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Q9NY25 (CLC5A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:CLEC5A
Synonyms:CLECSF5, MDL1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length188 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. 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. Ref.1 Ref.5

Subunit structure

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. Ref.1 Ref.6

Subcellular location

Cell membrane; Single-pass type II membrane protein Ref.6.

Tissue specificity

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. Ref.1

Post-translational modification

N-glycosylated. Contains sialic acid residues By similarity.

Sequence similarities

Contains 1 C-type lectin domain.

Ontologies

Keywords
   Biological processHost-virus interaction
Immunity
Innate immunity
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   LigandLectin
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular defense response

Traceable author statement Ref.1. Source: ProtInc

innate immune response

Inferred from direct assay Ref.5. Source: UniProtKB

negative regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of myeloid cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

osteoblast development

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cytokine secretion

Inferred from electronic annotation. Source: Ensembl

response to virus

Inferred from direct assay Ref.5. Source: GOC

signal transduction

Traceable author statement Ref.1. Source: ProtInc

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcell surface

Inferred from sequence or structural similarity. Source: UniProtKB

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functioncarbohydrate binding

Inferred from electronic annotation. Source: InterPro

virus receptor activity

Inferred from direct assay Ref.5. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NY25-1)

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.
Isoform 2 (identifier: Q9NY25-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 188188C-type lectin domain family 5 member A
PRO_0000046632

Regions

Topological domain1 – 44Cytoplasmic Potential
Transmembrane5 – 2723Helical; Signal-anchor for type II membrane protein; Potential
Topological domain28 – 188161Extracellular Potential
Domain78 – 184107C-type lectin

Amino acid modifications

Glycosylation321N-linked (GlcNAc...) Potential
Glycosylation931N-linked (GlcNAc...) Potential
Glycosylation1441N-linked (GlcNAc...) Potential
Glycosylation1511N-linked (GlcNAc...) Potential
Disulfide bond71 ↔ 82 By similarity
Disulfide bond99 ↔ 183 By similarity
Disulfide bond161 ↔ 175 By similarity

Natural variations

Alternative sequence1161Missing in isoform 2.
VSP_012839
Natural variant1411R → H.
Corresponds to variant rs35942193 [ dbSNP | Ensembl ].
VAR_050110

Experimental info

Mutagenesis161K → I: Abolishes interaction with TYROBP. Ref.1

Secondary structure

...................... 188
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 94A2DBD520DC1985

FASTA18821,521
        10         20         30         40         50         60 
MNWHMIISGL IVVVLKVVGM TLFLLYFPQI FNKSNDGFTT TRSYGTVSQI FGSSSPSPNG 

        70         80         90        100        110        120 
FITTRSYGTV CPKDWEFYQA RCFFLSTSES SWNESRDFCK GKGSTLAIVN TPEKLKFLQD 

       130        140        150        160        170        180 
ITDAEKYFIG LIYHREEKRW RWINNSVFNG NVTNQNQNFN CATIGLTKTF DAASCDISYR 


RICEKNAK 

« Hide

Isoform 2 [UniParc].

Checksum: 9FC97A17AF8C62F9
Show »

FASTA18721,393

References

« Hide 'large scale' references
[1]"Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells."
Bakker A.B.H., Baker E., Sutherland G.R., Phillips J.H., Lanier L.L.
Proc. Natl. Acad. Sci. U.S.A. 96:9792-9796(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH TYROBP, MUTAGENESIS OF LYS-16.
[2]"Expression of MDL-1 in human blood and cell lines."
Mueller A., Merz H., Feller A.C.
Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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).
[5]"CLEC5A is critical for dengue-virus-induced lethal disease."
Chen S.T., Lin Y.L., Huang M.T., Wu M.F., Cheng S.C., Lei H.Y., Lee C.K., Chiou T.W., Wong C.H., Hsieh S.L.
Nature 453:672-676(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS A DENGUE VIRUS RECEPTOR.
[6]"Structural flexibility of the macrophage dengue virus receptor CLEC5A: Implications for ligand binding and signaling."
Watson A.A., Lebedev A.A., Hall B.A., Fenton-May A.E., Vagin A.A., Dejnirattisai W., Felce J., Mongkolsapaya J., Palma A.S., Liu Y., Feizi T., Screaton G.R., Murshudov G.N., O'Callaghan C.A.
J. Biol. Chem. 286:24208-24218(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 71-187, SUBUNIT, SUBCELLULAR LOCATION, INTERACTION WITH DENGUE VIRUS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS5870.1. [Q9NY25-1]
RefSeqNP_037384.1. NM_013252.2. [Q9NY25-1]
UniGeneHs.446235.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2YHFX-ray1.90A/B/C/D/E/F/G/H/I70-187[»]
ProteinModelPortalQ9NY25.
SMRQ9NY25. Positions 70-187.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-60627N.
STRING9606.ENSP00000265306.

Polymorphism databases

DMDM59797971.

Proteomic databases

PaxDbQ9NY25.
PRIDEQ9NY25.

Protocols and materials databases

DNASU23601.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000546910; ENSP00000449999; ENSG00000258227. [Q9NY25-1]
ENST00000567443; ENSP00000455144; ENSG00000261180. [Q9NY25-1]
GeneID23601.
KEGGhsa:23601.
UCSCuc003vwv.1. human. [Q9NY25-1]
uc003vww.1. human. [Q9NY25-2]

Organism-specific databases

CTD23601.
GeneCardsGC07M141627.
HGNCHGNC:2054. CLEC5A.
MIM604987. gene.
neXtProtNX_Q9NY25.
PharmGKBPA26583.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG269413.
HOGENOMHOG000252978.
HOVERGENHBG081250.
InParanoidQ9NY25.
KOK10073.
OMAFNCVTIG.
PhylomeDBQ9NY25.
TreeFamTF337735.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressQ9NY25.
BgeeQ9NY25.
CleanExHS_CLEC5A.
GenevestigatorQ9NY25.

Family and domain databases

Gene3D3.10.100.10. 1 hit.
InterProIPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR016187. C-type_lectin_fold.
[Graphical view]
PfamPF00059. Lectin_C. 1 hit.
[Graphical view]
SMARTSM00034. CLECT. 1 hit.
[Graphical view]
SUPFAMSSF56436. SSF56436. 1 hit.
PROSITEPS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9NY25.
GeneWikiCLEC5A.
GenomeRNAi23601.
NextBio46284.
PROQ9NY25.
SOURCESearch...

Entry information

Entry nameCLC5A_HUMAN
AccessionPrimary (citable) accession number: Q9NY25
Secondary accession number(s): Q52M11, Q9UKQ0
Entry history
Integrated into UniProtKB/Swiss-Prot: February 15, 2005
Last sequence update: October 1, 2000
Last modified: July 9, 2014
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM