Details for: SLC27A2

Gene ID: 11001

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: SLC27A2

Ensembl ID: ENSG00000140284

Description: solute carrier family 27 member 2

Cell Significance Landscape

Associated with

Significant Cells

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

  • hepatocyte CL0000182
    CSI 9.57
    rCSI 17.13%
    PRS 95.15
  • placental villous trophoblast CL2000060
    CSI 9.55
    rCSI 14.76%
    PRS 95.62
  • colon epithelial cell CL0011108
    CSI 7.78
    rCSI 8.15%
    PRS 95.49
  • secretory cell CL0000151
    CSI 6.9
    rCSI 7.2%
    PRS 96.31
  • stem cell CL0000034
    CSI 5.84
    rCSI 5.63%
    PRS 95.31
  • squamous epithelial cell CL0000076
    CSI 5.7
    rCSI 13.52%
    PRS 93.48
  • midzonal region hepatocyte CL0019028
    CSI 4.09
    rCSI 9.6%
    PRS 94.32
  • centrilobular region hepatocyte CL0019029
    CSI 3.78
    rCSI 9.85%
    PRS 93.39
  • enterocyte CL0000584
    CSI 3.64
    rCSI 5.87%
    PRS 94.26
  • hematopoietic precursor cell CL0008001
    CSI 3.62
    rCSI 3.73%
    PRS 98.42
  • epithelial cell of proximal tubule CL0002306
    CSI 3.4
    rCSI 8.31%
    PRS 92.71
  • ciliated cell CL0000064
    CSI 3.35
    rCSI 5.43%
    PRS 92.53
  • intrahepatic cholangiocyte CL0002538
    CSI 3.34
    rCSI 8.02%
    PRS 96.23
  • periportal region hepatocyte CL0019026
    CSI 3.33
    rCSI 12.95%
    PRS 93.87
  • club cell CL0000158
    CSI 3.3
    rCSI 4.83%
    PRS 95.06
  • nasal mucosa goblet cell CL0002480
    CSI 3.13
    rCSI 3.64%
    PRS 96.16
  • Kupffer cell CL0000091
    CSI 3.02
    rCSI 6.9%
    PRS 97.21
  • lung ciliated cell CL1000271
    CSI 2.78
    rCSI 3.21%
    PRS 93.64
  • hepatic stellate cell CL0000632
    CSI 2.77
    rCSI 10.38%
    PRS 95.24
  • multi-ciliated epithelial cell CL0005012
    CSI 2.7
    rCSI 2.69%
    PRS 93.53
  • ciliated epithelial cell CL0000067
    CSI 2.64
    rCSI 2.32%
    PRS 91.78
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.63
    rCSI 3.72%
    PRS 95.8
  • retinal pigment epithelial cell CL0002586
    CSI 2.53
    rCSI 5.01%
    PRS 94.69
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.5
    rCSI 3.11%
    PRS 89.16
  • choroid plexus epithelial cell CL0000706
    CSI 2.39
    rCSI 3.91%
    PRS 93.46
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.38
    rCSI 2.15%
    PRS 96.52
  • transit amplifying cell of colon CL0009011
    CSI 2.26
    rCSI 2.65%
    PRS 97.17
  • BEST4+ enteroycte CL4030026
    CSI 2.26
    rCSI 2.81%
    PRS 95.98
  • intestinal epithelial cell CL0002563
    CSI 2.19
    rCSI 2.29%
    PRS 95.44
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.01
    rCSI 2.4%
    PRS 90.69
  • tracheal goblet cell CL1000329
    CSI 1.8
    rCSI 3.93%
    PRS 97.14
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 1.67
    rCSI 3.34%
    PRS 98.71
  • deuterosomal cell CL4033044
    CSI 1.33
    rCSI 4.51%
    PRS 92.51
  • parietal epithelial cell CL1000452
    CSI 1.25
    rCSI 3.34%
    PRS 94.49
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.22
    rCSI 2.77%
    PRS 91.99
  • bronchial goblet cell CL1000312
    CSI 1.2
    rCSI 4.81%
    PRS 97.92

