MCEE_HUMAN
ID MCEE_HUMAN Reviewed; 176 AA.
AC Q96PE7; Q53TP1; Q8WW63;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Methylmalonyl-CoA epimerase, mitochondrial {ECO:0000305};
DE EC=5.1.99.1 {ECO:0000269|PubMed:11481338};
DE AltName: Full=DL-methylmalonyl-CoA racemase {ECO:0000303|PubMed:11481338};
DE Flags: Precursor;
GN Name=MCEE {ECO:0000312|HGNC:HGNC:16732};
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], FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Liver;
RX PubMed=11481338; DOI=10.1074/jbc.m107232200;
RA Bobik T.A., Rasche M.E.;
RT "Identification of the human methylmalonyl-CoA racemase gene based on the
RT analysis of prokaryotic gene arrangements. Implications for decoding the
RT human genome.";
RL J. Biol. Chem. 276:37194-37198(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-104.
RC TISSUE=Liver;
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 [5]
RP INVOLVEMENT IN MCEED.
RX PubMed=16752391; DOI=10.1002/humu.20373;
RA Bikker H., Bakker H.D., Abeling N.G.G.M., Poll-The B.T., Kleijer W.J.,
RA Rosenblatt D.S., Waterham H.R., Wanders R.J.A., Duran M.;
RT "A homozygous nonsense mutation in the methylmalonyl-CoA epimerase gene
RT (MCEE) results in mild methylmalonic aciduria.";
RL Hum. Mutat. 27:640-643(2006).
RN [6]
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 [7]
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 [8]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 45-176 IN COMPLEX WITH COBALT.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human methylmalonyl-CoA epimerase, MCEE.";
RL Submitted (APR-2011) to the PDB data bank.
CC -!- FUNCTION: Methylmalonyl-CoA epimerase involved in propionyl-CoA
CC metabolism. {ECO:0000269|PubMed:11481338}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-methylmalonyl-CoA = (S)-methylmalonyl-CoA;
CC Xref=Rhea:RHEA:20553, ChEBI:CHEBI:57326, ChEBI:CHEBI:57327;
CC EC=5.1.99.1; Evidence={ECO:0000269|PubMed:11481338};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20555;
CC Evidence={ECO:0000305|PubMed:11481338};
CC -!- INTERACTION:
CC Q96PE7; Q6RW13: AGTRAP; NbExp=4; IntAct=EBI-10292326, EBI-741181;
CC Q96PE7; Q6RW13-2: AGTRAP; NbExp=6; IntAct=EBI-10292326, EBI-11522760;
CC Q96PE7; P60033: CD81; NbExp=3; IntAct=EBI-10292326, EBI-712921;
CC Q96PE7; Q96DZ9: CMTM5; NbExp=4; IntAct=EBI-10292326, EBI-2548702;
CC Q96PE7; Q96DZ9-2: CMTM5; NbExp=6; IntAct=EBI-10292326, EBI-11522780;
CC Q96PE7; Q9UNK0: STX8; NbExp=3; IntAct=EBI-10292326, EBI-727240;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000305}.
CC -!- DISEASE: Methylmalonyl-CoA epimerase deficiency (MCEED) [MIM:251120]:
CC Autosomal recessive inborn error of amino acid metabolism, involving
CC valine, threonine, isoleucine and methionine. This organic aciduria may
CC present in the neonatal period with life-threatening metabolic
CC acidosis, hyperammonemia, feeding difficulties, pancytopenia and coma.
CC {ECO:0000269|PubMed:16752391}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the methylmalonyl-CoA epimerase family.
CC {ECO:0000305}.
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DR EMBL; AF364547; AAK52052.1; -; mRNA.
DR EMBL; AC007881; AAY14749.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99778.1; -; Genomic_DNA.
DR EMBL; BC020825; AAH20825.1; -; mRNA.
DR CCDS; CCDS1915.1; -.
DR RefSeq; NP_115990.3; NM_032601.3.
DR PDB; 3RMU; X-ray; 1.80 A; A/B/C/D=45-176.
DR PDB; 6QH4; X-ray; 1.92 A; A/B/C/D=45-176.
DR PDBsum; 3RMU; -.
DR PDBsum; 6QH4; -.
DR AlphaFoldDB; Q96PE7; -.
DR SMR; Q96PE7; -.
DR BioGRID; 124208; 9.
DR IntAct; Q96PE7; 4.
DR STRING; 9606.ENSP00000244217; -.
DR SwissLipids; SLP:000001255; -.
DR iPTMnet; Q96PE7; -.
DR PhosphoSitePlus; Q96PE7; -.
DR BioMuta; MCEE; -.
DR UCD-2DPAGE; Q96PE7; -.
DR EPD; Q96PE7; -.
DR jPOST; Q96PE7; -.
DR MassIVE; Q96PE7; -.
DR MaxQB; Q96PE7; -.
DR PaxDb; Q96PE7; -.
DR PeptideAtlas; Q96PE7; -.
DR PRIDE; Q96PE7; -.
DR ProteomicsDB; 77685; -.
DR Antibodypedia; 31195; 203 antibodies from 22 providers.
DR DNASU; 84693; -.
DR Ensembl; ENST00000244217.6; ENSP00000244217.5; ENSG00000124370.11.
DR GeneID; 84693; -.
DR KEGG; hsa:84693; -.
DR MANE-Select; ENST00000244217.6; ENSP00000244217.5; NM_032601.4; NP_115990.3.
DR UCSC; uc002shs.3; human.
DR CTD; 84693; -.
DR DisGeNET; 84693; -.
DR GeneCards; MCEE; -.
DR GeneReviews; MCEE; -.
DR HGNC; HGNC:16732; MCEE.
DR HPA; ENSG00000124370; Low tissue specificity.
DR MalaCards; MCEE; -.
DR MIM; 251120; phenotype.
DR MIM; 608419; gene.
DR neXtProt; NX_Q96PE7; -.
DR OpenTargets; ENSG00000124370; -.
DR Orphanet; 308425; Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency.
DR PharmGKB; PA30683; -.
DR VEuPathDB; HostDB:ENSG00000124370; -.
DR eggNOG; KOG2944; Eukaryota.
DR GeneTree; ENSGT00940000153941; -.
DR HOGENOM; CLU_046006_5_0_1; -.
DR InParanoid; Q96PE7; -.
DR OMA; IHHICYE; -.
DR OrthoDB; 1543116at2759; -.
DR PhylomeDB; Q96PE7; -.
DR TreeFam; TF313417; -.
DR BioCyc; MetaCyc:HS13124-MON; -.
DR BRENDA; 5.1.99.1; 2681.
DR PathwayCommons; Q96PE7; -.
DR Reactome; R-HSA-71032; Propionyl-CoA catabolism.
DR SignaLink; Q96PE7; -.
DR BioGRID-ORCS; 84693; 16 hits in 1081 CRISPR screens.
DR ChiTaRS; MCEE; human.
DR GenomeRNAi; 84693; -.
DR Pharos; Q96PE7; Tbio.
DR PRO; PR:Q96PE7; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q96PE7; protein.
DR Bgee; ENSG00000124370; Expressed in body of pancreas and 177 other tissues.
DR ExpressionAtlas; Q96PE7; baseline and differential.
DR Genevisible; Q96PE7; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004493; F:methylmalonyl-CoA epimerase activity; IDA:UniProtKB.
DR GO; GO:0046491; P:L-methylmalonyl-CoA metabolic process; IDA:UniProtKB.
DR GO; GO:0019626; P:short-chain fatty acid catabolic process; TAS:Reactome.
DR CDD; cd07249; MMCE; 1.
DR Gene3D; 3.10.180.10; -; 1.
DR InterPro; IPR029068; Glyas_Bleomycin-R_OHBP_Dase.
DR InterPro; IPR017515; MeMalonyl-CoA_epimerase.
DR InterPro; IPR037523; VOC.
DR SUPFAM; SSF54593; SSF54593; 1.
DR TIGRFAMs; TIGR03081; metmalonyl_epim; 1.
DR PROSITE; PS51819; VOC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cobalt; Isomerase; Metal-binding; Mitochondrion;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..36
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 37..176
FT /note="Methylmalonyl-CoA epimerase, mitochondrial"
FT /id="PRO_0000012283"
FT DOMAIN 47..176
FT /note="VOC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT BINDING 50
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /evidence="ECO:0000269|Ref.8"
FT BINDING 122
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /evidence="ECO:0000269|Ref.8"
FT BINDING 172
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /evidence="ECO:0000269|Ref.8"
FT MOD_RES 114
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9D1I5"
FT MOD_RES 150
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9D1I5"
FT MOD_RES 150
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9D1I5"
FT VARIANT 76
FT /note="A -> V (in dbSNP:rs11541017)"
FT /id="VAR_049248"
FT VARIANT 104
FT /note="R -> L (in dbSNP:rs6748672)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_019511"
FT STRAND 45..54
FT /evidence="ECO:0007829|PDB:3RMU"
FT HELIX 58..67
FT /evidence="ECO:0007829|PDB:3RMU"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:3RMU"
FT HELIX 80..82
FT /evidence="ECO:0007829|PDB:3RMU"
FT STRAND 84..90
FT /evidence="ECO:0007829|PDB:3RMU"
FT STRAND 92..101
FT /evidence="ECO:0007829|PDB:3RMU"
FT HELIX 109..114
FT /evidence="ECO:0007829|PDB:3RMU"
FT STRAND 119..128
FT /evidence="ECO:0007829|PDB:3RMU"
FT HELIX 130..139
FT /evidence="ECO:0007829|PDB:3RMU"
FT STRAND 155..161
FT /evidence="ECO:0007829|PDB:3RMU"
FT HELIX 163..166
FT /evidence="ECO:0007829|PDB:6QH4"
FT STRAND 171..175
FT /evidence="ECO:0007829|PDB:3RMU"
SQ SEQUENCE 176 AA; 18749 MW; F783E5DF5D778220 CRC64;
MARVLKAAAA NAVGLFSRLQ APIPTVRASS TSQPLDQVTG SVWNLGRLNH VAIAVPDLEK
AAAFYKNILG AQVSEAVPLP EHGVSVVFVN LGNTKMELLH PLGRDSPIAG FLQKNKAGGM
HHICIEVDNI NAAVMDLKKK KIRSLSEEVK IGAHGKPVIF LHPKDCGGVL VELEQA
