Full text data of ACSL6
ACSL6
(ACS2, FACL6, KIAA0837, LACS5)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Long-chain-fatty-acid--CoA ligase 6; 6.2.1.3 (Long-chain acyl-CoA synthetase 6; LACS 6)
Long-chain-fatty-acid--CoA ligase 6; 6.2.1.3 (Long-chain acyl-CoA synthetase 6; LACS 6)
Comments
Isoform Q9UKU0-3 was detected.
Isoform Q9UKU0-3 was detected.
Comments
Isoform Q9UKU0-3 was detected.
Isoform Q9UKU0-3 was detected.
UniProt
Q9UKU0
ID ACSL6_HUMAN Reviewed; 697 AA.
AC Q9UKU0; J3KPG3; O94924; O95829; Q108M9; Q108N0; Q4G191; Q86TN7;
read moreDT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 4.
DT 22-JAN-2014, entry version 129.
DE RecName: Full=Long-chain-fatty-acid--CoA ligase 6;
DE EC=6.2.1.3;
DE AltName: Full=Long-chain acyl-CoA synthetase 6;
DE Short=LACS 6;
GN Name=ACSL6; Synonyms=ACS2, FACL6, KIAA0837, LACS5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND TISSUE SPECIFICITY.
RX PubMed=10548543; DOI=10.1042/0264-6021:3440135;
RA Malhotra K.T., Malhotra K., Lubin B.H., Kuypers F.A.;
RT "Identification and molecular characterization of acyl-CoA synthetase
RT in human red cells and erythroid precursor.";
RL Biochem. J. 344:135-143(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND CHROMOSOMAL TRANSLOCATION
RP WITH ETV6.
RC TISSUE=Bone marrow;
RX PubMed=10502316;
RX DOI=10.1002/(SICI)1098-2264(199911)26:3<192::AID-GCC2>3.0.CO;2-E;
RA Yagasaki F., Jinnai I., Yoshida S., Yokoyama Y., Matsuda A.,
RA Kusumoto S., Kobayashi H., Terasaki H., Ohyashiki K., Asou N.,
RA Murohashi I., Bessho M., Hirashima K.;
RT "Fusion of TEL/ETV6 to a novel ACS2 in myelodysplastic syndrome and
RT acute myelogenous leukemia with t(5;12)(q31;p13).";
RL Genes Chromosomes Cancer 26:192-202(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), NUCLEOTIDE SEQUENCE [MRNA] OF
RP 253-374 (ISOFORM 5), AND ALTERNATIVE SPLICING (ISOFORM 8).
RX PubMed=16834775; DOI=10.1186/1471-2199-7-21;
RA Soupene E., Kuypers F.A.;
RT "Multiple erythroid isoforms of human long-chain acyl-CoA synthetases
RT are produced by switch of the fatty acid gate domains.";
RL BMC Mol. Biol. 7:21-21(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M.,
RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Brain;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE
RP SPLICING (ISOFORM 8).
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 7 AND 9).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Activation of long-chain fatty acids for both synthesis
CC of cellular lipids, and degradation via beta-oxidation. Plays an
CC important role in fatty acid metabolism in brain and the acyl-CoAs
CC produced may be utilized exclusively for the synthesis of the
CC brain lipid.
CC -!- CATALYTIC ACTIVITY: ATP + a long-chain fatty acid + CoA = AMP +
CC diphosphate + an acyl-CoA.
CC -!- COFACTOR: Magnesium.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane; Single-pass
CC type III membrane protein (By similarity). Peroxisome membrane;
CC Single-pass type III membrane protein (By similarity). Microsome
CC membrane; Single-pass type III membrane protein (By similarity).
CC Endoplasmic reticulum membrane; Single-pass type III membrane
CC protein (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=9;
CC Name=4;
CC IsoId=Q9UKU0-4; Sequence=Displayed;
CC Name=1; Synonyms=Long, v2;
CC IsoId=Q9UKU0-1; Sequence=VSP_037819;
CC Name=2; Synonyms=Short;
CC IsoId=Q9UKU0-2; Sequence=VSP_021024, VSP_000241;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q9UKU0-3; Sequence=VSP_021024;
CC Note=No experimental confirmation available;
CC Name=5; Synonyms=v4;
CC IsoId=Q9UKU0-5; Sequence=VSP_037823;
CC Name=6; Synonyms=v5;
CC IsoId=Q9UKU0-6; Sequence=VSP_037821;
CC Name=7; Synonyms=v3;
CC IsoId=Q9UKU0-7; Sequence=VSP_037820, VSP_037822;
CC Name=8; Synonyms=v1;
CC IsoId=Q9UKU0-8; Sequence=VSP_037819, VSP_021024;
CC Note=No experimental confirmation available;
CC Name=9;
CC IsoId=Q9UKU0-9; Sequence=VSP_046954;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed predominantly in erythrocyte
CC precursors, in particular in reticulocytes, fetal blood cells
CC derived from fetal liver, hemopoietic stem cells from cord blood,
CC bone marrow and brain.
CC -!- DEVELOPMENTAL STAGE: Expression is low at earlier stages of
CC erythroid development but is very high in reticulocytes.
CC -!- DISEASE: Note=A chromosomal aberration involving ACSL6 may be a
CC cause of myelodysplastic syndrome with basophilia. Translocation
CC t(5;12)(q31;p13) with ETV6.
CC -!- DISEASE: Note=A chromosomal aberration involving ACSL6 may be a
CC cause of acute myelogenous leukemia with eosinophilia.
CC Translocation t(5;12)(q31;p13) with ETV6.
