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FLASH GENE

Symbol

ACSL4

contributors: mct - updated : 06-10-2017

HGNC name	acyl-CoA synthetase long-chain family member 4
HGNC id	3571

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004458 16 splicing 5039 NP_004449 74.4 670 . expressed in human arterial smooth muscle cells (SMCs) . localized to the inner side of the plasma membrane including microvilli, and was also present in the cytosol 2014 24201376 ACSL4 v1 being 97p100 identical to the rat homolog NM_022977 17 splicing 5351 NP_075266 79.2 711 highly expressed in the brain 2014 24201376 not found in rat a 41 aa longer hydrophobic N terminus which may impact localization containing an additional 313nt 5' exon introducing an earlier inframe start codon NM_001318510 16 - 5058 NP_001305439 74.4 670 - 2014 24201376 NM_001318509 16 - 5349 NP_001305438 79.2 711 contains an additional N-terminal hydrophobic region; this isoform was located at the endoplasmic reticulum and on lipid droplets 2014 24201376 ACSL4v2

EXPRESSION

Type

widely

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 Digestive liver       highly Homo sapiens Endocrine pancreas         Homo sapiens Nervous brain       specific Homo sapiens Respiratory lung       moderately Homo sapiens Urinary kidney       highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine   Nervous central     specific Homo sapiens Nervous peripherous     specific Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Endocrine islet cell (alpha,beta...) Homo sapiens Lymphoid/Immune lymphocyte Nervous neuron

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two domains of homology with click beetle luciferase, enzyme containing 25-AA consensus sequence, (FACs signature motif)
	a N terminal insertion sequence in transcripts from brain and retina

conjugated

PhosphoP

HOMOLOGY

interspecies	homolog to murine Facl4
	homolog to C.elegans F37C12.

intraspecies

Homologene

FAMILY	long-chain fatty-acid-coenzyme A ligase family
	ATP-dependent AMP-binding enzyme family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria,outer
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,peroxisome
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,cytosolic,microsome

basic FUNCTION	converting free long-chain fatty acids into fatty acyl-CoA esters
	playing a role in lipid biosynthesis and fatty acid degradation
	utilizing preferentially arachidonate and eicosapentaenoate as substrat
	might play a role in the growth of hepatic cancer cells
	involved in learning and memory
	its expression controls both lipooxygenase and cyclooxygenase metabolism of arachidonic acid
	modulates PGE&
	8322; release from human smooth muscle cells and may regulate a number of processes dependent on the release of arachidonic acid-derived lipid mediators in the arterial wall
	plays crucial roles in physiological functions such as steroid synthesis and in pathological processes such as tumorigenesis
	specifically expressed in brain and playing an important role in arachidonate metabolism and neuronal differentiation in the brain
	might play a key role in brain function, especially neuronal cells
	might play an important role during neuronal differentiation at the early phase
	key enzyme in steroidogenesis
	phosphoprotein whose phosphorylation is hormone-dependent
	acts as a dimer and phosphorylation occurs after dimer formation
	is involved in several cellular functions including steroidogenesis, synaptic development and cancer metastasis
	is required for ferroptotic cancer cell death, and is not only a sensitive monitor of ferroptosis, but also an important contributor of ferroptosis
	ACSL4 is an essential component for ferroptosis execution
	involvement of ACSL4 and ACSL3 in insulin secretion

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development

text	mental development

PATHWAY

metabolism

lipid/lipoprotein

signaling

lipid metabolism

a component	protein complex consisting HTATIP2, SH3GLB1, and ACSL4 that interacts with RAB5a and regulates EGFR endocytosis and signaling

INTERACTION

DNA

RNA

small molecule	metal binding, cofactor, nucleotide,
	magnesium Mg2+
	AMP

protein	interaction with PTPN11 (involvement of PTPN11 activity in the regulation of the expression of the fatty acid-metabolizing enzyme ACSL4)
	PPARD-mediated regulatory mechanism for ACSL4 expression in liver tissue and cultured hepatic cells

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

MRX68 , MRX63 , AMME

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in breast cancer, colon and hepatocellular carcinoma

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer digestive liver new potential therapeutic target for Hepatocellular Carcinoma as an independent adverse prognostic parameter cancer     ACSL4 inhibition is a viable therapeutic approach to preventing ferroptosis-related diseases

ANIMAL & CELL MODELS

mice heterozygocis for Facl4 deficiency (Cho, 2001)