Details for: SELE

Gene ID: 6401

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: SELE

Ensembl ID: ENSG00000007908

Description: selectin E

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • retinal blood vessel endothelial cell CL0002585
    CSI 5.48
    rCSI 8.75%
    PRS 99.76
  • blood vessel endothelial cell CL0000071
    CSI 4.37
    rCSI 9.07%
    PRS 99.47
  • vein endothelial cell CL0002543
    CSI 3.39
    rCSI 9.26%
    PRS 99.69
  • vein endothelial cell of respiratory system CL4033008
    CSI 2.71
    rCSI 18.62%
    PRS 99.73
  • endothelial cell of lymphatic vessel CL0002138
    CSI 2.28
    rCSI 4.52%
    PRS 99.58
  • endothelial cell of venule CL1000414
    CSI 1.84
    rCSI 16.32%
    PRS 99.65
  • endothelial cell of placenta CL0009092
    CSI 1.4
    rCSI 6.89%
    PRS 99.54
  • endothelial cell of vascular tree CL0002139
    CSI 1.3
    rCSI 7.1%
    PRS 98.46
  • prostate gland microvascular endothelial cell CL2000059
    CSI 1.07
    rCSI 25.65%
    PRS 99.67

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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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
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    • 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 [SELE](/details-gene/6401), or Selectin E, is a protein-coding gene located on chromosome 1q24.2. It encodes E-selectin, a calcium-dependent lectin and cell adhesion molecule expressed on the surface of endothelial cells. The primary function of [SELE](/details-gene/6401) is to mediate the initial tethering and rolling of leukocytes on the vascular endothelium during the inflammatory response. This role is underscored by its high and specific expression in various endothelial cell types, particularly `[retinal blood vessel endothelial cell](/details-cell/CL0002585)` and `[blood vessel endothelial cell](/details-cell/CL0000071)`. Its involvement in leukocyte trafficking makes it a critical component of innate immunity and a key player in inflammatory pathologies, with genetic variants associated with cardiovascular diseases such as atherosclerosis ([OMIM](/omim/131210)). ## Cellular Roles and Expression Landscape The expression profile of [SELE](/details-gene/6401) firmly establishes its role as a key functional marker of the vascular endothelium. **Overall**, the gene shows the highest significance in a range of endothelial cell populations, with a particularly high Cell Significance Index (CSI) in `[retinal blood vessel endothelial cell](/details-cell/CL0002585)` (CSI: 5.48) and `[blood vessel endothelial cell](/details-cell/CL0000071)` (CSI: 4.37). Its prominent expression extends to more specialized endothelial subtypes, including `[vein endothelial cell](/details-cell/CL0002543)` and `[endothelial cell of lymphatic vessel](/details-cell/CL0002138)`. This expression pattern highlights [SELE](/details-gene/6401) as a crucial workhorse molecule across the circulatory system, essential for immune surveillance and response. The function of [SELE](/details-gene/6401) is induced by inflammatory cytokines like IL-1 and TNF-alpha, which promote its transcription and cell surface presentation on endothelial cells, thereby enabling the recruitment of leukocytes to sites of inflammation or injury ([Link](https://doi.org/10.1126/science.2466335)). The specificity of its expression to the endothelial lineage suggests a highly specialized function in mediating interactions between the blood and surrounding tissues. ## Pathways and Molecular Function Functionally, [SELE](/details-gene/6401) is integral to processes governing inflammation and vascular interactions. Its gene ontology annotations are dominated by its role in `[Leukocyte cell-cell adhesion](/details-term/GO:0007159)`, `[Leukocyte tethering or rolling](/details-term/GO:0050901)`, and the broader `[Inflammatory response](/details-term/GO:0006954)`. These biological processes are directly executed through its molecular function as a carbohydrate-binding protein (`[Oligosaccharide binding](/details-term/GO:0070492)`) that specifically recognizes sialylated Lewis X (sLeX) and related glycans on the surface of leukocytes ([Link](https://doi.org/10.1126/science.1701274)). This interaction is a cornerstone of the Reactome pathway `[Cell surface interactions at the vascular wall](/details-pathway/R-HSA-202733)`. As a transmembrane receptor located on the `[External side of plasma membrane](/details-term/GO:0009897)`, E-selectin captures circulating leukocytes from the bloodstream, initiating a cascade of events that leads to their extravasation into tissues. This function is critical for host defense but also contributes to the pathology of chronic inflammatory diseases. ## Research Directions The established role of [SELE](/details-gene/6401) in inflammation and its genetic association with atherosclerosis ([Link](https://doi.org/10.1093/hmg/3.11.1935), [Link](https://doi.org/10.1007/bf00218826)) provide a strong foundation for further investigation into its contribution to vascular disease. Understanding how its function is modulated in chronic versus acute inflammatory settings is a key area for future research. Based on the available data, several testable hypotheses can be proposed: 1. The Ser128Arg polymorphism in [SELE](/details-gene/6401), a known risk factor for coronary artery disease ([Link](https://doi.org/10.1007/bf02256419)), enhances the avidity of E-selectin for its ligands under hemodynamic shear stress, leading to excessive leukocyte recruitment and contributing to the formation of atherosclerotic plaques. 2. In pathological contexts such as cancer metastasis, tumor cells that express high levels of E-selectin ligands (e.g., sLeX) hijack the [SELE](/details-gene/6401)-mediated adhesion mechanism to facilitate their extravasation and the formation of distant metastases. A key experimental approach to test the first hypothesis would be: * **To investigate the impact of the Ser128Arg polymorphism on endothelial function**, one could use CRISPR-Cas9 to engineer this specific variant into human induced pluripotent stem cells (hiPSCs). These hiPSCs would then be differentiated into `[blood vessel endothelial cells](/details-cell/CL0000071)` and cultured in a microfluidic device that simulates arterial shear stress. The adhesion dynamics (tethering frequency, rolling velocity, and firm adhesion) of primary human neutrophils or monocytes on endothelial monolayers expressing either the wild-type or Ser128Arg variant of E-selectin could then be quantified using live-cell imaging. This would provide direct evidence of the polymorphism's functional consequences on leukocyte-endothelial interactions. Given its role as a cell surface receptor that is upregulated during inflammation and mediates pathological cell adhesion, [SELE](/details-gene/6401) represents a compelling therapeutic target. The most viable strategy would be **inhibition** of its function. Development of monoclonal antibodies or small molecule inhibitors that block the ligand-binding domain of E-selectin could prevent the initial step of leukocyte recruitment in a variety of acute and chronic inflammatory diseases, including ischemia-reperfusion injury, sepsis, and atherosclerosis. Such a targeted approach could offer anti-inflammatory benefits with potentially fewer side effects than broad-spectrum immunosuppressants.

