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FLASH GENE

Symbol

ACKR2

contributors: mct - updated : 18-12-2013

HGNC name	chemokine binding protein 2
HGNC id	1565

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

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 Cardiovascular vessel         Homo sapiens Lymphoid/Immune lymphatic vessel         Homo sapiens Reproductive female system placenta       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell Homo sapiens Nervous astrocyte Homo sapiens Adult

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal, pregnancy

Text	primarily, in placenta and fetal liver

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	seven transmembrane segments (7TM) receptor
	conserved 58-AA C terminus, with a serine cluster controling the constitutive phosphorylation, high stability, and intracellular trafficking itinerary of the receptor, but indispensable for scavenging because it prevents initial chemokine engagement of ACKR2 from inhibiting subsequent chemokine uptake

HOMOLOGY

interspecies

homolog to murine Cmkbr9

Homologene

FAMILY	G protein coupled receptor superfamily (family 1)
	beta chemokine receptor
	chemokine decoy receptor family

CATEGORY

immunity/defense , receptor membrane G

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endosome

basic FUNCTION	plays a nonredundant role in the protection against fetal loss caused by systemic inflammation and antiphospholipid antibodies
	heptahelical receptor that suppresses inflammation and tumorigenesis by scavenging extracellular pro-inflammatory CC chemokines
	plays a negative role in the growth and metastasis of breast cancer
	role of the chemokine scavenger receptor D6 in balancing inflammation and immune activation
	key regulator of lymphatic function and a novel, and indispensable, contributor to the integration of innate and adaptive immune responses
	scavenger activity in acute inflammation, and may have additional roles in chronic inflammatory conditions possibly promoting immune activation
	is able to bind and drive to degradative compartments most inflammatory CC chemokines and is able to convey G-protein independent signaling events to optimize its scavenging activity
	specifically involved in regulating the ability of lymphatic endothelial cells (LEC) to discriminate between mature and immature dendritic cells (DCs) 1)
	essential regulator of inflammatory leukocyte interactions with LECs and is required for immature/mature DC discrimination by LECs 1)

CELLULAR PROCESS

cell communication

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule

protein	with affinity binding for monocyte chemoattractant protein 1 (SCYA2) and 2 (SCYA8)
	CCL2 binding to primary adult human astrocytes is CCR2-independent and is likely to be mediated via the ACKR2 decoy chemokine receptor
	control of CCR2 ligands by ACKR2 regulates the traffic of Ly6C(high) monocytes and controls their immunosuppressive potential
	engagement of ACKR2 by its ligands activates a ARRB1-dependent, G protein-independent signaling pathway that results in the phosphorylation of the actin-binding protein cofilin through the RAC1-PAK1-LIMK1 cascade

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in patients with COPD as compared with both smoker and nonsmoker control subjects

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

mice lacking D6 expression in the nonhematopoietic compartment have a selective increase in the number of Ly6C(high) monocytes in the circulation and in secondary lymphoid tissues