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Protein

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

Gene

Acsl6

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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.

Miscellaneous

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

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
  • decanoate-CoA ligase activity Source: UniProtKB-EC
  • enzyme binding Source: RGD
  • 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: RGD
  • 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

Keywordsi

Molecular functionLigase
Biological processFatty acid metabolism, Lipid metabolism
LigandATP-binding, Magnesium, Nucleotide-binding

Enzyme and pathway databases

BRENDAi6.2.1.3 5301
ReactomeiR-RNO-75876 Synthesis of very long-chain fatty acyl-CoAs

Chemistry databases

SwissLipidsiSLP:000001686

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi69403 Acsl6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei25 – 45Helical; Signal-anchor for type III membrane proteinSequence analysisAdd BLAST21
Topological domaini46 – 697CytoplasmicSequence analysisAdd BLAST652

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001931171 – 697Long-chain-fatty-acid--CoA ligase 6Add BLAST697

Proteomic databases

PaxDbiP33124
PRIDEiP33124

PTM databases

iPTMnetiP33124
PhosphoSitePlusiP33124

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

BgeeiENSRNOG00000026745
ExpressionAtlasiP33124 baseline and differential
GenevisibleiP33124 RN

Interactioni

GO - Molecular functioni

  • enzyme binding Source: RGD
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000055608

Structurei

3D structure databases

ProteinModelPortaliP33124
SMRiP33124
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1256 Eukaryota
COG1022 LUCA
GeneTreeiENSGT00690000101725
HOGENOMiHOG000159459
HOVERGENiHBG050452
InParanoidiP33124
KOiK01897
PhylomeDBiP33124

Family and domain databases

InterProiView protein in InterPro
IPR020845 AMP-binding_CS
IPR000873 AMP-dep_Synth/Lig
PfamiView protein in Pfam
PF00501 AMP-binding, 1 hit
PROSITEiView protein in PROSITE
PS00455 AMP_BINDING, 1 hit

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

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_057107306 – 319SQWAP…VHFSY → KVIFPRQDDVLISF in isoform 2. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_057108329 – 330MV → VI in isoform 2. 1 Publication2

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_006246223.3 [P33124-2]
XP_006246286.1, XM_006246224.3 [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

Similar proteinsi

Entry informationi

Entry nameiACSL6_RAT
AccessioniPrimary (citable) accession number: P33124
Secondary accession number(s): Q63835, Q6IU14
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: April 25, 2018
This is version 135 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health