SAST_HUMAN
ID SAST_HUMAN Reviewed; 265 AA.
AC Q9NV23; Q5VUB6; Q9NUW1;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=S-acyl fatty acid synthase thioesterase, medium chain;
DE EC=3.1.2.14 {ECO:0000269|PubMed:26663084};
DE AltName: Full=Augmented in rheumatoid arthritis 1;
DE Short=AURA1;
DE AltName: Full=Oleoyl-ACP hydrolase;
DE AltName: Full=Thioesterase 2 {ECO:0000303|PubMed:26663084};
DE Short=TE2 {ECO:0000303|PubMed:26663084};
DE AltName: Full=Thioesterase II;
DE AltName: Full=Thioesterase domain-containing protein 1;
GN Name=OLAH {ECO:0000312|HGNC:HGNC:25625}; Synonyms=THEDC1;
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] (ISOFORMS 1 AND 2).
RC TISSUE=Placenta;
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=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [5]
RP TISSUE SPECIFICITY.
RX PubMed=6589427; DOI=10.1093/jnci/73.2.323;
RA Smith S., Pasco D., Pawlak J., Thompson B.J., Stampfer M., Nandi S.;
RT "Thioesterase II, a new marker enzyme for human cells of breast epithelial
RT origin.";
RL J. Natl. Cancer Inst. 73:323-329(1984).
RN [6]
RP TISSUE SPECIFICITY (ISOFORM 2).
RX PubMed=17082220; DOI=10.1093/dnares/dsl006;
RA Nakamura N., Shimaoka Y., Tougan T., Onda H., Okuzaki D., Zhao H.,
RA Fujimori A., Yabuta N., Nagamori I., Tanigawa A., Sato J., Oda T.,
RA Hayashida K., Suzuki R., Yukioka M., Nojima H., Ochi T.;
RT "Isolation and expression profiling of genes upregulated in bone marrow-
RT derived mononuclear cells of rheumatoid arthritis patients.";
RL DNA Res. 13:169-183(2006).
RN [7] {ECO:0007744|PDB:4XJV}
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS), CATALYTIC ACTIVITY, FUNCTION, AND
RP ACTIVE SITE.
RX PubMed=26663084; DOI=10.1074/jbc.m115.702597;
RA Ritchie M.K., Johnson L.C., Clodfelter J.E., Pemble C.W. IV, Fulp B.E.,
RA Furdui C.M., Kridel S.J., Lowther W.T.;
RT "Crystal Structure and Substrate Specificity of Human Thioesterase 2:
RT insights into the molecular basis for the modulation of fatty acid
RT synthase.";
RL J. Biol. Chem. 291:3520-3530(2016).
CC -!- FUNCTION: Contributes to the release of free fatty acids from fatty
CC acid synthase (FASN). Has broad substrate specificity, giving rise to a
CC range of free fatty acids with chain lengths between 10 and 16 carbon
CC atoms (C10 - C16). {ECO:0000269|PubMed:26663084}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-[ACP] + H2O = (9Z)-octadecenoate + H(+) +
CC holo-[ACP]; Xref=Rhea:RHEA:15057, Rhea:RHEA-COMP:9685, Rhea:RHEA-
CC COMP:9924, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:64479, ChEBI:CHEBI:78783; EC=3.1.2.14;
CC Evidence={ECO:0000269|PubMed:26663084};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=decanoyl-CoA + H2O = CoA + decanoate + H(+);
CC Xref=Rhea:RHEA:40059, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:27689, ChEBI:CHEBI:57287, ChEBI:CHEBI:61430;
CC Evidence={ECO:0000250|UniProtKB:P08635};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40060;
CC Evidence={ECO:0000250|UniProtKB:P08635};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoyl-CoA + H2O = CoA + dodecanoate + H(+);
CC Xref=Rhea:RHEA:30135, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:18262, ChEBI:CHEBI:57287, ChEBI:CHEBI:57375;
CC Evidence={ECO:0000250|UniProtKB:P08635};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30136;
CC Evidence={ECO:0000250|UniProtKB:P08635};
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:0000250|UniProtKB:P08635};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40120;
CC Evidence={ECO:0000250|UniProtKB:P08635};
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;
CC Evidence={ECO:0000250|UniProtKB:P08635};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16646;
CC Evidence={ECO:0000250|UniProtKB:P08635};
CC -!- SUBUNIT: Interacts (via C-terminus) with FASN.
CC {ECO:0000250|UniProtKB:P08635}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P08635}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NV23-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NV23-2; Sequence=VSP_040022;
CC -!- TISSUE SPECIFICITY: Detected both in lactating and non-lactating breast
CC epithelium (at protein level) (PubMed:6589427). Isoform 2 is up-
CC regulated in bone marrow-derived mononuclear cells of rheumatoid
CC arthritis patients (PubMed:17082220). {ECO:0000269|PubMed:17082220,
CC ECO:0000269|PubMed:6589427}.
CC -!- SIMILARITY: Belongs to the thioesterase family. {ECO:0000305}.
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DR EMBL; AK001844; BAA91937.1; -; mRNA.
DR EMBL; AK001968; BAA92007.1; -; mRNA.
DR EMBL; AL590365; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471072; EAW86244.1; -; Genomic_DNA.
DR EMBL; CH471072; EAW86245.1; -; Genomic_DNA.
DR EMBL; BC050372; AAH50372.1; -; mRNA.
DR EMBL; BR000403; FAA00320.1; -; mRNA.
DR CCDS; CCDS31152.1; -. [Q9NV23-1]
DR CCDS; CCDS7106.1; -. [Q9NV23-2]
DR RefSeq; NP_001034791.1; NM_001039702.2. [Q9NV23-1]
DR RefSeq; NP_060794.1; NM_018324.2. [Q9NV23-2]
DR RefSeq; XP_016871865.1; XM_017016376.1. [Q9NV23-2]
DR PDB; 4XJV; X-ray; 2.80 A; A=1-265.
DR PDBsum; 4XJV; -.
DR AlphaFoldDB; Q9NV23; -.
DR SMR; Q9NV23; -.
DR BioGRID; 120588; 1.
DR ESTHER; human-OLAH; Thioesterase.
DR iPTMnet; Q9NV23; -.
DR PhosphoSitePlus; Q9NV23; -.
DR BioMuta; OLAH; -.
DR DMDM; 52783423; -.
DR EPD; Q9NV23; -.
DR MassIVE; Q9NV23; -.
DR MaxQB; Q9NV23; -.
DR PeptideAtlas; Q9NV23; -.
DR PRIDE; Q9NV23; -.
DR ProteomicsDB; 82739; -. [Q9NV23-1]
DR ProteomicsDB; 82740; -. [Q9NV23-2]
DR Antibodypedia; 4213; 50 antibodies from 14 providers.
DR DNASU; 55301; -.
DR Ensembl; ENST00000378217.3; ENSP00000367462.3; ENSG00000152463.15. [Q9NV23-2]
DR Ensembl; ENST00000378228.8; ENSP00000367473.4; ENSG00000152463.15. [Q9NV23-1]
DR GeneID; 55301; -.
DR KEGG; hsa:55301; -.
DR MANE-Select; ENST00000378228.8; ENSP00000367473.4; NM_001039702.3; NP_001034791.1.
DR UCSC; uc001int.3; human. [Q9NV23-1]
DR CTD; 55301; -.
DR DisGeNET; 55301; -.
DR GeneCards; OLAH; -.
DR HGNC; HGNC:25625; OLAH.
DR HPA; ENSG00000152463; Tissue enhanced (lymphoid tissue, testis).
DR neXtProt; NX_Q9NV23; -.
DR OpenTargets; ENSG00000152463; -.
DR PharmGKB; PA134955731; -.
DR VEuPathDB; HostDB:ENSG00000152463; -.
DR GeneTree; ENSGT00390000015518; -.
DR HOGENOM; CLU_070456_3_0_1; -.
DR InParanoid; Q9NV23; -.
DR OMA; ALCRLIC; -.
DR OrthoDB; 1324961at2759; -.
DR PhylomeDB; Q9NV23; -.
DR TreeFam; TF331555; -.
DR BioCyc; MetaCyc:HS07821-MON; -.
DR PathwayCommons; Q9NV23; -.
DR Reactome; R-HSA-75105; Fatty acyl-CoA biosynthesis.
DR BioGRID-ORCS; 55301; 11 hits in 1072 CRISPR screens.
DR ChiTaRS; OLAH; human.
