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MCCC1 methylcrotonyl-CoA carboxylase subunit 1 [ Homo sapiens (human) ]

Gene ID: 56922, updated on 11-Apr-2024

Summary

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Official Symbol
MCCC1provided by HGNC
Official Full Name
methylcrotonyl-CoA carboxylase subunit 1provided by HGNC
Primary source
HGNC:HGNC:6936
See related
Ensembl:ENSG00000078070 MIM:609010; AllianceGenome:HGNC:6936
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
MCCA; MCC-B; MCCCalpha
Summary
This gene encodes the large subunit of 3-methylcrotonyl-CoA carboxylase. This enzyme functions as a heterodimer and catalyzes the carboxylation of 3-methylcrotonyl-CoA to form 3-methylglutaconyl-CoA. Mutations in this gene are associated with 3-Methylcrotonylglycinuria, an autosomal recessive disorder of leucine catabolism. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in fat (RPKM 22.0), kidney (RPKM 20.5) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
3q27.1
Exon count:
23
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (183015218..183116196, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (185820313..185922411, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (182733006..182817375, complement)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene defective in cullin neddylation 1 domain containing 1 Neighboring gene C9orf85 pseudogene 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14934 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14935 Neighboring gene uncharacterized LOC105374246 Neighboring gene uncharacterized LOC124906309 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20884 Neighboring gene uncharacterized LOC105374247 Neighboring gene lysosomal associated membrane protein 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20885 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:182877289-182877788 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20886 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14936 Neighboring gene small nucleolar RNA, C/D box 3 pseudogene 4

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. 3-Methylcrotonyl-CoA carboxylase deficiency newborn screening in a population of 536,008: is routine screening necessary? Wang H, et al. J Pediatr Endocrinol Metab, 2019 Dec 18. PMID 31730530
  2. [Clinical and mutational features of maternal 3-methylcrotonyl coenzyme deficiency]. Gong LF, et al. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2013 Oct. PMID 24078573
  3. MCCC1/LAMP3 reduces risk of sporadic Parkinson's disease in Han Chinese. Li NN, et al. Acta Neurol Scand, 2013 Aug. PMID 23496138
  4. Inhibition of 3-methylcrotonyl-CoA carboxylase explains the increased excretion of 3-hydroxyisovaleric acid in valproate-treated patients. Luís PB, et al. J Inherit Metab Dis, 2012 May. PMID 22189597
  5. Cryptic exon activation by disruption of exon splice enhancer: novel mechanism causing 3-methylcrotonyl-CoA carboxylase deficiency. Stucki M, et al. J Biol Chem, 2009 Oct 16. PMID 19706617, Free PMC Article

See all (109) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Methylcrotonyl-CoA carboxylase subunit 1 (MCCA) regulates multidrug resistance in multiple myeloma.
    Title: Methylcrotonyl-CoA carboxylase subunit 1 (MCCA) regulates multidrug resistance in multiple myeloma.
  2. Association study of MCCC1/LAMP3 and DGKQ variants with Parkinson's disease in patients of Malay ancestry.
    Title: Association study of MCCC1/LAMP3 and DGKQ variants with Parkinson's disease in patients of Malay ancestry.
  3. SNPs in SNCA, MCCC1, DLG2, GBF1 and MBNL2 are associated with Parkinson's disease in southern Chinese population.
    Title: SNPs in SNCA, MCCC1, DLG2, GBF1 and MBNL2 are associated with Parkinson's disease in southern Chinese population.
  4. Mutation in the methylcrotonoyl-CoA carboxylase gene is associated with 3-Methylcrotonyl-CoA carboxylase deficiency leading to feeding difficulties and vomiting.
    Title: 3-Methylcrotonyl-CoA carboxylase deficiency newborn screening in a population of 536,008: is routine screening necessary?
  5. Mutations on MCCC1 and MCCC2 genes are the major genetic causes for the increased C5-OH in neonates
    Title: [Genetic analysis of newborns with abnormal metabolism of 3-hydroxyisovalerylcarnitine].
  6. MCCC1 plays an essential role in virus-triggered, MAVS-mediated activation of NF-kappaB signaling.
    Title: Methylcrotonoyl-CoA carboxylase 1 potentiates RLR-induced NF-κB signaling by targeting MAVS complex.
  7. This study reports data mainly obtained from the Portuguese newborn screening program collected over a ten-year period. Analysis of the MCCC1 and MCCC2 genes yielded 26 previously unreported mutations and a variant of clinically unknown significance.
    Title: 3-Methylcrotonyl-CoA carboxylase deficiency: Mutational spectrum derived from comprehensive newborn screening.
  8. Our study provides strong support for the susceptibility role of RAB7L1/NUCKS1 rs823118 and MCCC1 rs12637471 in sporadic Parkinson's disease in a Han Chinese population
    Title: Association of three candidate genetic variants in RAB7L1/NUCKS1, MCCC1 and STK39 with sporadic Parkinson's disease in Han Chinese.
  9. Novel mutations in MCCC1 gene were identified in Chinese population. The expression profiles of two splice mutations (c.639+2T>A and c.639+5G>T) were also characterized.
    Title: Identification of eight novel mutations and transcript analysis of two splicing mutations in Chinese newborns with MCC deficiency.
  10. Four new point mutations were detected in the MCCC1 gene in patients with maternal 3-methylcrotonyl coenzyme deficiency.
    Title: [Clinical and mutational features of maternal 3-methylcrotonyl coenzyme deficiency].
Submit: New GeneRIF Correction See all GeneRIFs (22)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
3-methylcrotonyl-CoA carboxylase 1 deficiency
MedGen: C0268600 OMIM: 210200 GeneReviews: Not available
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EBI GWAS Catalog

Description
An atlas of genetic influences on human blood metabolites.
EBI GWAS Catalog
Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies.
EBI GWAS Catalog
Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.
EBI GWAS Catalog
Web-based genome-wide association study identifies two novel loci and a substantial genetic component for Parkinson's disease.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Pr55(Gag) gag HIV-1 Gag interacts with MCCC1 as demonstrated by proximity dependent biotinylation proteomics PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ25545, DKFZp686B20267

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables biotin binding NAS
Non-traceable Author Statement
more info
 PubMed 
enables biotin carboxylase activity NAS
Non-traceable Author Statement
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
contributes_to methylcrotonoyl-CoA carboxylase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
contributes_to methylcrotonoyl-CoA carboxylase activity IDA
Inferred from Direct Assay
more info
 PubMed 
contributes_to methylcrotonoyl-CoA carboxylase activity NAS
Non-traceable Author Statement
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in L-leucine catabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in L-leucine catabolic process ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
involved_in L-leucine catabolic process NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in biotin metabolic process NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in branched-chain amino acid catabolic process NAS
Non-traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
part_of 3-methylcrotonyl-CoA carboxylase complex, mitochondrial IPI
Inferred from Physical Interaction
more info
 PubMed 
part_of 3-methylcrotonyl-CoA carboxylase complex, mitochondrial NAS
Non-traceable Author Statement
more info
 PubMed 
part_of 3-methylcrotonyl-CoA carboxylase complex, mitochondrial TAS
Traceable Author Statement
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
part_of methylcrotonoyl-CoA carboxylase complex IDA
Inferred from Direct Assay
more info
 PubMed 
located_in mitochondrial matrix IDA
Inferred from Direct Assay
more info
 PubMed 
located_in mitochondrial matrix NAS
Non-traceable Author Statement
more info
 PubMed 
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial
Names
3-methylcrotonyl-CoA carboxylase 1
3-methylcrotonyl-CoA carboxylase biotin-containing subunit
3-methylcrotonyl-CoA:carbon dioxide ligase subunit alpha
MCCase subunit alpha
methylcrotonoyl-CoA carboxylase 1 (alpha)
methylcrotonoyl-CoA carboxylase alpha
methylcrotonoyl-Coenzyme A carboxylase 1 (alpha)
NP_001280202.1
NP_001350809.1
NP_064551.3
XP_011511294.1
XP_047304542.1
XP_047304543.1
XP_047304544.1
XP_047304545.1
XP_047304546.1
XP_047304547.1
XP_054203243.1
XP_054203244.1
XP_054203245.1
XP_054203246.1
XP_054203247.1
XP_054203248.1
XP_054203249.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008100.2 RefSeqGene

    Range
    21700..105978
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001293273.2 → NP_001280202.1  methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial isoform 2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded protein (isoform 2) has a shorter and distinct N-terminus, compared to isoform 1.
    Source sequence(s)
    AB029826, BC004214, CR749608
    UniProtKB/TrEMBL
    Q68D27
    Conserved Domains (3) summary
    cd06850
    Location:534 → 597
    biotinyl_domain; The biotinyl-domain or biotin carboxyl carrier protein (BCCP) domain is present in all biotin-dependent enzymes, such as acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, geranyl-CoA carboxylase, ...
    smart00878
    Location:266 → 372
    Biotin_carb_C; Biotin carboxylase C-terminal domain
    pfam02786
    Location:48 → 252
    CPSase_L_D2; Carbamoyl-phosphate synthase L chain, ATP binding domain

  2. NM_001363880.1 → NP_001350809.1  methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial isoform 3

    Status: VALIDATED

    Description
    Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1.
    Source sequence(s)
    AC104641, AC108741
    Consensus CDS
    CCDS87170.1
    UniProtKB/TrEMBL
    E9PHF7, Q68D27
    Conserved Domains (1) summary
    cl27361
    Location:2 → 607
    Biotin_carb_C; Biotin carboxylase C-terminal domain

  3. NM_020166.5 → NP_064551.3  methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial isoform 1 precursor

    See identical proteins and their annotated locations for NP_064551.3

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (1).
    Source sequence(s)
    AB029826, AL556872, BC004214
    Consensus CDS
    CCDS3241.1
    UniProtKB/Swiss-Prot
    Q59ES4, Q96RQ3, Q9H959, Q9NS97
    UniProtKB/TrEMBL
    A0A0S2Z693, E9PG35
    Related
    ENSP00000265594.4, ENST00000265594.9
    Conserved Domains (5) summary
    cd06850
    Location:651 → 714
    biotinyl_domain; The biotinyl-domain or biotin carboxyl carrier protein (BCCP) domain is present in all biotin-dependent enzymes, such as acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, geranyl-CoA carboxylase, ...
    smart00878
    Location:383 → 489
    Biotin_carb_C; Biotin carboxylase C-terminal domain
    COG4770
    Location:49 → 716
    PccA; Acetyl/propionyl-CoA carboxylase, alpha subunit [Lipid transport and metabolism]
    pfam00289
    Location:49 → 157
    CPSase_L_chain; Carbamoyl-phosphate synthase L chain, N-terminal domain
    pfam02786
    Location:163 → 369
    CPSase_L_D2; Carbamoyl-phosphate synthase L chain, ATP binding domain

RNA

  1. NR_120639.2 RNA Sequence

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) lacks two internal exons, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AB029826, AK294882, AL556872, BC004214
    Related
    ENST00000495767.5

  2. NR_120640.2 RNA Sequence

    Status: VALIDATED

    Description
    Transcript Variant: This variant (4) has multiple differences, compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.
    Source sequence(s)
    AC104641, AL556872, BC004214, BC042453
    Related
    ENST00000497959.5

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    183015218..183116196 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047448586.1 → XP_047304542.1  methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial isoform X1

  2. XM_011512992.3 → XP_011511294.1  methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial isoform X2

    UniProtKB/TrEMBL
    Q68D27
    Conserved Domains (5) summary
    cd06850
    Location:613 → 676
    biotinyl_domain; The biotinyl-domain or biotin carboxyl carrier protein (BCCP) domain is present in all biotin-dependent enzymes, such as acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, geranyl-CoA carboxylase, ...
    smart00878
    Location:345 → 451
    Biotin_carb_C; Biotin carboxylase C-terminal domain
    COG4770
    Location:11 → 678
    PccA; Acetyl/propionyl-CoA carboxylase, alpha subunit [Lipid transport and metabolism]
    pfam00289
    Location:11 → 119
    CPSase_L_chain; Carbamoyl-phosphate synthase L chain, N-terminal domain
    pfam02786
    Location:125 → 331
    CPSase_L_D2; Carbamoyl-phosphate synthase L chain, ATP binding domain

  3. XM_047448588.1 → XP_047304544.1  methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial isoform X4

    UniProtKB/TrEMBL
    E9PHF7
    Related
    ENSP00000419898.1, ENST00000492597.5

  4. XM_047448589.1 → XP_047304545.1  methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial isoform X4

    UniProtKB/TrEMBL
    E9PHF7

  5. XM_047448587.1 → XP_047304543.1  methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial isoform X3

  6. XM_047448591.1 → XP_047304547.1  methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial isoform X6

  7. XM_047448590.1 → XP_047304546.1  methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial isoform X5

    Related
    ENSP00000486824.1, ENST00000629669.2

RNA

  1. XR_007095707.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    185820313..185922411 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054347268.1 → XP_054203243.1  methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial isoform X1

  2. XM_054347269.1 → XP_054203244.1  methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial isoform X2

  3. XM_054347271.1 → XP_054203246.1  methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial isoform X4

  4. XM_054347272.1 → XP_054203247.1  methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial isoform X4

  5. XM_054347270.1 → XP_054203245.1  methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial isoform X3

  6. XM_054347274.1 → XP_054203249.1  methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial isoform X6

  7. XM_054347273.1 → XP_054203248.1  methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial isoform X5

RNA

  1. XR_008486750.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q96RQ3.3 GenPept UniProtKB/Swiss-Prot:Q96RQ3

Gene LinkOut

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