CLEC4D

Functionⁱ

A calcium-dependent lectin involved in innate recognition of pathogen-associated molecular patterns (PAMPs). 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 trehalose 6,6'-dimycolate (TDM) 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). Functions as an endocytic receptor. 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 similarity2 Publications

Sites

Feature key	Position(s)	DescriptionActions	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: UniProtKB-KW
immunoglobulin receptor binding Source: Ensembl

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

adaptive immune response Source: UniProtKB-KW
defense response to bacterium Source: Ensembl
Fc-gamma receptor signaling pathway Source: Ensembl
innate immune response Source: UniProtKB-KW
neutrophil degranulation Source: Reactome
positive regulation of myeloid dendritic cell activation Source: UniProtKB
stimulatory C-type lectin receptor signaling pathway Source: Reactome
T cell differentiation involved in immune response Source: Ensembl

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Biological process	Adaptive immunity, Immunity, Innate immunity
Ligand	Calcium, Lectin, Metal-binding

Enzyme and pathway databases

Reactomeⁱ	R-HSA-5621480 Dectin-2 family R-HSA-6798695 Neutrophil degranulation

Reactomeⁱ

R-HSA-5621480 Dectin-2 family
R-HSA-6798695 Neutrophil degranulation

Protein family/group databases

UniLectinⁱ	Q8WXI8

UniLectinⁱ

Q8WXI8

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: C-type lectin domain family 4 member D Alternative name(s): C-type lectin superfamily member 8 C-type lectin-like receptor 6 Short name: CLEC-6
Gene namesⁱ	Name:CLEC4DCombined sources Synonyms:CLECSF81 Publication, MCL2 Publications
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 12

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000166527.7
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:14554 CLEC4D
MIMⁱ	609964 gene
neXtProtⁱ	NX_Q8WXI8

Topology

Feature key	Position(s)	DescriptionActions	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

Membrane

Pathology & 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

DisGeNET More...DisGeNETⁱ	338339
Open Targets More...OpenTargetsⁱ	ENSG00000166527
PharmGKBⁱ	PA134916109

Polymorphism and mutation 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	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, Glycoprotein

Proteomic databases

PaxDbⁱ	Q8WXI8
PeptideAtlas More...PeptideAtlasⁱ	Q8WXI8
PRIDEⁱ	Q8WXI8
ProteomicsDBⁱ	75069

PTM databases

iPTMnetⁱ	Q8WXI8
PhosphoSitePlusⁱ	Q8WXI8

Expressionⁱ

Tissue specificityⁱ

Expressed weakly in peripheral blood leukocytes, bone marrow and spleen. Expression is confined mostly in monocytes and macrophage and seems to be up-regulated by IL-6, IL-10, TNF-alpha and IFN-gamma.1 Publication

Inductionⁱ

By autocrine inflammatory stimuli.1 Publication

Gene expression databases

Bgeeⁱ	ENSG00000166527
CleanExⁱ	HS_CLEC4D
ExpressionAtlasⁱ	Q8WXI8 baseline and differential
Genevisibleⁱ	Q8WXI8 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	HPA004906

HPAⁱ

HPA004906

Interactionⁱ

Subunit structureⁱ

Heterodimer with CLEC4E; disulfide-linked. CLEC4E acts as a bridge for interaction between CLEC4D and FCER1G to form a functional complex.By similarity

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
ACTN2	P35609	3	EBI-12703404,EBI-77797

With

Entry

#Exp.

IntAct

Notes

ACTN2

P35609

3

EBI-12703404,EBI-77797

GO - Molecular functionⁱ

immunoglobulin receptor binding Source: Ensembl

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

IntActⁱ	Q8WXI8, 3 interactors
STRINGⁱ	9606.ENSP00000299665

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Show more details

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	63 – 67	Combined sources	5
Beta strandⁱ	81 – 85	Combined sources	5
Beta strandⁱ	88 – 91	Combined sources	4
Beta strandⁱ	94 – 103	Combined sources	10
Helixⁱ	105 – 113	Combined sources	9
Turnⁱ	114 – 116	Combined sources	3
Beta strandⁱ	118 – 120	Combined sources	3
Helixⁱ	125 – 132	Combined sources	8
Beta strandⁱ	141 – 147	Combined sources	7
Beta strandⁱ	150 – 152	Combined sources	3
Beta strandⁱ	181 – 187	Combined sources	7
Beta strandⁱ	189 – 198	Combined sources	10
Beta strandⁱ	203 – 210	Combined sources	8
Beta strandⁱ	212 – 214	Combined sources	3

3D structure databases

ProteinModelPortalⁱ	Q8WXI8
SMRⁱ	Q8WXI8
ModBaseⁱ	Search...
MobiDBⁱ	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 helix

Phylogenomic databases

eggNOGⁱ	ENOG410IS3N Eukaryota ENOG410XYR0 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00920000149038
HOGENOMⁱ	HOG000059556
HOVERGENⁱ	HBG050992
InParanoidⁱ	Q8WXI8
KEGG Orthology (KO) More...KOⁱ	K10058
OMAⁱ	RAFQSNC
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0K6R
PhylomeDBⁱ	Q8WXI8
TreeFamⁱ	TF333341

Family and domain databases

Conserved Domains Database More...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
Pfam protein domain database More...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

Sequenceⁱ

Sequence statusⁱ: Complete.

