SPMIP10

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SPMIP10 is a protein that in Homo sapiens is encoded by the SPMIP10 gene.

SPMIP10 - Gene[edit]

Common Aliases[edit]

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.[1]

Cytogenetic Locus[edit]

Ideogram of the SPMIP10 Gene Location on Chromosome 5. The gene location is indicated by the red line.

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).[1]

Topological Features[edit]

SPMIP10 is a 478 bp long protein-coding gene.[2] 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.[2]

SPMIP10 - Transcript[edit]

Known Isoforms[edit]

There are no known isoforms for SPMIP10 in humans.[2][3]

SPMIP10 - Protein[edit]

Compositional Analysis[edit]

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%).[4][5][6]

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.[5]

Domains[edit]

SPMIP10 contains a domain of unknown function, DUF4513, from positions 33-452.[7]

Predicted Tertiary Structure[edit]

SPMIP10 has a tertiary structure that includes both beta sheets and alpha helices.[8][9] These structures, predicted by AlphaFold and iTasser, are shown in the below images.

SPMIP10 predicted tertiary structure. Generated using AlphaFold.
SPMIP10 predicted tertiary structure. Generated using iTasser.

SPMIP10 - Gene Level Regulation[edit]

Expression Pattern[edit]

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.[10] 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.[10] 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.[10] 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.[10]

Microarray Expression Data[edit]

SPMIP10 Microarray Expression Schematic in the Human Brain. Yellow boxes indicate areas of dense expression in the posterior lobe. Data obtained from the Allen Brain Atlas website.

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).[11] 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.[11] Table 1 summarizes these findings.

Table 1: Human brain structures expressing higher amounts of SPMIP10
Structure Location Function z-score
Lobule VIIIA Posterior Lobe Vasopressin and Oxytocin production 4.3958
Basomedial nucleus Amygdala Decision-making and adaptation of instinctive behaviors inn response to environmental stimuli 3.7596
Superior parietal lobule Parietal lobe Sensory perception and integration 3.114
Lobule VIIB Posterior lobe Vasopressin and Oxytocin production 3.0986
Lobule VIIIA Posterior lobe Vasopressin and Oxytocin production 3.0757
Lobule IX Posterior lobe Vasopressin and Oxytocin production 3.0531
Lobule VIIIA Posterior lobe Vasopressin and Oxytocin production 3.0018

SPMIP10 - Transcript Level Regulation[edit]

5’ UTR[edit]

There is no 5’ UTR for SPMIP10 because its first exon begins at the start of translation.[7]

3’ UTR

The 3' UTR sequence of SPMIP10 in humans is highly conserved in various mammals. It is predicted to contain 3 stem loops.[12][13][14]

Translation Initiation and Enhancers[edit]

SPMIP10 Transcription Regulation Diagram. Two predicated enhancers (E2405703 and E2405704) and an initiation region (Tex43_1) are labeled.

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).[15] These findings are depicted in the SPMIP10 Transcription Regulation Diagram.

SPMIP10 - Protein Level Regulation[edit]

Subcellular Localization[edit]

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.[16][17]

Post-translational Modifications[edit]

Annotated Conserved Post-translational Modifications for SPMIP10 Diagram. Longer ticks indicate higher confidence scores.

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.[18][19][20][21]

SPMIP10 Homology and Evolution[edit]

Paralogs[edit]

There are no known paralogs of SPMIP10 in humans.[3][7]

Orthologs[edit]

The SPMIP10 protein is only found in vertebrates.[6] 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.[3][6][22]

Table 2: SPMIP10 orthologs organized by median date of divergence and sequence identity percentage
SPMIP10 Genus/Species Common Name Taxonomic Group Est. Date of Divergence (MYA) Accession Number Sequence Length (aa) Sequence Identity (%) Sequence Similarity (%)
Mammals Homo sapiens Humans Hominidae 0 MYA NP_997291.1 134 100 100
Lemur catta Ring-tailed lemur Primates 74 MYA XP_045421967.1 134 91.8 94.8
Callorhinus ursinus Northern fur seal Carnivora 94 MYA XP_025716752.1 134 86.6 91.8
Pteropus vampyrus Large flying fox Chiroptera 94 MYA XP_011356632.1 134 79.1 87.3
Phascolarctos cinereus Koala Diprotodontia 160 MYA XP_020863037.1 133 58.2 70.2
Tachyglossus aculeatus Australian echidna Monotremata 180 MYA XP_038625455.1 236 26.5 34.6
Reptilia Crocodylus porosus Australian saltwater crocodile Crocodylia 319 MYA XP_019410982.1 116 48.1 64.4
Gopherus evgoodei Goodes thornscrub tortoise Testudines 319 MYA XP_030422994.1 116 46.3 59.0
Lacerta agilis Sand lizard Squamata 319 MYA XP_033019986.1 131 44.6 61.2
Alligator mississippiensis American alligator Crocodylia 319 MYA XP_059580882.1 132 40.9 52.6
Aves Dromaius novaehollandiae Emu Casuariiformes 319 MYA XP_025971178.1 108 41.8 56.7
Antrostomus carolinensis Chuck-wills-widow Caprimulgiformes 319 MYA XP_028940340.1 159 35.7 48.0
Gavia stellata Red-throated loon Gaviiformes 319 MYA XP_059690006.1 145 30.1 42.8
Nipponia nippon Crested ibis Pelecaniformes 319 MYA XP_009470769.1 90 25.0 35.1
Buceros rhinoceros silvestris Rhinoceros hornbill Bucerotiformes 319 MYA XP_010133851.1 138 23.2 39.3
Amphibian Rana temporaria Common frog Anura 352 MYA XP_040200566.1 155 37.1 54.7
Bufo bufo Common toad Anura 352 MYA XP_040276142.1 169 33.7 50.3
Geotrypetes seraphini Gaboon caecilian Gymnophiona 352 MYA XP_033815079.1 119 32.4 50.0
Xenopus tropicalis Tropical clawed frog Anura 352 MYA XP_002931758.1 174 27.7 42.4
Fish Protopterus annectens West African lungfish Lepidosireniformes 408 MYA XP_043916719.1 116 35.5 48.6
Labrus bergylta Labrus bergylta Labriformes 429 MYA XP_020509209.2 152 32.2 42.8
Petromyzon marinus Sea lamprey Petromyzontiformes 563 MYA XP_032809373.1 115 30.3 47.9
Anabas testudineus Climbing perch Perciformes 429 MYA XP_026199556.1 147 27.9 44.2
Graph 1: Corrected sequence divergence vs estimated date of divergence for SPMIP10, Cytochrome C and Fibrinogen Alpha.

SPMIP10 Rate of Divergence[edit]

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.

SPMIP10 - Functions and Clinical Significance[edit]

Predicted Function[edit]

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.[23] 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.[23] SPMIP10 enveloping of CCDC105 provides the promoter with stabilization.[24]

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.[25] 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.[25]

Clinical Significance[edit]

The duplication of SPMIP10 correlates with karyotypically balanced chromosomal rearrangements associates with decreased cognitive abilities as well as craniofacial and hand dysmorphisms.[26]

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.[27]

Diseased cells expressing low levels of EVI1 have higher mean expression of SPMIP10 than diseased cells expressing elevated levels.[28]

References[edit]

  1. ^ a b "Gene Cards". GeneCards.
  2. ^ a b c "sperm-associated microtubule inner protein 10 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov.
  3. ^ a b c "BLAST: Basic Local Alignment Search Tool". blast.ncbi.nlm.nih.gov.
  4. ^ "Expasy Compute pI/Mw tool".
  5. ^ a b Institute, European Bioinformatics. "EMBL-EBI homepage". www.ebi.ac.uk.
  6. ^ a b c "National Center for Biotechnology Information". www.ncbi.nlm.nih.gov.
  7. ^ a b c "NCBI Nucleotide entry on SPMIP10 humans". 24 September 2023.
  8. ^ "AlphaFold Protein Structure Database". alphafold.ebi.ac.uk.
  9. ^ "I-TASSER server for protein structure and function prediction". zhanggroup.org.
  10. ^ a b c d "SPMIP10 sperm microtubule inner protein 10 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov.
  11. ^ a b "Microarray Data :: Allen Brain Atlas: Human Brain". human.brain-map.org.
  12. ^ "RNA Folding Form". www.unafold.org.
  13. ^ "EMBOSS Needle".
  14. ^ "SPMIP10 orthologs". NCBI.
  15. ^ "Human hg38 chr5:126,631,705-126,636,284 UCSC Genome Browser v458". genome.ucsc.edu.
  16. ^ "PSORT WWW Server". psort.hgc.jp.
  17. ^ "Bioinformatic Tools and Services - DTU Health Tech". services.healthtech.dtu.dk.
  18. ^ Zhao Q, Xie Y, Zheng Y, Jiang S, Liu W, Mu W, Liu Z, Zhao Y, Xue Y, Ren J. (2014). "GPS-SUMO: a tool for the prediction of sumoylation sites and SUMO-interaction motifs". Nucleic Acids Res. 42 (42): W325-30. doi:10.1093/nar/gku383. PMC 4086084. PMID 24880689.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  19. ^ 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 (2021). "Posttranscriptional regulation of de novo lipogenesis by glucose-induced O-GlcNAcylation". Mol Cell. 6 (81(9)): 1890–1904.e7. doi:10.1016/j.molcel.2021.02.009. PMID 33657401.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  20. ^ Guo Y, Ning W, Jiang P, Lin S, Wang C, Tan X, Yao L, Peng D, Xue Y** (2020). "GPS-PBS: A deep learning framework to predict phosphorylation sites that specifically interact with phosphoprotein-binding domains". Cells. 20 (9(5)): 1266. doi:10.3390/cells9051266. PMC 7290655. PMID 32443803.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  21. ^ Guo Y, Peng D, Zhou J, Lin S, Wang C, Ning W, Xu H, Deng W, Xue Y (2019). "iEKPD 2.0: an update with rich annotations for eukaryotic protein kinases, protein phosphatases and proteins containing phosphoprotein-binding domains". Nucleic Acids Res. 47 (47(D1)): D344–D350. doi:10.1093/nar/gky1063. PMC 6324023. PMID 30380109.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  22. ^ Kumar S, Suleski M, Craig JM, Kasprowicz AE, Sanderford M, Li M, Stecher G, Hedges SB (2022). "TimeTree 5: An Expanded Resource for Species Divergence Times". Mol Biol Evol. 39 (8). doi:10.1093/molbev/msac174. PMC 9400175. PMID 35932227.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  23. ^ a b Miguel Ricardo Leung, Marc C. Roelofs, Riccardo Zenezini Chiozzi, Johannes F. Hevler, Albert J. R. Heck, Tzviya Zeev-Ben-Mordehai (2022). [htps://doi.org/10.1101/2022.09.29.510157 "Unraveling the intricate microtubule inner protein networks that reinforce mammalian sperm flagella [Preprint]"]. bioRxiv. doi:10.1101/2022.09.29.510157. S2CID 252716669.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  24. ^ Miyata H, Oura S, Morohoshi A, et al. (2021). "SPATA33 localizes calcineurin to the mitochondria and regulates sperm motility in mice". Proc Natl Acad Sci USA. 118 (35). Bibcode:2021PNAS..11806673M. doi:10.1073/pnas.2106673118. PMC 8536318. PMID 34446558.
  25. ^ a b Defosset, A.; Merlat, D.; Poidevin, L.; Nevers, Y.; Kress, A.; Poch, O.; Lecompte, O. (2021). "Novel Approach Combining Transcriptional and Evolutionary Signatures to Identify New Multiciliation Genes". Genes. 12 (9): 1452. doi:10.3390/genes12091452. PMC 8470418. PMID 34573434.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  26. ^ Fonseca, A.C.S.; Bonaldi, A.; Fonseca, S.A.S.; et al. (2015). "The segregation of different submicroscopic imbalances underlying the clinical variability associated with a familial karyotypically balanced translocation". Mol Cytogenet. 8 (8): 106. doi:10.1186/s13039-015-0205-9. PMC 4696321. PMID 26719771.
  27. ^ Yang, A., Zhu, Z., Kapranov, P., McKeon, F., Church, G. M., Gingeras, T. R., & Struhl, K. (2006). "Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells". Molecular Cell. 24 (4): 593–602. doi:10.1016/j.molcel.2006.10.018. PMID 17188034.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  28. ^ Saito, Y., Nakahata, S., Yamakawa, N., Kaneda, K., Ichihara, E., Suekane, A., & Morishita, K. (2011). "CD52 as a molecular target for immunotherapy to treat acute myeloid leukemia with high EVI1". Leukemia. 25 (6): 921–931. doi:10.1038/leu.2011.36. PMID 21394097. S2CID 23918930.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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