SNAP47

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]

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.

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]

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.

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.

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.

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 eukayotes but not bacteria or Archaea. A selected list of orthologs obtained are shown below.[8]

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]