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Protein

Long-chain-fatty-acid--CoA ligase 6

Gene

Acsl6

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Activation of long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation. Plays an important role in fatty acid metabolism in brain and the acyl-CoAs produced may be utilized exclusively for the synthesis of the brain lipid.

Catalytic activityi

ATP + a long-chain fatty acid + CoA = AMP + diphosphate + an acyl-CoA.

Cofactori

Kineticsi

  1. KM=12210 µM for ATP (Isoform 1)1 Publication
  2. KM=4.7 µM for CoA (Isoform 1)1 Publication
  3. KM=6.0 µM for palmitate (Isoform 1)1 Publication
  4. KM=3.0 µM for oleate (Isoform 1)1 Publication
  5. KM=9.7 µM for arachidonate (Isoform 1)1 Publication
  6. KM=1480 µM for ATP (Isoform 2)1 Publication
  7. KM=2.4 µM for CoA (Isoform 2)1 Publication
  8. KM=3.6 µM for palmitate (Isoform 2)1 Publication
  9. KM=5.3 µM for oleate (Isoform 2)1 Publication
  10. KM=6.5 µM for arachidonate (Isoform 2)1 Publication
  1. Vmax=208 nmol/min/mg enzyme with palmitate as substrate (Isoform 1)1 Publication
  2. Vmax=153 nmol/min/mg enzyme with oleate as substrate (Isoform 1)1 Publication
  3. Vmax=139 nmol/min/mg enzyme with arachidonate as substrate (Isoform 1)1 Publication
  4. Vmax=739 nmol/min/mg enzyme with palmitate as substrate (Isoform 2)1 Publication
  5. Vmax=1088 nmol/min/mg enzyme with oleate as substrate (Isoform 2)1 Publication
  6. Vmax=1212 nmol/min/mg enzyme with arachidonate as substrate (Isoform 2)1 Publication

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • long-chain fatty acid-CoA ligase activity Source: RGD
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

  • cellular response to insulin stimulus Source: RGD
  • fatty acid transport Source: RGD
  • long-chain fatty acid metabolic process Source: RGD
  • neuroblast proliferation Source: Ensembl
  • neuron development Source: RGD
  • phospholipid biosynthetic process Source: RGD
  • positive regulation of neuron projection development Source: RGD
  • positive regulation of plasma membrane long-chain fatty acid transport Source: RGD
  • positive regulation of triglyceride biosynthetic process Source: RGD
  • response to gravity Source: RGD
  • response to hypoxia Source: RGD
  • response to nutrient Source: RGD
  • response to steroid hormone Source: RGD
  • triglyceride metabolic process Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Fatty acid metabolism, Lipid metabolism

Keywords - Ligandi

ATP-binding, Magnesium, Nucleotide-binding

Enzyme and pathway databases

BRENDAi6.2.1.3. 5301.
ReactomeiREACT_346713. Synthesis of very long-chain fatty acyl-CoAs.

Names & Taxonomyi

Protein namesi
Recommended name:
Long-chain-fatty-acid--CoA ligase 6 (EC:6.2.1.3)
Alternative name(s):
Long-chain acyl-CoA synthetase 6
Short name:
LACS 6
Long-chain-fatty-acid--CoA ligase, brain isozyme
Gene namesi
Name:Acsl6
Synonyms:Acs2, Facl6
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi69403. Acsl6.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei25 – 4521Helical; Signal-anchor for type III membrane proteinSequence AnalysisAdd
BLAST
Topological domaini46 – 697652CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome, Mitochondrion, Mitochondrion outer membrane, Peroxisome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 697697Long-chain-fatty-acid--CoA ligase 6PRO_0000193117Add
BLAST

Proteomic databases

PaxDbiP33124.
PRIDEiP33124.

PTM databases

PhosphoSiteiP33124.

Expressioni

Tissue specificityi

Expressed predominantly in brain and, to a much lesser extent, in heart and adrenal.

Developmental stagei

Isoform 1 is detected 10 days after birth, and increased in a coordinate fashion during the development of brain, and the amount did not decrease when myelination was completed.1 Publication

Gene expression databases

ExpressionAtlasiP33124. baseline and differential.
GenevisibleiP33124. RN.

Interactioni

Protein-protein interaction databases

MINTiMINT-4564901.
STRINGi10116.ENSRNOP00000055608.

Structurei

3D structure databases

ProteinModelPortaliP33124.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1022.
GeneTreeiENSGT00690000101725.
HOGENOMiHOG000159459.
HOVERGENiHBG050452.
InParanoidiP33124.
KOiK01897.
OMAiERMVQSV.
OrthoDBiEOG71CFKN.
PhylomeDBiP33124.

Family and domain databases

InterProiIPR020845. AMP-binding_CS.
IPR000873. AMP-dep_Synth/Lig.
[Graphical view]
PfamiPF00501. AMP-binding. 1 hit.
[Graphical view]
PROSITEiPS00455. AMP_BINDING. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P33124-1) [UniParc]FASTAAdd to basket

Also known as: ACSL6_vs1

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MQTQEILRIL RLPELSDLGQ FFRSLSATTL VSMGALAAIL AYWLTHRPKA
60 70 80 90 100
LQPPCNLLMQ SEEVEDSGGA RRSVIGDCTQ LLTHYYDDAR TMYQVFRRGL
110 120 130 140 150
SISGNGPCLG FRKPEQPYQW LSYQEVAKRA EFLGSGLLQH DCKVGTEQFI
160 170 180 190 200
GVFAQNRPEW IIAELACYTY SMVVVPLYDT LGPGSIRYII NTADICTVIV
210 220 230 240 250
DKPHKAILLL EHVERKETPG LKLVILMEPF DDALRERGKK CGVDIKSMQA
260 270 280 290 300
IEDSGQENHR VPVPPRPDDL SIVCFTSGTT GNPKGAMLTH GNVVADFSGF
310 320 330 340 350
LKVTESQWAP TCADVHFSYL PLAHMFERMV QSVVYCHGGR VGFFQGDIRL
360 370 380 390 400
LSDDMKALRP TIFPVVPRLL NRMYDKIFHQ ADTSLKRWLL EFAAKRKQAE
410 420 430 440 450
VRSGIIRNNS IWDELFFNKI QASLGGHVRM IVTGAAPASP TVLGFLRAAL
460 470 480 490 500
GCQVYEGYGQ TECTAGCTFT TPGDWTSGHV GAPLPCNHIK LVDAEELNYW
510 520 530 540 550
TSKGEGEICV KGPNVFKGYL KDEDRTKEAL DSDGWLHTGD IGKWLPEGTL
560 570 580 590 600
KIIDRKKHIF KLAQGEYVAP EKIENIYIRS EPVAQIYVHG DSLKAFLVGI
610 620 630 640 650
VVPDPEVMPC WAQKKGIEGN YQELCKSKEL KKAILDDMVM LGKESGLHSF
660 670 680 690
EQVKAIYIHC DMFSVQNGLL TPTLKAKRPE LREYFKKQIE ELYSISM
Note: Contains exon 14.
Length:697
Mass (Da):78,180
Last modified:October 1, 1993 - v1
Checksum:i0B0CA7EFD653E2BE
GO
Isoform 2 (identifier: P33124-2) [UniParc]FASTAAdd to basket

Also known as: ACSL6_vs2

The sequence of this isoform differs from the canonical sequence as follows:
     306-319: SQWAPTCADVHFSY → KVIFPRQDDVLISF
     329-330: MV → VI

Note: Contains exon 13. No differences in the affinity for fatty acids and CoA. Decreased affinity for ATP. Could play an important role at lower ATP levels. Expressed at lower level in the brain compared to isoform 1.1 Publication
Show »
Length:697
Mass (Da):78,227
Checksum:i521753E09FB712FC
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti558 – 5581H → D in AAB19809 (PubMed:1654331).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei306 – 31914SQWAP…VHFSY → KVIFPRQDDVLISF in isoform 2. 1 PublicationVSP_057107Add
BLAST
Alternative sequencei329 – 3302MV → VI in isoform 2. 1 PublicationVSP_057108

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S56508 mRNA. Translation: AAB19809.2.
D10041 mRNA. Translation: BAA00932.1.
CB582512 mRNA. No translation available.
AY625254 mRNA. Translation: AAT41589.1.
PIRiJX0205.
RefSeqiNP_570095.1. NM_130739.1.
XP_006246285.1. XM_006246223.2. [P33124-2]
XP_006246286.1. XM_006246224.2. [P33124-2]
UniGeneiRn.33697.

Genome annotation databases

EnsembliENSRNOT00000030760; ENSRNOP00000033248; ENSRNOG00000026745. [P33124-1]
GeneIDi117243.
KEGGirno:117243.
UCSCiRGD:69403. rat. [P33124-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S56508 mRNA. Translation: AAB19809.2.
D10041 mRNA. Translation: BAA00932.1.
CB582512 mRNA. No translation available.
AY625254 mRNA. Translation: AAT41589.1.
PIRiJX0205.
RefSeqiNP_570095.1. NM_130739.1.
XP_006246285.1. XM_006246223.2. [P33124-2]
XP_006246286.1. XM_006246224.2. [P33124-2]
UniGeneiRn.33697.

3D structure databases

ProteinModelPortaliP33124.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-4564901.
STRINGi10116.ENSRNOP00000055608.

PTM databases

PhosphoSiteiP33124.

Proteomic databases

PaxDbiP33124.
PRIDEiP33124.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000030760; ENSRNOP00000033248; ENSRNOG00000026745. [P33124-1]
GeneIDi117243.
KEGGirno:117243.
UCSCiRGD:69403. rat. [P33124-1]

Organism-specific databases

CTDi23305.
RGDi69403. Acsl6.

Phylogenomic databases

eggNOGiCOG1022.
GeneTreeiENSGT00690000101725.
HOGENOMiHOG000159459.
HOVERGENiHBG050452.
InParanoidiP33124.
KOiK01897.
OMAiERMVQSV.
OrthoDBiEOG71CFKN.
PhylomeDBiP33124.

Enzyme and pathway databases

BRENDAi6.2.1.3. 5301.
ReactomeiREACT_346713. Synthesis of very long-chain fatty acyl-CoAs.

Miscellaneous databases

NextBioi620076.
PROiP33124.

Gene expression databases

ExpressionAtlasiP33124. baseline and differential.
GenevisibleiP33124. RN.

Family and domain databases

InterProiIPR020845. AMP-binding_CS.
IPR000873. AMP-dep_Synth/Lig.
[Graphical view]
PfamiPF00501. AMP-binding. 1 hit.
[Graphical view]
PROSITEiPS00455. AMP_BINDING. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning and sequencing of cDNA encoding the phosphatidylinositol kinase from rat brain."
    Yamakawa A., Nishizawa M., Fujiwara K.T., Kawai S., Kawasaki H., Suzuki K., Takenawa T.
    J. Biol. Chem. 266:17580-17583(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 491-503; 544-551; 573-579 AND 633-636.
    Tissue: Brain.
  2. Cited for: RETRACTION.
  3. "Cloning and functional expression of a novel long-chain acyl-CoA synthetase expressed in brain."
    Fujino T., Yamamoto T.
    J. Biochem. 111:197-203(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Strain: Wistar.
    Tissue: Brain.
  4. "Characterization of recombinant long-chain rat acyl-CoA synthetase isoforms 3 and 6: identification of a novel variant of isoform 6."
    Van Horn C.G., Caviglia J.M., Li L.O., Wang S., Granger D.A., Coleman R.A.
    Biochemistry 44:1635-1642(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES.
    Tissue: Brain.
  5. "Amgen rat EST program."
    Amgen EST program
    Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-160 (ISOFORM 1).
    Tissue: Spinal ganglion.
  6. "Biochemical studies of two rat acyl-CoA synthetases, ACS1 and ACS2."
    Iijima H., Fujino T., Minekura H., Suzuki H., Kang M.-J., Yamamoto T.T.
    Eur. J. Biochem. 242:186-190(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE.

Entry informationi

Entry nameiACSL6_RAT
AccessioniPrimary (citable) accession number: P33124
Secondary accession number(s): Q63835, Q6IU14
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: June 24, 2015
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

5 rat isozymes encoded by different genes have been described. ACSL6 corresponds to isozyme 2 (ACS2).1 Publication

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.