UniProtKB - O35547 (ACSL4_RAT)
Long-chain-fatty-acid--CoA ligase 4
Acsl4
Functioni
Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:28209804, PubMed:23766516, PubMed:9096315).
Preferentially activates arachidonate and eicosapentaenoate as substrates (PubMed:9096315).
Preferentially activates 8,9-EET > 14,15-EET > 5,6-EET > 11,12-EET (PubMed:23766516).
Modulates glucose-stimulated insulin secretion by regulating the levels of unesterified EETs (PubMed:23766516).
Modulates prostaglandin E2 secretion (By similarity).
By similarity3 PublicationsMiscellaneous
Catalytic activityi
- EC:6.2.1.33 PublicationsThis reaction proceeds in the forward1 Publication direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate1 PublicationEC:6.2.1.151 PublicationThis reaction proceeds in the forward1 Publication direction.
- 15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + ATP + CoA = 15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-CoA + AMP + diphosphate1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + ATP + CoA = 12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = 5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 5,6-epoxy-(8Z,11Z,14Z)-eicosatrienoate + ATP + CoA = 5,6-epoxy-(8Z,11Z,14Z)-eicosatrienoyl-CoA + AMP + diphosphate1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate + ATP + CoA = 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoyl-CoA + AMP + diphosphate2 PublicationsThis reaction proceeds in the forward2 Publications direction.
- 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoate + ATP + CoA = 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoyl-CoA + AMP + diphosphate2 PublicationsThis reaction proceeds in the forward2 Publications direction.
- 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate + ATP + CoA = 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoyl-CoA + AMP + diphosphate2 PublicationsThis reaction proceeds in the forward2 Publications direction.
- This reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
Cofactori
Activity regulationi
Kineticsi
- KM=34 µM for ATP1 Publication
- KM=4.1 µM for CoA1 Publication
- KM=5.4 µM for palmitate1 Publication
- KM=19.5 µM for oleate1 Publication
- KM=10 µM for arachidonate1 Publication
- KM=4.5 µM for palmitate (when expressed in bacteria)1 Publication
- KM=2.9 µM for stearate (when expressed in bacteria)1 Publication
- KM=16.7 µM for oleate (when expressed in bacteria)1 Publication
- KM=4 µM for linoleate (when expressed in bacteria)1 Publication
- KM=11.4 µM for arachidonate (when expressed in bacteria)1 Publication
- KM=24.8 µM for palmitate (when expressed in mammalian cell)1 Publication
- KM=12.5 µM for stearate (when expressed in mammalian cell)1 Publication
- KM=3.6 µM for oleate (when expressed in mammalian cell)1 Publication
- KM=13.3 µM for linoleate (when expressed in mammalian cell)1 Publication
- KM=7.5 µM for arachidonate (when expressed in mammalian cell)1 Publication
- Vmax=2800 nmol/min/mg enzyme with palmitate as substrate1 Publication
- Vmax=673 nmol/min/mg enzyme with oleate as substrate1 Publication
- Vmax=4200 nmol/min/mg enzyme with arachidonate as substrate1 Publication
- Vmax=4451 nmol/min/mg enzyme with palmitate as substrate (when expressed in bacteria)1 Publication
- Vmax=2737 nmol/min/mg enzyme with stearate as substrate (when expressed in bacteria)1 Publication
- Vmax=2366 nmol/min/mg enzyme with oleate as substrate (when expressed in bacteria)1 Publication
- Vmax=1231 nmol/min/mg enzyme with linoleate as substrate (when expressed in bacteria)1 Publication
- Vmax=7180 nmol/min/mg enzyme with arachidonate as substrate (when expressed in bacteria)1 Publication
- Vmax=1990 nmol/min/mg enzyme with palmitate as substrate (when expressed in mammalian cell)1 Publication
- Vmax=1240 nmol/min/mg enzyme with stearate as substrate (when expressed in mammalian cell)1 Publication
- Vmax=466 nmol/min/mg enzyme with oleate as substrate (when expressed in mammalian cell)1 Publication
- Vmax=1011 nmol/min/mg enzyme with linoleate as substrate (when expressed in mammalian cell)1 Publication
- Vmax=4339 nmol/min/mg enzyme with arachidonate as substrate (when expressed in mammalian cell)1 Publication
GO - Molecular functioni
- arachidonate-CoA ligase activity Source: UniProtKB
- ATP binding Source: UniProtKB-KW
- long-chain fatty acid-CoA ligase activity Source: UniProtKB
- very long-chain fatty acid-CoA ligase activity Source: RGD
GO - Biological processi
- dendritic spine development Source: RGD
- embryonic process involved in female pregnancy Source: RGD
- fatty acid metabolic process Source: RGD
- fatty acid transport Source: RGD
- lipid metabolic process Source: RGD
- long-chain fatty acid metabolic process Source: UniProtKB
