MCCC1

UniProt ID: Q96RQ3
Organism: Homo sapiens
Review Status: INITIALIZED
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Gene Description

MCCC1 is the biotin-containing alpha subunit of mitochondrial 3-methylcrotonyl-CoA carboxylase (MCC), a biotin-dependent carboxylase (EC 6.4.1.4). MCC catalyses the ATP-dependent carboxylation of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA, the committed carboxylation step of the leucine (and isovalerate) catabolic pathway, downstream of isovaleryl-CoA dehydrogenase. The holoenzyme is an alpha6-beta6 dodecamer assembled from six MCCC1 subunits and six MCCC2 subunits: MCCC1 carries the biotin carboxylase and biotinyl (biotin-carboxyl-carrier) domains, holds the covalently attached biotin cofactor (on a conserved lysine) and binds ATP, while MCCC2 provides the carboxyltransferase activity. The protein is synthesized with an N-terminal mitochondrial transit peptide and functions in the mitochondrial matrix. Loss of MCC activity due to biallelic variants in MCCC1 (or its partner MCCC2) causes 3-methylcrotonyl-CoA carboxylase deficiency, an autosomal recessive organic aciduria that is one of the most common findings on newborn tandem mass spectrometry screening and is frequently benign or asymptomatic.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004485 methylcrotonoyl-CoA carboxylase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetically inferred core molecular function of the MCC alpha subunit. The contributes_to qualifier correctly reflects that the full carboxylase activity is a property of the assembled alpha6-beta6 holoenzyme to which MCCC1 contributes.
Reason: This is the core molecular function of MCCC1. The IBA is consistent with the biochemically characterized activity of the human enzyme.
Supporting Evidence:
PMID:17360195
a heteromultimeric complex that is composed of alpha and beta subunits which are encoded by distinct genes
GO:0005739 mitochondrion
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetic inference of mitochondrial localization. Correct but less specific than the mitochondrial matrix localization supported by direct evidence.
Reason: MCCC1 is a mitochondrial matrix protein; the mitochondrion annotation is correct though the matrix term is more informative.
Supporting Evidence:
PMID:16023992
are imported into the mitochondrial matrix by the classical pathway involving cleavable amino-terminal targeting presequences
GO:0004485 methylcrotonoyl-CoA carboxylase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: Electronic inference (RHEA:13589 / EC 6.4.1.4) of the core carboxylase activity, consistent with the curated catalytic activity in UniProt.
Reason: Correctly maps the EC 6.4.1.4 / RHEA:13589 reaction to the core MCC activity.
Supporting Evidence:
PMID:17360195
a heteromultimeric complex that is composed of alpha and beta subunits which are encoded by distinct genes
GO:0005524 ATP binding
IEA
GO_REF:0000002 		ACCEPT
Summary: InterPro-based inference of ATP binding, consistent with the ATP-grasp domain of the biotin carboxylase module that binds ATP during the carboxylation reaction.
Reason: MCCC1 contains an ATP-grasp domain and binds ATP as part of the biotin carboxylation half-reaction (curated ATP-binding residues in UniProt).
Supporting Evidence:
PMID:11401427
biotin carboxylase, and biotin-carrier domains
GO:0005759 mitochondrial matrix
IEA
GO_REF:0000120 		ACCEPT
Summary: Electronic inference of mitochondrial matrix localization (UniProt-SubCell SL-0170), matching direct experimental evidence.
Reason: MCCC1 is imported into and functions in the mitochondrial matrix.
Supporting Evidence:
PMID:16023992
are imported into the mitochondrial matrix by the classical pathway involving cleavable amino-terminal targeting presequences
GO:0046872 metal ion binding
IEA
GO_REF:0000002 		ACCEPT
Summary: InterPro (ATP-grasp) inference of metal ion binding. ATP-grasp carboxylase domains use a divalent metal (Mg2+) for ATP-dependent catalysis, so a generic metal-ion-binding inference is biologically plausible but uninformative.
Reason: Divalent metal (Mg2+) coordination is expected for the ATP-grasp biotin carboxylase reaction; the generic term is a reasonable, if low-information, InterPro inference and is not contradicted by evidence.
