Details for: SLC45A3

Gene ID: 85414

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: SLC45A3

Ensembl ID: ENSG00000158715

Description: solute carrier family 45 member 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • basophil CL0000767
    CSI 4.57
    rCSI 9.67%
    PRS 98.35
  • luminal cell of prostate epithelium CL0002340
    CSI 4.5
    rCSI 24.19%
    PRS 98.19
  • common myeloid progenitor CL0000049
    CSI 3.63
    rCSI 2.93%
    PRS 98.49
  • granulocyte CL0000094
    CSI 3.47
    rCSI 5.3%
    PRS 98.53
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 2.91
    rCSI 3.53%
    PRS 84.24
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.3
    rCSI 2.08%
    PRS 97.39
  • foveolar cell of stomach CL0002179
    CSI 1.93
    rCSI 4.1%
    PRS 97.73
  • eosinophil CL0000771
    CSI 1.48
    rCSI 9.72%
    PRS 99.14

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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    • High
    • Medium
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    • 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 [SLC45A3](/details-gene/85414), or Solute Carrier Family 45 Member 3, is a protein-coding gene located on chromosome 1q32.1. It functions primarily as a sugar transporter, with annotated roles in hexose and sucrose transport ([GO:0008645](https://www.ebi.ac.uk/QuickGO/term/GO:0008645), [GO:0015770](https://www.ebi.ac.uk/QuickGO/term/GO:0015770)). Also known as prostein, this protein is characterized by its highly specific expression in the [luminal cell of prostate epithelium](/details-cell/CL0002340) [Link](https://pubmed.ncbi.nlm.nih.gov/11245466/), making it a key marker for this tissue. Additionally, expression data reveals a significant role in hematopoietic cells, particularly those of the myeloid lineage such as [basophils](/details-cell/CL0000767) and [granulocytes](/details-cell/CL0000094), suggesting a dual function in both glandular epithelium and the immune system. ## Cellular Roles and Expression Landscape The expression profile of [SLC45A3](/details-gene/85414) highlights its importance in distinct and seemingly unrelated cellular contexts. **Overall**, the gene shows the highest significance in [basophils](/details-cell/CL0000767) (CSI: 4.57) and [luminal cells of prostate epithelium](/details-cell/CL0002340) (CSI: 4.50), establishing it as a top-tier marker for these two cell types. Its role in the hematopoietic system is further emphasized by high significance scores in progenitor cells, including [common myeloid progenitors](/details-cell/CL0000049) (CSI: 3.63) and [megakaryocyte-erythroid progenitor cells](/details-cell/CL0000050) (CSI: 2.30), as well as mature myeloid cells like [granulocytes](/details-cell/CL0000094) (CSI: 3.47) and [eosinophils](/details-cell/CL0000771) (CSI: 1.48). This pattern suggests a sustained and crucial role for [SLC45A3](/details-gene/85414) throughout myeloid lineage development and function. A notable expression is also observed in the adaptive immune system, specifically in [CD8-positive, alpha-beta memory T cells, CD45RO-positive](/details-cell/CL0001203) (CSI: 2.91). This is consistent with research identifying a T-cell epitope from this protein in the context of prostate cancer [Link](https://doi.org/10.1038/sj.bjc.6601642). The gene's strong association with prostate tissue is a defining feature, supported by early research identifying it as a prostate-specific protein [Link](https://pubmed.ncbi.nlm.nih.gov/11245466/). The high CSI score in luminal prostate cells underscores its potential role in the normal physiological and secretory functions of the prostate gland. ## Pathways and Molecular Function Functionally, [SLC45A3](/details-gene/85414) is annotated as a transporter protein integral to the [plasma membrane](/details-cell/GO:0005886). Its primary molecular function is related to sugar transport, specifically [sucrose:proton symporter activity](/details-cell/GO:0008506) and general [sugar transmembrane transporter activity](/details-cell/GO:0051119). These functions are part of broader biological processes and pathways including: * **Hexose Transport:** The gene is involved in [hexose transmembrane transport](/details-cell/GO:0008645) and the Reactome pathway for [Cellular hexose transport](/details-cell/R-HSA-189200), indicating a role in cellular energy metabolism by facilitating the uptake of simple sugars. * **Metabolic Regulation:** Beyond transport, it is implicated in the [positive regulation of the glucose metabolic process](/details-cell/GO:0010907) and the [positive regulation of the fatty acid biosynthetic process](/details-cell/GO:0045723). This suggests that its transport activity is directly linked to the control of key anabolic and catabolic pathways within the cell. * **General Transport:** It is a component of the broader Reactome pathways for [Slc-mediated transmembrane transport](/details-cell/R-HSA-425407) and the [Transport of small molecules](/details-cell/R-HSA-382551). * **Neural Development:** An unexpected annotated function is its role in the [regulation of oligodendrocyte differentiation](/details-cell/GO:0048713), suggesting a potential function in the central nervous system that is not captured by its top expressed cell types in general surveys. The high demand for glucose in activated immune cells and secretory epithelial cells provides a clear biological context for the high expression of a sugar transporter like [SLC45A3](/details-gene/85414) in these tissues. ## Research Directions The dual-specificity of [SLC45A3](/details-gene/85414) in prostate epithelium and myeloid cells presents unique avenues for research in both oncology and immunology. ### Proposed Hypotheses 1. **Role in Prostate Cancer Metabolism:** Given its function as a sugar transporter and its high expression in prostate cells, [SLC45A3](/details-gene/85414) may play a critical role in fueling the high metabolic demands of prostate cancer cells. Its dysregulation could be a key event that supports tumor growth and survival by altering nutrient availability. 2. **Function in Myeloid Cell Activation:** The high expression of [SLC45A3](/details-gene/85414) in [granulocytes](/details-cell/CL0000094) and [basophils](/details-cell/CL0000767) suggests it is essential for their effector functions. We hypothesize that [SLC45A3](/details-gene/85414)-mediated glucose uptake is a rate-limiting step for the metabolic reprogramming required for processes like degranulation, phagocytosis, and the respiratory burst upon immune activation. ### Key Experimental Approach To test the hypothesis regarding its role in myeloid cell function, a conditional knockout mouse model could be generated where *Slc45a3* is specifically deleted in the myeloid lineage (e.g., using a Lyz2-Cre driver). Bone marrow-derived [granulocytes](/details-cell/CL0000094) or peritoneal [basophils](/details-cell/CL0000767) could be isolated from both knockout and wild-type mice. The functional capacity of these cells could then be assessed *in vitro* following stimulation. Key readouts would include measuring degranulation via enzymatic assays (e.g., beta-hexosaminidase release), assessing respiratory burst through a DHR-123 assay, and quantifying metabolic changes using Seahorse XF analysis or radiolabeled glucose uptake assays. A significant impairment in these functions in the knockout cells would confirm the critical role of [SLC45A3](/details-gene/85414) in myeloid cell activation. ### Therapeutic Potential [SLC45A3](/details-gene/85414) represents an exceptionally promising therapeutic target, particularly in prostate cancer. Its high tissue-specificity and membrane localization make it an ideal candidate for targeted therapies. Because it has been shown to be a source of T-cell epitopes recognized in prostate cancer patients [Link](https://doi.org/10.1038/sj.bjc.6601642), it is a prime target for immunotherapeutic strategies. Potential approaches include the development of therapeutic vaccines to elicit a T-cell response against [SLC45A3](/details-gene/85414)-expressing tumor cells, or engineering CAR-T cells directed against an extracellular domain of the protein. Such therapies would aim for targeted elimination of cancer cells while potentially sparing most healthy tissues due to the gene's restricted expression profile.

