Q9NY25 (CLC5A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	CLEC5A
Synonyms:	CLECSF5, MDL1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	188 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Host-virus interaction Immunity Innate immunity
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	Lectin
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular 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 osteoblast development Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cytokine secretion Inferred from electronic annotation. Source: Compara signal transduction Traceable author statement Ref.1. Source: ProtInc virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cell surface Inferred from sequence or structural similarity. Source: UniProtKB integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	carbohydrate binding Inferred from electronic annotation. Source: InterPro viral 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 188

188

C-type lectin domain family 5 member A

PRO_0000046632

Regions

Topological domain

1 – 4

4

Cytoplasmic Potential

Transmembrane

5 – 27

23

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

28 – 188

161

Extracellular Potential

Domain

78 – 184

107

C-type lectin

Amino acid modifications

Glycosylation

32

1

N-linked (GlcNAc...) Potential

Glycosylation

93

1

N-linked (GlcNAc...) Potential

Glycosylation

144

1

N-linked (GlcNAc...) Potential

Glycosylation

151

1

N-linked (GlcNAc...) Potential

Disulfide bond

71 ↔ 82

By similarity

Disulfide bond

99 ↔ 183

By similarity

Disulfide bond

161 ↔ 175

By similarity

Natural variations

Alternative sequence

116

1

Missing in isoform 2.

VSP_012839

Natural variant

141

1

R → H.
Corresponds to variant rs35942193 [ dbSNP | Ensembl ].

VAR_050110

Experimental info

Mutagenesis

16

1

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

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

188

Helix Strand Turn

Details...

Beta strand

76 – 78

3

Beta strand

81 – 85

5

Helix

92 – 100

9

Turn

101 – 103

3

Helix

112 – 122

11

Beta strand

127 – 133

7

Turn

135 – 137

3

Beta strand

138 – 142

5

Turn

143 – 145

3

Beta strand

152 – 154

3

Beta strand

161 – 173

13

Beta strand

179 – 186

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 94A2DBD520DC1985	FASTA	188	21,521
	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
	Isoform 2 [UniParc]. Checksum: 9FC97A17AF8C62F9	FASTA	187	21,393
	10 20 30 40 50 60 MNWHMIISGL IVVVLKVVGM TLFLLYFPQI FNKSNDGFTT TRSYGTVSQI FGSSSPSPNG 70 80 90 100 110 120 FITTRSYGTV CPKDWEFYQA RCFFLSTSES SWNESRDFCK GKGSTLAIVN TPEKLFLQDI 130 140 150 160 170 180 TDAEKYFIGL IYHREEKRWR WINNSVFNGN VTNQNQNFNC ATIGLTKTFD AASCDISYRR ICEKNAK

References

	« Hide 'large scale' referencesShow '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. , 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.

Web resources

Functional Glycomics Gateway - Glycan Binding

MDL-1

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.

IPI

IPI00001675.
IPI00552895.

RefSeq

NP_037384.1. NM_013252.2.

UniGene

Hs.446235.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2YHF	X-ray	1.90	A/B/C/D/E/F/G/H/I	71-187	[»]

ProteinModelPortal

Q9NY25.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000265306.

Polymorphism databases

DMDM

59797971.

Proteomic databases

PaxDb

Q9NY25.

PRIDE

Q9NY25.

Protocols and materials databases

DNASU

23601.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000546910; ENSP00000449999; ENSG00000258227.
ENST00000567443; ENSP00000455144; ENSG00000261180.

GeneID

23601.

KEGG

hsa:23601.

UCSC

uc003vwv.1. human.
uc003vww.1. human.

Organism-specific databases

CTD

23601.

GeneCards

GC07M141627.

HGNC

HGNC:2054. CLEC5A.

MIM

604987. gene.

neXtProt

NX_Q9NY25.

PharmGKB

PA26583.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG269413.

HOGENOM

HOG000252978.

HOVERGEN

HBG081250.

InParanoid

Q9NY25.

KO

K10073.

OMA

KWRWINN.

OrthoDB

EOG473PSF.

PhylomeDB

Q9NY25.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q9NY25.

Bgee

Q9NY25.

CleanEx

HS_CLEC5A.

Genevestigator

Q9NY25.

GermOnline

ENSG00000090269. Homo sapiens.

Family and domain databases

Gene3D

3.10.100.10. 1 hit.

InterPro

IPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR016187. C-type_lectin_fold.
[Graphical view]

Pfam

PF00059. Lectin_C. 1 hit.
[Graphical view]

SMART

SM00034. CLECT. 1 hit.
[Graphical view]

SUPFAM

SSF56436. C-type_lectin_fold. 1 hit.

PROSITE

PS00615. C_TYPE_LECTIN_1. False negative.
PS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9NY25.

GenomeRNAi

23601.

NextBio

46284.

SOURCE

Search...

Entry information

Entry name

CLC5A_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.