Biology:C1orf141

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Short description: Protein

Chromosome 1 open reading frame 141, or C1orf141 is a protein which, in humans, is encoded by gene C1orf141.[1] It is a precursor protein that becomes active after cleavage.[2] The function is not yet well understood, but it is suggested to be active during development[3]

Gene

Locus

This gene is located on chromosome 1 at position 1p31.3. It is encoded on the antisense strand of DNA spanning from 67,092,176 to 67,141,646 and has 10 total exons. It overlaps slightly with the gene IL23R being encoded on the sense strand.[1]

Chromosome 1 spanning from 66,924,895 to 67,267,726.[1]

Transcription regulation

A specific promoter region has not been predicted for C1orf141 so the 1000 base pairs upstream of the start of transcription was analyzed for transcription factor binding sites.[4] The transcription factors below represent a subset of the transcription factor binding sites found within this region that give an idea of the kind of factors that could bind to the promoter[4]

mRNA

Alternative Splicing

The C1orf141 gene appears to have two common isoforms and seven less common transcript variants.[1]

C1orf141 Isoforms
Name mRNA Length (base pairs) Protein Length (amino acids)
C1orf141 Isoform 1 2177 400
C1orf141 Isoform 2 2203 217
C1orf141 Isoform X1 2348 471
C1orf141 Isoform X2 2265 458
C1orf141 Isoform X3 1875 333
C1orf141 Isoform X4 920 243
C1orf141 Isoform X5 612 154
C1orf141 Isoform X6 639 146
C1orf141 Isoform X7 514 138

Protein

The primary encoded precursor protein (C1orf141 Isoform 1) consists of 400 amino acid residues and is 2177 base pairs long. It consists of 7 exons and a domain of unknown function DUF4545.[5] Its predicted molecular mass is 54.4 kDa and predicted isoelectric point is 9.63.[6]

Composition

Conceptual Translation of C1orf141 that shows predicted Post-translational modifications.

The C1orf141 precursor protein has more lysine amino acid residues and less glycine amino acid residues than expected when compared to other human proteins. The sequence has 11.7% lysine and only 2.1% glycine.[6]

Post-translational modifications

C1orf141 is modified post translation to form a mature protein product. It undergoes O-linked glycosylation, sumoylation, glycation, and phosphorylation.[7][8][9][10] One N-terminal cleavage occurs followed by acetylation. Propeptide cleavage occurs at the start site of the final exon.[2]

Model of the Tertiary Structure for precursor human protein C1orf141 as predicted by I-TASSER.[11]

Structure

The secondary structure for uncleaved C1orf141 consists primarily of alpha helices with a few small segments of beta sheets. These helices can be seen in the model of the tertiary structure predicted by the I-TASSER program.[11] The program Phyre2 also predicts the protein to be made up primarily of alpha helices.[12] After propeptide cleavage of C1orf141, I-TASSER predicts that only alpha helices remain.

Interactions

There are currently no experimentally confirmed interactions for C1orf141. The STRING database for protein interactions identified ten potential proteins that interact with C1orf141 through text mining.[13] These include SALT1, C8orf74, SHCBP1L, ACTL9, RBM44, CCDC116, ADO, WDR78, ZNF365, SPATA45.[14][15][16][17] Through investigation of the papers where these interaction predictions were found, a solid link was not clear for any of the identified proteins.

Expression

Expression data for C1orf141 from HPA RNA-Seq normal tissues project.[3]

C1orf141 is expressed in 30 different tissues but primarily in the testes.[1] Other tissues where expression is above baseline levels are the brain, lungs, and ovaries.[3]

Localization

The subcellular localization for C1orf141 is predicted to be in the nucleus. There are two nuclear localization signals within the protein sequence, one of which stays present after propeptide cleavage.[18]

