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CD209 CD209 molecule [ Homo sapiens (human) ]

Gene ID: 30835, updated on 23-Sep-2014
Official Symbol
CD209provided by HGNC
Official Full Name
CD209 moleculeprovided by HGNC
Primary source
HGNC:HGNC:1641
See related
Ensembl:ENSG00000090659; HPRD:05241; MIM:604672; Vega:OTTHUMG00000182530
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CDSIGN; CLEC4L; DC-SIGN; DC-SIGN1
Summary
This gene encodes a transmembrane receptor and is often referred to as DC-SIGN because of its expression on the surface of dendritic cells and macrophages. The encoded protein is involved in the innate immune system and recognizes numerous evolutionarily divergent pathogens ranging from parasites to viruses with a large impact on public health. The protein is organized into three distinct domains: an N-terminal transmembrane domain, a tandem-repeat neck domain and C-type lectin carbohydrate recognition domain. The extracellular region consisting of the C-type lectin and neck domains has a dual function as a pathogen recognition receptor and a cell adhesion receptor by binding carbohydrate ligands on the surface of microbes and endogenous cells. The neck region is important for homo-oligomerization which allows the receptor to bind multivalent ligands with high avidity. Variations in the number of 23 amino acid repeats in the neck domain of this protein are rare but have a significant impact on ligand binding ability. This gene is closely related in terms of both sequence and function to a neighboring gene (GeneID 10332; often referred to as L-SIGN). DC-SIGN and L-SIGN differ in their ligand-binding properties and distribution. Alternative splicing results in multiple variants.[provided by RefSeq, Feb 2009]
See CD209 in Epigenomics, MapViewer
Location:
19p13
Exon count:
7
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 19 NC_000019.10 (7739993..7747611, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (7804879..7812499, complement)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene Fc fragment of IgE, low affinity II, receptor for (CD23) Neighboring gene C-type lectin domain family 4, member G Neighboring gene zinc finger (CCCH type), RNA-binding motif and serine/arginine rich 2 pseudogene Neighboring gene ribosomal protein L21 pseudogene 129 Neighboring gene C-type lectin domain family 4, member M

