THEM5_HUMAN
ID THEM5_HUMAN Reviewed; 247 AA.
AC Q8N1Q8; Q5T1C3;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Acyl-coenzyme A thioesterase THEM5;
DE Short=Acyl-CoA thioesterase THEM5;
DE EC=3.1.2.2 {ECO:0000269|PubMed:22586271};
DE AltName: Full=Acyl-coenzyme A thioesterase 15;
DE AltName: Full=Thioesterase superfamily member 5;
GN Name=THEM5; Synonyms=ACOT15;
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 [LARGE SCALE MRNA], AND VARIANT VAL-206.
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-206.
RC TISSUE=Heart, and Lung;
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).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 35-247, CATALYTIC ACTIVITY,
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF GLY-160; ASP-167 AND THR-183.
RX PubMed=22586271; DOI=10.1128/mcb.00312-12;
RA Zhuravleva E., Gut H., Hynx D., Marcellin D., Bleck C.K., Genoud C.,
RA Cron P., Keusch J.J., Dummler B., Esposti M.D., Hemmings B.A.;
RT "Acyl coenzyme A thioesterase Them5/Acot15 is involved in cardiolipin
RT remodeling and fatty liver development.";
RL Mol. Cell. Biol. 32:2685-2697(2012).
CC -!- FUNCTION: Has acyl-CoA thioesterase activity towards long-chain (C16
CC and C18) fatty acyl-CoA substrates, with a preference for linoleoyl-CoA
CC and other unsaturated long-chain fatty acid-CoA esters
CC (PubMed:22586271). Plays an important role in mitochondrial fatty acid
CC metabolism, and in remodeling of the mitochondrial lipid cardiolipin
CC (PubMed:22586271). Required for normal mitochondrial function
CC (PubMed:22586271). {ECO:0000269|PubMed:22586271}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + hexadecanoyl-CoA = CoA + H(+) + hexadecanoate;
CC Xref=Rhea:RHEA:16645, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379; EC=3.1.2.2;
CC Evidence={ECO:0000269|PubMed:22586271};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16646;
CC Evidence={ECO:0000305|PubMed:22586271};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z)-octadecadienoyl-CoA + H2O = (9Z,12Z)-octadecadienoate
CC + CoA + H(+); Xref=Rhea:RHEA:40143, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30245, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57383; Evidence={ECO:0000269|PubMed:22586271};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40144;
CC Evidence={ECO:0000305|PubMed:22586271};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + tetradecanoyl-CoA = CoA + H(+) + tetradecanoate;
CC Xref=Rhea:RHEA:40119, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30807, ChEBI:CHEBI:57287, ChEBI:CHEBI:57385;
CC Evidence={ECO:0000269|PubMed:22586271};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40120;
CC Evidence={ECO:0000305|PubMed:22586271};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-CoA + H2O = (9Z)-octadecenoate + CoA + H(+);
CC Xref=Rhea:RHEA:40139, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:57287, ChEBI:CHEBI:57387;
CC Evidence={ECO:0000269|PubMed:22586271};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40140;
CC Evidence={ECO:0000305|PubMed:22586271};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-hexadecenoyl-CoA + H2O = (9Z)-hexadecenoate + CoA + H(+);
CC Xref=Rhea:RHEA:40131, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:32372, ChEBI:CHEBI:57287, ChEBI:CHEBI:61540;
CC Evidence={ECO:0000269|PubMed:22586271};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40132;
CC Evidence={ECO:0000305|PubMed:22586271};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + H2O = (5Z,8Z,11Z,14Z)-
CC eicosatetraenoate + CoA + H(+); Xref=Rhea:RHEA:40151,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32395,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57368;
CC Evidence={ECO:0000269|PubMed:22586271};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40152;
CC Evidence={ECO:0000305|PubMed:22586271};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + octadecanoyl-CoA = CoA + H(+) + octadecanoate;
CC Xref=Rhea:RHEA:30139, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:25629, ChEBI:CHEBI:57287, ChEBI:CHEBI:57394;
CC Evidence={ECO:0000269|PubMed:22586271};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30140;
CC Evidence={ECO:0000305|PubMed:22586271};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.4 uM for palmitoyl-CoA (C16:0) {ECO:0000269|PubMed:22586271};
CC KM=4.2 uM for stearoyl-CoA (C18:0) {ECO:0000269|PubMed:22586271};
CC KM=2.9 uM for oleoyl-CoA (C18:1) {ECO:0000269|PubMed:22586271};
CC KM=4.2 uM for linoleoyl-CoA (C18:2) {ECO:0000269|PubMed:22586271};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:22586271}.
