AMACR_RAT
ID AMACR_RAT Reviewed; 382 AA.
AC P70473; O09176;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Alpha-methylacyl-CoA racemase;
DE EC=5.1.99.4 {ECO:0000269|PubMed:8020470, ECO:0000269|PubMed:9106621};
DE AltName: Full=2-arylpropionyl-CoA epimerase {ECO:0000303|PubMed:9106621};
DE AltName: Full=2-methylacyl-CoA racemase {ECO:0000250|UniProtKB:Q9UHK6};
GN Name=Amacr;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 11-382, FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=9106621; DOI=10.1124/mol.51.4.576;
RA Reichel C., Brugger R., Bang H., Geisslinger G., Brune K.;
RT "Molecular cloning and expression of a 2-arylpropionyl-coenzyme A
RT epimerase: a key enzyme in the inversion metabolism of ibuprofen.";
RL Mol. Pharmacol. 51:576-582(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-382.
RC TISSUE=Liver;
RX PubMed=9307041; DOI=10.1042/bj3260883;
RA Schmitz W., Helander H.M., Hiltunen J.K., Conzelmann E.;
RT "Molecular cloning of cDNA species for rat and mouse liver alpha-
RT methylacyl-CoA racemases.";
RL Biochem. J. 326:883-889(1997).
RN [3]
RP PARTIAL NUCLEOTIDE SEQUENCE.
RX PubMed=10770938; DOI=10.1074/jbc.m002067200;
RA Kotti T.J., Savolainen K., Helander H.M., Yagi A., Novikov D.K.,
RA Kalkkinen N., Conzelmann E., Hiltunen J.K., Schmitz W.;
RT "In mouse alpha-methylacyl-CoA racemase, the same gene product is
RT simultaneously located in mitochondria and peroxisomes.";
RL J. Biol. Chem. 275:20887-20895(2000).
RN [4]
RP PROTEIN SEQUENCE OF 103-117, AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=8615858; DOI=10.1016/0006-2952(95)02054-3;
RA Reichel C., Bang H., Brune K., Geisslinger G., Menzel S.;
RT "2-arylpropionyl-CoA epimerase: partial peptide sequences and tissue
RT localization.";
RL Biochem. Pharmacol. 50:1803-1806(1995).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC TISSUE=Liver;
RX PubMed=8020470; DOI=10.1111/j.1432-1033.1994.tb18870.x;
RA Schmitz W., Fingerhut R., Conzelmann E.;
RT "Purification and properties of an alpha-methylacyl-CoA racemase from rat
RT liver.";
RL Eur. J. Biochem. 222:313-323(1994).
RN [6]
RP SUBCELLULAR LOCATION.
RC TISSUE=Liver;
RX PubMed=7649182; DOI=10.1111/j.1432-1033.1995.tb20766.x;
RA Schmitz W., Albers C., Fingerhut R., Conzelmann E.;
RT "Purification and characterization of an alpha-methylacyl-CoA racemase from
RT human liver.";
RL Eur. J. Biochem. 231:815-822(1995).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=11060359;
RA Ferdinandusse S., Denis S., Ijlst L., Dacremont G., Waterham H.R.,
RA Wanders R.J.;
RT "Subcellular localization and physiological role of alpha-methylacyl-CoA
RT racemase.";
RL J. Lipid Res. 41:1890-1896(2000).
CC -!- FUNCTION: Catalyzes the interconversion of (R)- and (S)-stereoisomers
CC of alpha-methyl-branched-chain fatty acyl-CoA esters (PubMed:8020470,
CC PubMed:9106621). Acts only on coenzyme A thioesters, not on free fatty
CC acids, and accepts as substrates a wide range of alpha-methylacyl-CoAs,
CC including pristanoyl-CoA, trihydroxycoprostanoyl-CoA (an intermediate
CC in bile acid synthesis), and arylpropionic acids like the anti-
CC inflammatory drug ibuprofen (2-(4-isobutylphenyl)propionic acid) but
CC neither 3-methyl-branched nor linear-chain acyl-CoAs (PubMed:8020470,
CC PubMed:9106621). {ECO:0000269|PubMed:8020470,
CC ECO:0000269|PubMed:9106621}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (2S)-2-methylacyl-CoA = a (2R)-2-methylacyl-CoA;
CC Xref=Rhea:RHEA:12657, ChEBI:CHEBI:57313, ChEBI:CHEBI:57314;
CC EC=5.1.99.4; Evidence={ECO:0000269|PubMed:8020470,
CC ECO:0000269|PubMed:9106621};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12658;
CC Evidence={ECO:0000305|PubMed:8020470};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:12659;
CC Evidence={ECO:0000305|PubMed:8020470};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oyl-
CC CoA = (25S)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oyl-
CC CoA; Xref=Rhea:RHEA:40455, ChEBI:CHEBI:58677, ChEBI:CHEBI:77251;
CC Evidence={ECO:0000250|UniProtKB:Q9UHK6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40456;
CC Evidence={ECO:0000250|UniProtKB:Q9UHK6};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:40457;
CC Evidence={ECO:0000250|UniProtKB:Q9UHK6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R,6)-dimethylheptanoyl-CoA = (2S,6)-dimethylheptanoyl-CoA;
CC Xref=Rhea:RHEA:46732, ChEBI:CHEBI:86982, ChEBI:CHEBI:86983;
CC Evidence={ECO:0000250|UniProtKB:Q9UHK6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46733;
CC Evidence={ECO:0000250|UniProtKB:Q9UHK6};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=76 uM for pristanoyl-CoA {ECO:0000269|PubMed:7649182};
CC KM=60 uM for trihydroxycoprostanoyl-CoA {ECO:0000269|PubMed:7649182};
CC Vmax=3.5 umol/min/mg enzyme for pristanoyl-CoA
CC {ECO:0000269|PubMed:7649182};
CC Vmax=31 umol/min/mg enzyme for trihydroxycoprostanoyl-CoA
CC {ECO:0000269|PubMed:7649182};
CC pH dependence:
CC Optimum pH is 6-7. {ECO:0000269|PubMed:7649182};
CC -!- PATHWAY: Lipid metabolism; bile acid biosynthesis.
