P70473 (AMACR_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Alpha-methylacyl-CoA racemase
EC=5.1.99.4

Alternative name(s):
2-arylpropionyl-CoA epimerase
2-methylacyl-CoA racemase

Gene names

Name:

Amacr

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	382 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Racemization of 2-methyl-branched fatty acid CoA esters. Responsible for the conversion of pristanoyl-CoA and C27-bile acyl-CoAs to their (S)-stereoisomers. Has a role in drug metabolism as well as probably in lipid metabolism. The 2-arylpropionic acid (2-APA's) derivatives, including ibuprofen, are the most widely used anti-inflammatory analgesic cyclooxygenase inhibitors. The (-)-R-enantiomer, which is inactive in terms of cyclooxygenase inhibition, is epimerized in vivo via this enzyme to the cyclooxygenase-inhibiting (+)-S-enantiomer.
Catalytic activity	(2S)-2-methylacyl-CoA = (2R)-2-methylacyl-CoA.
Pathway	Lipid metabolism; bile acid biosynthesis. Lipid metabolism; fatty acid metabolism.
Subunit structure	Monomer.
Subcellular location	Peroxisome. Mitochondrion.
Sequence similarities	Belongs to the CaiB/BaiF CoA-transferase family.
Sequence caution	The sequence AAB72145.1 differs from that shown. Reason: Erroneous initiation. The sequence CAA69358.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Mitochondrion Peroxisome
Molecular function	Isomerase
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	bile acid biosynthetic process Inferred from direct assay. Source: RGD
Cellular component	mitochondrion Inferred from direct assay. Source: RGD peroxisome Inferred from direct assay. Source: HGNC
Molecular function	alpha-methylacyl-CoA racemase activity Inferred from direct assay Ref.5. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 382	381	Alpha-methylacyl-CoA racemase		PRO_0000194707
Regions
	Motif	380 – 382	3	Microbody targeting signal By similarity
Sites
	Active site	152	1	Nucleophile By similarity
Experimental info
	Sequence conflict	70 – 71	2	CA → FS in CAA69358. Ref.1
	Sequence conflict	80	1	F → L in CAA69358. Ref.1
	Sequence conflict	166	1	L → V in CAA69358. Ref.1
	Sequence conflict	324	1	C → F in CAA69358. Ref.1
	Sequence conflict	328	1	A → S in CAA69358. Ref.1
	Sequence conflict	336	1	A → S in CAA69358. Ref.1
	Sequence conflict	340 – 341	2	AK → SQ in CAA69358. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P70473 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: B6FC51DB167F4767	FASTA	382	41,828
	10 20 30 40 50 60 MALRGVRVLE LAGLAPGPFC GMILADFGAE VVLVDRLGSV NHPSHLARGK RSLALDLKRS 70 80 90 100 110 120 PGAAVLRRMC ARADVLLEPF RCGVMEKLQL GPETLRQDNP KLIYARLSGF GQSGIFSKVA 130 140 150 160 170 180 GHDINYVALS GVLSKIGRSG ENPYPPLNLL ADFGGGGLMC TLGILLALFE RTRSGLGQVI 190 200 210 220 230 240 DANMVEGTAY LSTFLWKTQA MGLWAQPRGQ NLLDGGAPFY TTYKTADGEF MAVGAIEPQF 250 260 270 280 290 300 YTLLLKGLGL ESEELPSQMS IEDWPEMKKK FADVFARKTK AEWCQIFDGT DACVTPVLTL 310 320 330 340 350 360 EEALHHQHNR ERGSFITDEE QHACPRPAPQ LSRTPAVPSA KRDPSVGEHT VEVLKDYGFS 370 380 QEEIHQLHSD RIIESNKLKA NL

References

[1]	"Molecular cloning and expression of a 2-arylpropionyl-coenzyme A epimerase: a key enzyme in the inversion metabolism of ibuprofen." Reichel C., Brugger R., Bang H., Geisslinger G., Brune K. Mol. Pharmacol. 51:576-582(1997) [PubMed: 9106621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 11-382. Strain: Sprague-Dawley. Tissue: Liver.
[2]	"Molecular cloning of cDNA species for rat and mouse liver alpha-methylacyl-CoA racemases." Schmitz W., Helander H.M., Hiltunen J.K., Conzelmann E. Biochem. J. 326:883-889(1997) [PubMed: 9307041] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-382. Tissue: Liver.
[3]	"In mouse alpha-methylacyl-CoA racemase, the same gene product is simultaneously located in mitochondria and peroxisomes." Kotti T.J., Savolainen K., Helander H.M., Yagi A., Novikov D.K., Kalkkinen N., Conzelmann E., Hiltunen J.K., Schmitz W. J. Biol. Chem. 275:20887-20895(2000) [PubMed: 10770938] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE.
[4]	"2-arylpropionyl-CoA epimerase: partial peptide sequences and tissue localization." Reichel C., Bang H., Brune K., Geisslinger G., Menzel S. Biochem. Pharmacol. 50:1803-1806(1995) [PubMed: 8615858] [Abstract] Cited for: PROTEIN SEQUENCE OF 103-117, TISSUE SPECIFICITY. Tissue: Liver.
[5]	"Purification and properties of an alpha-methylacyl-CoA racemase from rat liver." Schmitz W., Fingerhut R., Conzelmann E. Eur. J. Biochem. 222:313-323(1994) [PubMed: 8020470] [Abstract] Cited for: CHARACTERIZATION. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y08172 mRNA. Translation: CAA69358.1. Different initiation. U89905 mRNA. Translation: AAB72145.1. Different initiation.
IPI	IPI00188858.
RefSeq	NP_036948.1. NM_012816.1.
UniGene	Rn.2590.
3D structure databases
ProteinModelPortal	P70473.
ModBase	Search...
Protein-protein interaction databases
STRING	P70473.
Proteomic databases
PRIDE	P70473.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	25284.
KEGG	rno:25284.
UCSC	NM_012816. rat.
Organism-specific databases
CTD	23600.
RGD	3048. Amacr.
Phylogenomic databases
eggNOG	maNOG13861.
HOVERGEN	HBG060891.
Enzyme and pathway databases
BioCyc	MetaCyc:MONOMER-14326.
Gene expression databases
ArrayExpress	P70473.
Genevestigator	P70473.
GermOnline	ENSRNOG00000018662. Rattus norvegicus.
Family and domain databases
InterPro	IPR003673. CoA-Trfase_fam_III. IPR023606. CoA-Trfase_III_dom. [Graphical view]
Gene3D	G3DSA:3.40.50.10540. CoA-Trfase_fam_III. 1 hit.
KO	K01796.
PANTHER	PTHR11837. CAIB_BAIF. 1 hit.
Pfam	PF02515. CoA_transf_3. 1 hit. [Graphical view]
SUPFAM	SSF89796. CoA-Trfase_fam_III. 1 hit.
ProtoNet	Search...
Other
NextBio	606013.

Entry information

Entry name

AMACR_RAT

Accession

Primary (citable) accession number: P70473
Secondary accession number(s): O09176

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	January 23, 2007
Last modified:	November 16, 2011
This is version 85 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program