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Replication interactions

Interaction Pubs
Knockdown of DC-SIGN (CD209) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env Binding of HIV-1 gp120 to DC-SIGN leads to excessive ASK-1 activation and promotes ASK-1-dependent apoptosis in human dendritic cells PubMed
env Binding of HIV-1 gp120 to DC-SIGN sensitizes monocyte-derived dendritic cells for CD40L-mediated apoptosis PubMed
env HIV-1 gp120 downregulates HIV-1 Nef dependent IL-6 release, which requires the interaction of gp120 with DC-SIGN in immature dentritic cells PubMed
env CD4-linker-DC-SIGN fusion proteins enhance binding affinity to HIV-1 gp140 and gp120 in comparison to sCD4 and sDC-SIGN. These fusion proteins inhibit HIV-1 capture and transfer via DC-SIGN-expressing cells and iMDDCs PubMed
env DC-SIGN is strongly upregulated in M2a-polarized monocyte-derived-macrophages (MDMs), which leads to facilitate HIV-1 entry via gp120/gp41 and DNA synthesis in M2a-MDMs and to efficiently transmit both R5 and X4 HIV-1 to CD4+ T cells PubMed
env Enrichment of oligomannose N-glycans on HIV-1 gp120 enhances DC-SIGN binding but reduces the subsequent transmission to target cells PubMed
env DC-SIGN engagement by HIV-1 gp120 on dendritic cell (DC) surface subsequently activates Cdc42, Pak1, and Wasp, leading to an increase in membrane extensions at the DC surface PubMed
env AM3 (Inmunoferon) inhibits the interaction of DC-SIGN with both ICAM3 and HIV-1 gp120 protein and blocks the DC-SIGN-dependent capture of HIV virions and the HIV trans-infection capability of DC-SIGN transfectants PubMed
env Raji-DC-SIGN cells preferentially enhance CXCR4 usage of dual-tropic HIV-1 with higher V3 charges in gp120 PubMed
env DC-SIGN triacidic cluster (353EEE355) mutant is impaired in receptor-mediated endocytosis of HIV-1 gp120 in transfected human myeloid K-562 cells PubMed
env One HIV-1 gp120 triple glycosylation mutant form 134mut (carrying N293Q, N382Q, and N388Q mutations in gp120) exhibits a significant increase in sensitivity to both mannan competition and endoglycosidase H digestion in a DC-SIGN binding assay PubMed
env Mermaid shares glycan specificity with DC-SIGN and inhibits the interaction between DC-SIGN and HIV-1 gp120 PubMed
env Oligomannose glycans play as ligands for DC-SIGN, and can inhibit the binding of gp120 to 2G12 and recombinant dimeric DC-SIGN PubMed
env End-stage CCR5-tropic HIV-1 have a reduced ability to use DC-SIGN resulting from the loss of potential N-linked glycosylation sites (PNGS) in the gp120 V2 and V4 regions, which are present in the majority of chronic stage CCR5-tropic variants PubMed
env Expression of CD4 on Raji B cells strongly inhibits DC-SIGN-mediated HIV-1 (gp120) transmission to T cells; co-expression of CD4 and DC-SIGN in Raji cells promotes internalization and intracellular retention of HIV-1 PubMed
env Monoclonal antibodies produced from hybridoma clones recognize DC-SIGN on monocyte-derived dendritic cells and on dermal-type macrophages to interfere with DC-SIGN binding to HIV-1 gp120 PubMed
env Glycopolymers effectively prevent the interactions between a human dendritic cell associated lectin (DC-SIGN) and the HIV-1 gp120 PubMed
env HIV-1 gp120 N275Q or N351Q mutants isolated from recombinant CRF07_BC decrease significantly to the DC-SIGN-binding capacity, indicating that the N275 and N351 glycan sites mediate the interaction between CRF07_BC gp120 and DC-SIGN PubMed
env Using an siRNA approach indicates DC-SIGN is not required for efficient trans-enhancement of HIV-1 (gp120) infectivity by dendritic cells (DCs) PubMed
env Bile salt-stimulated lipase (BSSL) isolated from human milk binds to DC-SIGN, preventing HIV-1 gp120 from interacting with this receptor PubMed
env HIV-1 gp120 binds to B cells through mannose C-type lectin receptors (MCLRs), such as DC-SIGN, mannose receptor, and langerin PubMed
env Interaction of gp120 with DC-SIGN activates Raf-1 and phosphorylates Raf-1 at positions Ser338, Tyr340, and Tyr341 PubMed
env DC-SIGN-mediated blockage of HIV budding is due to internalization of gp120 by DC-SIGN. The 364 amino-acid residues of extracellular and transmembrane domains in DC-SIGN are essential for the blockage PubMed
env Human milk oligosaccharides reduce HIV-1-gp120 binding to dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN) PubMed
env Crystal structures of carbohydrate-recognition domains of DC-SIGN and of DC-SIGNR in combination with binding studies reveal that these receptors selectively recognize endogenous high-mannose oligosaccharides of HIV-1 gp120 PubMed
env The cis expression of DC-SIGN on multiple lymphoid cell lines enables more efficient entry and replication of CXCR4-tropic and CCR5/CXCR4 dual-tropic HIV-1 through its binding to the HIV-1 gp120-CD4-CXCR4 complex PubMed
env Bovine lactoferrin (bLF) binds strongly to DC-SIGN, thus blocking the interaction between DC-SIGN and HIV-1 gp120 and preventing virus capture and subsequent transmission; bLF is a much more efficient inhibitor of transmission than human lactoferrin PubMed
env Binding of HIV-1 gp120 to DC-SIGN does not result in increased adhesion levels of LFA-1 to its ligand ICAM-1 in both immature dendritic cells (DC) and Raji-DC-SIGN cells PubMed
env DC-SIGN tetramers are essential for high affinity interactions with the HIV-1 high mannose glycoprotein gp120 PubMed
env Mutagenesis of conserved residues (Gly-346, Glu-347, Asn-349, Glu-354, and Asp-355) of DC-SIGN significantly compromises binding to HIV-1 gp120 PubMed
env DC-SIGN and MBL bind primarily to glycans on HIV-1 gp120/gp41; preincubation of CXCR4-, CCR5- or dual-tropic HIV-1 strains with MBL prevents DC-SIGN-mediated trans infection of T cells PubMed
env The HIV-1 gp120 binding site in DC-SIGN is different from that of ICAM-2 and ICAM-3; alanine-scanning mutagenesis of DC-SIGN at N311, R345, V351, G352, E353, S360, G361, and N362 abrogate ICAM-2/3 binding, whereas the HIV-1 gp120 interaction is unaffected PubMed
env A dendritic cells (DC)-specific C-type lectin, DC-SIGN, is highly expressed on DC present in mucosal tissues, binds to the HIV-1 envelope glycoprotein gp120, and facilitates infection of HIV-1 permissive cells in trans PubMed
Envelope surface glycoprotein gp160, precursor env CD4-linker-DC-SIGN fusion proteins enhance binding affinity to HIV-1 gp140 and gp120 in comparison to sCD4 and sDC-SIGN. These fusion proteins inhibit HIV-1 capture and transfer via DC-SIGN-expressing cells and iMDDCs PubMed
env Enrichment of oligomannose N-glycans on HIV-1 gp140 enhances DC-SIGN binding but reduces the subsequent transmission to target cells PubMed
env DC-SIGN binding to the HIV envelope protein effectively increases exposure of the CD4 binding site, which leads to enhance the relative rate of infection of the CD4-dependent strain PubMed
env DC-SIGN increases the binding affinity of trimeric gp140 envelope glycoproteins to CD4 on permissive cell surface PubMed
Nef nef HIV-1 gp120 downregulates HIV-1 Nef dependent IL-6 release, which requires the interaction of gp120 with DC-SIGN in immature dentritic cells PubMed
nef Mutation of the dileucine motif at amino acids 165-166 of HIV-1 Nef abolishes the Nef-mediated upregulation of DC-SIGN on the surface of HIV-1 infected dendritic cells PubMed
nef HIV-1 Nef upregulates DC-SIGN in HIV-1 infected dendritic cells by inhibiting DC-SIGN endocytosis, which dramatically increases clustering of dendritic cells with T lymphocytes, thereby enhancing HIV-1 transmission PubMed
nef Substitution of HIV-1 Nef acidic residue E160 with uncharged residues impairs the ability of Nef to upregulate the expression of DC-SIGN and the invariant chain of MHC class II at the cell surface PubMed

Go to the HIV-1, Human Interaction Database

  • Measles, organism-specific biosystem (from KEGG)
    Measles, organism-specific biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
  • Measles, conserved biosystem (from KEGG)
    Measles, conserved biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
  • Phagosome, organism-specific biosystem (from KEGG)
    Phagosome, organism-specific biosystemPhagocytosis is the process of taking in relatively large particles by a cell, and is a central mechanism in the tissue remodeling, inflammation, and defense against infectious agents. A phagosome is...
  • Phagosome, conserved biosystem (from KEGG)
    Phagosome, conserved biosystemPhagocytosis is the process of taking in relatively large particles by a cell, and is a central mechanism in the tissue remodeling, inflammation, and defense against infectious agents. A phagosome is...
  • Tuberculosis, organism-specific biosystem (from KEGG)
    Tuberculosis, organism-specific biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
  • Tuberculosis, conserved biosystem (from KEGG)
    Tuberculosis, conserved biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • MGC129965

Gene Ontology Provided by GOA

Function Evidence Code Pubs
carbohydrate binding NAS
Non-traceable Author Statement
more info
PubMed 
mannose binding TAS
Traceable Author Statement
more info
PubMed 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
peptide antigen binding NAS
Non-traceable Author Statement
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
virion binding TAS
Traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
antigen processing and presentation NAS
Non-traceable Author Statement
more info
PubMed 
cell-cell recognition TAS
Traceable Author Statement
more info
PubMed 
endocytosis IEA
Inferred from Electronic Annotation
more info
 
heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules TAS
Traceable Author Statement
more info
PubMed 
innate immune response IEA
Inferred from Electronic Annotation
more info
 
intracellular signal transduction NAS
Non-traceable Author Statement
more info
PubMed 
intracellular transport of virus TAS
Traceable Author Statement
more info
PubMed 
leukocyte cell-cell adhesion NAS
Non-traceable Author Statement
more info
PubMed 
modulation by virus of host morphology or physiology TAS
Traceable Author Statement
more info
PubMed 
peptide antigen transport NAS
Non-traceable Author Statement
more info
PubMed 
regulation of T cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
viral genome replication NAS
Non-traceable Author Statement
more info
PubMed 
virion attachment to host cell TAS
Traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
cell surface IDA
Inferred from Direct Assay
more info
 
cytoplasm NAS
Non-traceable Author Statement
more info
PubMed 
extracellular vesicular exosome IDA
Inferred from Direct Assay
more info
 
integral component of membrane IEA
Inferred from Electronic Annotation
more info
 
membrane TAS
Traceable Author Statement
more info
PubMed 
plasma membrane IEA
Inferred from Electronic Annotation
more info
 
Preferred Names
CD209 antigen
Names
CD209 antigen
HIV gpl20-binding protein
C-type lectin domain family 4 member L
C-type lectin domain family 4, member L
dendritic cell-specific ICAM-3-grabbing non-integrin 1
dendritic cell-specific intracellular adhesion molecules (ICAM)-3 grabbing non-integrin

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_012167.1 

    Range
    5001..12586
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001144893.1NP_001138365.1  CD209 antigen isoform 5

    See proteins identical to NP_001138365.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) has multiple differences in the coding region but maintains the reading frame, compared to variant 1. This variant encodes isoform 5, which is shorter than isoform 1. The encoded isoform (5) lacks the transmembrane domain and has 4.5 repeats in the neck domain.
    Source sequence(s)
    AC008763, AK313585, AY042227
    Consensus CDS
    CCDS59344.1
    UniProtKB/TrEMBL
    B2R907
    UniProtKB/TrEMBL
    M0R0P0
    UniProtKB/Swiss-Prot
    Q9NNX6
    Conserved Domains (2) summary
    cd03590
    Location:120243
    CLECT_DC-SIGN_like; C-type lectin-like domain (CTLD) of the type found in human dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and the related receptor, DC-SIGN receptor (DC-SIGNR)
    pfam10018
    Location:38100
    Med4; Vitamin-D-receptor interacting Mediator subunit 4
  2. NM_001144894.1NP_001138366.1  CD209 antigen isoform 6

    See proteins identical to NP_001138366.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) lacks multiple exons in the coding region but maintains the reading frame, compared to variant 1. The encoded isoform (6) is shorter and lacks the transmembrane domain compared to isoform 1.
    Source sequence(s)
    AC008763, AK313585, AY042226
    Consensus CDS
    CCDS45949.1
    UniProtKB/TrEMBL
    B2R907
    UniProtKB/Swiss-Prot
    Q9NNX6
    Conserved Domains (2) summary
    cd03590
    Location:212335
    CLECT_DC-SIGN_like; C-type lectin-like domain (CTLD) of the type found in human dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and the related receptor, DC-SIGN receptor (DC-SIGNR)
    cl19113
    Location:47184
    ApoLp-III_like; Apolipophorin-III and similar insect proteins
  3. NM_001144895.1NP_001138367.1  CD209 antigen isoform 7

    See proteins identical to NP_001138367.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) uses an alternate in-frame splice site in the coding region, compared to variant 1. This results in a shorter protein (isoform 7) compared to isoform 1. The encoded isoform (7) has 4.5 repeats in the neck domain.
    Source sequence(s)
    AC008763, AK313585, AY042223
    Consensus CDS
    CCDS45952.1
    UniProtKB/TrEMBL
    B2R907
    UniProtKB/Swiss-Prot
    Q9NNX6
    Conserved Domains (2) summary
    cd03590
    Location:164287
    CLECT_DC-SIGN_like; C-type lectin-like domain (CTLD) of the type found in human dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and the related receptor, DC-SIGN receptor (DC-SIGNR)
    pfam10018
    Location:82144
    Med4; Vitamin-D-receptor interacting Mediator subunit 4
  4. NM_001144896.1NP_001138368.1  CD209 antigen isoform 3

    See proteins identical to NP_001138368.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate in-frame exon in the coding region, compared to variant 1. The encoded isoform (3) is shorter and lacks the transmembrane domain compared to isoform 1.
    Source sequence(s)
    AC008763, AK313585, AY042225
    Consensus CDS
    CCDS45950.1
    UniProtKB/TrEMBL
    B2R907
    UniProtKB/Swiss-Prot
    Q9NNX6
    Conserved Domains (1) summary
    cd03590
    Location:232355
    CLECT_DC-SIGN_like; C-type lectin-like domain (CTLD) of the type found in human dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and the related receptor, DC-SIGN receptor (DC-SIGNR)
  5. NM_001144897.1NP_001138369.1  CD209 antigen isoform 4

    See proteins identical to NP_001138369.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses an alternate in-frame splice site in the coding region, compared to variant 1. This results in a shorter protein (isoform 4) compared to isoform 1.
    Source sequence(s)
    AC008763, AK313585, AY042222
    Consensus CDS
    CCDS45951.1
    UniProtKB/TrEMBL
    B2R907
    UniProtKB/Swiss-Prot
    Q9NNX6
    Conserved Domains (2) summary
    cd03590
    Location:256373
    CLECT_DC-SIGN_like; C-type lectin-like domain (CTLD) of the type found in human dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and the related receptor, DC-SIGN receptor (DC-SIGNR)
    cl01234
    Location:38184
    PilO; Pilus assembly protein, PilO
  6. NM_001144899.1NP_001138371.1  CD209 antigen isoform 8

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8) uses an alternate in-frame splice site in the coding region, compared to variant 1. This results in a shorter protein (isoform 8) compared to isoform 1. The encoded isoform (8) has 1.5 repeats in the neck domain.
    Source sequence(s)
    AC008763, AK304190, AK313585
    Consensus CDS
    CCDS59345.1
    UniProtKB/TrEMBL
    B2R907
    UniProtKB/TrEMBL
    B4E2A8
    UniProtKB/TrEMBL
    X6RB12
    Conserved Domains (1) summary
    cd03590
    Location:95218
    CLECT_DC-SIGN_like; C-type lectin-like domain (CTLD) of the type found in human dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and the related receptor, DC-SIGN receptor (DC-SIGNR)
  7. NM_021155.3NP_066978.1  CD209 antigen isoform 1

    See proteins identical to NP_066978.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    AC008763, AK313585, AY042221
    Consensus CDS
    CCDS12186.1
    UniProtKB/TrEMBL
    B2R907
    UniProtKB/Swiss-Prot
    Q9NNX6
    Related
    ENSP00000315477, OTTHUMP00000269508, ENST00000315599, OTTHUMT00000462241
    Conserved Domains (2) summary
    cd03590
    Location:256379
    CLECT_DC-SIGN_like; C-type lectin-like domain (CTLD) of the type found in human dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and the related receptor, DC-SIGN receptor (DC-SIGNR)
    cl01234
    Location:38184
    PilO; Pilus assembly protein, PilO

RNA

  1. NR_026692.1 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) has an alternate 5' exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AC008763, AK313585, AY042229

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000019.10 

    Range
    7739993..7747611
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005272472.2XP_005272529.1  

    Related
    ENSP00000377728, OTTHUMP00000269509, ENST00000394173, OTTHUMT00000462242
    Conserved Domains (1) summary
    cd03590
    Location:118241
    CLECT_DC-SIGN_like; C-type lectin-like domain (CTLD) of the type found in human dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and the related receptor, DC-SIGN receptor (DC-SIGNR)

Alternate HuRef

Genomic

  1. AC_000151.1 

    Range
    7474941..7482525
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018930.2 

    Range
    7804605..7812189
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)