ID AMACR_HUMAN Reviewed; 382 AA. AC Q9UHK6; A5YM47; B8Y916; B8Y918; F8W9N1; O43673; Q3KT79; Q96GH1; Q9Y3Q1; DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot. DT 30-NOV-2010, sequence version 2. DT 27-MAR-2024, entry version 193. DE RecName: Full=Alpha-methylacyl-CoA racemase; DE EC=5.1.99.4 {ECO:0000269|PubMed:7649182}; DE AltName: Full=2-methylacyl-CoA racemase {ECO:0000303|PubMed:11060344}; GN Name=AMACR; 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), VARIANTS ASP-175; SER-201; THR-261 RP AND LYS-277, SUBCELLULAR LOCATION, AND MICROBODY TARGETING. RX PubMed=11060344; RA Amery L., Fransen M., De Nys K., Mannaerts G.P., Van Veldhoven P.P.; RT "Mitochondrial and peroxisomal targeting of 2-methylacyl-CoA racemase in RT humans."; RL J. Lipid Res. 41:1752-1759(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, RP VARIANT AMACRD PRO-52, VARIANT CBAS4 PRO-107, VARIANTS SER-201 AND LYS-277, RP CHARACTERIZATION OF VARIANT AMACRD PRO-52, AND CHARACTERIZATION OF VARIANT RP CBAS4 PRO-107. RX PubMed=10655068; DOI=10.1038/72861; RA Ferdinandusse S., Denis S., Clayton P.T., Graham A., Rees J.E., Allen J.T., RA McLean B.N., Brown A.Y., Vreken P., Waterham H.R., Wanders R.J.A.; RT "Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase RT cause adult-onset sensory motor neuropathy."; RL Nat. Genet. 24:188-191(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AND VARIANTS SER-201 AND LYS-277. RC TISSUE=Prostate cancer; RX PubMed=15880524; DOI=10.1002/pros.20277; RA Mubiru J.N., Valente A.J., Troyer D.A.; RT "A variant of the alpha-methyl-acyl-CoA racemase gene created by a deletion RT in exon 5 and its expression in prostate cancer."; RL Prostate 65:117-123(2005). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS MET-9; ASP-175; RP SER-201; THR-261 AND LYS-277. RA Albers C., Schmitz W., Conzelmann E.; RT "Human alpha-methylacyl-CoA racemase cDNA sequence."; RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT MET-9. RA Ouyang B., Leung Y.-K., Wang V., Chung E., Levin L., Bracken B., Cheng L., RA Ho S.-M.; RT "Expression of alpha-methylacyl-CoA racemase spliced variants in normal and RT malignant prostate tissue."; RL Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT MET-9. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Salivary gland; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT MET-9. 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT MET-9. RC TISSUE=Kidney; 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 [11] RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, SUBCELLULAR LOCATION, AND RP BIOPHYSICOCHEMICAL PROPERTIES. 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 [12] RP FUNCTION, CATALYTIC ACTIVITY, AND 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). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [15] RP VARIANT CBAS4 PRO-52. RX PubMed=12512044; DOI=10.1053/gast.2003.50017; RA Setchell K.D.R., Heubi J.E., Bove K.E., O'Connell N.C., Brewsaugh T., RA Steinberg S.J., Moser A., Squires R.H. Jr.; RT "Liver disease caused by failure to racemize trihydroxycholestanoic acid: RT gene mutation and effect of bile acid therapy."; RL Gastroenterology 124:217-232(2003). CC -!- FUNCTION: Catalyzes the interconversion of (R)- and (S)-stereoisomers CC of alpha-methyl-branched-chain fatty acyl-CoA esters (PubMed:7649182, CC PubMed:10655068, PubMed:11060359). Acts only on coenzyme A thioesters, CC not on free fatty acids, and accepts as substrates a wide range of CC alpha-methylacyl-CoAs, including pristanoyl-CoA, CC trihydroxycoprostanoyl-CoA (an intermediate in bile acid synthesis), CC and arylpropionic acids like the anti-inflammatory drug ibuprofen (2- CC (4-isobutylphenyl)propionic acid) but neither 3-methyl-branched nor CC linear-chain acyl-CoAs (PubMed:7649182, PubMed:10655068, CC PubMed:11060359). {ECO:0000269|PubMed:10655068, CC ECO:0000269|PubMed:11060359, ECO:0000269|PubMed:7649182}. 