Q96PE7 (MCEE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Methylmalonyl-CoA epimerase, mitochondrial
EC=5.1.99.1

Alternative name(s):
DL-methylmalonyl-CoA racemase

Gene names

Name:

MCEE

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	176 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)

Catalytic activity	(R)-methylmalonyl-CoA = (S)-methylmalonyl-CoA.
Subcellular location	Mitochondrion Probable.
Involvement in disease	Defects in MCEE are a cause of methylmalonyl-CoA epimerase deficiency (MCEED) [MIM:251120]; also known as methylmalonyl-CoA racemase deficiency or methylmalonic aciduria type 3. MCEE deficiency is an autosomal recessive inborn error of amino acid metabolism, involving valine, threonine, isoleucine and methionine. This organic aciduria may present in the neonatal period with life-threatening metabolic acidosis, hyperammonemia, feeding difficulties, pancytopenia and coma. Ref.5
Sequence similarities	Belongs to the glyoxalase I family.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Transit peptide
Molecular function	Isomerase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	L-methylmalonyl-CoA metabolic process Inferred from direct assay Ref.1. Source: UniProtKB fatty acid beta-oxidation Traceable author statement. Source: Reactome
Cellular component	mitochondrial matrix Traceable author statement. Source: Reactome
Molecular function	methylmalonyl-CoA epimerase activity Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 36

36

Mitochondrion Potential

Chain

37 – 176

140

Methylmalonyl-CoA epimerase, mitochondrial

PRO_0000012283

Regions

Compositional bias

138 – 141

4

Poly-Lys

Amino acid modifications

Modified residue

114

1

N6-acetyllysine Ref.6

Natural variations

Natural variant

76

1

A → V.
Corresponds to variant rs11541017 [ dbSNP | Ensembl ].

VAR_049248

Natural variant

104

1

R → L. Ref.4
Corresponds to variant rs6748672 [ dbSNP | Ensembl ].

VAR_019511

Secondary structure

1

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176

Helix Strand Turn

Details...

Beta strand

48 – 54

7

Helix

58 – 67

10

Beta strand

85 – 90

6

Beta strand

95 – 100

6

Turn

112 – 114

3

Beta strand

122 – 128

7

Helix

130 – 139

10

Beta strand

158 – 161

4

Beta strand

171 – 175

5

Sequences

	Sequence		Length	Mass (Da)
	Q96PE7 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: F783E5DF5D778220	FASTA	176	18,749
	10 20 30 40 50 60 MARVLKAAAA NAVGLFSRLQ APIPTVRASS TSQPLDQVTG SVWNLGRLNH VAIAVPDLEK 70 80 90 100 110 120 AAAFYKNILG AQVSEAVPLP EHGVSVVFVN LGNTKMELLH PLGRDSPIAG FLQKNKAGGM 130 140 150 160 170 HHICIEVDNI NAAVMDLKKK KIRSLSEEVK IGAHGKPVIF LHPKDCGGVL VELEQA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of the human methylmalonyl-CoA racemase gene based on the analysis of prokaryotic gene arrangements. Implications for decoding the human genome." Bobik T.A., Rasche M.E. J. Biol. Chem. 276:37194-37198(2001) [PubMed: 11481338] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Liver.
[2]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	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].
[4]	"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], VARIANT LEU-104. Tissue: Liver.
[5]	"A homozygous nonsense mutation in the methylmalonyl-CoA epimerase gene (MCEE) results in mild methylmalonic aciduria." Bikker H., Bakker H.D., Abeling N.G.G.M., Poll-The B.T., Kleijer W.J., Rosenblatt D.S., Waterham H.R., Wanders R.J.A., Duran M. Hum. Mutat. 27:640-643(2006) [PubMed: 16752391] [Abstract] Cited for: INVOLVEMENT IN MCEED.
[6]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-114, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF364547 mRNA. Translation: AAK52052.1.
AC007881 Genomic DNA. Translation: AAY14749.1.
CH471053 Genomic DNA. Translation: EAW99778.1.
BC020825 mRNA. Translation: AAH20825.1.

IPI

IPI00107722.

RefSeq

NP_115990.3. NM_032601.3.

UniGene

Hs.94949.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3RMU	X-ray	1.80	A/B/C/D	45-176	[»]

ProteinModelPortal

Q96PE7.

SMR

Q96PE7. Positions 45-176.

ModBase

Search...

Protein-protein interaction databases

STRING

Q96PE7.

PTM databases

PhosphoSite

Q96PE7.

Polymorphism databases

DMDM

50401130.

2D gel databases

UCD-2DPAGE

Q96PE7.

Proteomic databases

PRIDE

Q96PE7.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000244217; ENSP00000244217; ENSG00000124370.

GeneID

84693.

KEGG

hsa:84693.

UCSC

uc002shs.2. human.

Organism-specific databases

CTD

84693.

GeneCards

GC02M071336.

H-InvDB

HIX0002148.

HGNC

HGNC:16732. MCEE.

HPA

HPA035196.

MIM

251120. phenotype.
608419. gene.

neXtProt

NX_Q96PE7.

Orphanet

27. Vitamin B12-unresponsive methylmalonic aciduria.

PharmGKB

PA30683.

GenAtlas

Search...

Phylogenomic databases

GeneTree

ENSGT00390000004772.

HOGENOM

HBG704761.

HOVERGEN

HBG052426.

InParanoid

Q96PE7.

OMA

CYEVDDI.

OrthoDB

EOG44J2KB.

PhylomeDB

Q96PE7.

Enzyme and pathway databases

BRENDA

5.1.99.1. 2681.

Reactome

REACT_22258. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpress

Q96PE7.

Bgee

Q96PE7.

CleanEx

HS_MCEE.

Genevestigator

Q96PE7.

GermOnline

ENSG00000124370. Homo sapiens.

Family and domain databases

InterPro

IPR004360. Glyas_Fos-R_dOase.
IPR017515. MeMalonyl-CoA_epimerase.
[Graphical view]

KO

K05606.

Pfam

PF00903. Glyoxalase. 1 hit.
[Graphical view]

TIGRFAMs

TIGR03081. Metmalonyl_epim. 1 hit.

ProtoNet

Search...

Other

NextBio

74761.

SOURCE

Search...

Entry information

Entry name

MCEE_HUMAN

Accession

Primary (citable) accession number: Q96PE7
Secondary accession number(s): Q53TP1, Q8WW63

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	December 1, 2001
Last modified:	January 25, 2012
This is version 83 of the entry and version 1 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.