Details for: BTBD6

Gene ID: 90135

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: BTBD6

Ensembl ID: ENSG00000184887

Description: BTB domain containing 6

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • bronchus fibroblast of lung CL2000093
    CSI 4.7
    rCSI 3.82%
    PRS 93.5
  • transit amplifying cell of colon CL0009011
    CSI 3.09
    rCSI 3.63%
    PRS 93.97
  • CD4-positive helper T cell CL0000492
    CSI 3.03
    rCSI 2.3%
    PRS 98.56
  • myoepithelial cell CL0000185
    CSI 2.97
    rCSI 7.5%
    PRS 95.35
  • ionocyte CL0005006
    CSI 2.95
    rCSI 3.16%
    PRS 94.85
  • goblet cell CL0000160
    CSI 2.82
    rCSI 2.67%
    PRS 91.9
  • pancreatic A cell CL0000171
    CSI 2.79
    rCSI 2.92%
    PRS 95.07
  • group 3 innate lymphoid cell CL0001071
    CSI 2.74
    rCSI 2.06%
    PRS 95.79
  • intestine goblet cell CL0019031
    CSI 2.64
    rCSI 2.34%
    PRS 92.03
  • ciliated epithelial cell CL0000067
    CSI 2.63
    rCSI 2.32%
    PRS 86.98
  • multi-ciliated epithelial cell CL0005012
    CSI 2.63
    rCSI 2.62%
    PRS 89.27
  • cerebral cortex endothelial cell CL1001602
    CSI 2.62
    rCSI 4.52%
    PRS 90.19
  • extravillous trophoblast CL0008036
    CSI 2.6
    rCSI 3.22%
    PRS 92.55
  • colonocyte CL1000347
    CSI 2.59
    rCSI 3.71%
    PRS 92.2
  • stem cell CL0000034
    CSI 2.42
    rCSI 2.34%
    PRS 91.24
  • epithelial cell of lung CL0000082
    CSI 2.42
    rCSI 2.01%
    PRS 94.94
  • CD8-positive, alpha-beta memory T cell CL0000909
    CSI 2.34
    rCSI 2.44%
    PRS 97.75
  • colon epithelial cell CL0011108
    CSI 2.23
    rCSI 2.34%
    PRS 91.98
  • epithelial cell CL0000066
    CSI 2.18
    rCSI 3.35%
    PRS 83.45
  • radial glial cell CL0000681
    CSI 1.96
    rCSI 2.72%
    PRS 92.52
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 1.84
    rCSI 5.44%
    PRS 93.57
  • fallopian tube secretory epithelial cell CL4030006
    CSI 1.71
    rCSI 1.64%
    PRS 92.74
  • basal cell of epidermis CL0002187
    CSI 1.4
    rCSI 2.48%
    PRS 68.69
  • colon goblet cell CL0009039
    CSI 1.22
    rCSI 2.9%
    PRS 94.8
  • suprabasal keratinocyte CL4033013
    CSI 1.19
    rCSI 1.94%
    PRS 69.01
  • retinal ganglion cell CL0000740
    CSI 1.1
    rCSI 2.42%
    PRS 85.92
  • microcirculation associated smooth muscle cell CL0008035
    CSI 1.09
    rCSI 3.16%
    PRS 93.29
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.01
    rCSI 2.45%
    PRS 82.45
  • intestinal crypt stem cell of colon CL0009043
    CSI 0.57
    rCSI 4.31%
    PRS 96.65

