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Q9UKU0 (ACSL6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
Gene names
Name:ACSL6
Synonyms:ACS2, FACL6, KIAA0837, LACS5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length697 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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 activity

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

Cofactor

Magnesium.

Subcellular location

Mitochondrion outer membrane; Single-pass type III membrane protein By similarity. Peroxisome membrane; Single-pass type III membrane protein By similarity. Microsome membrane; Single-pass type III membrane protein By similarity. Endoplasmic reticulum membrane; Single-pass type III membrane protein By similarity.

Tissue specificity

Expressed predominantly in erythrocyte precursors, in particular in reticulocytes, fetal blood cells derived from fetal liver, hemopoietic stem cells from cord blood, bone marrow and brain. Ref.1

Developmental stage

Expression is low at earlier stages of erythroid development but is very high in reticulocytes.

Involvement in disease

A chromosomal aberration involving ACSL6 may be a cause of myelodysplastic syndrome with basophilia. Translocation t(5;12)(q31;p13) with ETV6.

A chromosomal aberration involving ACSL6 may be a cause of acute myelogenous leukemia with eosinophilia. Translocation t(5;12)(q31;p13) with ETV6.

A chromosomal aberration involving ACSL6 may be a cause of acute eosinophilic leukemia (AEL). Translocation t(5;12)(q31;p13) with ETV6.

Sequence similarities

Belongs to the ATP-dependent AMP-binding enzyme family.

Sequence caution

The sequence AAH26161.1 differs from that shown. Reason: Erroneous termination at position 72. Translated as Arg.

The sequence BAA74860.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processFatty acid metabolism
Lipid metabolism
   Cellular componentEndoplasmic reticulum
Membrane
Microsome
Mitochondrion
Mitochondrion outer membrane
Peroxisome
   Coding sequence diversityAlternative splicing
Chromosomal rearrangement
   DomainTransmembrane
Transmembrane helix
   LigandATP-binding
Magnesium
Nucleotide-binding
   Molecular functionLigase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processacyl-CoA metabolic process

Non-traceable author statement Ref.1. Source: UniProtKB

cellular lipid metabolic process

Traceable author statement. Source: Reactome

cellular response to insulin stimulus

Inferred from electronic annotation. Source: Ensembl

fatty acid transport

Inferred from electronic annotation. Source: Ensembl

long-chain fatty acid metabolic process

Inferred from direct assay PubMed 20429931PubMed 20429931. Source: UniProtKB

long-chain fatty-acyl-CoA biosynthetic process

Traceable author statement. Source: Reactome

neuroblast proliferation

Inferred from electronic annotation. Source: Ensembl

neuron development

Inferred from electronic annotation. Source: Ensembl

phospholipid biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuron projection development

Inferred from electronic annotation. Source: Ensembl

positive regulation of plasma membrane long-chain fatty acid transport

Inferred from electronic annotation. Source: Ensembl

positive regulation of triglyceride biosynthetic process

Inferred from electronic annotation. Source: Ensembl

response to gravity

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

response to nutrient

Inferred from electronic annotation. Source: Ensembl

response to steroid hormone

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

triglyceride biosynthetic process

Traceable author statement. Source: Reactome

   Cellular_componentendoplasmic reticulum membrane

Traceable author statement. Source: Reactome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from direct assay Ref.3PubMed 20429931PubMed 20429931PubMed 20429931. Source: UniProtKB

mitochondrial outer membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: Ensembl

peroxisomal membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Non-traceable author statement Ref.1. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

enzyme binding

Inferred from physical interaction PubMed 20429931PubMed 20429931PubMed 20429931. Source: UniProtKB

long-chain fatty acid-CoA ligase activity

Inferred from direct assay PubMed 20429931PubMed 20429931. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay PubMed 20429931PubMed 20429931PubMed 20429931PubMed 20429931. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 9 isoforms produced by alternative splicing. [Align] [Select]
Isoform 4 (identifier: Q9UKU0-4)

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.
Isoform 1 (identifier: Q9UKU0-1)

