Details for: SIGLEC1

Gene ID: 6614

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: SIGLEC1

Ensembl ID: ENSG00000088827

Description: sialic acid binding Ig like lectin 1

Cell Significance Landscape

Associated with

Significant Cells

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

  • Hofbauer cell CL3000001
    CSI 19.77
    rCSI 37.31%
    PRS 76.17
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 9.51
    rCSI 11.48%
    PRS 74.7
  • alternatively activated macrophage CL0000890
    CSI 3.01
    rCSI 3.78%
    PRS 77.58
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 2.63
    rCSI 6.86%
    PRS 65.63
  • myeloid dendritic cell CL0000782
    CSI 2.42
    rCSI 3.51%
    PRS 81.3
  • Kupffer cell CL0000091
    CSI 2.28
    rCSI 5.21%
    PRS 65.89
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 2.2
    rCSI 2.88%
    PRS 79.07
  • myeloid leukocyte CL0000766
    CSI 2.19
    rCSI 2.02%
    PRS 67.62
  • CD14-positive monocyte CL0001054
    CSI 2.13
    rCSI 2.65%
    PRS 76.43
  • elicited macrophage CL0000861
    CSI 2.07
    rCSI 1.9%
    PRS 74.89
  • lung interstitial macrophage CL4033043
    CSI 1.9
    rCSI 4.28%
    PRS 82.03
  • mononuclear phagocyte CL0000113
    CSI 1.68
    rCSI 3.7%
    PRS 69.79
  • monocyte CL0000576
    CSI 1.59
    rCSI 2.87%
    PRS 77.79
  • alveolar macrophage CL0000583
    CSI 1.41
    rCSI 2.33%
    PRS 71.11
  • lung macrophage CL1001603
    CSI 1.36
    rCSI 3.05%
    PRS 73.68
  • colon macrophage CL0009038
    CSI 0.83
    rCSI 3.83%
    PRS 83.22
  • intermediate monocyte CL0002393
    CSI 0.66
    rCSI 1%
    PRS 70.55
  • metallothionein-positive alveolar macrophage CL4033042
    CSI 0.49
    rCSI 5.37%
    PRS 83.35