Supporting Evidence:
PMID:22869039
biotin carboxylase (BC), carboxyltransferase (CT), and biotin-carboxyl carrier protein components
GO:0005515 protein binding
IPI
PMID:17360195
Expression, purification, characterization of human 3-methyl... 		MARK AS OVER ANNOTATED
Summary: IntAct protein-binding annotation capturing the MCCC1-MCCC2 (Q9HCC0) interaction, i.e. assembly of the MCC holoenzyme. The bare protein binding term is uninformative; the biologically meaningful interaction is captured by the methylcrotonoyl-CoA carboxylase complex annotation.
Reason: Bare GO:0005515 provides no functional information beyond the fact of an interaction. The relevant partner here is the obligate holoenzyme subunit MCCC2, already captured by GO:1905202 (methylcrotonoyl-CoA carboxylase complex). Retained (not removed) per curation policy on protein-binding IPIs.
Supporting Evidence:
PMID:17360195
stoichiometry of alpha and beta subunits are at a one:one ratio
GO:0005515 protein binding
IPI
PMID:27499296
Mitochondrial Protein Interaction Mapping Identifies Regulat... 		MARK AS OVER ANNOTATED
Summary: IntAct protein-binding annotation from a high-throughput mitochondrial interaction mapping study (partner MCCC2/Q9HCC0). Uninformative bare-binding term.
Reason: Bare GO:0005515 from a high-throughput screen; the meaningful holoenzyme partnership with MCCC2 is captured by GO:1905202. Retained per policy on protein-binding IPIs.
Supporting Evidence:
PMID:27499296
Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function
GO:0005515 protein binding
IPI
PMID:28514442
Architecture of the human interactome defines protein commun... 		MARK AS OVER ANNOTATED
Summary: IntAct protein-binding annotation from the BioPlex human interactome (partner OXCT2/Q9BYC2). Bare-binding term with no functional content.
Reason: Bare GO:0005515 from high-throughput AP-MS. The OXCT2 co-purification is a mitochondrial-matrix proximity/co-complex observation without established functional meaning for MCCC1. Retained per policy on protein-binding IPIs.
Supporting Evidence:
PMID:28514442
Architecture of the human interactome defines protein communities and disease networks
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling... 		MARK AS OVER ANNOTATED
Summary: IntAct protein-binding annotation from BioPlex 3.0 (partner OXCT2/Q9BYC2). Bare-binding term.
Reason: Bare GO:0005515 from high-throughput interactome data; no specific molecular function conveyed. Retained per policy on protein-binding IPIs.
Supporting Evidence:
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling... 		MARK AS OVER ANNOTATED
Summary: Second IntAct protein-binding annotation from BioPlex 3.0 for the same paper, capturing the MCCC1-MCCC2 (Q9HCC0) holoenzyme interaction. Bare-binding term.
Reason: Bare GO:0005515 from a high-throughput screen; the MCCC2 partnership is already represented by GO:1905202. Retained per policy on protein-binding IPIs.
Supporting Evidence:
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome
GO:0005515 protein binding
IPI
PMID:40205054
Multimodal cell maps as a foundation for structural and func... 		MARK AS OVER ANNOTATED
Summary: IntAct protein-binding annotation from a multimodal cell-mapping resource (partner MCCC2/Q9HCC0). Bare-binding term.
Reason: Bare GO:0005515 from a high-throughput mapping study; the MCCC2 holoenzyme partnership is captured by GO:1905202. Retained per policy on protein-binding IPIs.
Supporting Evidence:
PMID:40205054
Multimodal cell maps as a foundation for structural and functional genomics
GO:0006552 L-leucine catabolic process
IEA
GO_REF:0000120 		ACCEPT
Summary: Electronic inference (UniPathway UPA00363, L-leucine degradation) of the core biological process in which MCC acts.
Reason: MCC catalyses the committed carboxylation step of leucine catabolism; this is the core biological process.
Supporting Evidence:
PMID:11401427
plays an essential role in the catabolism of leucine and isovalerate
GO:0005759 mitochondrial matrix
IDA
PMID:17360195
Expression, purification, characterization of human 3-methyl... 		ACCEPT
Summary: Direct assignment (ComplexPortal) of mitochondrial matrix localization for the MCC complex, consistent with import studies.
Reason: MCCC1 is a mitochondrial matrix protein; this is the core cellular location.
Supporting Evidence:
PMID:16023992
are imported into the mitochondrial matrix by the classical pathway involving cleavable amino-terminal targeting presequences
GO:0009083 branched-chain amino acid catabolic process
NAS
PMID:17360195
Expression, purification, characterization of human 3-methyl... 		KEEP AS NON CORE
Summary: Leucine is a branched-chain amino acid, so MCC participation in leucine catabolism is subsumed by branched-chain amino acid catabolism. This parent term is correct but less specific than L-leucine catabolic process.
Reason: Biologically correct but a generalization of the more precise leucine-catabolism annotation; MCC specifically acts on the leucine branch, not other BCAAs (valine/isoleucine).
Supporting Evidence:
PMID:11401427
plays an essential role in the catabolism of leucine and isovalerate
GO:1905202 methylcrotonoyl-CoA carboxylase complex
IPI
PMID:17360195
Expression, purification, characterization of human 3-methyl... 		ACCEPT
Summary: MCCC1 is a subunit of the alpha6-beta6 methylcrotonoyl-CoA carboxylase holoenzyme, directly demonstrated by expression, purification and characterization of the assembled human complex.
Reason: Core cellular-component annotation; MCCC1 is an integral subunit of the MCC complex.
Supporting Evidence:
PMID:17360195
a heteromultimeric complex that is composed of alpha and beta subunits which are encoded by distinct genes
GO:0005739 mitochondrion
IDA
GO_REF:0000052 		ACCEPT
Summary: Immunofluorescence-based (HPA) mitochondrial localization. Correct but less specific than the mitochondrial matrix.
Reason: Consistent with the established mitochondrial matrix localization; the matrix term is more informative.
Supporting Evidence:
PMID:16023992
are imported into the mitochondrial matrix by the classical pathway involving cleavable amino-terminal targeting presequences
GO:0004485 methylcrotonoyl-CoA carboxylase activity
EXP
PMID:32561715
Leucine regulates autophagy via acetylation of the mTORC1 co... 		ACCEPT
Summary: Experimental-code annotation of the core carboxylase activity. UniProt attaches the catalytic-activity claim to this paper, which studies MCCC1 as the leucine-metabolizing enzyme via knockdown; the enzymatic function itself is most directly supported by the biochemical characterization in PMID:17360195.
Reason: The core molecular function of MCCC1. The annotated activity is well established biochemically for the assembled MCC enzyme.
Supporting Evidence:
PMID:32561715
the Leu-metabolizing enzyme MCCC1
PMID:17360195
a heteromultimeric complex that is composed of alpha and beta subunits which are encoded by distinct genes
GO:0005739 mitochondrion
HTP
PMID:34800366
Quantitative high-confidence human mitochondrial proteome an... 		ACCEPT
Summary: High-throughput mitochondrial proteomics detection. Correct but less specific than the mitochondrial matrix.
Reason: Consistent with the established mitochondrial localization of MCCC1.
Supporting Evidence:
PMID:34800366
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-9909466 		ACCEPT
Summary: Reactome traceable-author-statement placing MCCC1 in the mitochondrial matrix, consistent with all other localization evidence.
Reason: Core cellular location, consistent with direct import/localization studies.
Supporting Evidence:
PMID:16023992
are imported into the mitochondrial matrix by the classical pathway involving cleavable amino-terminal targeting presequences
GO:1905202 methylcrotonoyl-CoA carboxylase complex
IDA
PMID:17360195
Expression, purification, characterization of human 3-methyl... 		ACCEPT
Summary: Direct-assignment (UniProt) membership in the MCC holoenzyme complex, duplicate of the ComplexPortal IPI annotation.
Reason: Core cellular-component annotation; MCCC1 is an integral subunit of the MCC complex.
Supporting Evidence:
PMID:17360195
a heteromultimeric complex that is composed of alpha and beta subunits which are encoded by distinct genes
GO:0004485 methylcrotonoyl-CoA carboxylase activity
IDA
PMID:17360195
Expression, purification, characterization of human 3-methyl... 		ACCEPT
Summary: Direct assay of the recombinant human MCC holoenzyme with measurable carboxylase kinetics; MCCC1 contributes the biotin carboxylase and biotinyl components of the activity.
