disrupted in schizophrenia 1 protein (DISC1, KIAA0457)

Function: - role in the regulation of multiple aspects of embryonic & adult neurogenesis - required for neural progenitor proliferation in the ventrical/subventrical zone during embryonic brain development & in the adult dentate gyrus of the hippocampus - participates in the Wnt-mediated neural progenitor proliferation as a positive regulator by modulating GSK3B activity & CTNNB1 abundance - role as a modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including neuron positioning, dendritic development & synapse formation - inhibits activation of AKT-mTOR signaling upon interaction with CCDC88A - regulates migration of early-born granule cell precursors toward the dentate gyrus during hippocampal development - plays a role, together with PCNT, in the microtubule network formation - interacts with NDEL1 - interacts with CCDC88A (via C- terminus); the interaction is direct - interacts with GSK3B - interacts with tubulin alpha, ACTN2, ANKHD1, ATF4, ATF5, CEP63, EIF3S3, MAP1A, NDEL1, PAFAH1B1, RANBP9, SPTBN4, SYNE1 & TRAF3IP1. - interaction with microtubules may be mediated in part by TRAF3IP1. - interacts (via C-terminal) with PCNT Compartment: - cytoplasm. cytoplasm, cytoskeleton, centrosome. cytoplasm, cytoskeleton - localizes to neurites - colocalizes with NDEL1 in the perinuclear region & the centrosome (putative) - localizes to punctate cytoplasmic foci which overlap in part with mitochondria - colocalizes with PCNT at the centrosome Alternative splicing: named isoforms=4 Expression: - ubiquitous - highly expressed in the dentate gyrus of the hippocampus - also expressed in the temporal cortex & parahippocampal cortex & cells of the white matter - expression rises within the dentate gyrus & temporal cortex from the neonatal period to infancy, declines markedly in adolescence, & declines further with aging Pathology: - chromosomal translocation t(1;11)(q42.1;q14.3) involving DISC1 segregates with schizophrenia & related psychiatric disorders in a large Scottish family - the truncated DISC1 protein produced by this translocation is unable to interact with ATF4, ATF5 & NDEL1 - genetic variation in DISC1 is associated with susceptibility to schizophrenia type 9

Properties

SIZE: entity length = 854 aa MW = 94 kD COMPARTMENT: mitochondria cytoplasm cell nucleus MOTIF: MAP1A interaction {1-292} TRAF3IP1 interaction {293-696} MOTIF: coiled coil {366-394} punctate cytoplasmic foci {440-597} domain {446-854} MOTIF: coiled coil {452-505} ATF4/ATF5 interaction {598-854} coiled coil {602-666} PAFAH1B1 interaction {727-854} NDEL1 interaction {802-835} coiled coil {802-830}

Database Correlations

OMIM correlations MORBIDMAP 605210 UniProt Q9NRI5 Entrez Gene 27185 Kegg hsa:27185

References

UniProt :accession Q9NRI5