CC -!- INTERACTION:
CC Q8N1Q8; P43364-2: MAGEA11; NbExp=3; IntAct=EBI-10264970, EBI-10178634;
CC Q8N1Q8; P57105: SYNJ2BP; NbExp=3; IntAct=EBI-10264970, EBI-1049004;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:22586271}.
CC -!- SIMILARITY: Belongs to the THEM4/THEM5 thioesterase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK095283; BAC04521.1; -; mRNA.
DR EMBL; AL450992; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC101610; AAI01611.1; -; mRNA.
DR EMBL; BC112239; AAI12240.1; -; mRNA.
DR CCDS; CCDS1005.1; -.
DR RefSeq; NP_872384.1; NM_182578.3.
DR PDB; 4AE7; X-ray; 1.45 A; A=35-247.
DR PDBsum; 4AE7; -.
DR AlphaFoldDB; Q8N1Q8; -.
DR SMR; Q8N1Q8; -.
DR BioGRID; 129888; 18.
DR IntAct; Q8N1Q8; 3.
DR STRING; 9606.ENSP00000357807; -.
DR SwissLipids; SLP:000000659; -.
DR iPTMnet; Q8N1Q8; -.
DR PhosphoSitePlus; Q8N1Q8; -.
DR BioMuta; THEM5; -.
DR DMDM; 145566964; -.
DR MassIVE; Q8N1Q8; -.
DR PaxDb; Q8N1Q8; -.
DR PeptideAtlas; Q8N1Q8; -.
DR PRIDE; Q8N1Q8; -.
DR Antibodypedia; 34076; 64 antibodies from 13 providers.
DR DNASU; 284486; -.
DR Ensembl; ENST00000368817.10; ENSP00000357807.4; ENSG00000196407.12.
DR GeneID; 284486; -.
DR KEGG; hsa:284486; -.
DR MANE-Select; ENST00000368817.10; ENSP00000357807.4; NM_182578.4; NP_872384.2.
DR UCSC; uc021oyw.2; human.
DR CTD; 284486; -.
DR DisGeNET; 284486; -.
DR GeneCards; THEM5; -.
DR HGNC; HGNC:26755; THEM5.
DR HPA; ENSG00000196407; Tissue enriched (skin).
DR MIM; 615653; gene.
DR neXtProt; NX_Q8N1Q8; -.
DR OpenTargets; ENSG00000196407; -.
DR PharmGKB; PA142670814; -.
DR VEuPathDB; HostDB:ENSG00000196407; -.
DR eggNOG; KOG4781; Eukaryota.
DR GeneTree; ENSGT00940000161937; -.
DR HOGENOM; CLU_072603_0_0_1; -.
DR InParanoid; Q8N1Q8; -.
DR OMA; QVEGQGY; -.
DR OrthoDB; 1322443at2759; -.
DR PhylomeDB; Q8N1Q8; -.
DR TreeFam; TF332518; -.
DR PathwayCommons; Q8N1Q8; -.
DR Reactome; R-HSA-77289; Mitochondrial Fatty Acid Beta-Oxidation.
DR SABIO-RK; Q8N1Q8; -.
DR SignaLink; Q8N1Q8; -.
DR BioGRID-ORCS; 284486; 18 hits in 1066 CRISPR screens.
DR GenomeRNAi; 284486; -.
DR Pharos; Q8N1Q8; Tbio.
DR PRO; PR:Q8N1Q8; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8N1Q8; protein.
DR Bgee; ENSG00000196407; Expressed in skin of leg and 98 other tissues.
DR ExpressionAtlas; Q8N1Q8; baseline and differential.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0102991; F:myristoyl-CoA hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0016290; F:palmitoyl-CoA hydrolase activity; IDA:UniProtKB.
DR GO; GO:0035965; P:cardiolipin acyl-chain remodeling; ISS:UniProtKB.
DR GO; GO:0006631; P:fatty acid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0035336; P:long-chain fatty-acyl-CoA metabolic process; IDA:UniProtKB.
DR InterPro; IPR029069; HotDog_dom_sf.
DR InterPro; IPR006683; Thioestr_dom.
DR Pfam; PF03061; 4HBT; 1.
DR SUPFAM; SSF54637; SSF54637; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Fatty acid metabolism; Hydrolase; Lipid metabolism;
KW Mitochondrion; Reference proteome.
FT CHAIN 1..247
FT /note="Acyl-coenzyme A thioesterase THEM5"
FT /id="PRO_0000284519"
FT ACT_SITE 167
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT VARIANT 55
FT /note="Y -> S (in dbSNP:rs16833597)"
FT /id="VAR_031764"
FT VARIANT 197
FT /note="D -> G (in dbSNP:rs6587625)"
FT /id="VAR_031765"
FT VARIANT 206
FT /note="L -> V (in dbSNP:rs6587624)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_031766"
FT MUTAGEN 160
FT /note="G->A: Strongly reduces enzyme activity. Abolishes
FT enzyme activity; when associated with A-183."
FT /evidence="ECO:0000269|PubMed:22586271"
FT MUTAGEN 167
FT /note="D->A: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:22586271"
FT MUTAGEN 183
FT /note="T->A: Reduces enzyme activity. Abolishes enzyme
FT activity; when associated with A-160."
FT /evidence="ECO:0000269|PubMed:22586271"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:4AE7"
FT HELIX 64..79
FT /evidence="ECO:0007829|PDB:4AE7"
FT HELIX 116..118
FT /evidence="ECO:0007829|PDB:4AE7"
FT TURN 123..125
FT /evidence="ECO:0007829|PDB:4AE7"
FT STRAND 126..134
FT /evidence="ECO:0007829|PDB:4AE7"
FT TURN 135..138
FT /evidence="ECO:0007829|PDB:4AE7"
FT STRAND 139..146
FT /evidence="ECO:0007829|PDB:4AE7"
FT HELIX 148..150
FT /evidence="ECO:0007829|PDB:4AE7"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:4AE7"
FT HELIX 159..178
FT /evidence="ECO:0007829|PDB:4AE7"
FT STRAND 180..190
FT /evidence="ECO:0007829|PDB:4AE7"
FT STRAND 200..210
FT /evidence="ECO:0007829|PDB:4AE7"
FT STRAND 213..221
FT /evidence="ECO:0007829|PDB:4AE7"
FT STRAND 228..238
FT /evidence="ECO:0007829|PDB:4AE7"
SQ SEQUENCE 247 AA; 27677 MW; 55117AE70FFC183F CRC64;
MIRRCFQVAA RLGHHRGLLE APRILPRLNP ASAFGSSTDS MFSRFLPEKT DLKDYALPNA
SWCSDMLSLY QEFLEKTKSS GWIKLPSFKS NRDHIRGLKL PSGLAVSSDK GDCRIFTRCI
QVEGQGFEYV IFFQPTQKKS VCLFQPGSYL EGPPGFAHGG SLAAMMDETF SKTAFLAGEG
LFTLSLNIRF KNLIPVDSLV VMDVELDKIE DQKLYMSCIA HSRDQQTVYA KSSGVFLQLQ
LEEESPQ