Reason: This is the primary experimental evidence for the core molecular function of MCC and is the best-supported carboxylase-activity annotation.
Supporting Evidence:
PMID:17360195
possesses K(m) values (ATP: 45+/-11microM; 3-methylcrotonyl-CoA: 74+/-7microM) similar to those reported for the native enzyme
GO:0004075 biotin carboxylase activity
NAS
PMID:22869039
Structure and function of biotin-dependent carboxylases. 		MARK AS OVER ANNOTATED
Summary: Biotin carboxylase (BC) is a component activity of the biotin carboxylase domain that MCCC1 contributes to the holoenzyme; it is a partial reaction, not the committed cellular molecular function of MCC (methylcrotonoyl-CoA carboxylase activity).
Reason: The BC half-reaction is a mechanistic sub-step shared by all biotin-dependent carboxylases and is captured within GO:0004485; asserting a standalone biotin carboxylase activity for MCCC1 over-annotates a domain-level partial reaction. Sourced from a family-level review (NAS).
Supporting Evidence:
PMID:22869039
biotin carboxylase (BC), carboxyltransferase (CT), and biotin-carboxyl carrier protein components
GO:0004485 methylcrotonoyl-CoA carboxylase activity
NAS
PMID:11170888
The molecular basis of 3-methylcrotonylglycinuria, a disorde... 		ACCEPT
Summary: Non-traceable assertion of the core carboxylase activity from the primary MCCA characterization paper.
Reason: Core molecular function; consistent with all experimental and inferred evidence.
Supporting Evidence:
PMID:11170888
MCC, an heteromeric enzyme consisting of alpha (biotin-containing) and beta subunits
GO:0004485 methylcrotonoyl-CoA carboxylase activity
NAS
PMID:11181649
The molecular basis of human 3-methylcrotonyl-CoA carboxylas... 		ACCEPT
Summary: Non-traceable assertion of the core carboxylase activity from an independent primary characterization of MCC deficiency.
Reason: Core molecular function; consistent with all other evidence.
Supporting Evidence:
PMID:11181649
MCC is a heteromeric mitochondrial enzyme composed of biotin-containing alpha subunits and smaller beta subunits
GO:0004485 methylcrotonoyl-CoA carboxylase activity
NAS
PMID:11401427
Human biotin-containing subunit of 3-methylcrotonyl-CoA carb... 		ACCEPT
Summary: Non-traceable assertion of the core carboxylase activity from the MCCA cDNA/genomic characterization paper.
Reason: Core molecular function; consistent with all other evidence.
Supporting Evidence:
PMID:11401427
plays an essential role in the catabolism of leucine and isovalerate
GO:0006768 biotin metabolic process
NAS
PMID:22869039
Structure and function of biotin-dependent carboxylases. 		MARK AS OVER ANNOTATED
Summary: MCCC1 uses biotin as a covalently attached cofactor but does not participate in biotin biosynthesis or turnover. Annotating a biotin metabolic process conflates the requirement for the biotin cofactor with actual biotin metabolism.
Reason: MCCC1's biological process is leucine catabolism; its dependence on the biotin cofactor does not make it a participant in biotin metabolism. Sourced from a family-level review (NAS).
Supporting Evidence:
PMID:22869039
Biotin-dependent carboxylases include acetyl-CoA carboxylase (ACC),
GO:1905202 methylcrotonoyl-CoA carboxylase complex
NAS
PMID:11170888
The molecular basis of 3-methylcrotonylglycinuria, a disorde... 		ACCEPT
Summary: Non-traceable assertion of MCC complex membership from the primary MCCA characterization.
Reason: Core cellular-component annotation; MCCC1 is an integral subunit of the MCC holoenzyme.
Supporting Evidence:
PMID:11170888
MCC, an heteromeric enzyme consisting of alpha (biotin-containing) and beta subunits
GO:1905202 methylcrotonoyl-CoA carboxylase complex
NAS
PMID:11181649
The molecular basis of human 3-methylcrotonyl-CoA carboxylas... 		ACCEPT
Summary: Non-traceable assertion of MCC complex membership from an independent primary study.
Reason: Core cellular-component annotation; MCCC1 is an integral subunit of the MCC holoenzyme.
