OCTC_HUMAN
ID OCTC_HUMAN Reviewed; 612 AA.
AC Q9UKG9; A4D1D6; E7EQF2; Q86V17; Q8IUW9; Q9Y6I2;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Peroxisomal carnitine O-octanoyltransferase;
DE Short=COT;
DE EC=2.3.1.137 {ECO:0000269|PubMed:10486279};
GN Name=CROT; Synonyms=COT;
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 1), FUNCTION, SUBUNIT, AND CATALYTIC
RP ACTIVITY.
RC TISSUE=Skin;
RX PubMed=10486279; DOI=10.1006/bbrc.1999.1340;
RA Ferdinandusse S., Mulders J., Ijlst L., Denis S., Dacremont G.,
RA Waterham H.R., Wanders R.J.A.;
RT "Molecular cloning and expression of human carnitine octanoyltransferase:
RT evidence for its role in the peroxisomal beta-oxidation of branched-chain
RT fatty acids.";
RL Biochem. Biophys. Res. Commun. 263:213-218(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Kim D.G., Hlubb C.W., Yun J., Mihalik S.J.;
RT "Cloning of the human gene for carnitine octanoyltransferase.";
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Skin;
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 [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [8]
RP 3D-STRUCTURE MODELING.
RX PubMed=11790793; DOI=10.1074/jbc.m111628200;
RA Morillas M., Gomez-Puertas P., Rubi B., Clotet J., Arino J., Valencia A.,
RA Hegardt F.G., Serra D., Asins G.;
RT "Structural model of a malonyl-CoA-binding site of carnitine
RT octanoyltransferase and carnitine palmitoyltransferase I: mutational
RT analysis of a malonyl-CoA affinity domain.";
RL J. Biol. Chem. 277:11473-11480(2002).
CC -!- FUNCTION: Beta-oxidation of fatty acids. The highest activity concerns
CC the C6 to C10 chain length substrate. Converts the end product of
CC pristanic acid beta oxidation, 4,8-dimethylnonanoyl-CoA, to its
CC corresponding carnitine ester. {ECO:0000269|PubMed:10486279}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-carnitine + octanoyl-CoA = CoA + O-octanoyl-(R)-carnitine;
CC Xref=Rhea:RHEA:17177, ChEBI:CHEBI:16347, ChEBI:CHEBI:18102,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57386; EC=2.3.1.137;
CC Evidence={ECO:0000269|PubMed:10486279};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-carnitine + 4,8-dimethylnonanoyl-CoA = CoA + O-4,8-
CC dimethylnonanoyl-(R)-carnitine; Xref=Rhea:RHEA:44860,
CC ChEBI:CHEBI:16347, ChEBI:CHEBI:57287, ChEBI:CHEBI:77061,
CC ChEBI:CHEBI:84654; Evidence={ECO:0000269|PubMed:10486279};
CC -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation.
CC -!- SUBUNIT: Monomer. {ECO:0000305|PubMed:10486279}.
CC -!- INTERACTION:
CC Q9UKG9-2; P55212: CASP6; NbExp=3; IntAct=EBI-25835363, EBI-718729;
CC Q9UKG9-2; P99999: CYCS; NbExp=3; IntAct=EBI-25835363, EBI-446479;
CC Q9UKG9-2; O00291: HIP1; NbExp=3; IntAct=EBI-25835363, EBI-473886;
CC Q9UKG9-2; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-25835363, EBI-5280197;
CC Q9UKG9-2; P62826: RAN; NbExp=3; IntAct=EBI-25835363, EBI-286642;
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9UKG9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UKG9-2; Sequence=VSP_045213, VSP_045214;
CC Name=3;
CC IsoId=Q9UKG9-3; Sequence=VSP_046953;
CC -!- SIMILARITY: Belongs to the carnitine/choline acetyltransferase family.
CC {ECO:0000305}.
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DR EMBL; AF168793; AAF03234.1; -; mRNA.
DR EMBL; AF073770; AAD41654.1; -; mRNA.
DR EMBL; AC005045; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236949; EAL24177.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76954.1; -; Genomic_DNA.
DR EMBL; BC039004; AAH39004.1; -; mRNA.
DR EMBL; BC051874; AAH51874.1; -; mRNA.
DR CCDS; CCDS47634.1; -. [Q9UKG9-3]
DR CCDS; CCDS5604.1; -. [Q9UKG9-1]
DR CCDS; CCDS59062.1; -. [Q9UKG9-2]
DR PIR; JC7101; JC7101.
