Details for: SEC14L2

Gene ID: 23541

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: SEC14L2

Ensembl ID: ENSG00000100003

Description: SEC14 like lipid binding 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • retinal pigment epithelial cell CL0002586
    CSI 8.28
    rCSI 16.43%
    PRS 92.22
  • Mueller cell CL0000636
    CSI 4.18
    rCSI 9.55%
    PRS 90.2
  • T follicular helper cell CL0002038
    CSI 3.83
    rCSI 2.86%
    PRS 98.67
  • midzonal region hepatocyte CL0019028
    CSI 3.82
    rCSI 8.96%
    PRS 91.78
  • secretory cell CL0000151
    CSI 3.77
    rCSI 3.94%
    PRS 93.9
  • hepatocyte CL0000182
    CSI 3.06
    rCSI 5.48%
    PRS 93.19
  • squamous epithelial cell CL0000076
    CSI 2.49
    rCSI 5.9%
    PRS 91.38
  • stem cell CL0000034
    CSI 2.44
    rCSI 2.35%
    PRS 92.21
  • periportal region hepatocyte CL0019026
    CSI 2.36
    rCSI 9.19%
    PRS 91.46
  • retinal rod cell CL0000604
    CSI 2.33
    rCSI 4.1%
    PRS 91.52
  • choroid plexus epithelial cell CL0000706
    CSI 2.22
    rCSI 3.64%
    PRS 89.89
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.21
    rCSI 2.76%
    PRS 84
  • club cell CL0000158
    CSI 2.21
    rCSI 3.23%
    PRS 91.84
  • colonocyte CL1000347
    CSI 2.08
    rCSI 2.98%
    PRS 93.04
  • ependymal cell CL0000065
    CSI 2.06
    rCSI 4.17%
    PRS 80.86
  • basal cell CL0000646
    CSI 2.04
    rCSI 2.73%
    PRS 92.48
  • rod bipolar cell CL0000751
    CSI 2.01
    rCSI 3.62%
    PRS 91.06
  • luminal epithelial cell of mammary gland CL0002326
    CSI 2.01
    rCSI 3.66%
    PRS 97.2
  • retinal cone cell CL0000573
    CSI 1.72
    rCSI 2.77%
    PRS 88.71
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.6
    rCSI 3.58%
    PRS 86.16
  • amacrine cell CL0000561
    CSI 1.57
    rCSI 4.54%
    PRS 88.69
  • glial cell CL0000125
    CSI 1.55
    rCSI 5.89%
    PRS 89.82
  • retinal ganglion cell CL0000740
    CSI 1.32
    rCSI 2.92%
    PRS 87.33
  • neural progenitor cell CL0011020
    CSI 1.19
    rCSI 5.25%
    PRS 86.05
  • ON midget ganglion cell CL4033046
    CSI 0.28
    rCSI 5.6%
    PRS 88.17

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 [SEC14L2](/details-gene/23541), or SEC14 like lipid binding 2, is a protein-coding gene located on chromosome 22q12.2. Functionally, it is characterized as a phospholipid and vitamin E-binding protein that acts as a ligand-dependent transcriptional activator. It is involved in biological processes such as the positive regulation of transcription ([GO:0045893](https://www.ebi.ac.uk/QuickGO/term/GO:0045893)) and the regulation of cholesterol biosynthesis ([GO:0045540](https://www.ebi.ac.uk/QuickGO/term/GO:0045540)), as established in several studies ([Link](https://doi.org/10.1006/bbrc.2001.5162), [Link](https://doi.org/10.1073/pnas.041620398)). **Overall**, expression data reveals that [SEC14L2](/details-gene/23541) is a highly significant marker in specialized metabolic and barrier tissues, showing its most prominent significance in [retinal pigment epithelial cell](/details-cell/CL0002586) and various subtypes of [hepatocyte](/details-cell/CL0000182). This expression pattern is consistent with its dual roles in managing lipid-soluble vitamins essential for retinal health and regulating cholesterol metabolism in the liver. ## Cellular Roles and Expression Landscape The expression profile of [SEC14L2](/details-gene/23541) highlights its importance in specific, high-activity cell types. **Overall**, the gene's significance is most pronounced in the eye and liver. It exhibits an exceptionally high Cell Significance Index (CSI) in [retinal pigment epithelial cell](/details-cell/CL0002586) (CSI: 8.28), a cell type critical for the function and maintenance of photoreceptors. Its significance in other retinal cells, such as the [Mueller cell](/details-cell/CL0000636) (CSI: 4.18), further underscores a specialized role in retinal biology. This is consistent with its function as a tocopherol (vitamin E)-associated protein, as vitamin E is a crucial antioxidant in the retina ([Link](https://doi.org/10.1074/jbc.m000851200)). A second major site of [SEC14L2](/details-gene/23541) activity is the liver, with high significance in [midzonal region hepatocyte](/details-cell/CL0019028) (CSI: 3.82), [hepatocyte](/details-cell/CL0000182) (CSI: 3.06), and [periportal region hepatocyte](/details-cell/CL0019026) (CSI: 2.36). This aligns with its identified role as a supernatant protein factor that enhances cholesterol biosynthesis ([Link](https://doi.org/10.1073/pnas.041620398)). Beyond these primary sites, [SEC14L2](/details-gene/23541) also shows notable significance in a subset of immune cells, particularly the [T follicular helper cell](/details-cell/CL0002038) (CSI: 3.83), suggesting a potential role in modulating immune cell function, possibly through lipid sensing. It is also significant across a range of secretory and epithelial cells, including [secretory cell](/details-cell/CL0000151) (CSI: 3.77), [squamous epithelial cell](/details-cell/CL0000076) (CSI: 2.49), and [club cell](/details-cell/CL0000158) (CSI: 2.21), indicating a broader involvement in cellular maintenance and metabolism in barrier tissues. ## Pathways and Molecular Function The functions of [SEC14L2](/details-gene/23541) are primarily linked to lipid binding and transcriptional regulation. Its molecular function as a phospholipid binder ([GO:0005543](https://www.ebi.ac.uk/QuickGO/term/GO:0005543)) and vitamin E binder ([GO:0008431](https://www.ebi.ac.uk/QuickGO/term/GO:0008431)) positions it as a sensor of intracellular lipid-soluble molecules. Upon ligand binding, it appears to translocate from the cytoplasm ([GO:0005737](https://www.ebi.ac.uk/QuickGO/term/GO:0005737)) to the nucleus ([GO:0005634](https://www.ebi.ac.uk/QuickGO/term/GO:0005634)) to act as a transcriptional activator ([Link](https://doi.org/10.1006/bbrc.2001.5162)). This mechanism directly underlies its involvement in key biological processes. Its role in the regulation of the cholesterol biosynthetic process ([GO:0045540](https://www.ebi.ac.uk/QuickGO/term/GO:0045540)) is consistent with its high expression in [hepatocytes](/details-cell/CL0000182), the central hub of cholesterol metabolism. Research has identified it as the supernatant protein factor that facilitates the conversion of squalene to lanosterol, a key step in cholesterol synthesis ([Link](https://doi.org/10.1073/pnas.041620398)). Its connection to vitamin E homeostasis is particularly relevant to its high significance in [retinal pigment epithelial cell](/details-cell/CL0002586), which are responsible for supplying photoreceptors with essential nutrients and protecting them from oxidative damage. ## Research Directions The specific and high-level expression of [SEC14L2](/details-gene/23541) in metabolically active tissues provides a strong basis for further investigation into its role in health and disease. **Proposed Hypotheses:** 1. Given its exceptional significance in [retinal pigment epithelial cell](/details-cell/CL0002586) and its vitamin E binding capacity, [SEC14L2](/details-gene/23541) may function as a master regulator of an antioxidant transcriptional program in the RPE. We hypothesize that dysfunction or downregulation of [SEC14L2](/details-gene/23541) impairs the RPE's ability to protect photoreceptors from oxidative stress, thereby contributing to the pathogenesis of age-related macular degeneration or other retinal dystrophies. 2. Based on its high expression in [hepatocytes](/details-cell/CL0000182) and role in cholesterol synthesis, we hypothesize that [SEC14L2](/details-gene/23541) acts as a sensor that integrates signals from lipid-soluble vitamins (e.g., tocopherol) with the metabolic state of the cell to fine-tune the rate of cholesterol biosynthesis, potentially acting in concert with or parallel to the canonical SREBP pathway. 3. The unexpected high significance in [T follicular helper cell](/details-cell/CL0002038) suggests a role in immunometabolism. We hypothesize that [SEC14L2](/details-gene/23541) senses the lipid-rich microenvironment of the germinal center to modulate the metabolic fitness and effector function of Tfh cells, thereby influencing the quality and magnitude of the antibody response. **Key Experimental Approach:** To test the first hypothesis regarding the role of [SEC14L2](/details-gene/23541) in retinal protection, a conditional knockout mouse model could be generated. Using a Cre-Lox system with an RPE-specific promoter (e.g., VMD2-Cre), [SEC14L2](/details-gene/23541) would be selectively deleted in retinal pigment epithelial cells. These knockout mice and wild-type controls would be subjected to a light-induced retinal damage model. The impact of [SEC14L2](/details-gene/23541) loss would be evaluated by measuring retinal function (electroretinography), photoreceptor survival (histology and TUNEL staining), and lipid peroxidation markers in retinal tissue. RNA-sequencing of RPE cells isolated from these mice would be performed to identify the downstream transcriptional network regulated by [SEC14L2](/details-gene/23541) in response to oxidative stress. **Therapeutic Potential:** As an intracellular lipid-binding protein and transcriptional regulator, [SEC14L2](/details-gene/23541) is a potential target for small molecule modulators. Its therapeutic relevance is likely context-dependent. Small molecule agonists that enhance its transcriptional activity in a vitamin E-dependent manner could represent a novel therapeutic avenue for retinal degenerative diseases by bolstering the natural antioxidant defenses of the RPE. Conversely, in the context of hypercholesterolemia, selective inhibitors of its function in [hepatocytes](/details-cell/CL0000182) might offer an alternative strategy to lower cholesterol synthesis, although its efficacy relative to existing targets would require extensive investigation.

Genular Protein ID: 467094180

Symbol: S14L2_HUMAN

Name: SEC14-like protein 2

UniProtKB Accession Codes:

O76054 B7Z8Q1 F5H3U4 Q53EQ2 Q6PD61 Q9ULN4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 DrugBank 6 EMBL 7 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 9 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 4 PDBsum 4 PIR 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 RefSeq 3 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10829015

Title: A novel human tocopherol-associated protein: cloning, in vitro expression, and characterization.

PubMed ID: 10829015

DOI: 10.1074/jbc.m000851200

PubMed ID: 11444841

Title: Tocopherol-associated protein is a ligand-dependent transcriptional activator.

PubMed ID: 11444841

DOI: 10.1006/bbrc.2001.5162

PubMed ID: 11226224

Title: Supernatant protein factor, which stimulates the conversion of squalene to lanosterol, is a cytosolic squalene transfer protein and enhances cholesterol biosynthesis.

PubMed ID: 11226224

DOI: 10.1073/pnas.041620398

PubMed ID: 10574461

Title: Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain.

PubMed ID: 10574461

DOI: 10.1093/dnares/6.5.329

PubMed ID: 15461802

Title: A genome annotation-driven approach to cloning the human ORFeome.

PubMed ID: 15461802

DOI: 10.1186/gb-2004-5-10-r84

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 10591208

Title: The DNA sequence of human chromosome 22.

PubMed ID: 10591208

DOI: 10.1038/990031

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: 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

PubMed ID: 12429094

Title: Crystal structure of the human supernatant protein factor.

PubMed ID: 12429094

DOI: 10.1016/s0969-2126(02)00884-5

Sequence Information:

  • Length: 403
  • Mass: 46145
  • Checksum: D846747EC8D1513E
  • Sequence:
    • MSGRVGDLSP RQKEALAKFR ENVQDVLPAL PNPDDYFLLR WLRARSFDLQ KSEAMLRKHV 
EFRKQKDIDN IISWQPPEVI QQYLSGGMCG YDLDGCPVWY DIIGPLDAKG LLFSASKQDL 
LRTKMRECEL LLQECAHQTT KLGRKVETIT IIYDCEGLGL KHLWKPAVEA YGEFLCMFEE 
NYPETLKRLF VVKAPKLFPV AYNLIKPFLS EDTRKKIMVL GANWKEVLLK HISPDQVPVE 
YGGTMTDPDG NPKCKSKINY GGDIPRKYYV RDQVKQQYEH SVQISRGSSH QVEYEILFPG 
CVLRWQFMSD GADVGFGIFL KTKMGERQRA GEMTEVLPNQ RYNSHLVPED GTLTCSDPGI 
YVLRFDNTYS FIHAKKVNFT VEVLLPDKAS EEKMKQLGAG TPK

Genular Protein ID: 4279549167

Symbol: B7Z3Z8_HUMAN

Name: N/A

UniProtKB Accession Codes:

B7Z3Z8

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 1 Gene3D 2 InterPro 5 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 4 PeptideAtlas 1 Pfam 1 RefSeq 1 SMART 1 SUPFAM 2

Sequence Information:

  • Length: 349
  • Mass: 39917
  • Checksum: DD6386A6E0BDBF05
  • Sequence:
    • MLRKHVEFRK QKDIDNIISW QPPEVIQQYL SGGMCGYDLD GCPVWYDIIG PLDAKGLLFS 
ASKQDLLRTK MRECELLLQE CAHQTTKLGR KVETITIIYD CEGLGLKHLW KPAVEAYGEF 
LCMFEENYPE TLKRLFVVKA PKLFPVAYNL IKPFLSEDTR KKIMVLGANW KEVLLKHISP 
DQVPVEYGGT MTDPDGNPKC KSKINYGGDI PRKYYVRDQV KQQYEHSVQI SRGSSHQVEY 
EILFPGCVLR WQFMSDGADV GFGIFLKTKM GERQRAGEMT EVLPNQRYNS HLVPEDGTLT 
CSDPGIYVLR FDNTYSFIHA KKVNFTVEVL LPDKASEEKM KQLGAGTPK