Wikipedia

Uncharacterized protein C15orf32

Uncharacterized Protein C15orf32 is a protein which in humans is encoded by the C15orf32 gene and is located on chromosome 15, location 15q26.1.[3] Variants of C15orf32 have been linked to bipolar disorder,[4][5] alcohol use disorder,[6] and acute myeloid leukemia.[7]

C15orf32
Identifiers
AliasesC15orf32, chromosome 15 open reading frame 32, chromosome 15 putative open reading frame 32
External IDsHomoloGene: 89189; GeneCards: C15orf32; OMA:C15orf32 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

145858

n/a

Ensembl

ENSG00000183643

n/a

UniProt

Q32M92

n/a

RefSeq (mRNA)

NM_001301106
NM_153040

n/a

RefSeq (protein)

NP_001288035
NP_694585

n/a

Location (UCSC)Chr 15: 92.47 – 92.5 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human
Location of C15orf32 on chromosome 15[3]

Gene

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C15orf32, which stands for chromosome 15 open reading frame 32, is a gene on the plus strand of chromosome 15, on the cytogenetic band 15q26.1. C15orf32 is 29,464 bases long; on Genome Reference Consortium Human Build 38, it spans bases 92,471,654-92,501,117. It contains 3 exons.[3]

Transcripts

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Two isoforms of C15orf32 exist. The longer transcript, known as transcript variant 2 on NCBI, is 1,764 bases long.[8] The other is transcript 1 and is 1,726 bases long.[9]

 
Chou–Fasman secondary structure prediction for C15orf32[10]

Proteins

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The transcript variant 2 of the C15orf32 gene encodes a 178 amino acid protein and has a molecular mass of 20,262 Da. Its basal isoelectric point is 9.34.[11] Transcript variant 1 is missing amino acids 166–178.[3] There is significantly large spacing between the glutamic acid residues at locations 12 and 23.[12]

Structure

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Tertiary structure predicted by I-TASSER for C15orf32 with highest confidence[13]

A transmembrane segment is predicted between amino acids 51 and 71 by Phobius[14] and amino acids 57 and 71 by SAPS.[12] The N-terminus is predicted to be outside of the cytoplasm, and the C-terminus within the cytoplasm.[14] The Chou–Fasman algorithm predicts a beta sheet in this region, as well as much of region between amino acids 114 and 147.[10] I-TASSER was used to predict the tertiary structure.[13] The top model predicted eight alpha helices, including one between amino acids 51 and 71 concurrent with the transmembrane segment predicted earlier, although this structure had low confidence.

Regulation

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Gene level

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The promoter region of C15orf32 is predicted to span base pairs 92,470,677-92,471,777 according to Gene2Promoter tool by Genomatix.[15] The most commonly predicted transcription factor families by the MatInspector tool from Genomatix within this promoter region were SOX, nuclear receptor subfamily 2, and retinoid X receptor.[15] Transcription factor binding sites that have been determined experimentally include STAT1, MAFK, and JUND and are located within the second intron.[16] C15orf32 is expressed most notably in testes, brain, heart, and early in the development of fetuses, although expression is very low.[17] Exposure to some compounds such as bromelain, Bortezomib, estrogen, and 4-hydroxytamoxifen lead to increase in C15orf32 expression in breast cancer cells.[18][19][20]

 
Possible secondary structures of the 5' and 3' UTR C15orf32 mRNA, predicted by mfold[21]

Transcript level

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Possible secondary structures of the 5' and 3' untranslated region in C15orf32 mRNA is given to the left and was predicted by mfold.[21] It is mostly linear, with a number of small stem-loops. According to TargetScan, sites targeted by miRNA families miR-193a-5p and miR-365-3p within the 3' UTR are broadly conserved among vertebrates.[22]

Protein level

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Immunohistochemical staining shows that C15orf32 is localized within cells to the cytoplasm and membranes, including the nucleus.[23] Both PSORTII and DeepLoc strongly predict localization to the nucleus.[24][25] Thr41 has been shown to be phosphorylated post-translation[11] 26 other potential phosphorylation sites were predicted using NetPhos, with the most likely phosphorylation sites being 6S by PKC, 32T by PKG, 83T by PKC, 89S by PKC, and 162S by PKA.[26] A sumoylation site is predicted at amino acids 107–110.[27] 11 mucin type GalNAc O-glycosylation were predicted using NetOGlyc, 9 of which occurred in the first 50 base pairs.[28]

Interactions

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Experimental evidence shows potential interaction between C15orf32 and PKD2, ALG9, DISP1, NPC1, FZD2, FAM69A, ATP6V1G2, ASIC1, DPY19L4, SPPL2B, and HGSNAT.[29]

