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Protein

C-type lectin domain family 6 member A

Gene

Clec6a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Binds high-mannose carbohydrates in a Ca2+-dependent manner. Functional receptor for alpha-mannans on C.albicans hypheas. Plays an important role in the host defense against C.albicans infection by inducing TH17 cell differentiation. Recognizes also, in a mannose-dependent manner, allergens from house dust mite and fungi, by promoting cysteinyl leukotriene production. Recognizes soluble elements from the eggs of Shistosoma mansoni altering adaptive immune responses. Transduces signals through an Fc receptor gamma chain /FCER1G and Syk-CARD9-NF-kappa-B-dependent pathway.5 Publications

GO - Molecular functioni

  • carbohydrate binding Source: UniProtKB

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • defense response to fungus Source: UniProtKB
  • innate immune response Source: UniProtKB
  • positive regulation of cytokine secretion Source: UniProtKB
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • stimulatory C-type lectin receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Adaptive immunity, Immunity, Innate immunity

Keywords - Ligandi

Lectin

Enzyme and pathway databases

ReactomeiR-MMU-5621480. Dectin-2 family.

Names & Taxonomyi

Protein namesi
Recommended name:
C-type lectin domain family 6 member A
Alternative name(s):
C-type lectin superfamily member 10
Dendritic cell-associated C-type lectin 2
Short name:
DC-associated C-type lectin 2
Short name:
Dectin-2
Gene namesi
Name:Clec6a
Synonyms:Clec4n, Clecsf10, Dectin2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1861231. Clec4n.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2020CytoplasmicSequence analysisAdd
BLAST
Transmembranei21 – 4323Helical; Signal-anchor for type II membrane proteinSequence analysisAdd
BLAST
Topological domaini44 – 209166ExtracellularSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Disruption phenotypei

Deficient mice are healthy, fertile, with normal lymphoid cells, but show reduced survival after intravenous Candida albicans infection. In deficient mice fungal burden is higher in kidneys of mutant and in response to yeast antigen inflammatory cytokines and Th17 cells are reduced.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi17 – 171R → V: Does not affect association with Fc receptor gamma chain. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 209209C-type lectin domain family 6 member APRO_0000046636Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi79 ↔ 90PROSITE-ProRule annotation
Disulfide bondi107 ↔ 202PROSITE-ProRule annotation
Glycosylationi131 – 1311N-linked (GlcNAc...)Sequence analysis
Disulfide bondi176 ↔ 194PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ9JKF4.
PaxDbiQ9JKF4.
PRIDEiQ9JKF4.

Expressioni

Tissue specificityi

Expressed by the XS52 DC (dendritic cell) line (at protein level). Expressed constitutively by the epidermis, and skin resident DC appear to be the major source of this expression. Expressed in the spleen and thymus. Expression was undetectable in non-DC lines, including macrophage lines (J774 and Raw), T-cell lines (7-17, HDK-1, and D10), B-cell hybridoma (5C5), a keratinocyte line (Pam 212), and a fibroblast line (NS01).1 Publication

Gene expression databases

BgeeiQ9JKF4.
CleanExiMM_CLEC4N.
ExpressionAtlasiQ9JKF4. baseline and differential.
GenevisibleiQ9JKF4. MM.

Interactioni

Subunit structurei

Associated with FCER1G.

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000024118.

Structurei

3D structure databases

ProteinModelPortaliQ9JKF4.
SMRiQ9JKF4. Positions 79-206.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini86 – 203118C-type lectinPROSITE-ProRule annotationAdd
BLAST

Domaini

A short stretch of the intracellular domain (AA 8-14) proximal to the transmembrane domain is required for association with Fc receptor gamma chain.

Sequence similaritiesi

Contains 1 C-type lectin domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IS3R. Eukaryota.
ENOG410Z760. LUCA.
GeneTreeiENSGT00760000118924.
HOGENOMiHOG000059556.
HOVERGENiHBG050992.
InParanoidiQ9JKF4.
KOiK17514.
OMAiHNSICEM.
OrthoDBiEOG7J9VQH.
PhylomeDBiQ9JKF4.
TreeFamiTF333341.

