SPMIP10

SPMIP10 (or Sperm Microtubule Inner Protein 10) is also known as Testis Expressed 43, C5orf48, Tseg7, Sperm Associated Microtubule Inner Protein 10, and Testis Specific Expressed Gene 73.{{Cite web |title=Gene Cards |url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=SPMIP10 |website=GeneCards}}

File:Ideogram of SPMIP10s location on chromosome 5.png

SPMIP10 is located on the plus strand of the long arm of chromosome 5, band 23, sub-band 2 (5q23.2, see the ideogram of the SPMIP10 gene location on chromosome 5).

SPMIP10 is a 478 bp long protein-coding gene.{{Cite web|url=https://www.ncbi.nlm.nih.gov/protein/NP_997291.1|title=sperm-associated microtubule inner protein 10 [Homo sapiens] - Protein - NCBI|website=www.ncbi.nlm.nih.gov}} SPMIP10 contains three exons. Exon 1 spans from position 1–116, exon 2 spans from positions 117–225, and exon 3 spans from positions 226–478 in the SPMIP10 DNA sequence.

There are no known isoforms for SPMIP10 in humans.{{Cite web|url=https://blast.ncbi.nlm.nih.gov/Blast.cgi|title=BLAST: Basic Local Alignment Search Tool|website=blast.ncbi.nlm.nih.gov}}

SPMIP10 has a predicted molecular weight (Mw) of 15.5 kda and a theoretical isoelectric point (pI) of 9.3. Similar predicted molecular weights and theoretical isoelectric points are seen for various close orthologs (mammals, sequence identity >79%). Varying predicted molecular weights and theoretical isoelectric points are seen in distant orthologs (non-mammal vertebrates, sequence identity <79%).{{Cite web|url=https://web.expasy.org/cgi-bin/compute_pi/pi_tool|title=Expasy Compute pI/Mw tool}}{{Cite web|url=https://www.ebi.ac.uk/|title=EMBL-EBI homepage|first=European Bioinformatics|last=Institute|website=www.ebi.ac.uk}}{{Cite web|url=https://www.ncbi.nlm.nih.gov/|title=National Center for Biotechnology Information|website=www.ncbi.nlm.nih.gov}}

SPMIP10 protein in humans, as well as various closely related organism, has higher levels than normal of histidine and lower than normal levels of alanine.

SPMIP10 contains a domain of unknown function, DUF4513, from positions 33-452.{{Cite web |title=NCBI Nucleotide entry on SPMIP10 humans |date=24 September 2023 |url=https://www.ncbi.nlm.nih.gov/nuccore/NM_207408.3 }}

SPMIP10 has a tertiary structure that includes both beta sheets and alpha helices.{{Cite web|url=https://alphafold.ebi.ac.uk/entry/Q6ZNM6|title=AlphaFold Protein Structure Database|website=alphafold.ebi.ac.uk}}{{Cite web|url=https://zhanggroup.org/I-TASSER/|title=I-TASSER server for protein structure and function prediction|website=zhanggroup.org}} These structures, predicted by AlphaFold and iTasser, are shown in the below images.

File:SPMIP10 predicted tertiary structure.png

File:SPMIP10 predicted tertiary structure - 2.png

SPMIP10 mRNA expression data, obtained from NCBI Gene, shows that SPMIP10 is expressed in varying amounts in both fetal (highest between the 10th and 15th week of development) and adult human tissues.{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene/389320#gene-expression|title=SPMIP10 sperm microtubule inner protein 10 [Homo sapiens (human)] - Gene - NCBI|website=www.ncbi.nlm.nih.gov}} There is SPMIP10 expression seen in heart tissues (approximately 0.049 RPKM) and kidney tissues (approximately 0.064 RPKM) at week 10 and in intestine tissues at 15 weeks (approximately 0.016 RPKM) in fetal tissues. RNA sequencing (RNA-seq) of total SPMIP10 RNA from 20 human tissues showed expression levels at approximately 0.064 reads per kilobase, per million mapped reads (RPKM) in cerebellum tissue. Transcription profiling by high throughput sequencing of 16 human tissues indicated high tests expression (approximately 6.5 RPKM) and low expression levels in lymph node and thyroid tissues. RNA-seq of 95 human individuals showed the highest expression levels of SPMIP10 mRNA expression in the testis at approximately 4.6 RPKM with minute amounts seen in colon and small intestine tissue samples.

File:SPMIP10 microarray expression data in the human brain.png

An experiment, from the Allen Brain Atlas site, indicated low amounts of SPMIP10 expression throughout various structures in the human brain (see SPMIP10 Microarray Expression Schematic in the Human Brain).{{Cite web|url=https://human.brain-map.org/microarray/search/show?exact_match=true&search_term=TEX43&search_type=gene&donors=12876,9861,10021,14380,15697|title=Microarray Data :: Allen Brain Atlas: Human Brain|website=human.brain-map.org}} Higher amounts of expression for SPMIP10 in the human brain were found in the posterior lobe, parietal lobe, and the amygdala. Higher amounts were primarily seen concentrated in the posterior lobe. Table 1 summarizes these findings.