CC -!- DISEASE: Note=A chromosomal aberration involving ACSL6 may be a
CC cause of acute eosinophilic leukemia (AEL). Translocation
CC t(5;12)(q31;p13) with ETV6.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme
CC family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH26161.1; Type=Erroneous termination; Positions=72; Note=Translated as Arg;
CC Sequence=BAA74860.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; AF129166; AAD47199.1; -; mRNA.
DR EMBL; AF099740; AAD17853.1; -; mRNA.
DR EMBL; DQ083030; AAZ30713.1; -; mRNA.
DR EMBL; DQ083031; AAZ30714.1; -; mRNA.
DR EMBL; AB020644; BAA74860.1; ALT_INIT; mRNA.
DR EMBL; CR606980; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC025772; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC026398; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC034228; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC026161; AAH26161.1; ALT_SEQ; mRNA.
DR EMBL; BC047453; AAH47453.1; -; mRNA.
DR RefSeq; NP_001009185.1; NM_001009185.2.
DR RefSeq; NP_001192176.1; NM_001205247.1.
DR RefSeq; NP_001192177.1; NM_001205248.1.
DR RefSeq; NP_001192179.1; NM_001205250.1.
DR RefSeq; NP_001192180.1; NM_001205251.1.
DR RefSeq; NP_056071.2; NM_015256.3.
DR RefSeq; XP_005271997.1; XM_005271940.1.
DR UniGene; Hs.14945; -.
DR ProteinModelPortal; Q9UKU0; -.
DR SMR; Q9UKU0; 222-605.
DR IntAct; Q9UKU0; 1.
DR STRING; 9606.ENSP00000296869; -.
DR PhosphoSite; Q9UKU0; -.
DR DMDM; 146322303; -.
DR PaxDb; Q9UKU0; -.
DR PRIDE; Q9UKU0; -.
DR DNASU; 23305; -.
DR Ensembl; ENST00000296869; ENSP00000296869; ENSG00000164398.
DR Ensembl; ENST00000357096; ENSP00000349608; ENSG00000164398.
DR Ensembl; ENST00000379240; ENSP00000368542; ENSG00000164398.
DR Ensembl; ENST00000379244; ENSP00000368546; ENSG00000164398.
DR Ensembl; ENST00000379246; ENSP00000368548; ENSG00000164398.
DR Ensembl; ENST00000379249; ENSP00000368551; ENSG00000164398.
DR Ensembl; ENST00000379255; ENSP00000368557; ENSG00000164398.
DR Ensembl; ENST00000379264; ENSP00000368566; ENSG00000164398.
DR Ensembl; ENST00000379272; ENSP00000368574; ENSG00000164398.
DR Ensembl; ENST00000413683; ENSP00000415140; ENSG00000164398.
DR Ensembl; ENST00000543479; ENSP00000442124; ENSG00000164398.
DR GeneID; 23305; -.
DR KEGG; hsa:23305; -.
DR UCSC; uc003kwa.2; human.
DR CTD; 23305; -.
DR GeneCards; GC05M131147; -.
DR HGNC; HGNC:16496; ACSL6.
DR HPA; HPA040470; -.
DR MIM; 604443; gene.
DR neXtProt; NX_Q9UKU0; -.
DR PharmGKB; PA27970; -.
DR eggNOG; COG1022; -.
DR HOGENOM; HOG000159459; -.
DR HOVERGEN; HBG050452; -.
DR KO; K01897; -.
DR OMA; MFERMVQ; -.
DR OrthoDB; EOG71CFKN; -.
DR BioCyc; MetaCyc:HS15193-MONOMER; -.
DR BRENDA; 6.2.1.3; 2681.
DR Reactome; REACT_111217; Metabolism.
DR GeneWiki; ACSL6; -.
DR GenomeRNAi; 23305; -.
DR NextBio; 13615790; -.
DR PRO; PR:Q9UKU0; -.
DR ArrayExpress; Q9UKU0; -.
DR Bgee; Q9UKU0; -.
DR CleanEx; HS_ACSL6; -.
DR Genevestigator; Q9UKU0; -.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0005778; C:peroxisomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; NAS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004467; F:long-chain fatty acid-CoA ligase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0015908; P:fatty acid transport; IEA:Ensembl.
DR GO; GO:0035338; P:long-chain fatty-acyl-CoA biosynthetic process; TAS:Reactome.
DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0048666; P:neuron development; IEA:Ensembl.
DR GO; GO:0008654; P:phospholipid biosynthetic process; IEA:Ensembl.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0010747; P:positive regulation of plasma membrane long-chain fatty acid transport; IEA:Ensembl.
DR GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; IEA:Ensembl.
DR GO; GO:0009629; P:response to gravity; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0048545; P:response to steroid hormone stimulus; IEA:Ensembl.
DR GO; GO:0019432; P:triglyceride biosynthetic process; TAS:Reactome.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR Pfam; PF00501; AMP-binding; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Chromosomal rearrangement;
KW Complete proteome; Endoplasmic reticulum; Fatty acid metabolism;
KW Ligase; Lipid metabolism; Magnesium; Membrane; Microsome;
KW Mitochondrion; Mitochondrion outer membrane; Nucleotide-binding;
KW Peroxisome; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1 697 Long-chain-fatty-acid--CoA ligase 6.
FT /FTId=PRO_0000193115.
FT TRANSMEM 25 45 Helical; Signal-anchor for type III
FT membrane protein; (Potential).
FT TOPO_DOM 46 697 Cytoplasmic (Potential).
FT VAR_SEQ 1 1 M -> MLTFFLVSGGSLWLFVEFVLSLLEKM (in
FT isoform 1 and isoform 8).
FT /FTId=VSP_037819.
FT VAR_SEQ 1 1 M -> MPEFVLSLLEKM (in isoform 9).
FT /FTId=VSP_046954.
FT VAR_SEQ 31 65 Missing (in isoform 7).
FT /FTId=VSP_037820.
FT VAR_SEQ 192 192 T -> TGLSCQEGASATASTQ (in isoform 6).
FT /FTId=VSP_037821.
FT VAR_SEQ 306 345 Missing (in isoform 7).
FT /FTId=VSP_037822.
FT VAR_SEQ 306 330 KVIFPRQDDVLISFLPLAHMFERVI -> SQWAPTCADVHI
FT SYLPLAHMFERMV (in isoform 3, isoform 2
FT and isoform 8).
FT /FTId=VSP_021024.
FT VAR_SEQ 306 312 Missing (in isoform 5).
FT /FTId=VSP_037823.
FT VAR_SEQ 653 697 VKAIHIHSDMFSVQNGLLTPTLKAKRPELREYFKKQIEELY
FT SISM -> DLPQCLIQIKVFSKY (in isoform 2).
FT /FTId=VSP_000241.
FT CONFLICT 19 19 G -> E (in Ref. 1; AAD47199).
FT CONFLICT 46 46 H -> Q (in Ref. 1; AAD47199).
FT CONFLICT 257 257 E -> A (in Ref. 7; AAH47453).
FT CONFLICT 260 260 Q -> L (in Ref. 7; AAH26161).
FT CONFLICT 356 356 K -> R (in Ref. 3; AAZ30714).
FT CONFLICT 696 696 S -> P (in Ref. 1; AAD47199 and 3;
FT AAZ30714).
SQ SEQUENCE 697 AA; 77752 MW; AC566177B47D0975 CRC64;
MQTQEILRIL RLPELGDLGQ FFRSLSATTL VSMGALAAIL AYWFTHRPKA LQPPCNLLMQ
SEEVEDSGGA RRSVIGSGPQ LLTHYYDDAR TMYQVFRRGL SISGNGPCLG FRKPKQPYQW
LSYQEVADRA EFLGSGLLQH NCKACTDQFI GVFAQNRPEW IIVELACYTY SMVVVPLYDT
LGPGAIRYII NTADISTVIV DKPQKAVLLL EHVERKETPG LKLIILMDPF EEALKERGQK
CGVVIKSMQA VEDCGQENHQ APVPPQPDDL SIVCFTSGTT GNPKGAMLTH GNVVADFSGF
LKVTEKVIFP RQDDVLISFL PLAHMFERVI QSVVYCHGGR VGFFQGDIRL LSDDMKALCP
TIFPVVPRLL NRMYDKIFSQ ANTPLKRWLL EFAAKRKQAE VRSGIIRNDS IWDELFFNKI
QASLGGCVRM IVTGAAPASP TVLGFLRAAL GCQVYEGYGQ TECTAGCTFT TPGDWTSGHV
GAPLPCNHIK LVDVEELNYW ACKGEGEICV RGPNVFKGYL KDPDRTKEAL DSDGWLHTGD
IGKWLPAGTL KIIDRKKHIF KLAQGEYVAP EKIENIYIRS QPVAQIYVHG DSLKAFLVGI
VVPDPEVMPS WAQKRGIEGT YADLCTNKDL KKAILEDMVR LGKESGLHSF EQVKAIHIHS
DMFSVQNGLL TPTLKAKRPE LREYFKKQIE ELYSISM
//
ID ACSL6_HUMAN Reviewed; 697 AA.
AC Q9UKU0; J3KPG3; O94924; O95829; Q108M9; Q108N0; Q4G191; Q86TN7;
read moreDT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 4.
DT 22-JAN-2014, entry version 129.
DE RecName: Full=Long-chain-fatty-acid--CoA ligase 6;
DE EC=6.2.1.3;
DE AltName: Full=Long-chain acyl-CoA synthetase 6;
DE Short=LACS 6;
GN Name=ACSL6; Synonyms=ACS2, FACL6, KIAA0837, LACS5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND TISSUE SPECIFICITY.
RX PubMed=10548543; DOI=10.1042/0264-6021:3440135;
RA Malhotra K.T., Malhotra K., Lubin B.H., Kuypers F.A.;
RT "Identification and molecular characterization of acyl-CoA synthetase
RT in human red cells and erythroid precursor.";
RL Biochem. J. 344:135-143(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND CHROMOSOMAL TRANSLOCATION
RP WITH ETV6.
RC TISSUE=Bone marrow;
RX PubMed=10502316;
RX DOI=10.1002/(SICI)1098-2264(199911)26:3<192::AID-GCC2>3.0.CO;2-E;
RA Yagasaki F., Jinnai I., Yoshida S., Yokoyama Y., Matsuda A.,
RA Kusumoto S., Kobayashi H., Terasaki H., Ohyashiki K., Asou N.,
RA Murohashi I., Bessho M., Hirashima K.;
RT "Fusion of TEL/ETV6 to a novel ACS2 in myelodysplastic syndrome and
RT acute myelogenous leukemia with t(5;12)(q31;p13).";
RL Genes Chromosomes Cancer 26:192-202(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), NUCLEOTIDE SEQUENCE [MRNA] OF
RP 253-374 (ISOFORM 5), AND ALTERNATIVE SPLICING (ISOFORM 8).
RX PubMed=16834775; DOI=10.1186/1471-2199-7-21;
RA Soupene E., Kuypers F.A.;
RT "Multiple erythroid isoforms of human long-chain acyl-CoA synthetases
RT are produced by switch of the fatty acid gate domains.";
RL BMC Mol. Biol. 7:21-21(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M.,
RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Brain;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE
RP SPLICING (ISOFORM 8).
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 7 AND 9).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Activation of long-chain fatty acids for both synthesis
CC of cellular lipids, and degradation via beta-oxidation. Plays an
CC important role in fatty acid metabolism in brain and the acyl-CoAs
CC produced may be utilized exclusively for the synthesis of the
CC brain lipid.
CC -!- CATALYTIC ACTIVITY: ATP + a long-chain fatty acid + CoA = AMP +
CC diphosphate + an acyl-CoA.
CC -!- COFACTOR: Magnesium.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane; Single-pass
CC type III membrane protein (By similarity). Peroxisome membrane;
CC Single-pass type III membrane protein (By similarity). Microsome
CC membrane; Single-pass type III membrane protein (By similarity).
CC Endoplasmic reticulum membrane; Single-pass type III membrane
CC protein (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=9;
CC Name=4;
CC IsoId=Q9UKU0-4; Sequence=Displayed;
CC Name=1; Synonyms=Long, v2;
CC IsoId=Q9UKU0-1; Sequence=VSP_037819;
CC Name=2; Synonyms=Short;
CC IsoId=Q9UKU0-2; Sequence=VSP_021024, VSP_000241;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q9UKU0-3; Sequence=VSP_021024;
CC Note=No experimental confirmation available;
CC Name=5; Synonyms=v4;
CC IsoId=Q9UKU0-5; Sequence=VSP_037823;
CC Name=6; Synonyms=v5;
CC IsoId=Q9UKU0-6; Sequence=VSP_037821;
CC Name=7; Synonyms=v3;
CC IsoId=Q9UKU0-7; Sequence=VSP_037820, VSP_037822;
CC Name=8; Synonyms=v1;
CC IsoId=Q9UKU0-8; Sequence=VSP_037819, VSP_021024;
CC Note=No experimental confirmation available;
CC Name=9;
CC IsoId=Q9UKU0-9; Sequence=VSP_046954;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed predominantly in erythrocyte
CC precursors, in particular in reticulocytes, fetal blood cells
CC derived from fetal liver, hemopoietic stem cells from cord blood,
CC bone marrow and brain.
CC -!- DEVELOPMENTAL STAGE: Expression is low at earlier stages of
CC erythroid development but is very high in reticulocytes.
CC -!- DISEASE: Note=A chromosomal aberration involving ACSL6 may be a
CC cause of myelodysplastic syndrome with basophilia. Translocation
CC t(5;12)(q31;p13) with ETV6.
CC -!- DISEASE: Note=A chromosomal aberration involving ACSL6 may be a
CC cause of acute myelogenous leukemia with eosinophilia.
CC Translocation t(5;12)(q31;p13) with ETV6.
CC -!- DISEASE: Note=A chromosomal aberration involving ACSL6 may be a
CC cause of acute eosinophilic leukemia (AEL). Translocation
CC t(5;12)(q31;p13) with ETV6.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme
CC family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH26161.1; Type=Erroneous termination; Positions=72; Note=Translated as Arg;
CC Sequence=BAA74860.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; AF129166; AAD47199.1; -; mRNA.
DR EMBL; AF099740; AAD17853.1; -; mRNA.
DR EMBL; DQ083030; AAZ30713.1; -; mRNA.
DR EMBL; DQ083031; AAZ30714.1; -; mRNA.
DR EMBL; AB020644; BAA74860.1; ALT_INIT; mRNA.
DR EMBL; CR606980; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC025772; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC026398; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC034228; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC026161; AAH26161.1; ALT_SEQ; mRNA.
DR EMBL; BC047453; AAH47453.1; -; mRNA.
DR RefSeq; NP_001009185.1; NM_001009185.2.
DR RefSeq; NP_001192176.1; NM_001205247.1.
DR RefSeq; NP_001192177.1; NM_001205248.1.
DR RefSeq; NP_001192179.1; NM_001205250.1.
DR RefSeq; NP_001192180.1; NM_001205251.1.
DR RefSeq; NP_056071.2; NM_015256.3.
DR RefSeq; XP_005271997.1; XM_005271940.1.
DR UniGene; Hs.14945; -.
DR ProteinModelPortal; Q9UKU0; -.
DR SMR; Q9UKU0; 222-605.
DR IntAct; Q9UKU0; 1.
DR STRING; 9606.ENSP00000296869; -.
DR PhosphoSite; Q9UKU0; -.
DR DMDM; 146322303; -.
DR PaxDb; Q9UKU0; -.
DR PRIDE; Q9UKU0; -.
DR DNASU; 23305; -.
DR Ensembl; ENST00000296869; ENSP00000296869; ENSG00000164398.
DR Ensembl; ENST00000357096; ENSP00000349608; ENSG00000164398.
DR Ensembl; ENST00000379240; ENSP00000368542; ENSG00000164398.
DR Ensembl; ENST00000379244; ENSP00000368546; ENSG00000164398.
DR Ensembl; ENST00000379246; ENSP00000368548; ENSG00000164398.
DR Ensembl; ENST00000379249; ENSP00000368551; ENSG00000164398.
DR Ensembl; ENST00000379255; ENSP00000368557; ENSG00000164398.
DR Ensembl; ENST00000379264; ENSP00000368566; ENSG00000164398.
DR Ensembl; ENST00000379272; ENSP00000368574; ENSG00000164398.
DR Ensembl; ENST00000413683; ENSP00000415140; ENSG00000164398.
DR Ensembl; ENST00000543479; ENSP00000442124; ENSG00000164398.
DR GeneID; 23305; -.
DR KEGG; hsa:23305; -.
DR UCSC; uc003kwa.2; human.
DR CTD; 23305; -.
DR GeneCards; GC05M131147; -.
DR HGNC; HGNC:16496; ACSL6.
DR HPA; HPA040470; -.
DR MIM; 604443; gene.
DR neXtProt; NX_Q9UKU0; -.
DR PharmGKB; PA27970; -.
DR eggNOG; COG1022; -.
DR HOGENOM; HOG000159459; -.
DR HOVERGEN; HBG050452; -.
DR KO; K01897; -.
DR OMA; MFERMVQ; -.
DR OrthoDB; EOG71CFKN; -.
DR BioCyc; MetaCyc:HS15193-MONOMER; -.
DR BRENDA; 6.2.1.3; 2681.
DR Reactome; REACT_111217; Metabolism.
DR GeneWiki; ACSL6; -.
DR GenomeRNAi; 23305; -.
DR NextBio; 13615790; -.
DR PRO; PR:Q9UKU0; -.
DR ArrayExpress; Q9UKU0; -.
DR Bgee; Q9UKU0; -.
DR CleanEx; HS_ACSL6; -.
DR Genevestigator; Q9UKU0; -.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0005778; C:peroxisomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; NAS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004467; F:long-chain fatty acid-CoA ligase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0015908; P:fatty acid transport; IEA:Ensembl.
DR GO; GO:0035338; P:long-chain fatty-acyl-CoA biosynthetic process; TAS:Reactome.
DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0048666; P:neuron development; IEA:Ensembl.
DR GO; GO:0008654; P:phospholipid biosynthetic process; IEA:Ensembl.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0010747; P:positive regulation of plasma membrane long-chain fatty acid transport; IEA:Ensembl.
DR GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; IEA:Ensembl.
DR GO; GO:0009629; P:response to gravity; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0048545; P:response to steroid hormone stimulus; IEA:Ensembl.
DR GO; GO:0019432; P:triglyceride biosynthetic process; TAS:Reactome.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR Pfam; PF00501; AMP-binding; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Chromosomal rearrangement;
KW Complete proteome; Endoplasmic reticulum; Fatty acid metabolism;
KW Ligase; Lipid metabolism; Magnesium; Membrane; Microsome;
KW Mitochondrion; Mitochondrion outer membrane; Nucleotide-binding;
KW Peroxisome; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1 697 Long-chain-fatty-acid--CoA ligase 6.
FT /FTId=PRO_0000193115.
FT TRANSMEM 25 45 Helical; Signal-anchor for type III
FT membrane protein; (Potential).
FT TOPO_DOM 46 697 Cytoplasmic (Potential).
FT VAR_SEQ 1 1 M -> MLTFFLVSGGSLWLFVEFVLSLLEKM (in
FT isoform 1 and isoform 8).
FT /FTId=VSP_037819.
FT VAR_SEQ 1 1 M -> MPEFVLSLLEKM (in isoform 9).
FT /FTId=VSP_046954.
FT VAR_SEQ 31 65 Missing (in isoform 7).
FT /FTId=VSP_037820.
FT VAR_SEQ 192 192 T -> TGLSCQEGASATASTQ (in isoform 6).
FT /FTId=VSP_037821.
FT VAR_SEQ 306 345 Missing (in isoform 7).
FT /FTId=VSP_037822.
FT VAR_SEQ 306 330 KVIFPRQDDVLISFLPLAHMFERVI -> SQWAPTCADVHI
FT SYLPLAHMFERMV (in isoform 3, isoform 2
FT and isoform 8).
FT /FTId=VSP_021024.
FT VAR_SEQ 306 312 Missing (in isoform 5).
FT /FTId=VSP_037823.
FT VAR_SEQ 653 697 VKAIHIHSDMFSVQNGLLTPTLKAKRPELREYFKKQIEELY
FT SISM -> DLPQCLIQIKVFSKY (in isoform 2).
FT /FTId=VSP_000241.
FT CONFLICT 19 19 G -> E (in Ref. 1; AAD47199).
FT CONFLICT 46 46 H -> Q (in Ref. 1; AAD47199).
FT CONFLICT 257 257 E -> A (in Ref. 7; AAH47453).
FT CONFLICT 260 260 Q -> L (in Ref. 7; AAH26161).
FT CONFLICT 356 356 K -> R (in Ref. 3; AAZ30714).
FT CONFLICT 696 696 S -> P (in Ref. 1; AAD47199 and 3;
FT AAZ30714).