Function

The function of C1orf141 is not yet fully understood and has not been experimentally confirmed. However, expression data shows that the protein is active in some developmental stages. RNA-Seq data taken at different stages of development show expression at varying levels throughout.[3] Expression rates are seen at higher levels in the fetal developmental stage than the adult in the protein's ETS profile.[19] Microarray data for cumulus cells during natural and stimulated in vitro fertilization show relatively high levels of expression.[20] There is no significant change in expression in adult tissue disease states.[19]

Homology

Paralogs

There are no paralogs for C1orf141[21]

Orthologs

Orthologous sequences are seen primarily in other mammalian species. The most distant ortholog identified through a NCBI BLAST search is a Reptilian species, but that is the only non-mammalian species.[21] This list contains a subset of the species identified as orthologs to display the diversity of the species where orthologs can be found. Each species was compared to the human C1orf141 isoform that includes each coding exon, isoform X1.[1]

C1orf141 Orthologs
Genus and Species Common Name Taxonomic Group Accession Number Date of Divergence (millions of years) Sequence Length (amino acids) Sequence Identity Sequence Similarity
Homo sapiens Human Primate XP_011539768.1 0 471 100% 100%
Gorilla gorilla gorilla Western Lowland Gorilla Primate XP_018892062.1 8.61 469 97% 98%
Otolemur garnettii Northern Greater Galago Primate XP_023365656.1 84 457 59% 70%
Tupaia chinensis Northern Treeshrew Scandentia XP_006171456.1 88 468 62% 74%
Oryctolagus

cuniculus

European Rabbit Lagomorpha XP_017201685.1 88 470 56% 68%
Fukomys damarensis Damaraland Mole Rat Rodentia XP_010603404.1 88 479 54% 66%
Chinchilla lanigera Long-tailed Chincilla Rodentia XP_013369940.1 94 476 50% 65%
Ochotona princeps American Pika Lagomorpha XP_012783463.1 94 450 50% 67%
Miniopterus natalensis Natal long-fingered bat Chiroptera XP_016064273.1 94 390 63% 72%
Panthera pardus Leopard Carnivora XP_019304485.1 94 450 62% 74%
Enhydra lutris kenyoni Sea Otter Carnivora XP_022351992.1 94 451 62% 74%
Balaenoptera acutorostrata scammoni Minke Whale Cetacea XP_007164359.1 94 432 60% 60%
Delphinapterus leucas Beluga Whale Cetacea XP_022436606.1 94 432 59% 72%
Sus scrofa Wild Boar Cetartiodactyla XP_005656203.1 94 442 56% 70%
Pteropus vampyrus Large Flying Fox Chiroptera XP_011367916.1 94 470 56% 68%
Ovis aries Sheep Cetartiodactyla XP_012026840.1 94 431 55% 69%
Bos taurus Cattle Cetartiodactyla NP_001070559.1 94 430 54% 69%
Condylura cristata Star-nosed Mole Eulipotyphla XP_012577585.1 94 432 52% 64%
Desmodus rotundus Common Vampire Bat Chiroptera XP_024421106.1 94 398 48% 59%
Sarcophilus harrisii Tasmanian Devil Marsupiala XP_012405605.1 160 356 43% 63%
Phascolarctos cinereus Koala Marsupiala XP_020848724.1 160 204 29% 50%
Monodelphis domestica Gray Short-tailed Opossum Marsupiala XP_007480481.1 160 524 25% 48%
Pogona vitticeps Central Bearded Dragon Reptilia XP_020661721.1 320 501 28% 54%

Evolutionary History

Using the Molecular Clock Hypothesis, the m value (the number of corrected amino acid changes per 100 residues) was calculated for C1orf141 and plotted against the divergence of species. When compared to the same m value plot for hemoglobin, fibrinogen alpha chain, and cytochrome c, it is clear that the C1orf141 gene is evolving at a faster rate than all three.

