Details for: ADGRE1

Gene ID: 2015

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: ADGRE1

Ensembl ID: ENSG00000174837

Description: adhesion G protein-coupled receptor E1

Cell Significance Landscape

Associated with

Significant Cells

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

  • myeloid leukocyte CL0000766
    CSI 7.33
    rCSI 6.76%
    PRS 99.45
  • Kupffer cell CL0000091
    CSI 3.67
    rCSI 8.4%
    PRS 99.17
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 3.09
    rCSI 2.38%
    PRS 99.69
  • intermediate monocyte CL0002393
    CSI 2.5
    rCSI 3.78%
    PRS 99.72

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
    • 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 [ADGRE1](/details-gene/2015) (Adhesion G Protein-Coupled Receptor E1), also known as EMR1, is a protein-coding gene located on chromosome 19p13.3-p13.2. It encodes a member of the adhesion G protein-coupled receptor (GPCR) family, characterized by a large extracellular region with multiple EGF-like domains and a seven-transmembrane domain ([Link](https://doi.org/10.1124/pr.114.009647)). Functionally, [ADGRE1](/details-gene/2015) is involved in signal transduction ([R-HSA-162582](https://reactome.org/content/detail/R-HSA-162582)) and cell adhesion ([GO:0007155](https://www.ebi.ac.uk/QuickGO/term/GO:0007155)). Its expression is highly restricted to the myeloid lineage, making it a key cell surface marker for various immune cells, including monocytes, macrophages, and eosinophils. It is associated with OMIM entry [600493](https://omim.org/entry/600493). ## Cellular Roles and Expression Landscape The expression profile of [ADGRE1](/details-gene/2015) strongly indicates a specialized role within the myeloid compartment of the immune system. **Overall**, it shows the highest significance in [myeloid leukocytes](/details-cell/CL0000766) (CSI: 7.33), highlighting its role as a defining marker for this entire lineage. Its prominence extends to both circulating and tissue-resident myeloid populations. Specifically, it is a significant marker for liver-resident macrophages, known as [Kupffer cells](/details-cell/CL0000091) (CSI: 3.67), as well as subsets of circulating monocytes, including [CD14-low, CD16-positive monocytes](/details-cell/CL0002396) (CSI: 3.09) and [intermediate monocytes](/details-cell/CL0002393) (CSI: 2.50). This pattern suggests that [ADGRE1](/details-gene/2015) is not only involved in the identity of these cells but likely plays a functional role in their activity in both the bloodstream and peripheral tissues. Notably, [ADGRE1](/details-gene/2015) is the human ortholog of the well-established murine macrophage marker F4/80 and has also been identified as a specific receptor on eosinophils, further cementing its role as a key myeloid cell surface protein ([Link](https://doi.org/10.1002/eji.200737553)). ## Pathways and Molecular Function [ADGRE1](/details-gene/2015) functions as a G protein-coupled receptor ([GO:0004930](https://www.ebi.ac.uk/QuickGO/term/GO:0004930)) located on the external side of the plasma membrane ([GO:0009897](https://www.ebi.ac.uk/QuickGO/term/GO:0009897)). Its involvement in the G protein-coupled receptor signaling pathway ([GO:0007186](https://www.ebi.ac.uk/QuickGO/term/GO:0007186)) and more specifically, pathways related to Class B/2 Secretin family receptors ([R-HSA-373080](https://reactome.org/content/detail/R-HSA-373080)), suggests it transduces extracellular signals into intracellular responses. Consistent with its high expression in immune cells, it is annotated with a role in the adaptive immune response ([GO:0002250](https://www.ebi.ac.uk/QuickGO/term/GO:0002250)). Its function in cell adhesion ([GO:0007155](https://www.ebi.ac.uk/QuickGO/term/GO:0007155)), combined with its calcium ion binding capability ([GO:0005509](https://www.ebi.ac.uk/QuickGO/term/GO:0005509)), is consistent with a role in mediating cell-cell or cell-matrix interactions, which are critical for immune cell trafficking, tissue localization, and activation. ## Research Directions The specific expression of [ADGRE1](/details-gene/2015) on myeloid cells, particularly macrophages and eosinophils, positions it as a protein of significant interest in both homeostasis and disease. Future research should focus on elucidating the precise functional consequences of its activation in different cellular contexts. **Testable Hypotheses:** 1. Engagement of [ADGRE1](/details-gene/2015) on tissue-resident macrophages, such as [Kupffer cells](/details-cell/CL0000091), by an endogenous ligand in the liver microenvironment is a key signal that regulates their inflammatory state and phagocytic capacity during homeostasis and response to injury. 2. In allergic diseases, ligand-mediated cross-linking of [ADGRE1](/details-gene/2015) on eosinophils serves as a primary activation signal, triggering degranulation and the release of cytotoxic proteins and inflammatory mediators, thereby contributing directly to tissue pathology. **Proposed Experiment:** To test the second hypothesis regarding eosinophil activation, one could perform an *in vitro* stimulation assay. Primary eosinophils isolated from the peripheral blood of healthy donors and allergic patients would be cultured and treated with a specific agonistic anti-ADGRE1 antibody to mimic ligand binding. The functional consequences could be assessed by quantifying the release of eosinophil peroxidase (EPO) via an enzymatic assay to measure degranulation, measuring calcium flux using flow cytometry, and evaluating the secretion of key cytokines/chemokines like IL-4, IL-13, and eotaxin using ELISA or multiplex assays. A blocking antibody or shRNA-mediated knockdown of [ADGRE1](/details-gene/2015) would serve as a crucial control to validate the specificity of the observed effects. **Therapeutic Potential:** Given its high and specific expression on the surface of eosinophils, [ADGRE1](/details-gene/2015) represents a highly promising therapeutic target for eosinophil-driven disorders, such as eosinophilic esophagitis, severe asthma, and hypereosinophilic syndromes ([Link](https://doi.org/10.1016/j.jaci.2013.11.041)). The therapeutic strategy would likely involve **inhibition** or depletion. A humanized monoclonal antibody could be developed to either block ligand binding and subsequent cell activation or to target eosinophils for depletion via antibody-dependent cell-mediated cytotoxicity (ADCC). Its restricted expression profile suggests that such a therapy would have a favorable safety profile with limited off-target effects on non-myeloid cells.

Genular Protein ID: 3573759261

Symbol: AGRE1_HUMAN

Name: EGF-like module receptor 1

UniProtKB Accession Codes:

Q14246 A6NHV2 B7Z486 B7Z489 E7EPX9 E9PD45 H9KV79 Q2I7G5 Q6ZMN0 Q8NGA7

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 BioMuta 1 CCDS 5 CDD 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 9 Ensembl 5 ExpressionAtlas 1 GO 9 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 12 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 2 PRO 1 PROSITE 7 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 5 RNAct 1 Reactome 1 RefSeq 5 SMART 3 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 7601460

Title: EMR1, an unusual member in the family of hormone receptors with seven transmembrane segments.

PubMed ID: 7601460

DOI: 10.1016/0888-7543(95)80218-b

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

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: 17823986

Title: EMR1, the human homolog of F4/80, is an eosinophil-specific receptor.

PubMed ID: 17823986

DOI: 10.1002/eji.200737553

PubMed ID: 24530099

Title: The eosinophil surface receptor epidermal growth factor-like module containing mucin-like hormone receptor 1 (EMR1): a novel therapeutic target for eosinophilic disorders.

PubMed ID: 24530099

DOI: 10.1016/j.jaci.2013.11.041

PubMed ID: 25713288

Title: International union of basic and clinical pharmacology. XCIV. Adhesion G protein-coupled receptors.

PubMed ID: 25713288

DOI: 10.1124/pr.114.009647

Sequence Information:

  • Length: 886
  • Mass: 97683
  • Checksum: 07322996EEF5A6F1
  • Sequence:
    • MRGFNLLLFW GCCVMHSWEG HIRPTRKPNT KGNNCRDSTL CPAYATCTNT VDSYYCACKQ 
GFLSSNGQNH FKDPGVRCKD IDECSQSPQP CGPNSSCKNL SGRYKCSCLD GFSSPTGNDW 
VPGKPGNFSC TDINECLTSS VCPEHSDCVN SMGSYSCSCQ VGFISRNSTC EDVDECADPR 
ACPEHATCNN TVGNYSCFCN PGFESSSGHL SFQGLKASCE DIDECTEMCP INSTCTNTPG 
SYFCTCHPGF APSNGQLNFT DQGVECRDID ECRQDPSTCG PNSICTNALG SYSCGCIAGF 
HPNPEGSQKD GNFSCQRVLF KCKEDVIPDN KQIQQCQEGT AVKPAYVSFC AQINNIFSVL 
DKVCENKTTV VSLKNTTESF VPVLKQISTW TKFTKEETSS LATVFLESVE SMTLASFWKP 
SANITPAVRT EYLDIESKVI NKECSEENVT LDLVAKGDKM KIGCSTIEES ESTETTGVAF 
VSFVGMESVL NERFFKDHQA PLTTSEIKLK MNSRVVGGIM TGEKKDGFSD PIIYTLENIQ 
PKQKFERPIC VSWSTDVKGG RWTSFGCVIL EASETYTICS CNQMANLAVI MASGELTMDF 
SLYIISHVGI IISLVCLVLA IATFLLCRSI RNHNTYLHLH LCVCLLLAKT LFLAGIHKTD 
NKMGCAIIAG FLHYLFLACF FWMLVEAVIL FLMVRNLKVV NYFSSRNIKM LHICAFGYGL 
PMLVVVISAS VQPQGYGMHN RCWLNTETGF IWSFLGPVCT VIVINSLLLT WTLWILRQRL 
SSVNAEVSTL KDTRLLTFKA FAQLFILGCS WVLGIFQIGP VAGVMAYLFT IINSLQGAFI 
FLIHCLLNGQ VREEYKRWIT GKTKPSSQSQ TSRILLSSMP SASKTG

Genular Protein ID: 2702111616

Symbol: A8K653_HUMAN

Name: N/A

UniProtKB Accession Codes:

A8K653

Database IDs:

ARBA 13 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 4 Gene3D 3 InterPro 12 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 2 PROSITE 9 PROSITE-ProRule 1 PeptideAtlas 1 Pfam 3 RefSeq 1 SAM 3 SMART 3 SUPFAM 3

Sequence Information:

  • Length: 821
  • Mass: 90334
  • Checksum: 0DD2C0AF81639AFA
  • Sequence:
    • MRGFNLLLFW GCCVMHSWEG HIRPTRKPNT KGNNCRDSTL CPAYATCTNT VDSYYCACKQ 
GFLSSNGQNH FKDPGVRCKD IDECSQSPQP CGPNSSCKNL SGRYKCSCLD GFSSPTGNDW 
VPGKPGNFSC TDINECLTSS VCPEHSDCVN SMGSYSCICQ VGFISRNSTC EDVDECADPR 
ACPEHATCNS TVGNFSCFCN PGFESSSGHL SFQGLKASCE DIDECTEMCP INSTCTNTPG 
SYFCTCHPGF APSNGQLNFT DQGVECRDID ECRQDPSTCG PNSICTNALG SYSCGCIAGF 
HPNPEGSQKD GNFSCQRVLF KCKEDVIPDN KQIQQCQEGT AVKPAYVSFC AQINNIFSVL 
DKVCENKTTV VSLKNTTESF VPVLKQISMW TKFTKEETSS LATVFLESVE SMTLASFWKP 
SANVTPAVRT EYLDIESKVI NKECSEENVT LDLVAKGDKM KIGCSTIEES ESTETTGVAF 
VSFVGMESVL NERFFQDHQA PLTTSEIKLK MNSRVVGGIM TGEKKDGFSD PIIYTLENVQ 
PKQKFERPIC VSWSTDVKGG RWTSFGCVIL EASETYTICS CNQMANLAVI MASGELTTGC 
AIIAGFLHYL FLACFFWMLV EAVILFLMVR NLKVVNYFSS RNIKMLHICA FGYGLPMLVV 
VISASVQPQG YGMHNRCWLN TETGFIWSFL GPVCTVIVIN SLLLTWTLWI LRQRLSSVNA 
EVSTLKDTRL LTFKAFAQLF ILGCSWVLGI FQIGPVAGVM AYLFTIINSL QGAFIFLIHC 
LLNGQVREEY KRWITGKTKP SSQSQTSRIL LSSMPSASKT G

Genular Protein ID: 1205474800

Symbol: A8K2Y6_HUMAN

Name: N/A

UniProtKB Accession Codes:

A8K2Y6

Database IDs:

ARBA 13 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 2 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 4 Gene3D 3 InterPro 12 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 2 PROSITE 9 PROSITE-ProRule 1 PeptideAtlas 1 Pfam 3 RefSeq 1 SAM 3 SMART 3 SUPFAM 3

Sequence Information:

  • Length: 889
  • Mass: 97998
  • Checksum: E61DE6022E5A961E
  • Sequence:
    • MRGFNLLLFW GCCVMHSWEG HIRPTRKPNT KGNNCRDSTL CPAYATCTNT VDSYYCACKQ 
GFLSSNGQNH FKDPGVRCKD IDECSQSPQP CGPNSSCKNL SGRYKCSCLD GFSSPTGNDW 
VPGKPGNFSC TDINECLTSS VCPEHSDCVN SMGSYSCSCQ VGFISRNSTC EDVDECADPR 
ACPEHATCNN TVGNYSCFCN PGFESSSGHL SFQGLKASCE DIDECTEMCP INSTCTNTPG 
SYFCTCHPGF APSNGQLNFT DQGVECRDID ECRQDPSTCG PNSICTNALG SYSCGCIAGF 
HPNPEGSQKD GNFSCQRVLF KCKEDVIPDN KQIQQCQEGT AVKPAYVSFC AQINNIFSVL 
DKVCENKTTV VSLKNTTESF VPVLKQISTW TKFTKEETSS LATVFLESVE SMTLASFWKP 
SANVTPAVRT EYLDIESKVI NKECSEENVT LDLVAKGDKM KIGCSTIEES ESTETTGVAF 
VSFVGMESVL NERFFQDHQA PLTTSEIKLK MNSRVVGGIM TGEKKDGFSD PIIYTLENVQ 
PKQKFERPIC VSWSTDVKGG RWTSFGCVIL EASETYTICS CNQMANLAVI MASGELTMDF 
SLYIISHVGI IISLVCLVLA IATFLLCRSI RNHNTYLHLH LCVCLLLAKT LFLAGIHKTD 
NKMGCAIIAG FLHYLFLACF FWMLVEAVIL FLMVRNLKVV NYFSSRNIKM LHICAFGYGL 
PMLVVVISAS VQPQGYGMHN RCWLNTETGF IWSFLGPVCT VIVTLQINSL LLTWTLWILR 
QRLSSVNAEV STLKDTRLLT FKAFAQLFIL GCSWVLGIFQ IGPVAGVMAY LFTIINSLQG 
AFIFLIHCLL NGQVREEYKR WITGKTKPSS QSQTSRILLS SMPSASKTG