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Q96RQ3 (MCCA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial

Short name=MCCase subunit alpha
EC=6.4.1.4
Alternative name(s):
3-methylcrotonyl-CoA carboxylase 1
3-methylcrotonyl-CoA carboxylase biotin-containing subunit
3-methylcrotonyl-CoA:carbon dioxide ligase subunit alpha
Gene names
Name:MCCC1
Synonyms:MCCA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length725 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Biotin-attachment 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

Cofactor

Biotin.

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.8.

Involvement in disease

Methylcrotonoyl-CoA carboxylase 1 deficiency (MCC1D) [MIM:210200]: 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.1 Ref.3 Ref.4 Ref.12

Sequence similarities

Contains 1 ATP-grasp domain.

Contains 1 biotin carboxylation domain.

Contains 1 biotinyl-binding domain.

Sequence caution

The sequence BAD92974.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentMitochondrion
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainTransit peptide
   LigandATP-binding
Biotin
Nucleotide-binding
   Molecular functionLigase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processbiotin metabolic process

Non-traceable author statement Ref.2. Source: UniProtKB

branched-chain amino acid catabolic process

Traceable author statement. Source: Reactome

cellular nitrogen compound metabolic process

Traceable author statement. Source: Reactome

leucine catabolic process

Non-traceable author statement Ref.1. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

vitamin metabolic process

Traceable author statement. Source: Reactome

water-soluble vitamin metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

mitochondrial inner membrane

Inferred from electronic annotation. Source: Ensembl

mitochondrial matrix

Non-traceable author statement Ref.1. Source: UniProtKB

mitochondrion

Inferred from direct assay. Source: HPA

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

biotin binding

Non-traceable author statement Ref.2. Source: UniProtKB

biotin carboxylase activity

Inferred from electronic annotation. Source: InterPro

metal ion binding

Inferred from electronic annotation. Source: InterPro

methylcrotonoyl-CoA carboxylase activity

Inferred from direct assay Ref.9. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.9. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 4141Mitochondrion Ref.8
Chain42 – 725684Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial
PRO_0000002833

Regions

Domain48 – 494447Biotin carboxylation
Domain167 – 364198ATP-grasp
Domain629 – 71486Biotinyl-binding

Sites

Active site3391 By similarity
Binding site1631ATP By similarity
Binding site2471ATP By similarity
Binding site2821ATP By similarity

Amino acid modifications

Modified residue2371N6-acetyllysine By similarity
Modified residue4941N6-acetyllysine By similarity
Modified residue5811N6-acetyllysine; alternate By similarity
Modified residue5811N6-succinyllysine; alternate By similarity
Modified residue6811N6-biotinyllysine By similarity

Natural variations

Natural variant2761C → R in MCC1D. Ref.12
VAR_067197
Natural variant2811R → Q in MCC1D. Ref.12
VAR_067198
Natural variant2891A → V in MCC1D; mild form. Ref.4
VAR_012785
Natural variant3251M → R in MCC1D. Ref.1
VAR_012786
Natural variant3851R → S in MCC1D; severe form. Ref.1 Ref.4
Corresponds to variant rs28934881 [ dbSNP | Ensembl ].
VAR_012787
Natural variant4371L → P in MCC1D; severe form. Ref.4
Corresponds to variant rs28934882 [ dbSNP | Ensembl ].
VAR_012788
Natural variant4641H → P. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7
Corresponds to variant rs2270968 [ dbSNP | Ensembl ].
VAR_012789
Natural variant5321D → H in MCC1D; severe form. Ref.4
VAR_012790
Natural variant5351S → F in MCC1D; asymptomatic form. Ref.3
VAR_012791
Natural variant5601N → T.
Corresponds to variant rs35219417 [ dbSNP | Ensembl ].
VAR_038631

Experimental info

Sequence conflict2321R → W in BAD92974. Ref.6
Sequence conflict4691F → L in AAK67986. Ref.3

Secondary structure

............. 725
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q96RQ3 [UniParc].

Last modified May 30, 2006. Version 3.
Checksum: B84AD23806035A40

FASTA72580,473
        10         20         30         40         50         60 
MAAASAVSVL LVAAERNRWH RLPSLLLPPR TWVWRQRTMK YTTATGRNIT KVLIANRGEI 

        70         80         90        100        110        120 
ACRVMRTAKK LGVQTVAVYS EADRNSMHVD MADEAYSIGP APSQQSYLSM EKIIQVAKTS 

       130        140        150        160        170        180 
AAQAIHPGCG FLSENMEFAE LCKQEGIIFI GPPPSAIRDM GIKSTSKSIM AAAGVPVVEG 

       190        200        210        220        230        240 
YHGEDQSDQC LKEHARRIGY PVMIKAVRGG GGKGMRIVRS EQEFQEQLES ARREAKKSFN 

       250        260        270        280        290        300 
DDAMLIEKFV DTPRHVEVQV FGDHHGNAVY LFERDCSVQR RHQKIIEEAP APGIKSEVRK 

       310        320        330        340        350        360 
KLGEAAVRAA KAVNYVGAGT VEFIMDSKHN FCFMEMNTRL QVEHPVTEMI TGTDLVEWQL 

       370        380        390        400        410        420 
RIAAGEKIPL SQEEITLQGH AFEARIYAED PSNNFMPVAG PLVHLSTPRA DPSTRIETGV 

       430        440        450        460        470        480 
RQGDEVSVHY DPMIAKLVVW AADRQAALTK LRYSLRQYNI VGLHTNIDFL LNLSGHPEFE 

       490        500        510        520        530        540 
AGNVHTDFIP QHHKQLLLSR KAAAKESLCQ AALGLILKEK AMTDTFTLQA HDQFSPFSSS 

       550        560        570        580        590        600 
SGRRLNISYT RNMTLKDGKN NVAIAVTYNH DGSYSMQIED KTFQVLGNLY SEGDCTYLKC 

       610        620        630        640        650        660 
SVNGVASKAK LIILENTIYL FSKEGSIEID IPVPKYLSSV SSQETQGGPL APMTGTIEKV 

       670        680        690        700        710        720 
FVKAGDKVKA GDSLMVMIAM KMEHTIKSPK DGTVKKVFYR EGAQANRHTP LVEFEEEESD 


KRESE 

« Hide

References

« Hide 'large scale' references
[1]"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], VARIANTS MCC1D ARG-325 AND SER-385.
[2]"Human biotin-containing subunit of 3-methylcrotonyl-CoA carboxylase gene (MCCA): cDNA sequence, genomic organization, localization to chromosomal band 3q27, and expression."
Obata K., Fukuda T., Morishita R., Abe S., Asakawa S., Yamaguchi S., Yoshino M., Ihara K., Murayama K., Shigemoto K., Shimizu N., Kondo I.
Genomics 72:145-152(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"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], VARIANT MCC1D PHE-535, VARIANT PRO-464.
[4]"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], VARIANTS MCC1D VAL-289; SER-385; PRO-437 AND HIS-532, VARIANT PRO-464.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PRO-464.
[6]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PRO-464.
Tissue: Aorta.
[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], VARIANT PRO-464.
Tissue: Skeletal muscle.
[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 42-47, 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.
[10]"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].
[11]"Solution structure of RSGI RUH-072, an apo-biotinyl domain from human acetyl coenzyme A carboxylase."
RIKEN structural genomics initiative (RSGI)
Submitted (SEP-2007) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 640-725.
[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 MCC1D ARG-276 AND GLN-281.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF310972 mRNA. Translation: AAG53095.1.
AB029826 mRNA. Translation: BAA99407.1.
AF297332 mRNA. Translation: AAK67986.1.
AF310339 mRNA. Translation: AAG50245.1.
AK023051 mRNA. Translation: BAB14377.1.
AB209737 mRNA. Translation: BAD92974.1. Different initiation.
BC004214 mRNA. Translation: AAH04214.1.
BC004187 mRNA. Translation: AAH04187.1.
CCDSCCDS3241.1.
RefSeqNP_064551.3. NM_020166.3.
UniGeneHs.47649.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2EJMNMR-A640-725[»]
ProteinModelPortalQ96RQ3.
SMRQ96RQ3. Positions 47-725.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121249. 25 interactions.
IntActQ96RQ3. 3 interactions.
STRING9606.ENSP00000265594.

Chemistry

DrugBankDB00121. Biotin.

PTM databases

PhosphoSiteQ96RQ3.

Polymorphism databases

DMDM108861983.

Proteomic databases

MaxQBQ96RQ3.
PaxDbQ96RQ3.
PRIDEQ96RQ3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265594; ENSP00000265594; ENSG00000078070.
GeneID56922.
KEGGhsa:56922.
UCSCuc003fle.3. human.

Organism-specific databases

CTD56922.
GeneCardsGC03M182733.
HGNCHGNC:6936. MCCC1.
HPAHPA008310.
MIM210200. phenotype.
609010. gene.
neXtProtNX_Q96RQ3.
Orphanet6. Isolated 3-methylcrotonyl-CoA carboxylase deficiency.
PharmGKBPA30680.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4770.
HOGENOMHOG000008989.
HOVERGENHBG000555.
InParanoidQ96RQ3.
KOK01968.
OMAVDNPRHV.
OrthoDBEOG7RZ5PH.
PhylomeDBQ96RQ3.
TreeFamTF105650.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000078070-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
UniPathwayUPA00363; UER00861.

Gene expression databases

ArrayExpressQ96RQ3.
BgeeQ96RQ3.
CleanExHS_MCCC1.
GenevestigatorQ96RQ3.

Family and domain databases

Gene3D3.30.1490.20. 1 hit.
3.30.470.20. 1 hit.
3.40.50.20. 1 hit.
InterProIPR011761. ATP-grasp.
IPR013815. ATP_grasp_subdomain_1.
IPR013816. ATP_grasp_subdomain_2.
IPR001882. Biotin_BS.
IPR011764. Biotin_carboxylation_dom.
IPR005482. Biotin_COase_C.
IPR000089. Biotin_lipoyl.
IPR005481. CarbamoylP_synth_lsu_N.
IPR005479. CbamoylP_synth_lsu-like_ATP-bd.
IPR016185. PreATP-grasp_dom.
IPR011054. Rudment_hybrid_motif.
IPR011053. Single_hybrid_motif.
[Graphical view]
PfamPF02785. Biotin_carb_C. 1 hit.
PF00364. Biotin_lipoyl. 1 hit.
PF00289. CPSase_L_chain. 1 hit.
PF02786. CPSase_L_D2. 1 hit.
[Graphical view]
SMARTSM00878. Biotin_carb_C. 1 hit.
[Graphical view]
SUPFAMSSF51230. SSF51230. 1 hit.
SSF51246. SSF51246. 1 hit.
SSF52440. SSF52440. 1 hit.
PROSITEPS50975. ATP_GRASP. 1 hit.
PS50979. BC. 1 hit.
PS00188. BIOTIN. 1 hit.
PS50968. BIOTINYL_LIPOYL. 1 hit.
PS00867. CPSASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMCCC1. human.
EvolutionaryTraceQ96RQ3.
GenomeRNAi56922.
NextBio62428.
PROQ96RQ3.
SOURCESearch...

Entry information

Entry nameMCCA_HUMAN
AccessionPrimary (citable) accession number: Q96RQ3
Secondary accession number(s): Q59ES4, Q9H959, Q9NS97
Entry history
Integrated into UniProtKB/Swiss-Prot: March 5, 2002
Last sequence update: May 30, 2006
Last modified: July 9, 2014
This is version 147 of the entry and version 3 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 3

Human chromosome 3: entries, gene names and cross-references to MIM