The reference OMIM entry for this protein is 604569

Contactin-associated protein-like 2; cntnap2
Contactin-associated protein 2; caspr2
Neurexin iv, drosophila, homolog of; nrxn4

DESCRIPTION

The CNTNAP2 gene encodes a neuronal transmembrane protein member of the neurexin superfamily involved in neural-glia interactions and clustering of potassium channels in myelinated axons. Rapid conduction in myelinated axons depends on the generation of specialized subcellular domains to which different sets of ion channels are localized. Contactin-associated protein (CNTNAP1; 602346) is another member of the neurexin superfamily (summary by Poliak et al., 1999).

CLONING

By searching sequence databases for homologs of CASPR, Poliak et al. (1999) identified several CASPR-related ESTs from various nervous system sources. They used 1 of these ESTs to isolate human brain and spinal cord cDNAs representing the entire CASPR2 coding sequence. The structural organization of the deduced 1,333-amino acid CASPR2 protein is very similar to that of CASPR and the related Drosophila Nrx IV, all having the hallmarks of type I transmembrane proteins. The extracellular region of CASPR2 is a mosaic of domains, including discoidin/neuropilin- and fibrinogen-like domains, 2 epidermal growth factor (EGF; 131530) repeats, and 4 domains similar to a region in laminin A (150320), referred to as the G domain. The extracellular region of CASPR2 also contains 12 potential N-linked glycosylation sites. CASPR2 has a short C-terminal region containing a binding site for type II PDZ domains. CASPR2 shares 45% amino acid sequence identity with CASPR and 34% identity with Drosophila Nrx IV. Recombinant CASPR2 expressed in mammalian cells had an apparent molecular mass of 180 kD. Northern blot analysis of human tissues detected 9- and 10-kb CASPR2 transcripts in brain, but only the 9-kb transcript in spinal cord. Low levels of CASPR2 mRNA were also detected in the ovary and prostate. The authors determined the expression pattern of CASPR2 within the adult human central nervous system. Like the spinal cord, the corpus callosum expressed only the 9-kb CASPR2 transcript. The 9-kb transcript was also the predominant transcript in the medulla, substantia nigra, and caudate nucleus. All the other regions examined, namely cerebellum, cortex, occipital pole, frontal lobe, temporal lobe, putamen, amygdala, hippocampus, subthalamic nucleus, and thalamus, expressed similar levels of the 9- and 10-kb CASPR2 transcripts. Immunolocalization of Caspr2 in adult rat brain demonstrated that Caspr2 is differentially expressed in distinct neuronal structures, including the soma and dendrites, and in specific short-segmented pairs along myelinated axons. Caspr2 expression in myelinated nerves was mostly confined to the axon at the juxtaparanodal region and to some isolated paranodal loops. In the juxtaparanodal region, Caspr2 precisely colocalized with Shaker-like potassium channels. Caspr2 specifically associated with Kv1.1 (176260), Kv1.2 (176262), and their Kv-beta-2 subunit (601142). This association involved the C-terminal region of Caspr2. Poliak et al. (1999) suggested that CASPR2 may stabilize the localization of potassium channels in the juxtaparanodal region, and that CASPR2 family members may play a role in the local differentiation of the axon into distinct functional subdomains. Krumbiegel et al. (2011) performed comprehensive mRNA and protein expression analysis in ocular tissues from eyes with PEX syndrome/glaucoma (177650) and normal and glaucomatous control eyes. Quantitative real-time PCR showed ubiquitous expression of CNTNAP2 in virtually ... More on the omim web site

Subscribe to this protein entry history

April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 604569 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).