SQ SEQUENCE 697 AA; 77752 MW; AC566177B47D0975 CRC64;
MQTQEILRIL RLPELGDLGQ FFRSLSATTL VSMGALAAIL AYWFTHRPKA LQPPCNLLMQ
SEEVEDSGGA RRSVIGSGPQ LLTHYYDDAR TMYQVFRRGL SISGNGPCLG FRKPKQPYQW
LSYQEVADRA EFLGSGLLQH NCKACTDQFI GVFAQNRPEW IIVELACYTY SMVVVPLYDT
LGPGAIRYII NTADISTVIV DKPQKAVLLL EHVERKETPG LKLIILMDPF EEALKERGQK
CGVVIKSMQA VEDCGQENHQ APVPPQPDDL SIVCFTSGTT GNPKGAMLTH GNVVADFSGF
LKVTEKVIFP RQDDVLISFL PLAHMFERVI QSVVYCHGGR VGFFQGDIRL LSDDMKALCP
TIFPVVPRLL NRMYDKIFSQ ANTPLKRWLL EFAAKRKQAE VRSGIIRNDS IWDELFFNKI
QASLGGCVRM IVTGAAPASP TVLGFLRAAL GCQVYEGYGQ TECTAGCTFT TPGDWTSGHV
GAPLPCNHIK LVDVEELNYW ACKGEGEICV RGPNVFKGYL KDPDRTKEAL DSDGWLHTGD
IGKWLPAGTL KIIDRKKHIF KLAQGEYVAP EKIENIYIRS QPVAQIYVHG DSLKAFLVGI
VVPDPEVMPS WAQKRGIEGT YADLCTNKDL KKAILEDMVR LGKESGLHSF EQVKAIHIHS
DMFSVQNGLL TPTLKAKRPE LREYFKKQIE ELYSISM
//
MIM
604443
*RECORD*
*FIELD* NO
604443
*FIELD* TI
*604443 ACYL-CoA SYNTHETASE LONG CHAIN FAMILY, MEMBER 6; ACSL6
;;FATTY ACID CoA LIGASE, LONG CHAIN 6; FACL6;;
read moreLONG CHAIN ACYL-CoA SYNTHETASE 2; LACS2;;
LONG CHAIN ACYL-CoA SYNTHETASE 5; LACS5;;
ACYL-CoA SYNTHETASE 2; ACS2;;
KIAA0837
ACS2/ETV6 FUSION GENE, INCLUDED
*FIELD* TX
DESCRIPTION
Long chain acyl-CoA synthetases (EC 6.2.1.3), such as ACSL6, catalyze
the formation of acyl-CoA from fatty acids, ATP, and CoA (Malhotra et
al., 1999).
CLONING
By sequencing clones obtained from a size-fractionated brain cDNA
library, Nagase et al. (1998) cloned ACSL6, which they designated
KIAA0837. The transcript contains repetitive elements in its 3-prime
region, and the deduced 745-amino acid protein shares a high degree of
similarity with rat brain long chain fatty acid CoA ligase. RT-PCR ELISA
detected very high ACSL6 expression in whole adult brain and in all
specific adult brain regions examined. Expression was lower in heart and
fetal brain, and much lower in all other tissues examined.
In a patient with refractory anemia with excess blasts with basophilia,
a patient with acute myelogenous leukemia (AML) with eosinophilia, and a
patient with acute eosinophilic leukemia (AEL), Yagasaki et al. (1999)
identified ACSL6, which they called ACS2, as an ETV6 (600618) fusion
partner in a recurrent t(5;12)(q31;p13) translocation. Northern blot
analysis detected high levels of ACS2 expression in brain, fetal liver,
and bone marrow, and the gene was found to be highly conserved in man
and rat.
Using degenerate primers based on conserved regions of acyl-CoA
synthetases, Malhotra et al. (1999) cloned ACSL6, which they called
LACS5, from a K562 erythroid cell line cDNA library. The deduced
697-amino acid protein has a calculated molecular mass of 77.6 kD. It
has a transmembrane region and a predicted extended cytoplasmic tail of
657 amino acids. Northern blot analysis detected variable expression of
2.9- and 6.3-kb transcripts in K562 cells, fetal blood derived from
liver cells, reticulocytes, bone marrow, and cord blood. LACS5 was also
expressed in human brain as transcripts of 9.4 kb and 2.9 kb. Western
blot analysis of human erythrocyte ghosts detected LACS5 at an apparent
molecular mass of 78 kD.
Using the central portion of mouse Pahx (PHYH; 602026) as bait in a
yeast 2-hybrid screen of a mouse brain cDNA library, Kee et al. (2003)
cloned Acsl6. The deduced 722-amino acid mouse protein has a calculated
molecular mass of 81 kD. Northern blot analysis detected high expression
of a 2.6-kb transcript in brain and testis, with weaker expression in
heart and skeletal muscle. A transcript of about 6.5 kb was also
detected in brain. Expression of the 6.5-kb transcript in brain began at
birth and increased to a maximum level in adult mice. Western blot
analysis detected a 95-kD Acsl6 protein in brain, heart, and testis.
By searching databases for sequences containing acyl-CoA synthetase
motifs 1 and 2, Watkins et al. (2007) identified 2 splice variants of
human ACSL6 that result from the use of alternative exons 11. Both
variants encode proteins of 722 amino acids that differ internally
within acyl-CoA synthetase motif 4. Phylogenetic analysis revealed that
ACSL5 belongs to a family of long chain acyl-CoA synthetases.
GENE STRUCTURE
Watkins et al. (2007) determined that the ACSL6 gene contains 22 exons,
including 2 alternative exons 11.
MAPPING
By sequence analysis, Yagasaki et al. (1999) mapped the ACSL6 gene to
chromosome 5q31.
GENE FUNCTION
Malhotra et al. (1999) showed that recombinant human LACS5 had acyl-CoA
synthetase activity with palmitic acid, oleic acid, and arachidonic
acid.
Kee et al. (2003) found that expression of Acsl6 increased in PC12 rat
pheochromocytoma cells during nerve growth factor (see 162030)-induced
neurite outgrowth. Expression of Acsl6 in PC12 cells increased the
formation of arachidonoyl-CoA more than palmitoyl-CoA or oleoyl-CoA.
Marszalek et al. (2005) found that overexpression of Acsl6 in
differentiated PC12 cells enhanced docosahexaenoic acid (DHA)
internalization, conversion of DHA to DHA-CoA, and accumulation of
DHA-CoA.