Also known as: Long; v2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MLTFFLVSGGSLWLFVEFVLSLLEKM
Isoform 2 (identifier: Q9UKU0-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     306-330: KVIFPRQDDVLISFLPLAHMFERVI → SQWAPTCADVHISYLPLAHMFERMV
     653-697: VKAIHIHSDMFSVQNGLLTPTLKAKRPELREYFKKQIEELYSISM → DLPQCLIQIKVFSKY
Note: No experimental confirmation available.
Isoform 3 (identifier: Q9UKU0-3)

The sequence of this isoform differs from the canonical sequence as follows:
     306-330: KVIFPRQDDVLISFLPLAHMFERVI → SQWAPTCADVHISYLPLAHMFERMV
Note: No experimental confirmation available.
Isoform 5 (identifier: Q9UKU0-5)

Also known as: v4;

The sequence of this isoform differs from the canonical sequence as follows:
     306-312: Missing.
Isoform 6 (identifier: Q9UKU0-6)

Also known as: v5;

The sequence of this isoform differs from the canonical sequence as follows:
     192-192: T → TGLSCQEGASATASTQ
Isoform 7 (identifier: Q9UKU0-7)

Also known as: v3;

The sequence of this isoform differs from the canonical sequence as follows:
     31-65: Missing.
     306-345: Missing.
Isoform 8 (identifier: Q9UKU0-8)

Also known as: v1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MLTFFLVSGGSLWLFVEFVLSLLEKM
     306-330: KVIFPRQDDVLISFLPLAHMFERVI → SQWAPTCADVHISYLPLAHMFERMV
Note: No experimental confirmation available.
Isoform 9 (identifier: Q9UKU0-9)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MPEFVLSLLEKM
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 697697Long-chain-fatty-acid--CoA ligase 6
PRO_0000193115

Regions

Transmembrane25 – 4521Helical; Signal-anchor for type III membrane protein; Potential
Topological domain46 – 697652Cytoplasmic Potential

Natural variations

Alternative sequence11M → MLTFFLVSGGSLWLFVEFVL SLLEKM in isoform 1 and isoform 8.
VSP_037819
Alternative sequence11M → MPEFVLSLLEKM in isoform 9.
VSP_046954
Alternative sequence31 – 6535Missing in isoform 7.
VSP_037820
Alternative sequence1921T → TGLSCQEGASATASTQ in isoform 6.
VSP_037821
Alternative sequence306 – 34540Missing in isoform 7.
VSP_037822
Alternative sequence306 – 33025KVIFP…FERVI → SQWAPTCADVHISYLPLAHM FERMV in isoform 3, isoform 2 and isoform 8.
VSP_021024
Alternative sequence306 – 3127Missing in isoform 5.
VSP_037823
Alternative sequence653 – 69745VKAIH…YSISM → DLPQCLIQIKVFSKY in isoform 2.
VSP_000241

Experimental info

Sequence conflict191G → E in AAD47199. Ref.1
Sequence conflict461H → Q in AAD47199. Ref.1
Sequence conflict2571E → A in AAH47453. Ref.7
Sequence conflict2601Q → L in AAH26161. Ref.7
Sequence conflict3561K → R in AAZ30714. Ref.3
Sequence conflict6961S → P in AAD47199. Ref.1
Sequence conflict6961S → P in AAZ30714. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 4 [UniParc].

Last modified March 6, 2007. Version 4.
Checksum: AC566177B47D0975

FASTA69777,752
        10         20         30         40         50         60 
MQTQEILRIL RLPELGDLGQ FFRSLSATTL VSMGALAAIL AYWFTHRPKA LQPPCNLLMQ 

        70         80         90        100        110        120 
SEEVEDSGGA RRSVIGSGPQ LLTHYYDDAR TMYQVFRRGL SISGNGPCLG FRKPKQPYQW 

       130        140        150        160        170        180 
LSYQEVADRA EFLGSGLLQH NCKACTDQFI GVFAQNRPEW IIVELACYTY SMVVVPLYDT 

       190        200        210        220        230        240 
LGPGAIRYII NTADISTVIV DKPQKAVLLL EHVERKETPG LKLIILMDPF EEALKERGQK 

       250        260        270        280        290        300 
CGVVIKSMQA VEDCGQENHQ APVPPQPDDL SIVCFTSGTT GNPKGAMLTH GNVVADFSGF 

       310        320        330        340        350        360 
LKVTEKVIFP RQDDVLISFL PLAHMFERVI QSVVYCHGGR VGFFQGDIRL LSDDMKALCP 

       370        380        390        400        410        420 
TIFPVVPRLL NRMYDKIFSQ ANTPLKRWLL EFAAKRKQAE VRSGIIRNDS IWDELFFNKI 

       430        440        450        460        470        480 
QASLGGCVRM IVTGAAPASP TVLGFLRAAL GCQVYEGYGQ TECTAGCTFT TPGDWTSGHV 

       490        500        510        520        530        540 
GAPLPCNHIK LVDVEELNYW ACKGEGEICV RGPNVFKGYL KDPDRTKEAL DSDGWLHTGD 

       550        560        570        580        590        600 
IGKWLPAGTL KIIDRKKHIF KLAQGEYVAP EKIENIYIRS QPVAQIYVHG DSLKAFLVGI 

       610        620        630        640        650        660 
VVPDPEVMPS WAQKRGIEGT YADLCTNKDL KKAILEDMVR LGKESGLHSF EQVKAIHIHS 

       670        680        690 
DMFSVQNGLL TPTLKAKRPE LREYFKKQIE ELYSISM 

« Hide

Isoform 1 (Long) (v2) [UniParc].

Checksum: 2B7D408F2F77C1FB
Show »

FASTA72280,610
Isoform 2 (Short) [UniParc].

Checksum: E57CDD86836E7D64
Show »

FASTA66774,175
Isoform 3 [UniParc].

Checksum: F70642502C212FA7
Show »

FASTA69777,671
Isoform 5 (v4) [UniParc].

Checksum: 3D96A1B1433CF6F9
Show »

FASTA69076,883
Isoform 6 (v5) [UniParc].

Checksum: 1BC1636243762146
Show »

FASTA71279,144
Isoform 7 (v3) [UniParc].

Checksum: E5BE0D13E92599ED
Show »

FASTA62269,222
Isoform 8 (v1) [UniParc].

Checksum: 702D63A8B72BE729
Show »

FASTA72280,529
Isoform 9 [UniParc].

Checksum: DD0FE6A5EDA476D0
Show »

FASTA70879,040

References

« Hide 'large scale' references
[1]"Identification and molecular characterization of acyl-CoA synthetase in human red cells and erythroid precursor."
Malhotra K.T., Malhotra K., Lubin B.H., Kuypers F.A.
Biochem. J. 344:135-143(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY.
[2]"Fusion of TEL/ETV6 to a novel ACS2 in myelodysplastic syndrome and acute myelogenous leukemia with t(5;12)(q31;p13)."
Yagasaki F., Jinnai I., Yoshida S., Yokoyama Y., Matsuda A., Kusumoto S., Kobayashi H., Terasaki H., Ohyashiki K., Asou N., Murohashi I., Bessho M., Hirashima K.
Genes Chromosomes Cancer 26:192-202(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), CHROMOSOMAL TRANSLOCATION WITH ETV6.
Tissue: Bone marrow.
[3]"Multiple erythroid isoforms of human long-chain acyl-CoA synthetases are produced by switch of the fatty acid gate domains."
Soupene E., Kuypers F.A.
BMC Mol. Biol. 7:21-21(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), NUCLEOTIDE SEQUENCE [MRNA] OF 253-374 (ISOFORM 5), ALTERNATIVE SPLICING (ISOFORM 8).
[4]"Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:355-364(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[5]"Full-length cDNA libraries and normalization."
Li W.B., Gruber C., Jessee J., Polayes D.
Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
Tissue: Brain.
[6]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 8).
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 7 AND 9).
Tissue: Testis.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF129166 mRNA. Translation: AAD47199.1.
AF099740 mRNA. Translation: AAD17853.1.
DQ083030 mRNA. Translation: AAZ30713.1.
DQ083031 mRNA. Translation: AAZ30714.1.
AB020644 mRNA. Translation: BAA74860.1. Different initiation.
CR606980 mRNA. No translation available.
AC025772 Genomic DNA. No translation available.
AC026398 Genomic DNA. No translation available.
AC034228 Genomic DNA. No translation available.
BC026161 mRNA. Translation: AAH26161.1. Sequence problems.
BC047453 mRNA. Translation: AAH47453.1.
CCDSCCDS34228.1. [Q9UKU0-8]
CCDS34229.1. [Q9UKU0-1]
CCDS56381.1. [Q9UKU0-3]
CCDS56382.1. [Q9UKU0-7]
CCDS56383.1. [Q9UKU0-9]
RefSeqNP_001009185.1. NM_001009185.2. [Q9UKU0-1]
NP_001192176.1. NM_001205247.1.
NP_001192177.1. NM_001205248.1. [Q9UKU0-3]
NP_001192179.1. NM_001205250.1. [Q9UKU0-9]
NP_001192180.1. NM_001205251.1. [Q9UKU0-7]
NP_056071.2. NM_015256.3. [Q9UKU0-8]
XP_006714642.1. XM_006714579.1. [Q9UKU0-4]
XP_006714643.1. XM_006714580.1. [Q9UKU0-4]
UniGeneHs.14945.

