UniProtKB - Q8WXI8 (CLC4D_HUMAN)
C-type lectin domain family 4 member D
CLEC4D
Functioni
Calcium-dependent lectin that acts as a pattern recognition receptor (PRR) of the innate immune system: recognizes damage-associated molecular patterns (DAMPs) of pathogen-associated molecular patterns (PAMPs) of bacteria and fungi (PubMed:23602766, PubMed:23911656).
The PAMPs include alpha-mannans on C.albicans hypheas and mycobacterial trehalose 6,6'-dimycolate (TDM) (PubMed:23602766, PubMed:23911656).
Interacts with signaling adapter Fc receptor gamma chain/FCER1G, likely via CLEC4E, to form a functional complex in myeloid cells (By similarity).
Binding of mycobacterial TDM or C.albicans alpha-mannans to this receptor complex leads to phosphorylation of the immunoreceptor tyrosine-based activation motif (ITAM) of FCER1G, triggering activation of SYK, CARD9 and NF-kappa-B, consequently driving maturation of antigen-presenting cells and shaping antigen-specific priming of T-cells toward effector T-helper 1 and T-helper 17 cell subtypes (PubMed:23602766, PubMed:23911656).
The heterodimer formed with CLEC6A is active against fungal infection (PubMed:23911656).
Functions as an endocytic receptor (PubMed:14971047).
May be involved in antigen uptake at the site of infection, either for clearance of the antigen, or for processing and further presentation to T-cells (PubMed:14971047).
By similarity3 PublicationsSites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 173 | Calcium1 Publication | 1 | |
Metal bindingi | 175 | Calcium1 Publication | 1 | |
Metal bindingi | 195 | Calcium1 Publication | 1 | |
Metal bindingi | 196 | Calcium; via carbonyl oxygen1 Publication | 1 |
GO - Molecular functioni
- carbohydrate binding Source: GO_Central
- immunoglobulin receptor binding Source: Ensembl
- mannose binding Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
- pattern recognition receptor activity Source: UniProtKB
GO - Biological processi
- adaptive immune response Source: UniProtKB-KW
- antifungal innate immune response Source: UniProtKB
- defense response to bacterium Source: Ensembl
- Fc-gamma receptor signaling pathway Source: Ensembl
- immune response Source: GO_Central
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
- positive regulation of myeloid dendritic cell activation Source: UniProtKB
- T cell differentiation involved in immune response Source: Ensembl
Keywordsi
Biological process | Adaptive immunity, Immunity, Innate immunity |
Ligand | Calcium, Lectin, Metal-binding |
Enzyme and pathway databases
PathwayCommonsi | Q8WXI8 |
Reactomei | R-HSA-5621480, Dectin-2 family R-HSA-6798695, Neutrophil degranulation |
SignaLinki | Q8WXI8 |
Protein family/group databases
UniLectini | Q8WXI8 |
Names & Taxonomyi
Protein namesi | Recommended name: C-type lectin domain family 4 member DAlternative name(s): C-type lectin superfamily member 8 C-type lectin-like receptor 6 Short name: CLEC-6 Dendritic cell-associated C-type lectin 31 Publication Short name: DC-associated C-type lectin 31 Publication Short name: Dectin-31 Publication CD_antigen: CD368 |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:14554, CLEC4D |
MIMi | 609964, gene |
neXtProti | NX_Q8WXI8 |
VEuPathDBi | HostDB:ENSG00000166527 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Single-pass type II membrane protein Curated
Plasma Membrane
- external side of plasma membrane Source: GO_Central
- plasma membrane Source: UniProtKB
Other locations
- ficolin-1-rich granule membrane Source: Reactome
- integral component of membrane Source: UniProtKB-KW
- specific granule membrane Source: Reactome
- tertiary granule membrane Source: Reactome
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 17 | CytoplasmicSequence analysisAdd BLAST | 17 | |
Transmembranei | 18 – 38 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 21 | |
Topological domaini | 39 – 215 | ExtracellularSequence analysisAdd BLAST | 177 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 173 | E → Q: No effect on already low affinity binding to trehalose-6,6'-dimycolate. 1 Publication | 1 | |
Mutagenesisi | 175 | D → N: No effect on already low affinity binding to trehalose-6,6'-dimycolate. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 338339 |
OpenTargetsi | ENSG00000166527 |
PharmGKBi | PA134916109 |
Miscellaneous databases
Pharosi | Q8WXI8, Tbio |
Genetic variation databases
BioMutai | CLEC4D |
DMDMi | 73916933 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000046616 | 1 – 215 | C-type lectin domain family 4 member DAdd BLAST | 215 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 45 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 84 ↔ 95 | PROSITE-ProRule annotation | ||
Glycosylationi | 102 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 111 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 112 ↔ 207 | PROSITE-ProRule annotation | ||
Disulfide bondi | 182 ↔ 199 | PROSITE-ProRule annotation |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
MassIVEi | Q8WXI8 |
PaxDbi | Q8WXI8 |
PeptideAtlasi | Q8WXI8 |
PRIDEi | Q8WXI8 |
PTM databases
GlyGeni | Q8WXI8, 3 sites |
iPTMneti | Q8WXI8 |
PhosphoSitePlusi | Q8WXI8 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000166527, Expressed in bone marrow and 96 other tissues |
ExpressionAtlasi | Q8WXI8, baseline and differential |
Genevisiblei | Q8WXI8, HS |
Organism-specific databases
HPAi | ENSG00000166527, Tissue enriched (bone) |
Interactioni
Subunit structurei
Heterodimer with CLEC4E; disulfide-linked (By similarity). CLEC4E acts as a bridge for interaction between CLEC4D and FCER1G to form a functional complex (By similarity). Heterodimer with CLEC6A; this heterodimer forms a pattern recognition receptor (PRR) against fungal infection (PubMed:23911656).