There is no 5’ UTR for SPMIP10 because its first exon begins at the start of translation.

3’ UTR

The 3' UTR sequence of SPMIP10 in humans is highly conserved in various mammals. It is predicted to contain 3 stem loops.{{Cite web|url=http://www.unafold.org/mfold/applications/rna-folding-form.php|title=RNA Folding Form|website=www.unafold.org}}{{Cite web |title=EMBOSS Needle |url=https://www.ebi.ac.uk/}}{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene/389320/ortholog/|title=SPMIP10 orthologs|website=NCBI}}

File:SPMIP10 predicted.jpg

Utilizing UCSC Genome Browser, a transcription initiation site (Tex43_1) for SPMIP10 was located at positions 126,631,722 - 126,631,782 on chromosome 5 along with two enhancers (E2405703 and E2405704).{{Cite web|url=https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=chr5:126631705-126636284&hgsid=1836689112_H0mSPcjJHk4u9CjbW5MuN4ITbrS2|title=Human hg38 chr5:126,631,705-126,636,284 UCSC Genome Browser v458|website=genome.ucsc.edu}} These findings are depicted in the SPMIP10 Transcription Regulation Diagram.

SPMIP10 protein is predicted to be localized in the nucleus and cytoplasm, primarily. DEEPLOC-2.0 indicates that SPMIP10 is located in the cytoplasm and contains a nuclear export signal at positions 130-134 of the protein.{{Cite web|url=https://psort.hgc.jp/|title=PSORT WWW Server|website=psort.hgc.jp}}{{Cite web|url=https://services.healthtech.dtu.dk/|title=Bioinformatic Tools and Services - DTU Health Tech|website=services.healthtech.dtu.dk}}

File:Annotated SPMIP10 diagram.jpg

SPMIP10 has predicted SUMOylation sites (positions 107, 13, 65, 25, 54, 29, and 41), O-glycosylation sites (positions 10 and 122), and phosphoprotein-binding domains (SH2/LCK at position 30, SH2/CISH at position 30, and PBD at position 24). The locations of these modifications are labeled in the Annotated Conserved Post-translational Modifications for SPMIP10 Diagram.{{Cite journal |last=Zhao Q, Xie Y, Zheng Y, Jiang S, Liu W, Mu W, Liu Z, Zhao Y, Xue Y, Ren J. |date=2014 |title=GPS-SUMO: a tool for the prediction of sumoylation sites and SUMO-interaction motifs |journal=Nucleic Acids Res |volume=42 |issue=42 |pages=W325-30|doi=10.1093/nar/gku383 |pmid=24880689 |pmc=4086084 }}{{Cite journal |last=Tan W, Jiang P, Zhang W, Hu Z, Lin S, Chen L, Li Y, Peng C, Li Z, Sun A, Chen Y, Zhu W, Xue Y, Yao Y, Li X, Song Q, He F, Qin W, Pei H |date=2021 |title=Posttranscriptional regulation of de novo lipogenesis by glucose-induced O-GlcNAcylation |journal=Mol Cell |volume=6 |issue=81(9) |pages=1890–1904.e7|doi=10.1016/j.molcel.2021.02.009 |pmid=33657401 |doi-access=free }}{{Cite journal |last=Guo Y, Ning W, Jiang P, Lin S, Wang C, Tan X, Yao L, Peng D, Xue Y** |date=2020 |title=GPS-PBS: A deep learning framework to predict phosphorylation sites that specifically interact with phosphoprotein-binding domains |journal=Cells |volume=20 |issue=9(5) |pages=1266|doi=10.3390/cells9051266 |pmid=32443803 |pmc=7290655 |doi-access=free }}{{Cite journal |last=Guo Y, Peng D, Zhou J, Lin S, Wang C, Ning W, Xu H, Deng W, Xue Y |date=2019 |title=iEKPD 2.0: an update with rich annotations for eukaryotic protein kinases, protein phosphatases and proteins containing phosphoprotein-binding domains. |journal=Nucleic Acids Res |volume=47 |issue=47(D1) |pages=D344–D350|doi=10.1093/nar/gky1063 |pmid=30380109 |pmc=6324023 }}

There are no known paralogs of SPMIP10 in humans.

