Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

6.2.1.3

Official Name

long-chain-fatty-acid---CoA ligase

Name from literature

arachidonyl coA synthetase

Pathway from literature

esterification of arachidonic acid by many human cells

Pathway from KEGG

Lipid Metabolism; Fatty acid metabolism; map00071

Cellular Processes; Endocrine System; Adipocytokine signaling pathway; map04920

Cellular Processes; Endocrine System; PPAR signaling pathway; map03320

Organisms

Human (9606)

Genome localization

4q34-q35[2180 ], 5q31[23305 ], 2q34-q35[2181 ], Xq22.3-q23[2182 ], 10q25.1-q25.2[51703 ],

Comments

Acts on a wide range of long-chain saturated and unsaturated fatty acids, but the enzymes from different tissues show some variation in specificity. The liver enzyme acts on acids from C6 to C20; that from brain shows high activity up to C24.

Rate-limiting Description

"Taken together, these results support the hypotheses that ACSs are rate-limiting for fatty acid internalization and that ACS2 enhances neurite outgrowth by promoting PUFA internalization." (15051725)

Regulatory Information

Upstream transcription factor

6720

Regulatory type

Detail

key enzyme;

"The recently cloned human acyl-CoA-synthetase 5 (ACS5) is predominantly found in the small intestine and represents a key enzyme in providing cytosolic acyl-CoA thioesters." (14608540)

phosphorylation;

"Large-scale characterization of HeLa cell nuclear phosphoproteins." (15302935)

transcriptional factor;SREBP-1c(6720)

"SREBP-1c-mediated insulin regulation of acyl-CoA synthestase 5 expression indicate that ACS-5 is involved in the anabolic fate of fatty acids." (16198472)

phosphorylation;

O14975

phosphorylation;

O60488

phosphorylation;

O95573

phosphorylation;

P33121

phosphorylation;

Q96GR2

phosphorylation;

O95573:from_uniprot:593_Phosphoserine

phosphorylation;

P33121:from_uniprot:84_Phosphotyrosine

phosphorylation;

Q96GR2:from_uniprot:135_Phosphotyrosine

phosphorylation;

Q96GR2:from_uniprot:138_Phosphotyrosine

phosphorylation;

Q96GR2:from_uniprot:139_Phosphotyrosine

phosphorylation;

Q96GR2:from_uniprot:658_Phosphotyrosine

Gene ontology

Gene ontology

GO:0000287 (F) magnesium ion binding [Q9UKU0, O60488, Q9ULC5, P33121, O95573 ];
GO:0016020 (C) membrane [Q5FVE4 ];
GO:0004321 (F) fatty-acyl-CoA synthase activity [O95573 ];
GO:0007275 (P) multicellular organismal development [Q5FVE4 ];
GO:0005829 (C) cytosol [P33121 ];
GO:0006637 (P) acyl-CoA metabolic process [Q9UKU0 ];
GO:0030154 (P) cell differentiation [Q5FVE4 ];
GO:0016291 (F) acyl-CoA thioesterase activity [Q5FVE4 ];
GO:0016021 (C) integral to membrane [O14975, Q9UKU0, O60488, Q9ULC5, P33121, O95573 ];
GO:0007283 (P) spermatogenesis [Q5FVE4 ];
GO:0005515 (F) protein binding [O95573 ];
GO:0007611 (P) learning or memory [O60488 ];
GO:0008152 (P) metabolic process [A6GV77 ];
GO:0005783 (C) endoplasmic reticulum [Q96GR2 ];
GO:0005739 (C) mitochondrion [Q5FVE4 ];
GO:0000166 (F) nucleotide binding [O14975 ];
GO:0005778 (C) peroxisomal membrane [O14975, Q9UKU0, O60488, Q9ULC5, P33121, O95573 ];
GO:0005886 (C) plasma membrane [Q9UKU0, O60488 ];
GO:0031410 (C) cytoplasmic vesicle [Q96GR2 ];
GO:0004467 (F) long-chain-fatty-acid-CoA ligase activity [Q9UKU0, A6GV77, Q5FVE4, O14975, Q96GR2, O60488, P33121, Q9ULC5, O95573 ];
GO:0005789 (C) endoplasmic reticulum membrane [O14975, Q9UKU0, O60488, Q9ULC5, P33121, O95573 ];
GO:0006631 (P) fatty acid metabolic process [Q96GR2, O60488, Q9ULC5, Q5FVE4, O95573 ];
GO:0046320 (P) regulation of fatty acid oxidation [P33121 ];
GO:0007586 (P) digestion [P33121 ];
GO:0005792 (C) microsome [Q96GR2, Q9UKU0, O60488, Q9ULC5, P33121, Q5FVE4, O95573 ];
GO:0005741 (C) mitochondrial outer membrane [Q9UKU0, O60488, Q9ULC5, P33121, O95573 ];
GO:0005782 (C) peroxisomal matrix [O14975 ];
GO:0000038 (P) very-long-chain fatty acid metabolic process [O14975 ];

