Human Gene CLSTN1 (uc001aqh.3) Description and Page Index
Description: Homo sapiens calsyntenin 1 (CLSTN1), transcript variant 1, mRNA. RefSeq Summary (NM_001009566): This gene is a member of the calsyntenin family, a subset of the cadherin superfamily. The encoded transmembrane protein, also known as alcadein-alpha, is thought to bind to kinesin-1 motors to mediate the axonal anterograde transport of certain types of vesicle. Amyloid precursor protein (APP) is trafficked via these vesicles and so this protein is being investigated to see how it might contribute to the mechanisms underlying Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]. Transcript (Including UTRs) Position: hg19 chr1:9,789,079-9,884,550 Size: 95,472 Total Exon Count: 19 Strand: - Coding Region Position: hg19 chr1:9,790,566-9,883,791 Size: 93,226 Coding Exon Count: 19
ID:CSTN1_HUMAN DESCRIPTION: RecName: Full=Calsyntenin-1; AltName: Full=Alcadein-alpha; Short=Alc-alpha; AltName: Full=Alzheimer-related cadherin-like protein; AltName: Full=Non-classical cadherin XB31alpha; Contains: RecName: Full=Soluble Alc-alpha; Short=SAlc-alpha; Contains: RecName: Full=CTF1-alpha; AltName: Full=C-terminal fragment 1-alpha; Flags: Precursor; FUNCTION: Induces KLC1 association with vesicles and functions as a cargo in axonal anterograde transport. Complex formation with APBA2 and APP, stabilizes APP metabolism and enhances APBA2- mediated suppression of beta-APP40 secretion, due to the retardation of intracellular APP maturation. In complex with APBA2 and C99, a C-terminal APP fragment, abolishes C99 interaction with PSEN1 and thus APP C99 cleavage by gamma-secretase, most probably through stabilization of the direct interaction between APBA2 and APP. The intracellular fragment AlcICD suppresses APBB1-dependent transactivation stimulated by APP C-terminal intracellular fragment (AICD), most probably by competing with AICD for APBB1- binding. May modulate calcium-mediated postsynaptic signals (By similarity). SUBUNIT: Directly interacts with APBA2. Forms a tripartite complex with APBA2 and APP. The CTF1 chain interacts with PSEN1. The intracellular fragment AlcICD interacts with APBB1; this interaction stabilizes AlcICD metabolism. Interacts with KLC1 and APBB1 (By similarity). SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus membrane. Cell projection. Cell junction, synapse, postsynaptic cell membrane; Single-pass type I membrane protein (By similarity). Nucleus. Note=Neurite tips. Localized in the postsynaptic membrane of both excitatory and inhibitory synapses (By similarity). The AlcICD fragment is translocated to the nucleus upon interaction with APBB1. TISSUE SPECIFICITY: Expressed in the brain and, a lower level, in the heart, skeletal muscle, kidney and placenta. Accumulates in dystrophic neurites around the amyloid core of Alzheimer disease senile plaques (at protein level). DOMAIN: The cytoplasmic domain is involved in interaction with APBA2, as well as the binding of synaptic Ca(2+) (By similarity). PTM: Proteolytically processed under normal cellular conditions. A primary zeta-cleavage generates a large extracellular (soluble) N- terminal domain (sAlc) and a short C-terminal transmembrane fragment (CTF1). A secondary cleavage catalyzed by presenilin gamma-secretase within the transmembrane domain releases the beta- Alc-alpha chain in the extracellular milieu and produces an intracellular fragment (AlcICD). This processing is strongly suppressed in the tripartite complex formed with APBA2 and APP, which seems to prevent the association with PSEN1. SIMILARITY: Contains 2 cadherin domains. SEQUENCE CAUTION: Sequence=BAA74934.2; Type=Erroneous initiation;
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 O94985
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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.