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   27-MAR-2024, entry version 120.
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   CCDS; CCDS91900.1; -. [Q3I5F7-1]
DR   RefSeq; NP_001032239.1; NM_001037162.1. [Q3I5F7-2]
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   PhosphoSitePlus; Q3I5F7; -.
DR   BioMuta; ACOT6; -.
DR   DMDM; 121942509; -.
DR   MassIVE; Q3I5F7; -.
DR   PaxDb; 9606-ENSP00000370531; -.
DR   PeptideAtlas; Q3I5F7; -.
DR   Antibodypedia; 63322; 51 antibodies from 18 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   AGR; HGNC:33159; -.
DR   CTD; 641372; -.
DR   DisGeNET; 641372; -.
DR   GeneCards; ACOT6; -.
DR   HGNC; HGNC:33159; ACOT6.
DR   HPA; ENSG00000205669; Tissue enhanced (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; GICEIPL; -.
DR   OrthoDB; 5356064at2759; -.
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; 13 hits in 1146 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 male germ line stem cell (sensu Vertebrata) in testis and 75 other cell types or tissues.
DR   ExpressionAtlas; Q3I5F7; baseline and differential.
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; Acyl-CoA thioester hydrolase/BAAT N-terminal domain; 1.
DR   Gene3D; 3.40.50.1820; alpha/beta hydrolase; 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   PANTHER; PTHR10824:SF17; ACYL-COENZYME A THIOESTERASE 6; 1.
DR   PANTHER; PTHR10824; ACYL-COENZYME A THIOESTERASE-RELATED; 1.
DR   Pfam; PF08840; BAAT_C; 1.
DR   Pfam; PF04775; Bile_Hydr_Trans; 1.
DR   PIRSF; PIRSF016521; Acyl-CoA_hydro; 1.
DR   SUPFAM; SSF53474; alpha/beta-Hydrolases; 1.
DR   Genevisible; Q3I5F7; HS.
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
     I
//