SPMAP1

The SPMAP1 gene consists of 6,303 bases. It has three exons and two large introns. The gene has no alternative splice sites.[https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=c17orf98&submit=Go Acieview entry on c17orf98]

The 5' UTR sequence of SPMAP1 is highly conserved in primates. No non-mammalian 5' UTR matches were able to be determined.[https://www.ebi.ac.uk/Tools/msa/clustalo/ ClustalW entry on c17orf98 5' UTR]

NCBI Blast entry on c17orf98 5' UTR

https://blast.ncbi.nlm.nih.gov/Blast.cgi?PROGRAM=blastn&PAGE_TYPE=BlastSearch&LINK_LOC=blastho

me SPMAP1 has 11 Alu repeats.[https://www.genomatix.de/cgibin/eldorado/eldorado.pl?s=0c99e39acf1f2c9dd47191b5b7f412b;SHOW%20_ANNOTATION=C17orf98;ELDORADO_VERSION=E33R1705 Genomatix El Derado etnry on c17orf98]{{Dead link|date=June 2019 |bot=InternetArchiveBot |fix-attempted=yes }}

GeneCards determined that SPMAP1 has five enhancer sequences. The role of the sequences may provide insight into the function of SPMAP1. Four of the five enhancers are active in the thymus. All five enhancers are active in the H1 hESC. Additionally, all five enhancers are active in iPS DF 19.11 derived from foreskin fibroblasts.{{cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=C17orf98|title=C17orf98 Gene - GeneCards - CQ098 Protein - CQ098 Antibody|first=GeneCards Human Gene|last=Database|website=www.genecards.org|access-date=2 May 2018}}

The SPMAP1 promoter has many transcription factors binding sites.{{Cite web|url=https://www.genomatix.de/cgibin/eldorado/eldorado.pl?s=0c99e39acf1f2c9dd47191b5b7f412b;SHOW_ANNOTATION=C17orf98;ELDORADO_VERSION=E33R1705|title=Genomatix El Derado etnry on c17orf98}}{{Dead link|date=June 2019 |bot=InternetArchiveBot |fix-attempted=yes }} SPMAP1's transcription factors are commonly found in hematopoietic cells, connective tissue, cardiovascular tissue, and the immune system. The presence of Krueppel Like Transcription Factors suggests a role for SPMAP1 in proliferation or apoptosis. The presence of SMAD indicates an involvement in the TGF-β pathway, while the presence of Myc related transcription factors indicates a potential proliferation function of the protein. Additionally, other SPMAP1 transcription factors, like RBPJ-Kappa are involved in proliferation and signalling.

Numerous SNPs were found in the 5' UTR, 3' UTR, and coding region of SPMAP1.[https://www.ncbi.nlm.nih.gov/genome/gdv/browser/?context=gene&acc=388381 NCBI Genome Data Viewer] Few SNPs were found in highly conserved regions. In all, four SNPs were found in the highly conserved amino acids. One SNP was found in the start codon sequence. Of these five, three had a SNP on the third position of the codon. Due to the wobble hypothesis, three of the five SNPs would have no effect on the overall protein structure.

SPMAP1 does not have any miRNA binding sites.Target Scan entry on c17orf98 http://www.targetscan.org/cgibin/targetscan/vert_71/view_gene.cgi?rs=ENST00000398575.4&taxid=9606&showcnc=0&shownc=0&shownc_nc=&showncf1=&showncf2=&subset=1{{Dead link|date=June 2019 |bot=InternetArchiveBot |fix-attempted=yes }} Its mRNA has low abundance (0.44%).[https://pax-db.org/protein/1858623# Pax-db entry on c17orf98]

The mRNA sequence has three hexaloops, none of which are significant.{{Cite web|url=http://unafold.rna.albany.edu/results/10/18May04-10-54-31/ |title=mFold entry on c17orf98 5' UTR}}{{Dead link|date=June 2019 |bot=InternetArchiveBot |fix-attempted=yes}}

SPMAP1 is a 17.6kDa protein. Distant orthologs are 5 to 6 kDa larger, but some of the discrepancies come from an added NLS sequence, which Homo sapiens does not have There are no positive or negative charge clusters. There are no transmembrane components. The isoelectric point is 9.80 / 17564.67 pI/Mw.ExPASy pI/mW entry on c17orf98 https://web.expasy.org/cgi-bin/compute_pi/pi_tool{{Dead link|date=November 2018 |bot=InternetArchiveBot |fix-attempted=yes }} SPMAP1 is hydrophobic and soluble. File:Secondary structure and Phosphorylation sites of C17orf98.png

Secondary structure of SPMAP1 consists of both beta sheets and alpha helices (see diagram on right). Results are confirmed in the tertiary structure, however, alpha helix and beta sheet numbers differ slightly (see diagram on right).

