Q9UHK6 (AMACR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

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

Gene names

Name:

AMACR

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	382 AA.
Sequence status	Complete.
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.
Catalytic activity	(2S)-2-methylacyl-CoA = (2R)-2-methylacyl-CoA.
Pathway	Lipid metabolism; bile acid biosynthesis. Lipid metabolism; fatty acid metabolism.
Subcellular location	Peroxisome. Mitochondrion Ref.1.
Involvement in disease	Defects in AMACR are the cause of alpha-methylacyl-CoA racemase deficiency (AMACRD) [MIM:614307]. AMACRD results in elevated plasma concentrations of pristanic acid C27-bile-acid intermediates. It can be associated with polyneuropathy, retinitis pigmentosa, epilepsy. Ref.2 Defects in AMACR are the cause of congenital bile acid synthesis defect type 4 (CBAS4) [MIM:214950]; also known as cholestasis, intrahepatic, with defective conversion of trihydroxycoprostanic acid to cholic acid or trihydroxycoprostanic acid in bile. Clinical features include neonatal jaundice, intrahepatic cholestasis, bile duct deficiency and absence of cholic acid from bile. Ref.2 Ref.11
Sequence similarities	Belongs to the CaiB/BaiF CoA-transferase family.
Sequence caution	The sequence ACL67853.1 differs from that shown. Reason: Aberrant splicing. The sequence ACL67854.1 differs from that shown. Reason: Aberrant splicing. The sequence CAB44062.1 differs from that shown. Reason: Frameshift at positions 62, 65 and 114.

Ontologies

Keywords
Cellular component	Mitochondrion Peroxisome
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Intrahepatic cholestasis
Molecular function	Isomerase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	bile acid biosynthetic process Traceable author statement. Source: Reactome fatty acid beta-oxidation using acyl-CoA oxidase Traceable author statement. Source: Reactome
Cellular component	mitochondrion Traceable author statement. Source: ProtInc peroxisomal matrix Traceable author statement. Source: Reactome
Molecular function	alpha-methylacyl-CoA racemase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UHK6-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9UHK6-2)

Also known as: IBLi;

The sequence of this isoform differs from the canonical sequence as follows:
     132-229: VLSKIGRSGE...YTTYRTADGE → GRNSIFKFFS...LRPCYFLGQK
     230-382: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform 3 (identifier: Q9UHK6-4)

