UniProtKB - O35488 (S27A2_MOUSE)
Protein
Very long-chain acyl-CoA synthetase
Gene
Slc27a2
Organism
Mus musculus (Mouse)
Status
Functioni
Acyl CoA synthetase that activates long-chain and very long-chain fatty acids (VLCFAs) by catalyzing the formation of fatty acyl-CoA (PubMed:15699031, PubMed:20530735). Can also activate branched-chain fatty acids such as phytanic acid and pristanic acid (By similarity). Does not activate C24 bile acids, cholate and chenodeoxycholate (By similarity). In vitro, activates 3-alpha,7-alpha,12-alpha-trihydroxy- 5-beta-cholestanate (THCA), the C27 precursor of cholic acid deriving from the de novo synthesis from cholesterol (By similarity). Exhibits long-chain fatty acids (LCFA) transport activity and plays an important role in hepatic fatty acid uptake (PubMed:20530735, PubMed:9671728, PubMed:15699031).By similarity3 Publications
Catalytic activityi
- EC:6.2.1.32 PublicationsThis reaction proceeds in the forward2 Publications 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.
- EC:6.2.1.24By similarityThis reaction proceeds in the forwardBy similarity direction.
- (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oate + ATP + CoA = (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oyl-CoA + AMP + diphosphateBy similarityEC:6.2.1.7By similarityThis reaction proceeds in the forwardBy similarity direction.
- a very long-chain fatty acid + ATP + CoA = a very long-chain fatty acyl-CoA + AMP + diphosphate2 PublicationsThis reaction proceeds in the forward2 Publications direction.
- This reaction proceeds in the backward3 Publications direction.
- This reaction proceeds in the forward1 Publication direction.
- (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + ATP + CoA = (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + AMP + diphosphateBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (9Z,12Z,15Z)-octadecatrienoate + ATP + CoA = (9Z,12Z,15Z)-octadecatrienoyl-CoA + AMP + diphosphateBy similarityThis reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 222 – 233 | AMPSequence analysisAdd BLAST | 12 |
GO - Molecular functioni
- acyl-CoA ligase activity Source: UniProtKB-EC
- arachidonate-CoA ligase activity Source: UniProtKB-EC
- ATP binding Source: UniProtKB-KW
- cholate-CoA ligase activity Source: UniProtKB-EC
- decanoate-CoA ligase activity Source: UniProtKB-EC
- enzyme binding Source: MGI
- fatty acid transmembrane transporter activity Source: MGI
- long-chain fatty acid-CoA ligase activity Source: MGI
- long-chain fatty acid transporter activity Source: UniProtKB
- phytanate-CoA ligase activity Source: MGI
- pristanate-CoA ligase activity Source: MGI
- very long-chain fatty acid-CoA ligase activity Source: UniProtKB
GO - Biological processi
- bile acid biosynthetic process Source: MGI
- fatty acid alpha-oxidation Source: MGI
- fatty acid beta-oxidation Source: MGI
- fatty acid transport Source: MGI
- long-chain fatty acid import into cell Source: MGI
- long-chain fatty acid metabolic process Source: MGI
- methyl-branched fatty acid metabolic process Source: MGI
- very long-chain fatty acid catabolic process Source: MGI
- very long-chain fatty acid metabolic process Source: MGI
Keywordsi
Molecular function | Ligase |
