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Protein

C-type lectin domain family 4 member A

Gene

CLEC4A

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

Functioni

C-type lectin receptor that binds carbohydrates mannose and fucose but also weakly interacts with N-acetylglucosamine (GlcNAc) in a Ca2+-dependent manner (PubMed:27015765). Involved in regulating immune reactivity (PubMed:18258799, PubMed:10438934). Once triggered by antigen, it is internalized by clathrin-dependent endocytosis and delivers its antigenic cargo into the antigen presentation pathway resulting in cross-priming of CD8+ T cells. This cross-presentation and cross-priming are enhanced by TLR7 and TLR8 agonists with increased expansion of the CD8+ T cells, high production of IFNG and TNF with reduced levels of IL4, IL5 and IL13 (PubMed:18258799, PubMed:20530286). In plasmacytoid dendritic cells, inhibits TLR9-mediated IFNA and TNF production (PubMed:18258799). May be involved via its ITIM motif (immunoreceptor tyrosine-based inhibitory motifs) in the inhibition of B-cell-receptor-mediated calcium mobilization and protein tyrosine phosphorylation (PubMed:10438934).4 Publications
(Microbial infection) Involved in the interaction between HIV-1 virus and dendritic cells. Enhances HIV-1 binding/entry and virus infection. Requires ITIM motif-associated signal transduction pathway involving phosphatases PTPN6 and PTPN11, SYK, Src kinases and MAP kinases.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi143Calcium 1; via carbonyl oxygenCombined sources1 Publication1
Metal bindingi145Calcium 1Combined sources1 Publication1
Metal bindingi149Calcium 1Combined sources1 Publication1
Metal bindingi195Calcium 2Combined sources1 Publication1
Metal bindingi197Calcium 2Combined sources1 Publication1
Metal bindingi201Calcium 2Combined sources1 Publication1
Binding sitei201MannoseCombined sources1 Publication1
Metal bindingi218Calcium 2Combined sources1 Publication1
Metal bindingi219Calcium 2Combined sources1 Publication1
Metal bindingi231Calcium 1Combined sources1 Publication1

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • carbohydrate binding Source: UniProtKB
  • mannose binding Source: UniProtKB
  • transmembrane signaling receptor activity Source: ProtInc

GO - Biological processi

Keywordsi

Biological processAdaptive immunity, Immunity, Innate immunity
LigandCalcium, Lectin, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-5621480 Dectin-2 family

Protein family/group databases

UniLectiniQ9UMR7

Names & Taxonomyi

Protein namesi
Recommended name:
C-type lectin domain family 4 member ACurated
Alternative name(s):
C-type lectin DDB27
C-type lectin superfamily member 6
Dendritic cell immunoreceptor
Lectin-like immunoreceptor
CD_antigen: CD367
Gene namesi
Name:CLEC4AImported
Synonyms:CLECSF61 Publication, DCIR1 Publication, LLIR
ORF Names:HDCGC13P
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000111729.12
HGNCiHGNC:13257 CLEC4A
MIMi605306 gene
neXtProtiNX_Q9UMR7

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 – 48CytoplasmicSequence analysisAdd BLAST48
Transmembranei49 – 69Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini70 – 237ExtracellularSequence analysisAdd BLAST168

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi6T → F: Decreases HIV-1 binding/entry in cells as well as virus replication. 1 Publication1
Mutagenesisi7Y → F: Decreases HIV-1 binding/entry in cells as well as virus replication. 1 Publication1

Organism-specific databases

DisGeNETi50856
OpenTargetsiENSG00000111729
PharmGKBiPA26584

Polymorphism and mutation databases

BioMutaiCLEC4A
DMDMi59797977

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000466121 – 237C-type lectin domain family 4 member AAdd BLAST237

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi106 ↔ 117PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi134 ↔ 230PROSITE-ProRule annotationCombined sources1 Publication
Glycosylationi185N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi203 ↔ 222PROSITE-ProRule annotationCombined sources1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9UMR7
PeptideAtlasiQ9UMR7
PRIDEiQ9UMR7
ProteomicsDBi85200
85201 [Q9UMR7-2]
85202 [Q9UMR7-3]
85203 [Q9UMR7-4]

PTM databases

iPTMnetiQ9UMR7
PhosphoSitePlusiQ9UMR7

Expressioni

Tissue specificityi

Expressed preferentially in hematopoietic tissues. Expressed in all circulating Ag-presenting cells such as dendritic cells, myeloid cells, monocytes, macrophages, B-cells and epidermal Langerhans cells (at protein level). Expressed in peripheral blood leukocytes, neutrophils, moderate quantities in spleen, lymph node, and bone marrow, and at very low levels in thymus.5 Publications

Inductioni

TNF alpha, IL-1 alpha, and LPS, down-regulated expression at the surface of neutrophils (at protein level) (PubMed:11994513). Expression is decreased in dendritic cells by signals inducing their maturation (e.g. CD40 ligand, TLR9 ligands, LPS, and TNF alpha) (PubMed:10438934, PubMed:18258799). Isoform 2: mRNA expression is up-regulated by agonists of neutrophils CSF2/GM-CSF, IL3/interleukin-3, IL4/interleukin-4 and IL13/interleukin-13 (PubMed:11994513).3 Publications

Gene expression databases

BgeeiENSG00000111729 Expressed in 177 organ(s), highest expression level in bone marrow
CleanExiHS_CLEC4A
ExpressionAtlasiQ9UMR7 baseline and differential
GenevisibleiQ9UMR7 HS

Organism-specific databases

HPAiHPA007842

Interactioni

Subunit structurei

May interact with PTPN6 via its ITIM motif.

Protein-protein interaction databases

BioGridi119158, 53 interactors
STRINGi9606.ENSP00000229332

Structurei

Secondary structure

1237
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9UMR7
SMRiQ9UMR7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini113 – 231C-type lectinPROSITE-ProRule annotationAdd BLAST119

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni195 – 197Mannose bindingCombined sources1 Publication3
Regioni207 – 209N-acetyl-D-glucosamine bindingCombined sources1 Publication3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi5 – 10ITIM motif1 Publication6

Domaini

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4297 Eukaryota
ENOG410XPJ1 LUCA
GeneTreeiENSGT00920000149038
HOGENOMiHOG000059556
HOVERGENiHBG050992
InParanoidiQ9UMR7
KOiK10057
OMAiSSNCYFI
OrthoDBiEOG091G0O28
PhylomeDBiQ9UMR7
TreeFamiTF333341

Family and domain databases

CDDicd03590 CLECT_DC-SIGN_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
IPR018378 C-type_lectin_CS
IPR033989 CD209-like_CTLD
IPR016187 CTDL_fold
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
PS00615 C_TYPE_LECTIN_1, 1 hit
PS50041 C_TYPE_LECTIN_2, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9UMR7-1) [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
MTSEITYAEV RFKNEFKSSG INTASSAASK ERTAPHKSNT GFPKLLCASL
60 70 80 90 100
LIFFLLLAIS FFIAFVIFFQ KYSQLLEKKT TKELVHTTLE CVKKNMPVEE
110 120 130 140 150
TAWSCCPKNW KSFSSNCYFI STESASWQDS EKDCARMEAH LLVINTQEEQ
160 170 180 190 200
DFIFQNLQEE SAYFVGLSDP EGQRHWQWVD QTPYNESSTF WHPREPSDPN
210 220 230
ERCVVLNFRK SPKRWGWNDV NCLGPQRSVC EMMKIHL
Length:237
Mass (Da):27,512
Last modified:May 1, 2000 - v1
Checksum:i1D07003E4C9CF96E
GO
Isoform 2 (identifier: Q9UMR7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     67-100: IFFQKYSQLLEKKTTKELVHTTLECVKKNMPVEE → K

Show »
Length:204
Mass (Da):23,575
Checksum:i52107ED59D9AEFE0
GO
Isoform 3 (identifier: Q9UMR7-3) [UniParc]FASTAAdd to basket
Also known as: llirV1

The sequence of this isoform differs from the canonical sequence as follows:
     28-67: ASKERTAPHKSNTGFPKLLCASLLIFFLLLAISFFIAFVI → V

Show »
Length:198
Mass (Da):23,203
Checksum:iD165142F9DA7EE85
GO
Isoform 4 (identifier: Q9UMR7-4) [UniParc]FASTAAdd to basket
Also known as: llirV2

The sequence of this isoform differs from the canonical sequence as follows:
     28-99: Missing.

Show »
Length:165
Mass (Da):19,280
Checksum:iE5CB43A6D3437B67
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A286YF15A0A286YF15_HUMAN
C-type lectin domain family 4 membe...
CLEC4A
84Annotation score:

Sequence cautioni

The sequence AAL56016 differs from that shown. Reason: Frameshift at position 229.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti130S → C in AAF75560 (PubMed:16541075).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02126036H → L3 PublicationsCorresponds to variant dbSNP:rs2024301Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01284228 – 99Missing in isoform 4. 1 PublicationAdd BLAST72
Alternative sequenceiVSP_04134828 – 67ASKER…IAFVI → V in isoform 3. 1 PublicationAdd BLAST40
Alternative sequenceiVSP_01284467 – 100IFFQK…MPVEE → K in isoform 2. 1 PublicationAdd BLAST34

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ133532 mRNA Translation: CAB54001.1
AF067800 mRNA Translation: AAF75560.1
AF328684 mRNA Translation: AAL56016.1 Frameshift.
AF109146 mRNA Translation: AAF14348.1
AF200738 mRNA Translation: AAG35593.1
AC006511 Genomic DNA No translation available.
AC092111 Genomic DNA No translation available.
BC074822 mRNA Translation: AAH74822.1
BC074874 mRNA Translation: AAH74874.1
BC117439 mRNA Translation: AAI17440.1
BC117441 mRNA Translation: AAI17442.1
CCDSiCCDS41745.1 [Q9UMR7-3]
CCDS8590.1 [Q9UMR7-1]
CCDS8591.1 [Q9UMR7-4]
CCDS8592.1 [Q9UMR7-2]
PIRiJC7608
RefSeqiNP_057268.1, NM_016184.3 [Q9UMR7-1]
NP_919429.2, NM_194447.2 [Q9UMR7-3]
NP_919430.1, NM_194448.2 [Q9UMR7-4]
NP_919432.1, NM_194450.2 [Q9UMR7-2]
UniGeneiHs.504657

Genome annotation databases

EnsembliENST00000229332; ENSP00000229332; ENSG00000111729 [Q9UMR7-1]
ENST00000345999; ENSP00000344646; ENSG00000111729 [Q9UMR7-4]
ENST00000352620; ENSP00000247243; ENSG00000111729 [Q9UMR7-2]
ENST00000360500; ENSP00000353690; ENSG00000111729 [Q9UMR7-3]
GeneIDi50856
KEGGihsa:50856
UCSCiuc001qtz.1 human [Q9UMR7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Functional Glycomics Gateway - Glycan Binding

DCIR

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ133532 mRNA Translation: CAB54001.1
AF067800 mRNA Translation: AAF75560.1
AF328684 mRNA Translation: AAL56016.1 Frameshift.
AF109146 mRNA Translation: AAF14348.1
AF200738 mRNA Translation: AAG35593.1
AC006511 Genomic DNA No translation available.
AC092111 Genomic DNA No translation available.
BC074822 mRNA Translation: AAH74822.1
BC074874 mRNA Translation: AAH74874.1
BC117439 mRNA Translation: AAI17440.1
BC117441 mRNA Translation: AAI17442.1
CCDSiCCDS41745.1 [Q9UMR7-3]
CCDS8590.1 [Q9UMR7-1]
CCDS8591.1 [Q9UMR7-4]
CCDS8592.1 [Q9UMR7-2]
PIRiJC7608
RefSeqiNP_057268.1, NM_016184.3 [Q9UMR7-1]
NP_919429.2, NM_194447.2 [Q9UMR7-3]
NP_919430.1, NM_194448.2 [Q9UMR7-4]
NP_919432.1, NM_194450.2 [Q9UMR7-2]
UniGeneiHs.504657

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5B1WX-ray3.05A/B/C/D106-237[»]
5B1XX-ray2.90A/B/C/D106-237[»]
ProteinModelPortaliQ9UMR7
SMRiQ9UMR7
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119158, 53 interactors
STRINGi9606.ENSP00000229332

Protein family/group databases

UniLectiniQ9UMR7

PTM databases

iPTMnetiQ9UMR7
PhosphoSitePlusiQ9UMR7

Polymorphism and mutation databases

BioMutaiCLEC4A
DMDMi59797977

Proteomic databases

PaxDbiQ9UMR7
PeptideAtlasiQ9UMR7
PRIDEiQ9UMR7
ProteomicsDBi85200
85201 [Q9UMR7-2]
85202 [Q9UMR7-3]
85203 [Q9UMR7-4]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000229332; ENSP00000229332; ENSG00000111729 [Q9UMR7-1]
ENST00000345999; ENSP00000344646; ENSG00000111729 [Q9UMR7-4]
ENST00000352620; ENSP00000247243; ENSG00000111729 [Q9UMR7-2]
ENST00000360500; ENSP00000353690; ENSG00000111729 [Q9UMR7-3]
GeneIDi50856
KEGGihsa:50856
UCSCiuc001qtz.1 human [Q9UMR7-1]

Organism-specific databases

CTDi50856
DisGeNETi50856
EuPathDBiHostDB:ENSG00000111729.12
GeneCardsiCLEC4A
HGNCiHGNC:13257 CLEC4A
HPAiHPA007842
MIMi605306 gene
neXtProtiNX_Q9UMR7
OpenTargetsiENSG00000111729
PharmGKBiPA26584
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4297 Eukaryota
ENOG410XPJ1 LUCA
GeneTreeiENSGT00920000149038
HOGENOMiHOG000059556
HOVERGENiHBG050992
InParanoidiQ9UMR7
KOiK10057
OMAiSSNCYFI
OrthoDBiEOG091G0O28
PhylomeDBiQ9UMR7
TreeFamiTF333341

Enzyme and pathway databases

ReactomeiR-HSA-5621480 Dectin-2 family

Miscellaneous databases

ChiTaRSiCLEC4A human
GeneWikiiCLEC4A
GenomeRNAii50856
PROiPR:Q9UMR7
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000111729 Expressed in 177 organ(s), highest expression level in bone marrow
CleanExiHS_CLEC4A
ExpressionAtlasiQ9UMR7 baseline and differential
GenevisibleiQ9UMR7 HS

Family and domain databases

CDDicd03590 CLECT_DC-SIGN_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
IPR018378 C-type_lectin_CS
IPR033989 CD209-like_CTLD
IPR016187 CTDL_fold
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
PS00615 C_TYPE_LECTIN_1, 1 hit
PS50041 C_TYPE_LECTIN_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCLC4A_HUMAN
AccessioniPrimary (citable) accession number: Q9UMR7
Secondary accession number(s): Q17R69
, Q8WXW9, Q9H2Z9, Q9NS33, Q9UI34
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 15, 2005
Last sequence update: May 1, 2000
Last modified: October 10, 2018
This is version 151 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 cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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