CCDC186 explained

CCDC186 is a protein that in humans is encoded by the CCDC186 gene[1] The CCDC186 gene is also known as the CTCL-tumor associated antigen with accession number NM_018017.[2]

Gene

Location

CCDC186 has the chromosome location of 10q25.3 and is 53,750 bases in size oriented on the minus strand. PSORTII Protein k-NN Prediction indicated that C10orf118 is 65.2% of the time nuclear, 17.4% cytosolic, 8.7% mitochondrial, 4.3% vesicles of secretory system, and 4.3% endoplasmic reticulum.[3]

Expression

Analysis of gene expression in humans and other species indicates C10orf118 is ubiquitously expressed in all tissue types at varying developmental stages. An EST profile from NCBI displayed the greatest expression in bone marrow, kidneys, and the prostate cell lines. Breakdown by health state indicates high expression of C10orf118 in bladder carcinoma and prostate cancer.[4]

Protein

General Properties

The protein of CCDC186 (NP_060487) is 898 amino acids in length. The predicted molecular weight is 103.7kdal and the isoelectric point is predicted to be 5.92.[5]

Composition

A serine rich region is observed in amino acids 710-747. A compositional analysis revealed that C10orf118 is Proline (1.1%) poor and Glutamic acid (14.1%) and Lysine (12.0%) rich.

Interactions

CCDC186 protein was found to interact with proteins PLEKAH5, Ezra, GAMMAHV.ORF23, and SMAD3.[6] [7]

Homology

Orthologous sequences of CCDC186 were not found to be in bacteria, archea, protist, or plants. CCDC186 has no human paralogs. The date of divergence for the orthologous sequences highly correlates with the sequences similarity in that the percent identity decreases as you go back in time. Closely related orthologs include mammals and birds and moderately related orthologs include other vertebrates such as fish, reptiles, and amphibians. Distantly related orthologous sequences are primarily observed in invertebrates.[8]

Sequence NumberGenus and speciesCommon nameDate of divergence (MYA)Accession numberSequence lengthSequence identitySequence similarityE-value
1Homo sapiens C10orf1180NM_018017898 aa100%100%0%
2Nomascus leucogenysNorthern White-cheeked Gibbon 19.9XP_003255542898 aa98%98%0%
3Chinchilla lanigeralong tailed chinchilla 90.9XP_013371303906 aa 90%94%0%
4Mus musculushouse mouse 90.9NP_739563917 aa84%91%0%
5Tursiops truncatusbottlense dolphin 97.5XP_004318425599 aa 60%68%0%
6Loxodonta africanaAfrican Bush Elephant 105XP_010596062805 aa 90%91%0%
7Egretta garzettalittle egret 320.5XP_009634185914 aa 75%83%0%
9Chelonia mydasgeen sea turtle 320.5XP_007056391920 aa76%83%0%
10Xenopus tropicaliswestern clawed frog 355.7XP_004919435878 aa71%83%0%
11Astyanax mexicanusMexican tetra 429.6XP_007259323987 aa71%82%5.00E-09
12Oryzias latipesJapanese rice fish 429.6XP_011486278991 aa58%71%0%
13Callorhinchus miliiAustralian ghostshark 482.9XP_007903851931 aa 65%79%0%
14Strongylocentrotus purpuratusSea Urchin 747.8XP_011675415884 aa 39%58%7.00E-84
15Octopus bimaculoidesCalifornia Two-spot Octopus 847XP_0147825871221 aa 42%60%3.00E-127
16Aplysiomorphasea hare 847Not found in BLAST1384 aa 42%63%3.00E-145
17Orussus abietinuswasp 847XP_0122889991057 aa 36%55%5.00E-100
18Atta cephalotesleafcutter ant 847XP_0120543111154 aa 35%55%9.00E-93
19Helobdella robustaleech 847ESO07814997 aa29%47%1.00E-50
20Caenorhabditis elegansnematode 847NP_871700743 aa 26%34%1.00E-25
21Trichoplax adhaerensNA936EDV25816976 aa26%46%2.00E-11

Motifs

Motif Information[9] Position(s)
N-glycosylation site33-36, 40-43, 109-112, 867-870
cAMP- and cGMP-dependent protein kinase phosphorylation site.238-241, 583-586, 794-797
Casein kinase II phosphorylation site.2-5, 10-13, 31-34, 36-39, 126-129, 130-133, 135-138, 139-142, 157-160, 228-231, 241-244, 256-259, 405-408, 440-443, 459-462, 490-493, 515-518, 611-614, 617-620, 625-628, 671-674, 690-693, 734-737, 869-872, 879-882
Leucine Zipper Pattern588-609, 870-891
N-myristoylation site32-37, 75-80, 86-91, 183-188, 721-726, 728-733, 745-750, 810-815, 828-833
Protein kinase C phosphorylation site12-14, 35-37, 49-51, 146-148, 228-230, 243-245, 250-252, 278-280, 347-349, 371-373, 405-407, 417-419, 490-492, 500-502, 581-583, 592-594, 596-598, 682-684, 690-692, 825-827, 869-871, 895-897
Tyrosine kinase phosphorylation site134-141, 514-522
Cullen Family Profile443-552
K-Box Domain Profile 526-619
Nebulin Repeat Profile521-531
Serine Rich Region 710-747
Rad50 zinc-hook domain profile460-562
ATP synthase B/B' CF(0)405-433
Alpha-2-macroglobulin RAP, C-terminal domain524-705
334-577

Post Translational Modification

CCDC186 is predicted to undergo multiple posttranslational modifications including predicted O-beta-GlcNAc attachment, phosphorylation, a nuclear export signal, glycation of lysines, GlcNAc O-glycosylation, N-glycosylation, and NetCorona sites.[10]

Clinical significance

Prior research indicates that the open reading frame of C10orf118 is linked to cutaneous T-cell lymphoma by a tumor antigen L14-2.[11] The protein CCDC186 is also found at higher than normal levels in the breast cancer cell line BC 8701.[12]

Further reading

Notes and References

  1. Oduru S, Campbell JL, Karri S, Hendry WJ, Khan SA, Williams SC . Gene discovery in the hamster: a comparative genomics approach for gene annotation by sequencing of hamster testis cDNAs . BMC Genomics . 4 . 1 . 22 . June 2003 . 12783626 . 161800 . 10.1186/1471-2164-4-22 . free .
  2. Web site: Entrez Gene: C10orf118 chromosome 10 open reading frame 118.
  3. Web site: PSORT II Prediction. psort.hgc.jp. 2016-04-24.
  4. Web site: Home - UniGene - NCBI. www.ncbi.nlm.nih.gov. 2016-04-24.
  5. Web site: SDSC Biology Workbench. seqtool.sdsc.edu. 2016-04-24. https://web.archive.org/web/20030811031200/http://seqtool.sdsc.edu/. 2003-08-11. dead.
  6. Web site:
    • in Literature citations
    . www.uniprot.org. 2016-04-24.
  7. Web site: CCDC186 - Coiled-coil domain-containing protein 186 - Homo sapiens (Human) - CCDC186 gene & protein.
  8. Web site: BLAST: Basic Local Alignment Search Tool. blast.ncbi.nlm.nih.gov. 2016-04-24.
  9. Web site: Motif Scan. myhits.isb-sib.ch. 2016-05-08.
  10. Web site: Welcome to CBS. www.cbs.dtu.dk. 2016-04-24.
  11. de la Peña M, García-Robles I . Intronic hammerhead ribozymes are ultraconserved in the human genome . EMBO Reports . 11 . 9 . 711–6 . September 2010 . 20651741 . 2933863 . 10.1038/embor.2010.100 .
  12. D’Angelo. M. L.. 2013. Identification of the "Uncharacterized Protein C10orf118" in Breast Cancer Cells and Its Role on the Hyaluronan Metabolism. Matrix Pathobiology, Signaling and Molecular Targets..