SPMIP10 is a protein that in Homo sapiens is encoded by the SPMIP10 gene.
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]
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.[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.
There are no known isoforms for SPMIP10 in humans.[3]
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.
SPMIP10 contains a domain of unknown function, DUF4513, from positions 33-452.[7]
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 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. 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.
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. Table 1 summarizes these findings.
| 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 |
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.[12] [13] [14]
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 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]
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]
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.[22]
| 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 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.[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. 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.
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]