3D structure databases

ProteinModelPortalQ9UKU0.
SMRQ9UKU0. Positions 222-605.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116897. 1 interaction.
IntActQ9UKU0. 1 interaction.
STRING9606.ENSP00000296869.

PTM databases

PhosphoSiteQ9UKU0.

Polymorphism databases

DMDM146322303.

Proteomic databases

MaxQBQ9UKU0.
PaxDbQ9UKU0.
PRIDEQ9UKU0.

Protocols and materials databases

DNASU23305.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000296869; ENSP00000296869; ENSG00000164398. [Q9UKU0-8]
ENST00000357096; ENSP00000349608; ENSG00000164398. [Q9UKU0-7]
ENST00000379240; ENSP00000368542; ENSG00000164398. [Q9UKU0-4]
ENST00000379244; ENSP00000368546; ENSG00000164398. [Q9UKU0-3]
ENST00000379246; ENSP00000368548; ENSG00000164398. [Q9UKU0-9]
ENST00000379249; ENSP00000368551; ENSG00000164398. [Q9UKU0-2]
ENST00000379255; ENSP00000368557; ENSG00000164398. [Q9UKU0-7]
ENST00000379264; ENSP00000368566; ENSG00000164398. [Q9UKU0-1]
ENST00000379272; ENSP00000368574; ENSG00000164398. [Q9UKU0-6]
ENST00000413683; ENSP00000415140; ENSG00000164398. [Q9UKU0-2]
ENST00000543479; ENSP00000442124; ENSG00000164398. [Q9UKU0-3]
GeneID23305.
KEGGhsa:23305.
UCSCuc003kvx.2. human. [Q9UKU0-8]
uc003kvy.2. human. [Q9UKU0-1]
uc003kvz.2. human. [Q9UKU0-7]
uc010jdn.2. human. [Q9UKU0-6]
uc010jdo.2. human. [Q9UKU0-3]

Organism-specific databases

CTD23305.
GeneCardsGC05M131147.
HGNCHGNC:16496. ACSL6.
HPAHPA040470.
MIM604443. gene.
neXtProtNX_Q9UKU0.
PharmGKBPA27970.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1022.
HOGENOMHOG000159459.
HOVERGENHBG050452.
KOK01897.
OMAMFERMVQ.
OrthoDBEOG71CFKN.
PhylomeDBQ9UKU0.
TreeFamTF313877.

Enzyme and pathway databases

BioCycMetaCyc:HS15193-MONOMER.
BRENDA6.2.1.3. 2681.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ9UKU0.
BgeeQ9UKU0.
CleanExHS_ACSL6.
GenevestigatorQ9UKU0.

Family and domain databases

InterProIPR020845. AMP-binding_CS.
IPR000873. AMP-dep_Synth/Lig.
[Graphical view]
PfamPF00501. AMP-binding. 1 hit.
[Graphical view]
PROSITEPS00455. AMP_BINDING. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiACSL6.
GenomeRNAi23305.
NextBio13615790.
PROQ9UKU0.
SOURCESearch...

Entry information

Entry nameACSL6_HUMAN
AccessionPrimary (citable) accession number: Q9UKU0
Secondary accession number(s): J3KPG3 expand/collapse secondary AC list , O94924, O95829, Q108M9, Q108N0, Q4G191, Q86TN7
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: March 6, 2007
Last modified: July 9, 2014
This is version 135 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM