Details for: SLC35D3

Gene ID: 340146

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: SLC35D3

Ensembl ID: ENSG00000182747

Description: solute carrier family 35 member D3

Cell Significance Landscape

Associated with

Significant Cells

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

  • lung neuroendocrine cell CL1000223
    CSI 5.39
    rCSI 7.97%
    PRS 98.84
  • enteroendocrine cell CL0000164
    CSI 2.5
    rCSI 3.42%
    PRS 98.48
  • neural progenitor cell CL0011020
    CSI 2.3
    rCSI 10.13%
    PRS 95.78

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

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  • Node Color (Target Cell CSI, relative to current network):
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  • 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 [SLC35D3](/details-gene/340146) is a protein-coding gene that encodes Solute Carrier Family 35 Member D3, a transmembrane transporter. Functionally, it is characterized as a UDP-glucose transporter, likely operating as an antiporter, and is primarily localized to the membranes of the endoplasmic reticulum, Golgi apparatus, and various vesicles ([Link](https://doi.org/10.7554/elife.65417)). Its expression profile suggests a specialized role in cellular secretion and metabolism, with the highest significance observed in secretory cell types such as [lung neuroendocrine cell](/details-cell/CL1000223)s and [enteroendocrine cell](/details-cell/CL0000164)s. The gene's involvement in processes like protein exit from the endoplasmic reticulum and platelet dense granule organization points to a crucial function in supplying UDP-glucose for glycosylation and the proper formation of secretory vesicles. ## Cellular Roles and Expression Landscape The expression pattern of [SLC35D3](/details-gene/340146) indicates a highly specialized function rather than a ubiquitous housekeeping role. **Overall**, the gene shows its highest significance in cell types associated with specialized secretory functions and development. - **High Significance in Neuroendocrine and Progenitor Cells:** The gene is most significant in [lung neuroendocrine cell](/details-cell/CL1000223) (CSI: 5.39), [enteroendocrine cell](/details-cell/CL0000164) (CSI: 2.50), and [neural progenitor cell](/details-cell/CL0011020) (CSI: 2.30). The strong association with two distinct neuroendocrine cell populations suggests a conserved and critical role in the synthesis, processing, or secretion of hormones and neuropeptides. Its presence in [neural progenitor cell](/details-cell/CL0011020)s suggests a potential role in neurodevelopment, possibly by providing UDP-glucose for the glycosylation of proteins essential for cell signaling, adhesion, or differentiation. This focused expression pattern implies that [SLC35D3](/details-gene/340146) is a key component of the molecular machinery required for the high-volume secretory activity characteristic of neuroendocrine cells. ## Pathways and Molecular Function Functional annotations for [SLC35D3](/details-gene/340146) are highly consistent with its cellular expression profile, centering on its role as a transporter within the secretory pathway. - **Molecular Function:** At the molecular level, [SLC35D3](/details-gene/340146) exhibits [UDP-glucose transmembrane transporter activity](/details-go/GO:0005460) and [antiporter activity](/details-go/GO:0015297). This defines its core mechanism: moving UDP-glucose across intracellular membranes, likely in exchange for another substrate. - **Biological Processes:** This transport activity is integral to several key biological processes. Its role in [protein exit from endoplasmic reticulum](/details-go/GO:0032527) and its [positive regulation](/details-go/GO:0070863) is consistent with the requirement of UDP-glucose for N-linked glycosylation, a critical quality control step for protein folding and export from the ER. Furthermore, its involvement in [platelet dense granule organization](/details-go/GO:0060155) reinforces its importance in the biogenesis of specialized secretory vesicles, a function that directly parallels its presumed role in neuroendocrine cells. The gene's connection to broader processes like [energy homeostasis](/details-go/GO:0097009) highlights the central role of UDP-glucose as a metabolic hub. - **Cellular Localization:** The protein is localized to the [endoplasmic reticulum](/details-go/GO:0005783), [Golgi apparatus](/details-go/GO:0005794), [early endosome membrane](/details-go/GO:0031901), and [synaptic vesicle membrane](/details-go/GO:0030672). This placement is optimal for its function, allowing it to supply UDP-glucose to the lumens of organelles where glycosylation and vesicle packaging occur, as supported by recent proteomic and metabolite profiling studies ([Link](https://doi.org/10.7554/elife.65417)). ## Research Directions The specific expression and established molecular function of [SLC35D3](/details-gene/340146) provide a strong foundation for targeted research into its physiological and pathological roles. ### Proposed Hypotheses 1. **Hypothesis 1: [SLC35D3](/details-gene/340146) is a rate-limiting factor for neuropeptide glycosylation and secretion in neuroendocrine cells.** Based on its high expression in [lung neuroendocrine cell](/details-cell/CL1000223)s and its role in supplying UDP-glucose to the ER/Golgi, we hypothesize that the activity of [SLC35D3](/details-gene/340146) is essential for the proper post-translational modification and subsequent packaging of hormones and neuropeptides. Its dysfunction would lead to impaired secretory granule formation and reduced neuroendocrine function. 2. **Hypothesis 2: [SLC35D3](/details-gene/340146) is critical for neuronal differentiation by regulating the glycosylation of cell-surface adhesion molecules.** Given its significance in [neural progenitor cell](/details-cell/CL0011020)s, we propose that [SLC35D3](/details-gene/340146) provides the necessary UDP-glucose for glycosylating key proteins involved in cell-cell recognition and signaling, thereby influencing progenitor cell migration and differentiation during neurodevelopment. ### Suggested Experimental Approach To test Hypothesis 1, one could utilize a human neuroendocrine tumor cell line (e.g., BON-1 or QGP-1) that expresses endogenous [SLC35D3](/details-gene/340146). A stable knockout of the gene could be generated using CRISPR-Cas9. A comparative analysis between wild-type and knockout cells would involve: - **Glycoproteomics:** Employ mass spectrometry-based techniques to assess global changes in the N-glycoproteome of secreted proteins to directly measure the impact on glycosylation. - **Secretory Function Assays:** Stimulate the cells and quantify the secretion of key neuroendocrine markers, such as chromogranin A or serotonin, using ELISA or HPLC to determine if secretion is compromised. - **Ultrastructural Analysis:** Use transmission electron microscopy to visualize and quantify the density and morphology of dense-core secretory granules, testing the prediction that their formation is impaired in knockout cells. ### Therapeutic Potential Given its highly specific expression in neuroendocrine lineages, [SLC35D3](/details-gene/340146) may represent a viable therapeutic target in diseases involving these cells, such as neuroendocrine tumors (NETs). Because it is an intracellular membrane transporter, it is more amenable to targeting by small molecule inhibitors than by antibodies. If its activity is shown to be essential for the survival, proliferation, or hormone hypersecretion of NETs, **inhibition** of its transport function could be a novel therapeutic strategy. The restricted expression pattern suggests that such an inhibitor might have a favorable safety profile with limited off-target effects.

Genular Protein ID: 2389369478

Symbol: S35D3_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q5M8T2 B4DI58 Q5QNZ6 Q6NX71

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 1 GO 15 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 Rhea 1 SMR 1 STRING 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

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: 34269178

Title: Localization, proteomics, and metabolite profiling reveal a putative vesicular transporter for UDP-glucose.

PubMed ID: 34269178

DOI: 10.7554/elife.65417

Sequence Information:

  • Length: 416
  • Mass: 44183
  • Checksum: 7995E3B253757C79
  • Sequence:
    • MRQLCRGRVL GISVAIAHGV FSGSLNILLK FLISRYQFSF LTLVQCLTSS TAALSLELLR 
RLGLIAVPPF GLSLARSFAG VAVLSTLQSS LTLWSLRGLS LPMYVVFKRC LPLVTMLIGV 
LVLKNGAPSP GVLAAVLITT CGAALAGAGD LTGDPIGYVT GVLAVLVHAA YLVLIQKASA 
DTEHGPLTAQ YVIAVSATPL LVICSFASTD SIHAWTFPGW KDPAMVCIFV ACILIGCAMN 
FTTLHCTYIN SAVTTSFVGV VKSIATITVG MVAFSDVEPT SLFIAGVVVN TLGSIIYCVA 
KFMETRKQSN YEDLEAQPRG EEAQLSGDQL PFVMEELPGE GGNGRSEGGE AAGGPAQESR 
QEVRGSPRGV PLVAGSSEEG SRRSLKDAYL EVWRLVRGTR YMKKDYLIEN EELPSP

Genular Protein ID: 350905897

Symbol: B7Z9Y0_HUMAN

Name: N/A

UniProtKB Accession Codes:

B7Z9Y0

Database IDs:

ARBA 1 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 3 InterPro 1 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 RefSeq 1 SAM 2

Sequence Information:

  • Length: 416
  • Mass: 44217
  • Checksum: B8F852DA71D7F476
  • Sequence:
    • MRQLCRGRVL GISVAIAHGV FSGSLNILLK FLISRYQFSF LTLVQCLTSS TAALSLELLR 
RLGLIAVPPF GLSLARSFAG VAVLSTLQSS LTLWSLRGLS LPMYVVFKRC LPLVTMFIGV 
LVLKNGAPSP GVLAAVLITT CGAALAGAGD LTGDPIGYVT GVLAVLVHAA YLVLIQKASA 
DTEHGPLTAQ YVIAVSATPL LVICSFASTD SIHAWTFPGW KDPAMVCIFV ACILIGCAMN 
FTTLHCTYIN SAVTTSFVGV VKSIATITVG MVAFSDVEPT SLFIAGVVVN TLGSIIYCVA 
KFMETRKQSN YEDLEAQPRG EEAQLSGDQL PFVMEELPGE GGNGRSEGGE AAGGPAQESR 
QEVRGSPRGV PLVAGSSEEG SRRSLKDAYL EVWRLVRGTR YMKKDYLIEN EELPSP