ACOT6_HUMAN
ID ACOT6_HUMAN Reviewed; 421 AA.
AC Q3I5F7; A0A2R8Y7H3;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 29-SEP-2021, sequence version 2.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Acyl-coenzyme A thioesterase 6 {ECO:0000305|PubMed:16940157};
DE Short=Acyl-CoA thioesterase 6 {ECO:0000305|PubMed:16940157};
DE EC=3.1.2.- {ECO:0000250|UniProtKB:Q32Q92};
GN Name=ACOT6 {ECO:0000312|HGNC:HGNC:33159};
GN Synonyms=C14orf42 {ECO:0000312|HGNC:HGNC:33159};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND SUBCELLULAR LOCATION.
RX PubMed=16940157; DOI=10.1096/fj.06-6042com;
RA Hunt M.C., Rautanen A., Westin M.A.K., Svensson L.T., Alexson S.E.H.;
RT "Analysis of the mouse and human acyl-CoA thioesterase (ACOT) gene clusters
RT shows that convergent, functional evolution results in a reduced number of
RT human peroxisomal ACOTs.";
RL FASEB J. 20:1855-1864(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Catalyzes the hydrolysis of acyl-CoAs into free fatty acids
CC and coenzyme A (CoASH), regulating their respective intracellular
CC levels. Catalyzes the hydrolysis of phytanoyl-CoA and pristanoyl-CoA,
CC two methyl-branched fatty acids derived from phytol, that enter the
CC body via the diet. {ECO:0000250|UniProtKB:Q32Q92}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + pristanoyl-CoA = 2,6,10,14-tetramethylpentadecanoate +
CC CoA + H(+); Xref=Rhea:RHEA:40415, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:77250,
CC ChEBI:CHEBI:77268; Evidence={ECO:0000250|UniProtKB:Q32Q92};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40416;
CC Evidence={ECO:0000250|UniProtKB:Q32Q92};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + phytanoyl-CoA = 3,7,11,15-tetramethylhexadecanoate + CoA
CC + H(+); Xref=Rhea:RHEA:40419, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:37257, ChEBI:CHEBI:57287, ChEBI:CHEBI:57391;
CC Evidence={ECO:0000250|UniProtKB:Q32Q92};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40420;
CC Evidence={ECO:0000250|UniProtKB:Q32Q92};
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC {ECO:0000250|UniProtKB:Q32Q92}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Peroxisome
CC {ECO:0000305|PubMed:16940157}. Note=Localization to the peroxisome is
CC uncertain since the potential C-terminal peroxisome targeting signal
CC found in the mouse ortholog is not perfectly conserved.
CC {ECO:0000305|PubMed:16940157}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000305|PubMed:16940157}. Note=Recombinant N-terminally GFP-tagged
CC protein localizes to the cytosol. {ECO:0000305|PubMed:16940157}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3I5F7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3I5F7-2; Sequence=VSP_061185;
CC -!- SIMILARITY: Belongs to the C/M/P thioester hydrolase family.
CC {ECO:0000305}.
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DR EMBL; DQ082756; AAZ31238.1; -; mRNA.
DR EMBL; AC005225; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC126378; AAI26379.1; -; mRNA.
DR EMBL; BC126380; AAI26381.1; -; mRNA.
DR CCDS; CCDS32118.1; -. [Q3I5F7-2]
DR RefSeq; NP_001032239.1; NM_001037162.1.
DR AlphaFoldDB; Q3I5F7; -.
DR SMR; Q3I5F7; -.
DR BioGRID; 534966; 7.
DR IntAct; Q3I5F7; 2.
DR STRING; 9606.ENSP00000370531; -.
DR ESTHER; human-ACOT6; Acyl-CoA_Thioesterase.
DR MEROPS; S09.944; -.
DR iPTMnet; Q3I5F7; -.
DR PhosphoSitePlus; Q3I5F7; -.
DR BioMuta; ACOT6; -.
DR DMDM; 121942509; -.
DR MassIVE; Q3I5F7; -.
DR PaxDb; Q3I5F7; -.
DR PeptideAtlas; Q3I5F7; -.
DR PRIDE; Q3I5F7; -.
DR Antibodypedia; 63322; 49 antibodies from 17 providers.
DR DNASU; 641372; -.
DR Ensembl; ENST00000381139.1; ENSP00000370531.1; ENSG00000205669.4. [Q3I5F7-2]
DR Ensembl; ENST00000645972.2; ENSP00000496277.1; ENSG00000205669.4. [Q3I5F7-1]
DR GeneID; 641372; -.
DR KEGG; hsa:641372; -.
DR MANE-Select; ENST00000645972.2; ENSP00000496277.1; NM_001365788.1; NP_001352717.1.
DR UCSC; uc001xop.3; human. [Q3I5F7-1]
DR CTD; 641372; -.
DR DisGeNET; 641372; -.
DR GeneCards; ACOT6; -.
DR HGNC; HGNC:33159; ACOT6.
DR HPA; ENSG00000205669; Tissue enhanced (brain, kidney, liver, skeletal muscle).
DR MIM; 614267; gene.
DR neXtProt; NX_Q3I5F7; -.
DR OpenTargets; ENSG00000205669; -.
DR PharmGKB; PA162375329; -.
DR VEuPathDB; HostDB:ENSG00000205669; -.
DR eggNOG; ENOG502QQ8Z; Eukaryota.
DR GeneTree; ENSGT01010000222336; -.
DR HOGENOM; CLU_029849_4_1_1; -.
DR InParanoid; Q3I5F7; -.
DR OMA; AWQRIQT; -.
DR OrthoDB; 1260385at2759; -.
DR PhylomeDB; Q3I5F7; -.
DR TreeFam; TF314911; -.
DR BRENDA; 3.1.2.20; 2681.
DR PathwayCommons; Q3I5F7; -.
DR Reactome; R-HSA-390247; Beta-oxidation of very long chain fatty acids.
DR SignaLink; Q3I5F7; -.
DR UniPathway; UPA00199; -.
DR BioGRID-ORCS; 641372; 12 hits in 1068 CRISPR screens.
DR ChiTaRS; ACOT6; human.
DR GenomeRNAi; 641372; -.
DR Pharos; Q3I5F7; Tdark.
DR PRO; PR:Q3I5F7; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q3I5F7; protein.
DR Bgee; ENSG00000205669; Expressed in right lobe of liver and 74 other tissues.
DR ExpressionAtlas; Q3I5F7; baseline and differential.
DR Genevisible; Q3I5F7; HS.
DR GO; GO:0005829; C:cytosol; IDA:HGNC-UCL.
DR GO; GO:0005782; C:peroxisomal matrix; TAS:Reactome.
DR GO; GO:0047617; F:acyl-CoA hydrolase activity; IBA:GO_Central.
DR GO; GO:0052689; F:carboxylic ester hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0006637; P:acyl-CoA metabolic process; IBA:GO_Central.
DR GO; GO:0006631; P:fatty acid metabolic process; IBA:GO_Central.
DR Gene3D; 2.60.40.2240; -; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR016662; Acyl-CoA_thioEstase_long-chain.
DR InterPro; IPR014940; BAAT_C.
DR InterPro; IPR006862; Thio_Ohase/aa_AcTrfase.
DR InterPro; IPR042490; Thio_Ohase/BAAT_N.
DR Pfam; PF08840; BAAT_C; 1.
DR Pfam; PF04775; Bile_Hydr_Trans; 1.
DR PIRSF; PIRSF016521; Acyl-CoA_hydro; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cytoplasm; Hydrolase; Peroxisome; Reference proteome;
KW Serine esterase.
FT CHAIN 1..421
FT /note="Acyl-coenzyme A thioesterase 6"
FT /id="PRO_0000305098"
FT MOTIF 419..421
FT /note="Peroxisome targeting signal"
FT /evidence="ECO:0000305"
FT ACT_SITE 232
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:O55137"
FT ACT_SITE 326
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:O55137"
FT ACT_SITE 360
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:O55137"
FT VAR_SEQ 1..214
FT /note="Missing (in isoform 2)"
FT /id="VSP_061185"
FT VARIANT 380
FT /note="E -> K (in dbSNP:rs17782052)"
FT /id="VAR_052302"
SQ SEQUENCE 421 AA; 46789 MW; CDEC8B80CAEF6F63 CRC64;
MAATLILEPA GRCCWDEPLR IAVRGLAPEQ PVTLRTSLRD EEGALFRAHA RYRADARDEL
DLERAPALGG SFAGLQPMGL LWALEPEKAL VRLVKRDVRT PFAVELEVLD GHDTEPGRLL
CLAQNKRDFL RPGVRREPVR AGPVRAALFL PPDEGPFPGI IDLFGSSRGL CEYRASLLAG
HGFAVLALAY FRFEDLPEDL NDVHLEYFEE AVDFMLQHPK VKGPSIALLG FSKGGDLCLS
MASFLKGITA TVLINACVAN TVAPLHYKDM IIPKLVDDLG KVKITKSGFL TFMDTWSNPL
EEHNHQSLVP LEKAQVPFLF IVGMDDQSWK SEFYAQIASE RLQAHGKERP QIICYPETGH
CIDPPYFPPS RASVHAVLGE AIFYGGEPKA HSKAQVDAWQ QIQTFFHKHL NGKKSVKHSK
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