HumanLectome - Human Lectin Entry

NCBI Summary

This gene encodes a C-type lectin that functions in cell adhesion and pathogen recognition. This receptor recognizes a wide range of evolutionarily divergent pathogens with a large impact on public health, including leprosy and tuberculosis mycobacteria, the Ebola, hepatitis C, HIV-1 and Dengue viruses, and the SARS-CoV acute respiratory syndrome coronavirus. The protein is organized into four distinct domains: a C-terminal carbohydrate recognition domain, a flexible tandem-repeat neck domain, a transmembrane region and an N-terminal cytoplasmic domain involved in internalization. This gene is closely related in terms of both sequence and function to a neighboring gene, CLEC4M (Gene ID: 10332), also known as L-SIGN. The two genes differ in viral recognition and expression patterns, with this gene showing high expression on the surface of dendritic cells. Polymorphisms in the neck region are associated with protection from HIV-1 infection, while single nucleotide polymorphisms in the promoter of this gene are associated with differing resistance and susceptibility to and severity of infectious disease, including rs4804803, which is associated with SARS severity. [provided by RefSeq, May 2020].

Protein

Protein (NP_066978)

Protein name

CLEC4L - DC-SIGN

Synonym(s)

CD209 antigen (C-type lectin domain family 4 member L) (Dendritic cell-specific ICAM-3-grabbing non-integrin 1) (DC-SIGN) (DC-SIGN1) (CD antigen CD209)

HGNC gene name

CD209

HGNC name

CD209 molecule

Protein_CD_name

CD209

Lectin confidence

Curated

UniLectin class

C-type lectin

C-type classification

CLEC4L

Known lectin group

C-type - Type II transmembrane receptors

Lectin fold

a/b mixed / C-type lectin-like

Glycan specificity

Man, Fuc, GlcNAc / Oligomannose and Lewis oligosaccharides

RefSeq accession

Gene ID

UniProt accession

Ensembl protein ID

UniRef cluster ID

LectomeXplore score

0.614

Reference

10.1038/nsmb784

Other links

PFAM, InterPro, CFG data

Protein sequence and protein families (fasta) (404 amino acids) Download

MSDSKEPRLQQLGLLEEEQLRGLGFRQTRGYKSLAGCLGHGPLVLQLLSFTLLAGLLVQVSKVPSSISQEQSRQDAIYQNLTQLKAAVGELSEKSKLQEIYQELTQLKAAVGELPEKSKLQEIYQELTRLKAAVGELPEKSKLQEIYQELTWLKAAVGELPEKSKMQEIYQELTRLKAAVGELPEKSKQQEIYQELTRLKAAVGELPEKSKQQEIYQELTRLKAAVGELPEKSKQQEIYQELTQLKAAVERLCHPCPWEWTFFQGNCYFMSNSQRNWHDSITACKEVGAQLVVIKSAEEQNFLQLQSSRSNRFTWMGLSDLNQEGTWQWVDGSPLLPSFKQYWNRGEPNNVGEEDCAEFSGNGWNDDKCNLAKFWICKKSAASCSRDEEQFLSPAPATPNPPPA

Mol* PDB structure viewerUniLectin3D

Select a PDB entry:

Structural models

AlphaFold v2: AF-Q9NNX6-F1 Download

Model Confidence:

Very high (pLDDT > 90)
Confident (90 > pLDDT > 70)
Low (70 > pLDDT > 50)
Very low (pLDDT < 50)

AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.

Oligomerization and Known Interactions

Homotetramer. Interacts with C1QBP; the interaction is indicative for a C1q:C1QBP:CD209 signaling complex. Interacts (via C-type lectin domain) with CEACAM1 (via Lewis X moieties); this interaction is regulated by the glycosylation pattern of CEACAM1 on cell types and regulates contact between dendritic cells and neutrophils (PubMed:16246332)

(Microbial infection) Interacts with HIV-1 and HIV-2 gp120 (PubMed:11799126, PubMed:12502850, PubMed:1518869)

(Microbial infection) Interacts with ebolavirus envelope glycoproteins (PubMed:12502850, PubMed:12504546)

(Microbial infection) Interacts with cytomegalovirus gB protein (PubMed:12433371, PubMed:22496863)

(Microbial infection) Interacts with HCV E2 protein (PubMed:15371595, PubMed:16816373)

(Microbial infection) Interacts with dengue virus major envelope protein E

(Microbial infection) Interacts with measles hemagglutinin

(Microbial infection) Interacts with herpes simplex virus 1 surface proteins

(Microbial infection) Interacts with Influenzavirus A hemagglutinin

(Microbial infection) Interacts with SARS-CoV spike glycoprotein

(Microbial infection) Interacts with Japanese encephalitis virus E protein

(Microbial infection) Interacts with Lassa virus Glycoprotein

(Microbial infection) Interacts with marburg virus glycoprotein

(Microbial infection) Interacts with Respiratory syncytial virus glycoprotein G

(Microbial infection) Interacts with Rift valley fever virus and uukuniemi virus envelope glycoprotein

(Microbial infection) Interacts with west-nile virus envelope glycoprotein

(Microbial infection) Interacts with whole M.bovis cells in a Ca(2+)-dependent and independent manner; in vitro experiments suggest it interacts with CH60.1 (groL1), DnaK, GADPH (gap) and LrpG (PubMed:21203928)

Annotation

Ligand

Glycan ligands from structural data

Name

aMan16(aMan13)aMan16Man

IUPAC

Man(a1-6)[Man(a1-3)]Man(a1-6)Man

PDB

1SL4

UniLectin3D

1SL4

Parent structures

GlyConnect Structures

Name

aMan12aMan13aMan

IUPAC

Man(a1-2)Man(a1-3)Man

PDB

2IT5

UniLectin3D

2IT5

Parent structures

GlyConnect Structures

Name

bGal14(aFuc13)bGlcNAc13bGal14Glc

IUPAC

Gal(b1-4)[Fuc(a1-3)]GlcNAc(b1-3)Gal(b1-4)Glc

PDB

1SL5

UniLectin3D

1SL5

Parent structures

GlyConnect Structures

Name

bGlcNAc12aMan13(bGlcNAc12aMan16)Man

IUPAC

GlcNAc(b1-2)Man(a1-3)[GlcNAc(b1-2)Man(a1-6)]Man

PDB

1K9I

UniLectin3D

1K9I

Parent structures

GlyConnect Structures

Name

aMan12aMan

IUPAC

Man(a1-2)Man

PDB

2IT6

UniLectin3D

2IT6

Parent structures

GlyConnect Structures

Name

Di-mannoside mimic, synthetic analog of trimannoside

IUPAC

Man

PDB

2XR5, 2XR6, 6GHV

UniLectin3D

2XR5, 2XR6, 6GHV

Parent structures

GlyConnect Structures

Expression

Human Protein Atlas

GeneCards

Functionality temporarily unavailable.

ProteomicsDB

References

NCBI References (10 PubMed Identifiers)

Lectins enhance SARS-CoV-2 infection and influence neutralizing antibodies. [34464958]

SARS-CoV-2 Impairs Dendritic Cells and Regulates DC-SIGN Gene Expression in Tissues. [34502134]

CD209L/L-SIGN and CD209/DC-SIGN act as receptors for SARS-CoV-2. [32607506]

COVID-19, Renin-Angiotensin System and Endothelial Dysfunction. [32660065]

DC-SIGN, DC-SIGNR and LSECtin: C-type lectins for infection. [24156700]

CD209 (DC-SIGN) -336A>G promoter polymorphism and severe acute respiratory syndrome in Hong Kong Chinese. [20359516]

DC-SIGN. a related gene, DC-SIGNR. and CD23 form a cluster on 19p13. [10975799]

DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. [10721995]

Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. [10721994]

Sequence and expression of a membrane-associated C-type lectin that exhibits CD4-independent binding of human immunodeficiency virus envelope glycoprotein gp120. [1518869]

UniProt Main References (39 PubMed Identifiers)

A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection. [11257134]

Extensive repertoire of membrane-bound and soluble dendritic cell-specific ICAM-3-grabbing nonintegrin 1 (DC-SIGN1) and DC-SIGN2 isoforms. Inter-individual variation in expression of DC-SIGN transcripts. [11337487]

Complete sequencing and characterization of 21,243 full-length human cDNAs. [14702039]

The DNA sequence and biology of human chromosome 19. [15057824]

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). [15489334]

DC-SIGN-ICAM-2 interaction mediates dendritic cell trafficking. [11017109]

A novel mechanism of carbohydrate recognition by the C-type lectins DC-SIGN and DC-SIGNR. Subunit organization and binding to multivalent ligands. [11384997]

Human cytomegalovirus binding to DC-SIGN is required for dendritic cell infection and target cell trans-infection. [12433371]

Identification of different binding sites in the dendritic cell-specific receptor DC-SIGN for intercellular adhesion molecule 3 and HIV-1. [11799126]

The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells. [11859097]

Differential N-linked glycosylation of human immunodeficiency virus and Ebola virus envelope glycoproteins modulates interactions with DC-SIGN and DC-SIGNR. [12502850]

DC-SIGN (CD209) mediates dengue virus infection of human dendritic cells. [12682107]

Inhibition of human immunodeficiency virus type 1 Env-mediated fusion by DC-SIGN. [12692233]

Cutting edge: carbohydrate profiling identifies new pathogens that interact with dendritic cell-specific ICAM-3-grabbing nonintegrin on dendritic cells. [12574325]

DC-SIGN: escape mechanism for pathogens. [12949494]

The role of dendritic cell C-type lectin receptors in HIV pathogenesis. [12960229]

DC-SIGN and DC-SIGNR bind ebola glycoproteins and enhance infection of macrophages and endothelial cells. [12504546]

L-SIGN (CD209L) and DC-SIGN (CD209) mediate transinfection of liver cells by hepatitis C virus. [15371595]

pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN. [15140961]

DC-SIGN and DC-SIGNR interact with the glycoprotein of Marburg virus and the S protein of severe acute respiratory syndrome coronavirus. [15479853]

Interactions of DC-SIGN with Mac-1 and CEACAM1 regulate contact between dendritic cells and neutrophils. [16246332]

A variant in the CD209 promoter is associated with severity of dengue disease. [15838506]

Deciphering the molecular bases of Mycobacterium tuberculosis binding to the lectin DC-SIGN reveals an underestimated complexity. [16092920]

Promoter variation in the DC-SIGN-encoding gene CD209 is associated with tuberculosis. [16379498]

Measles virus targets DC-SIGN to enhance dendritic cell infection. [16537615]

West Nile virus discriminates between DC-SIGN and DC-SIGNR for cellular attachment and infection. [16415006]

Expression of DC-SIGN and DC-SIGNR on human sinusoidal endothelium: a role for capturing hepatitis C virus particles. [16816373]

Identification of four novel DC-SIGN ligands on Mycobacterium bovis BCG. [21203928]

DC-SIGN, C1q, and gC1qR form a trimolecular receptor complex on the surface of monocyte-derived immature dendritic cells. [22700724]

Dendritic cells mediate herpes simplex virus infection and transmission through the C-type lectin DC-SIGN. [18796707]

N-linked glycosylation facilitates sialic acid-independent attachment and entry of influenza A viruses into cells expressing DC-SIGN or L-SIGN. [21191006]

DC-SIGN as a receptor for phleboviruses. [21767814]

Structural basis for selective recognition of oligosaccharides by DC-SIGN and DC-SIGNR. [11739956]

Human cytomegalovirus entry into dendritic cells occurs via a macropinocytosis-like pathway in a pH-independent and cholesterol-dependent manner. [22496863]

Respiratory syncytial virus glycoprotein G interacts with DC-SIGN and L-SIGN to activate ERK1 and ERK2. [22090124]

Distinct usage of three C-type lectins by Japanese encephalitis virus: DC-SIGN, DC-SIGNR, and LSECtin. [24623090]

Role of DC-SIGN in Lassa virus entry into human dendritic cells. [23966408]

Virus entry: old viruses, new receptors. [22440960]

All isoforms of this gene containing a lectin domain

NP_001138365.1, NP_001138366.1, NP_001138368.1, NP_066978.1, NP_001138371.1, NP_001138367.1, NP_001138369.1

RNA

RNA (Transcript ID: NM_021155.4)

RNA RefSeq ID

NM_021155.4

RNA name

CD209 molecule, transcript variant 1

Isoforms

All isoforms of CD209 containing a lectin domain

RNA Ensembl ID

ENST00000315599.12

Coding region

24..1238 (or 7743039.. 7747511)

mRNA location

7739993.. 7747534

NCBI Matured mRNA sequence 4284 NTP Download

m⁷G-5')ppp(5'-ACACUGGGGGAGAGUGGGGUGACAUGAGUGACUCCAAGGAACCAAGACUGCAGCAGCUGGGCCUCCUGGAGGAGGAACAGCUGAGAGGCCUUGGAUUCCGACAGACUCGAGGAUACAAGAGCUUAGCAGGGUGUCUUGGCCAUGGUCCCCUGGUGCUGCAACUCCUCUCCUUCACGCUCUUGGCUGGGCUCCUUGUCCAAGUGUCCAAGGUCCCCAGCUCCAUAAGUCAGGAACAAUCCAGGCAAGACGCGAUCUACCAGAACCUGACCCAGCUUAAAGCUGCAGUGGGUGAGCUCUCAGAGAAAUCCAAGCUGCAGGAGAUCUACCAGGAGCUGACCCAGCUGAAGGCUGCAGUGGGUGAGCUUCCAGAGAAAUCUAAGCUGCAGGAGAUCUACCAGGAGCUGACCCGGCUGAAGGCUGCAGUGGGUGAGCUUCCAGAGAAAUCUAAGCUGCAGGAGAUCUACCAGGAGCUGACCUGGCUGAAGGCUGCAGUGGGUGAGCUUCCAGAGAAAUCUAAGAUGCAGGAGAUCUACCAGGAGCUGACUCGGCUGAAGGCUGCAGUGGGUGAGCUUCCAGAGAAAUCUAAGCAGCAGGAGAUCUACCAGGAGCUGACCCGGCUGAAGGCUGCAGUGGGUGAGCUUCCAGAGAAAUCUAAGCAGCAGGAGAUCUACCAGGAGCUGACCCGGCUGAAGGCUGCAGUGGGUGAGCUUCCAGAGAAAUCUAAGCAGCAGGAGAUCUACCAGGAGCUGACCCAGCUGAAGGCUGCAGUGGAACGCCUGUGCCACCCCUGUCCCUGGGAAUGGACAUUCUUCCAAGGAAACUGUUACUUCAUGUCUAACUCCCAGCGGAACUGGCACGACUCCAUCACCGCCUGCAAAGAAGUGGGGGCCCAGCUCGUCGUAAUCAAAAGUGCUGAGGAGCAGAACUUCCUACAGCUGCAGUCUUCCAGAAGUAACCGCUUCACCUGGAUGGGACUUUCAGAUCUAAAUCAGGAAGGCACGUGGCAAUGGGUGGACGGCUCACCUCUGUUGCCCAGCUUCAAGCAGUAUUGGAACAGAGGAGAGCCCAACAACGUUGGGGAGGAAGACUGCGCGGAAUUUAGUGGCAAUGGCUGGAACGACGACAAAUGUAAUCUUGCCAAAUUCUGGAUCUGCAAAAAGUCCGCAGCCUCCUGCUCCAGGGAUGAAGAACAGUUUCUUUCUCCAGCCCCUGCCACCCCAAACCCCCCUCCUGCGUAGCAGAACUUCACCCCCUUUUAAGCUACAGUUCCUUCUCUCCAUCCUUCGACCUUCACAAAAUCUCUGGGACUGUUCUUUGUCAGAUUCUUCCUCCUUUAGAAGGCUGGGUCCCAUUCUGUCCUUCUUGUCAUGCCUCCAAUUUCCCCUGGUGUAGAGCUUGUUUUUCUGGCCCAUCCUUGGAGCUUUAUGAGUGAGCUGGUGUGGGAUGCCUUUGGGGGUGGACUUGUGUUCCAAGAAUCCACUCUCUCUUCCUUUUGGAGAUUAGGAUAUUUGGGUUGCCAUGUGUAGCUGCUAUGUCCCCUGGGGCGUUAUCUUAUACAUGCAAACCUACCAUCUGUUCAACUUCCACCUACCACCUCCUGCACCCCUUUGAUCGGGGACUUACUGGUUGCAAGAGCUCAUUUUGCAGGCUGGAAGCACCAGGGAAUUAAUUCCCCCAGUCAACCAAUGGCACCCAGAGAGGGCAUGGAGGCUCCACGCAACCCCUUCCACCCCCACAUCUUCCUUUGUCUUAUACAUGGCUUCCAUUUGGCUGUUUCUAAGUUGUAUUCUUUAUUUUAUUAUUAUUAUUACUAUUUUUCGAGAUGGAGUUUCACUCUUGUCGCUCAGGCUGGAGUGCCAUGGCGCGAUCUUGGCUCACUGCAACCUCUGCCUCCCGGGUUCAAGUGAUUCUCCUGCCUCAGCCUCACGAGUAGCUGGAAUUACAGGCAGGCGCCACCAGACCCGGCUAAUUUUUUGUAUUUUUAGUACAGAUGGGGUUUCUCCGUGUUGGUCAGGCUGGUCUUGAACUCCCGACCUCAGAUGAUCUGCCCGCCUCGGCCUCCCAAAAUUGCUGGGAUUACAGGUGUGAGCCACCGCGCCUGGCCUAUUAUUUUUUGUAAGAAUAAAACAGGUUUAUUGGGAUUUGGGACUCUGAACAGUUCUGUCUCUACUACCUGAUCUCCUCCUACCACGACUUUGGGAUCUAGAGGAGCUUUGGCUCCGGCUGUGACGGCUCCGGCCGUUCUCACUGCGGCUGCACCGGCCCCCGCUGCGGUCACUAUUUCUUCCUCUGCUAGGUGAAUUGUGCCUCUCCUGGCUCUUUGACAUGUGCUAGUGAGAUUUCUUCCUUUUCCUUUCGGAUUCCCCAUUUCUUUUGUAGGAAUGGUCUGGACUAGGGUUCUCCUUCCCCGCAGCCUGUAGUAUUCAUCGUGGUGGCCCACCCUCUCUCUCCCCUUGGAGCUCUUGCCAAAGGAGGAGACAAGCAGAGGUCUCUAUUGGAUUUCUCAACACCUGAAGAAAGUUGCAGUGUUUUCCUCUUGGACAUUGUUGUAUUUCAAAUAAACCACAAAUCAUCAUUUUCCACCGAGCCACUGGGCAGAAUUCACACUGAAGCUGUCGUCCUGCGUACAUACCAUCGUCCGUUAAACAGAGAAAGAGCUGCUUGGCAUUCUUCUUCCGACUGGUACUGAACAUAUAUACUUGCCCCUCAGGUGAGGUUCCAAGUUGCAACUGACCUUGAACUGAAUCACUCUCCCCACGUUAUUUUUUAAUUACUAUUUUUUUUUAAAGAUGGGGUCUUGCUCUGUCGCCAGGCUGGAGUGCAGUGGCGCGAUCUAGGCUCACUGCAACUUCCGCCUCCCGGGUUCAAGCGAUUCUCCUGCCUCAGCCUCCCGAGUAGCUGGGACUCCACUAAAAGUACAAAAAUUAGCUGGGCGUGCACCACUGCGCCCAGCUAAUUCUUGUAUUUUUGGUAGAGACGGGGUUUCAACAUGUUGACCAGGAUGGUCUCGAUCUCUUGACCUCGUGAUUCGCCCGCCGCGUCCUCCCAAAGUGCUGGGAUUACAGGCCUGAGCCACCGCGCCCAGUCUCUCCCCACGUUCUUGAACUCGGGCAGCACAUCCUCACAGAAAUCUAGGAACUGUUGGUAGGUUUCUUCCUCGCUGUACUCCAGGCUUGCUUCGGAGUCAUAGUCAUCCCUCCUGCACUGCUCCUUUCCAAACACUGUAAACAUGCUUUUAAUAAGAAGGGUAGGACUGGAUGUUGGGAAAUCAUGUGAACAUCUAUCUCCAAAUCUGCAAGCUCCUGUUUUACUGUAGAAGGGACAAUUAACUCCAUCCUUCUCCAUGACUCUGAAAUCCAAGGGGGGGUUCCGGGUUUUGCCAUGUGGCGCCAUUUUCCAACUCAUUUUCAGCCUGAUCCAGCAUCUUCUGGACAGCUUCCGGUUUUUGUUUCUUCUGUCGUUUCUGUUCCUCCUCCUCUCUCUCUUUCCUCUGCUGUUCUUCCCAUUGUUCCUUUAACUUUCGCUCUUGUUCUUGCCGUUUUCUAGCCACCUCUUCCUUUUCCUUCUUUAUUCUGAAUUCUUCUUGUGCCUUCUGCUCUCUCAGCAACCACUCCUCAUGUAAUCUUUGCCUCUCUCUUCCCCAUAGCUUUUCUAGUUGUUGUUUUUCAAUAAAAGUGUCCUCCUCUUUCUGUGAGAGUCCUGAGUCCCUCAGUGGAGCAAGUUCCUGCUGGCGUUUCUUUCGUUUCUCCUUCUUCAGGGCGGCCCUGUACUUUUUGUGGCUUGGUUUCUCUGGAAAUGUCACCUUUUCGGGCGCAGCCAUCUUGCCGGCACCGCCCCGCCCCUCUAGUUGUAUCCUUUAUAAUAAACUGGUAAACAUUGUAACCGCAGAUUCAGCCCAAUCUGGUUCAACUUUGUGUAAUAAAAUGGCGAGUUGUUUUUCAGUUGUCGUGGACCCCCAGGUUGCAAGUUACAUACCCUGGGCAUGUCCAGAUGAACGAAGCGUGCAAAUCCACGUGGAACCUAAGUGCUCAGACCGAGGAACAGGGACUGAGUUAAGAAGUGGACACCACGUGGCAUGAUCCUUGAUCCAAUCAGAUUGAGCCCUGGCGUGAUCCAGUCAGAUCAAGCCUCCUGAAUCCCCUCAUUACAAGAUCCAAUCAUAUCAUGCCUCACUACCCUCUGUAUAUAAAAUCUGCCCCAGCCUCCAACUUGGAGAGACAGAUUUGGGCCAGACUCCUGUGUCCUUGCUUGGCUGCCUUGCAAUAAAUUUUUCUCUCUACAAAA-3'- Poly-A tail

Coding region

mRNA-related data

DNA

DNA (Gene ID: 30835)

HGNC Gene symbol

CD209

HGNC Gene name

CD209 molecule

Chr. RefSeq ID

NC_000019.10

Chromosome N°

19 7743039.. 7747511

CDS location

7743039.. 7747511

DNA strand

strand -

CCDS ID

CCDS12186.1

Mouse ortholog gene

MGI:1916415;MGI:2157942;MGI:2157945;MGI:2157947;MGI:2157948

Gene Variant

ClinVar, dbVar

DNA Ensembl ID

ENSG00000090659

HGNC other symbol

DC-SIGN, hDC-SIGN, CDSIGN, DC-SIGN1, CLEC4L

UCSC ID

uc002mht.3

GeneBank

INSDC: M98457

GeneCards

1641

MIM

604672

VEGA ID

OTTHUMG00000182530

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