ID   AMACR_MOUSE             Reviewed;         381 AA.
AC   O09174; Q543Q9; Q9DCW6;
DT   27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 4.
DT   27-MAR-2024, entry version 182.
DE   RecName: Full=Alpha-methylacyl-CoA racemase;
DE            EC=5.1.99.4 {ECO:0000250|UniProtKB:Q9UHK6};
DE   AltName: Full=2-methylacyl-CoA racemase {ECO:0000250|UniProtKB:Q9UHK6};
GN   Name=Amacr; Synonyms=Macr1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Head, and Kidney;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   PROTEIN SEQUENCE OF 2-16, PARTIAL NUCLEOTIDE SEQUENCE, AND SUBCELLULAR
RP   LOCATION.
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   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 15-381.
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   [4]
RP   PROTEIN SEQUENCE OF 51-57, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   STRAIN=OF1; TISSUE=Hippocampus;
RA   Lubec G., Sunyer B., Chen W.-Q.;
RL   Submitted (JAN-2009) to UniProtKB.
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Pancreas,
RC   and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [6]
RP   SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-86; LYS-100 AND LYS-267, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA   Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA   Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT   "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT   pathways.";
RL   Mol. Cell 50:919-930(2013).
RN   [7]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-57; LYS-86; LYS-100 AND LYS-117,
RP   AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA   Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA   Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT   "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT   identifies substrates of SIRT3 in metabolic pathways.";
RL   Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC   -!- FUNCTION: Catalyzes the interconversion of (R)- and (S)-stereoisomers
CC       of alpha-methyl-branched-chain fatty acyl-CoA esters (By similarity).
CC       Acts only on coenzyme A thioesters, not on free fatty acids, and
CC       accepts as substrates a wide range of alpha-methylacyl-CoAs, including
CC       pristanoyl-CoA, trihydroxycoprostanoyl-CoA (an intermediate in bile
CC       acid synthesis), and arylpropionic acids like the anti-inflammatory
CC       drug ibuprofen (2-(4-isobutylphenyl)propionic acid) but neither 3-
CC       methyl-branched nor linear-chain acyl-CoAs (By similarity).
CC       {ECO:0000250|UniProtKB:Q9UHK6}.
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:0000250|UniProtKB:Q9UHK6};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12658;
CC         Evidence={ECO:0000250|UniProtKB:Q9UHK6};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:12659;
CC         Evidence={ECO:0000250|UniProtKB:Q9UHK6};
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   -!- PATHWAY: Lipid metabolism; bile acid biosynthesis.
CC   -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC   -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9UHK6}.
CC   -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:10770938}.
CC       Mitochondrion {ECO:0000269|PubMed:10770938}.
CC   -!- SIMILARITY: Belongs to the CoA-transferase III family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB72146.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AK048249; BAC33284.1; -; mRNA.
DR   EMBL; AK002401; BAB22072.2; -; mRNA.
DR   EMBL; U89906; AAB72146.1; ALT_INIT; mRNA.
DR   CCDS; CCDS27381.1; -.
DR   RefSeq; NP_032563.2; NM_008537.4.
DR   AlphaFoldDB; O09174; -.
DR   SMR; O09174; -.
DR   STRING; 10090.ENSMUSP00000066915; -.
DR   iPTMnet; O09174; -.
DR   PhosphoSitePlus; O09174; -.
DR   SwissPalm; O09174; -.
DR   EPD; O09174; -.
DR   jPOST; O09174; -.
DR   MaxQB; O09174; -.
DR   PaxDb; 10090-ENSMUSP00000066915; -.
DR   PeptideAtlas; O09174; -.
DR   ProteomicsDB; 296226; -.
DR   Pumba; O09174; -.
DR   Antibodypedia; 34888; 1188 antibodies from 44 providers.
DR   DNASU; 17117; -.
DR   Ensembl; ENSMUST00000070877.7; ENSMUSP00000066915.6; ENSMUSG00000022244.8.
DR   GeneID; 17117; -.
DR   KEGG; mmu:17117; -.
DR   UCSC; uc007vgw.1; mouse.
DR   AGR; MGI:1098273; -.