Tissue expression

Tissue From HPRD

Peripheral blood cell [09190 ];
Colon [03845, 16139, 02152 ];
Hippocampus [09190 ];
Colon epithelium [02152 ];
Corpus callosum [09190 ];
Lymph node [02152 ];
Fetus [09190, 02152 ];
Testis [09190, 03845, 16139, 02152 ];
Red blood cell [09190 ];
Brain [01068, 11935, 09190, 03845, 16139, 02152 ];
Spleen [09190, 03845, 16139, 02152 ];
Small intestine [16139, 02152 ];
Thalamus [09190 ];
Intestinal mucosa [16139 ];
Heart [01068, 11935, 09190, 03845, 16139, 02152 ];
Amygdala [09190 ];
Cerebellum [09190 ];
Adrenal medulla [02152 ];
Thyroid gland [02152 ];
Duodenum [01068 ];
Thymus [03845, 16139, 02152 ];
Substantia nigra [09190 ];
Spinal cord [09190, 02152 ];
Skin fibroblast [11935 ];
Caudate nucleus [09190 ];
Leukocyte [03845, 16139, 02152 ];
Intestine [03845 ];
Bone marrow [09190, 02152 ];
Liver [01068, 11935, 09190, 03845, 16139, 02152 ];
Skeletal muscle [01068, 09190, 16139, 02152 ];
Muscle [03845 ];
Prostate [03845, 16139, 02152 ];
Villus [16139 ];
Kidney [01068, 11935, 09190, 03845, 16139, 02152 ];
Adrenal gland [02152 ];
Lung [01068, 09190, 03845, 16139, 02152 ];
Ileum [02152 ];
Pancreas [01068, 11935, 09190, 03845, 16139, 02152 ];
Ovary [09190, 03845, 02152 ];
Adrenal cortex [02152 ];
Placenta [01068, 11935, 03845, 16139, 02152 ];
Trachea [02152 ];
Subthalamic nucleus [09190 ];
Stomach [02152 ];

Tissue specificity

Highly expressed in liver, heart, skeletal muscle, kidney and erythroid cells, and to a lesser extent in brain, lung, placenta and pancreas [P33121 ];

Expressed predominantly in erythrocyte precursors, in particular in reticulocytes, fetal blood cells derived from fetal liver, haemopoietic stem cells from cord blood, bone marrow, and brain [Q9UKU0 ];

Testis-specific [Q5FVE4 ];

Expressed primarily in brain. Expressed at lower level in testis and adrenal gland. Present in all regions of brain except pituitary [Q96GR2 ];

Expressed in liver, kidney, placenta and pancreas [O14975 ];

Subcellular localization

Localization

cell membrane [Q5FVE4 ];

mitochondrion [Q9UKU0, O60488, Q9ULC5, P33121, O95573 ];

endoplasmic reticulum [Q96GR2, O14975, Q9UKU0, O60488, Q9ULC5, P33121, O95573 ];

peroxisome [O14975, Q9UKU0, O60488, Q9ULC5, P33121, O95573 ];

microsome [Q96GR2, Q9UKU0, O60488, Q9ULC5, P33121, O95573 ];

membrane [O14975, Q9UKU0, O60488, Q9ULC5, P33121, O95573 ];

cytoplasm [Q96GR2, Q5FVE4 ];

Disease relevance

Disease

A chromosomal aberration involving ACSL6 may be a cause of acute myelogenous leukemia with eosinophilia. Translocation t(5;
12)(q31;
p13) with ETV6 [Q9UKU0 ];

Defects in ACSL4 may be a cause of AMME complex [MIM:300194];
also known as Alport syndrome with mental retardation, midface hypoplasia and elliptocytosis. The AMME complex is a contiguous gene deletion syndrome [O60488 ];

A chromosomal aberration involving ACSL6 may be a cause of myelodysplastic syndrome with basophilia. Translocation t(5;
12)(q31;
p13) with ETV6 [Q9UKU0 ];

Defects in ACSL4 are the cause of non-syndromic mental retardation X-linked type 63 (MRX63) [MIM:300387]. Mental retardation is a mental disorder characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Non-syndromic mental retardation patients do not manifest other clinical signs [O60488 ];

A chromosomal aberration involving ACSL6 may be a cause of acute eosinophilic leukemia (AEL). Translocation t(5;
12)(q31;
p13) with ETV6 [Q9UKU0 ];

Links

SwissProt

A6GV77; O14975; O60488; O95573; P33121; Q5FVE4; Q96GR2; Q9UKU0; Q9ULC5

Entrez Gene

2180; 2181; 2182; 23305; 51703

HPRD

16139; 11935; 02152; 01068; 03845; 09190



  Copyright 2009, Center for Bioinformatics 
  Last Modified: 2009-03-24  
  Design by Zhao Min