Neuronal vesicle trafficking-associated protein (IPR009431)

Short name: NSG

Overlapping homologous superfamilies


Family relationships



This family includes the neuron-enriched endosomal proteins NSG1 (NEEP21), NSG2 (P19) and NSG3 (calcyon, Caly). They interact with distinct elements of the endosomal and synaptic scaffolding machinery [PMID: 25376768]. NSG1 and NSG2 may not be resident endosomal proteins, and are also known as neuronal vesicle trafficking-associated proteins 1 and 2 respectively [PMID: 28874679]. NSG1/NEEP21 plays a role in the trafficking of multiple receptors, including the cell adhesion molecule L1/NgCAM, the neurotransmitter receptor GluA2, and beta-APP [PMID: 28299779]. The role of NSG2 is not known.

It was originally thought that the Neuron-specific vesicular protein calcyon (previously known as D1 dopamine receptor-interacting, calcyon), interacted directly with the D1 dopamine receptor (DRD1) to modulate neocortical and hippocampal neuronal excitability [PMID: 10698743] as well as cAMP-dependent signalling [PMID: 11929934]. However, this work was retracted, as it was shown that a direct interaction with the dopamine D1 receptor had been misinterpreted [PMID: 17170272]. However, it has been shown that calcyon induces D1DR to stimulate intracellular Ca2+ release, and this suggests a possible functional interaction between calcyon and D1DR, despite there being, as yet, no direct interaction between them. A recent study suggested that calcyon-containing vesicles might transport D1DR by associating calcyon with D1DR through their assembly to clathrin [PMID: 16595675]. However, as a single transmembrane protein, it is currently not clear how calcyon can regulate the internalization of D1DR from the plasma membrane to endocytic vesicles.

Calcyon is a brain-specific protein, mainly localized in the intracellular endosomal vesicles of dendritic spines in dopamine expressing pyramidal cells in the prefrontal cortex and hippocampus and dorsal striatum region [PMID: 11929934, PMID: 10698743]. Neuron-specific vesicular protein calcyon has implicated in clathrin-mediated endocytosis. It is exclusively expressed in neurons, and localized in moving vesicles and it thought to play a role in brain plasticity [PMID: 17885599]. Defective calcyon proteins have been implicated in both attention-deficit/hyperactivity disorder (ADHD) [PMID: 11923911, PMID: 17623072] and schizophrenia [PMID: 12622665].

GO terms

Biological Process

GO:0048268 clathrin coat assembly
GO:0007212 dopamine receptor signaling pathway

Molecular Function

GO:0032051 clathrin light chain binding

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.