DR RefSeq; NP_001137407.1; NM_001143935.1. [Q9UKG9-3]
DR RefSeq; NP_001230674.1; NM_001243745.1. [Q9UKG9-2]
DR RefSeq; NP_066974.2; NM_021151.3. [Q9UKG9-1]
DR AlphaFoldDB; Q9UKG9; -.
DR SMR; Q9UKG9; -.
DR BioGRID; 120098; 14.
DR IntAct; Q9UKG9; 14.
DR STRING; 9606.ENSP00000413575; -.
DR BindingDB; Q9UKG9; -.
DR ChEMBL; CHEMBL2206; -.
DR DrugBank; DB02648; (3-Carboxy-2-(R)-Hydroxy-Propyl)-Trimethyl-Ammonium.
DR DrugBank; DB03832; 3-Carboxy-N,N,N-Trimethyl-2-(Octanoyloxy)Propan-1-Aminium.
DR DrugBank; DB00583; Levocarnitine.
DR SwissLipids; SLP:000001055; -.
DR TCDB; 4.C.2.1.2; the carnitine o-acyl transferase (carat) family.
DR iPTMnet; Q9UKG9; -.
DR MetOSite; Q9UKG9; -.
DR PhosphoSitePlus; Q9UKG9; -.
DR BioMuta; CROT; -.
DR DMDM; 48429265; -.
DR EPD; Q9UKG9; -.
DR jPOST; Q9UKG9; -.
DR MassIVE; Q9UKG9; -.
DR MaxQB; Q9UKG9; -.
DR PaxDb; Q9UKG9; -.
DR PeptideAtlas; Q9UKG9; -.
DR PRIDE; Q9UKG9; -.
DR ProteomicsDB; 17560; -.
DR ProteomicsDB; 69947; -.
DR ProteomicsDB; 84787; -. [Q9UKG9-1]
DR Antibodypedia; 15286; 347 antibodies from 34 providers.
DR DNASU; 54677; -.
DR Ensembl; ENST00000331536.8; ENSP00000331981.4; ENSG00000005469.12. [Q9UKG9-1]
DR Ensembl; ENST00000412227.6; ENSP00000404867.2; ENSG00000005469.12. [Q9UKG9-2]
DR Ensembl; ENST00000419147.6; ENSP00000413575.2; ENSG00000005469.12. [Q9UKG9-3]
DR GeneID; 54677; -.
DR KEGG; hsa:54677; -.
DR MANE-Select; ENST00000331536.8; ENSP00000331981.4; NM_021151.4; NP_066974.2.
DR UCSC; uc003uis.4; human. [Q9UKG9-1]
DR CTD; 54677; -.
DR DisGeNET; 54677; -.
DR GeneCards; CROT; -.
DR HGNC; HGNC:2366; CROT.
DR HPA; ENSG00000005469; Low tissue specificity.
DR MIM; 606090; gene.
DR neXtProt; NX_Q9UKG9; -.
DR OpenTargets; ENSG00000005469; -.
DR PharmGKB; PA26887; -.
DR VEuPathDB; HostDB:ENSG00000005469; -.
DR eggNOG; KOG3718; Eukaryota.
DR GeneTree; ENSGT01050000244969; -.
DR HOGENOM; CLU_2482687_0_0_1; -.
DR InParanoid; Q9UKG9; -.
DR OMA; DVWAKDY; -.
DR OrthoDB; 559299at2759; -.
DR PhylomeDB; Q9UKG9; -.
DR TreeFam; TF313836; -.
DR BRENDA; 2.3.1.137; 2681.
DR PathwayCommons; Q9UKG9; -.
DR Reactome; R-HSA-389887; Beta-oxidation of pristanoyl-CoA.
DR Reactome; R-HSA-9033241; Peroxisomal protein import.
DR SignaLink; Q9UKG9; -.
DR UniPathway; UPA00659; -.
DR BioGRID-ORCS; 54677; 13 hits in 1084 CRISPR screens.
DR ChiTaRS; CROT; human.
DR GeneWiki; CROT_(gene); -.
DR GenomeRNAi; 54677; -.
DR Pharos; Q9UKG9; Tbio.
DR PRO; PR:Q9UKG9; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9UKG9; protein.
DR Bgee; ENSG00000005469; Expressed in esophagus squamous epithelium and 201 other tissues.
DR ExpressionAtlas; Q9UKG9; baseline and differential.
DR Genevisible; Q9UKG9; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005782; C:peroxisomal matrix; TAS:Reactome.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0008458; F:carnitine O-octanoyltransferase activity; IDA:UniProtKB.
DR GO; GO:0009437; P:carnitine metabolic process; ISS:UniProtKB.
