HGNC Approved Gene Symbol: SNPHCytogenetic location: 20p13 Genomic coordinates (GRCh38): 20:1,266,291-1,309,326 (from NCBI)▼ DescriptionSyntaphilin participa...
HGNC Approved Gene Symbol: SNPH
Cytogenetic location: 20p13 Genomic coordinates (GRCh38): 20:1,266,291-1,309,326 (from NCBI)
Syntaphilin participates in regulation of SNARE complex formation and subsequent neurotransmitter release (Lao et al., 2000).
▼ Cloning and Expression
By sequencing randomly selected cDNAs corresponding to relatively long transcripts from human brain, Nagase et al. (1997) cloned SNPH, which they called KIAA0374. The cDNA contains the complete syntaphilin coding sequence. The deduced syntaphilin protein has 538 amino acids. In vitro transcribed/translated syntaphilin protein had an apparent molecular mass of approximately 72 kD by SDS-PAGE. RT-PCR analysis of 14 human tissues indicated that syntaphilin is expressed only in brain.
To identify proteins that regulate synaptic vesicle exocytosis by binding to components of the SNARE complex, Lao et al. (2000) screened a human brain cDNA library using the yeast 2-hybrid system with the C-terminal half of syntaxin-1 (STX1A; 186590) as bait. They isolated a partial syntaphilin cDNA lacking 5-prime coding sequence. Lao et al. (2000) found that the deduced protein encoded by their syntaphilin cDNA was identical to that encoded by the KIAA0374 cDNA isolated by Nagase et al. (1997) except that it lacked 141 amino acids at the N terminus. Thus, they used the full-length KIAA0374 cDNA in their studies. The deduced 537-amino acid syntaphilin protein contains an N-terminal proline-rich domain, a predicted coiled-coil domain, a putative C-terminal transmembrane domain, and numerous consensus sites for protein phosphorylation. Whereas the calculated molecular mass of syntaphilin is 58 kD, recombinant syntaphilin expressed in a human cell line had a molecular mass of 68 kD by immunoblot analysis. The authors showed that syntaphilin competes with SNAP25 (600322) for binding to syntaxin-1 and inhibits SNARE complex formation by absorbing free syntaxin-1. Transient overexpression of syntaphilin in cultured hippocampal neurons significantly reduced neurotransmitter release. Furthermore, introduction of syntaphilin into presynaptic superior cervical ganglion neurons in culture inhibited synaptic transmission. Northern blot analysis of 8 different human tissues detected a 5.5-kb syntaphilin transcript only in brain. Immunoblot analysis found that syntaphilin protein is present in anatomically and functionally distinct areas of rat brain, including the cortex, hippocampus, olfactory bulb, striatum, midbrain, and pons. Subcellular localization studies on cultured hippocampal neurons showed that syntaphilin is expressed in the cell body of neurons and in a punctate pattern along the processes of the neurons. Syntaphilin and STX1A were to a large extent colocalized along the entire axon. Syntaphilin was partially colocalized with the presynaptic vesicle marker synaptophysin (313475). Subcellular fractionation studies on rat brain synaptosomes indicated that syntaphilin associates with membrane fractions but not the cytosolic fraction. Syntaphilin was present primarily in the plasma membrane fractions and to a lesser extent in the synaptic vesicle fraction. Lao et al. (2000) suggested that syntaphilin may function as a molecular clamp that controls free syntaxin-1 availability for the assembly of the SNARE complex, and thereby regulates synaptic vesicle exocytosis.
By radiation hybrid mapping, Nagase et al. (1997) mapped the SNPH gene to chromosome 20.