- long-chain fatty-acyl-CoA biosynthetic process Source: RGD
- long-chain fatty-acyl-CoA metabolic process Source: GO_Central
- neuron differentiation Source: GO_Central
- positive regulation of insulin secretion Source: UniProtKB
- response to interleukin-15 Source: RGD
- response to nutrient Source: RGD
- triglyceride biosynthetic process Source: RGD
Keywordsi
Molecular function | Ligase |
Biological process | Fatty acid metabolism, Lipid metabolism |
Ligand | ATP-binding, Magnesium, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 6.2.1.3, 5301 |
Reactomei | R-RNO-434313, Intracellular metabolism of fatty acids regulates insulin secretion R-RNO-75876, Synthesis of very long-chain fatty acyl-CoAs |
SABIO-RKi | O35547 |
Chemistry databases
SwissLipidsi | SLP:000001679 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:Acsl4 Synonyms:Acs4, Facl4 |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 69401, Acsl4 |
Subcellular locationi
Endoplasmic reticulum
- Microsome membrane By similarity; Single-pass type III membrane protein By similarity
- Endoplasmic reticulum membrane By similarity; Single-pass type III membrane protein By similarity
Mitochondrion
- Mitochondrion outer membrane By similarity; Single-pass type III membrane protein By similarity
Plasma membrane
- Cell membrane By similarity
Peroxisome
- Peroxisome membrane By similarity; Single-pass type III membrane protein By similarity
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Mitochondrion
- mitochondrial membrane Source: RGD
- mitochondrial outer membrane Source: UniProtKB-SubCell
- mitochondrion Source: RGD
Peroxisome
- peroxisomal membrane Source: UniProtKB-SubCell
- peroxisome Source: RGD
Plasma Membrane
- plasma membrane Source: GO_Central
Other locations
- cytoplasm Source: RGD
- integral component of membrane Source: UniProtKB-KW
- lipid droplet Source: RGD
- membrane Source: GO_Central
- mitochondria-associated endoplasmic reticulum membrane Source: RGD
- neuronal cell body Source: RGD
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 8 – 28 | Helical; Signal-anchor for type III membrane proteinSequence analysisAdd BLAST | 21 | |
Topological domaini | 29 – 711 | CytoplasmicCuratedAdd BLAST | 683 |
Keywords - Cellular componenti
Cell membrane, Endoplasmic reticulum, Membrane, Microsome, Mitochondrion, Mitochondrion outer membrane, PeroxisomePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000193111 | 1 – 711 | Long-chain-fatty-acid--CoA ligase 4Add BLAST | 711 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 447 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
jPOSTi | O35547 |
PaxDbi | O35547 |
PRIDEi | O35547 |
Expressioni
Inductioni
Gene expression databases
Bgeei | ENSRNOG00000019180, Expressed in liver and 21 other tissues |
Genevisiblei | O35547, RN |
Interactioni
Protein-protein interaction databases
IntActi | O35547, 1 interactor |
STRINGi | 10116.ENSRNOP00000026057 |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1180, Eukaryota |
GeneTreei | ENSGT00940000157427 |
HOGENOMi | CLU_000022_45_2_1 |
InParanoidi | O35547 |
OMAi | KIFQWAA |
OrthoDBi | 293865at2759 |
PhylomeDBi | O35547 |
TreeFami | TF314012 |
Family and domain databases
Gene3Di | 3.30.300.30, 1 hit 3.40.50.12780, 1 hit |
InterProi | View protein in InterPro IPR045851, AMP-bd_C_sf IPR020845, AMP-binding_CS IPR000873, AMP-dep_Synth/Lig IPR042099, ANL_N_sf |
Pfami | View protein in Pfam PF00501, AMP-binding, 1 hit |
PROSITEi | View protein in PROSITE PS00455, AMP_BINDING, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MKLKLNVLTI VLLPVHLLIT IYSALIFIPW YFLTNAKKKN AMAKRIKAKP
60 70 80 90 100
TSDKPGSPYR SVTHFDSLAV IDIPGADTLD KLFDHAVAKF GKKDSLGTRE
110 120 130 140 150
ILSEENEMQP NGKVFKKLIL GNYKWINYLE VNCRVNNFGS GLTALGLKPK
160 170 180 190 200
NTIAIFCETR AEWMIAAQTC FKYNFPLVTL YATLGKEAVV HGLNESEASY
210 220 230 240 250
LITSVELLES KLKAALLDIN CVKHIIYVDN KTINRAEYPE GLEIHSMQSV
260 270 280 290 300
EELGSKPENS SIPPSRPTPS DMAIVMYTSG STGRPKGVMM HHSNLIAGMT
310 320 330 340 350
GQCERIPGLG PKDTYIGYLP LAHVLELTAE ISCFTYGCRI GYSSPLTLSD
360 370 380 390 400
QSSKIKKGSK GDCTVLKPTL MAAVPEIMDR IYKNVMSKVQ EMNYIQKTLF
410 420 430 440 450
KIGYDYKLEQ IKKGYDAPLC NLILFKKVKA LLGGNVRMML SGGAPLSPQT
460 470 480 490 500
HRFMNVCFCC PIGQGYGLTE SCGAGTVTEV TDYTTGRVGA PLICCEIKLK
510 520 530 540 550
DWQEGGYTVH DKPNPRGEIV IGGQNISMGY FKNEEKTAED YSVDENGQRW
560 570 580 590 600
FCTGDIGEFH PDGCLQIIDR KKDLVKLQAG EYVSLGKVEA ALKNCPLIDN
610 620 630 640 650
ICAFAKSDQS YVISFVVPNQ KKLTLLAQQK GVEGSWVDIC NNPAMEAEIL
660 670 680 690 700
KEIREAANAM KLERFEIPIK VRLSPEPWTP ETGLVTDAFK LKRKELKNHY
710
LKDIERMYGG K
The sequence of this isoform differs from the canonical sequence as follows:
1-41: Missing.