DR   CTD; 23600; -.
DR   MGI; MGI:1098273; Amacr.
DR   VEuPathDB; HostDB:ENSMUSG00000022244; -.
DR   eggNOG; KOG3957; Eukaryota.
DR   GeneTree; ENSGT00940000157215; -.
DR   HOGENOM; CLU_033975_5_0_1; -.
DR   InParanoid; O09174; -.
DR   OMA; VVIDPFR; -.
DR   OrthoDB; 179764at2759; -.
DR   PhylomeDB; O09174; -.
DR   TreeFam; TF314188; -.
DR   BRENDA; 5.1.99.4; 3474.
DR   Reactome; R-MMU-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR   Reactome; R-MMU-193775; Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
DR   Reactome; R-MMU-389887; Beta-oxidation of pristanoyl-CoA.
DR   Reactome; R-MMU-9033241; Peroxisomal protein import.
DR   UniPathway; UPA00199; -.
DR   UniPathway; UPA00221; -.
DR   BioGRID-ORCS; 17117; 3 hits in 81 CRISPR screens.
DR   PRO; PR:O09174; -.
DR   Proteomes; UP000000589; Chromosome 15.
DR   RNAct; O09174; Protein.
DR   Bgee; ENSMUSG00000022244; Expressed in right kidney and 256 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR   GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR   GO; GO:0005777; C:peroxisome; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0008111; F:alpha-methylacyl-CoA racemase activity; ISS:UniProtKB.
DR   GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR   GO; GO:0006699; P:bile acid biosynthetic process; ISO:MGI.
DR   GO; GO:0008206; P:bile acid metabolic process; ISO:MGI.
DR   GO; GO:0006631; P:fatty acid metabolic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0008300; P:isoprenoid catabolic process; TAS:MGI.
DR   Gene3D; 3.30.1540.10; formyl-coa transferase, domain 3; 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   PANTHER; PTHR48228:SF5; ALPHA-METHYLACYL-COA RACEMASE; 1.
DR   PANTHER; PTHR48228; SUCCINYL-COA--D-CITRAMALATE COA-TRANSFERASE; 1.
DR   Pfam; PF02515; CoA_transf_3; 1.
DR   SUPFAM; SSF89796; CoA-transferase family III (CaiB/BaiF); 1.
DR   Genevisible; O09174; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Direct protein sequencing; Isomerase; Mitochondrion;
KW   Peroxisome; Reference proteome.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:10770938"
FT   CHAIN           2..381
FT                   /note="Alpha-methylacyl-CoA racemase"
FT                   /id="PRO_0000194706"
FT   REGION          316..344
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           379..381
FT                   /note="Microbody targeting signal"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UHK6"
FT   ACT_SITE        121
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:O06543"
FT   ACT_SITE        151
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:O06543"
FT   BINDING         36
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:O06543"
FT   BINDING         54..57
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:O06543"
FT   BINDING         120..125
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:O06543"
FT   MOD_RES         57
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         86
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         86
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         100
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         100
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         117
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         267
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   CONFLICT        178
FT                   /note="V -> I (in Ref. 3; AAB72146)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   381 AA;  41704 MW;  97FD19F9553FFE99 CRC64;
     MVLRGVRVVE LAGLAPGPFC GMVLADFGAE VVRVNRLGST GENFLARGKR SLALDLKRSQ
     GVTVLRRMCA RADVLLEPFR CGVMEKLQLG PETLLQDNPK LIYARLSGFG QSGIFSKVAG
     HDINYLALSG VLSKIGRSGE NPYPPLNLLA DFGGGGLMCT LGIVLALFER TRSGRGQVID
     SSMVEGTAYL SSFLWKTQPM GLWKQPRGQN ILDGGAPFYT TYKTADGEFM AVGAIEPQFY
     ALLLKGLGLE SEELPSQMSS ADWPEMKKKF ADVFAKKTKA EWCQIFDGTD ACVTPVLTFE
     EALHHQHNRE RASFITDGEQ LPSPRPAPLL SRTPAVPSAK RDPSVGEHTV EVLREYGFSQ
     EEILQLHSDR IVESDKLKAN L
//