By similarity1 PublicationBinary interactionsi
Q8WXI8
With | #Exp. | IntAct |
---|---|---|
ACTN2 [P35609] | 3 | EBI-12703404,EBI-77797 |
ANKRD46 - isoform 1 [Q86W74-2] | 3 | EBI-12703404,EBI-12109402 |
JAGN1 [Q8N5M9] | 3 | EBI-12703404,EBI-10266796 |
ZDHHC22 [Q8N966] | 3 | EBI-12703404,EBI-10268111 |
GO - Molecular functioni
- immunoglobulin receptor binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 130719, 261 interactors |
IntActi | Q8WXI8, 4 interactors |
STRINGi | 9606.ENSP00000299665 |
Miscellaneous databases
RNActi | Q8WXI8, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q8WXI8 |
BMRBi | Q8WXI8 |
SMRi | Q8WXI8 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 91 – 208 | C-type lectinPROSITE-ProRule annotationAdd BLAST | 118 |
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG4297, Eukaryota |
GeneTreei | ENSGT00940000162400 |
HOGENOMi | CLU_049894_7_5_1 |
InParanoidi | Q8WXI8 |
OMAi | WAWNDVP |
OrthoDBi | 1269095at2759 |
PhylomeDBi | Q8WXI8 |
TreeFami | TF333341 |
Family and domain databases
CDDi | cd03590, CLECT_DC-SIGN_like, 1 hit |
Gene3Di | 3.10.100.10, 1 hit |
InterProi | View protein in InterPro IPR001304, C-type_lectin-like IPR016186, C-type_lectin-like/link_sf IPR033989, CD209-like_CTLD IPR016187, CTDL_fold |
Pfami | View protein in Pfam PF00059, Lectin_C, 1 hit |
SMARTi | View protein in SMART SM00034, CLECT, 1 hit |
SUPFAMi | SSF56436, SSF56436, 1 hit |
PROSITEi | View protein in PROSITE PS50041, C_TYPE_LECTIN_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
10 20 30 40 50
MGLEKPQSKL EGGMHPQLIP SVIAVVFILL LSVCFIASCL VTHHNFSRCK
60 70 80 90 100
RGTGVHKLEH HAKLKCIKEK SELKSAEGST WNCCPIDWRA FQSNCYFPLT
110 120 130 140 150
DNKTWAESER NCSGMGAHLM TISTEAEQNF IIQFLDRRLS YFLGLRDENA
160 170 180 190 200
KGQWRWVDQT PFNPRRVFWH KNEPDNSQGE NCVVLVYNQD KWAWNDVPCN
210
FEASRICKIP GTTLN
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA6NHA5 | A6NHA5_HUMAN | C-type lectin domain family 4 membe... | CLEC4D | 144 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_021261 | 32 | S → G2 PublicationsCorresponds to variant dbSNP:rs4304840EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY297446 mRNA Translation: AAQ63173.1 AY486482 mRNA Translation: AAS59161.1 AY486483 mRNA Translation: AAS59162.1 AF411850 mRNA Translation: AAL37713.1 AY115592 mRNA Translation: AAM75389.1 BC032313 mRNA Translation: AAH32313.1 |
CCDSi | CCDS8593.1 |
RefSeqi | NP_525126.2, NM_080387.4 XP_011518934.1, XM_011520632.2 |
Genome annotation databases
Ensembli | ENST00000299665.3; ENSP00000299665.2; ENSG00000166527.8 |
GeneIDi | 338339 |
KEGGi | hsa:338339 |
MANE-Selecti | ENST00000299665.3; ENSP00000299665.2; NM_080387.5; NP_525126.2 |
UCSCi | uc001qun.4, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
Functional Glycomics Gateway - Glycan Binding MCL |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY297446 mRNA Translation: AAQ63173.1 AY486482 mRNA Translation: AAS59161.1 AY486483 mRNA Translation: AAS59162.1 AF411850 mRNA Translation: AAL37713.1 AY115592 mRNA Translation: AAM75389.1 BC032313 mRNA Translation: AAH32313.1 |
CCDSi | CCDS8593.1 |
RefSeqi | NP_525126.2, NM_080387.4 XP_011518934.1, XM_011520632.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2LS8 | NMR | - | A | 84-215 | [»] | |
3WHD | X-ray | 2.29 | A/C | 61-215 | [»] | |
AlphaFoldDBi | Q8WXI8 | |||||
BMRBi | Q8WXI8 | |||||
SMRi | Q8WXI8 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 130719, 261 interactors |
IntActi | Q8WXI8, 4 interactors |
STRINGi | 9606.ENSP00000299665 |
Protein family/group databases
UniLectini | Q8WXI8 |
PTM databases
GlyGeni | Q8WXI8, 3 sites |
iPTMneti | Q8WXI8 |
PhosphoSitePlusi | Q8WXI8 |
Genetic variation databases
BioMutai | CLEC4D |
DMDMi | 73916933 |
Proteomic databases
MassIVEi | Q8WXI8 |
PaxDbi | Q8WXI8 |
PeptideAtlasi | Q8WXI8 |
PRIDEi | Q8WXI8 |
Protocols and materials databases
ABCDi | Q8WXI8, 1 sequenced antibody |
Antibodypediai | 1467, 287 antibodies from 30 providers |
DNASUi | 338339 |
Genome annotation databases
Ensembli | ENST00000299665.3; ENSP00000299665.2; ENSG00000166527.8 |
GeneIDi | 338339 |
KEGGi | hsa:338339 |
MANE-Selecti | ENST00000299665.3; ENSP00000299665.2; NM_080387.5; NP_525126.2 |
UCSCi | uc001qun.4, human |
Organism-specific databases
CTDi | 338339 |
DisGeNETi | 338339 |
GeneCardsi | CLEC4D |
HGNCi | HGNC:14554, CLEC4D |
HPAi | ENSG00000166527, Tissue enriched (bone) |
MIMi | 609964, gene |
neXtProti | NX_Q8WXI8 |
OpenTargetsi | ENSG00000166527 |
PharmGKBi | PA134916109 |
VEuPathDBi | HostDB:ENSG00000166527 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4297, Eukaryota |
GeneTreei | ENSGT00940000162400 |
HOGENOMi | CLU_049894_7_5_1 |
InParanoidi | Q8WXI8 |
OMAi | WAWNDVP |
OrthoDBi | 1269095at2759 |
PhylomeDBi | Q8WXI8 |
TreeFami | TF333341 |
Enzyme and pathway databases
PathwayCommonsi | Q8WXI8 |
Reactomei | R-HSA-5621480, Dectin-2 family R-HSA-6798695, Neutrophil degranulation |
SignaLinki | Q8WXI8 |
Miscellaneous databases
BioGRID-ORCSi | 338339, 11 hits in 1071 CRISPR screens |
GenomeRNAii | 338339 |
Pharosi | Q8WXI8, Tbio |
PROi | PR:Q8WXI8 |
RNActi | Q8WXI8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000166527, Expressed in bone marrow and 96 other tissues |
ExpressionAtlasi | Q8WXI8, baseline and differential |
Genevisiblei | Q8WXI8, HS |
Family and domain databases
CDDi | cd03590, CLECT_DC-SIGN_like, 1 hit |
Gene3Di | 3.10.100.10, 1 hit |
InterProi | View protein in InterPro IPR001304, C-type_lectin-like IPR016186, C-type_lectin-like/link_sf IPR033989, CD209-like_CTLD IPR016187, CTDL_fold |
Pfami | View protein in Pfam PF00059, Lectin_C, 1 hit |
SMARTi | View protein in SMART SM00034, CLECT, 1 hit |
SUPFAMi | SSF56436, SSF56436, 1 hit |
PROSITEi | View protein in PROSITE PS50041, C_TYPE_LECTIN_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CLC4D_HUMAN | |
Accessioni | Q8WXI8Primary (citable) accession number: Q8WXI8 Secondary accession number(s): Q8N5J5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 15, 2005 |
Last sequence update: | May 10, 2005 | |
Last modified: | May 25, 2022 | |
This is version 147 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human cell differentiation molecules
CD nomenclature of surface proteins of human leucocytes and list of entries - Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references