CYTOGENETICS
In a patient with refractory anemia with excess blasts with basophilia,
a patient with AML with eosinophilia, and a patient with AEL, Yagasaki
et al. (1999) identified ACS2 as an ETV6 fusion partner in a recurrent
t(5;12)(q31;p13) translocation. The ETV6/ACS2 fusion transcripts showed
an out-frame fusion of exon 1 of ETV6 to exon 1 of ACS2 in the AEL
patient, an out-frame fusion of exon 1 of ETV6 to exon 11 of ACS2 in the
AML patient, and a short in-frame fusion of exon 1 of ETV6 to the
3-prime untranslated region of ACS2 in the patient with refractory
anemia. Reciprocal ACS2/ETV6 transcripts were identified in 2 of the
cases. FISH with ETV6 cosmids on 12p13, and BACs and PIs on 5q31,
demonstrated that the 5q31 breakpoints of the AML and AEL cases involved
the 5-prime portion of the ACS2 gene, and that the 5q31 breakpoint of
the refractory anemia case involved the 3-prime portion of the ACS2
gene. None of the resulting chimeric transcripts except for the
ACS2/ETV6 transcript in the refractory anemia case led to a fusion
protein.
*FIELD* RF
1. Kee, H. J.; Koh, J. T.; Yang, S. Y.; Lee, Z. H.; Baik, Y. H.; Kim,
K. K.: A novel murine long-chain acyl-CoA synthetase expressed in
brain participates in neuronal cell proliferation. Biochem. Biophys.
Res. Commun. 305: 925-933, 2003.
2. Malhotra, K. T.; Malhotra, K.; Lubin, B. H.; Kuypers, F. A.: Identification
and molecular characterization of acyl-CoA synthetase in human erythrocytes
and erythroid precursors. Biochem. J. 344: 135-143, 1999.
3. Marszalek, J. R.; Kitidis, C.; DiRusso, C. C.; Lodish, H. F.:
Long-chain acyl-CoA synthetase 6 preferentially promotes DHA metabolism. J.
Biol. Chem. 280: 10817-10826, 2005.
4. Nagase, T.; Ishikawa, K.; Suyama, M.; Kikuno, R.; Hirosawa, M.;
Miyajima, N.; Tanaka, A.; Kotani, H.; Nomura, N.; Oharo, O.: 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. DNA Res. 5: 355-364, 1998.
5. Watkins, P. A.; Maiguel, D.; Jia, Z.; Pevsner, J.: Evidence for
26 distinct acyl-coenzyme A synthetase genes in the human genome. J.
Lipid Res. 48: 2736-2750, 2007.
6. Yagasaki, F.; Jinnai, I.; Yoshida, S.; Yokoyama, Y.; Matsuda, A.;
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.: Fusion of TEL/ETV6 to a
novel ACS2 in myelodysplastic syndrome and acute myelogenous leukemia
with t(5;12)(q31;p13). Genes Chromosomes Cancer 26: 192-202, 1999.
*FIELD* CN
Patricia A. Hartz - updated: 10/4/2011
Patricia A. Hartz - updated: 6/5/2009
*FIELD* CD
Victor A. McKusick: 1/19/2000
*FIELD* ED
mgross: 12/02/2011
mgross: 11/30/2011
terry: 10/4/2011
mgross: 6/11/2009
terry: 6/5/2009
ckniffin: 12/5/2008
terry: 9/19/2008
cwells: 11/7/2003
mgross: 9/19/2001
mgross: 2/22/2001
mgross: 1/19/2000
*RECORD*
*FIELD* NO
604443
*FIELD* TI
*604443 ACYL-CoA SYNTHETASE LONG CHAIN FAMILY, MEMBER 6; ACSL6
;;FATTY ACID CoA LIGASE, LONG CHAIN 6; FACL6;;
read moreLONG CHAIN ACYL-CoA SYNTHETASE 2; LACS2;;
LONG CHAIN ACYL-CoA SYNTHETASE 5; LACS5;;
ACYL-CoA SYNTHETASE 2; ACS2;;
KIAA0837
ACS2/ETV6 FUSION GENE, INCLUDED
*FIELD* TX
DESCRIPTION
Long chain acyl-CoA synthetases (EC 6.2.1.3), such as ACSL6, catalyze
the formation of acyl-CoA from fatty acids, ATP, and CoA (Malhotra et
al., 1999).
CLONING
By sequencing clones obtained from a size-fractionated brain cDNA
library, Nagase et al. (1998) cloned ACSL6, which they designated
KIAA0837. The transcript contains repetitive elements in its 3-prime
region, and the deduced 745-amino acid protein shares a high degree of
similarity with rat brain long chain fatty acid CoA ligase. RT-PCR ELISA
detected very high ACSL6 expression in whole adult brain and in all
specific adult brain regions examined. Expression was lower in heart and
fetal brain, and much lower in all other tissues examined.
In a patient with refractory anemia with excess blasts with basophilia,
a patient with acute myelogenous leukemia (AML) with eosinophilia, and a
patient with acute eosinophilic leukemia (AEL), Yagasaki et al. (1999)
identified ACSL6, which they called ACS2, as an ETV6 (600618) fusion
partner in a recurrent t(5;12)(q31;p13) translocation. Northern blot
analysis detected high levels of ACS2 expression in brain, fetal liver,
and bone marrow, and the gene was found to be highly conserved in man
and rat.
Using degenerate primers based on conserved regions of acyl-CoA
synthetases, Malhotra et al. (1999) cloned ACSL6, which they called
LACS5, from a K562 erythroid cell line cDNA library. The deduced
697-amino acid protein has a calculated molecular mass of 77.6 kD. It
has a transmembrane region and a predicted extended cytoplasmic tail of
657 amino acids. Northern blot analysis detected variable expression of
2.9- and 6.3-kb transcripts in K562 cells, fetal blood derived from
liver cells, reticulocytes, bone marrow, and cord blood. LACS5 was also
expressed in human brain as transcripts of 9.4 kb and 2.9 kb. Western
blot analysis of human erythrocyte ghosts detected LACS5 at an apparent
molecular mass of 78 kD.
Using the central portion of mouse Pahx (PHYH; 602026) as bait in a
yeast 2-hybrid screen of a mouse brain cDNA library, Kee et al. (2003)
cloned Acsl6. The deduced 722-amino acid mouse protein has a calculated
molecular mass of 81 kD. Northern blot analysis detected high expression
of a 2.6-kb transcript in brain and testis, with weaker expression in
heart and skeletal muscle. A transcript of about 6.5 kb was also
detected in brain. Expression of the 6.5-kb transcript in brain began at
birth and increased to a maximum level in adult mice. Western blot
analysis detected a 95-kD Acsl6 protein in brain, heart, and testis.
By searching databases for sequences containing acyl-CoA synthetase
motifs 1 and 2, Watkins et al. (2007) identified 2 splice variants of
human ACSL6 that result from the use of alternative exons 11. Both
variants encode proteins of 722 amino acids that differ internally
within acyl-CoA synthetase motif 4. Phylogenetic analysis revealed that
ACSL5 belongs to a family of long chain acyl-CoA synthetases.
GENE STRUCTURE
Watkins et al. (2007) determined that the ACSL6 gene contains 22 exons,
including 2 alternative exons 11.
MAPPING
By sequence analysis, Yagasaki et al. (1999) mapped the ACSL6 gene to
chromosome 5q31.
GENE FUNCTION
Malhotra et al. (1999) showed that recombinant human LACS5 had acyl-CoA
synthetase activity with palmitic acid, oleic acid, and arachidonic
acid.
Kee et al. (2003) found that expression of Acsl6 increased in PC12 rat
pheochromocytoma cells during nerve growth factor (see 162030)-induced
neurite outgrowth. Expression of Acsl6 in PC12 cells increased the
formation of arachidonoyl-CoA more than palmitoyl-CoA or oleoyl-CoA.
Marszalek et al. (2005) found that overexpression of Acsl6 in
differentiated PC12 cells enhanced docosahexaenoic acid (DHA)
internalization, conversion of DHA to DHA-CoA, and accumulation of
DHA-CoA.
CYTOGENETICS
In a patient with refractory anemia with excess blasts with basophilia,
a patient with AML with eosinophilia, and a patient with AEL, Yagasaki
et al. (1999) identified ACS2 as an ETV6 fusion partner in a recurrent
t(5;12)(q31;p13) translocation. The ETV6/ACS2 fusion transcripts showed
an out-frame fusion of exon 1 of ETV6 to exon 1 of ACS2 in the AEL
patient, an out-frame fusion of exon 1 of ETV6 to exon 11 of ACS2 in the
AML patient, and a short in-frame fusion of exon 1 of ETV6 to the
3-prime untranslated region of ACS2 in the patient with refractory
anemia. Reciprocal ACS2/ETV6 transcripts were identified in 2 of the
cases. FISH with ETV6 cosmids on 12p13, and BACs and PIs on 5q31,
demonstrated that the 5q31 breakpoints of the AML and AEL cases involved
the 5-prime portion of the ACS2 gene, and that the 5q31 breakpoint of
the refractory anemia case involved the 3-prime portion of the ACS2
gene. None of the resulting chimeric transcripts except for the
ACS2/ETV6 transcript in the refractory anemia case led to a fusion
protein.
*FIELD* RF
1. Kee, H. J.; Koh, J. T.; Yang, S. Y.; Lee, Z. H.; Baik, Y. H.; Kim,
K. K.: A novel murine long-chain acyl-CoA synthetase expressed in
brain participates in neuronal cell proliferation. Biochem. Biophys.
Res. Commun. 305: 925-933, 2003.
2. Malhotra, K. T.; Malhotra, K.; Lubin, B. H.; Kuypers, F. A.: Identification
and molecular characterization of acyl-CoA synthetase in human erythrocytes
and erythroid precursors. Biochem. J. 344: 135-143, 1999.
3. Marszalek, J. R.; Kitidis, C.; DiRusso, C. C.; Lodish, H. F.:
Long-chain acyl-CoA synthetase 6 preferentially promotes DHA metabolism. J.
Biol. Chem. 280: 10817-10826, 2005.
4. Nagase, T.; Ishikawa, K.; Suyama, M.; Kikuno, R.; Hirosawa, M.;
Miyajima, N.; Tanaka, A.; Kotani, H.; Nomura, N.; Oharo, O.: 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. DNA Res. 5: 355-364, 1998.
5. Watkins, P. A.; Maiguel, D.; Jia, Z.; Pevsner, J.: Evidence for
26 distinct acyl-coenzyme A synthetase genes in the human genome. J.
Lipid Res. 48: 2736-2750, 2007.
6. Yagasaki, F.; Jinnai, I.; Yoshida, S.; Yokoyama, Y.; Matsuda, A.;
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.: Fusion of TEL/ETV6 to a
novel ACS2 in myelodysplastic syndrome and acute myelogenous leukemia
with t(5;12)(q31;p13). Genes Chromosomes Cancer 26: 192-202, 1999.
*FIELD* CN
Patricia A. Hartz - updated: 10/4/2011
Patricia A. Hartz - updated: 6/5/2009
*FIELD* CD
Victor A. McKusick: 1/19/2000
*FIELD* ED
mgross: 12/02/2011
mgross: 11/30/2011
terry: 10/4/2011
mgross: 6/11/2009
terry: 6/5/2009
ckniffin: 12/5/2008
terry: 9/19/2008
cwells: 11/7/2003
mgross: 9/19/2001
mgross: 2/22/2001
mgross: 1/19/2000