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.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • 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 [SLC27A2](/details-gene/11001), or Solute Carrier Family 27 Member 2, is a protein-coding gene located on chromosome 15q21.2. It functions as a bifunctional protein, acting as both a fatty acid transporter and a very-long-chain acyl-CoA synthetase. It plays a crucial role in lipid metabolism, particularly in the transport and activation of long-chain and very-long-chain fatty acids. Its functions are integral to processes such as fatty acid beta-oxidation and bile acid biosynthesis [Link](https://doi.org/10.1074/jbc.m203295200). Reflecting its metabolic roles, [SLC27A2](/details-gene/11001) shows the highest significance in metabolically active cells, most notably [hepatocytes](/details-cell/CL0000182), [placental villous trophoblasts](/details-cell/CL2000060), and various epithelial cells lining the colon and kidney tubules. ## Cellular Roles and Expression Landscape The expression profile of [SLC27A2](/details-gene/11001) underscores its central role in tissues responsible for metabolic processing, nutrient absorption, and secretion. **Overall**, the gene is most significant in cell types with high lipid-handling requirements. Its highest significance is observed in [hepatocytes](/details-cell/CL0000182) (CSI: 9.57), including specific subtypes such as [midzonal](/details-cell/CL0019028), [centrilobular](/details-cell/CL0019029), and [periportal](/details-cell/CL0019026) region [hepatocytes](/details-cell/CL0000182). This is consistent with the liver's primary role in fatty acid metabolism and its specific function as a cholate:CoA ligase, which is essential for bile acid synthesis [Link](https://doi.org/10.1074/jbc.c000015200). High significance is also noted in [placental villous trophoblasts](/details-cell/CL2000060) (CSI: 9.55), suggesting a critical function in the transport of fatty acids from the mother to the fetus, a process vital for fetal development. Furthermore, [SLC27A2](/details-gene/11001) is a key marker in several epithelial cell types involved in absorption and barrier function. These include [colon epithelial cells](/details-cell/CL0011108) (CSI: 7.78), [enterocytes](/details-cell/CL0000584) (CSI: 3.64) in the small intestine, and [epithelial cells of the proximal tubule](/details-cell/CL0002306) (CSI: 3.40) in the kidney. This pattern suggests its involvement in the uptake and processing of dietary or reabsorbed fatty acids in these tissues. Its presence in various [secretory cells](/details-cell/CL0000151) and [club cells](/details-cell/CL0000158) may point to roles in the lipid composition of secreted products like mucus or surfactant. ## Pathways and Molecular Function The functional annotations for [SLC27A2](/details-gene/11001) align with its expression pattern, confirming its role as a key enzyme in lipid metabolism. The gene product is localized to the endoplasmic reticulum, peroxisomal membrane, and plasma membrane, allowing it to participate in both fatty acid uptake and intracellular processing. **Molecular Function:** [SLC27A2](/details-gene/11001) exhibits multiple ligase activities, including `very long-chain fatty acid-CoA ligase activity` ([GO:0031957](https://www.ebi.ac.uk/QuickGO/term/GO:0031957)), `arachidonate-CoA ligase activity` ([GO:0047676](https://www.ebi.ac.uk/QuickGO/term/GO:0047676)), and `cholate-CoA ligase activity` ([GO:0047747](https://www.ebi.ac.uk/QuickGO/term/GO:0047747)). These activities involve the ATP-dependent conversion of fatty acids to their acyl-CoA esters, which is the first committed step in their metabolism. It also functions as a `long-chain fatty acid transmembrane transporter` ([GO:0005324](https://www.ebi.ac.uk/QuickGO/term/GO:0005324)), facilitating the import of fatty acids into the cell [Link](https://doi.org/10.1152/ajpendo.00226.2010). **Biological Process & Pathways:** Its enzymatic functions are integral to several metabolic pathways. It is a key component of `Fatty acid metabolism` ([R-HSA-8978868](https://reactome.org/content/detail/R-HSA-8978868)), contributing to both `Fatty acid beta-oxidation` ([GO:0006635](https://www.ebi.ac.uk/QuickGO/term/GO:0006635)) and `Fatty-acyl-CoA biosynthetic process` ([GO:0046949](https://www.ebi.ac.uk/QuickGO/term/GO:0046949)). Its high expression in the liver is directly linked to its critical role in the `Synthesis of bile acids and bile salts` ([R-HSA-192105](https://reactome.org/content/detail/R-HSA-192105)). Additionally, its activity in peroxisomes is highlighted by its involvement in the `Alpha-oxidation of phytanate` ([R-HSA-389599](https://reactome.org/content/detail/R-HSA-389599)) and `Beta-oxidation of very long chain fatty acids` ([R-HSA-390247](https://reactome.org/content/detail/R-HSA-390247)) [Link](https://doi.org/10.1006/excr.1999.4757). ## Research Directions The specific expression patterns and core metabolic functions of [SLC27A2](/details-gene/11001) suggest several avenues for future research, particularly concerning its role in tissue-specific lipid homeostasis and metabolic disease. ### Proposed Hypotheses: 1. **Role in Intestinal Health:** Given its high expression in [colon epithelial cells](/details-cell/CL0011108), [SLC27A2](/details-gene/11001) may be a critical gatekeeper for the uptake and utilization of fatty acids derived from the gut microbiome and diet. Dysregulation of [SLC27A2](/details-gene/11001) in these cells could impair the colonic energy supply and compromise gut barrier function, potentially contributing to inflammatory bowel disease. 2. **Function in Fetal Development:** The pronounced expression of [SLC27A2](/details-gene/11001) in [placental villous trophoblasts](/details-cell/CL2000060) suggests it is essential for the active transport of specific long-chain polyunsaturated fatty acids (LCPUFAs), such as DHA and arachidonic acid, to the fetus. Genetic variants that reduce its transport efficiency could be associated with adverse neurodevelopmental outcomes or fetal growth restriction. ### Suggested Experimental Approach: To test the first hypothesis regarding its role in intestinal health, a combination of in vitro and in vivo models could be employed. Specifically, one could generate [colon epithelial cell](/details-cell/CL0011108) organoids from human induced pluripotent stem cells (iPSCs) and use CRISPR-Cas9 to knock out [SLC27A2](/details-gene/11001). The impact of its loss could be assessed by treating knockout and wild-type organoids with a mixture of stable isotope-labeled fatty acids (e.g., ¹³C-butyrate, ¹³C-palmitate). Subsequent lipidomic analysis via mass spectrometry would quantify differences in fatty acid uptake and incorporation into complex lipids. Furthermore, assays measuring epithelial barrier integrity (e.g., transepithelial electrical resistance) and mitochondrial respiration (e.g., Seahorse analysis) would reveal the functional consequences of impaired fatty acid metabolism. ### Therapeutic Potential: [SLC27A2](/details-gene/11001) presents a potential therapeutic target for metabolic diseases, primarily those centered in the liver. In conditions like non-alcoholic steatohepatitis (NASH), where excessive fatty acid uptake and lipotoxicity drive disease progression, targeted **inhibition** of [SLC27A2](/details-gene/11001) could reduce the metabolic burden on [hepatocytes](/details-cell/CL0000182). A small molecule inhibitor or siRNA-based therapeutic delivered specifically to the liver could decrease the synthesis of toxic lipid species and downstream inflammatory signaling. However, the systemic importance of fatty acid metabolism would require that any therapeutic strategy be highly tissue-specific to avoid adverse effects in other organs.

