C11orf98 Explained

C11orf98 is a protein-encoding gene on chromosome 11 in humans of unknown function. It is otherwise known as c11orf48.[1] The gene spans the chromosomal locus from 62,662,817-62,665,210.[2] There are 4 exons. It spans across 2,394 base pairs of DNA[3] and produces an mRNA that is 646 base pairs long.[4]

Gene

Expression

This gene is expressed at a very high level,4.4 times the average gene.[5] The c11orf98 protein is expressed in a wide array of tissues. RNA-seq dat showed this gene to be expressed highest in the appendix, lymph node, and thymus.[6]

An analysis via PSORT II concluded that the C11orf98 gene product is localized to the nucleus 82.6% reliability. This nuclear localization suggests that C11orf98 protein may have a function related to the expression and regulation of genes in the nucleus.

Regulation

Several different transcription factors are predicted to regulate the expression of the c11orf98 gene. These transcription factors were predicted based on DNA sequences found in the gene using Genomatix which also provided the name and description.[7]

NameTF Description
1V$ZIC3.03Zinc finger protein of the cerebellum (Zic3)
2V$SPZ1.01Spermatogenic Zip 1 transcription factor
3V$YB1.01Y box binding protein 1, has a preference for binding ssDNA
4V$PAX5PAX5 paired domain protein
5V$TCF21.02Transcription factor 21
6V$GFI1B.02Growth factor independence 1 zinc finger protein Gfi-1B
7V$SPI1.02SPI-1 proto-oncogene; hematopoietic transcription factor PU.1
8V$ZKSCAN3.01Zinc finger with KRAB and SCAN domains 3
9V$EGR2.03Early growth response 2
10V$ZNF300.01KRAB-containing zinc finger protein 300
11V$AP4.03Activating enhancer binding protein 4
12V$AML2.01RUNX3 (Runt-related transcription factor 3), AML2 (Acute myeloid leukemia 2)
13V$WHN.01Winged helix protein, involved in hair keratinization and thymus epithelium differentiation
14O$DINR.01Drosophila initiator motifs
15V$ZTRE.035' half site of ZTRE motif
16V$ZNF35.01Human zinc finger protein ZNF35
17V$SP1.02Stimulating protein 1, ubiquitous zinc finger transcription factor
18V$DMP1.02Cyclin D binding myb-like transcription factor
19V$ETV1.02Ets variant 1
20V$WT1.02Wilms Tumor Suppressor

Protein

The c11orf98 gene encodes a protein that is 123 amino acids long.[8] The predicted molecular weight of the protein is 14.2 kDa.[9] The basal isoelectric point was determined to be 11.53.[10] The protein's subcellular localization was predicted to be in the nucleus.[11] [12]

Domain

The c11orf98 protein contains a region of unknown function (DUF5564) that spans from amino acids 1-98. There are also 2 disordered regions within the protein that span from amino acids 1-21 and 32-123.[13] C11orf98 contains 4 bipartite nuclear localization signals (NLS_BP) which indicates the protein will be 'tagged' for import into the cell nucleus by nuclear transport. The NLS_BP sequence usually consists of positively charged arginines, which would also explain the arginine rich region (ARG_RICH).[14]

Structure

The secondary structures of the c11orf98 protein was predicted to have multiple alpha helices as well as beta sheets.[15] The tertiary structure was predicted using AlphaFold[16]

C11orf98 protein undergoes modifications following translation. The c11orf98 protein was predicted to have an amidation site. This functions as an active peptide precursor cleavage site. Next, a cAMP- and cGMP-dependent protein kinase phosphorylation site was predicted as well as other phosphorylation sites such as a Casein kinase II phosphorylation site and a protein kinase C phosphorylation site . An N-myristoylation site was predicted as well. Phosphorylation is significant because a phosphoryl group is added to the site, which only can occur in the nucleus or in cytosol. Myristoylation is significant because a myristoyl group (fatty acid group) is added to the site which helps anchor the transmembrane protein or cytosolic protein to the membrane.[17] [18] [12] There were twelve predicted o-beta-GlcNAc glycosylation sites. This is significant because this modification is exclusively found on nuclear and cytoplasmic proteins rather than membrane proteins and secretory proteins.[12] One sumoylation site was predicted. Sumoylation is a post-translational modification involved in nuclear-cytosolic transport, transcriptional regulation, apoptosis, protein stability, response to stress, and progression through the cell cycle.[19]

Interactions

[20]

Abbreviated Name Name Basis of ID Score Description
JUNC-junProximity-dependent biotin identificationVariousc-Jun, in combination with c-Fos, forms the AP-1 early response transcription factor
FBLFibrillarinProximity-dependent biotin identificationVariouscomponent of a nucleolar small nuclear ribonucleoprotein (snRNP) particle thought to participate in the first step in processing pre-ribosomal (r)RNA
ESR1Estrogen receptor 1 Tandem affinity purification0.35activated by the sex hormone estrogen, is a transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription
SCARB2Scavenger Receptor Class B Member 2Pull Down 0.35protein is primarily found in the membrane of cellular structures called lysosomes, which are specialized compartments that digest and recycle materials
OAS32'-5'-Oligoadenylate Synthetase 3Pull Down 0.35This enzyme is induced by interferons and catalyzes the 2', 5' oligomers of ATP

Homology and evolution

The c11orf98 gene has 148 orthologs.[21] The oldest ortholog appeared in invertebrates. Other orthologs were found in birds, reptiles, amphibians, fish, and invertebrates.[22]

Seq #
C11orf98Genus, SpeciesCommon NameTaxonomic GroupDivergence Date (Million Years Ago)[23] Accession Number[24] Query CoverSequence Length (aa)Sequence Identity (%)Sequence Similarity (%)
0MAMMALIAHomo sapienshumanPrimates0NP_001273015100123100100
1Pan Paniscusbonobo (pygmy chimpanzee)Primates6.7XP_008952146.110012399.2100
2Mus musculushouse mouseRodentia90NP_079739.110012382.9391.1
3AVESDromaius novaehollandiaeemuAves312XP_0259752909620035.643.4
4Apteryx mantelli North Island brown kiwiAves312XP_0138065429015548.461.9
5REPTILIAChelydra serpentinacomman snapping turtleReptilia312KAG6938024.19712762.274
6AMPHIBIANBufo bufo common toadAmphibian351.8XP_040265882.19813551.575
7Ranitomeya imitatormimic poison frogAmphibian351.8CAF5124592.1 599751.256.6
8FISHDanio reriozebrafishActinoptergyii (bony fish)435XP_009298201.1 6517733.743.7
9Perca flavescensyellow perchActinoptergyii (bony fish)435XP_028427042.1 9712958.371.2
10Rhincodon typuswhale sharkChondrichthyes473XP_020392632.1 9512559.173.2
11Carcharodon carchariasgreat white sharkChondrichthyes473XP_041069108.19513057.674.2
12Callorhinchus miliielephant sharkChondrichthyes473XP_007910732.16113447.163.6
13INVERTEBRATESStyela Clavastalked sea squirtChordata676XP_039269774.1 9112536.851.9
14Branchiostoma belcheribelcher's lanceletChordata684XP_019641031.1 9312739.955.8
15Priapulus caudatuspenis wormPriapulimorphida797XP_014677581.1 9515728.740.7
16Owenia fusiformistubewormPolychaeta797CAC9620481.19214834.250
17Lingula anatinalingulaBrachiopoda797XP_013399665.16914135.255.6
18Exaiptasia diaphanasea anemoneAnthozoa 824XP_020906605.17811030.652.4
19Actinia tenebrosaWaratah anemoneAnthozoa 824XP_031558418.1 7011336.257.5
20Nematostella vectensisStarlet sea anemoneAnthozoa 824XP_001639221.1 8011234.954

Evolution rate

The relative evolution rate for c11orf98 is slower than the rate of fibrinogen alpha, but faster than cytochrome c.[25] This is shown on the graph on the right

Phylogenetic tree

On the right is a phylogenetic tree displaying the evolutionary history of the gene.

Clinical significance

Currently, the c11orf98 gene is not associated with any disease or medical condition.

Notes and References

  1. Web site: C11orf98 chromosome 11 open reading frame 98 [Homo sapiens (human)] ]. Gene . NCBI. 2021-10-04.
  2. Web site: Human hg38 chr11:62,662,817-62,665,210 UCSC Genome Browser v424. 2021-12-16. genome.ucsc.edu.
  3. Web site: Human hg38 chr11:62,662,817-62,665,210 UCSC Genome Browser v424. 2021-12-16. genome.ucsc.edu.
  4. Web site: 2021-07-01. Homo sapiens chromosome 11 open reading frame 98 (C11orf98), transcript variant 1, mRNA. en-US.
  5. Web site: AceView: Gene:C11orf48andINTS5, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView.. 2021-12-16. www.ncbi.nlm.nih.gov.
  6. Web site: C11orf98 chromosome 11 open reading frame 98 [Homo sapiens (human)] - Gene - NCBI]. 2021-12-18. www.ncbi.nlm.nih.gov.
  7. Web site: GenoMatix. live. https://web.archive.org/web/20211216013155/https://www.genomatix.de/cgi-bin/eldorado/main.pl?s=4fe121b19854d768fcb2512dadbdbfc7 . 2021-12-16 .
  8. Web site: uncharacterized protein C11orf98 [Homo sapiens] - Protein - NCBI]. 2021-12-15. www.ncbi.nlm.nih.gov.
  9. Web site: SAPS Results. 2021-12-15. www.ebi.ac.uk.
  10. Web site: C11orf98 (human). 2021-12-15. www.phosphosite.org.
  11. Web site: PSORT II Prediction. 2021-12-15. psort.hgc.jp.
  12. Web site: Services. 2021-12-15. www.healthtech.dtu.dk. en.
  13. Web site: uncharacterized protein C11orf98 [Homo sapiens] - Protein - NCBI]. 2021-10-25. www.ncbi.nlm.nih.gov.
  14. Web site: Motif Scan. 2021-12-15. myhits.sib.swiss. en.
  15. Web site: Bioinformatics Toolkit. 2021-12-15. toolkit.tuebingen.mpg.de.
  16. Web site: AlphaFold Protein Structure Database. 2021-12-15. alphafold.ebi.ac.uk.
  17. Web site: Motif Scan. 2021-12-16. myhits.sib.swiss. en.
  18. Web site: GPS 5.0 - Kinase-specific Phosphorylation Site Prediction. 2021-12-16. gps.biocuckoo.cn.
  19. Web site: GPS-SUMO: Prediction of SUMOylation Sites & SUMO-interaction Motifs. 2021-12-16. sumosp.biocuckoo.org. 2013-05-10. https://web.archive.org/web/20130510131129/http://sumosp.biocuckoo.org/. dead.
  20. Web site: PSIQUIC View. live. https://web.archive.org/web/20100411073725/http://www.ebi.ac.uk:80/Tools/webservices/psicquic/view/main.xhtml? . 2010-04-11 .
  21. Web site: Gene: C11orf98. Ensembl.
  22. Web site: BLAST: Basic Local Alignment Search Tool. 2021-12-15. blast.ncbi.nlm.nih.gov.
  23. Web site: TimeTree :: The Timescale of Life. 2021-12-15. timetree.org.
  24. Web site: BLAST: Basic Local Alignment Search Tool. 2021-12-15. blast.ncbi.nlm.nih.gov.
  25. Web site: TimeTree :: The Timescale of Life. 2021-12-15. timetree.org.