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:8020470}.
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:11060359}.
CC Mitochondrion {ECO:0000269|PubMed:11060359,
CC ECO:0000269|PubMed:7649182}.
CC -!- SIMILARITY: Belongs to the CoA-transferase III family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB72145.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAA69358.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; Y08172; CAA69358.1; ALT_INIT; mRNA.
DR EMBL; U89905; AAB72145.1; ALT_INIT; mRNA.
DR AlphaFoldDB; P70473; -.
DR SMR; P70473; -.
DR BindingDB; P70473; -.
DR iPTMnet; P70473; -.
DR PhosphoSitePlus; P70473; -.
DR PaxDb; P70473; -.
DR PRIDE; P70473; -.
DR RGD; 3048; Amacr.
DR eggNOG; KOG3957; Eukaryota.
DR InParanoid; P70473; -.
DR BioCyc; MetaCyc:MON-14326; -.
DR BRENDA; 5.1.99.4; 5301.
DR Reactome; R-RNO-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-RNO-193775; Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
DR Reactome; R-RNO-389887; Beta-oxidation of pristanoyl-CoA.
DR Reactome; R-RNO-9033241; Peroxisomal protein import.
DR SABIO-RK; P70473; -.
DR UniPathway; UPA00199; -.
DR UniPathway; UPA00221; -.
DR PRO; PR:P70473; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005777; C:peroxisome; IDA:HGNC-UCL.
DR GO; GO:0008111; F:alpha-methylacyl-CoA racemase activity; IDA:RGD.
DR GO; GO:0006699; P:bile acid biosynthetic process; IDA:RGD.
DR GO; GO:0008206; P:bile acid metabolic process; IDA:RGD.
DR GO; GO:0006631; P:fatty acid metabolic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.30.1540.10; -; 1.
DR Gene3D; 3.40.50.10540; -; 1.
DR InterPro; IPR003673; CoA-Trfase_fam_III.
DR InterPro; IPR044855; CoA-Trfase_III_dom3_sf.
DR InterPro; IPR023606; CoA-Trfase_III_dom_1_sf.
DR Pfam; PF02515; CoA_transf_3; 1.
DR SUPFAM; SSF89796; SSF89796; 1.
PE 1: Evidence at protein level;
KW Acetylation; Direct protein sequencing; Isomerase; Mitochondrion;
KW Peroxisome; Reference proteome.
FT CHAIN 1..382
FT /note="Alpha-methylacyl-CoA racemase"
FT /id="PRO_0000194707"
FT REGION 319..347
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 380..382
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000250"
FT ACT_SITE 122
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:O06543"
FT ACT_SITE 152
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:O06543"
FT BINDING 36
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O06543"
FT BINDING 55..58
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O06543"
FT BINDING 121..126
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O06543"
FT MOD_RES 58
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O09174"
FT MOD_RES 87
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O09174"
FT MOD_RES 87
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O09174"
FT MOD_RES 101
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O09174"
FT MOD_RES 101
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O09174"
FT MOD_RES 118
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O09174"
FT MOD_RES 268
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O09174"
FT CONFLICT 70..71
FT /note="CA -> FS (in Ref. 1; CAA69358)"
FT /evidence="ECO:0000305"
FT CONFLICT 80
FT /note="F -> L (in Ref. 1; CAA69358)"
FT /evidence="ECO:0000305"
FT CONFLICT 166
FT /note="L -> V (in Ref. 1; CAA69358)"
FT /evidence="ECO:0000305"
FT CONFLICT 324
FT /note="C -> F (in Ref. 1; CAA69358)"
FT /evidence="ECO:0000305"
FT CONFLICT 328
FT /note="A -> S (in Ref. 1; CAA69358)"
FT /evidence="ECO:0000305"
FT CONFLICT 336
FT /note="A -> S (in Ref. 1; CAA69358)"
FT /evidence="ECO:0000305"
FT CONFLICT 340..341
FT /note="AK -> SQ (in Ref. 1; CAA69358)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 382 AA; 41828 MW; B6FC51DB167F4767 CRC64;
MALRGVRVLE LAGLAPGPFC GMILADFGAE VVLVDRLGSV NHPSHLARGK RSLALDLKRS
PGAAVLRRMC ARADVLLEPF RCGVMEKLQL GPETLRQDNP KLIYARLSGF GQSGIFSKVA
GHDINYVALS GVLSKIGRSG ENPYPPLNLL ADFGGGGLMC TLGILLALFE RTRSGLGQVI
DANMVEGTAY LSTFLWKTQA MGLWAQPRGQ NLLDGGAPFY TTYKTADGEF MAVGAIEPQF
YTLLLKGLGL ESEELPSQMS IEDWPEMKKK FADVFARKTK AEWCQIFDGT DACVTPVLTL
EEALHHQHNR ERGSFITDEE QHACPRPAPQ LSRTPAVPSA KRDPSVGEHT VEVLKDYGFS
QEEIHQLHSD RIIESNKLKA NL