Biological process | Fatty acid metabolism, Lipid metabolism |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-MMU-193368, Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol R-MMU-193775, Synthesis of bile acids and bile salts via 24-hydroxycholesterol R-MMU-389599, Alpha-oxidation of phytanate R-MMU-6798695, Neutrophil degranulation R-MMU-9033241, Peroxisomal protein import |
Chemistry databases
SwissLipidsi | SLP:000000430 |
Names & Taxonomyi
Protein namesi | Recommended name: Very long-chain acyl-CoA synthetase1 Publication (EC:6.2.1.-)Short name: VLACS1 Publication Short name: VLCSBy similarity Alternative name(s): Arachidonate--CoA ligase (EC:6.2.1.151 Publication) Fatty acid transport protein 23 Publications Short name: FATP-23 Publications Fatty-acid-coenzyme A ligase, very long-chain 1 Long-chain-fatty-acid--CoA ligase (EC:6.2.1.32 Publications) Phytanate--CoA ligase (EC:6.2.1.24By similarity) Solute carrier family 27 member 2 THCA-CoA ligase (EC:6.2.1.7By similarity) Very long-chain-fatty-acid-CoA ligase |
Gene namesi | Name:Slc27a2 Synonyms:Acsvl1, Facvl1, Fatp2, Vlacs, Vlcs |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1347099, Slc27a2 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Multi-pass membrane protein Sequence analysis
Peroxisome
- Peroxisome membrane 1 Publication; Peripheral membrane protein By similarity
Endoplasmic reticulum
- Endoplasmic reticulum membrane By similarity; Multi-pass membrane protein Sequence analysis
- Microsome By similarity
Endoplasmic reticulum
- endoplasmic reticulum Source: MGI
- endoplasmic reticulum lumen Source: UniProtKB
- endoplasmic reticulum membrane Source: MGI
- integral component of endoplasmic reticulum membrane Source: MGI
Mitochondrion
- mitochondrion Source: MGI
Peroxisome
- integral component of peroxisomal membrane Source: UniProtKB
- peroxisomal membrane Source: MGI
- peroxisome Source: UniProtKB
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- intracellular membrane-bounded organelle Source: MGI
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 4 | LumenalBy similarity | 4 | |
Transmembranei | 5 – 27 | HelicalSequence analysisAdd BLAST | 23 | |
Topological domaini | 28 – 106 | CytoplasmicBy similarityAdd BLAST | 79 | |
Transmembranei | 107 – 127 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 128 – 267 | LumenalBy similarityAdd BLAST | 140 | |
Transmembranei | 268 – 288 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 289 – 620 | CytoplasmicBy similarityAdd BLAST | 332 |
Keywords - Cellular componenti
Cell membrane, Endoplasmic reticulum, Membrane, Microsome, PeroxisomePathology & Biotechi
Disruption phenotypei
Conditional knockout in liver results in decreased long-chain fatty acids (LCFA) uptake by hepatocytes and decreased peroxisomal long chain and very long-chain acyl-CoA synthetase (VLACS) activity.1 Publication
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000193205 | 1 – 620 | Very long-chain acyl-CoA synthetaseAdd BLAST | 620 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 291 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 577 | PhosphothreonineCombined sources | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
jPOSTi | O35488 |
MaxQBi | O35488 |
PaxDbi | O35488 |
PeptideAtlasi | O35488 |
PRIDEi | O35488 |
PTM databases
iPTMneti | O35488 |
PhosphoSitePlusi | O35488 |
SwissPalmi | O35488 |
Expressioni
Tissue specificityi
Strong expression in liver and kidney (at protein level) (PubMed:20530735, PubMed:11980911, PubMed:9671728). Lower expression in brain and testis, no expression in skeletal muscle and spleen (PubMed:11980911). Shows uniform distribution in liver acinus (PubMed:11980911).3 Publications
