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DEP Domain Containing Protein 1B also known as XTP1, XTP8,HBV XAg-Transactivated Protein 8, [formerly refered as BRCC3] is a human protein encoded by a gene of similar name located on chromosome 5.[1][2][3]
Gene Structure[edit]
Gene Neighborhood[edit]
DEPDC1B is found on the long arm of chromosome 5 (5q12.1), spanning 103kb on the minus strand. The gene neighborhood of DEPDC1B includes 5 other genes. Downstream are two genes SEPT21 and PDE4D. Upstream are another two genes ELOV7 and KRT8P31. On the complement strand is another gene in the same region PART1.[2]
Promoter[edit]
DEPDC1B promoter region contains several transcription factors associated with proteins of ubiquitous expression. These transcription factors possess a central theme of cellular proliferation, cell cycle regulation, apoptosis, and differentiation. Few promoters unique to tumor suppression or tumorgenesis exist within the region as well (ETS1, IRF, etc...).
mRNA Structure[edit]
Splice Variants[edit]
DEPDC1B possesses 13 mRNA splice variants that form two isoforms. Isoform 1 is the longest and is the most commonly used version of the gene[6]. It is composed of 11 exons and is 103254bp in length[2]. Isoform 2 is the second confirmed transcript variant. It is composed of 10 exons, missing the tenth exon of the first variant.
Secondary Structure[edit]
DEPDC1B is predicted to be predominantly alpha-helical. No significant beta-strands or beta structures exist with the protein.
Stem Loops and Binding miRNA[edit]
Protein Structure[edit]
Sequence[edit]
The DEPDC1B gene possesses two novel proteoforms. The longest variation, coded by mRNA isoform 1, is the most commonly used. The protein is 529 amino acids in length.
The second novel proteoform, DEPDC1B.2 is coded by 10 exons, missing the 10th exon from the longest variation. The protein is 467 amino acids in length.
Domains[edit]
DEPDC1B contains two structural domains: a DEP domain and a RhoGAP domain.
The DEP domain is primarily found in proteins involved in G-protein signalling pathways and regulation of GTPase.[4][5] As well, experimental evidence suggests that the DEP domain determines the subcellular target of some GTPase Activating proteins.[6] In the DEPDC1B protein electronic inference has verified the GTPase activator activity function.[7] The solution structure of human containing DEP domain containing proteins verifies the the secondary structure of the domain: containing three alpha-helices and two beta-strands within the approximate 80 amino acid region of the domain.[8][9]
The RhoGAP domain is another structural domain known to interact with GTPase and small GTPase. Research concerning the domain in other proteins indicates an approximately similar function among the domain in various proteins. The domain has been verified to interact with other proteins to form complexes or interact with other strcuutres of the cell such as the cytoskeleton or plasma membrane.[10]
Regulation[edit]
DEPDC1B protein product is highly phosphorylated after translation. A single sumolaytion site, found within the RhoGAP domain, indicates the possible interaction of the protein with a SUMO protein, enabling or inhibiting interaction with other proteins. A single palmitoylation site, found within the RhoGAP domain, indicates the possible interaction of the DEPDC1B protein product with a membrane via lipid anchor.
No conserved glycolation sites are predicted within the mature DEPDC1B protein product. No signal peptide or transmembrane domains are predicted within human or any ortholog protein. Similarly, no membrane anchors are predicted. No prenylation sites are predicted in any DEPDC1B ortholog.
Expression[edit]
Expression of DEPDC1B is reported to be largely ubiquitous throughout human tissue. High level of gene expression is observed in all periods of life, except early zygote stages. Experimental evidence suggests that DEPDC1B
Interactions[edit]
No interactions of DEPDC1B within any other protein product characterized by experimentation have been verified.
Coexpression of DEPDC1B with ECT2 in cell cycle regulation and DNA synthesis was verified by experimentation.
Homology[edit]
Orthologs[edit]
DEPDC1B is unique to Chordates in Kingdom Anamalia.
| Genus and Species | Common Name | Class | Divergence (mya)[11] | Accession | Percent Identity[12] |
|---|---|---|---|---|---|
| Nomascus leucogenys | Northern white-cheeked gibbon | Mammalia | 20.4 | XP_003266016 [1] | 98% |
| Papio anubis | Olive Baboon | Mammalia | 29 | XP_003899752 [2] | 98% |
| Mus musculus | House Mouse | Mammalia | 92.3 | NP_848798 [3] | 94% |
| Pteropus alecto | Black Flying Fox | Mammalia | 94.2 | XP_006906108 [4] | 96% |
| Felis catus | Domestic Cat | Mammalia | 94.2 | XP_003981045 [5] | 96% |
| Bos taurus | Cow | Mammalia | 94.2 | XP_005221558 [6] | 95% |
| Monodelphis domestica | Gray short-tailed opossum | Mammalia | 162.6 | XP_001363879 [7] | 88% |
| Ficedula albicollis | Collared Flycatcher | Ave | 296 | XP_005060715 [8] | 77% |
| Taeniopygia guttata | Zebra Finch | Ave | 296 | XP_002188294 [9] | 76% |
| Gallus gallus | Chicken | Ave | 296 | NP_001006576 [10] | 75% |
| Anolis carolinensis | Green Anole | Reptilia | 296 | XP_003216290 [11] | 76% |
| Xenopus tropicalis | Western clawed frog | Amphibia | 371.2 | NP_001121488 [12] | 68% |
| Lepisosteus oculatus | Spotted gar | Actinopterygii | 400.1 | XP_006626875 [13] | 68% |
| Maylandia zebra | Zebra Mbuna | Actinopterygii | 400.1 | XP_004566850 [14] | 57% |
Paralogs[edit]
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DEPDC1B possesses two significant paralogs - DEPDC1A and DEPDC7
DEPDC1A has been researched in several disease states. High expression of the protein in Multiple Myeloma (MM) malignant plasma cells is associated with patient fatality. The high expression has been confirmed using conditional lentiviral vector delivery “to inhibit growth of human melanoma cell lines (HMCLs), with a block in G2 phase of the cell cycle, p53 phosphorylation and stabilization, and p21Cip1 accumulation”9.[13] In the same study it was concluded that DEPDC1A may contribute to the plasmablast features of MM cells, blocking differentiation. Study of DEPDC1A in bladder carcinogenesis revealed the gene as a possible antigen for the formation of bladder cancer cells. Using microarray and northern blotting confirmed the presence of unsubstantial amounts of the protein with in the normal tissues, excluding the testis. Currently the gene is a potential target molecule for therapeutic treatment of bladder carcinogenesis.[14]
No data detailing signigicant function in DEPD7 has been published or recorded.
References[edit]
- ^ Morimoto, K. (1996). Characterization of a unique variant of bat rabies virus responsible for newly emerging human cases in North America. Proceedings of the National Academy of Sciences, 93(11), 5653–5658. doi:10.1073/pnas.93.11.5653
- ^ a b Entrez Gene: DEPDC1B http://www.ncbi.nlm.nih.gov/gene?LinkName=protein_gene&from_uid=223633999
- ^ Gene Cards: DEPDC1B http://www.genecards.org/cgi-bin/carddisp.pl?gene=DEPDC1B
- ^ Burchett SA (October 2000). "Regulators of G protein signaling: a bestiary of modular protein binding domains". J. Neurochem. 75 (4): 1335–51. doi:10.1046/j.1471-4159.2000.0751335.x. PMID 1098781
- ^ Wong HC, Mao J, Nguyen JT, Srinivas S, Zhang W, Liu B, Li L, Wu D, Zheng J (December 2000). "Structural basis of the recognition of the dishevelled DEP domain in the Wnt signaling pathway". Nat. Struct. Biol. 7 (12): 1178–84. doi:10.1038/82047. PMID 11101902
- ^ Martemyanov, K, et. al. (2003).The DEP Domain Determines Subcellular Targeting of the GTPase Activating Protein RGS9 In Vivo. The Journal of Neuroscience, 23(12), 10175-10181.
- ^ Q8WUY9 (DEP1B_HUMAN) http://www.uniprot.org/uniprot/Q8WUY9
- ^ Zhang HP, Hayashi F, Yokoyama S. (2007) Solution structure of the dep domain from human dep domain-containing protein 1. http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?uid=2ysr
- ^ Madej T, Addess KJ, Fong JH, Geer LY, Geer RC, Lanczycki CJ, Liu C, Lu S, Marchler-Bauer A, Panchenko AR, Chen J, Thiessen PA, Wang Y, Zhang D, Bryant SH. "MMDB: 3D structures and macromolecular interactions." Nucleic Acids Res. 2012 Jan; 40(Database issue):D461-4
- ^ Peck, J., Douglas, G., Wu, C. H., & Burbelo, P. D. (2002). Human RhoGAP domain-containing proteins: structure, function and evolutionary relationships. FEBS Letters, 528(1-3), 27–34. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/12297274
- ^ Hedges SB, Dudley J & Kumar S (2006) TimeTree: a public knowledge-base of divergence times among organisms. Bioinformatics 22:2971-2972
- ^ NCBI BLAST http://blast.ncbi.nlm.nih.gov/Blast.cgi
- ^ Kassambara, A., Schoenhals, M., & Klein, B. (2014). Inhibition of DEPDC1A , a Bad Prognostic Marker in Multiple Myeloma , Delays Growth and Induces Mature Plasma Cell Markers in Malignant Plasma Cells Results Increased Expression of DEPDC1A Gene in Multiple Myeloma Cells Compared to Normal Bone Marrow Plasma Cells in Association with a Poor Prognosis, 1–15.
- ^ Kanehira, M., Harada, Y., Takata, R., Shuin, T., Miki, T., Fujioka, T., … Katagiri, T. (2007). Involvement of upregulation of DEPDC1 (DEP domain containing 1) in bladder carcinogenesis. Oncogene, 26(44), 6448–55. doi:10.1038/sj.onc.1210466