CCDC177 has one variant, which encodes Isoform 1 in humans. The mRNA sequence for this variant is 4,182 base pairs in length.[5] Both exons are present in the variant, however the coding region is entirely within Exon 2.
Protein
[edit]The predicted tertiary structure of human CCDC177 protein from AlphaFold.[8]
CCDC177 Isoform 1 in humans is 707 amino acids long[5] with a predicted molecular weight of 80 kDa.[9] It is rich in arginine, and glutamate, and poor in isoleucine relative to other proteins. The isoelectric point is 11.[10] The human protein is also rich in arginine-glutamate motifs, which are implicated in cell survival signaling.[11]
Proteins of the coiled coil domain containing (CCDC) family contain large coiled helical domains.[7][12] The coiled helical domain within the human CCDC177 protein fully overlaps the domain of unknown function (DUF4659).
Large-scale Analysis of the Human Transcriptome [Profile GDS596] from NCBI GeoProfiles.[13]
CCDC177 mRNA is ubiquitously expressed across adult human tissues, but is low in expression in fetal tissues throughout the body. It is also less abundant in immune cells such as B cells, T cells, and NK cells.[13]
Human CCDC177 contains multiple nuclear localization signals, indicating that is found in the nucleus.[14] The protein also contains multiple nuclear export signals, indicating protein movement between the nucleus and cytosol.[15] The locations of the various kinases phosphorylating the CCDC177 protein implicate phosphorylation in CCDC177's movement between the nucleus and cytosol.[16]
The types of kinases that phosphorylate highly conserved serine residues (conserved across current CCDC177 orthologs) in the CCDC177 protein sequence are located in the nucleus and cytosol. These kinases include Protein Kinase A which is located in the cytosol and nucleus,[19]Cyclin-dependent kinase 5 located in the cytosol,[20] and Protein Kinase C located in the nucleus.[21]
CCDC177 post-translational modifications and other notable motifs. Created using IBS-Data Visualization[22]Human CCDC177 Conceptual Translation annotated with specific motifs of interest, signal sequences, post-translational modifications and other predicted domains. Labels for each annotation are found in the margins of the conceptual translation.
The following graph shows the rate of evolution of CCDC177 compared to that of Cytochrome C and Fibrinogen Alpha.Circles indicate similar species. Made using Phylogeny.fr[25]
Human CCDC177 protein has notable interactions with the following proteins which are all associated with development and stem cell differentiation. All of the following proteins are located in the nucleus. These interactions implicate human CCDC177 in developmental processes and cell survival, and support its location in the nucleus.
MYC binding protein 2 (MYCBP2) regulates neuronal growth and is required for proper axon growth.[26]
Forkhead box protein N4 (FOXN4) is a transcription factor required for neural development and growth. It is especially important for specifying the fates of multipotent retinal progenitors.[27]
Histone Deacetylase 5 (HDAC5) deacetylates lysine residues on the N-terminus tail of core histones and promotes cell cycle progression.[28]
T-cell acute lymphocytic leukemia protein 1 (TAL1) is an oncogenic transcription factor in T-cell acute lymphoblastic leukemia, and is implicated in hematopoietic stem cell differentiation.[29]
The CCDC177 gene can be utilized to develop prognostic tumor markers for neuroblastomas,[30]thyroid cancer,[31] and lung cancer.[32]CCDC177 is a methylation-driven gene in thyroid cancer, which was determined by examining proliferation and invasion of thyroid cancer (TC) cells in CCDC177 knockdown vectors. TC cells containing knockdown CCDC177 were highly proliferative and invasive.
Prognostic tumor methylation markers were discovered in human neuroblastoma as well.[33] 78 significantly differentially methylated regions were identified from 396 sequenced tumor profiles. Methylation-specific PCR assays were also developed to determine which regions accurately predict survival outcomes. 5 of the 78 assays, including one located in CCDC177, predicted event-free survival. CCDC177 mRNA is also integral to the accurate prediction of overall survival in lung squamous cell carcinoma (LUSC) patients.
^ abOehl-Jaschkowitz B, Vanakker OM, De Paepe A, Menten B, Martin T, Weber G, et al. (March 2014). "Deletions in 14q24.1q24.3 are associated with congenital heart defects, brachydactyly, and mild intellectual disability". American Journal of Medical Genetics. Part A. 164A (3): 620–626. doi:10.1002/ajmg.a.36321. PMID24357125. S2CID36417832.
^ abLiu Z, Yan W, Liu S, Liu Z, Xu P, Fang W (July 2023). "Regulatory network and targeted interventions for CCDC family in tumor pathogenesis". Cancer Letters. 565: 216225. doi:10.1016/j.canlet.2023.216225. PMID37182638. S2CID258683797.
^Ino H, Chiba T (September 1996). "Intracellular localization of cyclin-dependent kinase 5 (CDK5) in mouse neuron: CDK5 is located in both nucleus and cytoplasm". Brain Research. 732 (1–2): 179–185. doi:10.1016/0006-8993(96)00523-9. PMID8891282. S2CID20687258.
^Ringvold HC, Khalil RA (2017-01-01), Khalil RA (ed.), "Chapter Six - Protein Kinase C as Regulator of Vascular Smooth Muscle Function and Potential Target in Vascular Disorders", Advances in Pharmacology, Vascular Pharmacology, vol. 78, Academic Press, pp. 203–301, doi:10.1016/bs.apha.2016.06.002, PMC5319769, PMID28212798
^Ju Q, Zhao YJ, Ma S, Li XM, Zhang H, Zhang SQ, et al. (July 2020). "Genome-wide analysis of prognostic-related lncRNAs, miRNAs and mRNAs forming a competing endogenous RNA network in lung squamous cell carcinoma". Journal of Cancer Research and Clinical Oncology. 146 (7): 1711–1723. doi:10.1007/s00432-020-03224-8. PMID32356177. S2CID216650042.