Clinical significance

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Variants of C15orf32 has been linked to several traits through genome wide association studies. The rs8040009 SNP in the 3’ UTR had a strong association with bipolar I disorder in a population of Han Chinese.[4] Three SNPs within C15orf32, including rs1455773 in exon 1 which causes a missense mutation from alanine to threonine at position 17,[30] were also associated with bipolar disorder in an Australian cohort.[5] This SNP was also linked to alcohol use disorder and heaviness of drinking.[6] The rs1455774 SNP, located in the 5’ UTR, is located within the target sites of miRNA has-miR-539 and has-let-7i* which affects the expression of these miRNAs, which may increase breast cancer susceptibility.[31] The rs11635085 SNP was linked to increased antibody IgG levels after exposure to casein, a dietary antigen, in Mexican Americans.[32] The rs1455782 SNP was linked to decreased forced vital capacity, which is a measure of pulmonary function.[33] The rs12148722 SNP was mildly associated with velopharyngeal dysfunction.[34] A haplotype block within C15orf32 was associated with acute myeloid leukemia.[7] A deletion in 15q26.1 including genes ST8SIA2, C15orf32, and FAM174B was found in a patient with epilepsy and autism spectrum disorder.[35]

Homology

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Homologs of C15orf32 have been described in 39 other mammals.[36] No known orthologs exist outside of mammals.

Scientific name Common name Order Date of divergence (MYA, estimated) Sequence ID Length % Identity % Similarity
Pan paniscus Bonobo Primates 6.7 XP_003816836.1 178 100.00 100
Colobus angolensis palliatus Tanzanian black-and-white colobus Primates 29.44 XP_011802791.1 165 81.21 83.03
Cebus capucinus imitator Panamanian white-faced capuchin Primates 43.2 XP_017372471.1 158 63.92 72.78
Marmota flaviventris Yellow-bellied marmot Rodentia 90 XP_027811208.1 171 53.80 61.99
Cavia porcellus Guinea pig Rodentia 90 XP_005008701.1 91 50.55 63.74
Urocitellus parryii Arctic ground squirrel Rodentia 90 XP_026249828.1 169 49.70 59.76
Heterocephalus glaber Naked mole-rat Rodentia 90 XP_021120379.1 157 47.77 56.69
Octodon degus Common degu Rodentia 90 XP_012369204.1 113 38.94 54.87
Ceratotherium simum simum Southern white rhinoceros Perissodactyla 96 XP_014644154.1 101 57.43 72.28
Tursiops truncatus Common bottlenose dolphin Artiodactyla 96 XP_019801175.1 120 53.33 67.5
Sus scrofa Wild boar Artiodactyla 96 XP_020955730.1 121 52.07 65.29
Balaenoptera acutorostrata scammoni North Pacific Minke whale Artiodactyla 96 XP_028020695.1 161 50.93 62.73
Equus caballus Horse Perissodactyla 96 XP_023505656.1 172 50.00 61.63
Felis catus Cat Carnivora 96 XP_006944424.1 89 49.44 58.43
Odobenus rosmarus divergens Pacific walrus Carnivora 96 XP_012420660.1 77 46.75 58.44
Lagenorhynchus obliquidens Pacific white-sided dolphin Artiodactyla 96 XP_026938944.1 180 44.44 55.56
Lipotes vexillifer Baiji Artiodactyla 96 XP_007472421.1 165 43.64 54.55
Panthera pardus Leopard Carnivora 96 XP_019315554.1 99 43.43 50.51
Orcinus orca Killer whale Artiodactyla 96 XP_012389158.1 162 43.21 53.7
Canis lupus dingo Dingo Carnivora 96 XP_025294087.1 149 36.24 44.3

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000183643 – Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ a b c d "C15orf32 Gene - GeneCards | C15orf32 RNA Gene". www.genecards.org. Retrieved 2020-03-02.
  4. ^ a b Lee MT, Chen CH, Lee CS, Chen CC, Chong MY, Ouyang WC, et al. (May 2011). "Genome-wide association study of bipolar I disorder in the Han Chinese population". Molecular Psychiatry. 16 (5): 548–56. doi:10.1038/mp.2010.43. PMID 20386566.
  5. ^ a b McAuley EZ, Scimone A, Tiwari Y, Agahi G, Mowry BJ, Holliday EG, et al. (2012-05-31). "Identification of sialyltransferase 8B as a generalized susceptibility gene for psychotic and mood disorders on chromosome 15q25-26". PLOS ONE. 7 (5): e38172. Bibcode:2012PLoSO...738172M. doi:10.1371/journal.pone.0038172. PMC 3364966. PMID 22693595.
  6. ^ a b Heath AC, Whitfield JB, Martin NG, Pergadia ML, Goate AM, Lind PA, et al. (September 2011). "A quantitative-trait genome-wide association study of alcoholism risk in the community: findings and implications". Biological Psychiatry. 70 (6): 513–8. doi:10.1016/j.biopsych.2011.02.028. PMC 3210694. PMID 21529783.
  7. ^ a b Lv H, Zhang M, Shang Z, Li J, Zhang S, Lian D, Zhang R (January 2017). "Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia". Oncotarget. 8 (5): 7891–7899. doi:10.18632/oncotarget.13631. PMC 5352368. PMID 27903959.
  8. ^ "Homo sapiens chromosome 15 putative open reading frame 32 (C15orf32), transcript variant 2, long non-coding RNA". 2019-10-06. {{cite journal}}: Cite journal requires |journal= (help)
  9. ^ "Homo sapiens chromosome 15 putative open reading frame 32 (C15orf32), transcript variant 1, long non-coding RNA". 2019-10-06. {{cite journal}}: Cite journal requires |journal= (help)
  10. ^ a b "CFSSP: Chou & Fasman Secondary Structure Prediction Server". www.biogem.org. Retrieved 2020-05-03.
  11. ^ a b "C15orf32 (human)". www.phosphosite.org. Retrieved 2020-03-02.
  12. ^ a b "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2020-05-03.
  13. ^ a b "I-TASSER server for protein structure and function prediction". zhanglab.ccmb.med.umich.edu. Retrieved 2020-05-03.
  14. ^ a b "Phobius". phobius.sbc.su.se. Retrieved 2020-05-03.
  15. ^ a b "Genomatix - NGS Data Analysis & Personalized Medicine". www.genomatix.de. Archived from the original on 2001-02-24. Retrieved 2020-05-03.
  16. ^ "ORegAnno Temporary Homepage". www.oreganno.org. Archived from the original on 2021-03-21. Retrieved 2020-05-03.
  17. ^ "C15orf32 Gene Expression - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-05-03.
  18. ^ Fouz N, Amid A, Hashim YZ (August 2014). "Gene expression analysis in MCF-7 breast cancer cells treated with recombinant bromelain". Applied Biochemistry and Biotechnology. 173 (7): 1618–39. doi:10.1007/s12010-014-0947-6. PMID 24928548. S2CID 207356247.
  19. ^ "GDS4089 / ILMN_1773848". www.ncbi.nlm.nih.gov. Retrieved 2020-05-03.
  20. ^ "GDS4065 / 1553482_at". www.ncbi.nlm.nih.gov. Retrieved 2020-05-03.
  21. ^ a b "RNA Folding Form | mfold.rit.albany.edu". unafold.rna.albany.edu. Retrieved 2020-05-03.
  22. ^ "TargetScanHuman 7.2". www.targetscan.org. Retrieved 2020-05-03.
  23. ^ "Anti-C15orf32 antibody produced in rabbit HPA041883". Immunohistochemistry. Retrieved 2020-05-03.
  24. ^ "PSORT II server - GenScript". www.genscript.com. Retrieved 2020-05-03.
  25. ^ "DeepLoc - 1.0". DTU Health Tech.
  26. ^ "NetPhos 3.1: Generic phosphorylation sites in eukaryotic proteins". healthtech.dtu.dk. Retrieved 2020-05-03.
  27. ^ "SUMOplot™ Analysis Program | Abcepta". www.abcepta.com. Retrieved 2020-05-03.
  28. ^ "NetOGlyc - 4.0". DTU Health Tech.
  29. ^ "C15orf32 Result Summary | BioGRID". thebiogrid.org. Retrieved 2020-05-03.
  30. ^ "UniProtKB/SwissProt variant VAR_050884". web.expasy.org. Retrieved 2020-03-02.
  31. ^ Nicoloso MS, Sun H, Spizzo R, Kim H, Wickramasinghe P, Shimizu M, et al. (April 2010). "Single-nucleotide polymorphisms inside microRNA target sites influence tumor susceptibility". Cancer Research. 70 (7): 2789–98. doi:10.1158/0008-5472.CAN-09-3541. PMC 2853025. PMID 20332227.
  32. ^ Rubicz R, Yolken R, Alaedini A, Drigalenko E, Charlesworth JC, Carless MA, et al. (July 2014). "Genome-wide genetic and transcriptomic investigation of variation in antibody response to dietary antigens". Genetic Epidemiology. 38 (5): 439–46. doi:10.1002/gepi.21817. PMC 4171053. PMID 24962563.
  33. ^ Wilk JB, Walter RE, Laramie JM, Gottlieb DJ, O'Connor GT (September 2007). "Framingham Heart Study genome-wide association: results for pulmonary function measures". BMC Medical Genetics. 8 Suppl 1 (1): S8. doi:10.1186/1471-2350-8-S1-S8. PMC 1995616. PMID 17903307.
  34. ^ Chernus J, Roosenboom J, Ford M, Lee MK, Emanuele B, Anderton J, et al. (May 2018). "GWAS reveals loci associated with velopharyngeal dysfunction". Scientific Reports. 8 (1): 8470. Bibcode:2018NatSR...8.8470C. doi:10.1038/s41598-018-26880-w. PMC 5981322. PMID 29855589.
  35. ^ Kamien B, Harraway J, Lundie B, Smallhorne L, Gibbs V, Heath A, Fullerton JM (March 2014). "Characterization of a 520 kb deletion on chromosome 15q26.1 including ST8SIA2 in a patient with behavioral disturbance, autism spectrum disorder, and epilepsy". American Journal of Medical Genetics. Part A. 164A (3): 782–8. doi:10.1002/ajmg.a.36345. PMID 24357335. S2CID 27921887.
  36. ^ "HomoloGene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-03-02.
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