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_060224 | 1 – 41 | Missing in isoform Short. Add BLAST | 41 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D85189 mRNA Translation: BAA22195.1 FM034112 mRNA No translation available. |
RefSeqi | NP_446075.1, NM_053623.1 [O35547-2] XP_006257376.1, XM_006257314.3 [O35547-1] XP_006257377.1, XM_006257315.3 [O35547-2] XP_006257378.1, XM_006257316.2 [O35547-2] |
Genome annotation databases
Ensembli | ENSRNOT00000026057; ENSRNOP00000026057; ENSRNOG00000019180 [O35547-2] |
GeneIDi | 113976 |
KEGGi | rno:113976 |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D85189 mRNA Translation: BAA22195.1 FM034112 mRNA No translation available. |
RefSeqi | NP_446075.1, NM_053623.1 [O35547-2] XP_006257376.1, XM_006257314.3 [O35547-1] XP_006257377.1, XM_006257315.3 [O35547-2] XP_006257378.1, XM_006257316.2 [O35547-2] |
3D structure databases
SMRi | O35547 |
ModBasei | Search... |
Protein-protein interaction databases
IntActi | O35547, 1 interactor |
STRINGi | 10116.ENSRNOP00000026057 |
Chemistry databases
SwissLipidsi | SLP:000001679 |
Proteomic databases
jPOSTi | O35547 |
PaxDbi | O35547 |
PRIDEi | O35547 |
Genome annotation databases
Ensembli | ENSRNOT00000026057; ENSRNOP00000026057; ENSRNOG00000019180 [O35547-2] |
GeneIDi | 113976 |
KEGGi | rno:113976 |
Organism-specific databases
CTDi | 2182 |
RGDi | 69401, Acsl4 |
Phylogenomic databases
eggNOGi | KOG1180, Eukaryota |
GeneTreei | ENSGT00940000157427 |
HOGENOMi | CLU_000022_45_2_1 |
InParanoidi | O35547 |
OMAi | KIFQWAA |
OrthoDBi | 293865at2759 |
PhylomeDBi | O35547 |
TreeFami | TF314012 |
Enzyme and pathway databases
BRENDAi | 6.2.1.3, 5301 |
Reactomei | R-RNO-434313, Intracellular metabolism of fatty acids regulates insulin secretion R-RNO-75876, Synthesis of very long-chain fatty acyl-CoAs |
SABIO-RKi | O35547 |
Miscellaneous databases
PROi | PR:O35547 |
Gene expression databases
Bgeei | ENSRNOG00000019180, Expressed in liver and 21 other tissues |
Genevisiblei | O35547, RN |
Family and domain databases
Gene3Di | 3.30.300.30, 1 hit 3.40.50.12780, 1 hit |
InterProi | View protein in InterPro IPR045851, AMP-bd_C_sf IPR020845, AMP-binding_CS IPR000873, AMP-dep_Synth/Lig IPR042099, ANL_N_sf |
Pfami | View protein in Pfam PF00501, AMP-binding, 1 hit |
PROSITEi | View protein in PROSITE PS00455, AMP_BINDING, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ACSL4_RAT | |
Accessioni | O35547Primary (citable) accession number: O35547 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 15, 1998 |
Last sequence update: | July 31, 2019 | |
Last modified: | February 23, 2022 | |
This is version 148 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families