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FLASH GENE

Symbol

FLII

contributors: mct - updated : 10-12-2017

HGNC name	flightless I homolog (Drosophila)
HGNC id	3750

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
SPECIAL FEATURE	overlapping, gene in gene, opposite orientation, tail to tail
text	overlapping 3'end of LLGL1
STRUCTURE	14.10 kb     30 Exon(s)

10 Kb 5' upstream gene genomic sequence study

text structure

3' and overlaps with the 3' and OFLLGL1 gene

MAPPING

cloned

Y

linked

status

confirmed

Map	see SMCR (phenotype)

regionally located

within the Smith-Magenis critical region

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002018 30 - 4176 NP_002009 - 1269 - 2002 11971982 NM_001256265 29 - 4222 NP_001243194 - 1214 - 2002 11971982 NM_001256264 30 - 4208 NP_001243193 - 1258 - 2002 11971982

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 heart       highly Respiratory lung       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum cardiac     Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	sixteen N terminal, leucine-rich repeat motifs (LRR), with LXXLL motif within the LRR domain of FLII interacting directly with the DNA-binding domain of PPARG
	five C terminal gelsolin-like domains, involved in capping and severing actin filaments

HOMOLOGY

interspecies	homolog to Drosophila flightless (fli) 1
	homolog to murine Fliih

Homologene

FAMILY

gelsolin superfamily of actin-remodeling proteins

CATEGORY

motor/contractile

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton
	intracellular,nucleus,nucleoplasm
text	distributed throughout the cytosol and in focal adhesions

basic FUNCTION	playing a key role in embryonic cellularization by interacting with both the cytoskeleton and other cellular components
	actin-remodeling protein that influences diverse processes including cell migration and gene transcription and links signal transduction with cytoskeletal regulation 0)
	regulates cell migration through its localization to focal adhesions and its ability to cap actin filaments, which collectively affect focal adhesion maturation
	may contribute to the inhibitory effect of chronic wound fluid on fibroblast function
	is a component of the MLXIPL transcriptional complex and negatively regulates MLXIPL function in cancer cells
	important role for FLII in the development and regulation of the epidermal barrier, which may contribute to the impaired healing and skin fragility of epidermolysis bullosa (EB) patients
	functions in PPARG activation as a molecular switch to repress transcriptional activity by interrupting formation of the PPARG/RXRA complex
	is a negative regulator of wound healing
	actin remodeling protein that affects cellular processes including adhesion, proliferation and migration
	enhances cutaneous squamous cell carcinoma tumor progression by decreasing apoptosis and enhancing tumor cell invasion
	FLII and LRRFIP2 repress caspase-1 activation, which could be restored through the severing of actin filaments in a Ca2+-dependent process
	both LRRFIP2 and FliI control the localization of NLRP3 with F-actin as well as the activity of NLRP3 inflammasome

CELLULAR PROCESS

cell organization/biogenesis

PHYSIOLOGICAL PROCESS

text	muscle contraction

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	is a substrate of SGK3 that functions downstream of PI 3-kinase and SGK3 can associate with FLII and phosphorylate FLII at residues Ser(436) and Thr(818)
	FLII can bind directly to both ESR1 and ACTL6A, an actin-related component of the SWI/SNF complex, suggesting that FLII may recruit SWI/SNF to ESR1 target genes via interaction with ACTL6A
	FLII is a novel NXN-binding partner (binds to NXN and other related proteins, such as Rod-derived cone viability factor (NXNL1)
	with FLAp (linking FLII to the actin cytoskeleton)
	three regulators of the actin cytoskeleton--AMOTL2, SPATA13 and FLII--interact with PHLDB2
	LRRFIP2 enhances the interaction between FLII and CASP1, facilitating the inhibitory effect of FLII on CASP1 activation
	FLII binds directly to and suppresses the transcriptional activity of PPARG
	FLII interacts with MYH9 to promote cell extension formation, which enables collagen remodeling in fibroblasts
	FLII is recruited to the NLRP3 inflammasome by leucine-rich repeat FliI-interaction protein 2 (LRRFIP2), an NLRP3-associated protein

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional   deletion     constantly, in Smith-Magenis syndrome (SMCR) constitutional     --over   increased in the blistered skin of patients with epidermolysis bullosa (EB) tumoral     --over   negatively regulated MLXIPL mediated transcription in cancer cells

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer skin   targeting FLII may be a potential strategy for reducing the severity of cutaneous squamous cell carcinoma obesity     FLII may serve as a novel therapeutic target in the treatment of adiposity-related metabolic syndromes

ANIMAL & CELL MODELS