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Protein

C-type lectin domain family 5 member A

Gene

CLEC5A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Functions as a positive regulator of osteoclastogenesis. Cell surface receptor that signals via TYROBP. Regulates inflammatory responses. Acts as a key regulator of synovial injury and bone erosion during autoimmune joint inflammation (By similarity). Critical macrophage receptor for dengue virus serotypes 1-4.By similarity1 Publication
(Microbial infection) May act as a receptor for dengue virus on macrophages. The binding of dengue virus to CLEC5A triggers signaling through the phosphylation of TYROBP, this interaction does not result in viral entry, but stimulates proinflammatory cytokine release.2 Publications

GO - Molecular functioni

  • carbohydrate binding Source: UniProtKB-KW
  • virus receptor activity Source: UniProtKB

GO - Biological processi

  • cellular defense response Source: ProtInc
  • innate immune response Source: UniProtKB
  • myeloid cell differentiation Source: Ensembl
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of myeloid cell apoptotic process Source: Ensembl
  • osteoblast development Source: UniProtKB
  • positive regulation of cytokine secretion Source: Ensembl
  • signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Host cell receptor for virus entry, Receptor

Keywords - Biological processi

Host-virus interaction, Immunity, Innate immunity

Keywords - Ligandi

Lectin

Enzyme and pathway databases

BioCyciZFISH:ENSG00000090269-MONOMER.
ReactomeiR-HSA-2172127. DAP12 interactions.
R-HSA-6798695. Neutrophil degranulation.

Names & Taxonomyi

Protein namesi
Recommended name:
C-type lectin domain family 5 member A
Alternative name(s):
C-type lectin superfamily member 5
Myeloid DAP12-associating lectin 1
Short name:
MDL-1
Gene namesi
Name:CLEC5A
Synonyms:CLECSF5, MDL1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:2054. CLEC5A.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 4CytoplasmicSequence analysis4
Transmembranei5 – 27Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST23
Topological domaini28 – 188ExtracellularSequence analysisAdd BLAST161

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi16K → I: Abolishes interaction with TYROBP. 1 Publication1

Organism-specific databases

DisGeNETi23601.
OpenTargetsiENSG00000258227.
PharmGKBiPA26583.

Polymorphism and mutation databases

BioMutaiCLEC5A.
DMDMi59797971.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000466321 – 188C-type lectin domain family 5 member AAdd BLAST188

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi32N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi71 ↔ 82PROSITE-ProRule annotation
Glycosylationi93N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi99 ↔ 183PROSITE-ProRule annotation
Glycosylationi144N-linked (GlcNAc...)Sequence analysis1
Glycosylationi151N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi161 ↔ 175PROSITE-ProRule annotation

Post-translational modificationi

N-glycosylated. Contains sialic acid residues (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9NY25.
PeptideAtlasiQ9NY25.
PRIDEiQ9NY25.

Expressioni

Tissue specificityi

Expressed in peripheral blood monocytes and in the monocyte/macrophage cell lines U-937 and Mono-Mac-6, but not in cell lines of other origins. Expression is down-regulated when monocytes differentiate into dendritic cells.1 Publication

Gene expression databases

BgeeiENSG00000258227.
CleanExiHS_CLEC5A.
ExpressionAtlasiQ9NY25. baseline and differential.
GenevisibleiQ9NY25. HS.

Interactioni

Subunit structurei

Monomer. Homodimer. The majority of CLEC5A is expressed as a monomeric form on macrophages. Interacts with TYROBP/DAP12. The interaction with TYROBP is required for CLEC5 cell surface expression. Interacts with HCST/DAP10. Forms an CLEC5A/TYROBP/HCST trimolecular complex depending almost solely on TYROBP.1 Publication
(Microbial infection) Interacts with dengue virus envelope protein E (PubMed:18496526, PubMed:21566123).2 Publications

Protein-protein interaction databases

BioGridi117135. 17 interactors.
DIPiDIP-60627N.
STRINGi9606.ENSP00000449999.

Structurei

Secondary structure

1188
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi76 – 78Combined sources3
Beta strandi81 – 85Combined sources5
Helixi92 – 100Combined sources9
Turni101 – 103Combined sources3
Helixi112 – 122Combined sources11
Beta strandi127 – 133Combined sources7
Turni135 – 137Combined sources3
Beta strandi138 – 142Combined sources5
Turni143 – 145Combined sources3
Beta strandi152 – 154Combined sources3
Beta strandi161 – 173Combined sources13
Beta strandi179 – 186Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2YHFX-ray1.90A/B/C/D/E/F/G/H/I70-187[»]
ProteinModelPortaliQ9NY25.
SMRiQ9NY25.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9NY25.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini78 – 184C-type lectinPROSITE-ProRule annotationAdd BLAST107

Sequence similaritiesi

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

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4297. Eukaryota.
ENOG410XPJ1. LUCA.
GeneTreeiENSGT00730000111396.
HOGENOMiHOG000252978.
HOVERGENiHBG081250.
InParanoidiQ9NY25.
KOiK10073.
OMAiFNCVTIG.
OrthoDBiEOG091G0NHI.
PhylomeDBiQ9NY25.
TreeFamiTF337735.

Family and domain databases

Gene3Di3.10.100.10. 1 hit.
InterProiIPR001304. C-type_lectin-like.
IPR016186. C-type_lectin-like/link.
IPR016187. CTDL_fold.
[Graphical view]
PfamiPF00059. Lectin_C. 1 hit.
[Graphical view]
SMARTiSM00034. CLECT. 1 hit.
[Graphical view]
SUPFAMiSSF56436. SSF56436. 1 hit.
PROSITEiPS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NY25-1) [UniParc]FASTAAdd to basket

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
MNWHMIISGL IVVVLKVVGM TLFLLYFPQI FNKSNDGFTT TRSYGTVSQI
60 70 80 90 100
FGSSSPSPNG FITTRSYGTV CPKDWEFYQA RCFFLSTSES SWNESRDFCK
110 120 130 140 150
GKGSTLAIVN TPEKLKFLQD ITDAEKYFIG LIYHREEKRW RWINNSVFNG
160 170 180
NVTNQNQNFN CATIGLTKTF DAASCDISYR RICEKNAK
Length:188
Mass (Da):21,521
Last modified:October 1, 2000 - v1
Checksum:i94A2DBD520DC1985
GO
Isoform 2 (identifier: Q9NY25-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     116-116: Missing.

Show »
Length:187
Mass (Da):21,393
Checksum:i9FC97A17AF8C62F9
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050110141R → H.Corresponds to variant rs35942193dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_012839116Missing in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF139768 mRNA. Translation: AAF02491.1.
AJ271684 mRNA. Translation: CAB71334.1.
AC073647 Genomic DNA. Translation: AAS07444.1.
BC093714 mRNA. Translation: AAH93714.1.
BC112099 mRNA. Translation: AAI12100.1.
BC113098 mRNA. Translation: AAI13099.1.
CCDSiCCDS5870.1. [Q9NY25-1]
RefSeqiNP_037384.1. NM_013252.2. [Q9NY25-1]
UniGeneiHs.446235.

Genome annotation databases

EnsembliENST00000546910; ENSP00000449999; ENSG00000258227. [Q9NY25-1]
GeneIDi23601.
KEGGihsa:23601.
UCSCiuc003vwv.1. human. [Q9NY25-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Functional Glycomics Gateway - Glycan Binding

MDL-1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF139768 mRNA. Translation: AAF02491.1.
AJ271684 mRNA. Translation: CAB71334.1.
AC073647 Genomic DNA. Translation: AAS07444.1.
BC093714 mRNA. Translation: AAH93714.1.
BC112099 mRNA. Translation: AAI12100.1.
BC113098 mRNA. Translation: AAI13099.1.
CCDSiCCDS5870.1. [Q9NY25-1]
RefSeqiNP_037384.1. NM_013252.2. [Q9NY25-1]
UniGeneiHs.446235.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2YHFX-ray1.90A/B/C/D/E/F/G/H/I70-187[»]
ProteinModelPortaliQ9NY25.
SMRiQ9NY25.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117135. 17 interactors.
DIPiDIP-60627N.
STRINGi9606.ENSP00000449999.

Polymorphism and mutation databases

BioMutaiCLEC5A.
DMDMi59797971.

Proteomic databases

PaxDbiQ9NY25.
PeptideAtlasiQ9NY25.
PRIDEiQ9NY25.

Protocols and materials databases

DNASUi23601.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000546910; ENSP00000449999; ENSG00000258227. [Q9NY25-1]
GeneIDi23601.
KEGGihsa:23601.
UCSCiuc003vwv.1. human. [Q9NY25-1]

Organism-specific databases

CTDi23601.
DisGeNETi23601.
GeneCardsiCLEC5A.
HGNCiHGNC:2054. CLEC5A.
MIMi604987. gene.
neXtProtiNX_Q9NY25.
OpenTargetsiENSG00000258227.
PharmGKBiPA26583.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4297. Eukaryota.
ENOG410XPJ1. LUCA.
GeneTreeiENSGT00730000111396.
HOGENOMiHOG000252978.
HOVERGENiHBG081250.
InParanoidiQ9NY25.
KOiK10073.
OMAiFNCVTIG.
OrthoDBiEOG091G0NHI.
PhylomeDBiQ9NY25.
TreeFamiTF337735.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000090269-MONOMER.
ReactomeiR-HSA-2172127. DAP12 interactions.
R-HSA-6798695. Neutrophil degranulation.

Miscellaneous databases

EvolutionaryTraceiQ9NY25.
GeneWikiiCLEC5A.
GenomeRNAii23601.
PROiQ9NY25.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000258227.
CleanExiHS_CLEC5A.
ExpressionAtlasiQ9NY25. baseline and differential.
GenevisibleiQ9NY25. HS.

Family and domain databases

Gene3Di3.10.100.10. 1 hit.
InterProiIPR001304. C-type_lectin-like.
IPR016186. C-type_lectin-like/link.
IPR016187. CTDL_fold.
[Graphical view]
PfamiPF00059. Lectin_C. 1 hit.
[Graphical view]
SMARTiSM00034. CLECT. 1 hit.
[Graphical view]
SUPFAMiSSF56436. SSF56436. 1 hit.
PROSITEiPS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCLC5A_HUMAN
AccessioniPrimary (citable) accession number: Q9NY25
Secondary accession number(s): Q52M11, Q9UKQ0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 15, 2005
Last sequence update: October 1, 2000
Last modified: November 30, 2016
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.