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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Comma-separated if multiple.
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  • 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 [BTBD6](/details-gene/90135) (BTB domain containing 6) is a protein-coding gene located on chromosome 14q32.33. As its name suggests, it encodes a protein featuring a BTB (Broad-Complex, Tramtrack and Bric a brac) domain, which typically functions as a protein-protein interaction motif often involved in the formation of Cullin-RING E3 ubiquitin ligase complexes. Functional annotations strongly implicate [BTBD6](/details-gene/90135) in protein metabolism, particularly within the [Adaptive immune system](/details-cell/R-HSA-1280218) and pathways related to [antigen processing and presentation](/details-cell/R-HSA-983169). Its expression profile is broad, showing significant levels in diverse cell types including structural cells like [bronchus fibroblast of lung](/details-cell/CL2000093), proliferative intestinal cells, and immune cells such as [CD4-positive helper T cell](/details-cell/CL0000492), suggesting a fundamental role in protein turnover across multiple biological contexts. ## Cellular Roles and Expression Landscape The expression pattern of [BTBD6](/details-gene/90135) indicates its importance across a wide spectrum of cellular lineages and functions. **Overall**, the gene shows its highest significance in [bronchus fibroblast of lung](/details-cell/CL2000093) (CSI: 4.70), suggesting a key role in this structural cell type. Beyond fibroblasts, [BTBD6](/details-gene/90135) is highly significant in several distinct functional categories: * **Proliferative and Stem Cells:** It is a notable gene in the [transit amplifying cell of colon](/details-cell/CL0009011) (CSI: 3.09) and [stem cell](/details-cell/CL0000034) (CSI: 2.42), which may point to a role in regulating cell division or differentiation in rapidly renewing tissues. * **Immune System:** Consistent with its annotated functions, [BTBD6](/details-gene/90135) is significantly expressed in both adaptive and innate immune cells, including [CD4-positive helper T cell](/details-cell/CL0000492) (CSI: 3.03) and [group 3 innate lymphoid cell](/details-cell/CL0001071) (CSI: 2.74). * **Epithelial and Secretory Cells:** The gene shows high significance in various specialized epithelial cells such as [myoepithelial cell](/details-cell/CL0000185) (CSI: 2.97), [goblet cell](/details-cell/CL0000160) (CSI: 2.82), [ionocyte](/details-cell/CL0005006) (CSI: 2.95), and [ciliated epithelial cell](/details-cell/CL0000067) (CSI: 2.63). This broad expression in mucosal and glandular tissues suggests a housekeeping or universally important function in protein regulation. * **Endocrine and Other Specialized Cells:** Its significance in [pancreatic A cell](/details-cell/CL0000171) (CSI: 2.79) and [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 2.62) further underscores its widespread functional relevance. The diverse array of cell types where [BTBD6](/details-gene/90135) is significantly expressed suggests it is not a specific lineage marker but rather a component of a fundamental cellular process, likely related to protein turnover, that is active in many different physiological contexts. ## Pathways and Molecular Function The functional annotations for [BTBD6](/details-gene/90135) provide strong evidence for its role as a regulator of protein stability. Its molecular function is defined as [protein binding](/details-cell/GO:0005515), and it is localized to the [cytosol](/details-cell/GO:0005829). While GO annotations also suggest an involvement in [neurogenesis](/details-cell/GO:0022008), the most detailed insights come from Reactome pathway analysis. [BTBD6](/details-gene/90135) is a component of several critical pathways related to protein degradation and immunity: * **Antigen Presentation:** It is implicated in [Antigen processing: ubiquitination & proteasome degradation](/details-cell/R-HSA-983168) and [Class i mhc mediated antigen processing & presentation](/details-cell/R-HSA-983169). This is highly consistent with its expression in immune cells and suggests it may act as a substrate-recognition unit within an E3 ubiquitin ligase complex that targets proteins for degradation, generating peptides for MHC Class I loading. * **General Protein Metabolism:** Its role is further contextualized by its involvement in broader pathways like [Metabolism of proteins](/details-cell/R-HSA-392499) and [Post-translational protein modification](/details-cell/R-HSA-597592). This aligns with the function of BTB-domain proteins in mediating ubiquitination, a key post-translational modification. These annotations, particularly the link to ubiquitination and antigen processing, provide a mechanistic basis for its significant expression in both immune cells and other highly active cell types that require stringent protein quality control. ## Research Directions The available data suggests that [BTBD6](/details-gene/90135) is a broadly important regulator of protein turnover with a particularly salient role in the immune system. Future research should focus on elucidating its specific substrates and its precise function within E3 ligase complexes. ### Proposed Hypotheses 1. **[BTBD6](/details-gene/90135) functions as a substrate-recognition subunit of a Cullin-RING E3 ubiquitin ligase complex that specifically targets proteins for proteasomal degradation as part of the MHC Class I antigen presentation pathway in immune and non-immune cells.** 2. **In rapidly dividing cells like [transit amplifying cell of colon](/details-cell/CL0009011), [BTBD6](/details-gene/90135) regulates the cell cycle by targeting key cell cycle-associated proteins (e.g., cyclins or CDK inhibitors) for ubiquitination and degradation, thereby controlling the G1/S transition or mitotic entry.** 3. **The function of [BTBD6](/details-gene/90135) is essential for maintaining protein homeostasis in metabolically active secretory cells, such as [goblet cell](/details-cell/CL0000160) and [pancreatic A cell](/details-cell/CL0000171), by mediating the degradation of misfolded or excess proteins within the cytosol.** ### Key Experimental Approach To test the primary hypothesis regarding its role in antigen presentation, a definitive experiment would be to identify the [BTBD6](/details-gene/90135) interactome. One could perform co-immunoprecipitation of epitope-tagged [BTBD6](/details-gene/90135) from a human cell line (e.g., HEK293T or an immune cell line like Jurkat) followed by mass spectrometry (IP-MS). This would identify its binding partners, confirming its association with Cullin proteins (like CUL3) and revealing its specific protein substrates. Subsequent functional validation could involve CRISPR-Cas9-mediated knockout of [BTBD6](/details-gene/90135), followed by analysis of MHC Class I surface levels and the ability of these cells to present specific antigens to cognate T cells. ### Therapeutic Potential As a component of the ubiquitin-proteasome system, [BTBD6](/details-gene/90135) could represent a potential therapeutic target. The BTB domain serves as a protein-protein interaction module, making it amenable to targeting by novel modalities like molecular glues or proteolysis-targeting chimeras (PROTACs). If [BTBD6](/details-gene/90135) is found to mediate the degradation of a tumor suppressor, its inhibition could be beneficial in cancer therapy. Conversely, if it targets oncoproteins or viral proteins for destruction, strategies to enhance its activity could be explored. Its specific substrates must be identified before its therapeutic potential can be fully evaluated.