Genular Protein ID: 2712225366

Symbol: LYAM2_HUMAN

Name: E-selectin

UniProtKB Accession Codes:

P16581 A2RRD6 P16111

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 3 CTD 1 ChEBI 8 ChEMBL 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 3 EMBL 15 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 29 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HPA 1 IDEAL 1 InParanoid 1 IntAct 1 InterPro 10 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 7 PDBsum 7 PIR 1 PRINTS 1 PRO 1 PROSITE 6 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 1 SIGNOR 1 SMART 3 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 UniLectin 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 1689848

Title: Endothelial leukocyte adhesion molecule 1: direct expression cloning and functional interactions.

PubMed ID: 1689848

DOI: 10.1073/pnas.87.5.1673

PubMed ID: 2466335

Title: Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins.

PubMed ID: 2466335

DOI: 10.1126/science.2466335

PubMed ID: 1703529

Title: Structure and chromosomal location of the gene for endothelial-leukocyte adhesion molecule 1.

PubMed ID: 1703529

DOI: 10.1016/s0021-9258(18)52267-5

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 1701274

Title: ELAM-1 mediates cell adhesion by recognition of a carbohydrate ligand, sialyl-Lex.

PubMed ID: 1701274

DOI: 10.1126/science.1701274

PubMed ID: 18606703

Title: Endoglycan, a member of the CD34 family of sialomucins, is a ligand for the vascular selectins.

PubMed ID: 18606703

DOI: 10.4049/jimmunol.181.2.1480

PubMed ID: 28011641

Title: Glycan Bound to the Selectin Low Affinity State Engages Glu-88 to Stabilize the High Affinity State under Force.

PubMed ID: 28011641

DOI: 10.1074/jbc.m116.767186

PubMed ID: 7681016

Title: Modelling the carbohydrate recognition domain of human E-selectin.

PubMed ID: 7681016

DOI: 10.1016/0014-5793(93)80026-q

PubMed ID: 7509040

Title: Insight into E-selectin/ligand interaction from the crystal structure and mutagenesis of the lec/EGF domains.

PubMed ID: 7509040

DOI: 10.1038/367532a0

PubMed ID: 11081633

Title: Insights into the molecular basis of leukocyte tethering and rolling revealed by structures of P- and E-selectin bound to SLe(X) and PSGL-1.

PubMed ID: 11081633

DOI: 10.1016/s0092-8674(00)00138-0

PubMed ID: 26117840

Title: E-selectin ligand complexes adopt an extended high-affinity conformation.

PubMed ID: 26117840

DOI: 10.1093/jmcb/mjv046

PubMed ID: 7533025

Title: E-selectin polymorphism and atherosclerosis: an association study.

PubMed ID: 7533025

DOI: 10.1093/hmg/3.11.1935

PubMed ID: 8557254

Title: DNA polymorphisms in adhesion molecule genes -- a new risk factor for early atherosclerosis.

PubMed ID: 8557254

DOI: 10.1007/bf00218826

PubMed ID: 9933738

Title: A PstI polymorphism detects the mutation of serine-128 to arginine in CD 62E gene - a risk factor for coronary artery disease.

PubMed ID: 9933738

DOI: 10.1007/bf02256419

PubMed ID: 10391210

Title: Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis.

PubMed ID: 10391210

DOI: 10.1038/10297

PubMed ID: 10982036

Title: Relationship between E-selectin L/F554 polymorphism and blood pressure in the Stanislas cohort.

PubMed ID: 10982036

DOI: 10.1007/s004390000325

PubMed ID: 12649084

Title: E-selectin polymorphism associated with myocardial infarction causes enhanced leukocyte-endothelial interactions under flow conditions.

PubMed ID: 12649084

DOI: 10.1161/01.atv.0000067427.40133.59

PubMed ID: 24688092

Title: Implications of the E-selectin S128R mutation for drug discovery.

PubMed ID: 24688092

DOI: 10.1093/glycob/cwu026

PubMed ID: 25787250

Title: Neomorphic effects of recurrent somatic mutations in Yin Yang 1 in insulin-producing adenomas.

PubMed ID: 25787250

DOI: 10.1073/pnas.1503696112

Sequence Information:

  • Length: 610
  • Mass: 66655
  • Checksum: 7D43E3C0D1229229
  • Sequence:
    • MIASQFLSAL TLVLLIKESG AWSYNTSTEA MTYDEASAYC QQRYTHLVAI QNKEEIEYLN 
SILSYSPSYY WIGIRKVNNV WVWVGTQKPL TEEAKNWAPG EPNNRQKDED CVEIYIKREK 
DVGMWNDERC SKKKLALCYT AACTNTSCSG HGECVETINN YTCKCDPGFS GLKCEQIVNC 
TALESPEHGS LVCSHPLGNF SYNSSCSISC DRGYLPSSME TMQCMSSGEW SAPIPACNVV 
ECDAVTNPAN GFVECFQNPG SFPWNTTCTF DCEEGFELMG AQSLQCTSSG NWDNEKPTCK 
AVTCRAVRQP QNGSVRCSHS PAGEFTFKSS CNFTCEEGFM LQGPAQVECT TQGQWTQQIP 
VCEAFQCTAL SNPERGYMNC LPSASGSFRY GSSCEFSCEQ GFVLKGSKRL QCGPTGEWDN 
EKPTCEAVRC DAVHQPPKGL VRCAHSPIGE FTYKSSCAFS CEEGFELHGS TQLECTSQGQ 
WTEEVPSCQV VKCSSLAVPG KINMSCSGEP VFGTVCKFAC PEGWTLNGSA ARTCGATGHW 
SGLLPTCEAP TESNIPLVAG LSAAGLSLLT LAPFLLWLRK CLRKAKKFVP ASSCQSLESD 
GSYQKPSYIL