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 "C1orf141 chromosome 1 open reading frame 141 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/400757. 
  2. ↑ 2.0 2.1 "ProP 1.0 Server". http://www.cbs.dtu.dk/services/ProP/. 
  3. ↑ 3.0 3.1 3.2 3.3 "C1orf141 Gene Expression - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene/400757/?report=expression. 
  4. ↑ 4.0 4.1 "Genomatix: Gene2Promoter Subtasks". https://www.genomatix.de/cgi-bin/c2p/c2p.pl?s=3ae873c3461062587df37031241f7460. 
  5. ↑ "C1orf141 Gene (Protein Coding)". https://www.genecards.org/cgi-bin/carddisp.pl?gene=C1orf141. 
  6. ↑ 6.0 6.1 "SAPS < Sequence Statistics < EMBL-EBI". https://www.ebi.ac.uk/Tools/seqstats/saps/. 
  7. ↑ "NetOGlyc 4.0 Server" (in en). http://www.cbs.dtu.dk/services/NetOGlyc/. 
  8. ↑ "SUMOplot™ Analysis Program | Abgent". https://www.abgent.com/sumoplot. 
  9. ↑ "NetGlycate 1.0 Server" (in en). http://www.cbs.dtu.dk/services/NetGlycate/. 
  10. ↑ "NetPhos 3.1 Server". http://www.cbs.dtu.dk/services/NetPhos/. 
  11. ↑ 11.0 11.1 "I-TASSER results". https://zhanglab.ccmb.med.umich.edu/I-TASSER/output/S463439/. 
  12. ↑ "PHYRE2 Protein Fold Recognition Server". http://www.sbg.bio.ic.ac.uk/phyre2/html/page.cgi?id=index. 
  13. ↑ "C1orf141 protein (human) - STRING interaction network". https://string-db.org/cgi/network.pl?taskId=h662ZstDL43j. 
  14. ↑ Sammut, Stephen J.; Feichtinger, Julia; Stuart, Nicholas; Wakeman, Jane A.; Larcombe, Lee; McFarlane, Ramsay J. (2014-05-06). "A novel cohort of cancer-testis biomarker genes revealed through meta-analysis of clinical data sets.". Oncoscience 1 (5): 349–359. doi:10.18632/oncoscience.37. ISSN 2331-4737. PMID 25594029. 
  15. ↑ Swami, Meera (2014). "Genome-wide association study identifies three new melanoma susceptibility loci". Nature Medicine 17 (11): 1357. doi:10.1038/nm.2568. ISSN 1078-8956. 
  16. ↑ Lu, Weining; Quintero-Rivera, Fabiola; Fan, Yanli; Alkuraya, Fowzan S.; Donovan, Diana J.; Xi, Qiongchao; Turbe-Doan, Annick; Li, Qing-Gang et al. (2007). "NFIA Haploinsufficiency Is Associated with a CNS Malformation Syndrome and Urinary Tract Defects". PLOS Genetics 3 (5): e80. doi:10.1371/journal.pgen.0030080. ISSN 1553-7390. PMID 17530927. 
  17. ↑ Yao, Fang; Zhang, Chi; Du, Wei; Liu, Chao; Xu, Ying (2015-09-16). "Identification of Gene-Expression Signatures and Protein Markers for Breast Cancer Grading and Staging". PLOS ONE 10 (9): e0138213. doi:10.1371/journal.pone.0138213. ISSN 1932-6203. PMID 26375396. Bibcode: 2015PLoSO..1038213Y. 
  18. ↑ "Welcome to psort.org!!". https://www.psort.org/. 
  19. ↑ 19.0 19.1 "EST Profile - Hs.666621". https://www.ncbi.nlm.nih.gov/UniGene/ESTProfileViewer.cgi?uglist=Hs.666621. 
  20. ↑ "Modified natural and stimulated in vitro fertilization cycles: cumulus cells - - GEO DataSets - NCBI". https://www.ncbi.nlm.nih.gov/gds?LinkName=geoprofiles_gds&from_uid=109695771. 
  21. ↑ 21.0 21.1 "BLAST: Basic Local Alignment Search Tool". https://blast.ncbi.nlm.nih.gov/Blast.cgi. 



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