Genular Protein ID: 1721208352

Symbol: S27A2_HUMAN

Name: Arachidonate--CoA ligase

UniProtKB Accession Codes:

O14975 A8K2J7 Q53FY6 Q6PF09

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEBI 76 ChEMBL 1 ChiTaRS 1 DNASU 1 DisGeNET 1 DrugBank 1 EC 4 EMBL 7 Ensembl 2 ExpressionAtlas 1 GO 27 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 6 RefSeq 2 Rhea 29 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissLipids 3 SwissPalm 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10198260

Title: Human very-long-chain acyl-CoA synthetase: cloning, topography, and relevance to branched-chain fatty acid metabolism.

PubMed ID: 10198260

DOI: 10.1006/bbrc.1999.0510

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

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: 10640429

Title: Intraperoxisomal localization of very-long-chain fatty acyl-CoA synthetase: implication in X-adrenoleukodystrophy.

PubMed ID: 10640429

DOI: 10.1006/excr.1999.4757

PubMed ID: 10749848

Title: The human liver-specific homolog of very long-chain acyl-CoA synthetase is cholate:CoA ligase.

PubMed ID: 10749848

DOI: 10.1074/jbc.c000015200

PubMed ID: 11980911

Title: Participation of two members of the very long-chain acyl-CoA synthetase family in bile acid synthesis and recycling.

PubMed ID: 11980911

DOI: 10.1074/jbc.m203295200

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 20530735

Title: FATP2 is a hepatic fatty acid transporter and peroxisomal very long-chain acyl-CoA synthetase.

PubMed ID: 20530735

DOI: 10.1152/ajpendo.00226.2010

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 22022213

Title: Overexpression of CD36 and acyl-CoA synthetases FATP2, FATP4 and ACSL1 increases fatty acid uptake in human hepatoma cells.

PubMed ID: 22022213

DOI: 10.7150/ijms.8.599

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21768100

Title: Human fatty acid transport protein 2a/very long chain acyl-CoA synthetase 1 (FATP2a/Acsvl1) has a preference in mediating the channeling of exogenous n-3 fatty acids into phosphatidylinositol.

PubMed ID: 21768100

DOI: 10.1074/jbc.m111.226316

PubMed ID: 24269233

Title: Identification of acyl-CoA synthetases involved in the mammalian sphingosine 1-phosphate metabolic pathway.

PubMed ID: 24269233

DOI: 10.1016/j.bbrc.2013.11.036

PubMed ID: 23186163

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

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

Sequence Information:

  • Length: 620
  • Mass: 70312
  • Checksum: 752E2FFBB2E47C26
  • Sequence:
    • MLSAIYTVLA GLLFLPLLVN LCCPYFFQDI GYFLKVAAVG RRVRSYGKRR PARTILRAFL 
EKARQTPHKP FLLFRDETLT YAQVDRRSNQ VARALHDHLG LRQGDCVALL MGNEPAYVWL 
WLGLVKLGCA MACLNYNIRA KSLLHCFQCC GAKVLLVSPE LQAAVEEILP SLKKDDVSIY 
YVSRTSNTDG IDSFLDKVDE VSTEPIPESW RSEVTFSTPA LYIYTSGTTG LPKAAMITHQ 
RIWYGTGLTF VSGLKADDVI YITLPFYHSA ALLIGIHGCI VAGATLALRT KFSASQFWDD 
CRKYNVTVIQ YIGELLRYLC NSPQKPNDRD HKVRLALGNG LRGDVWRQFV KRFGDICIYE 
FYAATEGNIG FMNYARKVGA VGRVNYLQKK IITYDLIKYD VEKDEPVRDE NGYCVRVPKG 
EVGLLVCKIT QLTPFNGYAG AKAQTEKKKL RDVFKKGDLY FNSGDLLMVD HENFIYFHDR 
VGDTFRWKGE NVATTEVADT VGLVDFVQEV NVYGVHVPDH EGRIGMASIK MKENHEFDGK 
KLFQHIADYL PSYARPRFLR IQDTIEITGT FKHRKMTLVE EGFNPAVIKD ALYFLDDTAK 
MYVPMTEDIY NAISAKTLKL