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Q9R007

- CLC5A_MOUSE

UniProt

Q9R007 - CLC5A_MOUSE

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Protein
C-type lectin domain family 5 member A
Gene
Clec5a, Clecsf5, Mdl1
Organism
Mus musculus (Mouse)
Status
Reviewed - 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. 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.4 Publications

GO - Molecular functioni

  1. carbohydrate binding Source: InterPro
  2. protein binding Source: UniProtKB
  3. virus receptor activity Source: UniProtKB

GO - Biological processi

  1. innate immune response Source: UniProtKB
  2. negative regulation of apoptotic process Source: UniProtKB
  3. negative regulation of myeloid cell apoptotic process Source: MGI
  4. osteoblast development Source: UniProtKB
  5. positive regulation of cytokine secretion Source: UniProtKB
  6. response to virus Source: GOC
Complete GO annotation...

Keywords - Biological processi

Immunity, Innate immunity

Keywords - Ligandi

Lectin

Enzyme and pathway databases

ReactomeiREACT_188188. DAP12 interactions.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 6

Organism-specific databases

MGIiMGI:1345151. Clec5a.

Subcellular locationi

Cell membrane; Single-pass type II membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 44Cytoplasmic Reviewed prediction
Transmembranei5 – 2521Helical; Signal-anchor for type II membrane protein; Reviewed prediction
Add
BLAST
Topological domaini26 – 190165Extracellular Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. cell surface Source: UniProtKB
  2. integral component of membrane Source: UniProtKB-KW
  3. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 190190C-type lectin domain family 5 member A
PRO_0000046633Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi51 – 511N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi101 ↔ 185 By similarity
Glycosylationi146 – 1461N-linked (GlcNAc...) Reviewed prediction
Glycosylationi153 – 1531N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi163 ↔ 177 By similarity

Post-translational modificationi

N-glycosylated. Contains sialic acid residues.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PRIDEiQ9R007.

Expressioni

Tissue specificityi

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).3 Publications

Inductioni

Up-regulated during the differentiation of myeloid cell line 32Dcl3 into neutrophils.

Gene expression databases

BgeeiQ9R007.
CleanExiMM_CLEC5A.
GenevestigatoriQ9R007.

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.3 Publications

Protein-protein interaction databases

DIPiDIP-48775N.

Structurei

3D structure databases

ProteinModelPortaliQ9R007.
SMRiQ9R007. Positions 72-189.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini80 – 186107C-type lectin
Add
BLAST

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG269413.
GeneTreeiENSGT00730000111396.
HOGENOMiHOG000252978.
HOVERGENiHBG081250.
InParanoidiQ3SXC9.
KOiK10073.
OMAiFNCVTIG.
OrthoDBiEOG7GQXX7.
PhylomeDBiQ9R007.
TreeFamiTF337735.

Family and domain databases

Gene3Di3.10.100.10. 1 hit.
InterProiIPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR016187. C-type_lectin_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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 3 (identifier: Q9R007-3) [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

MNWHMIISGL IVVVIKVVGM TFFLLYFPQV FGKSNDGFVP TESYGTTSVQ    50
NVSQIFGRND ESTMPTRSYG TVCPRNWDFH QGKCFFFSFS ESPWKDSMDY 100
CATQGSTLAI VNTPEKLKYL QDIAGIENYF IGLVRQPGEK KWRWINNSVF 150
NGNVTNQDQN FDCVTIGLTK TYDAASCEVS YRWICEMNAK 190
Length:190
Mass (Da):21,696
Last modified:June 28, 2011 - v2
Checksum:iAB6AACB3A8D36637
GO
Isoform 1 (identifier: Q9R007-1) [UniParc]FASTAAdd to Basket

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

Show »
Length:165
Mass (Da):19,055
Checksum:i626D64392A513282
GO
Isoform 2 (identifier: Q9R007-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:189
Mass (Da):21,567
Checksum:i28C26A90421D745D
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei28 – 5730PQVFG…SQIFG → SQIFG in isoform 1.
VSP_041577Add
BLAST
Alternative sequencei118 – 1181Missing in isoform 2.
VSP_012840

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS20036.1. [Q9R007-3]
CCDS20037.1. [Q9R007-1]
RefSeqiNP_001033693.1. NM_001038604.1. [Q9R007-3]
NP_067339.1. NM_021364.2. [Q9R007-1]
UniGeneiMm.103765.

Genome annotation databases

EnsembliENSMUST00000101491; ENSMUSP00000099030; ENSMUSG00000029915. [Q9R007-1]
ENSMUST00000129948; ENSMUSP00000121848; ENSMUSG00000029915. [Q9R007-3]
ENSMUST00000177178; ENSMUSP00000135240; ENSMUSG00000029915.
GeneIDi23845.
KEGGimmu:23845.
UCSCiuc009bna.1. mouse. [Q9R007-3]
uc009bnb.1. mouse. [Q9R007-1]
uc009bnc.1. mouse. [Q9R007-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Functional Glycomics Gateway - Glycan Binding

MDL-1

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS20036.1. [Q9R007-3 ]
CCDS20037.1. [Q9R007-1 ]
RefSeqi NP_001033693.1. NM_001038604.1. [Q9R007-3 ]
NP_067339.1. NM_021364.2. [Q9R007-1 ]
UniGenei Mm.103765.

3D structure databases

ProteinModelPortali Q9R007.
SMRi Q9R007. Positions 72-189.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

DIPi DIP-48775N.

Proteomic databases

PRIDEi Q9R007.

Protocols and materials databases

DNASUi 23845.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000101491 ; ENSMUSP00000099030 ; ENSMUSG00000029915 . [Q9R007-1 ]
ENSMUST00000129948 ; ENSMUSP00000121848 ; ENSMUSG00000029915 . [Q9R007-3 ]
ENSMUST00000177178 ; ENSMUSP00000135240 ; ENSMUSG00000029915 .
GeneIDi 23845.
KEGGi mmu:23845.
UCSCi uc009bna.1. mouse. [Q9R007-3 ]
uc009bnb.1. mouse. [Q9R007-1 ]
uc009bnc.1. mouse. [Q9R007-2 ]

Organism-specific databases

CTDi 23601.
MGIi MGI:1345151. Clec5a.

Phylogenomic databases

eggNOGi NOG269413.
GeneTreei ENSGT00730000111396.
HOGENOMi HOG000252978.
HOVERGENi HBG081250.
InParanoidi Q3SXC9.
KOi K10073.
OMAi FNCVTIG.
OrthoDBi EOG7GQXX7.
PhylomeDBi Q9R007.
TreeFami TF337735.

Enzyme and pathway databases

Reactomei REACT_188188. DAP12 interactions.

Miscellaneous databases

NextBioi 303527.
PROi Q9R007.
SOURCEi Search...

Gene expression databases

Bgeei Q9R007.
CleanExi MM_CLEC5A.
Genevestigatori Q9R007.

Family and domain databases

Gene3Di 3.10.100.10. 1 hit.
InterProi IPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR016187. C-type_lectin_fold.
[Graphical view ]
Pfami PF00059. Lectin_C. 1 hit.
[Graphical view ]
SMARTi SM00034. CLECT. 1 hit.
[Graphical view ]
SUPFAMi SSF56436. SSF56436. 1 hit.
PROSITEi PS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiCLC5A_MOUSE
AccessioniPrimary (citable) accession number: Q9R007
Secondary accession number(s): Q3SXC9, Q3UV97, Q8BL24
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 15, 2005
Last sequence update: June 28, 2011
Last modified: September 3, 2014
This is version 106 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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