Biology:CORO6

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A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Coronin-6 also known as coronin-like protein E (Clipin-E) is a protein that in humans is encoded by the CORO6 gene.

Coronin-6 is belongs to coronin family which is an actin binding protein.[1][2] Human CORO6 gene is located on chromosome 17 on the cytogenetic band 17 p11.2.[3] Gene CORO6 is well conserved across domain of eukaryotic organisms from animal to fungi.[4]

Expression

EST profile

Based on the EST profile, CORO6 expressed in high level at the larynx, nerve and muscle. CORO6 has also been shown to be expressed in high levels in the breast (mammary gland) tumor. During the human development stage, the higher level of CORO6 expressed at blastocyst and adult.[5]

Transcript Variant

Alternative mRNAs are shown aligned from 5' to 3' on a virtual genome where introns have been shrunk to a minimal length. Exon size is proportional to length, intron height reflects the number of cDNAs supporting each intron. Introns of the same color are identical, of different colors are different. 'Good proteins' are pink, partial or not-good proteins are yellow, uORFs are green. 5' cap or3' poly A flags show completeness of the transcript . CORO6 contains 21 distinct gt-ag introns. Transcription produces 10 alternatively spliced mRNA. There are 3 probable alternative promoters, and validated alternative polyadenylation sites.[6]

ACEview, predicted alternative splicing sites.png

Structure

CORO6 protein sequence contains WD-40 repeats. WD40 domain is a structural motif found in Eukaryotes and cover variety of functions, such as adaptor or regulatory modules in signal transduction, pre-mRNA processing and cytoskeletal assembly. It usually terminating at WD dipeptide at its C-terminus and is about 40 residues long, so called WD40.[7]

The structure of CORO6 is predicted by using Phyre2 program. It is similar to the crystal structure of murine coronin-1. 390 residues ( 83% of CORO6 protein sequence) have been modelled with 100.0% confidence by the single highest scoring template. Image coloured by rainbow N → C terminus

Homology

Paralogs

Human proteins which are the paralogs to CORO6, CORO1A, CORO1B, CORO1C, CORO2A, CORO2B, CORO7

The table compared Homo sapiens protein CORO6 to its paralogs

Name of paralogs CORO6 CORO1A CORO1B CORO2A CORO2B CORO7
Accession number NP_116243 NP_009005 NP_065174 NP_438171 NP_006082 NP_078811
Sequence length 472 aa 461 aa 489 aa 525 aa 480 aa 925 aa
Sequence identity 67% 67% 45% 45% 32%
Sequence similarity 81% 80% 64% 63% 49%

By comparing its paralogs we found that CORO1A and CORO1B are most related to CORO6.

Orthologs

CORO6 is highly conserved throughout the organisms from vertebrate to fungus, the organisms listed in the table are some representatives.

Genus and species (Orthologs comparison) Homo sapiens Pan troglodytes Canis familiaris Anolis carolinensis Danio rerio Saccharomyces cerevisiae Plasmodium falciparum
Common name Human Chimpanzee Dog Lizard Zebrafish Baker's Yeast Malaria parasite
Date of divergence from human lineage 6.3 MYA 94.2 MYA 269 MYA 400.1 MYA 1215.8 MYA 1381.2 MYA
Accession number NP_116243 XP_001137660 XP_548302 XP_0003227217 NP_956690 NP_013533 XP_001350896
Sequence length 472 aa 471 aa 472 aa 471 aa 436 aa 651 aa 602 aa
Sequence identity to human 96% 98% 83% 78% 42% 31%
Sequence similarity to human 97% 99% 90% 90% 62% 52%
CORO6 nasal epithelium response to house dust mite allergen in vitro.png

Clinical significance

There are several clinical studies about that have been performed by using microarray indicating that CORO6 is positively related to allergic nasal epithelium response to house dust mite allergen in vitro.[8]

Model organisms

Model organisms have been used in the study of CORO6 function. A conditional knockout mouse line called Coro6tm1e(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[9] Male and female animals underwent a standardized phenotypic screen[10] to determine the effects of deletion.[11][12][13][14] Additional screens performed: - In-depth immunological phenotyping[15]

References

  1. de Hostos EL, Eugenio L (September 1999). "The coronin family of actin-associated proteins". Trends Cell Biol 9 (9): 345–50. doi:10.1016/S0962-8924(99)01620-7. PMID 10461187. 
  2. "Cronin-6 Homo Sapiens". NCBI. https://www.ncbi.nlm.nih.gov/protein/NP_116243.2. Retrieved 28 April 2013. 
  3. "CORO6". GeneCards. https://www.genecards.org/cgi-bin/carddisp.pl?gene=CORO6&search=coro6. Retrieved 28 April 2013. 
  4. "CORO6". HomoloGene. https://www.ncbi.nlm.nih.gov/homologene?Db=homologene&Cmd=Retrieve&list_uids=104099. Retrieved 28 April 2013. 
  5. "CORO6 expression level.". EST profile. https://www.ncbi.nlm.nih.gov/UniGene/ESTProfileViewer.cgi?uglist=Hs.143046. Retrieved 28 April 2013. 
  6. "CORO6". ACEview. https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=coro6&submit=Go. 
  7. "WD-40 superfamily". conserved domain. https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cl02567. Retrieved 28 April 2013. 
  8. "Allergic nasal epithelium response to house dust mite allergen in vitro.pnj". GEO profile. https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS3082:1552301_a_at. Retrieved 9 May 2013. 
  9. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. 
  10. 10.0 10.1 "International Mouse Phenotyping Consortium". http://www.mousephenotype.org/data/search?q=Coro6#fq=*:*&facet=gene. 
  11. "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. June 2011. doi:10.1038/nature10163. PMID 21677750. 
  12. "Mouse library set to be knockout". Nature 474 (7351): 262–3. June 2011. doi:10.1038/474262a. PMID 21677718. 
  13. "A mouse for all reasons". Cell 128 (1): 9–13. Jan 2007. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  14. "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell 154 (2): 452–64. 2013. doi:10.1016/j.cell.2013.06.022. PMID 23870131. 
  15. 15.0 15.1 "Infection and Immunity Immunophenotyping (3i) Consortium". http://www.immunophenotyping.org/data/search?keys=Coro6&field_gene_construct_tid=All. 

External links