Family and domain databases

Gene3Di3.10.100.10. 1 hit.
InterProiIPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR018378. C-type_lectin_CS.
IPR016187. C-type_lectin_fold.
[Graphical view]
PfamiPF00059. Lectin_C. 1 hit.
[Graphical view]
SMARTiSM00034. CLECT. 1 hit.
[Graphical view]
SUPFAMiSSF56436. SSF56436. 1 hit.
PROSITEiPS00615. C_TYPE_LECTIN_1. 1 hit.
PS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9JKF4-1) [UniParc]FASTAAdd to basket

Also known as: Alpha

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVQERQSQGK GVCWTLRLWS AAVISMLLLS TCFIASCVVT YQFIMDQPSR
60 70 80 90 100
RLYELHTYHS SLTCFSEGTM VSEKMWGCCP NHWKSFGSSC YLISTKENFW
110 120 130 140 150
STSEQNCVQM GAHLVVINTE AEQNFITQQL NESLSYFLGL SDPQGNGKWQ
160 170 180 190 200
WIDDTPFSQN VRFWHPHEPN LPEERCVSIV YWNPSKWGWN DVFCDSKHNS

ICEMKKIYL
Length:209
Mass (Da):24,324
Last modified:October 1, 2000 - v1
Checksum:i7AB8BDC0DB1EA5ED
GO
Isoform 2 (identifier: Q9JKF4-2) [UniParc]FASTAAdd to basket

Also known as: Beta

The sequence of this isoform differs from the canonical sequence as follows:
     39-72: Missing.

Show »
Length:175
Mass (Da):20,313
Checksum:iE1C9632687BF0EA9
GO
Isoform 3 (identifier: Q9JKF4-3) [UniParc]FASTAAdd to basket

Also known as: Gamma

The sequence of this isoform differs from the canonical sequence as follows:
     142-182: Missing.

Show »
Length:168
Mass (Da):19,332
Checksum:iCF2ADDFE054EB038
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei39 – 7234Missing in isoform 2. 1 PublicationVSP_012846Add
BLAST
Alternative sequencei142 – 18241Missing in isoform 3. 1 PublicationVSP_012847Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF240357 mRNA. Translation: AAF67177.1.
AF240358 mRNA. Translation: AAF67178.1.
AF240359 mRNA. Translation: AAF67179.1.
BC023008 mRNA. Translation: AAH23008.1.
CCDSiCCDS20512.1. [Q9JKF4-1]
CCDS51895.1. [Q9JKF4-2]
RefSeqiNP_001177250.1. NM_001190321.1. [Q9JKF4-2]
NP_064385.1. NM_020001.2. [Q9JKF4-1]
UniGeneiMm.271782.

Genome annotation databases

EnsembliENSMUST00000024118; ENSMUSP00000024118; ENSMUSG00000023349. [Q9JKF4-1]
ENSMUST00000112554; ENSMUSP00000108173; ENSMUSG00000023349. [Q9JKF4-2]
GeneIDi56620.
KEGGimmu:56620.
UCSCiuc009dqe.2. mouse. [Q9JKF4-1]
uc009dqf.2. mouse. [Q9JKF4-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Functional Glycomics Gateway - Glycan Binding

Dectin-2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF240357 mRNA. Translation: AAF67177.1.
AF240358 mRNA. Translation: AAF67178.1.
AF240359 mRNA. Translation: AAF67179.1.
BC023008 mRNA. Translation: AAH23008.1.
CCDSiCCDS20512.1. [Q9JKF4-1]
CCDS51895.1. [Q9JKF4-2]
RefSeqiNP_001177250.1. NM_001190321.1. [Q9JKF4-2]
NP_064385.1. NM_020001.2. [Q9JKF4-1]
UniGeneiMm.271782.

3D structure databases

ProteinModelPortaliQ9JKF4.
SMRiQ9JKF4. Positions 79-206.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000024118.

Proteomic databases

MaxQBiQ9JKF4.
PaxDbiQ9JKF4.
PRIDEiQ9JKF4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000024118; ENSMUSP00000024118; ENSMUSG00000023349. [Q9JKF4-1]
ENSMUST00000112554; ENSMUSP00000108173; ENSMUSG00000023349. [Q9JKF4-2]
GeneIDi56620.
KEGGimmu:56620.
UCSCiuc009dqe.2. mouse. [Q9JKF4-1]
uc009dqf.2. mouse. [Q9JKF4-2]

Organism-specific databases

CTDi56620.
MGIiMGI:1861231. Clec4n.

Phylogenomic databases

eggNOGiENOG410IS3R. Eukaryota.
ENOG410Z760. LUCA.
GeneTreeiENSGT00760000118924.
HOGENOMiHOG000059556.
HOVERGENiHBG050992.
InParanoidiQ9JKF4.
KOiK17514.
OMAiHNSICEM.
OrthoDBiEOG7J9VQH.
PhylomeDBiQ9JKF4.
TreeFamiTF333341.

Enzyme and pathway databases

ReactomeiR-MMU-5621480. Dectin-2 family.

Miscellaneous databases

PROiQ9JKF4.
SOURCEiSearch...

Gene expression databases

BgeeiQ9JKF4.
CleanExiMM_CLEC4N.
ExpressionAtlasiQ9JKF4. baseline and differential.
GenevisibleiQ9JKF4. MM.

Family and domain databases

Gene3Di3.10.100.10. 1 hit.
InterProiIPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR018378. C-type_lectin_CS.
IPR016187. C-type_lectin_fold.
[Graphical view]
PfamiPF00059. Lectin_C. 1 hit.
[Graphical view]
SMARTiSM00034. CLECT. 1 hit.
[Graphical view]
SUPFAMiSSF56436. SSF56436. 1 hit.
PROSITEiPS00615. C_TYPE_LECTIN_1. 1 hit.
PS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning of a second dendritic cell-associated C-type lectin (dectin-2) and its alternatively spliced isoforms."
    Ariizumi K., Shen G.-L., Shikano S., Ritter R. III, Zukas P., Edelbaum D., Morita A., Takashima A.
    J. Biol. Chem. 275:11957-11963(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), TISSUE SPECIFICITY.
    Strain: BALB/cJ.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: FVB/N-3.
    Tissue: Mammary tumor.
  3. "Dectin-2 is a pattern recognition receptor for fungi that couples with the Fc receptor gamma chain to induce innate immune responses."
    Sato K., Yang X.L., Yudate T., Chung J.S., Wu J., Luby-Phelps K., Kimberly R.P., Underhill D., Cruz P.D. Jr., Ariizumi K.
    J. Biol. Chem. 281:38854-38866(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH FCER1G, MUTAGENESIS OF ARG-17.
  4. "Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection."
    Robinson M.J., Osorio F., Rosas M., Freitas R.P., Schweighoffer E., Gross O., Verbeek J.S., Ruland J., Tybulewicz V., Brown G.D., Moita L.F., Taylor P.R., Reis e Sousa C.
    J. Exp. Med. 206:2037-2051(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. "Dectin-2 recognition of house dust mite triggers cysteinyl leukotriene generation by dendritic cells."
    Barrett N.A., Maekawa A., Rahman O.M., Austen K.F., Kanaoka Y.
    J. Immunol. 182:1119-1128(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Spleen.
  7. "Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans."
    Saijo S., Ikeda S., Yamabe K., Kakuta S., Ishigame H., Akitsu A., Fujikado N., Kusaka T., Kubo S., Chung S.H., Komatsu R., Miura N., Adachi Y., Ohno N., Shibuya K., Yamamoto N., Kawakami K., Yamasaki S.
    , Saito T., Akira S., Iwakura Y.
    Immunity 32:681-691(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  8. "Schistosoma mansoni triggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses."
    Ritter M., Gross O., Kays S., Ruland J., Nimmerjahn F., Saijo S., Tschopp J., Layland L.E., Prazeres da Costa C.
    Proc. Natl. Acad. Sci. U.S.A. 107:20459-20464(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiCLC6A_MOUSE
AccessioniPrimary (citable) accession number: Q9JKF4
Secondary accession number(s): Q9JKF2, Q9JKF3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 15, 2005
Last sequence update: October 1, 2000
Last modified: June 8, 2016
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.