Genular Protein ID: 3910170077

Symbol: S45A3_HUMAN

Name: Solute carrier family 45 member 3

UniProtKB Accession Codes:

Q96JT2 A8K2U9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 2 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 1 GO 9 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 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 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 4 Rhea 1 SMR 1 STRING 1 SUPFAM 1 SwissPalm 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 11245466

Title: Identification and characterization of prostein, a novel prostate-specific protein.

PubMed ID: 11245466

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 14997204

Title: Identification of an HLA-A(*)0201-restricted T-cell epitope derived from the prostate cancer-associated protein prostein.

PubMed ID: 14997204

DOI: 10.1038/sj.bjc.6601642

Sequence Information:

  • Length: 553
  • Mass: 59323
  • Checksum: 0AFA23FBC742A667
  • Sequence:
    • MVQRLWVSRL LRHRKAQLLL VNLLTFGLEV CLAAGITYVP PLLLEVGVEE KFMTMVLGIG 
PVLGLVCVPL LGSASDHWRG RYGRRRPFIW ALSLGILLSL FLIPRAGWLA GLLCPDPRPL 
ELALLILGVG LLDFCGQVCF TPLEALLSDL FRDPDHCRQA YSVYAFMISL GGCLGYLLPA 
IDWDTSALAP YLGTQEECLF GLLTLIFLTC VAATLLVAEE AALGPTEPAE GLSAPSLSPH 
CCPCRARLAF RNLGALLPRL HQLCCRMPRT LRRLFVAELC SWMALMTFTL FYTDFVGEGL 
YQGVPRAEPG TEARRHYDEG VRMGSLGLFL QCAISLVFSL VMDRLVQRFG TRAVYLASVA 
AFPVAAGATC LSHSVAVVTA SAALTGFTFS ALQILPYTLA SLYHREKQVF LPKYRGDTGG 
ASSEDSLMTS FLPGPKPGAP FPNGHVGAGG SGLLPPPPAL CGASACDVSV RVVVGEPTEA 
RVVPGRGICL DLAILDSAFL LSQVAPSLFM GSIVQLSQSV TAYMVSAAGL GLVAIYFATQ 
VVFDKSDLAK YSA