The KCTD family of proteins: structure, function, disease relevance

Abstract

The family of potassium channel tetramerizationdomain (KCTD) proteins consists of 26 members with mostly unknown functions. The name of the protein family is due to the sequence similarity between the conserved N-terminal region of KCTD proteins and the tetramerization domain in some voltage-gated potassium channels. Dozens of publications suggest that KCTD proteins have roles in various biological processes and diseases. In this review, we summarize the character of Bric-a-brack,Tram-track, Broad complex(BTB) of KCTD proteins, their roles in the ubiquitination pathway, and the roles of KCTD mutants in diseases. Furthermore, we review potential downstream signaling pathways and discuss future studies that should be performed.

Salinity-induced changes in gene expression from anterior and posterior gills of Callinectes sapidus (Crustacea: Portunidae) with implications for crustacean ecological genomics

“…For example, a neuropeptide Y receptor, which is a neurotransmitter conserved across nearly all animals that functions in G-protein signaling and regulates a variety of physiological functions (Alfalah and Michel, 2004), was upregulated in posterior gills. Another possible target upregulated in posterior gills was the BTB/POZ domain-containing protein KCTD16, which is also involved in G-protein signaling as well as K + channel function (Liu et al , 2007). Because an as-of-yet unidentified hormone found in the X-organ of the crustacean eyestalk is likely responsible for regulating CAc induction under low salinity (Henry and Campoverde, 2006), examining the acute expression as well as activity of these proteins specifically in crustacean eyestalks during salinity transfer could be a logical next step towards identifying the hormonal basis of osmoregulatory mechanisms in crustaceans.…”

Genes regulated by potassium channel tetramerization domain containing 15 (Kctd15) in the developing neural crest

“…The family is composed of over 20 genes/proteins in different vertebrate species and can be subdivided into seven subgroups on the basis of sequence similarity (Liu et al, 2013; Skoblov et al, 2013). A number of Kctd genes have been associated with human diseases, as summarized by Liu and colleagues (Liu et al, 2013). All members of the family share a Bric-a-brack, Tram-track, Broad complex (BTB) domain usually located in the N-terminal half of the protein.…”

Progressive myoclonic epilepsy-associated geneKctd7regulates retinal neurovascular patterning and function

“…How might Kctd7 function in neurons to impact the vasculature? While the details of Kctd7 cellular biology remain obscure, data support potential mechanisms that center on potassium conductance (reviewed in Liu et al, 2013). KCTD7 is part of a family of proteins that contain the T1 tetramerization domain of voltage gated potassium channels (Kreusch et al, 1998;Stogios et al, 2005).…”

“…Since mouse models for this disease have not been available, its pathogenesis is not well understood. Second, KCTD7 is part of a large family of related proteins that regulate a diverse array of functions ranging from potassium channel tetramerization to ubiquitination (Kreusch et al 1998;Krek, W, 2003;Genschik et al, 2013;Liu et al, 2013). But whether and how such proteins can influence the vasculature remains unknown.…”