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 [SIGLEC1](/details-gene/6614), also known as Sialoadhesin (CD169), is a cell surface receptor belonging to the Siglec family of sialic acid-binding immunoglobulin-like lectins. Located on chromosome 20p13, this protein plays a crucial role in cell-cell adhesion, pathogen recognition, and the regulation of immune responses. **Overall**, its expression is highly specific to macrophage and dendritic cell populations, including [Hofbauer cells](/details-cell/CL3000001) and [CD1c-positive myeloid dendritic cells](/details-cell/CL0002399), establishing it as a key marker for these myeloid lineages. Functionally, [SIGLEC1](/details-gene/6614) is implicated in the [adaptive immune system](/details-pathway/R-HSA-1280218) and inflammatory responses, and it has been identified as a host factor that can be exploited by various viruses, such as HIV-1, Ebola, and SARS-CoV-2, to facilitate their entry into and transmission between cells ([Link](https://doi.org/10.1371/journal.ppat.1006181), [Link](https://doi.org/10.1038/s41564-019-0453-2), [Link](https://doi.org/10.1038/s41423-021-00794-6)). ## Cellular Roles and Expression Landscape The expression profile of [SIGLEC1](/details-gene/6614) firmly establishes its identity as a marker of the mononuclear phagocyte system. **Overall**, the gene exhibits its highest significance in specialized tissue-resident macrophage populations and dendritic cells. The most prominent expression is observed in [Hofbauer cells](/details-cell/CL3000001) (CSI: 19.77), which are macrophages found in the placenta, and [CD1c-positive myeloid dendritic cells](/details-cell/CL0002399) (CSI: 9.51), a key subset of antigen-presenting cells. High significance is also consistently noted across various other macrophage subtypes, including [alternatively activated macrophages](/details-cell/CL0000890), [Kupffer cells](/details-cell/CL0000091) in the liver, and [alveolar macrophages](/details-cell/CL0000583) in the lung, as well as in circulating [monocytes](/details-cell/CL0000576) ([Link](https://doi.org/10.1182/blood.v97.1.288)). This specific expression pattern across professional antigen-presenting cells underscores its role in pathogen capture and immune surveillance at mucosal and systemic interfaces. ## Pathways and Molecular Function The functions of [SIGLEC1](/details-gene/6614) are centered on immune recognition and response modulation. Its molecular function as a carbohydrate-binding protein ([GO:0030246](https://www.ebi.ac.uk/QuickGO/term/GO:0030246)) allows it to mediate [cell-cell adhesion](/details-pathway/GO:0098609), a process critical for [immunoregulatory interactions between a lymphoid and a non-lymphoid cell](/details-pathway/R-HSA-198933). A critical aspect of [SIGLEC1](/details-gene/6614) function is its involvement in host-pathogen interactions. It acts as a receptor for sialylated ligands on the surface of various pathogens, leading to virion binding ([GO:0046790](https://www.ebi.ac.uk/QuickGO/term/GO:0046790)) and subsequent uptake via [clathrin-dependent endocytosis](/details-pathway/GO:0075512). This mechanism has been shown to be exploited by HIV-1 to enhance macrophage-to-T cell transmission ([Link](https://doi.org/10.1371/journal.ppat.1006181)), by Ebola virus to gain cellular entry ([Link](https://doi.org/10.1038/s41564-019-0453-2)), by SARS-CoV-2 for trans-infection by dendritic cells ([Link](https://doi.org/10.1038/s41423-021-00794-6)), and by meningococcal bacteria to enhance uptake ([Link](https://doi.org/10.1046/j.1365-2958.2003.03634.x)). Furthermore, engagement of [SIGLEC1](/details-gene/6614) can modulate the host immune response; for instance, it has been shown to suppress antiviral innate immunity by negatively regulating type I interferon production ([GO:0032480](https://www.ebi.ac.uk/QuickGO/term/GO:0032480)) through the degradation of TBK1 ([Link](https://doi.org/10.1038/cr.2015.108)). ## Research Directions The dual role of [SIGLEC1](/details-gene/6614) as both an immune receptor and a portal for pathogen entry presents compelling avenues for future research. Its high specificity for macrophages and dendritic cells makes it an attractive target for modulating immune responses and preventing infections. ### Proposed Hypotheses 1. Given its exceptionally high expression in placental [Hofbauer cells](/details-cell/CL3000001) and its known role as a viral receptor, we hypothesize that [SIGLEC1](/details-gene/6614) is a key mediator of vertical transmission for sialylated pathogens (e.g., Zika virus, cytomegalovirus) from mother to fetus by facilitating viral capture and transport across the placental barrier. 2. Based on its function in suppressing type I interferon production ([Link](https://doi.org/10.1038/cr.2015.108)), we hypothesize that pathogens binding to [SIGLEC1](/details-gene/6614) on dendritic cells and macrophages not only gain entry but also actively dampen the local antiviral state, thereby delaying immune activation and creating a favorable niche for initial replication. ### Experimental Approach To test the second hypothesis, an *in vitro* co-culture system could be established. Primary human [monocytes](/details-cell/CL0000576) would be differentiated into macrophages or dendritic cells. [SIGLEC1](/details-gene/6614) expression would be knocked out using CRISPR-Cas9 in one cohort, with a non-targeting gRNA serving as a control. These wild-type and knockout cells would then be challenged with a sialylated virus known to interact with [SIGLEC1](/details-gene/6614), such as SARS-CoV-2 pseudovirus. The induction of type I interferons (IFN-β) and pro-inflammatory cytokines (e.g., IL-6, TNF-α) would be quantified at both the mRNA (RT-qPCR) and protein (ELISA/CBA) levels over a time course. A significantly more robust and rapid interferon and inflammatory response in the [SIGLEC1](/details-gene/6614)-knockout cells compared to controls would provide strong evidence that pathogen engagement of this receptor constitutes an immune evasion strategy. ### Therapeutic Potential [SIGLEC1](/details-gene/6614) represents a promising therapeutic target for infectious diseases. As a cell surface receptor that facilitates the entry of multiple, structurally diverse viruses, its **inhibition** is a viable strategy. The development of high-affinity monoclonal antibodies or small-molecule inhibitors that block the sialic acid-binding domain could function as broad-spectrum antiviral agents. This approach would prevent viral attachment and internalization, effectively neutralizing pathogens before they can establish infection. The reported success of anti-Siglec-1 antibodies in blocking Ebola virus uptake provides proof-of-concept for this strategy ([Link](https://doi.org/10.1038/s41564-019-0453-2)).

