. Mice deficient in the Contactin-5 gene exhibit aberrant responses to acoustic stimuli. Contactin-5 may play a role in maturation of glutamatergic synapses in the brainstem during the final stages of auditory development. Contactin-5 gene may contribute to human neurological disorders.
Copine-1(CPNE1) encodes a calcium-dependent protein which belongs to the copine family. CPNE1contains two N-terminal type II C2 domains and an integrin A domain-like sequence in the C-terminus. However, CPNE1 does not contain a predicted signal sequence or transmembrane domains. CPNE1 may regulate molecular events at the interface of the cell membrane and cytoplasm. CPNE1 has a broad tissue distribution and it may function in membrane trafficking.
Ubiquinone Biosynthesis Protein COQ7 Homolog (COQ7) is a mitochondrion inner membrane and peripheral membrane protein which belongs to the COQ7 family. It is expressed dominantly in heart and skeletal muscle. COQ7 is synthesized as a preprotein that is imported into the mitochondrial matrix, where the sequence is cleaved off and the mature protein becomes loosely associated with the inner membrane. COQ7 is involved in lifespan determination in ubiquinone-independent manner and also involved in ubiquinone biosynthesis. COQ7 is potential central metabolic regulator. Human COQ7 protein contains 179 amino acids, is mostly helical, and contains an alpha-helical membrane insertion. It has been shown that mutations in the gene are associated with increased life span. Defects of the gene slow down a variety of developmental and physiological processes, including the cell cycle, embryogenesis, post-embryonic growth, rhythmic behaviors and aging.
Corneodesmosin is a protein that is encoded by the CDSN gene in humans. This gene encodes a protein found in corneodesmosomes, which localize to human epidermis and other cornified squamous epithelia. During maturation of the cornified layers, the protein undergoes a series of cleavages, which are thought to be required for desquamation.
Cornulin is a member of the fused gene family of molecular chaperones. Human Cornulin contains N-terminus EF-hand domains and Ca2+ binding domains, and two glutamine- and threonine-rich 60 amino acid repeats in its C-terminus. Cornulin involves in the mucosal/epithelial immune response and epidermal differentiation. Cornulin is a survival factor that participates in the clonogenicity of squamous esophageal epithelium cell lines, attenuates deoxycholic acid (DCA)-induced apoptotic cell death and release of calcium. When Cornulin is overexpressed in oral squamous carcinoma cell lines, it regulates negatively cell proliferation by the induction of G1 arrest.
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