Q8WXI8-1 [UniParc]FASTA Add to basket

« Hide

        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

Length:215

Mass (Da):24,704

Last modified:May 10, 2005 - v2

Checksum:ⁱ938B68661AAC175B

GO

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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS8593.1
NCBI Reference Sequences More...RefSeqⁱ	NP_525126.2, NM_080387.4 XP_011518934.1, XM_011520632.2
UniGeneⁱ	Hs.351811

Genome annotation databases

Ensemblⁱ	ENST00000299665; ENSP00000299665; ENSG00000166527
GeneIDⁱ	338339
KEGGⁱ	hsa:338339
UCSC genome browser More...UCSCⁱ	uc001qun.4 human

Keywords - Coding sequence diversityⁱ

Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length
Q8WXI8	C-type lectin domain family 4 member D (Fragment)		HUMAN		144
UPI000D50012F		PANPA		218
CLEC4D isoform 2		PANTR		215
C-type lectin domain family 4 member D		NOMLE		215
C-type lectin domain family 4 member D		GORGO		215
+6

Protein	Similar proteins		Species	Score	Length
Q8WXI8	C-type lectin domain family 4 member D (Fragment)		HUMAN		144
UPI000D50012F		PANPA		218
CLEC4D isoform 2		PANTR		215
C-type lectin domain family 4 member D		GORGO		215
C-type lectin domain family 4 member D		NOMLE		215
+35

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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS8593.1
NCBI Reference Sequences More...RefSeqⁱ	NP_525126.2, NM_080387.4 XP_011518934.1, XM_011520632.2
UniGeneⁱ	Hs.351811

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...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	[»]
ProteinModelPortalⁱ	Q8WXI8
SMRⁱ	Q8WXI8
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

IntActⁱ	Q8WXI8, 3 interactors
STRINGⁱ	9606.ENSP00000299665

Protein family/group databases

UniLectinⁱ	Q8WXI8

UniLectinⁱ

Q8WXI8

PTM databases

iPTMnetⁱ	Q8WXI8
PhosphoSitePlusⁱ	Q8WXI8

Polymorphism and mutation databases

BioMutaⁱ	CLEC4D
DMDMⁱ	73916933

Proteomic databases

PaxDbⁱ	Q8WXI8
PeptideAtlas More...PeptideAtlasⁱ	Q8WXI8
PRIDEⁱ	Q8WXI8
ProteomicsDBⁱ	75069

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	338339
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000299665; ENSP00000299665; ENSG00000166527
GeneIDⁱ	338339
KEGGⁱ	hsa:338339
UCSC genome browser More...UCSCⁱ	uc001qun.4 human

Organism-specific databases

CTDⁱ	338339
DisGeNET More...DisGeNETⁱ	338339
EuPathDBⁱ	HostDB:ENSG00000166527.7
GeneCardsⁱ	CLEC4D
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:14554 CLEC4D
Human Protein Atlas More...HPAⁱ	HPA004906
MIMⁱ	609964 gene
neXtProtⁱ	NX_Q8WXI8
Open Targets More...OpenTargetsⁱ	ENSG00000166527
PharmGKBⁱ	PA134916109
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	ENOG410IS3N Eukaryota ENOG410XYR0 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00920000149038
HOGENOMⁱ	HOG000059556
HOVERGENⁱ	HBG050992
InParanoidⁱ	Q8WXI8
KEGG Orthology (KO) More...KOⁱ	K10058
OMAⁱ	RAFQSNC
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0K6R
PhylomeDBⁱ	Q8WXI8
TreeFamⁱ	TF333341

Enzyme and pathway databases

Reactomeⁱ	R-HSA-5621480 Dectin-2 family R-HSA-6798695 Neutrophil degranulation

Reactomeⁱ

R-HSA-5621480 Dectin-2 family
R-HSA-6798695 Neutrophil degranulation

Miscellaneous databases

GenomeRNAiⁱ	338339
Protein Ontology More...PROⁱ	PR:Q8WXI8
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000166527
CleanExⁱ	HS_CLEC4D
ExpressionAtlasⁱ	Q8WXI8 baseline and differential
Genevisibleⁱ	Q8WXI8 HS

Family and domain databases

Conserved Domains Database More...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
Pfam protein domain database More...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
ProtoNetⁱ	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:	July 18, 2018
	This is version 126 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, Complete proteome, Reference proteome

Documents

Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
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

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UniProtKB - Q8WXI8 (CLC4D_HUMAN)

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C-type lectin domain family 4 member D

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Sites

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

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Plasma Membrane

Other locations

Topology

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Organism-specific databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Phylogenomic databases

Family and domain databases

Natural variant

Sequence databases

Genome annotation databases

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<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