UniProtKB - O14975 (S27A2_HUMAN)
Protein
Very long-chain acyl-CoA synthetase
Gene
SLC27A2
Organism
Homo sapiens (Human)
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:10198260, PubMed:10749848, PubMed:11980911). Can also activate branched-chain fatty acids such as phytanic acid and pristanic acid (PubMed:10198260). Does not activate C24 bile acids, cholate and chenodeoxycholate (PubMed:11980911). 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 (PubMed:11980911). Exhibits long-chain fatty acids (LCFA) transport activity and plays an important role in hepatic fatty acid uptake (PubMed:20530735).4 Publications
Exhibits both long-chain fatty acids (LCFA) transport activity and acyl CoA synthetase towards very long-chain fatty acids (PubMed:21768100). Shows a preference for generating CoA derivatives of n-3 fatty acids, which are preferentially trafficked into phosphatidylinositol (PubMed:21768100).1 Publication
Exhibits long-chain fatty acids (LCFA) transport activity but lacks acyl CoA synthetase towards very long-chain fatty acids.1 Publication
Catalytic activityi
- EC:6.2.1.33 PublicationsThis reaction proceeds in the forward3 Publications direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphateBy similarityEC:6.2.1.15By similarityThis reaction proceeds in the forwardBy similarity direction.
- EC:6.2.1.241 PublicationThis reaction proceeds in the forward1 Publication direction.
- (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oate + ATP + CoA = (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oyl-CoA + AMP + diphosphate1 PublicationEC:6.2.1.71 PublicationThis reaction proceeds in the forward1 Publication direction.
- a very long-chain fatty acid + ATP + CoA = a very long-chain fatty acyl-CoA + AMP + diphosphate4 PublicationsThis reaction proceeds in the forward3 Publications direction.
- This reaction proceeds in the backward2 Publications direction.
- This reaction proceeds in the forward2 Publications direction.
- (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + ATP + CoA = (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + AMP + diphosphate1 PublicationThis reaction proceeds in the forward1 Publication direction.This reaction proceeds in the forward1 Publication direction.
- (9Z,12Z,15Z)-octadecatrienoate + ATP + CoA = (9Z,12Z,15Z)-octadecatrienoyl-CoA + AMP + diphosphate1 PublicationThis reaction proceeds in the forward1 Publication direction.This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward3 Publications direction.
- This reaction proceeds in the forward1 Publication direction.This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
Kineticsi
- KM=12 µM for palmitic acid1 Publication
- Vmax=1.4 nmol/min/mg enzyme for palmitic acid1 Publication
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: UniProtKB
- fatty acid transmembrane transporter activity Source: GO_Central
- long-chain fatty acid-CoA ligase activity Source: UniProtKB
- long-chain fatty acid transporter activity Source: UniProtKB
- phytanate-CoA ligase activity Source: UniProtKB
- pristanate-CoA ligase activity Source: UniProtKB
- very long-chain fatty acid-CoA ligase activity Source: UniProtKB
GO - Biological processi
- bile acid biosynthetic process Source: UniProtKB
- fatty acid alpha-oxidation Source: UniProtKB
- fatty acid beta-oxidation Source: UniProtKB
- long-chain fatty acid import into cell Source: UniProtKB
- long-chain fatty acid metabolic process Source: UniProtKB
- methyl-branched fatty acid metabolic process Source: UniProtKB
