Human Gene DISC1 (ENST00000366637.8) Description and Page Index
Description: Homo sapiens DISC1 scaffold protein (DISC1), transcript variant Lv, mRNA. (from RefSeq NM_001012957) RefSeq Summary (NM_001012957): This gene encodes a protein with multiple coiled coil motifs which is located in the nucleus, cytoplasm and mitochondria. The protein is involved in neurite outgrowth and cortical development through its interaction with other proteins. This gene is disrupted in a t(1;11)(q42.1;q14.3) translocation which segregates with schizophrenia and related psychiatric disorders in a large Scottish family. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]. Gencode Transcript: ENST00000366637.8 Gencode Gene: ENSG00000162946.22 Transcript (Including UTRs) Position: hg38 chr1:231,626,815-232,041,127 Size: 414,313 Total Exon Count: 13 Strand: + Coding Region Position: hg38 chr1:231,626,868-232,036,831 Size: 409,964 Coding Exon Count: 13
ID:DISC1_HUMAN DESCRIPTION: RecName: Full=Disrupted in schizophrenia 1 protein; FUNCTION: Involved in the regulation of multiple aspects of embryonic and adult neurogenesis. Required for neural progenitor proliferation in the ventrical/subventrical zone during embryonic brain development and in the adult dentate gyrus of the hippocampus. Participates in the Wnt-mediated neural progenitor proliferation as a positive regulator by modulating GSK3B activity and CTNNB1 abundance. Plays a 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 and synapse formation. Inhibits the activation of AKT-mTOR signaling upon interaction with CCDC88A. Regulates the migration of early-born granule cell precursors toward the dentate gyrus during the hippocampal development. Plays a role, together with PCNT, in the microtubule network formation. SUBUNIT: Interacts with NDEL1. Interacts with CCDC88A (via C- terminus); the interaction is direct. Interacts with GSK3B (By similarity). Interacts with tubulin alpha, ACTN2, ANKHD1, ATF4, ATF5, CEP63, EIF3S3, MAP1A, NDEL1, PAFAH1B1, RANBP9, SPTBN4, SYNE1 and TRAF3IP1. Interaction with microtubules may be mediated in part by TRAF3IP1. Interacts (via C-terminal) with PCNT. Interacts with CHCHD6. INTERACTION: P35609:ACTN2; NbExp=3; IntAct=EBI-529989, EBI-77797; Q8IWZ3-1:ANKHD1; NbExp=6; IntAct=EBI-529989, EBI-1785446; P18848:ATF4; NbExp=3; IntAct=EBI-529989, EBI-492498; Q9Y2D1:ATF5; NbExp=8; IntAct=EBI-529989, EBI-492509; Q6VMQ6:ATF7IP; NbExp=3; IntAct=EBI-529989, EBI-928732; Q6ZP82:CCDC141; NbExp=5; IntAct=EBI-529989, EBI-928795; Q96MT8:CEP63; NbExp=7; IntAct=EBI-529989, EBI-741977; P10909:CLU; NbExp=4; IntAct=EBI-529989, EBI-1104674; P12110:COL6A2; NbExp=3; IntAct=EBI-529989, EBI-928749; Q13561:DCTN2; NbExp=3; IntAct=EBI-529989, EBI-715074; Q03001:DST; NbExp=5; IntAct=EBI-529989, EBI-310758; Q14204:DYNC1H1; NbExp=3; IntAct=EBI-529989, EBI-356015; O15372:EIF3H; NbExp=8; IntAct=EBI-529989, EBI-709735; Q15811:ITSN1; NbExp=3; IntAct=EBI-529989, EBI-602041; Q9Y496:KIF3A; NbExp=3; IntAct=EBI-529989, EBI-1104844; Q9UPN3:MACF1; NbExp=5; IntAct=EBI-529989, EBI-522925; P78559:MAP1A; NbExp=3; IntAct=EBI-529989, EBI-929047; Q9GZM8:NDEL1; NbExp=13; IntAct=EBI-529989, EBI-928842; Q99784:OLFM1; NbExp=3; IntAct=EBI-529989, EBI-1105073; O95613:PCNT; NbExp=5; IntAct=EBI-529989, EBI-530012; Q96S59:RANBP9; NbExp=6; IntAct=EBI-529989, EBI-636085; Q01082:SPTBN1; NbExp=3; IntAct=EBI-529989, EBI-351561; Q9H254:SPTBN4; NbExp=3; IntAct=EBI-529989, EBI-308543; Q8NF91:SYNE1; NbExp=6; IntAct=EBI-529989, EBI-928867; Q8TDR0:TRAF3IP1; NbExp=10; IntAct=EBI-529989, EBI-928811; O75962:TRIO; NbExp=3; IntAct=EBI-529989, EBI-718519; SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, centrosome. Cell junction, synapse, postsynaptic cell membrane, postsynaptic density (By similarity). Note=Colocalizes with NDEL1 in the perinuclear region and the centrosome (By similarity). Localizes to punctate cytoplasmic foci which overlap in part with mitochondria. Colocalizes with PCNT at the centrosome. TISSUE SPECIFICITY: Ubiquitous. Highly expressed in the dentate gyrus of the hippocampus. Also expressed in the temporal and parahippocampal cortices and cells of the white matter. DEVELOPMENTAL STAGE: Expression rises within the dentate gyrus and temporal cortex from the neonatal period to infancy, declines markedly in adolescence, and declines further with aging. DISEASE: Note=A chromosomal aberration involving DISC1 segregates with schizophrenia and related psychiatric disorders in a large Scottish family. Translocation t(1;11)(q42.1;q14.3). The truncated DISC1 protein produced by this translocation is unable to interact with ATF4, ATF5 and NDEL1. DISEASE: Genetic variation in DISC1 is associated with susceptibility to schizophrenia type 9 (SCZD9) [MIM:604906]. A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. SEQUENCE CAUTION: Sequence=BAA32302.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=CAH70955.1; Type=Erroneous gene model prediction; Sequence=CAI15677.1; Type=Erroneous gene model prediction; Sequence=CAI17204.1; Type=Erroneous gene model prediction; Sequence=CAI21886.1; Type=Erroneous gene model prediction; Sequence=CAI22543.1; Type=Erroneous gene model prediction; Sequence=CAI23013.1; Type=Erroneous gene model prediction;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9NRI5
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.