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Protein

C-type lectin domain family 5 member A

Gene

CLEC5A

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

Functioni

Functions as a positive regulator of osteoclastogenesis (By similarity). Cell surface receptor that signals via TYROBP (PubMed:10449773). Regulates inflammatory responses (By similarity).By similarity1 Publication
(Microbial infection) Critical macrophage receptor for dengue virus serotypes 1-4 (PubMed:18496526, PubMed:21566123). The binding of dengue virus to CLEC5A triggers signaling through the phosphorylation of TYROBP (PubMed:18496526). This interaction does not result in viral entry, but stimulates proinflammatory cytokine release (PubMed:18496526).2 Publications

Miscellaneous

Acts as a key regulator of synovial injury and bone erosion during autoimmune joint inflammation when its activation leads to enhanced recruitment of inflammatory macrophages and neutrophils to the joints.By similarity

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionHost cell receptor for virus entry, Receptor
Biological processHost-virus interaction, Immunity, Innate immunity
LigandLectin

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000258227.6
HGNCiHGNC:2054 CLEC5A
MIMi604987 gene
neXtProtiNX_Q9NY25

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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...) asparagineSequence analysis1
Disulfide bondi71 ↔ 82PROSITE-ProRule annotation
Glycosylationi93N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi99 ↔ 183PROSITE-ProRule annotation
Glycosylationi144N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi151N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi161 ↔ 175PROSITE-ProRule annotation

Post-translational modificationi

N-glycosylated. Contains sialic acid residues.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9NY25
PeptideAtlasiQ9NY25
PRIDEiQ9NY25
ProteomicsDBi83151
83152 [Q9NY25-2]

Expressioni

Tissue specificityi

Highly expressed in bone marrow with lower levels in synovium, lung and bronchus (PubMed:20212065). 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 (PubMed:10449773). Expression is down-regulated when monocytes differentiate into dendritic cells (PubMed:10449773).2 Publications

Gene expression databases

BgeeiENSG00000258227 Expressed in 97 organ(s), highest expression level in bone marrow
CleanExiHS_CLEC5A
ExpressionAtlasiQ9NY25 baseline and differential
GenevisibleiQ9NY25 HS

Organism-specific databases

HPAiHPA054137

Interactioni

Subunit structurei

Monomer (PubMed:21566123). Homodimer (PubMed:21566123). The majority of CLEC5A is expressed as a monomeric form on macrophages (PubMed:21566123). Interacts with TYROBP/DAP12 (PubMed:10449773). The interaction with TYROBP is required for CLEC5A cell surface expression (PubMed:10449773). Interacts with HCST/DAP10 (By similarity). Forms a CLEC5A/TYROBP/HCST trimolecular complex depending almost solely on TYROBP (By similarity).By similarity2 Publications
(Microbial infection) Interacts with dengue virus envelope protein E (PubMed:18496526, PubMed:21566123).2 Publications

Protein-protein interaction databases

BioGridi117135, 18 interactors
DIPiDIP-60627N
STRINGi9606.ENSP00000449999

Structurei

Secondary structure

1188
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9NY25
SMRiQ9NY25
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9NY25

Family & Domainsi

Domains and Repeats

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

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4297 Eukaryota
ENOG410XPJ1 LUCA
GeneTreeiENSGT00910000144330
HOGENOMiHOG000252978
HOVERGENiHBG081250
InParanoidiQ9NY25
KOiK10073
OMAiELSWNKS
OrthoDBiEOG091G0NHI
PhylomeDBiQ9NY25
TreeFamiTF337735

Family and domain databases

CDDicd03593 CLECT_NK_receptors_like, 1 hit
Gene3Di3.10.100.10, 1 hit
InterProiView protein in InterPro
IPR001304 C-type_lectin-like
IPR016186 C-type_lectin-like/link_sf
IPR016187 CTDL_fold
IPR033992 NKR-like_CTLD
PfamiView protein in Pfam
PF00059 Lectin_C, 1 hit
SMARTiView protein in SMART
SM00034 CLECT, 1 hit
SUPFAMiSSF56436 SSF56436, 1 hit
PROSITEiView protein in PROSITE
PS50041 C_TYPE_LECTIN_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q14DL9Q14DL9_HUMAN
C-type lectin domain family 5 membe...
CLEC5A
165Annotation score:
C9JPR7C9JPR7_HUMAN
C-type lectin domain family 5 membe...
CLEC5A
155Annotation score:
F8WCL0F8WCL0_HUMAN
C-type lectin domain family 5 membe...
CLEC5A
53Annotation score:
C9JCE4C9JCE4_HUMAN
C-type lectin domain family 5 membe...
CLEC5A
84Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050110141R → H. Corresponds to variant dbSNP:rs35942193Ensembl.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

Similar proteinsi

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, 18 interactors
DIPiDIP-60627N
STRINGi9606.ENSP00000449999

Polymorphism and mutation databases

BioMutaiCLEC5A
DMDMi59797971

Proteomic databases

PaxDbiQ9NY25
PeptideAtlasiQ9NY25
PRIDEiQ9NY25
ProteomicsDBi83151
83152 [Q9NY25-2]

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
EuPathDBiHostDB:ENSG00000258227.6
GeneCardsiCLEC5A
HGNCiHGNC:2054 CLEC5A
HPAiHPA054137
MIMi604987 gene
neXtProtiNX_Q9NY25
OpenTargetsiENSG00000258227
PharmGKBiPA26583
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4297 Eukaryota
ENOG410XPJ1 LUCA
GeneTreeiENSGT00910000144330
HOGENOMiHOG000252978
HOVERGENiHBG081250
InParanoidiQ9NY25
KOiK10073
OMAiELSWNKS
OrthoDBiEOG091G0NHI
PhylomeDBiQ9NY25
TreeFamiTF337735

Enzyme and pathway databases

ReactomeiR-HSA-2172127 DAP12 interactions
R-HSA-6798695 Neutrophil degranulation

Miscellaneous databases

EvolutionaryTraceiQ9NY25
GeneWikiiCLEC5A
GenomeRNAii23601
PROiPR:Q9NY25
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000258227 Expressed in 97 organ(s), highest expression level in bone marrow
CleanExiHS_CLEC5A
ExpressionAtlasiQ9NY25 baseline and differential
GenevisibleiQ9NY25 HS

Family and domain databases

CDDicd03593 CLECT_NK_receptors_like, 1 hit
Gene3Di3.10.100.10, 1 hit
InterProiView protein in InterPro
IPR001304 C-type_lectin-like
IPR016186 C-type_lectin-like/link_sf
IPR016187 CTDL_fold
IPR033992 NKR-like_CTLD
PfamiView protein in Pfam
PF00059 Lectin_C, 1 hit
SMARTiView protein in SMART
SM00034 CLECT, 1 hit
SUPFAMiSSF56436 SSF56436, 1 hit
PROSITEiView protein in PROSITE
PS50041 C_TYPE_LECTIN_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCLC5A_HUMAN
AccessioniPrimary (citable) accession number: Q9NY25
Secondary accession number(s): Q52M11, Q9UKQ0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 15, 2005
Last sequence update: October 1, 2000
Last modified: November 7, 2018
This is version 140 of the entry and version 1 of the sequence. See 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
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