DR GenomeRNAi; 55301; -.
DR Pharos; Q9NV23; Tbio.
DR PRO; PR:Q9NV23; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9NV23; protein.
DR Bgee; ENSG00000152463; Expressed in right testis and 118 other tissues.
DR ExpressionAtlas; Q9NV23; baseline and differential.
DR Genevisible; Q9NV23; HS.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0047381; F:dodecanoyl-[acyl-carrier-protein] hydrolase activity; IDA:UniProtKB.
DR GO; GO:0016295; F:myristoyl-[acyl-carrier-protein] hydrolase activity; IDA:UniProtKB.
DR GO; GO:0102991; F:myristoyl-CoA hydrolase activity; IEA:RHEA.
DR GO; GO:0004320; F:oleoyl-[acyl-carrier-protein] hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0016296; F:palmitoyl-[acyl-carrier-protein] hydrolase activity; IDA:UniProtKB.
DR GO; GO:0016290; F:palmitoyl-CoA hydrolase activity; IEA:RHEA.
DR GO; GO:0008610; P:lipid biosynthetic process; IBA:GO_Central.
DR GO; GO:0051792; P:medium-chain fatty acid biosynthetic process; IDA:UniProtKB.
DR DisProt; DP02795; -.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR012223; TEII.
DR InterPro; IPR001031; Thioesterase.
DR PANTHER; PTHR11487; PTHR11487; 1.
DR Pfam; PF00975; Thioesterase; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Fatty acid biosynthesis; Fatty acid metabolism; Hydrolase;
KW Lipid biosynthesis; Lipid metabolism; Reference proteome.
FT CHAIN 1..265
FT /note="S-acyl fatty acid synthase thioesterase, medium
FT chain"
FT /id="PRO_0000180358"
FT ACT_SITE 101
FT /evidence="ECO:0000305|PubMed:26663084"
FT ACT_SITE 237
FT /evidence="ECO:0000250|UniProtKB:P08635"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P08635"
FT VAR_SEQ 55
FT /note="V -> ETASHHVAKAGLKLRRSSDPPASAYPCAGVSHRRREPPCLAKILGLF
FT WILIFFM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_040022"
FT STRAND 27..32
FT /evidence="ECO:0007829|PDB:4XJV"
FT STRAND 47..51
FT /evidence="ECO:0007829|PDB:4XJV"
FT HELIX 79..83
FT /evidence="ECO:0007829|PDB:4XJV"
FT HELIX 87..90
FT /evidence="ECO:0007829|PDB:4XJV"
FT STRAND 95..100
FT /evidence="ECO:0007829|PDB:4XJV"
FT HELIX 102..116
FT /evidence="ECO:0007829|PDB:4XJV"
FT STRAND 123..129
FT /evidence="ECO:0007829|PDB:4XJV"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:4XJV"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:4XJV"
FT HELIX 149..157
FT /evidence="ECO:0007829|PDB:4XJV"
FT HELIX 173..190
FT /evidence="ECO:0007829|PDB:4XJV"
FT STRAND 202..209
FT /evidence="ECO:0007829|PDB:4XJV"
FT HELIX 217..223
FT /evidence="ECO:0007829|PDB:4XJV"
FT STRAND 224..226
FT /evidence="ECO:0007829|PDB:4XJV"
FT STRAND 228..236
FT /evidence="ECO:0007829|PDB:4XJV"
FT HELIX 239..241
FT /evidence="ECO:0007829|PDB:4XJV"
FT HELIX 243..259
FT /evidence="ECO:0007829|PDB:4XJV"
SQ SEQUENCE 265 AA; 29931 MW; C67722F3CAD2D2C7 CRC64;
MERGDQPKRT RNENIFNCLY KNPEATFKLI CFPWMGGGST HFAKWGQDTH DLLEVHSLRL
PGRESRVEEP LENDISQLVD EVVCALQPVI QDKPFAFFGH SMGSYIAFRT ALGLKENNQP
EPLHLFLSSA TPVHSKAWHR IPKDDELSEE QISHYLMEFG GTPKHFAEAK EFVKQCSPII
RADLNIVRSC TSNVPSKAVL SCDLTCFVGS EDIAKDMEAW KDVTSGNAKI YQLPGGHFYL
LDPANEKLIK NYIIKCLEVS SISNF
