Q9R007 (CLC5A_MOUSE) 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

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	190 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. Critical macrophage receptor for dengue virus serotypes 1-4. The binding of dengue virus to CLEC5A triggers signaling through phosphylation of TYROBP, this interaction does not result in viral entry but stimulates proinflammatory cytokine release. Ref.1 Ref.5 Ref.7 Ref.8
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 Ref.7
Subcellular location	Cell membrane; Single-pass type II membrane protein Ref.6.
Tissue specificity	Expressed in macrophage cell line J-774, but not in T-cell lines, B-cell lines, or mast cell lines. Strong expression in bone marrow cells or thioglycollate induced neutrophils (at protein level). Ref.1 Ref.6 Ref.8
Induction	Up-regulated during the differentiation of myeloid cell line 32Dcl3 into neutrophils.
Post-translational modification	N-glycosylated. Contains sialic acid residues. Ref.6 Ref.7
Involvement in disease	Involved in the pathogenetic mechanisms of Japanese encephalitis virus (JEV) infection of the brain. JEV infection of young mice results in increased expression of CLEC5A in spleen and brain with consequent activation of proinflammatory cytokines secretion.
Sequence similarities	Contains 1 C-type lectin domain.

Ontologies

Keywords
Biological process	Immunity Innate immunity
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	Lectin
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	innate immune response Inferred from direct assay Ref.6. Source: UniProtKB negative regulation of apoptotic process Inferred from direct assay Ref.6. Source: UniProtKB osteoblast development Inferred from direct assay Ref.7. Source: UniProtKB positive regulation of cytokine secretion Inferred from mutant phenotype Ref.5. Source: UniProtKB
Cellular_component	cell surface Inferred from direct assay Ref.6. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
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 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 3 (identifier: Q9R007-3)

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 1 (identifier: Q9R007-1)

The sequence of this isoform differs from the canonical sequence as follows:
     28-57: PQVFGKSNDGFVPTESYGTTSVQNVSQIFG → SQIFG

Isoform 2 (identifier: Q9R007-2)

The sequence of this isoform differs from the canonical sequence as follows:
     118-118: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 190	190	C-type lectin domain family 5 member A		PRO_0000046633
Regions
	Topological domain	1 – 4	4	Cytoplasmic Potential
	Transmembrane	5 – 25	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	26 – 190	165	Extracellular Potential
	Domain	80 – 186	107	C-type lectin
Amino acid modifications
	Glycosylation	51	1	N-linked (GlcNAc...) Potential
	Glycosylation	146	1	N-linked (GlcNAc...) Potential
	Glycosylation	153	1	N-linked (GlcNAc...) Potential
	Disulfide bond	101 ↔ 185		By similarity
	Disulfide bond	163 ↔ 177		By similarity
Natural variations
	Alternative sequence	28 – 57	30	PQVFG…SQIFG → SQIFG in isoform 1.		VSP_041577
	Alternative sequence	118	1	Missing in isoform 2.		VSP_012840

Sequences

	Sequence		Length	Mass (Da)
	Isoform 3 [UniParc]. Last modified June 28, 2011. Version 2. Checksum: AB6AACB3A8D36637	FASTA	190	21,696
	10 20 30 40 50 60 MNWHMIISGL IVVVIKVVGM TFFLLYFPQV FGKSNDGFVP TESYGTTSVQ NVSQIFGRND 70 80 90 100 110 120 ESTMPTRSYG TVCPRNWDFH QGKCFFFSFS ESPWKDSMDY CATQGSTLAI VNTPEKLKYL 130 140 150 160 170 180 QDIAGIENYF IGLVRQPGEK KWRWINNSVF NGNVTNQDQN FDCVTIGLTK TYDAASCEVS 190 YRWICEMNAK
	Isoform 1 [UniParc]. Checksum: 626D64392A513282	FASTA	165	19,055
	10 20 30 40 50 60 MNWHMIISGL IVVVIKVVGM TFFLLYFSQI FGRNDESTMP TRSYGTVCPR NWDFHQGKCF 70 80 90 100 110 120 FFSFSESPWK DSMDYCATQG STLAIVNTPE KLKYLQDIAG IENYFIGLVR QPGEKKWRWI 130 140 150 160 NNSVFNGNVT NQDQNFDCVT IGLTKTYDAA SCEVSYRWIC EMNAK
	Isoform 2 [UniParc]. Checksum: 28C26A90421D745D	FASTA	189	21,567
	10 20 30 40 50 60 MNWHMIISGL IVVVIKVVGM TFFLLYFPQV FGKSNDGFVP TESYGTTSVQ NVSQIFGRND 70 80 90 100 110 120 ESTMPTRSYG TVCPRNWDFH QGKCFFFSFS ESPWKDSMDY CATQGSTLAI VNTPEKLYLQ 130 140 150 160 170 180 DIAGIENYFI GLVRQPGEKK WRWINNSVFN GNVTNQDQNF DCVTIGLTKT YDAASCEVSY RWICEMNAK

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 1), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH TYROBP. Strain: BALB/c. Tissue: Myeloid.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Adipose tissue and Bone.
[3]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases 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 3).
[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]	"Expression and functional role of MDL-1 (CLEC5A) in mouse myeloid lineage cells." Aoki N., Kimura Y., Kimura S., Nagato T., Azumi M., Kobayashi H., Sato K., Tateno M. J. Leukoc. Biol. 85:508-517(2009) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, INTERACTION WITH HCST, SUBCELLULAR LOCATION, GLYCOSYLATION, SIALIC ACID CONTENT.
[7]	"Signal adaptor DAP10 associates with MDL-1 and triggers osteoclastogenesis in cooperation with DAP12." Inui M., Kikuchi Y., Aoki N., Endo S., Maeda T., Sugahara-Tobinai A., Fujimura S., Nakamura A., Kumanogoh A., Colonna M., Takai T. Proc. Natl. Acad. Sci. U.S.A. 106:4816-4821(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HCST, GLYCOSYLATION, FUNCTION.
[8]	"Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis." Joyce-Shaikh B., Bigler M.E., Chao C.C., Murphy E.E., Blumenschein W.M., Adamopoulos I.E., Heyworth P.G., Antonenko S., Bowman E.P., McClanahan T.K., Phillips J.H., Cua D.J. J. Exp. Med. 207:579-589(2010) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, FUNCTION.
[9]	"Expression profile of Japanese encephalitis virus induced neuroinflammation and its implication in disease severity." Gupta N., Lomash V., Rao P.V. J. Clin. Virol. 49:4-10(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN JAPANESE ENCEPHALITIS VIRUS INFECTION.
+	Additional computationally mapped references.

Web resources

Functional Glycomics Gateway - Glycan Binding

MDL-1

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF139769 mRNA. Translation: AAF02492.1. AK036697 mRNA. Translation: BAC29537.1. AK046600 mRNA. Translation: BAC32802.1. AK137482 mRNA. Translation: BAE23374.1. CH466533 Genomic DNA. Translation: EDL13570.1. BC104364 mRNA. Translation: AAI04365.1. BC104365 mRNA. Translation: AAI04366.1.
IPI	IPI00126729. IPI00553591. IPI00652111.
RefSeq	NP_001033693.1. NM_001038604.1. NP_067339.1. NM_021364.2.
UniGene	Mm.103765.
3D structure databases
ProteinModelPortal	Q9R007.
SMR	Q9R007. Positions 72-189.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-48775N.
Proteomic databases
PRIDE	Q9R007.
Protocols and materials databases
DNASU	23845.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000101491; ENSMUSP00000099030; ENSMUSG00000029915. ENSMUST00000129948; ENSMUSP00000121848; ENSMUSG00000029915. ENSMUST00000177178; ENSMUSP00000135240; ENSMUSG00000029915.
GeneID	23845.
KEGG	mmu:23845.
UCSC	uc009bna.1. mouse. uc009bnb.1. mouse. uc009bnc.1. mouse.
Organism-specific databases
CTD	23601.
MGI	MGI:1345151. Clec5a.
Phylogenomic databases
eggNOG	NOG269413.
GeneTree	ENSGT00680000099819.
HOGENOM	HOG000252978.
HOVERGEN	HBG081250.
InParanoid	Q3SXC9.
KO	K10073.
OMA	KWRWINN.
OrthoDB	EOG473PSF.
Gene expression databases
Bgee	Q9R007.
CleanEx	MM_CLEC5A.
Genevestigator	Q9R007.
GermOnline	ENSMUSG00000029915. Mus musculus.
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
NextBio	303527.
SOURCE	Search...

Entry information

Entry name

CLC5A_MOUSE

Accession

Primary (citable) accession number: Q9R007
Secondary accession number(s): Q3SXC9, Q3UV97, Q8BL24

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 15, 2005
Last sequence update:	June 28, 2011
Last modified:	May 29, 2013
This is version 94 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program