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FLASH GENE

Symbol

ANXA6

contributors: shn/npt - updated : 04-03-2020

HGNC name	annexin A6
HGNC id	544

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	ubiquitous

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       moderately Digestive liver         Homo sapiens Lymphoid/Immune spleen       highly   thymus       moderately Nervous nerve       highly Urinary kidney       moderately

tissue

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

cells

System Cell Pubmed Species Stage Rna symbol not specific chondrocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a relatively short N terminus
	a C terminal "core" region containing four repeats homolog to the endonexin fold
	contains 8 annexin repeats

conjugated

PhosphoP , Other

HOMOLOGY

interspecies	ortholog to anxa6, Danio rerio
	ortholog to ANXA6, Pan troglodytes
	ortholog to Anxa6, Rattus norvegicus
	ortholog to Anxa6, Mus musculus

Homologene

FAMILY	calcium-dependent membrane and phospholipid binding protein
	annexin family

CATEGORY

regulatory , transport

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,peroxisome
	intracellular,cytoplasm,organelle,endosome
	intracellular,cytoplasm,cytosolic

basic FUNCTION	mediating the endosome aggregation and vesicle fusion in secreting epithelia during exocytosis
	regulating the release of calcium Ca2+ from intracellular strores
	a retinoid binding activity
	putative roles in adhesion-related cellular processes that contribute to breast cancer progression
	may play a particular role in the organization of lipid microdomains in Niemann-Pick disease
	in the presence of calcium, ANXA6 re-located to the fractions enriched in detergent-resistant microdomains only in the Niemann-Pick disease cells, suggestive of ANXA6 participation in organization of these microdomains
	ANXA6 via its stimulatory actions on PRKCA and its role in mediating Ca(2+) flux across membranes regulates terminal differentiation and mineralization events of chondrocytes
	ANXA6-induced plasma membrane remodelling indicated that elevated ANXA6 expression decreased membrane order through the regulation of cellular cholesterol homeostasis and the actin cytoskeleton
	ANXA6 protein in adipocytes was upregulated by oxidative stress which might trigger ANXA6 induction in adipose tissues and contribute to impaired fat storage and adiponectin release
	implicated in many biological processes, including cell proliferation, survival, differentiation, inflammation, but also membrane repair and viral infection
	novel role for ANXA6 in articular chondrocytes via its modulation of WNT/CTNNB1 and NFKB1 signaling activities and the cross-talk between these two signaling pathways
	controls cholesterol and membrane transport in endo- and exocytosis, and modulates triglyceride accumulation and storage
	acts as a scaffolding protein for negative regulators of growth factor receptors and their effector pathways in many different cell types
	is a novel gatekeeper that controls cellular distribution of late endosome-cholesterol via regulation of a RAB7-GAP and membrane contact sites (MCS) formation
	stabilize and establish the formation of multifactorial signaling complexes

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

exocytosis transport

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding, other,
	calcium Ca2+
	phospholipid
	vitamin A (all-trans retinol)

protein	CD21
	Ras p21 regulatory protein p120GAP
	Ca(2+)-regulated EF-hand proteins S100A1 and S100B
	EBV/C3d receptor (CR2)
	active H-Ras (HRasG12V)
	ANXA6 inhibits DNM1L activity, and Ca2+-binding to ANXA6 relieves this inhibition to permit DNM1L-mediated mitochondrial fission
	cooperative mechanism where ANXA6 potentiates NPPA-dependent counterhypertrophic responses in cardiomyocytes by facilitating regulated traffic of pro-NPPA
	elevated ANXA6 levels cause late endosome (LE) cholesterol accumulation, ANXA6 and blockage of LE cholesterol transport are critical for endosomal function required for STX6-mediated recycling of integrins in cell migration
	PLA2G4A -dependent pathways contribute to the novel regulatory role of hepatic ANXA6 in lipid droplet (LD) formation
	ANXA6 acts as a scaffold for RASGRF2 and RAS proteins and its interaction with RASGRF2 is modulated by GTP and/or activation of Ras proteins

cell & other	cytoskeleton in a calcium-dependent manner
	interacts with membranes in a Ca2+-dependent manner

REGULATION

induced by

EBV

Other

phosphorylated in response to growth factor stimulation

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   contributes to breast cancer progression by promoting the loss of functional cell-cell and/or cell-ECM contacts and anchorage-independent cell proliferation tumoral     --low   is specifically reduced in human hepatocellular carcinoma suggesting a role of this protein in hepatocarcinogenesis

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed miscelleaneous pain   annexin A6 can be exploited to inhibit chronic mechanical pain

ANIMAL & CELL MODELS

Annexin A6-deficient mice showed increased sensitivity to mechanical stimuli