- neutrophil degranulation Source: Reactome
- protein targeting to peroxisome Source: Reactome
- very long-chain fatty acid catabolic process Source: GO_Central
Keywordsi
Molecular function | Ligase |
Biological process | Fatty acid metabolism, Lipid metabolism |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BioCyci | MetaCyc:HS06695-MONOMER |
PathwayCommonsi | O14975 |
Reactomei | R-HSA-193368, Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol R-HSA-193775, Synthesis of bile acids and bile salts via 24-hydroxycholesterol R-HSA-389599, Alpha-oxidation of phytanate R-HSA-6798695, Neutrophil degranulation R-HSA-9033241, Peroxisomal protein import |
SIGNORi | O14975 |
Protein family/group databases
TCDBi | 4.C.1.1.5, the fatty acid transporter (fat) family |
Chemistry databases
SwissLipidsi | SLP:000000428 SLP:000000431 [O14975-2] SLP:000000432 [O14975-1] |
Names & Taxonomyi
Protein namesi | Recommended name: Very long-chain acyl-CoA synthetase3 Publications (EC:6.2.1.-)Short name: VLACSBy similarity Short name: VLCS3 Publications Alternative name(s): Arachidonate--CoA ligase (EC:6.2.1.15By similarity) Fatty acid transport protein 21 Publication Short name: FATP-21 Publication Fatty-acid-coenzyme A ligase, very long-chain 1 Long-chain-fatty-acid--CoA ligase (EC:6.2.1.33 Publications) Phytanate--CoA ligase (EC:6.2.1.241 Publication) Solute carrier family 27 member 2 THCA-CoA ligase (EC:6.2.1.71 Publication) Very long-chain-fatty-acid-CoA ligase |
Gene namesi | Name:SLC27A2 Synonyms:ACSVL1, FACVL1, FATP2, VLACS |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:10996, SLC27A2 |
MIMi | 603247, gene |
neXtProti | NX_O14975 |
VEuPathDBi | HostDB:ENSG00000140284.10 |
Subcellular locationi
Plasma membrane
- Cell membrane By similarity; Multi-pass membrane protein Sequence analysis
Endoplasmic reticulum
- Endoplasmic reticulum membrane 2 Publications; Multi-pass membrane protein Sequence analysis
- Microsome 1 Publication
Peroxisome
- Peroxisome membrane 2 Publications; Peripheral membrane protein 1 Publication
Cytosol
- cytosol Source: Reactome
Endoplasmic reticulum
- endoplasmic reticulum Source: GO_Central
- endoplasmic reticulum lumen Source: UniProtKB
- endoplasmic reticulum membrane Source: UniProtKB
- integral component of endoplasmic reticulum membrane Source: UniProtKB
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Peroxisome
- integral component of peroxisomal membrane Source: UniProtKB
- peroxisomal membrane Source: UniProtKB
Plasma Membrane
- plasma membrane Source: Reactome
Other locations
- specific granule membrane Source: Reactome
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 4 | Lumenal1 Publication | 4 | |
Transmembranei | 5 – 27 | HelicalSequence analysisAdd BLAST | 23 | |
Topological domaini | 28 – 106 | Cytoplasmic1 PublicationAdd BLAST | 79 | |
Transmembranei | 107 – 127 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 128 – 261 | Lumenal1 PublicationAdd BLAST | 134 | |
Transmembranei | 262 – 282 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 283 – 620 | Cytoplasmic1 PublicationAdd BLAST | 338 |
Keywords - Cellular componenti
Cell membrane, Endoplasmic reticulum, Membrane, Microsome, PeroxisomePathology & Biotechi
Organism-specific databases
DisGeNETi | 11001 |
OpenTargetsi | ENSG00000140284 |
PharmGKBi | PA27971 |
Miscellaneous databases
Pharosi | O14975, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4326 |
DrugBanki | DB11936, Bempedoic acid |
Genetic variation databases