There are no N-terminal signal peptides. Cleavage motifs were not found. There are no ER membrane retention signals, nor peroxisomal targeting signal. SKL2 is not present, thus a secondary peroxisome signal is not present. There are no vacuolar targeting signals. There are no RNA binding motifs or actinin type actin binding motifs. There are no N-myristoylation pattern or prenylation patterns.[https://psort.hgc.jp/cgi-bin/runpsort.pl PSort II entry on C17orf98]{{Dead link|date=November 2018 |bot=InternetArchiveBot |fix-attempted=yes }}

File:Model swiss.png

Kinase finder at Cuckoo determined kinase binding sites for SPMAP1. There are many Serine/Threonine, and Tyrosine kinase phosphorylation sites.Bio Cockoo GPS entry on C17orf98 http://gps.biocu{{Dead link|date=June 2019 |bot=InternetArchiveBot |fix-attempted=yes }} Serine and Threonine kinase binding sites are the most prevalent above the statistically significant threshold. There are no SUMOylation sites.GPS Sumo entry on c17orf98 SPMAP1 gene has six sites on the sequence of possible O-GlcNAc sites.YinOyang entry on c17orf98

http://www.cbs.dtu.dk/services/YinOYang/ Highly conserved O-GlcNAc amino acid sites are 24, 32, 117, and 142. O-GlcNAc post-translational modification occurs on Ser/Thr residues, specifically on oncogenes, tumor suppressors, and proteins involved in growth factor signaling.{{cite journal|title=The Hexosamine Signaling Pathway: O-GlcNAc cycling in feast or famine|year= 2010|doi= 10.1016/j.bbagen.2009.07.017|pmc=2815088|last1= Hanover|first1= John A.|last2= Krause|first2= Michael W.|last3= Love|first3= Dona C.|journal= Biochimica et Biophysica Acta (BBA) - General Subjects|volume= 1800|issue= 2|pages= 80–95|pmid= 19647043}}

SPMAP1 has a Caspase3/7 motif, where either Caspase 3 or 7 would cleave. This supports the idea that SPMAP1 is involved in proliferation, as a proapoptotic caspase would want to destroy any protein driving proliferation. The protein also has a motif where peptidyl-prolyl cis-trans isomerase NIMA interacting 1 (Pin1) binds. Pin1 upregulation is involved in cancer and immune disorders.{{cite journal | vauthors = Esnault S, Braun RK, Shen ZJ, Xiang Z, Heninger E, Love RB, Sandor M, Malter JS | title = Pin1 modulates the type 1 immune response | journal = PLOS ONE | volume = 2 | issue = 2 | pages = e226 | date = February 2007 | pmid = 17311089 | pmc = 1790862 | doi = 10.1371/journal.pone.0000226 | bibcode = 2007PLoSO...2..226E | doi-access = free }} This supports the claim that SPMAP1 is involved in cancer, immune cells, and perhaps cancers of the immune system. Additionally, SPMAP1 protein has an IBM site, where inhibitors of apoptosis (IAPs) bind.[http://elm.eu.org/ Eukaryotic Linear Motif search on c17orf98 amino acid sequence] This again supports the idea of SPMAP1 being involved in inhibiting apoptosis, and logically, driving cancer. Furthermore, SPMAP1 has motifs where GRB2's SH2 domain binds. GRB2 is an adapter protein involved in the RAS signaling pathway, a pathway that when deregulated drives uncontrolled proliferation.

A duplication may have occurred at positions 59–71.

Homo sapiens

MAYLSECRLRLEKGFILDGVAVSTAARAYGRSRPKLWSAIPPYNAQQDYHARSYFQ SHVVPPLLRVVPPLLRKTDQDHGGTGRDGWIVDYIHIFGQGQRYLNRRNWAGTGHS LQQVTGHDHYNADLKPIDGFNGRFGYRRNTPALRQSTSVFGEVTHFPLF

There are no known associated proteins.BioGrid entry on c17orf98[https://mint.bio.uniroma2.it/index.php/results-interactions/?id=c17orf98 MINT entry on c17orf98]STRING entry on C17orf98PSICQUIC View entry on [http://www.ebi.ac.uk/Tools/webservices/psicquic/view/results.xhtml?conversationContext=3 c17orf98]

Protein abundance in Homo sapiens whole organism is quite low. No data is available for other species.pax-db entry on c17orf98 https://pax-db.org/protein/1858623# Allen Brain Atlas yields no brain atlas for SPMAP1.{{Cite web|url=http://human.brain-map.org/microarray/search/show?exact_match=true&search_term=C17orf98&search_type=gene&donors=9861,12876,14380,10021,15496,15697|title=Microarray Data :: Allen Brain Atlas: Human Brain|website=human.brain-map.org|access-date=2018-05-06}}

SPMAP1 protein has been found to be expressed in the [https://www.proteinatlas.org/ENSG00000275489-C17orf98/cell intermediate filaments and the nucleoli].Human Protein Atlas (sigma) entry on c17orf98 [https://web.archive.org/web/20160801082255/http://www.proteinatlas.org/ENSG00000275489-C17orf98/cell] A SPMAP1 antibody is available from Sigma-Aldrich.Sigma Aldrich entry on c17orf98 https://www.sigmaaldrich.com/catalog/product/sigma/hpa051696?lang=en®ion=US Additionally, SPMAP1 localizes in the cytoplasm. Distantly related SPMAP1 orthologs in organisms such as Macrostomum lignano and Amphimedon queenslandica exhibit nuclear expression.PSORT II entry on c17orf98 amino acid sequence

https://psort.hgc.jp/form2.html Nuclear localization signals are present in distantly related organisms in non-conserved sites. The results of the k-NN prediction is cytoplasmic localization.PSort II entry on C17orf98 https://psort.hgc.jp/cgi-bin/runpsort.pl{{Dead link|date=November 2018 |bot=InternetArchiveBot |fix-attempted=yes }} SPMAP1 is not a signal peptide.[http://www.cbs.dtu.dk/cgi-bin/webface2.fcgi?jobid=5AD7D62200000C8DFA04286C&wait=20 DTU Bioinformatics entry on c17orf98] The protein is a soluble.[http://harrier.nagahama-i-bio.ac.jp/sosui/cgi-bin/adv_sosui.cgi Expasy Sosui entry on C17orf98]

Like most proteins, SPMAP1 protein is highly expressed in the testes.[https://www.proteinatlas.org/ENSG00000275489-C17orf98/cell Protein Atlas entry on c17orf98] The protein is expressed on adult tissues as well as fetal tissue. The protein has been found to be mildly expressed in connective tissue.NCBI Unigene entry on c17orf98

www.ncbi.nlm.nih.gov/UniGene/clust.cgi?UGID=169593&TAXID=9606&SEARCH=c17orf98 Additionally, expression has been seen in the sperm, breast epithelial cells, and various cells of the immune system.{{Cite web|url=http://biogps.org/#goto=genereport&id=388381 |title=Bio GPS entry on c17orf98}}

Protein expression is elevated in many cancer patients. Specifically, protein expression has been shown to be high on colorectal, breast, prostate, and lung.Human Protein Atlas (sigma) entry on c17orf98 https://www.proteinatlas.org/ENSG00000275489-C17orf98/cell SPMAP1 is expressed in papillary thyroid cancer as well.NCBI GeoProfiles entry on c17orf98

https://www.ncbi.nlm.nih.gov/geoprofiles Additionally, mutations were found in SPMAP1 in endometrial, stomach, coloratura, and kidney cancer.Phosphosite entry on c17orf98 https://www.phosphosite.org/proteinAction.action?id=5156341&showAllSites=true SPMAP1 expression is elevated in cancer patients with BRCA. In kidney renal clear cell carcinoma patients, SPMAP1 expression dramatically decreased compared to the non cancerous state. In 80% of chromophobe renal cell carcinoma patients, at least one gene duplication SPMAP1 was present.

Protein expression is lower in males with teratozoospermia as compared to those without.{{Cite web|url=https://www.ncbi.nlm.nih.gov/geoprofiles/38165767 |title=C17orf98 - Teratozoospermia (HG-U133 2.0 )}} Many Geo Profile experiments have been conducted with SPMAP1, however, none yield data showing significant change in expression.{{Cite web|url=https://www.ncbi.nlm.nih.gov/geoprofiles/?term=c17orf98 |title=NCBI GeoProfiles entry on c17orf98}}

SPMAP1 is a slow mutating protein. It resembles cytochrome c in its rate of divergence, as determined by the molecular clock equations.{{cite web|url=https://www.nature.com/scitable/topicpage/the-molecular-clock-and-estimating-species-divergence-41971|title=The Molecular Clock and Estimating Species Divergence - Learn Science at Scitable|website=www.nature.com|access-date=2 May 2018}}

File:Unrooted c17orf98 Phylogenetic Tree.png

There are no known Homo sapiens paralogs for SPMAP1.Blast entry on c17orf98 https://blast.ncbi.nlm.nih.gov/Blast.cgi?PAGE=Proteins

SPMAP1 protein has additional distantly related orthologs across the metazoan kingdom. Its most distant relative is in the sponge family. There is no known ortholog in ctenophores, nematodes, bacteria, fungus, plants, or zebrafish. There are only two fish with the SPMAP1 gene. Model organisms such as Caenorhabditis elegans, and Drosophila melanogaster, do not have the gene.

SPMAP1 Orthologs

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