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Coiled-Coil Domain Containing Protein 166

CCDC166
Possible CCDC166 structure
Proposed structure of CCDC166

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Coiled-coil domain containing 166 is a protein that in humans is encoded by the CCDC166 gene. [1]

Coiled-Coil Domain Containing Protein 166 (CCDC166) is a gene that's function is not currently well understood. It contains a Coiled coil domain, hence the current origin of it's name. It is primarily expressed in the testes.

Gene

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The gene currently is known to contain only two exons, and one isoform. This primary transcript consists of 1317 DNA base pairs. Its location is on chromosome 8q24.3, between positions 143706694-143708109, on the + strand. The gene is located near BREA2 and MAPK15. [2]

Transcripts

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The gene has only a single transcript, due to only have two exons, both which are always transcribed. The coding portion of the mRNA is 1319 nucleotides.Cite error: There are <ref> tags on this page without content in them (see the help page). In tissues found to express the transcript for this gene it is typically found in low levels.Cite error: There are <ref> tags on this page without content in them (see the help page).

Protein

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CCDC166 has only one isoform in humans, which has a molecular weight of 48.7 kDa and is composed of 439 amino acids.Cite error: There are <ref> tags on this page without content in them (see the help page). The pI of the protein is 10.537. Cite error: There are <ref> tags on this page without content in them (see the help page). The protein has several amino acid repeat structures including; EREA, VQSL and (T)QLLH, all of which are conserved in mammals. Cite error: There are <ref> tags on this page without content in them (see the help page). The composition of the protein reveals that it is high in serine, lysine, and arginine.Cite error: There are <ref> tags on this page without content in them (see the help page). The protein contains three conserved domains including a coiled-coil domain between amino acids 27-74, a domain of unknown function between amino acids 72-260, and a serine-rich domain between amino acids 288-410.Cite error: There are <ref> tags on this page without content in them (see the help page). The structure is mainly composed of alpha-helices that form a larger coiled-coil. It also contains several coiled-coils. Cite error: There are <ref> tags on this page without content in them (see the help page).

Gene level regulation

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The gene seems to be expressed heavily in the testes, and this may be conserved in evolution. [3] [4] The promoter region contains several conserved transcription factor binding sites. Notably among them are the CREB family, KLFs, and perhaps the most telling of which is the presence of Testis-determining factor.Cite error: There are <ref> tags on this page without content in them (see the help page). These transcription factors are all important during the process of development.

Transcript Level Regulation

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In situ hybridization (ISH) data has found the gene's mRNAs are mostly found in the nucleus of Sertoli cell, with low expression in Leydig cells.Cite error: There are <ref> tags on this page without content in them (see the help page). The gene has also been found in other germ cell tumors.Cite error: There are <ref> tags on this page without content in them (see the help page). In addition the gene's primary transcript contains several miRNA binding sites, including: hsa-miR-2278, hsa-miR-3178, and hsa-miR-4516. Cite error: There are <ref> tags on this page without content in them (see the help page).

Protein Level Regulation

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CCDC166 is predicted to be regulated by SUMO protein. It has a conserved IKAD sequence at amino acid 220-223.Cite error: There are <ref> tags on this page without content in them (see the help page). This combined with a conserved nuclear localization signal of PKKKR starting at amino acid 3, supports that this protein is imported into the nucleus.Cite error: There are <ref> tags on this page without content in them (see the help page). The gene also contains several predicted phosphorylation sites, most of which are predicted to be clustered into the serine-rich domain. The occurences of highest probability occur at serine 10, serine 308, and serine 391.Cite error: There are <ref> tags on this page without content in them (see the help page).

Homology / Evolution

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While the current function of the gene is unknown, many mammals possess on ortholog of the gene. In various primate species studies, several species have been found to possess on orthologous gene that shares 90% sequence identity. [5] While the gene does not seem to have paralogs, it has homology that have been conserved throughout its evolutionary history. Evidence that it's function has been conserved comes from the promoter region, which has predicted SRY-transcription factors binding sites conserved from zebrafish all the way to humans.Cite error: There are <ref> tags on this page without content in them (see the help page).

"Evolutionary History of CCDC166"
Species Gene Name Date of Divergence Percent Similarity Accession Number
Human CCDC166 0 MYA 100% NP_001156386.1
Chimpanzees CCDC166 isoform 1 6.65 MYA 98% PNI46222.1
Grey Mouse Lemur CCDC166 74 MYA 76% XP_017516497.1
Horse CCDC166 96 MYA 85% XP_023504891.1
Florida Manatee CCDC166 105 MYA 79% XP_004387488.1
Japanese Gecko CCDC166-like protein 312 MYA 74% XP_007444987.1
Mallard Duck CCDC166-like protein 312 MYA 39% ENSAPLG00000001712
Mexican tetra CCDC166 435 MYA 26% ENSAMXG00000003745.1

Biochemistry

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Interactions

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The gene has been found to interact with FAT3, a tumor supressor gene, as well as INTS2 a gene that is involved in snRNA processing and transcription. Cite error: There are <ref> tags on this page without content in them (see the help page). Expression of CCDC166 has shown to be affected by methylphenidate, but the mechanism of this interaction is not known.Cite error: There are <ref> tags on this page without content in them (see the help page).

  1. ^ "Entrez Gene: Coiled-coil domain containing 166". Retrieved 2018-05-05.
  2. ^ https://www.ncbi.nlm.nih.gov/gene?cmd=retrieve&list_uids=100130274
  3. ^ 6. CCDC166. (n.d.). Retrieved April 02, 2018, from https://www.proteinatlas.org/ENSG00000255181-CCDC166/antibody
  4. ^ . EST Profile - Hs.730002. (n.d.). Retrieved April 02, 2018, from https://www.ncbi.nlm.nih.gov/UniGene/ESTProfileViewer.cgi?uglist=Hs.730002
  5. ^ http://www.uniprot.org/uniprot/P0CW27