The SPMIP10 protein is only found in vertebrates. Species containing the SPMIP10 protein include mammals (26.5-100% identity), reptiles (40.9-48.1% identity), birds (23.2-41.8% identity), amphibians (27.7-37.1% identity), and fish (27.9-35.5% identity). Table 2 contains twenty orthologs and their respective sequence identity in relation to SPMIP10 in humans.{{Cite journal |last=Kumar S, Suleski M, Craig JM, Kasprowicz AE, Sanderford M, Li M, Stecher G, Hedges SB |date=2022 |title=TimeTree 5: An Expanded Resource for Species Divergence Times |url=https://academic.oup.com/mbe/article/39/8/msac174/6657692 |journal=Mol Biol Evol|volume=39 |issue=8 |doi=10.1093/molbev/msac174 |pmid=35932227 |pmc=9400175 }}

File:Corrected sequence divergence.png

Graph 1 shows the corrected sequence divergence vs estimated date of divergence for SPMIP10 compared to Cytochrome C and Fibrinogen Alpha. SPMIP10 evolves at a pace similar to that of Fibrinogen Alpha than.

On the B-tubule of the flagellum microtubule doublets, ENKUR protein interacts with the loop region of the SPMIP10 protein providing flagellum reinforcement in mammalian sperm.{{Cite journal |last=Miguel Ricardo Leung, Marc C. Roelofs, Riccardo Zenezini Chiozzi, Johannes F. Hevler, Albert J. R. Heck, Tzviya Zeev-Ben-Mordehai |date=2022 |title=Unraveling the intricate microtubule inner protein networks that reinforce mammalian sperm flagella [Preprint] |url=https://doi.org/10.1101/2022.09.29.510157 |journal=bioRxiv|doi=10.1101/2022.09.29.510157 |s2cid=252716669 }} SPMIP10 binds closely to ENKUR and envelops itself around the inter-promoter interface of CCDC105, in this regard, SPMIP10 functions as a “staple” while interacting with protofilaments A12 and A11. SPMIP10 enveloping of CCDC105 provides the promoter with stabilization.{{Cite journal |vauthors=Miyata H, Oura S, Morohoshi A, et al. |date=2021 |title=SPATA33 localizes calcineurin to the mitochondria and regulates sperm motility in mice |journal=Proc Natl Acad Sci USA|volume=118 |issue=35 |doi=10.1073/pnas.2106673118 |pmid=34446558 |pmc=8536318 |bibcode=2021PNAS..11806673M |doi-access=free }}

A 4bp deletion, resulting in a frameshift mutation (introducing a premature stop condone 33 aa further), of SPMIP10 in mice has been shown to slightly decrease sperm velocity and motility, however not lower rates of fertilization.{{Cite journal |last=Defosset, A.; Merlat, D.; Poidevin, L.; Nevers, Y.; Kress, A.; Poch, O.; Lecompte, O. |date=2021 |title=Novel Approach Combining Transcriptional and Evolutionary Signatures to Identify New Multiciliation Genes |journal=Genes |volume=12 |issue=9 |pages=1452|doi=10.3390/genes12091452 |pmid=34573434 |doi-access=free |pmc=8470418 }} Wild-type mouse sperm maintained flexibility at both the mid and end pieces of the flagellum, while the SPMIP10 knock-out mouse sperm showed reduced flexibility at the endpiece of the flagellum.

The duplication of SPMIP10 correlates with karyotypically balanced chromosomal rearrangements associates with decreased cognitive abilities as well as craniofacial and hand dysmorphisms.{{Cite journal |last1=Fonseca |first1=A.C.S. |last2=Bonaldi |first2=A. |last3=Fonseca |first3=S.A.S. |display-authors=et al. |date=2015 |title=The segregation of different submicroscopic imbalances underlying the clinical variability associated with a familial karyotypically balanced translocation |journal=Mol Cytogenet |volume=8 |doi=10.1186/s13039-015-0205-9 |issue=8 |pages=106 |pmid=26719771 |doi-access=free |pmc=4696321 }}

The depletion of p63 in ME180 cells (human cervical adenocarcinoma epithelial cells) correlates with a decrease of SPMIP10 expression. Wild-type ME180 cells have slightly higher amounts of SMPIP10 expression on average than those that experienced a depletion of p63.{{Cite journal |last=Yang, A., Zhu, Z., Kapranov, P., McKeon, F., Church, G. M., Gingeras, T. R., & Struhl, K. |date=2006 |title=Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells |journal=Molecular Cell |volume=24 |issue=4 |pages=593–602|doi=10.1016/j.molcel.2006.10.018 |pmid=17188034 |doi-access=free }}

Diseased cells expressing low levels of EVI1 have higher mean expression of SPMIP10 than diseased cells expressing elevated levels.{{Cite journal |last=Saito, Y., Nakahata, S., Yamakawa, N., Kaneda, K., Ichihara, E., Suekane, A., & Morishita, K. |date=2011 |title=CD52 as a molecular target for immunotherapy to treat acute myeloid leukemia with high EVI1 |url=https://doi.org/10.1038/leu.2011.36 |journal=Leukemia |volume=25 |issue=6 |pages=921–931|doi=10.1038/leu.2011.36 |pmid=21394097 |s2cid=23918930 |url-access=subscription }}

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