Genular Protein ID: 3175592182

Symbol: SN_HUMAN

Name: Sialoadhesin

UniProtKB Accession Codes:

Q9BZZ2 Q96DL4 Q9GZS5 Q9H1H6 Q9H1H7 Q9H7L7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CPTC 1 CTD 1 ChEBI 3 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 2 EMBL 6 Ensembl 2 ExpressionAtlas 1 GO 12 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 4 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 1 RefSeq 8 SMART 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11133773

Title: Characterization of human sialoadhesin, a sialic acid binding receptor expressed by resident and inflammatory macrophage populations.

PubMed ID: 11133773

DOI: 10.1182/blood.v97.1.288

PubMed ID: 11780052

Title: The DNA sequence and comparative analysis of human chromosome 20.

PubMed ID: 11780052

DOI: 10.1038/414865a

PubMed ID: 11214971

Title: Characterization of long cDNA clones from human adult spleen.

PubMed ID: 11214971

DOI: 10.1093/dnares/7.6.357

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 12940982

Title: Recognition of sialylated meningococcal lipopolysaccharide by siglecs expressed on myeloid cells leads to enhanced bacterial uptake.

PubMed ID: 12940982

DOI: 10.1046/j.1365-2958.2003.03634.x

PubMed ID: 26358190

Title: Siglec1 suppresses antiviral innate immune response by inducing TBK1 degradation via the ubiquitin ligase TRIM27.

PubMed ID: 26358190

DOI: 10.1038/cr.2015.108

PubMed ID: 28129379

Title: Siglec-1 initiates formation of the virus-containing compartment and enhances macrophage-to-T cell transmission of HIV-1.

PubMed ID: 28129379

DOI: 10.1371/journal.ppat.1006181

PubMed ID: 31160823

Title: Anti-Siglec-1 antibodies block Ebola viral uptake and decrease cytoplasmic viral entry.

PubMed ID: 31160823

DOI: 10.1038/s41564-019-0453-2

PubMed ID: 33489013

Title: Dissemination of Mycobacterium tuberculosis is associated to a SIGLEC1 null variant that limits antigen exchange via trafficking extracellular vesicles.

PubMed ID: 33489013

DOI: 10.1002/jev2.12046

PubMed ID: 34782760

Title: SARS-CoV-2 interaction with Siglec-1 mediates trans-infection by dendritic cells.

PubMed ID: 34782760

DOI: 10.1038/s41423-021-00794-6

Sequence Information:

  • Length: 1709
  • Mass: 182624
  • Checksum: 587C7CCA0B789A6D
  • Sequence:
    • MGFLPKLLLL ASFFPAGQAS WGVSSPQDVQ GVKGSCLLIP CIFSFPADVE VPDGITAIWY 
YDYSGQRQVV SHSADPKLVE ARFRGRTEFM GNPEHRVCNL LLKDLQPEDS GSYNFRFEIS 
EVNRWSDVKG TLVTVTEEPR VPTIASPVEL LEGTEVDFNC STPYVCLQEQ VRLQWQGQDP 
ARSVTFNSQK FEPTGVGHLE TLHMAMSWQD HGRILRCQLS VANHRAQSEI HLQVKYAPKG 
VKILLSPSGR NILPGELVTL TCQVNSSYPA VSSIKWLKDG VRLQTKTGVL HLPQAAWSDA 
GVYTCQAENG VGSLVSPPIS LHIFMAEVQV SPAGPILENQ TVTLVCNTPN EAPSDLRYSW 
YKNHVLLEDA HSHTLRLHLA TRADTGFYFC EVQNVHGSER SGPVSVVVNH PPLTPVLTAF 
LETQAGLVGI LHCSVVSEPL ATLVLSHGGH ILASTSGDSD HSPRFSGTSG PNSLRLEIRD 
LEETDSGEYK CSATNSLGNA TSTLDFHANA ARLLISPAAE VVEGQAVTLS CRSGLSPTPD 
ARFSWYLNGA LLHEGPGSSL LLPAASSTDA GSYHCRARDG HSASGPSSPA VLTVLYPPRQ 
PTFTTRLDLD AAGAGAGRRG LLLCRVDSDP PARLQLLHKD RVVATSLPSG GGCSTCGGCS 
PRMKVTKAPN LLRVEIHNPL LEEEGLYLCE ASNALGNAST SATFNGQATV LAIAPSHTLQ 
EGTEANLTCN VSREAAGSPA NFSWFRNGVL WAQGPLETVT LLPVARTDAA LYACRILTEA 
GAQLSTPVLL SVLYPPDRPK LSALLDMGQG HMALFICTVD SRPLALLALF HGEHLLATSL 
GPQVPSHGRF QAKAEANSLK LEVRELGLGD SGSYRCEATN VLGSSNTSLF FQVRGAWVQV 
SPSPELQEGQ AVVLSCQVHT GVPEGTSYRW YRDGQPLQES TSATLRFAAI TLTQAGAYHC 
QAQAPGSATT SLAAPISLHV SYAPRHVTLT TLMDTGPGRL GLLLCRVDSD PPAQLRLLHG 
DRLVASTLQG VGGPEGSSPR LHVAVAPNTL RLEIHGAMLE DEGVYICEAS NTLGQASASA 
DFDAQAVNVQ VWPGATVREG QLVNLTCLVW TTHPAQLTYT WYQDGQQRLD AHSIPLPNVT 
VRDATSYRCG VGPPGRAPRL SRPITLDVLY APRNLRLTYL LESHGGQLAL VLCTVDSRPP 
AQLALSHAGR LLASSTAASV PNTLRLELRG PQPRDEGFYS CSARSPLGQA NTSLELRLEG 
VRVILAPEAA VPEGAPITVT CADPAAHAPT LYTWYHNGRW LQEGPAASLS FLVATRAHAG 
AYSCQAQDAQ GTRSSRPAAL QVLYAPQDAV LSSFRDSRAR SMAVIQCTVD SEPPAELALS 
HDGKVLATSS GVHSLASGTG HVQVARNALR LQVQDVPAGD DTYVCTAQNL LGSISTIGRL 
QVEGARVVAE PGLDVPEGAA LNLSCRLLGG PGPVGNSTFA WFWNDRRLHA EPVPTLAFTH 
VARAQAGMYH CLAELPTGAA ASAPVMLRVL YPPKTPTMMV FVEPEGGLRG ILDCRVDSEP 
LASLTLHLGS RLVASSQPQG APAEPHIHVL ASPNALRVDI EALRPSDQGE YICSASNVLG 
SASTSTYFGV RALHRLHQFQ QLLWVLGLLV GLLLLLLGLG ACYTWRRRRV CKQSMGENSV 
EMAFQKETTQ LIDPDAATCE TSTCAPPLG