Gene expression databases
Bgeei | ENSMUSG00000027359, Expressed in adult mammalian kidney and 242 other tissues |
ExpressionAtlasi | O35488, baseline and differential |
Genevisiblei | O35488, MM |
Interactioni
GO - Molecular functioni
- enzyme binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 205004, 4 interactors |
IntActi | O35488, 4 interactors |
MINTi | O35488 |
STRINGi | 10090.ENSMUSP00000057595 |
Miscellaneous databases
RNActi | O35488, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the ATP-dependent AMP-binding enzyme family.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1179, Eukaryota |
GeneTreei | ENSGT00940000161137 |
HOGENOMi | CLU_000022_46_2_1 |
InParanoidi | O35488 |
OMAi | PMACLNY |
OrthoDBi | 298283at2759 |
TreeFami | TF313430 |
Family and domain databases
Gene3Di | 3.40.50.12780, 1 hit |
InterProi | View protein in InterPro IPR025110, AMP-bd_C IPR020845, AMP-binding_CS IPR000873, AMP-dep_Synth/Lig IPR042099, AMP-dep_Synthh-like_sf IPR030305, FATP2 |
PANTHERi | PTHR43107:SF13, PTHR43107:SF13, 1 hit |
Pfami | View protein in Pfam PF00501, AMP-binding, 1 hit PF13193, AMP-binding_C, 1 hit |
PROSITEi | View protein in PROSITE PS00455, AMP_BINDING, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
O35488-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MLPVLYTGLA GLLLLPLLLT CCCPYLLQDV RYFLRLANMA RRVRSYRQRR
60 70 80 90 100
PVRTILRAFL EQARKTPHKP FLLFRDETLT YAQVDRRSNQ VARALHDQLG
110 120 130 140 150
LRQGDCVALF MGNEPAYVWI WLGLLKLGCP MACLNYNIRA KSLLHCFQCC
160 170 180 190 200
GAKVLLASPD LQEAVEEVLP TLKKDAVSVF YVSRTSNTNG VDTILDKVDG
210 220 230 240 250
VSAEPTPESW RSEVTFTTPA VYIYTSGTTG LPKAATINHH RLWYGTGLAM
260 270 280 290 300
SSGITAQDVI YTTMPLYHSA ALMIGLHGCI VVGATLALRS KFSASQFWDD
310 320 330 340 350
CRKYNVTVIQ YIGELLRYLC NTPQKPNDRD HKVKKALGNG LRGDVWREFI
360 370 380 390 400
KRFGDIHVYE FYASTEGNIG FVNYPRKIGA VGRANYLQRK VARYELIKYD
410 420 430 440 450
VEKDEPVRDA NGYCIKVPKG EVGLLVCKIT QLTPFIGYAG GKTQTEKKKL
460 470 480 490 500
RDVFKKGDIY FNSGDLLMID RENFVYFHDR VGDTFRWKGE NVATTEVADI
510 520 530 540 550
VGLVDFVEEV NVYGVPVPGH EGRIGMASLK IKENYEFNGK KLFQHIAEYL
560 570 580 590 600
PSYARPRFLR IQDTIEITGT FKHRKVTLME EGFNPTVIKD TLYFMDDAEK
610 620
TFVPMTENIY NAIIDKTLKL
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA2ANX6 | A2ANX6_MOUSE | Very long-chain acyl-CoA synthetase | Slc27a2 | 484 | Annotation score: |
Sequence cautioni
The sequence AAC40186 differs from that shown. Reason: Frameshift.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 35 | R → Q in AAB87982 (PubMed:11980911).Curated | 1 | |
Sequence conflicti | 168 | V → A in CAA11687 (PubMed:9559670).Curated | 1 | |
Sequence conflicti | 168 | V → A in AAB87982 (PubMed:11980911).Curated | 1 | |
Sequence conflicti | 234 – 235 | AA → SG in AAC40186 (PubMed:9671728).Curated | 2 | |
Sequence conflicti | 243 | W → R in AAC40186 (PubMed:9671728).Curated | 1 | |
Sequence conflicti | 247 | G → S in AAC40186 (PubMed:9671728).Curated | 1 | |
Sequence conflicti | 257 | Q → K in AAC40186 (PubMed:9671728).Curated | 1 | |
Sequence conflicti | 271 | A → T in AAC40186 (PubMed:9671728).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ223958 mRNA Translation: CAA11687.1 AF072757 mRNA Translation: AAC40186.1 Sequence problems. AF033031 mRNA Translation: AAB87982.1 AL831764 Genomic DNA No translation available. AL844555 Genomic DNA No translation available. BC013442 mRNA Translation: AAH13442.1 BC022170 mRNA Translation: AAH22170.1 BC024735 mRNA Translation: AAH24735.1 |
CCDSi | CCDS16683.1 |
RefSeqi | NP_036108.2, NM_011978.2 |
Genome annotation databases
Ensembli | ENSMUST00000061491; ENSMUSP00000057595; ENSMUSG00000027359 |
GeneIDi | 26458 |
KEGGi | mmu:26458 |
UCSCi | uc008mdq.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ223958 mRNA Translation: CAA11687.1 AF072757 mRNA Translation: AAC40186.1 Sequence problems. AF033031 mRNA Translation: AAB87982.1 AL831764 Genomic DNA No translation available. AL844555 Genomic DNA No translation available. BC013442 mRNA Translation: AAH13442.1 BC022170 mRNA Translation: AAH22170.1 BC024735 mRNA Translation: AAH24735.1 |
CCDSi | CCDS16683.1 |
RefSeqi | NP_036108.2, NM_011978.2 |
3D structure databases
SMRi | O35488 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 205004, 4 interactors |
IntActi | O35488, 4 interactors |
MINTi | O35488 |
STRINGi | 10090.ENSMUSP00000057595 |
Chemistry databases
SwissLipidsi | SLP:000000430 |
PTM databases
iPTMneti | O35488 |
PhosphoSitePlusi | O35488 |
SwissPalmi | O35488 |
Proteomic databases
jPOSTi | O35488 |
MaxQBi | O35488 |
PaxDbi | O35488 |
PeptideAtlasi | O35488 |
PRIDEi | O35488 |
Protocols and materials databases
Antibodypediai | 12170, 176 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000061491; ENSMUSP00000057595; ENSMUSG00000027359 |
GeneIDi | 26458 |
KEGGi | mmu:26458 |
UCSCi | uc008mdq.1, mouse |
Organism-specific databases
CTDi | 11001 |
MGIi | MGI:1347099, Slc27a2 |
Phylogenomic databases
eggNOGi | KOG1179, Eukaryota |
GeneTreei | ENSGT00940000161137 |
HOGENOMi | CLU_000022_46_2_1 |
InParanoidi | O35488 |
OMAi | PMACLNY |
OrthoDBi | 298283at2759 |
TreeFami | TF313430 |
Enzyme and pathway databases
Reactomei | R-MMU-193368, Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol R-MMU-193775, Synthesis of bile acids and bile salts via 24-hydroxycholesterol R-MMU-389599, Alpha-oxidation of phytanate R-MMU-6798695, Neutrophil degranulation R-MMU-9033241, Peroxisomal protein import |
Miscellaneous databases
BioGRID-ORCSi | 26458, 1 hit in 17 CRISPR screens |
ChiTaRSi | Slc27a2, mouse |
PROi | PR:O35488 |
RNActi | O35488, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000027359, Expressed in adult mammalian kidney and 242 other tissues |
ExpressionAtlasi | O35488, baseline and differential |
Genevisiblei | O35488, MM |
Family and domain databases
Gene3Di | 3.40.50.12780, 1 hit |
InterProi | View protein in InterPro IPR025110, AMP-bd_C IPR020845, AMP-binding_CS IPR000873, AMP-dep_Synth/Lig IPR042099, AMP-dep_Synthh-like_sf IPR030305, FATP2 |
PANTHERi | PTHR43107:SF13, PTHR43107:SF13, 1 hit |
Pfami | View protein in Pfam PF00501, AMP-binding, 1 hit PF13193, AMP-binding_C, 1 hit |
PROSITEi | View protein in PROSITE PS00455, AMP_BINDING, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | S27A2_MOUSE | |
Accessioni | O35488Primary (citable) accession number: O35488 Secondary accession number(s): O70550, O88560, Q91WV6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1998 |
Last sequence update: | July 27, 2011 | |
Last modified: | December 2, 2020 | |
This is version 158 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
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families