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FLASH GENE

Symbol

CLEC4A

contributors: SGE/npt - updated : 23-03-2010

HGNC name	C-type lectin domain family 4, member A
HGNC id	13257

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	12p13.31      Physical location : 8.276.227 - 8.291.203
Synonym name	C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 6
	lectin-like immunoreceptor
	dendritic cell immunoreceptor
	C-type lectin DDB27
Synonym symbol(s)	DCIR, LLIR, DDB27, CLECSF6, HDCGC13P

DNA

TYPE	functioning gene
STRUCTURE	14.98 kb     6 Exon(s)    1 Copie(s)

MAPPING

cloned

Y

linked

Y

status

provisional

regionally located

. being closely linked to other CTL/CTLD superfamily members in the natural killer gene complex region

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_016184 6 splicing 1284 NP_057268 27 237 peripheral blood leukocytes, spleen, lymph node, bone marrow Bates (1999) isoform 1 a single CRD, a double-cysteine motif at the strat of the lectin domain, a potential N-glycosylation site and an ITIM NM_194450 5 splicing 1185 NP_919432 23 204 epxression is up-regulated by agonists of neutrophils GM-CSF, IL-3, IL-4 and IL-13 Huang (2001) also known as C-type lectin DDB27 short form isoform 2, missing the transmembrane domain compared to isoform 1 NM_194447 5 splicing 1167 NP_919429 23 198 - Huang (2001) also known as LLIRv1 isoform 3, missing the transmembrane domain compared to isoform 1 NM_194448 4 splicing 1068 NP_919430 19 165 - Huang (2001) also known as LLIRv2 isoform 4, missing a region thought to be responsible for oligomerization compared to isoform 1

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Lymphoid/Immune lymph node           spleen       moderately   thymus       lowly   tonsils         Nervous spinal cord       lowly Respiratory lung       moderately   respiratory tract trachea     lowly Urinary kidney       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow       Connective bone       Nervous central

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte

cell lineage
cell lines	immature and mature monocyte-derived dendritic cells, monocytes, macrophages, B-cells, myeloid and plasmacytoid dendritic cells (Meyer-Wentrup 2009)
fluid/secretion	blood

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an ITIM motif (immunoreceptor tyrosine-based inhibitory motifs)
	a C-type lectin domain
	a single carbohydrate recognition domain (CRD)
	a double cysteine motif at the start of the lectin domain
	a potential N-glycosylation site
	a 49-aminoacid intracellular immunoreceptor tyrosine-based inhibitory motif (ITIM) proximal to the N terminus

conjugated

GlycoP

HOMOLOGY

Homologene

FAMILY

C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily

CATEGORY

adhesion , receptor membrane

SUBCELLULAR LOCALIZATION	plasma membrane
text	integral to plasma membrane
	type II membrane protein

basic FUNCTION	may be involved in regulating immune reactivity
	may play a role in modulating dendritic cells (DC) differentiation and/or maturation
	may be involved via its ITIM motif in the inhibition of B-cell-receptor-mediated calcium mobilization and protein tyrosine phosphorylation
	APC receptor that is endocytosed in a clathrin-dependent manner and inhibits TLR8-mediated cytokine production (Meyer-Wentrup 2009)

CELLULAR PROCESS	cell life, differentiation

PHYSIOLOGICAL PROCESS

immunity/defense

text	antimicrobial humoral response

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule	other,
	sugar

protein	PTPN6 via its ITIM motif (Huang 2001)
	lectin

cell & other

ligand for HIV1, participating in viral capture and transmission (Lambert 2008)

REGULATION

activated by

TP53

repressed by

IFN-gamma (Ronninger 2008)

ASSOCIATED DISORDERS

corresponding disease(s)

Susceptibility

Variant & Polymorphism SNP	polymorphism is associated with rheumatoid arthritis (Ronninger 2008, Lorentzen 2007)

Candidate gene
Marker
Therapy target	targeting CLEC4A can modulate plasmacytoid dendritic cell function and may be applied in disease prevention and treatment, inhibiting IFN-alpha production (Meyer-Wentrup 2008)

ANIMAL & CELL MODELS