Genular Protein ID: 2887930627

Symbol: BTBD6_HUMAN

Name: Lens BTB domain protein

UniProtKB Accession Codes:

Q96KE9 Q8IVQ7 Q9BR94

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 2 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 2 RefSeq 2 SMART 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 12508121

Title: The DNA sequence and analysis of human chromosome 14.

PubMed ID: 12508121

DOI: 10.1038/nature01348

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: 12107413

Title: Expressed sequence tag analysis of adult human lens for the NEIBank project: over 2000 non-redundant transcripts, novel genes and splice variants.

PubMed ID: 12107413

Sequence Information:

  • Length: 538
  • Mass: 58776
  • Checksum: 717B471D736033EF
  • Sequence:
    • MLLPLACLHG RVAQCLTSLL LLAEPLPRPR RGARARGAAS TGAEAAPAAP PAKMAAELYA 
PASAAAADLA NSNAGAAVGR KAGPRSPPSA PAPAPPPPAP APPTLGNNHQ ESPGWRCCRP 
TLRERNALMF NNELMADVHF VVGPPGATRT VPAHKYVLAV GSSVFYAMFY GDLAEVKSEI 
HIPDVEPAAF LILLKYMYSD EIDLEADTVL ATLYAAKKYI VPALAKACVN FLETSLEAKN 
ACVLLSQSRL FEEPELTQRC WEVIDAQAEM ALRSEGFCEI DRQTLEIIVT REALNTKEAV 
VFEAVLNWAE AECKRQGLPI TPRNKRHVLG RALYLVRIPT MTLEEFANGA AQSDILTLEE 
THSIFLWYTA TNKPRLDFPL TKRKGLAPQR CHRFQSSAYR SNQWRYRGRC DSIQFAVDRR 
VFIAGLGLYG SSSGKAEYSV KIELKRLGVV LAQNLTKFMS DGSSNTFPVW FEHPVQVEQD 
TFYTASAVLD GSELSYFGQE GMTEVQCGKV AFQFQCSSDS TNGTGVQGGQ IPELIFYA

Genular Protein ID: 2494916643

Symbol: A0A384NYR4_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A384NYR4

Database IDs:

ARBA 2 AlphaFoldDB 1 Antibodypedia 1 CDD 2 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 ExpressionAtlas 1 GO 2 Gene3D 2 InterPro 6 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 2 Pfam 3 RefSeq 1 SAM 1 SMART 2 SMR 1 SUPFAM 1 VEuPathDB 1

Sequence Information:

  • Length: 485
  • Mass: 53411
  • Checksum: B6D984D25DDD843B
  • Sequence:
    • MAAELYAPAS AAAADLANSN AGAAVGRKAG PRSPPSAPAP APPPPAPAPP TLGNNHQESP 
GWRCCRPTLR ERNALMFNNE LMADVHFVVG PPGATRTVPA HKYVLAVGSS VFYAMFYGDL 
AEVKSEIHIP DVEPAAFLIL LKYMYSDEID LEADTVLATL YAAKKYIVPA LAKACVNFLE 
TSLEAKNACV LLSQSRLFEE PELTQRCWEV IDAQAEMALR SEGFCEIDRQ TLEIIVTREA 
LNTKEAVVFE AVLNWAEAEC KRQGLPITPR NKRHVLGRAL YLVRIPTMTL EEFANGAAQS 
DILTLEETHS IFLWYTATNK PRLDFPLTKR KGLAPQRCHR FQSSAYRSNQ WRYRGRCDSI 
QFAVDRRVFI AGLGLYGSSS GKAEYSVKIE LKRLGVVLAQ NLTKFMSDGS SNTFPVWFEH 
PVQVEQDTFY TASAVLDGSE LSYFGQEGMT EVQCGKVAFQ FQCSSDSTNG TGVQGGQIPE 
LIFYA