C3orf56 is a protein encoding gene found on chromosome 3. Although, the structure and function of the protein is not well understood, it is known that the C3orf56 protein is exclusively expressed in metaphase II of oocytes and degrades as the oocyte develops towards the blastocyst stage. Degradation of the C3orf56 protein suggests that this gene plays a role in the progression from maternal to embryonic genome and in embryonic genome activation.[1]

Gene

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The C3orf56 gene is positioned at 3q21.3 on the plus strand and is 5,055 base pairs in length.[2] The gene occupies base pair 127193131 to 127198185.[3] C3orf56 has two aliases: FLJ40141 and LOC285311.[4]

Transcript

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The primary assembly contains 2 exons and is 242 amino acids in length.[5]

Protein

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C3orf56 has a predicted molecular weight of 26 kdal[6] and an isoelectric point of 8.48.[7]

 
Predicted tertiary structure of C3orf56.

Primary Structure

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C3orf56 is rich in proline, serine, and tryptophan.[8] It has one highly conserved internal repeat which spans from G85 to P125 and G146 to P178.[9]

Secondary Structure

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Only one highly conserved alpha helical structure was predicted.[10][11]

Tertiary Structure

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The tertiary structure of C3orf56 was predicted with a confidence score of -3.08.[12] It is suggested to possess many hydrogen bonds and salt bridges.[13]

Protein-Protein Interactions

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C3orf56 has been predicted to interact with tyrosine-protein kinase transmembrane receptor (ROR2)[14] and oocyte-expressed protein homolog (OOEP).[15]

Gene level regulation

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Expression

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C3orf56 has shown to be over-expressed in the testes.[16] Relative to the expression of all other genes, C3orf56 has shown an almost absence of expression in human tissues (excluding the ovary) than in metaphase II oocytes.[17] C3orf56 also has an expression relatively lower in the 8-cell embryo stage and significantly lower in the morula and blastocyst stages compared to the 1-cell, 2-cell, and 4-cell stages.[18]

 
C3orf56 expression throughout embryonic development.
 
C3orf56 expression in oocytes.

RNA binding proteins and transcription factors

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RNA binding proteins seem to be conserved within the 5’ UTR and show some functional significance with sex and development.[19] Many predicted transcription factors also demonstrated a functional importance in development.[20]

Transcript level regulation

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Predicted stem loops

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Hypothetical stem loops appear to be slightly more prevalent in the 3’ UTR sequence with more conservation of stem loops in the 5’ UTR sequence.[21]

Protein level regulation

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Post-translational modifications

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C3orf56 has many predicted post-translational modifications. Predicted protein kinase C phosphorylation sites were found at and S6-K8, K181-C183, and S228-R230.[22] Predicted casein kinase II phosphorylation sites at S109-S112, S213-E186, and S218-L220.[23] General phosphorylation sites were predicted at T3, S6, S21, S109, T160, and S227.[24] N-myristoylation sites were predicted to be found at G2-E7, G26-S31, G38-S43, and G146-S151.[25]

Localization

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A potential nuclear localization signal was found at position P231 to R238 along with a suggested nuclear tendency.[26]

Evolutionary History

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The earliest appearance of the C3orf56 gene was approximately 102 million years ago within the species Orycteropus afer. Compared to the speed at which the proteins fibrinogen alpha and cytochrome c evolved, C3orf56 evolves very rapidly. This relationship was limited to more recently diverged species.

 
The corrected % divergence (m) was calculated and plotted against date of divergence (MYA) for proteins C3orf56, fibrinogen alpha, and cytochrome c.

Homology

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C3orf56 has numerous orthologs that are only within various placental mammals.[27] No known paralogs of C3orf56 exist at this time.

Table 1 Orthologs of C3orf56
Genus and Species Common Name Taxonmic Order Date of Divergence (MYA) Accession Number Sequence Length (aa) % Sequence Identity % Sequence Similarity
Homo sapiens Human Primate 0 NP_001007535.1 242 100 100
Rhinopithecus bieti Black Snub-nosed Monkey Primate 29 XP_017740448.1 248 87 89
Saimiri boliviensis boliviensis Bolivian Squirrel Monkey Primate 43 XP_003944171.1 249 76 79
Galeopterus variegatus Flying Lemur Dermoptera 83 XP_008592749.1 222 57 64
Castor canadensis Beaver Rodentia 89 XP_020010355.1 204 50 56
Jaculus jaculus Lesser Egyptian Jerboa Rodentia 89 XP_012805719.1 226 38 49
Heterocephalus glaber Naked Mole Rat Rodentia 89 XP_012924683.1 264 38 49
Mirounga leonina Southern Elephant Seal Carnivora 94 XP_034854170.1 178 57 64
Phocoena sinus Vaquita Artiodactyla 94 XP_032503804.1 236 57 61
Eumetopias jubatus Northern Sea Lion Carnivora 94 XP_027957377.1 195 54 64
Canis lupus familiaris Dog Carnivora 94 XP_022263109.1 232 53 60
Ailuropoda melanoleuca Panda Carnivora 94 XP_011228030.2 175 52 58
Equus caballus Horse Perissodactyla 94 XP_014584106.2 240 49 58
Sus scrofa Wild Boar Cetartiodactyla 94 XP_020926903.1 231 49 56
Vicugna pacos Alpaca Artiodactyla 94 XP_031532218.1 366 49 56
Camelus dromedarius Arabian Camel Artiodactyla 94 XP_031325652.1 233 45 53
Enhydra lutris kenyoni Sea Otter Carnivora 94 XP_022377075.1 247 43 50
Crocuta crocuta Hyena Carnivora 94 KAF0873334.1 216 39 46
Bison bison bison Bison Artiodactyla 94 XP_010857995.1 273 34 21
Monodon monoceros Narwahl Cetacea 94 TKC45752.1 265 33 43
Orycteropus afer Aardvark Tubulidentata 102 XP_007951414.1 113 45 54

References

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  1. ^ Bouckenheimer J, Fauque P, Lecellier CH, Bruno C, Commes T, Lemaître JM, De Vos J, Assou S. Differential long non-coding RNA expression profiles in human oocytes and cumulus cells. Sci Rep. 2018 Feb 2;8(1):2202. doi: 10.1038/s41598-018-20727-0. PMID 29396444; PMCID: PMC5797088
  2. ^ C3orf56 chromosome 3 open reading frame 56 Homo sapiens - Gene - NCBI. (2020, August 22). Retrieved September 30, 2020, from https://www.ncbi.nlm.nih.gov/gene/285311
  3. ^ Database, G. (n.d.). C3orf56 Gene (Protein Coding). Retrieved September 30, 2020, from https://www.genecards.org/cgi-bin/carddisp.pl?gene=C3orf56
  4. ^ "C3orf56 Gene - GeneCards | CC056 Protein | CC056 Antibody". www.genecards.org. Retrieved 2020-12-19.
  5. ^ C3orf56 chromosome 3 open reading frame 56 [Homo sapiens (human)] - Gene - NCBI. (2020, August 22). Retrieved September 30, 2020, from https://www.ncbi.nlm.nih.gov/gene/285311
  6. ^ "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2020-12-17.
  7. ^ "ExPASy - Compute pI/Mw tool". web.expasy.org. Retrieved 2020-12-17.
  8. ^ "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2020-12-17.
  9. ^ "Dotlet JS". dotlet.vital-it.ch. Retrieved 2020-12-17.
  10. ^ "NPS@ : GOR4 secondary structure prediction". npsa-prabi.ibcp.fr. Retrieved 2020-12-17.
  11. ^ Prof. T. Ashok Kumar. "CFSSP: Chou & Fasman Secondary Structure Prediction Server". www.biogem.org. Retrieved 2020-12-17.
  12. ^ "I-TASSER results". zhanglab.ccmb.med.umich.edu. Retrieved 2020-12-19.
  13. ^ "iCn3D: Web-based 3D Structure Viewer". www.ncbi.nlm.nih.gov. Retrieved 2020-12-19.
  14. ^ "PSICQUIC View". www.ebi.ac.uk. Retrieved 2020-12-18.
  15. ^ "STRING: functional protein association networks". string-db.org. Retrieved 2020-12-18.
  16. ^ "C3orf56 chromosome 3 open reading frame 56 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-12-16.
  17. ^ "52817401 - GEO Profiles - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-12-17.
  18. ^ "74223601 - GEO Profiles - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-12-19.
  19. ^ "RBPDB: The database of RNA-binding specificities". rbpdb.ccbr.utoronto.ca. Retrieved 2020-12-19.
  20. ^ "Genomatix" (in German). Archived from the original on 2001-02-24. Retrieved 2020-12-19.
  21. ^ "RNAfold web server". rna.tbi.univie.ac.at. Retrieved 2020-12-19.
  22. ^ "Motif Scan". myhits.sib.swiss. Retrieved 2020-12-17.
  23. ^ "Motif Scan". myhits.sib.swiss. Retrieved 2020-12-17.
  24. ^ "NetPhos 3.1 Server". www.cbs.dtu.dk. Retrieved 2020-12-17.
  25. ^ "Motif Scan". myhits.sib.swiss. Retrieved 2020-12-17.
  26. ^ "PSORT II Prediction". psort.hgc.jp. Retrieved 2020-12-19.
  27. ^ BLAST: Basic Local Alignment Search Tool. (2020, September 29). Retrieved September 29, 2020, from https://blast.ncbi.nlm.nih.gov/Blast.cgi