DEPDC1B | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
Aliases | DEPDC1B , BRCC3, XTP1, DEP domain containing 1B | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 616073; MGI: 2145425; HomoloGene: 10157; GeneCards: DEPDC1B; OMA:DEPDC1B - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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DEP Domain Containing Protein 1B also known as XTP1, XTP8, HBV XAg-Transactivated Protein 8, [formerly referred to as BRCC3] is a human protein encoded by a gene of similar name located on chromosome 5. [5] [6] [7]
The precise function of DEPDC1B is currently unknown. Expression profiles indicate that DEPDC1B is highly expressed ubiquitously throughout human tissue. [8]
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. [6]
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. [9]
The following includes the top twenty Predicted Transcription Factors:
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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. It is composed of 11 exons and is 103254bp in length. Isoform 2 is the second confirmed transcript variant. It is composed of 10 exons, missing the tenth exon of the first variant. The missing exon is 186bp in length. [10] See Protein Structure section for more detail...
DEPDC1B is predicted to be predominantly alpha-helical. No significant beta-strands or beta structures exist with the protein. . [11]
DEPDC1B is predicted to possess multiple stem loops in its 5' and 3' untranslated regions (UTR) [12] [13] . In the 3' UTR, miRNA has-miR-499-5p binds to a nucleotide region predicted as a stem loop. [14]
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. The missing 62 amino acids follow the RhoGAP domain, in a region predicted to be highly phosphorylated [15]
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. [16] [17] As well, experimental evidence suggests that the DEP domain determines the subcellular target of some GTPase Activating proteins. [18] In the DEPDC1B protein electronic inference has verified the GTPase activator activity function. [15] The solution structure of human containing DEP domain containing proteins verifies the secondary structure of the domain: containing three alpha-helices and two beta-strands within the approximate 80 amino acid region of the domain. [19] [20]
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 structures of the cell such as the cytoskeleton or plasma membrane. [21]
DEPDC1B protein product is predicted to be highly phosphorylated after translation. [22] A single sumoylation site, found within the RhoGAP domain, indicates the possible interaction of the protein with a SUMO protein, enabling or inhibiting interaction with other proteins. [23] A single palmitoylation site, found within the RhoGAP domain, indicates the possible interaction of the DEPDC1B protein product with a membrane via lipid anchor. [24]
No conserved glycosylation sites are predicted within the mature DEPDC1B protein product. [25] No signal peptide or transmembrane domains are predicted within human or any ortholog protein. [26] [27] No prenylation sites are predicted in any DEPDC1B orthologs. [28]
Expression of DEPDC1B is reported to be largely ubiquitous throughout mouse tissue. High level of gene expression is observed in all periods of life, except early zygote stages. [8] Experimental evidence suggests that DEPDC1B presents similar ubiquitous expression in all tissues. [29]
Differential expression profiles suggest that DEPDC1B is higher expressed in many cancerous disease states, including: papillary thyroid cancer, [30] breast cancer, [31] synovial sarcoma, [32] and prostatic cancer progression. [33] Also, DEPDC1B expression decreases in environments of beta-catenin depletion in multiple myeloma cell lines [34]
No interactions of DEPDC1B within any other protein product characterized by experimentation have been verified. [35]
Medium coexpression of DEPDC1B with ECT2 in cell cycle regulation and DNA synthesis was verified by similarity of expression in various tissues. [35] The remaining predicted interaction were determined via datamining.
DEPDC1B is unique to Chordates in Kingdom Animalia [36]
Multiple sequence alignments verify that DEPDC1B is highly conserved among orthologs. [37] [38] [39] [40] The two structural domains (DEP and RhoGAP) are the two most conserved elements of the proteins. Various motifs are also conserved throughout the protein. No data suggesting motif function could be determined. All predicted post-translational modification were confirmed to be conserved in the orthologous proteins.
DEPDC1B evolution is predicted to follow the general species evolution.
Genus and species | Common name | Class | Divergence (mya) [41] | Accession | Percent Identity [36] |
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Nomascus leucogenys | Northern white-cheeked gibbon | Mammalia | 20.4 | XP_003266016 | 98% |
Papio anubis | Olive baboon | Mammalia | 29 | XP_003899752 | 98% |
Mus musculus | House mouse | Mammalia | 92.3 | NP_848798 | 94% |
Pteropus alecto | Black flying fox | Mammalia | 94.2 | XP_006906108 | 96% |
Felis catus | Domestic cat | Mammalia | 94.2 | XP_003981045 | 96% |
Bos taurus | Cow | Mammalia | 94.2 | XP_005221558 | 95% |
Monodelphis domestica | Gray short-tailed opossum | Mammalia | 162.6 | XP_001363879 | 88% |
Ficedula albicollis | Collared flycatcher | Ave | 296 | XP_005060715 | 77% |
Taeniopygia guttata | Zebra finch | Ave | 296 | XP_002188294 | 76% |
Gallus gallus | Chicken | Ave | 296 | NP_001006576 | 75% |
Anolis carolinensis | Green anole | Reptilia | 296 | XP_003216290 | 76% |
Xenopus tropicalis | Western clawed frog | Amphibia | 371.2 | NP_001121488 | 68% |
Lepisosteus oculatus | Spotted gar | Actinopterygii | 400.1 | XP_006626875 | 68% |
Maylandia zebra | Zebra mbuna | Actinopterygii | 400.1 | XP_004566850 | 57% |
DEPDC1B possesses two significant paralogs - DEPDC1A and DEPDC7
Multiple sequence alignment and phylogenetic analysis indicates DEPDC1A as the most recent paralog, diverging approximately 600 million years ago. 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. [42] 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 within the normal tissues, excluding the testis. Currently the gene is a potential target molecule for therapeutic treatment of bladder carcinogenesis. [43]
No data detailing significant function in DEPD7 has been published or recorded.
Protein YIF1A is a Yip1 domain family proteins that in humans is encoded by the YIF1A gene.
Interferon-inducible GTPase 5 also known as immunity-related GTPase cinema 1 (IRGC1) is an enzyme that in humans is coded by the IRGC gene. It is predicted to behave like other proteins in the p47-GTPase-like and IRG families. It is most expressed in the testis.
NBEAL1 is a protein that in humans is encoded by the NBEAL1 gene. It is found on chromosome 2q33.2 of Homo sapiens.
Family with sequence similarity 63, member A is a protein that, is encoded by the FAM63A gene in humans,. It is located on the minus strand of chromosome 1 at locus 1q21.3.
C5orf34 is a protein that in humans is encoded by the C5orf34 gene (5p12).
CCDC92, or Limkain beta-2, is a protein which in humans is encoded by the CCDC92 gene. It is likely involved in DNA repair or reduction/oxidation reactions. The gene ubiquitously found in humans and is highly conserved across animals.
PRR29 is a protein encoded by the PRR29 gene located in humans on chromosome 17 at 17q23.
FAM71F2 or Family with Sequence Similarity 71 member F2 is a protein that in humans is encoded by the Family with Sequence Similarity 71 member F2 gene. This gene is highly active in the reproductive tissues, specifically the testis, and may serve as a potential biomarker for determining metastatic testicular cancer.
Retrotransposon Gag Like 6 is a protein encoded by the RTL6 gene in humans. RTL6 is a member of the Mart family of genes, which are related to Sushi-like retrotransposons and were derived from fish and amphibians. The RTL6 protein is localized to the nucleus and has a predicted leucine zipper motif that is known to bind nucleic acids in similar proteins, such as LDOC1.
BEND2 is a protein that in humans is encoded by the BEND2 gene. It is also found in other vertebrates, including mammals, birds, and reptiles. The expression of BEND2 in Homo sapiens is regulated and occurs at high levels in the skeletal muscle tissue of the male testis and in the bone marrow. The presence of the BEN domains in the BEND2 protein indicates that this protein may be involved in chromatin modification and regulation.
The Family with sequence similarity 149 member B1 is an uncharacterized protein encoded by the human FAM149B1 gene, with one alias KIAA0974. The protein resides in the nucleus of the cell. The predicted secondary structure of the gene contains multiple alpha-helices, with a few beta-sheet structures. The gene is conserved in mammals, birds, reptiles, fish, and some invertebrates. The protein encoded by this gene contains a DUF3719 protein domain, which is conserved across its orthologues. The protein is expressed at slightly below average levels in most human tissue types, with high expression in brain, kidney, and testes tissues, while showing relatively low expression levels in pancreas tissues.
LCHN is a protein that in humans is encoded by the KIAA1147 gene located on chromosome 7. It is likely part of the tripartite DENN domain family of proteins that often function as Rab-GEFs to regulate vesicular trafficking. Both the mRNA and protein have been shown to be upregulated following ischemic stroke, and to be produced at altered levels in patients with FTD-ALS, however the gene's contribution to these states is not well understood.
C15orf39 is a protein that in humans is encoded by the Chromosome 15 open reading frame 15 (C15orf39) gene.
Proline-rich basic protein 1(PROB1) is a protein encoded by the PROB1 gene located on human chromosome 5, open reading frame 65. PROB1 is also known as C5orf65 and weakly similar to basic proline-rich protein.
Cilia- and flagella-associated protein 299 (CFAP299), is a protein that in humans is encoded by the CFAP299 gene. CFAP299 is predicted to play a role in spermatogenesis and cell apoptosis.
C2orf16 is a protein that in humans is encoded by the C2orf16 gene. Isoform 2 of this protein is 1,984 amino acids long. The gene contains 1 exon and is located at 2p23.3. Aliases for C2orf16 include Open Reading Frame 16 on Chromosome 2 and P-S-E-R-S-H-H-S Repeats Containing Sequence.
ProteinFAM89A is a protein which in humans is encoded by the FAM89A gene. It is also known as chromosome 1 open reading frame 153 (C1orf153). Highest FAM89A gene expression is observed in the placenta and adipose tissue. Though its function is largely unknown, FAM89A is found to be differentially expressed in response to interleukin exposure, and it is implicated in immune responses pathways and various pathologies such as atherosclerosis and glioma cell expression.
Family with sequence 98, member C or FAM98C is a gene that encodes for FAM98C has two aliases FLJ44669 and hypothetical protein LOC147965. FAM98C has two paralogs in humans FAM98A and FAM98B. FAM98C can be characterized for being a Leucine-rich protein. The function of FAM98C is still not defined. FAM98C has orthologs in mammals, reptiles, and amphibians and has a distant orhtologs in Rhinatrema bivittatum and Nanorana parkeri.
C2orf72 is a gene in humans that encodes a protein currently named after its gene, C2orf72. It is also designated LOC257407 and can be found under GenBank accession code NM_001144994.2. The protein can be found under UniProt accession code A6NCS6.
Chromosome 13 Open Reading Frame 46 is a protein which in humans is encoded by the C13orf46 gene. In humans, C13orf46 is ubiquitously expressed at low levels in tissues, including the lungs, stomach, prostate, spleen, and thymus. This gene encodes eight alternatively spliced mRNA transcript, which produce five different protein isoforms.