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Q9HCC0 (MCCB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. 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·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial

Short name=MCCase subunit beta
EC=6.4.1.4
Alternative name(s):
3-methylcrotonyl-CoA carboxylase 2
3-methylcrotonyl-CoA carboxylase non-biotin-containing subunit
3-methylcrotonyl-CoA:carbon dioxide ligase subunit beta
Gene names
Name:MCCC2
Synonyms:MCCB
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length563 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Carboxyltransferase subunit of the 3-methylcrotonyl-CoA carboxylase, an enzyme that catalyzes the conversion of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA, a critical step for leucine and isovaleric acid catabolism. Ref.9

Catalytic activity

ATP + 3-methylcrotonoyl-CoA + HCO3- = ADP + phosphate + 3-methylglutaconyl-CoA. Ref.9

Pathway

Amino-acid degradation; L-leucine degradation; (S)-3-hydroxy-3-methylglutaryl-CoA from 3-isovaleryl-CoA: step 2/3.

Subunit structure

Probably a dodecamer composed of six biotin-containing alpha subunits (MCCC1) and six beta (MCCC2) subunits.

Subcellular location

Mitochondrion matrix Ref.2 Ref.8.

Involvement in disease

Methylcrotonoyl-CoA carboxylase 2 deficiency (MCC2D) [MIM:210210]: An autosomal recessive disorder of leucine catabolism. The phenotype is variable, ranging from neonatal onset with severe neurological involvement to asymptomatic adults. There is a characteristic organic aciduria with massive excretion of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine, usually in combination with a severe secondary carnitine deficiency.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.3 Ref.4 Ref.12

Sequence similarities

Belongs to the AccD/PCCB family.

Contains 1 carboxyltransferase domain.

Biophysicochemical properties

Kinetic parameters:

kcat is 4.0 sec(-1).

KM=45 µM for ATP Ref.9

KM=74 µM for 3-methylcrotonyl-CoA

Sequence caution

The sequence AAH14897.1 differs from that shown. Reason: Frameshift at position 359.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9HCC0-1)

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: Q9HCC0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     209-246: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2222Mitochondrion Ref.8
Chain23 – 563541Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial
PRO_0000000291

Regions

Domain55 – 557503Carboxyltransferase
Region343 – 37230Acyl-CoA binding Potential

Amino acid modifications

Modified residue701N6-acetyllysine; alternate By similarity
Modified residue701N6-succinyllysine; alternate By similarity
Modified residue1411N6-succinyllysine By similarity
Modified residue4951N6-acetyllysine; alternate By similarity
Modified residue4951N6-succinyllysine; alternate By similarity
Modified residue5111N6-acetyllysine By similarity

Natural variations

Alternative sequence209 – 24638Missing in isoform 2.
VSP_000069
Natural variant991E → Q in MCC2D; severe and mild form. Ref.3
Corresponds to variant rs28934883 [ dbSNP | Ensembl ].
VAR_012792
Natural variant1551R → Q in MCC2D; mild form. Ref.3
VAR_012793
Natural variant1671C → R in MCC2D. Ref.2
Corresponds to variant rs28934884 [ dbSNP | Ensembl ].
VAR_012794
Natural variant1731S → L in MCC2D; severe form. Ref.3
VAR_012795
Natural variant1931R → C in MCC2D; mild form. Ref.3
VAR_012796
Natural variant2181A → T in MCC2D. Ref.2
VAR_012797
Natural variant2681R → T in MCC2D; asymptomatic form. Ref.4
VAR_012798
Natural variant2801D → Y in MCC2D. Ref.12
Corresponds to variant rs119103226 [ dbSNP | Ensembl ].
VAR_067199
Natural variant3101P → R in MCC2D; mild form. Ref.3
VAR_012799
Natural variant3391V → M in MCC2D; severe form. Ref.3
VAR_012800
Natural variant4371I → V in MCC2D; mild form.
VAR_012801
Natural variant4591P → S in MCC2D. Ref.12
VAR_067200
Natural variant4781A → G.
Corresponds to variant rs35068278 [ dbSNP | Ensembl ].
VAR_038630

Sequences

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

Last modified March 1, 2001. Version 1.
Checksum: 8E3D401AF52DC7D2

FASTA56361,333
        10         20         30         40         50         60 
MWAVLRLALR PCARASPAGP RAYHGDSVAS LGTQPDLGSA LYQENYKQMK ALVNQLHERV 

        70         80         90        100        110        120 
EHIKLGGGEK ARALHISRGK LLPRERIDNL IDPGSPFLEL SQFAGYQLYD NEEVPGGGII 

       130        140        150        160        170        180 
TGIGRVSGVE CMIIANDATV KGGAYYPVTV KKQLRAQEIA MQNRLPCIYL VDSGGAYLPR 

       190        200        210        220        230        240 
QADVFPDRDH FGRTFYNQAI MSSKNIAQIA VVMGSCTAGG AYVPAMADEN IIVRKQGTIF 

       250        260        270        280        290        300 
LAGPPLVKAA TGEEVSAEDL GGADLHCRKS GVSDHWALDD HHALHLTRKV VRNLNYQKKL 

       310        320        330        340        350        360 
DVTIEPSEEP LFPADELYGI VGANLKRSFD VREVIARIVD GSRFTEFKAF YGDTLVTGFA 

       370        380        390        400        410        420 
RIFGYPVGIV GNNGVLFSES AKKGTHFVQL CCQRNIPLLF LQNITGFMVG REYEAEGIAK 

       430        440        450        460        470        480 
DGAKMVAAVA CAQVPKITLI IGGSYGAGNY GMCGRAYSPR FLYIWPNARI SVMGGEQAAN 

       490        500        510        520        530        540 
VLATITKDQR AREGKQFSSA DEAALKEPII KKFEEEGNPY YSSARVWDDG IIDPADTRLV 

       550        560 
LGLSFSAALN APIEKTDFGI FRM 

« Hide

Isoform 2 [UniParc].

Checksum: 344050ABB7A9DE8A
Show »

FASTA52557,519

References

« Hide 'large scale' references
[1]"Human non-biotin containing subunit gene of 3-methylcrotonyl-CoA carboxylase (MCCB)."
Fukuda T., Otsuka H., Morishita R., Takemoto Y., Sone M., Nakao M., Abe S., Kondo I.
Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
[2]"The molecular basis of 3-methylcrotonylglycinuria, a disorder of leucine catabolism."
Gallardo M.E., Desviat L.R., Rodriguez J.M., Esparza-Gordillo J., Perez-Cerda C., Perez B., Rodriguez-Pombo P., Criado O., Sanz R., Morton D.H., Gibson K.M., Le T.P., Ribes A., Rodriguez de Cordoba S., Ugarte M., Penalva M.A.
Am. J. Hum. Genet. 68:334-346(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, VARIANTS MCC2D ARG-167 AND THR-218.
[3]"The molecular basis of human 3-methylcrotonyl-CoA carboxylase deficiency."
Baumgartner M.R., Almashanu S., Suormala T., Obie C., Cole R.N., Packman S., Baumgartner E.R., Valle D.
J. Clin. Invest. 107:495-504(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS MCC2D GLN-99; GLN-155; LEU-173; CYS-193; ARG-310 AND MET-339.
[4]"Cloning of the human MCCA and MCCB genes and mutations therein reveal the molecular cause of 3-methylcrotonyl-CoA: carboxylase deficiency."
Holzinger A., Roeschinger W., Lagler F., Mayerhofer P.U., Lichtner P., Kattenfeld T., Thuy L.P., Nyhan W.L., Koch H.G., Muntau A.C., Roscher A.A.
Hum. Mol. Genet. 10:1299-1306(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT MCC2D THR-268.
[5]"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].
[6]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].
[7]"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] (ISOFORMS 1 AND 2).
Tissue: Testis and Uterus.
[8]"Mitochondrial targeting signals and mature peptides of 3-methylcrotonyl-CoA carboxylase."
Stadler S.C., Polanetz R., Meier S., Mayerhofer P.U., Herrmann J.M., Anslinger K., Roscher A.A., Roschinger W., Holzinger A.
Biochem. Biophys. Res. Commun. 334:939-946(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 23-28, SUBCELLULAR LOCATION.
Tissue: Kidney.
[9]"Expression, purification, characterization of human 3-methylcrotonyl-CoA carboxylase (MCCC)."
Chu C.H., Cheng D.
Protein Expr. Purif. 53:421-427(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
[10]The European IMAGE consortium
Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 469-563.
[11]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Mutational spectrum in eight Korean patients with 3-methylcrotonyl-CoA carboxylase deficiency."
Cho S.Y., Park H.D., Lee Y.W., Ki C.S., Lee S.Y., Sohn Y.B., Park S.W., Kim S.H., Ji S., Kim S.J., Choi E.W., Kim C.H., Ko A.R., Paik K.H., Lee D.H., Jin D.K.
Clin. Genet. 81:96-98(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MCC2D TYR-280 AND SER-459.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB050049 mRNA. Translation: BAB16880.1.
AB050050 Genomic DNA. Translation: BAB41121.1.
AF310971 mRNA. Translation: AAG53094.1.
AF301000 mRNA. Translation: AAK16404.1.
AF261884 mRNA. Translation: AAK49409.1.
AC138832 Genomic DNA. No translation available.
CH471084 Genomic DNA. Translation: EAW95693.1.
BC014897 mRNA. Translation: AAH14897.1. Frameshift.
BC065027 mRNA. Translation: AAH65027.1.
AL079298 mRNA. Translation: CAB45194.1.
CCDSCCDS34184.1. [Q9HCC0-1]
RefSeqNP_071415.1. NM_022132.4. [Q9HCC0-1]
XP_005248624.1. XM_005248567.1. [Q9HCC0-2]
UniGeneHs.604789.

3D structure databases

ProteinModelPortalQ9HCC0.
SMRQ9HCC0. Positions 28-563.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122050. 31 interactions.
IntActQ9HCC0. 12 interactions.
MINTMINT-8051924.
STRING9606.ENSP00000343657.

Chemistry

DrugBankDB00121. Biotin.

PTM databases

PhosphoSiteQ9HCC0.

Polymorphism databases

DMDM20138731.

2D gel databases

REPRODUCTION-2DPAGEIPI00784044.

Proteomic databases

MaxQBQ9HCC0.
PaxDbQ9HCC0.
PRIDEQ9HCC0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000323375; ENSP00000327308; ENSG00000131844. [Q9HCC0-2]
ENST00000340941; ENSP00000343657; ENSG00000131844. [Q9HCC0-1]
ENST00000575361; ENSP00000460647; ENSG00000262057. [Q9HCC0-1]
GeneID64087.
KEGGhsa:64087.
UCSCuc003kbs.4. human. [Q9HCC0-1]

Organism-specific databases

CTD64087.
GeneCardsGC05P070918.
HGNCHGNC:6937. MCCC2.
HPAHPA038300.
HPA038301.
MIM210210. phenotype.
609014. gene.
neXtProtNX_Q9HCC0.
Orphanet6. Isolated 3-methylcrotonyl-CoA carboxylase deficiency.
PharmGKBPA30681.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4799.
HOGENOMHOG000218692.
HOVERGENHBG052424.
InParanoidQ9HCC0.
KOK01969.
OMAYSSARCW.
PhylomeDBQ9HCC0.
TreeFamTF300446.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000131844-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
UniPathwayUPA00363; UER00861.

Gene expression databases

ArrayExpressQ9HCC0.
BgeeQ9HCC0.
CleanExHS_MCCC2.
GenevestigatorQ9HCC0.

Family and domain databases

Gene3D3.90.226.10. 2 hits.
InterProIPR000022. Carboxyl_trans.
IPR029045. ClpP/crotonase-like_dom.
IPR011763. COA_CT_C.
IPR011762. COA_CT_N.
[Graphical view]
PfamPF01039. Carboxyl_trans. 1 hit.
[Graphical view]
SUPFAMSSF52096. SSF52096. 2 hits.
PROSITEPS50989. COA_CT_CTER. 1 hit.
PS50980. COA_CT_NTER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi64087.
NextBio65884.
PROQ9HCC0.
SOURCESearch...

Entry information

Entry nameMCCB_HUMAN
AccessionPrimary (citable) accession number: Q9HCC0
Secondary accession number(s): A6NIY9, Q96C27, Q9Y4L7
Entry history
Integrated into UniProtKB/Swiss-Prot: March 5, 2002
Last sequence update: March 1, 2001
Last modified: July 9, 2014
This is version 134 of the entry and version 1 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