BioMutai | SLC27A2 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000193204 | 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-acetyllysineBy similarity | 1 | |
Modified residuei | 577 | PhosphothreonineCombined sources | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | O14975 |
jPOSTi | O14975 |
MassIVEi | O14975 |
MaxQBi | O14975 |
PaxDbi | O14975 |
PeptideAtlasi | O14975 |
PRIDEi | O14975 |
ProteomicsDBi | 48348 [O14975-1] 48349 [O14975-2] |
PTM databases
iPTMneti | O14975 |
MetOSitei | O14975 |
PhosphoSitePlusi | O14975 |
SwissPalmi | O14975 |
Expressioni
Tissue specificityi
Expressed in liver, kidney, placenta and pancreas.3 Publications
Gene expression databases
Bgeei | ENSG00000140284, Expressed in nephron tubule and 188 other tissues |
ExpressionAtlasi | O14975, baseline and differential |
Genevisiblei | O14975, HS |
Organism-specific databases
HPAi | ENSG00000140284, Tissue enriched (liver) |
Interactioni
GO - Molecular functioni
- enzyme binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 116194, 69 interactors |
IntActi | O14975, 38 interactors |
MINTi | O14975 |
STRINGi | 9606.ENSP00000267842 |
Chemistry databases
BindingDBi | O14975 |
Miscellaneous databases
RNActi | O14975, 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 | O14975 |
OMAi | PMACLNY |
OrthoDBi | 298283at2759 |
PhylomeDBi | O14975 |
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 |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
Isoform 1 (identifier: O14975-1) [UniParc]FASTAAdd to basket
Also known as: FATP2a1 Publication
This 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
MLSAIYTVLA GLLFLPLLVN LCCPYFFQDI GYFLKVAAVG RRVRSYGKRR
60 70 80 90 100
PARTILRAFL EKARQTPHKP FLLFRDETLT YAQVDRRSNQ VARALHDHLG
110 120 130 140 150
LRQGDCVALL MGNEPAYVWL WLGLVKLGCA MACLNYNIRA KSLLHCFQCC
160 170 180 190 200
GAKVLLVSPE LQAAVEEILP SLKKDDVSIY YVSRTSNTDG IDSFLDKVDE
210 220 230 240 250
VSTEPIPESW RSEVTFSTPA LYIYTSGTTG LPKAAMITHQ RIWYGTGLTF
260 270 280 290 300
VSGLKADDVI YITLPFYHSA ALLIGIHGCI VAGATLALRT KFSASQFWDD
310 320 330 340 350
CRKYNVTVIQ YIGELLRYLC NSPQKPNDRD HKVRLALGNG LRGDVWRQFV
360 370 380 390 400
KRFGDICIYE FYAATEGNIG FMNYARKVGA VGRVNYLQKK IITYDLIKYD
410 420 430 440 450
VEKDEPVRDE NGYCVRVPKG EVGLLVCKIT QLTPFNGYAG AKAQTEKKKL
460 470 480 490 500
RDVFKKGDLY FNSGDLLMVD HENFIYFHDR VGDTFRWKGE NVATTEVADT
510 520 530 540 550
VGLVDFVQEV NVYGVHVPDH EGRIGMASIK MKENHEFDGK KLFQHIADYL
560 570 580 590 600
PSYARPRFLR IQDTIEITGT FKHRKMTLVE EGFNPAVIKD ALYFLDDTAK
610 620
MYVPMTEDIY NAISAKTLKL
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketG3V1R7 | G3V1R7_HUMAN | Solute carrier family 27 (Fatty aci... | SLC27A2 hCG_39815 | 385 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_046533 | 48 | K → Q4 PublicationsCorresponds to variant dbSNP:rs1648348Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_042726 | 230 – 282 | Missing in isoform 2. 1 PublicationAdd BLAST | 53 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D88308 mRNA Translation: BAA23644.1 AF096290 mRNA Translation: AAC64973.1 AK223145 mRNA Translation: BAD96865.1 AK290262 mRNA Translation: BAF82951.1 AC009753 Genomic DNA No translation available. CH471082 Genomic DNA Translation: EAW77386.1 BC057770 mRNA Translation: AAH57770.1 |
CCDSi | CCDS10133.1 [O14975-1] CCDS53943.1 [O14975-2] |
RefSeqi | NP_001153101.1, NM_001159629.1 [O14975-2] NP_003636.2, NM_003645.3 [O14975-1] |
Genome annotation databases
Ensembli | ENST00000267842; ENSP00000267842; ENSG00000140284 [O14975-1] ENST00000380902; ENSP00000370289; ENSG00000140284 [O14975-2] |