DR GO; GO:0015936; P:coenzyme A metabolic process; ISS:UniProtKB.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IDA:UniProtKB.
DR GO; GO:0033540; P:fatty acid beta-oxidation using acyl-CoA oxidase; TAS:Reactome.
DR GO; GO:0006631; P:fatty acid metabolic process; IMP:UniProtKB.
DR GO; GO:0015908; P:fatty acid transport; IEA:Ensembl.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; IDA:UniProtKB.
DR GO; GO:0051791; P:medium-chain fatty acid metabolic process; IDA:UniProtKB.
DR Gene3D; 1.10.275.20; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 3.30.559.70; -; 1.
DR InterPro; IPR000542; Carn_acyl_trans.
DR InterPro; IPR042572; Carn_acyl_trans_N.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR039551; Cho/carn_acyl_trans.
DR InterPro; IPR042231; Cho/carn_acyl_trans_2.
DR PANTHER; PTHR22589; PTHR22589; 1.
DR Pfam; PF00755; Carn_acyltransf; 1.
DR PROSITE; PS00439; ACYLTRANSF_C_1; 1.
DR PROSITE; PS00440; ACYLTRANSF_C_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Acyltransferase; Alternative splicing; Fatty acid metabolism;
KW Lipid metabolism; Peroxisome; Reference proteome; Transferase; Transport.
FT CHAIN 1..612
FT /note="Peroxisomal carnitine O-octanoyltransferase"
FT /id="PRO_0000210169"
FT MOTIF 610..612
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 327
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 406
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250"
FT BINDING 410..417
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250"
FT BINDING 439
FT /ligand="(R)-carnitine"
FT /ligand_id="ChEBI:CHEBI:16347"
FT /evidence="ECO:0000250"
FT BINDING 441
FT /ligand="(R)-carnitine"
FT /ligand_id="ChEBI:CHEBI:16347"
FT /evidence="ECO:0000250"
FT BINDING 452
FT /ligand="(R)-carnitine"
FT /ligand_id="ChEBI:CHEBI:16347"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 40
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DC50"
FT MOD_RES 57
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DC50"
FT MOD_RES 406
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DC50"
FT MOD_RES 406
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DC50"
FT VAR_SEQ 38
FT /note="S -> SVTRTCYQIRGLDPDAKRGFLDLTREGIQ (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_046953"
FT VAR_SEQ 81..87
FT /note="LEEWWLN -> VFVVIIE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045213"
FT VAR_SEQ 88..612
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045214"
FT VARIANT 94
FT /note="R -> H (in dbSNP:rs3827653)"
FT /id="VAR_048612"
FT VARIANT 474
FT /note="V -> L (in dbSNP:rs7785206)"
FT /id="VAR_048613"
FT CONFLICT 144
FT /note="V -> L (in Ref. 1; AAF03234)"
FT /evidence="ECO:0000305"
FT CONFLICT 168
FT /note="V -> G (in Ref. 2; AAD41654)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 612 AA; 70178 MW; BFC4E0A09B191038 CRC64;
MENQLAKSTE ERTFQYQDSL PSLPVPSLEE SLKKYLESVK PFANQEEYKK TEEIVQKFQS
GIGEKLHQKL LERAKGKRNW LEEWWLNVAY LDVRIPSQLN VNFAGPAAHF EHYWPPKEGT
QLERGSITLW HNLNYWQLLR KEKVPVHKVG NTPLDMNQFR MLFSTCKVPG ITRDSIMNYF
RTESEGRSPN HIVVLCRGRA FVFDVIHEGC LVTPPELLRQ LTYIHKKCHS EPDGPGIAAL
TSEERTRWAK AREYLIGLDP ENLALLEKIQ SSLLVYSMED SSPHVTPEDY SEIIAAILIG
DPTVRWGDKS YNLISFSNGV FGCNCDHAPF DAMIMVNISY YVDEKIFQNE GRWKGSEKVR
DIPLPEELIF IVDEKVLNDI NQAKAQYLRE ASDLQIAAYA FTSFGKKLTK NKMLHPDTFI
QLALQLAYYR LHGHPGCCYE TAMTRHFYHG RTETMRSCTV EAVRWCQSMQ DPSVNLRERQ
QKMLQAFAKH NKMMKDCSAG KGFDRHLLGL LLIAKEEGLP VPELFTDPLF SKSGGGGNFV
LSTSLVGYLR VQGVVVPMVH NGYGFFYHIR DDRFVVACSA WKSCPETDAE KLVQLTFCAF
HDMIQLMNST HL
