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Q9UHK6 (AMACR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Alpha-methylacyl-CoA racemase

EC=5.1.99.4
Alternative name(s):
2-methylacyl-CoA racemase
Gene names
Name:AMACR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length382 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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

Alpha-methylacyl-CoA racemase deficiency (AMACRD) [MIM:614307]: A rare autosomal recessive peroxisomal disorder characterized by elevated plasma concentrations of pristanic acid C27-bile-acid intermediates, and adult onset of variable neurodegenerative symptoms affecting the central and peripheral nervous systems. Features may include seizures, visual failure, sensorimotor neuropathy, spasticity, migraine, and white matter hyperintensities on brain imaging.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2

Congenital bile acid synthesis defect 4 (CBAS4) [MIM:214950]: A disorder characterized by the presence of trihydroxycoprostanic acid in the bile and absence of cholic acid. Patients manifest neonatal jaundice, intrahepatic cholestasis and bile duct deficiency.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.12

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.

Alternative products

This entry describes 4 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.
Isoform 4 (identifier: Q9UHK6-5)

The sequence of this isoform differs from the canonical sequence as follows:
     378-382: VKASL → AGSKFWILYPTHSNIQK
Note: Expression is elevated in prostate cancer.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 382381Alpha-methylacyl-CoA racemase
PRO_0000194705

Regions

Motif380 – 3823Microbody targeting signal

Sites

Active site1521Nucleophile By similarity

Amino acid modifications

Modified residue581N6-acetyllysine By similarity
Modified residue871N6-acetyllysine; alternate By similarity
Modified residue871N6-succinyllysine; alternate By similarity
Modified residue2681N6-succinyllysine By similarity

Natural variations

Alternative sequence132 – 22998VLSKI…TADGE → GRNSIFKFFSVENSEIESVG STSRTEHVGWWSTFLYDLQD SRWGIHGCWSNRTPVLRAAD QRSLIPYFNLYLQFLNISMQ NLFKVHTLLRPCYFLGQK in isoform 2.
VSP_037321
Alternative sequence132 – 19867VLSKI…FLWKT → GRNSIFKFFSVENSEIESVG STSRTEHVGWWSTFLYDLQD SRWGIHGCWSNRTPVLRAAD QRTWTKV in isoform 3.
VSP_037323
Alternative sequence199 – 382184Missing in isoform 3.
VSP_037324
Alternative sequence230 – 382153Missing in isoform 2.
VSP_037326
Alternative sequence378 – 3825VKASL → AGSKFWILYPTHSNIQK in isoform 4.
VSP_044875
Natural variant91V → M. Ref.4 Ref.5 Ref.6 Ref.9 Ref.10
Corresponds to variant rs3195676 [ dbSNP | Ensembl ].
VAR_010660
Natural variant521S → P in AMACRD and CBAS4; inactive enzyme. Ref.2 Ref.12
VAR_010661
Natural variant1071L → P in CBAS4; inactive enzyme. Ref.2
VAR_010665
Natural variant1181R → Q.
Corresponds to variant rs16892150 [ dbSNP | Ensembl ].
VAR_055616
Natural variant1751G → D. Ref.1 Ref.4
Corresponds to variant rs10941112 [ dbSNP | Ensembl ].
VAR_010662
Natural variant2011L → S. Ref.1 Ref.2 Ref.3 Ref.4
Corresponds to variant rs2287939 [ dbSNP | Ensembl ].
VAR_010663
Natural variant2381P → S.
Corresponds to variant rs9282594 [ dbSNP | Ensembl ].
VAR_055617
Natural variant2391Q → H.
Corresponds to variant rs34677 [ dbSNP | Ensembl ].
VAR_055618
Natural variant2611M → I.
Corresponds to variant rs9282593 [ dbSNP | Ensembl ].
VAR_055619
Natural variant2611M → T. Ref.1 Ref.4
Corresponds to variant rs3195678 [ dbSNP | Ensembl ].
VAR_055620
Natural variant2771E → K. Ref.1 Ref.2 Ref.3 Ref.4
Corresponds to variant rs2278008 [ dbSNP | Ensembl ].
VAR_010664

Experimental info

Sequence conflict181P → R in CAB44062. Ref.1
Sequence conflict1281A → T in ABQ59031. Ref.7
Sequence conflict1501L → V in CAB44062. Ref.1
Sequence conflict1831N → D in AAD10205. Ref.4
Sequence conflict2571N → S in AAD10205. Ref.4
Sequence conflict3271P → L in CAB44062. Ref.1
Sequence conflict340 – 3423FKR → SKG in CAB44062. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 30, 2010. Version 2.
Checksum: E967D3221A90BEF8

FASTA38242,387
        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 

« Hide

Isoform 2 (IBLi) [UniParc].

Checksum: FC361E1AC140CAF4
Show »

FASTA22925,914
Isoform 3 [UniParc].

Checksum: 1D677621A6EBD986
Show »

FASTA19822,183
Isoform 4 [UniParc].

Checksum: 55B6E53900632287
Show »

FASTA39443,860

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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]"A variant of the alpha-methyl-acyl-CoA racemase gene created by a deletion in exon 5 and its expression in prostate cancer."
Mubiru J.N., Valente A.J., Troyer D.A.
Prostate 65:117-123(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), VARIANTS SER-201 AND LYS-277.
Tissue: Prostate cancer.
[4]"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.
[5]"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.
[6]"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.
[7]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Salivary gland.
[8]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]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. expand/collapse author list , 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.
[10]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANT MET-9.
Tissue: Kidney.
[11]"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] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
Tissue: Liver.
[12]"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] [Europe PMC] [Abstract]
Cited for: VARIANT CBAS4 PRO-52.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ130733 mRNA. Translation: CAB44062.1. Frameshift.
AF158378 mRNA. Translation: AAF22610.1.
AY935981 mRNA. Translation: AAY16192.1.
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.
RefSeqNP_001161067.1. NM_001167595.1.
NP_055139.4. NM_014324.5.
NP_976316.1. NM_203382.2.
UniGeneHs.508343.

3D structure databases

ProteinModelPortalQ9UHK6.
SMRQ9UHK6. Positions 3-338.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117134. 3 interactions.
STRING9606.ENSP00000334424.

PTM databases

PhosphoSiteQ9UHK6.

Polymorphism databases

DMDM313104070.

Proteomic databases

PaxDbQ9UHK6.
PRIDEQ9UHK6.

Protocols and materials databases

DNASU23600.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000335606; ENSP00000334424; ENSG00000242110. [Q9UHK6-1]
ENST00000382072; ENSP00000371504; ENSG00000242110. [Q9UHK6-4]
ENST00000382085; ENSP00000371517; ENSG00000242110. [Q9UHK6-5]
ENST00000441713; ENSP00000403800; ENSG00000242110. [Q9UHK6-2]
ENST00000506639; ENSP00000427227; ENSG00000242110. [Q9UHK6-2]
GeneID23600.
KEGGhsa:23600.
UCSCuc003jig.3. human. [Q9UHK6-1]
uc003jih.3. human. [Q9UHK6-4]

Organism-specific databases

CTD23600.
GeneCardsGC05M033986.
HGNCHGNC:451. AMACR.
HPACAB001809.
HPA019527.
HPA020912.
MIM214950. phenotype.
604489. gene.
614307. phenotype.
neXtProtNX_Q9UHK6.
Orphanet79095. Congenital bile acid synthesis defect type 4.
PharmGKBPA24757.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1804.
HOGENOMHOG000219744.
HOVERGENHBG060891.
KOK01796.
OMAGSHDLNY.
OrthoDBEOG78SQJF.
PhylomeDBQ9UHK6.
TreeFamTF314188.

Enzyme and pathway databases

BioCycMetaCyc:HS01416-MONOMER.
BRENDA5.1.99.4. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKQ9UHK6.
UniPathwayUPA00199.
UPA00221.

Gene expression databases

BgeeQ9UHK6.
CleanExHS_AMACR.
GenevestigatorQ9UHK6.

Family and domain databases

Gene3D3.40.50.10540. 2 hits.
InterProIPR003673. CoA-Trfase_fam_III.
IPR023606. CoA-Trfase_III_dom.
[Graphical view]
PANTHERPTHR11837. PTHR11837. 1 hit.
PfamPF02515. CoA_transf_3. 1 hit.
[Graphical view]
SUPFAMSSF89796. SSF89796. 1 hit.
ProtoNetSearch...

Other

GeneWikiAlpha-methylacyl-CoA_racemase.
GenomeRNAi23600.
NextBio46278.
PROQ9UHK6.
SOURCESearch...

Entry information

Entry nameAMACR_HUMAN
AccessionPrimary (citable) accession number: Q9UHK6
Secondary accession number(s): A5YM47 expand/collapse secondary AC list , B8Y916, B8Y918, F8W9N1, O43673, Q3KT79, Q96GH1, Q9Y3Q1
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: November 30, 2010
Last modified: April 16, 2014
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM