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FLASH GENE

Symbol

ARL6

contributors: shn/mct - updated : 15-12-2020

HGNC name	ADP-ribosylation factor-like 6
HGNC id	13210

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	BBS3 Bardet-Biedl syndrome 3 RP55 retinitis pigmentosa 55
Location	3q11.2      Physical location : 97.483.594 - 97.517.369
Synonym name	Bardet-Biedl syndrome 3 protein
	ARF-like 6
Synonym symbol(s)	BBS3, RP55, MGC32934, BBS3L

DNA

TYPE	functioning gene
STRUCTURE	50.01 kb     9 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - D3S1251 - D3S3619 - ARL6 - D3S1752 - D3S1603 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_032146 9 splicing 4353 NP_115522 21.1 186 - 2004 20333246 NM_177976 9 splicing 4313 NP_816931 21.1 186 - 2004 20333246 encoding the same protein differing in the 5' UTR compared to variant 1 NM_001323513 9 - 4001 NP_001310442 - 193 in eye 2004 20333246 inclusion of a 13 base pair exon and a shift in the open reading frame generating different C-terminal regions BBS3L transcript is required for proper retinal function and organization BBS3L protein product plays an important role in eye structure and function NM_001278293 8 - 3988 NP_001265222 - 186 - 2004 20333246 NM_001323514 7 - 3932 NP_001310443 - 159 - 2004 20333246

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 Nervous brain       predominantly Urinary kidney       predominantly Visual eye retina fovea

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier lining

cells

System Cell Pubmed Species Stage Rna symbol Respiratory epithelial cell Visual cone photoreceptor Visual ganglion cell

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

HOMOLOGY

interspecies	ortholog to Arl6, Mus musculus
	ortholog to Arl6, Rattus norvegicus
	ortholog to ARL6, Pan troglodytes
	ortholog to arl6, Danio rerio

Homologene

FAMILY	small GTPase superfamily
	Arf family

CATEGORY

enzyme , regulatory , transport carrier

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
text	ciliated neurons
	membrane association increased following exposure to GTP-gammaS
	found in a ring-like pattern at the distal end of the basal body and most proximal region of the ciliary axoneme

basic FUNCTION	involved in protein transport, membrane trafficking or cell signaling during hematopoietic maturation
	required for the localization of G protein-coupled receptors to primary cilia on central neurons
	having a small monomeric GTPase activity
	is essential for flagellum biogenesis
	involved in planar cell polarity
	mediate LEPR trafficking and impaired LEPR signaling underlies energy imbalance in the disease
	role in mammalian ciliary (dis)assembly and Wnt signaling
	modulating membrane trafficking at the base of the ciliary organelle
	targets the BBSome to cilia when GTP bound and recruits the BBSome to membranes to assemble a polymerized coat
	play a central role in the regulation of the actin cytoskeleton and control the cilia length through alteration of RHOA levels
	IFT27 separates from IFT-B inside cilia to promote ARL6 activation, BBSome coat assembly, and subsequent ciliary exit
	localizes at the base of primary cilium, controls ciliogenesis and HH signaling

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

cellular trafficking transport

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule	nucleotide,
	GTP

protein	SEC61beta
	ARL6 and BBS1 regulate the ciliary trafficking of PKD1
	BBS1 with the M390R mutation, responsible for 30p100 of all reported BBS disease cases, fails to interact with ARL6-GTP
	IFT27 directly interacts with the nucleotide-free form of ARL6
	IFT-A complex and its membrane recruitment factor TULP3 complex promotes the entry of signaling receptors into cilia while the BBSome and its membrane recruitment factor ARL6GTP ferry activated signaling receptors out of cilia
	ARL6-BBS1 interaction is reinforced by BBS9
	IFT22 binds and stabilizes the Arf-like 6 GTPase BBS3, a BBS protein that is not part of the BBSome

cell & other

REGULATION

induced by

erythropoietin-induced maturation of J2E cells

repressed by

interleukin 6-induced differentiation of M1 monoblastoid cells

ASSOCIATED DISORDERS

corresponding disease(s)

BBS3 , RP55

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral       gain of function is significantly up regulated in cilia-dependent RMS cells and tissues

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	oligonucleotide knockdown in zebrafish results in the cardinal features of BBS in zebrafish, including defects to the ciliated Kupffer's Vesicle and delayed retrograde melanosome transpor
	Bbs3L-null mouse presents disruption of the normal photoreceptor architecture