Details for: DEPDC1

Gene ID: 55635

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: DEPDC1

Ensembl ID: ENSG00000024526

Description: DEP domain containing 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • neural crest cell CL0011012
    CSI 3.88
    rCSI 3.07%
    PRS 96.73
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.76
    rCSI 3.54%
    PRS 97.03
  • erythrocyte CL0000232
    CSI 2.5
    rCSI 5.68%
    PRS 96.89
  • placental villous trophoblast CL2000060
    CSI 2.36
    rCSI 3.64%
    PRS 97.34
  • fallopian tube secretory epithelial cell CL4030006
    CSI 2.33
    rCSI 2.24%
    PRS 97.53
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.2
    rCSI 2.55%
    PRS 95.25
  • large pre-B-II cell CL0000957
    CSI 1.72
    rCSI 4.9%
    PRS 97.46
  • promonocyte CL0000559
    CSI 1.55
    rCSI 2.65%
    PRS 98.85
  • erythroblast CL0000765
    CSI 1.14
    rCSI 3.02%
    PRS 97.66
  • primitive red blood cell CL0002355
    CSI 0.97
    rCSI 5.25%
    PRS 98.18

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [DEPDC1](/details-gene/55635) (DEP domain containing 1) is a protein-coding gene located on chromosome 1p31.3. Functionally, it is annotated as a GTPase activator and a component of a [transcription repressor complex](/details-go/GO:0017053) within the [nucleus](/details-go/GO:0005634), playing a role in [intracellular signal transduction](/details-go/GO:0035556) and the [negative regulation of dna-templated transcription](/details-go/GO:0045892). Expression data indicates its significance is highest in progenitor and developmental cell types, including [neural crest cell](/details-cell/CL0011012), [neuroblast (sensu Vertebrata)](/details-cell/CL0000031), and hematopoietic precursors like [erythrocyte](/details-cell/CL0000232) and [large pre-B-II cell](/details-cell/CL0000957). Notably, research has implicated the upregulation of [DEPDC1](/details-gene/55635) in the carcinogenesis of bladder cancer, suggesting a role in oncogenesis ([Link](https://doi.org/10.1038/sj.onc.1210466)). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [DEPDC1](/details-gene/55635) highlights its role in highly proliferative and developmental contexts. Its highest significance scores are observed in diverse precursor populations, suggesting a conserved function in regulating cell fate and differentiation. The gene is a prominent marker in cells associated with neurogenesis and neural development, as evidenced by its high significance in [neural crest cell](/details-cell/CL0011012) (CSI: 3.88) and [neuroblast (sensu Vertebrata)](/details-cell/CL0000031) (CSI: 2.76). This suggests [DEPDC1](/details-gene/55635) may be involved in the complex transcriptional programs that govern the differentiation and migration of these critical embryonic cell types. Concurrently, [DEPDC1](/details-gene/55635) shows high significance in various stages of hematopoiesis. It is a key marker in [erythrocyte](/details-cell/CL0000232) (CSI: 2.50), [large pre-B-II cell](/details-cell/CL0000957) (CSI: 1.72), [promonocyte](/details-cell/CL0000559) (CSI: 1.55), and [erythroblast](/details-cell/CL0000765) (CSI: 1.14). This pattern implies that [DEPDC1](/details-gene/55635) activity may be essential for maintaining cells in a progenitor state or for guiding early lineage commitment, with its downregulation potentially being a prerequisite for terminal differentiation. The high significance in [placental villous trophoblast](/details-cell/CL2000060) (CSI: 2.36) further reinforces its association with rapidly dividing, developmental tissues. ## Pathways and Molecular Function The molecular functions attributed to [DEPDC1](/details-gene/55635) are consistent with its expression in progenitor cells that require tight regulation of signaling and gene expression. Its involvement in a [transcription repressor complex](/details-go/GO:0017053) provides a direct mechanism for its role in controlling developmental programs. This function is further specified by research demonstrating that [DEPDC1](/details-gene/55635) can interfere with the transcriptional repression activity of ZNF224, a known oncogenic pathway in bladder cancer ([Link](https://doi.org/10.1158/0008-5472.can-10-0255)). Its annotated [Gtpase activator activity](/details-go/GO:0005096) suggests a role in modulating Rho or Ras family GTPases, which are central hubs in signaling pathways controlling cell proliferation, cytoskeletal organization, and migration. These processes are fundamental to the biology of the cell types where [DEPDC1](/details-gene/55635) is most significant, such as migrating [neural crest cells](/details-cell/CL0011012) and proliferating hematopoietic precursors. Furthermore, phosphoproteomic studies have identified [DEPDC1](/details-gene/55635) as a target of mitotic phosphorylation, indicating that its activity is likely regulated in a cell-cycle-dependent manner, a feature common to proteins that control proliferation and differentiation ([Link](https://doi.org/10.1073/pnas.0805139105)). ## Research Directions The established link between [DEPDC1](/details-gene/55635) upregulation and bladder cancer provides a strong foundation for further investigation into its oncogenic mechanisms and its role in normal development. Based on the available data, several testable hypotheses can be proposed: 1. Upregulation of [DEPDC1](/details-gene/55635) in bladder cancer promotes tumorigenesis by forming a repressive complex that silences key tumor suppressor genes, thereby preventing cell cycle exit and terminal differentiation of urothelial cells. 2. During normal hematopoiesis, the timely downregulation of [DEPDC1](/details-gene/55635) is a critical checkpoint for the terminal differentiation of progenitor cells like [erythroblasts](/details-cell/CL0000765). Persistent expression of [DEPDC1](/details-gene/55635) would arrest these cells in an immature, proliferative state. To test the first hypothesis, a compelling experimental approach would be to use a CRISPR-Cas9-based knockout or knockdown of [DEPDC1](/details-gene/55635) in bladder cancer cell lines that exhibit high endogenous expression. The effects on cell proliferation, apoptosis, and differentiation could be quantified. Concurrently, combining RNA-sequencing (to identify downregulated genes upon [DEPDC1](/details-gene/55635) knockout) with Chromatin Immunoprecipitation sequencing (ChIP-seq) for [DEPDC1](/details-gene/55635) or its binding partners would allow for the direct identification of its repressed gene targets. From a therapeutic standpoint, [DEPDC1](/details-gene/55635) represents a promising target for inhibition in bladder cancer. As an intracellular nuclear protein, it is not directly targetable with monoclonal antibodies. However, its function appears dependent on protein-protein interactions, such as with ZNF224, making it a candidate for disruption by small molecule inhibitors or cell-permeable peptides ([Link](https://doi.org/10.1158/0008-5472.can-10-0255)). A key challenge for such a therapy would be managing potential on-target toxicities in highly proliferative normal tissues, such as hematopoietic stem and progenitor cells, which also rely on [DEPDC1](/details-gene/55635) function.

Genular Protein ID: 1641140485

Symbol: DEP1A_HUMAN

Name: DEP domain-containing protein 1A

UniProtKB Accession Codes:

Q5TB30 A8QXE0 A8QXE1 Q05DU3 Q5TB28 Q9H9I3 Q9NX21 Q9NXZ0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 10 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 5 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 2 SMART 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 17452976

Title: Involvement of upregulation of DEPDC1 (DEP domain containing 1) in bladder carcinogenesis.

PubMed ID: 17452976

DOI: 10.1038/sj.onc.1210466

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 20587513

Title: Cell-permeable peptide DEPDC1-ZNF224 interferes with transcriptional repression and oncogenicity in bladder cancer cells.

PubMed ID: 20587513

DOI: 10.1158/0008-5472.can-10-0255

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

Sequence Information:

  • Length: 811
  • Mass: 92960
  • Checksum: F694E10FB79AF3B0
  • Sequence:
    • MESQGVPPGP YRATKLWNEV TTSFRAGMPL RKHRQHFKKY GNCFTAGEAV DWLYDLLRNN 
SNFGPEVTRQ QTIQLLRKFL KNHVIEDIKG RWGSENVDDN NQLFRFPATS PLKTLPRRYP 
ELRKNNIENF SKDKDSIFKL RNLSRRTPKR HGLHLSQENG EKIKHEIINE DQENAIDNRE 
LSQEDVEEVW RYVILIYLQT ILGVPSLEEV INPKQVIPQY IMYNMANTSK RGVVILQNKS 
DDLPHWVLSA MKCLANWPRS NDMNNPTYVG FERDVFRTIA DYFLDLPEPL LTFEYYELFV 
NILVVCGYIT VSDRSSGIHK IQDDPQSSKF LHLNNLNSFK STECLLLSLL HREKNKEESD 
STERLQISNP GFQERCAKKM QLVNLRNRRV SANDIMGGSC HNLIGLSNMH DLSSNSKPRC 
CSLEGIVDVP GNSSKEASSV FHQSFPNIEG QNNKLFLESK PKQEFLLNLH SEENIQKPFS 
AGFKRTSTLT VQDQEELCNG KCKSKQLCRS QSLLLRSSTR RNSYINTPVA EIIMKPNVGQ 
GSTSVQTAME SELGESSATI NKRLCKSTIE LSENSLLPAS SMLTGTQSLL QPHLERVAID 
ALQLCCLLLP PPNRRKLQLL MRMISRMSQN VDMPKLHDAM GTRSLMIHTF SRCVLCCAEE 
VDLDELLAGR LVSFLMDHHQ EILQVPSYLQ TAVEKHLDYL KKGHIENPGD GLFAPLPTYS 
YCKQISAQEF DEQKVSTSQA AIAELLENII KNRSLPLKEK RKKLKQFQKE YPLIYQKRFP 
TTESEAALFG DKPTIKQPML ILRKPKFRSL R