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:7649182}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12658; CC Evidence={ECO:0000305|PubMed:7649182}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:12659; CC Evidence={ECO:0000305|PubMed:7649182}; 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:0000269|PubMed:10655068}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40456; CC Evidence={ECO:0000305|PubMed:10655068}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:40457; CC Evidence={ECO:0000305|PubMed:10655068}; 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:0000269|PubMed:11060359}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46733; CC Evidence={ECO:0000305|PubMed:11060359}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=172 uM for pristanoyl-CoA {ECO:0000269|PubMed:7649182}; CC KM=31.6 uM for trihydroxycoprostanoyl-CoA CC {ECO:0000269|PubMed:7649182}; CC Vmax=0.1 umol/min/mg enzyme for pristanoyl-CoA CC {ECO:0000269|PubMed:7649182}; CC Vmax=0.3 umol/min/mg enzyme for trihydroxycoprostanoyl-CoA CC {ECO:0000269|PubMed:7649182}; CC pH dependence: CC Optimum pH is 7-8. {ECO:0000269|PubMed:7649182}; CC -!- PATHWAY: Lipid metabolism; bile acid biosynthesis. CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism. CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:7649182}. CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:11060344, CC ECO:0000269|PubMed:11060359, ECO:0000269|PubMed:7649182}. Mitochondrion CC {ECO:0000269|PubMed:11060344, ECO:0000269|PubMed:11060359, CC ECO:0000269|PubMed:7649182}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q9UHK6-1; Sequence=Displayed; CC Name=2; Synonyms=IBLi; CC IsoId=Q9UHK6-2; Sequence=VSP_037321, VSP_037326; CC Name=3; CC IsoId=Q9UHK6-4; Sequence=VSP_037323, VSP_037324; CC Name=4; CC IsoId=Q9UHK6-5; Sequence=VSP_044875; CC -!- DISEASE: Alpha-methylacyl-CoA racemase deficiency (AMACRD) CC [MIM:614307]: A rare autosomal recessive peroxisomal disorder CC characterized by elevated plasma concentrations of pristanic acid C27- CC bile-acid intermediates, and adult onset of variable neurodegenerative CC symptoms affecting the central and peripheral nervous systems. Features CC may include seizures, visual failure, sensorimotor neuropathy, CC spasticity, migraine, and white matter hyperintensities on brain CC imaging. {ECO:0000269|PubMed:10655068}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- DISEASE: Congenital bile acid synthesis defect 4 (CBAS4) [MIM:214950]: CC A disorder characterized by the presence of trihydroxycoprostanic acid CC in the bile and absence of cholic acid. Patients manifest neonatal CC jaundice, intrahepatic cholestasis and bile duct deficiency. CC {ECO:0000269|PubMed:10655068, ECO:0000269|PubMed:12512044}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 4]: Expression is elevated in prostate cancer. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the CoA-transferase III family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=ACL67853.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305}; CC Sequence=ACL67854.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305}; CC Sequence=CAB44062.1; Type=Frameshift; Evidence={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; AJ130733; CAB44062.1; ALT_FRAME; mRNA. DR EMBL; AF158378; AAF22610.1; -; mRNA. DR EMBL; AY935981; AAY16192.1; -; mRNA. DR EMBL; AF047020; AAD10205.1; -; mRNA. DR EMBL; FJ498906; ACL67853.1; ALT_SEQ; mRNA. DR EMBL; FJ498907; ACL67854.1; ALT_SEQ; mRNA. DR EMBL; FJ498908; ACL67855.1; -; mRNA. DR EMBL; BT007193; AAP35857.1; -; mRNA. DR EMBL; EF560721; ABQ59031.1; -; mRNA. DR EMBL; AC139783; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471118; EAX10816.1; -; Genomic_DNA. DR EMBL; BC009471; AAH09471.1; -; mRNA. DR CCDS; CCDS3902.1; -. [Q9UHK6-1] DR CCDS; CCDS3903.1; -. [Q9UHK6-4] DR CCDS; CCDS54836.1; -. [Q9UHK6-5] DR RefSeq; NP_001161067.1; NM_001167595.1. [Q9UHK6-5] DR RefSeq; NP_055139.4; NM_014324.5. [Q9UHK6-1] DR RefSeq; NP_976316.1; NM_203382.2. [Q9UHK6-4] DR AlphaFoldDB; Q9UHK6; -. DR SMR; Q9UHK6; -. DR BioGRID; 117134; 75. DR ELM; Q9UHK6; -. DR IntAct; Q9UHK6; 5. DR STRING; 9606.ENSP00000371517; -. DR SwissLipids; SLP:000001289; -. DR iPTMnet; Q9UHK6; -. DR PhosphoSitePlus; Q9UHK6; -. DR SwissPalm; Q9UHK6; -. DR BioMuta; AMACR; -. DR DMDM; 313104070; -. DR EPD; Q9UHK6; -. DR jPOST; Q9UHK6; -. DR MassIVE; Q9UHK6; -. DR MaxQB; Q9UHK6; -. DR PaxDb; 9606-ENSP00000371517; -. DR PeptideAtlas; Q9UHK6; -. DR ProteomicsDB; 30352; -. DR ProteomicsDB; 84369; -. [Q9UHK6-1] DR ProteomicsDB; 84370; -. [Q9UHK6-2] DR ProteomicsDB; 84371; -. [Q9UHK6-4] DR Pumba; Q9UHK6; -. DR Antibodypedia; 34888; 1188 antibodies from 44 providers. DR DNASU; 23600; -. DR Ensembl; ENST00000335606.11; ENSP00000334424.6; ENSG00000242110.9. [Q9UHK6-1] DR Ensembl; ENST00000382072.6; ENSP00000371504.2; ENSG00000242110.9. [Q9UHK6-4] DR Ensembl; ENST00000382085.7; ENSP00000371517.3; ENSG00000242110.9. [Q9UHK6-5] DR Ensembl; ENST00000506639.5; ENSP00000427227.1; ENSG00000242110.9. [Q9UHK6-2] DR GeneID; 23600; -. DR KEGG; hsa:23600; -. DR MANE-Select; ENST00000335606.11; ENSP00000334424.6; NM_014324.6; NP_055139.4. DR UCSC; uc003jig.4; human. [Q9UHK6-1] DR AGR; HGNC:451; -. DR CTD; 23600; -. DR DisGeNET; 23600; -. DR GeneCards; AMACR; -. DR HGNC; HGNC:451; AMACR. DR HPA; ENSG00000242110; Tissue enhanced (kidney, liver). DR MalaCards; AMACR; -. DR MIM; 214950; phenotype. DR MIM; 604489; gene. DR MIM; 614307; phenotype. DR neXtProt; NX_Q9UHK6; -. DR OpenTargets; ENSG00000242110; -. DR Orphanet; 79095; Congenital bile acid synthesis defect type 4. DR PharmGKB; PA24757; -. DR VEuPathDB; HostDB:ENSG00000242110; -. DR eggNOG; KOG3957; Eukaryota. DR GeneTree; ENSGT00940000157215; -. DR HOGENOM; CLU_1209467_0_0_1; -. DR InParanoid; Q9UHK6; -. DR OMA; VVIDPFR; -. DR OrthoDB; 179764at2759; -. DR PhylomeDB; Q9UHK6; -. DR TreeFam; TF314188; -. DR BioCyc; MetaCyc:HS01416-MONOMER; -. DR BRENDA; 5.1.99.4; 2681. DR PathwayCommons; Q9UHK6; -. DR Reactome; R-HSA-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol. DR Reactome; R-HSA-193775; Synthesis of bile acids and bile salts via 24-hydroxycholesterol. DR Reactome; R-HSA-389887; Beta-oxidation of pristanoyl-CoA. DR Reactome; R-HSA-9033241; Peroxisomal protein import. DR SABIO-RK; Q9UHK6; -. DR SignaLink; Q9UHK6; -. DR UniPathway; UPA00199; -. DR UniPathway; UPA00221; -. DR BioGRID-ORCS; 23600; 14 hits in 1161 CRISPR screens. DR GeneWiki; Alpha-methylacyl-CoA_racemase; -. DR GenomeRNAi; 23600; -. DR Pharos; Q9UHK6; Tbio. DR PRO; PR:Q9UHK6; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; Q9UHK6; Protein. DR Bgee; ENSG00000242110; Expressed in adult mammalian kidney and 107 other cell types or tissues. DR ExpressionAtlas; Q9UHK6; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005782; C:peroxisomal matrix; TAS:Reactome. DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0008111; F:alpha-methylacyl-CoA racemase activity; IDA:UniProtKB. DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB. DR GO; GO:0006699; P:bile acid biosynthetic process; TAS:Reactome. DR GO; GO:0008206; P:bile acid metabolic process; IDA:UniProtKB. DR GO; GO:0033540; P:fatty acid beta-oxidation using acyl-CoA oxidase; TAS:Reactome. 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; Q9UHK6; HS. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Disease variant; KW Intrahepatic cholestasis; Isomerase; Mitochondrion; Peroxisome; KW Reference proteome. FT CHAIN 1..382 FT /note="Alpha-methylacyl-CoA racemase" FT /id="PRO_0000194705" FT MOTIF 380..382 FT /note="Microbody targeting signal" FT /evidence="ECO:0000269|PubMed:11060344" 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 268 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:O09174" FT VAR_SEQ 132..229 FT /note="VLSKIGRSGENPYAPLNLLADFAGGGLMCALGIIMALFDRTRTGKGQVIDAN FT MVEGTAYLSSFLWKTQKLSLWEAPRGQNMLDGGAPFYTTYRTADGE -> GRNSIFKFF FT SVENSEIESVGSTSRTEHVGWWSTFLYDLQDSRWGIHGCWSNRTPVLRAADQRSLIPYF FT NLYLQFLNISMQNLFKVHTLLRPCYFLGQK (in isoform 2)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_037321" FT VAR_SEQ 132..198 FT /note="VLSKIGRSGENPYAPLNLLADFAGGGLMCALGIIMALFDRTRTGKGQVIDAN FT MVEGTAYLSSFLWKT -> GRNSIFKFFSVENSEIESVGSTSRTEHVGWWSTFLYDLQD FT SRWGIHGCWSNRTPVLRAADQRTWTKV (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.6" FT /id="VSP_037323" FT VAR_SEQ 199..382 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.6" FT /id="VSP_037324" FT VAR_SEQ 230..382 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_037326" FT VAR_SEQ 378..382 FT /note="VKASL -> AGSKFWILYPTHSNIQK (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15880524" FT /id="VSP_044875" FT VARIANT 9 FT /note="V -> M (in dbSNP:rs3195676)" FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.4, FT ECO:0000269|Ref.5, ECO:0000269|Ref.6, ECO:0000269|Ref.9" FT /id="VAR_010660" FT VARIANT 52 FT /note="S -> P (in AMACRD and CBAS4; inactive enzyme; FT dbSNP:rs121917814)" FT /evidence="ECO:0000269|PubMed:10655068, FT ECO:0000269|PubMed:12512044" FT /id="VAR_010661" FT VARIANT 107 FT /note="L -> P (in CBAS4; inactive enzyme; FT dbSNP:rs121917816)" FT /evidence="ECO:0000269|PubMed:10655068" FT /id="VAR_010665" FT VARIANT 118 FT /note="R -> Q (in dbSNP:rs16892150)" FT /id="VAR_055616" FT VARIANT 175 FT /note="G -> D (in dbSNP:rs10941112)" FT /evidence="ECO:0000269|PubMed:11060344, ECO:0000269|Ref.4" FT /id="VAR_010662" FT VARIANT 201 FT /note="L -> S (in dbSNP:rs2287939)" FT /evidence="ECO:0000269|PubMed:10655068, FT ECO:0000269|PubMed:11060344, ECO:0000269|PubMed:15880524, FT ECO:0000269|Ref.4" FT /id="VAR_010663" FT VARIANT 238 FT /note="P -> S (in dbSNP:rs9282594)" FT /id="VAR_055617" FT VARIANT 239 FT /note="Q -> H (in dbSNP:rs34677)" FT /id="VAR_055618" FT VARIANT 261 FT /note="M -> I (in dbSNP:rs9282593)" FT /id="VAR_055619" FT VARIANT 261 FT /note="M -> T (in dbSNP:rs3195678)" FT /evidence="ECO:0000269|PubMed:11060344, ECO:0000269|Ref.4" FT /id="VAR_055620" FT VARIANT 277 FT /note="E -> K (in dbSNP:rs2278008)" FT /evidence="ECO:0000269|PubMed:10655068, FT ECO:0000269|PubMed:11060344, ECO:0000269|PubMed:15880524, FT ECO:0000269|Ref.4" FT /id="VAR_010664" FT CONFLICT 18 FT /note="P -> R (in Ref. 1; CAB44062)" FT /evidence="ECO:0000305" FT CONFLICT 128 FT /note="A -> T (in Ref. 7; ABQ59031)" FT /evidence="ECO:0000305" FT CONFLICT 150 FT /note="L -> V (in Ref. 1; CAB44062)" FT /evidence="ECO:0000305" FT CONFLICT 183 FT /note="N -> D (in Ref. 4; AAD10205)" FT /evidence="ECO:0000305" FT CONFLICT 257 FT /note="N -> S (in Ref. 4; AAD10205)" FT /evidence="ECO:0000305" FT CONFLICT 327 FT /note="P -> L (in Ref. 1; CAB44062)" FT /evidence="ECO:0000305" FT CONFLICT 340..342 FT /note="FKR -> SKG (in Ref. 1; CAB44062)" FT /evidence="ECO:0000305" SQ SEQUENCE 382 AA; 42387 MW; E967D3221A90BEF8 CRC64; MALQGISVVE LSGLAPGPFC AMVLADFGAR VVRVDRPGSR YDVSRLGRGK RSLVLDLKQP RGAAVLRRLC KRSDVLLEPF RRGVMEKLQL GPEILQRENP RLIYARLSGF GQSGSFCRLA GHDINYLALS GVLSKIGRSG ENPYAPLNLL ADFAGGGLMC ALGIIMALFD RTRTGKGQVI DANMVEGTAY LSSFLWKTQK LSLWEAPRGQ NMLDGGAPFY TTYRTADGEF MAVGAIEPQF YELLIKGLGL KSDELPNQMS MDDWPEMKKK FADVFAEKTK AEWCQIFDGT DACVTPVLTF EEVVHHDHNK ERGSFITSEE QDVSPRPAPL LLNTPAIPSF KRDPFIGEHT EEILEEFGFS REEIYQLNSD KIIESNKVKA SL //