The sequence of this isoform differs from the canonical sequence as follows:
     132-198: VLSKIGRSGE...AYLSSFLWKT → GRNSIFKFFS...AADQRTWTKV
     199-382: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 382	382	Alpha-methylacyl-CoA racemase		PRO_0000194705
Regions
	Motif	380 – 382	3	Microbody targeting signal
Sites
	Active site	152	1	Nucleophile By similarity
Natural variations
	Alternative sequence	132 – 229	98	VLSKI…TADGE → GRNSIFKFFSVENSEIESVG STSRTEHVGWWSTFLYDLQD SRWGIHGCWSNRTPVLRAAD QRSLIPYFNLYLQFLNISMQ NLFKVHTLLRPCYFLGQK in isoform 2.		VSP_037321
	Alternative sequence	132 – 198	67	VLSKI…FLWKT → GRNSIFKFFSVENSEIESVG STSRTEHVGWWSTFLYDLQD SRWGIHGCWSNRTPVLRAAD QRTWTKV in isoform 3.		VSP_037323
	Alternative sequence	199 – 382	184	Missing in isoform 3.		VSP_037324
	Alternative sequence	230 – 382	153	Missing in isoform 2.		VSP_037326
	Natural variant	9	1	V → M. Ref.3 Ref.4 Ref.5 Ref.8 Ref.9 Corresponds to variant rs3195676 [ dbSNP | Ensembl ].		VAR_010660
	Natural variant	52	1	S → P in AMACRD and CBAS4; inactive enzyme. Ref.2 Ref.11		VAR_010661
	Natural variant	107	1	L → P in CBAS4; inactive enzyme. Ref.2		VAR_010665
	Natural variant	118	1	R → Q. Corresponds to variant rs16892150 [ dbSNP | Ensembl ].		VAR_055616
	Natural variant	175	1	G → D. Ref.1 Ref.3 Corresponds to variant rs10941112 [ dbSNP | Ensembl ].		VAR_010662
	Natural variant	201	1	L → S. Ref.1 Ref.2 Ref.3 Corresponds to variant rs2287939 [ dbSNP | Ensembl ].		VAR_010663
	Natural variant	238	1	P → S. Corresponds to variant rs9282594 [ dbSNP | Ensembl ].		VAR_055617
	Natural variant	239	1	Q → H. Corresponds to variant rs34677 [ dbSNP | Ensembl ].		VAR_055618
	Natural variant	261	1	M → I. Corresponds to variant rs9282593 [ dbSNP | Ensembl ].		VAR_055619
	Natural variant	261	1	M → T. Ref.1 Ref.3 Corresponds to variant rs3195678 [ dbSNP | Ensembl ].		VAR_055620
	Natural variant	277	1	E → K. Ref.1 Ref.2 Ref.3 Corresponds to variant rs2278008 [ dbSNP | Ensembl ].		VAR_010664
Experimental info
	Sequence conflict	18	1	P → R in CAB44062. Ref.1
	Sequence conflict	128	1	A → T in ABQ59031. Ref.6
	Sequence conflict	150	1	L → V in CAB44062. Ref.1
	Sequence conflict	183	1	N → D in AAD10205. Ref.3
	Sequence conflict	257	1	N → S in AAD10205. Ref.3
	Sequence conflict	327	1	P → L in CAB44062. Ref.1
	Sequence conflict	340 – 342	3	FKR → SKG in CAB44062. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 30, 2010. Version 2. Checksum: E967D3221A90BEF8	FASTA	382	42,387
	10 20 30 40 50 60 MALQGISVVE LSGLAPGPFC AMVLADFGAR VVRVDRPGSR YDVSRLGRGK RSLVLDLKQP 70 80 90 100 110 120 RGAAVLRRLC KRSDVLLEPF RRGVMEKLQL GPEILQRENP RLIYARLSGF GQSGSFCRLA 130 140 150 160 170 180 GHDINYLALS GVLSKIGRSG ENPYAPLNLL ADFAGGGLMC ALGIIMALFD RTRTGKGQVI 190 200 210 220 230 240 DANMVEGTAY LSSFLWKTQK LSLWEAPRGQ NMLDGGAPFY TTYRTADGEF MAVGAIEPQF 250 260 270 280 290 300 YELLIKGLGL KSDELPNQMS MDDWPEMKKK FADVFAEKTK AEWCQIFDGT DACVTPVLTF 310 320 330 340 350 360 EEVVHHDHNK ERGSFITSEE QDVSPRPAPL LLNTPAIPSF KRDPFIGEHT EEILEEFGFS 370 380 REEIYQLNSD KIIESNKVKA SL
	Isoform 2 (IBLi) [UniParc]. Checksum: FC361E1AC140CAF4	FASTA	229	25,914
	10 20 30 40 50 60 MALQGISVVE LSGLAPGPFC AMVLADFGAR VVRVDRPGSR YDVSRLGRGK RSLVLDLKQP 70 80 90 100 110 120 RGAAVLRRLC KRSDVLLEPF RRGVMEKLQL GPEILQRENP RLIYARLSGF GQSGSFCRLA 130 140 150 160 170 180 GHDINYLALS GGRNSIFKFF SVENSEIESV GSTSRTEHVG WWSTFLYDLQ DSRWGIHGCW 190 200 210 220 SNRTPVLRAA DQRSLIPYFN LYLQFLNISM QNLFKVHTLL RPCYFLGQK
	Isoform 3 [UniParc]. Checksum: 1D677621A6EBD986	FASTA	198	22,183
	10 20 30 40 50 60 MALQGISVVE LSGLAPGPFC AMVLADFGAR VVRVDRPGSR YDVSRLGRGK RSLVLDLKQP 70 80 90 100 110 120 RGAAVLRRLC KRSDVLLEPF RRGVMEKLQL GPEILQRENP RLIYARLSGF GQSGSFCRLA 130 140 150 160 170 180 GHDINYLALS GGRNSIFKFF SVENSEIESV GSTSRTEHVG WWSTFLYDLQ DSRWGIHGCW 190 SNRTPVLRAA DQRTWTKV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mitochondrial and peroxisomal targeting of 2-methylacyl-CoA racemase in humans." Amery L., Fransen M., De Nys K., Mannaerts G.P., Van Veldhoven P.P. J. Lipid Res. 41:1752-1759(2000) [PubMed: 11060344] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS ASP-175; SER-201; THR-261 AND LYS-277, SUBCELLULAR LOCATION, MICROBODY TARGETING.
[2]	"Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy." Ferdinandusse S., Denis S., Clayton P.T., Graham A., Rees J.E., Allen J.T., McLean B.N., Brown A.Y., Vreken P., Waterham H.R., Wanders R.J.A. Nat. Genet. 24:188-191(2000) [PubMed: 10655068] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT AMACRD PRO-52, VARIANT CBAS4 PRO-107, VARIANTS SER-201 AND LYS-277, CHARACTERIZATION OF VARIANT AMACRD PRO-52, CHARACTERIZATION OF VARIANT CBAS4 PRO-107.
[3]	"Human alpha-methylacyl-CoA racemase cDNA sequence." Albers C., Schmitz W., Conzelmann E. Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS MET-9; ASP-175; SER-201; THR-261 AND LYS-277.
[4]	"Expression of alpha-methylacyl-CoA racemase spliced variants in normal and malignant prostate tissue." Ouyang B., Leung Y.-K., Wang V., Chung E., Levin L., Bracken B., Cheng L., Ho S.-M. Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT MET-9.
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANT MET-9.
[6]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Salivary gland.
[7]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed: 15372022] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT MET-9.
[9]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANT MET-9. Tissue: Kidney.
[10]	"Purification and characterization of an alpha-methylacyl-CoA racemase from human liver." Schmitz W., Albers C., Fingerhut R., Conzelmann E. Eur. J. Biochem. 231:815-822(1995) [PubMed: 7649182] [Abstract] Cited for: CHARACTERIZATION. Tissue: Liver.
[11]	"Liver disease caused by failure to racemize trihydroxycholestanoic acid: gene mutation and effect of bile acid therapy." Setchell K.D.R., Heubi J.E., Bove K.E., O'Connell N.C., Brewsaugh T., Steinberg S.J., Moser A., Squires R.H. Jr. Gastroenterology 124:217-232(2003) [PubMed: 12512044] [Abstract] Cited for: VARIANT CBAS4 PRO-52.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ130733 mRNA. Translation: CAB44062.1. Frameshift. AF158378 mRNA. Translation: AAF22610.1. AF047020 mRNA. Translation: AAD10205.1. FJ498906 mRNA. Translation: ACL67853.1. Sequence problems. FJ498907 mRNA. Translation: ACL67854.1. Sequence problems. FJ498908 mRNA. Translation: ACL67855.1. BT007193 mRNA. Translation: AAP35857.1. EF560721 mRNA. Translation: ABQ59031.1. AC139783 Genomic DNA. No translation available. CH471118 Genomic DNA. Translation: EAX10816.1. BC009471 mRNA. Translation: AAH09471.1.
IPI	IPI00914928. IPI00930327. IPI00930713.
RefSeq	NP_055139.4. NM_014324.5. NP_976316.1. NM_203382.2.
UniGene	Hs.508343.
3D structure databases
ProteinModelPortal	Q9UHK6.
SMR	Q9UHK6. Positions 2-358.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9UHK6.
PTM databases
PhosphoSite	Q9UHK6.
Polymorphism databases
DMDM	13626118.
Proteomic databases
PRIDE	Q9UHK6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000335606; ENSP00000334424; ENSG00000242110.
GeneID	23600.
KEGG	hsa:23600.
Organism-specific databases
CTD	23600.
GeneCards	GC05M033986.
HGNC	HGNC:451. AMACR.
HPA	CAB001809. HPA019527. HPA020912.
MIM	214950. phenotype. 604489. gene. 614307. phenotype.
neXtProt	NX_Q9UHK6.
Orphanet	79095. Congenital bile acid synthesis defect type 4. 140450. Hereditary motor and sensory neuropathy.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG19016.
GeneTree	ENSGT00530000063418.
HOVERGEN	HBG060891.
OrthoDB	EOG4WQ12V.
PhylomeDB	Q9UHK6.
Enzyme and pathway databases
BRENDA	5.1.99.4. 2681.
Reactome	REACT_22258. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	Q9UHK6.
Bgee	Q9UHK6.
CleanEx	HS_AMACR.
Genevestigator	Q9UHK6.
GermOnline	ENSG00000082196. Homo sapiens.
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
SOURCE	Search...

Entry information

Entry name

AMACR_HUMAN

Accession

Primary (citable) accession number: Q9UHK6
Secondary accession number(s): A5YM47 , B8Y916, B8Y918, O43673, Q96GH1, Q9Y3Q1

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	November 30, 2010
Last modified:	January 25, 2012
This is version 103 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.