SNPH Human
Description
Neuronal Function
SNPH regulates synaptic vesicle dynamics by binding syntaxin-1, a core component of the SNARE complex .
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Inhibits SNARE complex formation, preventing premature synaptic vesicle fusion .
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Anchors mitochondria to axonal microtubules, maintaining stationary populations critical for energy supply and synaptic function .
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Modulates endocytosis: Blocks dynamin-mediated vesicle retrieval, affecting neurotransmitter recycling .
Cancer-Related Functions
In tumors, SNPH acquires distinct roles linked to mitochondrial dynamics and metastasis:
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Suppresses mitochondrial motility: Prevents cortical cytoskeleton accumulation, limiting invasion .
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Buffers oxidative stress: Maintains complex II-dependent bioenergetics, supporting tumor growth under stress .
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Regulates proliferation-motility balance: Stress-induced SNPH downregulation shifts cells toward invasion .
Table 2: Comparative Functions of SNPH in Neurons vs. Cancer Cells
Ubiquitination
SNPH is ubiquitinated at Lys111 and Lys153 by the E3 ligase CHIP (STUB1), which:
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Stabilizes microtubule binding, inhibiting mitochondrial motility .
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Blocks Drp1 recruitment, reducing mitochondrial fission and dynamics .
Mutations at these sites (K111R, K153R) enhance mitochondrial trafficking and tumor chemotaxis .
Alternative Splicing
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L-SNPH: Brain-specific isoform linked to synaptic regulation .
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S-SNPH: Tumor-associated isoform with a mitochondrial localization signal (MLS), enabling cytoskeletal modulation .
Neurological Insights
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Mitochondrial docking: SNPH loss in mice increases mobile axonal mitochondria, impairing synaptic function .
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Neurodegeneration: Dysregulated SNPH may contribute to mitochondrial dyshomeostasis in Alzheimer’s or Huntington’s disease .
Oncological Relevance
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Metastasis suppression: SNPH depletion promotes mitochondrial cortical redistribution, enhancing invasion .
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Therapeutic target: Overexpression of SNPH in tumors reduces metastatic dissemination in xenograft models .
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Neutrophil migration: Low SNPH in tumor-bearing mice correlates with increased PMN-MDSC migration, promoting pre-metastatic niche formation .
Applications and Future Directions
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Research tools: Recombinant SNPH is used to study SNARE complex inhibition and mitochondrial dynamics .
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Therapeutic potential: Targeting SNPH ubiquitination or splicing may modulate cancer progression .
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Diagnostic biomarkers: SNPH expression levels could predict metastatic risk in cancers .
References
Product Specs
MGSSHHHHHH SSGLVPRGSH MAMSLPGSRR TSAGSRRRTS PPVSVRDAYG TSSLSSSSNS GSYKGSDSSP TPRRSMKYTL CSDNHGIKPPTPEQYLTPLQ QKEVCIRHLK ARLKDTQDRL QDRDTEIDDL KTQLSRMQED WIEEECHRVE AQLALKEARK EIKQLKQVID TVKNNLIDKDKGLQKYFVDI NIQNKKLETL LHSMEVAQNG MAKEDGTGES AGGSPARSLT RSSTYTKLSD PAVCGDRQPG DPSSGSAEDG ADSGFAAADD
TLSRTDALEA SSLLSSGVDC GTEETSLHSS FGLGPRFPAS NTYEKLLCGM EAGVQASCMQ ERAIQTDFVQ YQPDLDTILE KVTQAQVCGTDPESGDRCPE LDAHPSGPRD PNSAVVVTVG DELEAPEPIT RGPTPQRPGA NPNPGQSVSV VCPMEEEEEA AVAEKEPKSY WSRH.
Product Science Overview
Syntaphilin is a neuron-specific protein encoded by the SNPH gene in humans. It plays a crucial role in the regulation of mitochondrial dynamics and synaptic function. Syntaphilin is known for its ability to inhibit the formation of the SNARE complex by binding to free syntaxin-1, thereby controlling synaptic vesicle docking and fusion .
Recombinant human syntaphilin is typically produced using bacterial expression systems, such as Escherichia coli (E. coli). The gene encoding syntaphilin is cloned into an expression vector, which is then introduced into the bacterial cells. The bacteria are cultured under conditions that induce the expression of the recombinant protein. After sufficient growth, the cells are harvested, lysed, and the recombinant protein is purified using affinity chromatography techniques. The purified protein often includes a His-tag to facilitate purification and detection .
Syntaphilin’s primary function involves its interaction with mitochondrial and cytoskeletal components. It acts as a static anchor for mitochondria in axons by binding to microtubules, thereby regulating mitochondrial mobility. This interaction is crucial for maintaining proper mitochondrial distribution within neurons, which is essential for neuronal function and energy homeostasis .
Additionally, syntaphilin undergoes post-translational modifications, such as ubiquitination, which regulate its function. Ubiquitination of syntaphilin by the E3 ligase CHIP on specific lysine residues (Lys111 and Lys153) anchors syntaphilin on tubulin, inhibiting mitochondrial motility and promoting mitochondrial dynamics . This regulation is vital for controlling mitochondrial trafficking and tumor cell motility, highlighting syntaphilin’s role in cellular processes beyond neuronal function .
