Wikipedia

SMIM15

SMIM15(small integral membrane protein 15) is a protein in humans that is encoded by the SMIM15 gene.[5] It is a transmembrane protein that interacts with PBX4.[6] Deletions where SMIM15 is located have produced mental defects and physical deformities.[7][8] The gene has been found to have ubiquitous but variable expression in many tissues throughout the body.[5]

SMIM15
Identifiers
AliasesSMIM15, C5orf43, small integral membrane protein 15
External IDsMGI: 1922866; HomoloGene: 90075; GeneCards: SMIM15; OMA:SMIM15 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

643155

75616

Ensembl

ENSG00000188725

ENSMUSG00000071180

UniProt

Q7Z3B0

Q3UTD9

RefSeq (mRNA)

NM_001048249

NM_001048250

RefSeq (protein)

NP_001041714

NP_001041715

Location (UCSC)Chr 5: 61.16 – 61.16 MbChr 13: 108.18 – 108.19 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Gene

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Small integral membrane protein 15 (SMIM15) is a protein in humans that is encoded by the SMIM15 gene.[5] It has also been known under the aliases C5orf43[5] and GC05M060454.[5] It is made up of 74 amino acids. It is located at 5q12.1.[5] SMIM15 has 4741 base pairs with three exons[5][9]

mRNA

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SMIM15 has zero isoforms[5] The 5' UTR region spans 420 bases and the 3' UTR spans 2243 bases.[9]

Table 1. Exon Locations within Human SMIM15 mRNA[10]
Exon Number of Base Pairs Start and End Locations
1 252 61162217 – 61162468
2 140 61161088 – 61161227
3 2496 61157704 – 61160199

Protein

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Primary sequence of SMIM15 is:[11] MFDIKAWAEY  VVEWAAKDPY  GFLTTVILAL  TPLFLASAVL  SWKLAKMIEA  REKEQKKKQK. RQENIAKAKR  LKKD

Molecular weight of SMIM15 has been found to be 8.6 kdal and it has a pI of 9.82.[12] There are no significant compositional features compositional features like charge clusters, hydrophobic segments, charge runs, patterns, multiplets or periodicities.[13]

Domains and motifs 

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Schematic of Human SMIM15 Domains

There is one transmembrane domain located from amino acids 20 – 42.[14][15]

The other domains include a luminal domain from amino acids 1 - 19 and cytosolic domain from amino acids 43 - 74.[14][15]

Secondary structure

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The secondary structure for SMIM15 is largely alpha-helical with alpha helices making up 62.16% (46 amino acids) of the protein.[16] Random coil makes up 25.68% (19 amino acids) and extended strands make up 12.16% (9 amino acids) of the SMIM15 protein.[16]

Post-translational modifications

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Figure 1. Conceptual Translation for the Human SMIM15

There are a number of post-translational modifications of the SMIM15 protein, which are shown in the Conceptual Translation of Human SMIM15 as shown in figure 1.

The predicted sites for sumoylation are at positions: 5, 67, 69, 72, 73.[17] It is known to affect protein stability, protect from degradation, cellular localization, protein-protein interactions and DNA binding.

The predicted sites for glycation are at positions: 5, 43, 58, 72, 73.[18] Glycation can lead to the creation of AGE (advanced glycation end products.[19] Glycation is a process in which proteins react with reducing sugar molecules, which will lead to impairment of the function and changes the characteristics of the protein.[20][21]

Finally, there are four predicted sites for phosphorylation of tyrosine on position 20, threonine on positions 25 and 31, and serine on position 41.[22] Phosphorylation will affect different cellular processes and thus regulating protein function.[23]

Subcellular localization

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SMIM15 has a transmembrane domain found within amino acids 20–42. There are cleavage sites at the C-terminous and nuclear localization signals.[24]

Expression

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SMIM15 has been found to have ubiquitous but variable expression in many different tissues throughout the body.[5] it has the highest level of expression within the prostate.[25] There are lower levels of expression within skeletal muscles compared to other tissues within the body.[26]

Regulation of expression

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Epigenetic

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SMIM15 has one CpG island within the promoter. SMIM15 has lower levels of H3K4Me1 but higher levels of H3K4Me3 and H3K27Ac across all of their cell lines[27]

Transcriptional

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The Promoter region for SMIM15 is 1049 base pairs long.[10] and it is known as GXP_922465. There are 431 different transcription binding factor sites,[10] some of these binding factors include GATA1, TGIF, LMX1A, and NKX61[10]

Translational and mRNA stability

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There are no known micro-RNA targets in the 3' UTR.[10] mRNA secondary structures exhibited a high number of predicted stem-loop structures. This could indicate high stability of the mRNA transcript, and some binding sites for regulatory mechanisms.

Function

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The function of SMIM15 is currently not well understood.

Interacting Proteins

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There is only one interacting protein currently identified.[28][29] This protein is PBX4 which is known for playing critical roles in embryonic development and cellular differentiation both as Hox cofactors and through Hox - independent pathways.[6] PBX4 is also a member of the pre-B cell leukemia transcription factor family.[6][30]

Clinical Significance

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Deletion of 5q12.1 can lead to the development of mental retardation and ocular defects.[7] Another deletion in the 5q12.1 - 5q12.3 region lead to mental-motor retardation and dysmorphia.[8] In terms of diseases, Caries is a multifactorial disease and little is still known about the host genetic factors influencing susceptibility. The interval 5q12.1-5q13.3 as linked to low caries susceptibility in Filipino families.[31]

Homology

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SMIM15 is conserved in both vertebrates and invertebrates. It is not found in insects or fungi. SMIM15 does not have any paralogs[5] and the farthest known relative of the Homo sapiens SMIM15 is found within Trichoplax sp.H2 with a date of divergence 747 MYA[32]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000188725 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000071180 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c d e f g h i j "SMIM15 small integral membrane protein 15 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 3 May 2020.
  6. ^ a b c "PBX4 PBX homeobox 4 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 3 May 2020.
  7. ^ a b Jaillard, Sylvie; Andrieux, Joris; Plessis, Ghislaine; Krepischi, Ana C. V.; Lucas, Josette; David, Véronique; Le Brun, Marine; Bertola, Debora R.; David, Albert; Belaud-Rotureau, Marc-Antoine; Mosser, Jean (April 2011). "5q12.1 deletion: delineation of a phenotype including mental retardation and ocular defects". American Journal of Medical Genetics. Part A. 155A (4): 725–731. doi:10.1002/ajmg.a.33758. ISSN 1552-4833. PMID 21594994. S2CID 45371630.
  8. ^ a b Cetin, Zafer; Yakut, Sezin; Clark, Ozden Altiok; Mihci, Ercan; Berker, Sibel; Luleci, Guven (1 March 2013). "A 5q12.1-5q12.3 microdeletion in a case with a balanced exceptional complex chromosomal rearrangement". Gene. 516 (1): 176–180. doi:10.1016/j.gene.2012.12.013. ISSN 1879-0038. PMID 23262338.
  9. ^ a b "Human Gene SMIM15 (ENST00000339020.8) Description and Page Index". genome.ucsc.edu. Retrieved 3 May 2020.
  10. ^ a b c d e "Genomatix: Annotation & Analysis". www.genomatix.de. Retrieved 3 May 2020.[permanent dead link]
  11. ^ "small integral membrane protein 15 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 3 May 2020.
  12. ^ "ExPASy - Compute pI/Mw tool". web.expasy.org. Retrieved 3 May 2020.
  13. ^ "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 3 May 2020.
  14. ^ a b "The Wayback Machine has not archived that URL". elm.eu.org. Retrieved 29 June 2023.[permanent dead link]
  15. ^ a b "5E97AC2D00000D9E239DE439 expired". www.cbs.dtu.dk. Retrieved 3 May 2020.[permanent dead link]
  16. ^ a b "Archived copy". Archived from the original on 20 April 2022. Retrieved 3 May 2020.{{cite web}}: CS1 maint: archived copy as title (link)
  17. ^ "GPS-SUMO: Prediction of SUMOylation Sites & SUMO-interaction Motifs". sumosp.biocuckoo.org. Archived from the original on 10 May 2013. Retrieved 3 May 2020.
  18. ^ "NetGlycate 1.0 Server". www.cbs.dtu.dk. Retrieved 3 May 2020.
  19. ^ Kim, Chan-Sik; Park, Sok; Kim, Junghyun (30 September 2017). "The role of glycation in the pathogenesis of aging and its prevention through herbal products and physical exercise". Journal of Exercise Nutrition & Biochemistry. 21 (3): 55–61. doi:10.20463/jenb.2017.0027. ISSN 2233-6834. PMC 5643203. PMID 29036767.
  20. ^ "Glycation", Wikipedia, 25 March 2020, retrieved 3 May 2020
  21. ^ Johansen, Morten Bo; Kiemer, Lars; Brunak, Søren (September 2006). "Analysis and prediction of mammalian protein glycation". Glycobiology. 16 (9): 844–853. doi:10.1093/glycob/cwl009. ISSN 0959-6658. PMID 16762979.
  22. ^ "5E9CF8E40000064EBE8DB075 expired". www.cbs.dtu.dk. Retrieved 3 May 2020.[permanent dead link]
  23. ^ "Phosphorylation - US". www.thermofisher.com. Retrieved 3 May 2020.
  24. ^ "ELM - Detail for TRG_NLS_Bipartite_1". elm.eu.org. Retrieved 3 May 2020.
  25. ^ "GDS423 / 45795_at". www.ncbi.nlm.nih.gov. Retrieved 3 May 2020.
  26. ^ "Tissue expression of SMIM15 - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 3 May 2020.
  27. ^ "Human hg38 chr5:61,153,557-61,167,851 UCSC Genome Browser v397". genome.ucsc.edu. Retrieved 3 May 2020.
  28. ^ "Home < IMEx". www.imexconsortium.org. Retrieved 3 May 2020.
  29. ^ "IntAct Portal". www.ebi.ac.uk. Retrieved 3 May 2020.
  30. ^ Laurent, Audrey; Bihan, Réjane; Omilli, Francis; Deschamps, Stéphane; Pellerin, Isabelle (2008). "PBX proteins: much more than Hox cofactors". The International Journal of Developmental Biology. 52 (1): 9–20. doi:10.1387/ijdb.072304al. ISSN 0214-6282. PMID 18033668.
  31. ^ Shimizu, T.; Deeley, K.; Briseño-Ruiz, J.; Faraco, I. M.; Poletta, F. A.; Brancher, J. A.; Pecharki, G. D.; Küchler, E. C.; Tannure, P. N.; Lips, A.; Vieira, T. C. S. (2013). "Fine-mapping of 5q12.1-13.3 unveils new genetic contributors to caries". Caries Research. 47 (4): 273–283. doi:10.1159/000346278. ISSN 1421-976X. PMC 3737367. PMID 23363935.
  32. ^ "TimeTree :: The Timescale of Life". www.timetree.org. Retrieved 3 May 2020.
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