DEPDC1B

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]

DEPDC1B
Identifiers
AliasesDEPDC1B, BRCC3, XTP1, DEP domain containing 1B
External IDsOMIM: 616073 MGI: 2145425 HomoloGene: 10157 GeneCards: DEPDC1B
Gene location (Human)
Chr.Chromosome 5 (human)[1]
Band5q12.1Start60,596,912 bp[1]
End60,700,190 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

55789

218581

Ensembl

ENSG00000035499

ENSMUSG00000021697

UniProt

Q8WUY9

Q8BH88

RefSeq (mRNA)

NM_001145208
NM_018369

NM_178683

RefSeq (protein)

NP_001138680
NP_060839

NP_848798

Location (UCSC)Chr 5: 60.6 – 60.7 MbChr 13: 108.32 – 108.41 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

The precise function of DEPDC1B is currently unknown. Expression profiles indicate that DEPDC1B is highly expressed ubiquitously throughout human tissue.[8]

Gene structure

Gene neighborhood
DEPDC1B gene locus

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]

Promoter

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:

mRNA structure

Splice variants
The two confirmed DEPDC1B mRNA splice variants

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...

Secondary structure

DEPDC1B is predicted to be predominantly alpha-helical. No significant beta-strands or beta structures exist with the protein. .[11]

Stem loops and binding miRNA

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]

Protein structure

Sequence

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]

Domains
Solution structure for the human DEP domain

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]

Post-translational modification

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 glycolation 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
Mouse DEPDC1B large-scale tissue expression

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]

Interactions

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.

Homology

Orthologs

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.

DEPDC1B Orthologs
Genus and species Common name Class Divergence (mya)[41] Accession Percent Identity[36]
Nomascus leucogenysNorthern white-cheeked gibbonMammalia20.4XP_003266016 98%
Papio anubis Olive baboonMammalia29XP_003899752 98%
Mus musculusHouse mouseMammalia92.3NP_848798 94%
Pteropus alectoBlack flying foxMammalia94.2XP_006906108 96%
Felis catusDomestic catMammalia94.2XP_003981045 96%
Bos taurusCowMammalia94.2XP_005221558 95%
Monodelphis domesticaGray short-tailed opossumMammalia162.6XP_001363879 88%
Ficedula albicollisCollared flycatcherAve296XP_005060715 77%
Taeniopygia guttataZebra finchAve296XP_002188294 76%
Gallus gallus ChickenAve296NP_001006576 75%
Anolis carolinensisGreen anoleReptilia296XP_003216290 76%
Xenopus tropicalisWestern clawed frogAmphibia371.2NP_001121488 68%
Lepisosteus oculatus Spotted garActinopterygii400.1XP_006626875 68%
Maylandia zebraZebra mbunaActinopterygii400.1XP_004566850 57%

Paralogs
Evolutionary relationship of DEPDC1B to paralogs - DEPDC1A and DEPDC7

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.

References
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