SNAP47

Last updated
SNAP47
Identifiers
Aliases SNAP47 , C1orf142, HEL170, SNAP-47, SVAP1, ESFI5812, HEL-S-290, synaptosome associated protein 47kDa, synaptosome associated protein 47, uncharacterized LOC100130093
External IDs MGI: 1915076 HomoloGene: 14206 GeneCards: SNAP47
Orthologs
SpeciesHumanMouse
Entrez

116841

67826

Ensembl

ENSG00000143740

ENSMUSG00000009894

UniProt

Q5SQN1

Q8R570

RefSeq (mRNA)

n/a

NM_144521
NM_001356452
NM_001356454

RefSeq (protein)

NP_653104
NP_001343381
NP_001343383

Location (UCSC)n/a Chr 11: 59.3 – 59.34 Mb
PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

Synaptosome-associated protein, 47 kDal (SNAP47) is a human protein encoded by the SNAP47 gene. [4] [5] [6] Other aliases of this gene are SVAP1, HEL170, ESFI5812, and HEL-S-290. SNAP47 is a synaptosome protein which is associated with the protein coding in multiple diseases, including non small cell lung cancer and schizophrenia. SNAP47 is a member of the SNAP protein family. SNAP proteins are t-snare proteins that are a component of SNARE complex. The SNARE complex mediates vesicle fusion by creating tight complex that brings vesicle and membrane together. [7] This protein causes ubiquitous expression in testis, ovary, and many other tissues [8]

Contents

Gene

The gene is located at 1q42.13, meaning on chromosome 1 on the long arm of the chromosome in region 42, sub region 13. There are a total of 13 exons and 12 introns. This gene spans 52,693 base pairs. It is encoded on the plus strand. The coordinates for this gene are 227728518-227781231. The gene is flanked by ZNF678 gene and PRSS38 gene on the chromosome while the same location on the minus strand JMJD4 gene. [8]

Protein

The most common isoform of SNAP47 is 419 amino acids long. [8] SNAP47 protein is a synaptosome associated protein. Its molecular weight has been found to be 47167 M. [8] SNARE complex (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) includes syntaxin proteins, VAMP proteins and SNAP proteins. SNARE proteins are generally known to be related to vesicle fusion - mediating exocytosis or neurotransmitter release. [9]

They have also been associated with BLOC-1 (biogenesis of lysosome-related organelles complex-1). Hippocampal neurons deficient in BLOC-1 suggest neurite outgrowth defects which when taken with association of SNARE leads to possible variants of genes encoding BLOC-1 - DTNBP1 - in Schizophrenia models.

C1orf142 model as proposed by I-Tasser. Image colored in rainbow from N to C terminus. Model on I-TASSER.png
C1orf142 model as proposed by I-Tasser. Image colored in rainbow from N to C terminus.

Secondary structure

The secondary structure of SNAP47 has some long alpha helices intermixed with beta sheet and random coils. [10] The alpha helix are placed at about amino acid 120-150 and amino acids 350-415. SNARE proteins are believed to form compact four-helix complex with membranes. [11] The two alpha helices found are consistent with this observation. [10]

Tertiary structure

I-TASSER assembled and then aligned possible SNAP47 tertiary sequence with 5VOX, a Yeast V-ATPase, and a Ufd2 complexed with ubiquitin-like domain Rad23. [12] The TM scores respectively were 0.917 and 0.584.

Regulation of gene expression

Gene level regulation

Promoter

SNAP47 carries 4 promoter regions that create different variants of transcription. These were identified using by Eldorado at Genomatix. Promoter B boosts transcript variant 2 - GXT_27753855. [13]

SNAP47 Promoters
PromoterNameStartEndLength (bp)Transcript
AGXP_67283722277271682277282071040GXT_27753854
BGXP_235582277275182277287461229GXT_2743329, GXT_2743651, GXT_27753855, GXT_27753856, GXT_27753857, GXT_27753859, GXT_27753858, GXT_24484547, GXT_22776811, GXT_24484548
CGXP_235012277338172277354921676GXT_2753839, GXT_27753860, GXT_27753861, GXT_2807628, GXT_27753862, GXT_27753863, GXT_27753864, GXT_23529849, GXT_26185912
DGXP_67283732277346952277357341040GXT_27753865
EGXP_31831672277351732277362171045GXT_26215912, GXT_24484549
FGXP_60214332277466892277481931505GXT_27136253, GXT_27136254

Transcription factors

Transcription Factors that have been predicted to attach to the promoter for SNAP47 are SP1, TATAB, and CARF. SP1 or Stimulating protein 1 had a matrix similarity of 1.0 and is a ubiquitous zinc finger transcription factor and is on the minus strand. TATAB is a TATA binding protein factor with a similar matrix of 0.945. CARF is a calcium response element with a matrix similarity of 0.928. SNAP25 decreases Ca2+ responsiveness in GABAargic synapses.

Expression pattern

RNAseq data display SNAP47 to be highly expressed in the adrenal gland, fetal brain, adult brain and the heart. [8] The adrenal gland, hormone producer, was transcribed at 8 reads per kilobase per million (RPKM). The lungs transcription is relatively low transcription except in a 17-week-old fetus. The transcription of the 17-week-old fetus lung is above 2 RPKM. There is low transcription rate (below 2 RPKM) found in the fetal liver, trachea, pancreas and bone marrow. In the cell, SNAP47 localizes cytoplasm, the endoplasmic reticulum (ER), and Vesicular-tubular cluster (ERGIC). [14]

The protein abundance is about average when compared to all the other proteins in humans. [15] However, the mRNA has a higher than average abundance seen in this microarray. The mRNA is at or above the 75th percentile in the microarray for most of the tissues tested. [16] This may suggest that there is a larger expression rate but the protein is used up quickly for its function.

Protein level regulation

Post-transnational modification

SNAP47 had multiple possible post-translational modifications. High conserved phosphorylation sites were predicted at Y15, S129, S262, and S284 - none with specific kinases. Protein Kinase C plays a role in several signal transduction cascades including calcium release. They had had scores of 0.830, 0.747, and 0.812 at S82, S223, and S231 respectively. [17]

Palmitoylation sites are important in anchoring the SNARE complex to the cytosolic side of membranes. Since many SNAP proteins do not have trans-membrane domains, these are common way of attachment. The Palitic acid is covalently attaches to a cysteine residue. Two Palmitoylation sites were predicted at the beginning of SNAP47 protein at Cys6 and Cys12.

Propeptide cleavage site was predicted at R417 [18] while an acetylation was predicted on S2.

Homology and evolution

Orthologs

As of June 2020, SNAP47 is conserved in 310 orthologs. C. lupus, a wolf/dog, has a 74.2% identity. M. mulatta, a monkey, was aligned with the Homo sapiens protein transcript and a 67.1% identical amino acids were found. [19] P. Marinus, a sea lamprey, is the most distant ortholog found at a 36.1% sequence identity. It was conserved in eukaryotes but not bacteria or Archaea. A selected list of orthologs obtained are shown below. [8]

SNAP 47 Orthologs
Genus/speciesCommon nameOrderDate of divergence (MYA)Accession numberSeq. length (a.a.)Seq. identity (%)Seq. similarity (%)
Homo sapiensHumanPrimates0NP_001310859.1419100100
Canis lupusWolfTherapsid29XP_022282898.141574.285.9
Rattus norvegicusBrown ratRodentia90NP_955421.141973.385.7
Mus musculusMouseRodentia90NP_001343381.167.181.1
Globicephala melasLong-finned whaleCetacea96XP_030700680.142078.889.3
Pteropus vampyrusLarge flying foxChiroptera96XP_011370249.141776.888.3
Loxodonta africanaElephantProboscidea105XP_010599029.142077.988.8
Echinops telfairiHedgehogsAfrosoricida105XP_004696933.142074.087.4
Gallus gallusChickenGalliformes312XP_418505.441959.879.4
Python bivittatusBurmese pythonSerpentes312XP_007439072.142257.376.2
Nestor notabilisKeaPsittaciformes312XP_010008684.137252.870.9
Xenopus tropicalisWestern clawed frogAnura352XP_031759647.141248.969.7
Latimeria chalumnaeWest Indian ocean coelacanthcoelacanth413XP_014340899.141853.974.2
Lepisosteus oculatusSpotted garLepisosteiformes435XP_015209714.142553.472.6
Oryzias melastigmaIndian medakaBeloniformes435XP_024129479.142250.668.9
Denticeps clupeoidesHerringClupeiformes435XP_028833542.142351.572.1
Danio rerioZebrafishCypriniformes435NP_001038902.141948.970.2
Cyprinus carpioCarp fishCypriniformes435XP_018975338.141948.170.5
Sinocyclocheilus grahamiGolden-line barbelCypriniformes435XP_016139191.133239.858.6
Amblyraja radiataThorny skateRajiformes473XP_032876175.142149.568.7
Petromyzon marinusSea lampreyPetromyzontiforme615XP_032802064.141636.154.4

Paralogs

SNAP47 has 3 known paralogs - SNAP23, SNAP25, SNAP 29. The sequence similarity and identity is lower than 30% for all three. This suggest low relationship between different SNAP proteins. SNAP23 and SNAP25 were 55% identical suggesting the relationship between those two paralogs are higher. There is some evidence that if SNAP29 was incapacitated, SNAP47 would be able to take over function of vesicle fusion however, it would not be efficient or successful. [20]

Sequence identity of paralog protein structure compared to SNAP47
ParalogsAccession numberSeq. Identity (%)Seq. Similarity (%)Gaps
SNAP29NP_004773.115.726.648.5
SNAP23NP_003816.214.424.151.4
SNAP25NP_001309831.111.020.165.0

Function/biochemistry

Example of SNAP25 SNARE acrivity resulting in neurotransmitter release of Ca . Hypothetic models of VAMP2 conformations and engagement in SNARE complex assembly for neurotransmitter release.pdf
Example of SNAP25 SNARE acrivity resulting in neurotransmitter release of Ca .

The paralogs, SNAP23 and SNAP25 are t-SNARE proteins, meaning it is present on the presynaptic plasma membrane that is being fused to (the target). [21] These proteins bind to syntaxin protein that attaches to the membrane. SNAP29, however, is binds to syntaxin on vesicles membranes rather than to plasma membranes. SNAP29 has also been found to be membrane bound with a large amount sticking into the cytoplasm. [21]

Interacting proteins

Many interacting proteins are related to vesicle-associated proteins. [22] Some important proteins that interact with the SNAP47 protein are vesicle-associated membrane protein (VAMP) and syntaxin (Stx) which are both used in the SNARE complex. [14] Various paralogs for VAMP and Stx were found as possible interactions. They were experimentally tested using anti-tag coimmunoprecipitation. VAMP4 and Stx-1A interact in the calcium dependent exocytosis. Golgin subfamily A member 2 protein (GOLGA2) is a protein used as a vesicle facilitating vesicle fusion with Golgi apparatus. A microarray as well as prey pooling approach were used to determine this interaction between GOLGA2 and SNAP47. A component of LINC (linker of Nucleoskeleton and cytoskeleton) Complex is the KASH5 protein that was found to interact with SNAP47 by a two hybrid and prey pooling approach.

Clinical significance

Two viruses that interact are rep and PVR proteins which are replicase polyprotein 1ab and Poliovirus receptor respectively. Replicase polyprotein 1ab protein is in the human Sars coronavirus. Rep is involved in the transcription and replication of viral RNAs. [23] An alternative name is the ORF1ab polyprotein. It contains the polyprotein cleavage proteinases. The optimum pH for the proteinase activity is 7.0. Pp1ab is known to be cleaved in 15 different chains including (not limited to) Host translation inhibitor nsp1, 3C-like proteinase, and helicase.  Not much is known in how it interacts with SNAP47.

The poliovirus receptor plays a role in cell motility during tumor cell invasion and migration. PVR binds to CD96 and CD226 - Natural killer cell receptors. This can cause PVR to possibly be transferred to NK cells and cause fratricide of Natural killer cells which can increase metastasizing possibilities. Although the lung does not seem to have a large expression of this protein, it has been found that C1orf142 has larger expression rates in cell line of giant cell lung carcinoma they have high metastatic potential. [24] Cell line 95D (high metastatic potential) was studied along with 95C (low metastatic potential) and it is suggested that there is a possible link between SNAP47 protein and metastasis in lung cancers.

Related Research Articles

<span class="mw-page-title-main">SNARE protein</span> Protein family

SNARE proteins – "SNAPREceptors" – are a large protein family consisting of at least 24 members in yeasts, more than 60 members in mammalian cells, and some numbers in plants. The primary role of SNARE proteins is to mediate the fusion of vesicles with the target membrane; this notably mediates exocytosis, but can also mediate the fusion of vesicles with membrane-bound compartments. The best studied SNAREs are those that mediate the release of synaptic vesicles containing neurotransmitters in neurons. These neuronal SNAREs are the targets of the neurotoxins responsible for botulism and tetanus produced by certain bacteria.

<span class="mw-page-title-main">SNAP25</span> Protein-coding gene in the species Homo sapiens

Synaptosomal-Associated Protein, 25kDa (SNAP-25) is a Target Soluble NSF (N-ethylmaleimide-sensitive factor) Attachment Protein Receptor (t-SNARE) protein encoded by the SNAP25 gene found on chromosome 20p12.2 in humans. SNAP-25 is a component of the trans-SNARE complex, which accounts for membrane fusion specificity and directly executes fusion by forming a tight complex that brings the synaptic vesicle and plasma membranes together.

<span class="mw-page-title-main">STX1A</span> Protein-coding gene in the species Homo sapiens

Syntaxin-1A is a protein that in humans is encoded by the STX1A gene.

<span class="mw-page-title-main">SNAP23</span> Protein-coding gene in the species Homo sapiens

Synaptosomal-associated protein 23 is a protein that in humans is encoded by the SNAP23 gene. Two alternative transcript variants encoding different protein isoforms have been described for this gene.

<span class="mw-page-title-main">STX4</span> Protein-coding gene in the species Homo sapiens

Syntaxin-4 is a protein that in humans is encoded by the STX4 gene.

<span class="mw-page-title-main">SYT1</span> Protein-coding gene in the species Homo sapiens

Synaptotagmin-1 is a protein that in humans is encoded by the SYT1 gene.

<span class="mw-page-title-main">VAMP2</span> Protein-coding gene in the species Homo sapiens

Vesicle-associated membrane protein 2 (VAMP2) is a protein that in humans is encoded by the VAMP2 gene.

<span class="mw-page-title-main">Vesicle-associated membrane protein 7</span> Protein-coding gene in the species Homo sapiens

Vesicle-associated membrane protein 7 (VAMP-7), is a protein that in humans is encoded by the VAMP7 gene also known as the or SYBL1 gene.

<span class="mw-page-title-main">STX6</span> Protein-coding gene in the species Homo sapiens

Syntaxin-6 is a protein that in humans is encoded by the STX6 gene.

<span class="mw-page-title-main">NAPA (gene)</span> Protein-coding gene in the species Homo sapiens

N-ethylmaleimide-sensitive factor Attachment Protein Alpha, also known as SNAP-α, is a SNAP protein that is involved in the intra-cellular trafficking and fusing of vesicles to target membranes in cells.

<span class="mw-page-title-main">VAMP3</span> Protein-coding gene in the species Homo sapiens

Vesicle-associated membrane protein 3 is a protein that in humans is encoded by the VAMP3 gene.

<span class="mw-page-title-main">STX2</span> Protein-coding gene in the species Homo sapiens

Syntaxin-2, also known as epimorphin, is a protein that in humans is encoded by the STX2 gene.

<span class="mw-page-title-main">Vesicle-associated membrane protein 8</span> Protein-coding gene in the species Homo sapiens

Vesicle-associated membrane protein 8 is a protein that in humans is encoded by the VAMP8 gene.

<span class="mw-page-title-main">SNAP29</span> Protein-coding gene in the species Homo sapiens

Synaptosomal-associated protein 29 is a protein that in humans is encoded by the SNAP29 gene.

<span class="mw-page-title-main">VAMP1</span> Protein-coding gene in the species Homo sapiens

Vesicle-associated membrane protein 1 (VAMP1) is a protein that in humans is encoded by the VAMP1 gene.

<span class="mw-page-title-main">Syntaxin 3</span> Protein-coding gene in the species Homo sapiens

Syntaxin 3, also known as STX3, is a protein which in humans is encoded by the STX3 gene.

<span class="mw-page-title-main">Syntaxin</span> Group of proteins

Syntaxins are a family of membrane integrated Q-SNARE proteins participating in exocytosis.

<span class="mw-page-title-main">ZCCHC18</span> Protein-coding gene in the species Homo sapiens

Zinc finger CCHC-type containing 18 (ZCCHC18) is a protein that in humans is encoded by ZCCHC18 gene. It is also known as Smad-interacting zinc finger protein 2 (SIZN2), para-neoplastic Ma antigen family member 7b (PNMA7B), and LOC644353. Other names such as zinc finger, CCHC domain containing 12 pseudogene 1, P0CG32, ZCC18_HUMAN had been used to describe this protein.

RING Finger Protein 227, also known as RNF227 and LINC02581, is a protein which in humans is encoded by the RNF227 gene. According to DNA microarray data, it is found in at least 15 tissues.

<span class="mw-page-title-main">TMEM248</span> Transmembrane protein 248/TMEM248 gene

Transmembrane protein 248, also known as C7orf42, is a gene that in humans encodes the TMEM248 protein. This gene contains multiple transmembrane domains and is composed of seven exons.TMEM248 is predicted to be a component of the plasma membrane and be involved in vesicular trafficking. It has low tissue specificity, meaning it is ubiquitously expressed in tissues throughout the human body. Orthology analyses determined that TMEM248 is highly conserved, having homology with vertebrates and invertebrates. TMEM248 may play a role in cancer development. It was shown to be more highly expressed in cases of colon, breast, lung, ovarian, brain, and renal cancers.

References

  1. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000009894 - Ensembl, May 2017
  2. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2020-07-28.
  5. ↑ "SNAP47 - Synaptosomal-associated protein 47 - Homo sapiens (Human) - SNAP47 gene & protein". www.uniprot.org. UniProt . Retrieved 2020-08-01.
  6. ↑ "SNAP47 synaptosome associated protein 47 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. National Center for Biotechnology Information, U.S. National Library of Medicine . Retrieved 2020-08-01.
  7. ↑ Rizo, Josep; Südhof, Thomas C. (August 2002). "Snares and Munc18 in synaptic vesicle fusion". Nature Reviews. Neuroscience. 3 (8): 641–653. doi:10.1038/nrn898. ISSN   1471-003X. PMID   12154365. S2CID   13351502.
  8. 1 2 3 4 5 6 "SNAP47 synaptosome associated protein 47 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-06-10.
  9. ↑ "SNAP47 Gene - GeneCards | SNP47 Protein | SNP47 Antibody". www.genecards.org. Retrieved 2020-06-18.
  10. 1 2 "Bioinformatics Toolkit". toolkit.tuebingen.mpg.de. Retrieved 2020-07-31.
  11. ↑ Holt, Matthew; Varoqueaux, Frédérique; Wiederhold, Katrin; Takamori, Shigeo; Urlaub, Henning; Fasshauer, Dirk; Jahn, Reinhard (2006-06-23). "Identification of SNAP-47, a Novel Qbc-SNARE with Ubiquitous Expression". Journal of Biological Chemistry. 281 (25): 17076–17083. doi: 10.1074/jbc.M513838200 . ISSN   0021-9258. PMID   16621800. S2CID   33998436.
  12. ↑ "I-TASSER results". zhanglab.ccmb.med.umich.edu. Retrieved 2020-08-01.
  13. ↑ Genomatix Software Suite (July 2020). "ElDorado". Genomatix.
  14. 1 2 Kuster, Aurelia; Nola, Sebastien; Dingli, Florent; Vacca, Barbara; Gauchy, Christian; Beaujouan, Jean-Claude; Nunez, Marcela; Moncion, Thomas; Loew, Damarys; Formstecher, Etienne; Galli, Thierry (2015-11-20). "The Q-soluble N -Ethylmaleimide-sensitive Factor Attachment Protein Receptor (Q-SNARE) SNAP-47 Regulates Trafficking of Selected Vesicle-associated Membrane Proteins (VAMPs)". Journal of Biological Chemistry. 290 (47): 28056–28069. doi: 10.1074/jbc.M115.666362 . ISSN   0021-9258. PMC   4653666 . PMID   26359495.
  15. ↑ "PAXdb: Protein Abundance Database". pax-db.org. Retrieved 2020-07-29.
  16. ↑ "GDS3113 / 194925". www.ncbi.nlm.nih.gov. Retrieved 2020-07-29.
  17. ↑ "NetPhos 3.1 Server". www.cbs.dtu.dk. Retrieved 2020-07-29.
  18. ↑ "ProP 1.0 Server". www.cbs.dtu.dk. Retrieved 2020-07-29.
  19. ↑ "EMBOSS Needle < Pairwise Sequence Alignment < EMBL-EBI". www.ebi.ac.uk. Retrieved 2020-06-18.
  20. ↑ "SNAP29 Gene - GeneCards | SNP29 Protein | SNP29 Antibody". www.genecards.org. Retrieved 2020-07-29.
  21. 1 2 Ramakrishnan, Neeliyath A.; Drescher, Marian J.; Drescher, Dennis G. (May 2012). "The SNARE complex in neuronal and sensory cells". Molecular and Cellular Neurosciences. 50 (1): 58–69. doi:10.1016/j.mcn.2012.03.009. ISSN   1044-7431. PMC   3570063 . PMID   22498053.
  22. ↑ "IntAct Molecular Interaction". www.ebi.ac.uk.
  23. ↑ "P0C6X7- Replicase polyprotein 1ab". UniProt.
  24. ↑ Sun, Wenjing; Guo, Changlong; Meng, Xiangning; Yu, Yang; Jin, Yan; Tong, Dandan; Geng, Jingshu; Huang, Qi; Qi, Jiping; Liu, An; Guan, Rongwei (2012-04-01). "Differential Expression of PAI-RBP1, C1orf142, and COTL1 in Non–Small Cell Lung Cancer Cell Lines With Different Tumor Metastatic Potential". Journal of Investigative Medicine. 60 (4): 689–694. doi:10.2310/jim.0b013e31824963b6. ISSN   1081-5589. PMID   22373659. S2CID   45294541.
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