GeneIDi | 11001 |
KEGGi | hsa:11001 |
UCSCi | uc001zxw.4, human [O14975-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D88308 mRNA Translation: BAA23644.1 AF096290 mRNA Translation: AAC64973.1 AK223145 mRNA Translation: BAD96865.1 AK290262 mRNA Translation: BAF82951.1 AC009753 Genomic DNA No translation available. CH471082 Genomic DNA Translation: EAW77386.1 BC057770 mRNA Translation: AAH57770.1 |
CCDSi | CCDS10133.1 [O14975-1] CCDS53943.1 [O14975-2] |
RefSeqi | NP_001153101.1, NM_001159629.1 [O14975-2] NP_003636.2, NM_003645.3 [O14975-1] |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 116194, 69 interactors |
IntActi | O14975, 38 interactors |
MINTi | O14975 |
STRINGi | 9606.ENSP00000267842 |
Chemistry databases
BindingDBi | O14975 |
ChEMBLi | CHEMBL4326 |
DrugBanki | DB11936, Bempedoic acid |
SwissLipidsi | SLP:000000428 SLP:000000431 [O14975-2] SLP:000000432 [O14975-1] |
Protein family/group databases
TCDBi | 4.C.1.1.5, the fatty acid transporter (fat) family |
PTM databases
iPTMneti | O14975 |
MetOSitei | O14975 |
PhosphoSitePlusi | O14975 |
SwissPalmi | O14975 |
Genetic variation databases
BioMutai | SLC27A2 |
Proteomic databases
EPDi | O14975 |
jPOSTi | O14975 |
MassIVEi | O14975 |
MaxQBi | O14975 |
PaxDbi | O14975 |
PeptideAtlasi | O14975 |
PRIDEi | O14975 |
ProteomicsDBi | 48348 [O14975-1] 48349 [O14975-2] |
Protocols and materials databases
Antibodypediai | 12170, 176 antibodies |
Genome annotation databases
Ensembli | ENST00000267842; ENSP00000267842; ENSG00000140284 [O14975-1] ENST00000380902; ENSP00000370289; ENSG00000140284 [O14975-2] |
GeneIDi | 11001 |
KEGGi | hsa:11001 |
UCSCi | uc001zxw.4, human [O14975-1] |
Organism-specific databases
CTDi | 11001 |
DisGeNETi | 11001 |
GeneCardsi | SLC27A2 |
HGNCi | HGNC:10996, SLC27A2 |
HPAi | ENSG00000140284, Tissue enriched (liver) |
MIMi | 603247, gene |
neXtProti | NX_O14975 |
OpenTargetsi | ENSG00000140284 |
PharmGKBi | PA27971 |
VEuPathDBi | HostDB:ENSG00000140284.10 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1179, Eukaryota |
GeneTreei | ENSGT00940000161137 |
HOGENOMi | CLU_000022_46_2_1 |
InParanoidi | O14975 |
OMAi | PMACLNY |
OrthoDBi | 298283at2759 |
PhylomeDBi | O14975 |
TreeFami | TF313430 |
Enzyme and pathway databases
BioCyci | MetaCyc:HS06695-MONOMER |
PathwayCommonsi | O14975 |
Reactomei | R-HSA-193368, Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol R-HSA-193775, Synthesis of bile acids and bile salts via 24-hydroxycholesterol R-HSA-389599, Alpha-oxidation of phytanate R-HSA-6798695, Neutrophil degranulation R-HSA-9033241, Peroxisomal protein import |
SIGNORi | O14975 |
Miscellaneous databases
BioGRID-ORCSi | 11001, 3 hits in 873 CRISPR screens |
ChiTaRSi | SLC27A2, human |
GeneWikii | SLC27A2 |
GenomeRNAii | 11001 |
Pharosi | O14975, Tbio |
PROi | PR:O14975 |
RNActi | O14975, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000140284, Expressed in nephron tubule and 188 other tissues |
ExpressionAtlasi | O14975, baseline and differential |
Genevisiblei | O14975, HS |
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_HUMAN | |
Accessioni | O14975Primary (citable) accession number: O14975 Secondary accession number(s): A8K2J7, Q53FY6, Q6PF09 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1998 |
Last sequence update: | October 5, 2010 | |
Last modified: | February 10, 2021 | |
This is version 174 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human chromosome 15
Human chromosome 15: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants