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

    Gene ID: 56922, updated on 10-Dec-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
    mouse all
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    Genomic context

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    See MCCC1 in Genome Data Viewer
    Location:
    3q27.1
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (183015218..183116196, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (185820313..185922411, complement)
    RS_2024_09 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. Familial hypotonia of childhood caused by isolated 3-methylcrotonyl-coenzyme A carboxylase deficiency. Elpeleg ON, et al. J Pediatr, 1992 Sep. PMID 1517917
    2. Methylcrotonyl-CoA carboxylase subunit 1 (MCCA) regulates multidrug resistance in multiple myeloma. Feng Y, et al. Life Sci, 2023 Nov 15. PMID 37805164
    3. 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
    4. MCCC1/LAMP3 reduces risk of sporadic Parkinson's disease in Han Chinese. Li NN, et al. Acta Neurol Scand, 2013 Aug. PMID 23496138
    5. 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

    See all (126) 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
    		Compare labs

    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)

    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
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    part_of methylcrotonoyl-CoA carboxylase complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of methylcrotonoyl-CoA carboxylase complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    part_of methylcrotonoyl-CoA carboxylase complex NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    part_of methylcrotonoyl-CoA carboxylase complex TAS
    Traceable Author Statement
    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
    		  
    located_in mitochondrion HTP PubMed 
    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_2024_08

    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

      UniProtKB/TrEMBL
      Q68D27

    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, Q68D27
      Related
      ENSP00000419898.1, ENST00000492597.5

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

      UniProtKB/TrEMBL
      E9PHF7, Q68D27

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

      UniProtKB/TrEMBL
      E9PG35

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

      UniProtKB/TrEMBL
      G5E9X5

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

      UniProtKB/TrEMBL
      G5E9X5
      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

      UniProtKB/TrEMBL
      Q68D27

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

      UniProtKB/TrEMBL
      Q68D27

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

      UniProtKB/TrEMBL
      Q68D27

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

      UniProtKB/TrEMBL
      Q68D27

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

      UniProtKB/TrEMBL
      E9PG35

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

      UniProtKB/TrEMBL
      G5E9X5

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

      UniProtKB/TrEMBL
      G5E9X5

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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