Supporting Evidence:
PMID:11181649
MCC is a heteromeric mitochondrial enzyme composed of biotin-containing alpha subunits and smaller beta subunits
GO:1905202 methylcrotonoyl-CoA carboxylase complex
NAS
PMID:11401427
Human biotin-containing subunit of 3-methylcrotonyl-CoA carb... 		ACCEPT
Summary: Non-traceable assertion of MCC complex membership from the MCCA cDNA characterization paper.
Reason: Core cellular-component annotation; MCCC1 is an integral subunit of the MCC holoenzyme.
Supporting Evidence:
PMID:11401427
MCCase consists of two subunits,
GO:1905202 methylcrotonoyl-CoA carboxylase complex
TAS
PMID:22869039
Structure and function of biotin-dependent carboxylases. 		ACCEPT
Summary: Traceable-author-statement membership in the MCC complex, from the biotin-dependent carboxylase structure/function review.
Reason: Core cellular-component annotation; MCC assembles into a defined holoenzyme.
Supporting Evidence:
PMID:22869039
biotin carboxylase (BC), carboxyltransferase (CT), and biotin-carboxyl carrier protein components
GO:0005759 mitochondrial matrix
IDA
PMID:16023992
Mitochondrial targeting signals and mature peptides of 3-met... 		ACCEPT
Summary: Direct experimental evidence (protein import and presequence-cleavage analysis) that MCCC1 localizes to the mitochondrial matrix.
Reason: Primary experimental support for the core mitochondrial matrix location.
Supporting Evidence:
PMID:16023992
are imported into the mitochondrial matrix by the classical pathway involving cleavable amino-terminal targeting presequences
GO:0006552 L-leucine catabolic process
ISS
PMID:11170888
The molecular basis of 3-methylcrotonylglycinuria, a disorde... 		ACCEPT
Summary: Sequence-similarity-based assignment of the core leucine catabolic process, supported in the same work by an mccA-null fungal model demonstrating the in vivo role of MCC in leucine catabolism.
Reason: Core biological process; MCC catalyses the committed carboxylation step of leucine degradation.
Supporting Evidence:
PMID:11170888
to demonstrate, in vivo, the involvement of MCC in leucine catabolism
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-3065959 		ACCEPT
Summary: Reactome traceable-author-statement placing MCCC1 in the mitochondrial matrix (protein degradation reaction context).
Reason: Core cellular location, consistent with all other evidence.
Supporting Evidence:
PMID:16023992
are imported into the mitochondrial matrix by the classical pathway involving cleavable amino-terminal targeting presequences
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-3323111 		ACCEPT
Summary: Reactome traceable-author-statement placing MCCC1 in the mitochondrial matrix.
Reason: Core cellular location, consistent with all other evidence.
Supporting Evidence:
PMID:16023992
are imported into the mitochondrial matrix by the classical pathway involving cleavable amino-terminal targeting presequences
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-508308 		ACCEPT
Summary: Reactome traceable-author-statement placing MCCC1 in the mitochondrial matrix (carboxylation reaction context).
Reason: Core cellular location, consistent with all other evidence.
Supporting Evidence:
PMID:16023992
are imported into the mitochondrial matrix by the classical pathway involving cleavable amino-terminal targeting presequences
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-70773 		ACCEPT
Summary: Reactome traceable-author-statement placing MCCC1 in the mitochondrial matrix (carboxylation reaction context).
Reason: Core cellular location, consistent with all other evidence.
Supporting Evidence:
PMID:16023992
are imported into the mitochondrial matrix by the classical pathway involving cleavable amino-terminal targeting presequences
GO:0005829 cytosol
TAS
Reactome:R-HSA-2993799 		MARK AS OVER ANNOTATED
Summary: Reactome models newly translated carboxylase subunits transiently in the cytosol before mitochondrial import (HLCS biotinylation / translocation reactions). MCCC1 is not a steady-state cytosolic protein; its mature functional location is the mitochondrial matrix.
Reason: The cytosolic annotation reflects a transient pre-import biosynthetic intermediate in the Reactome pathway, not a functional cytosolic localization. MCCC1 carries a cleavable mitochondrial transit peptide and functions in the matrix.
Supporting Evidence:
PMID:16023992
are imported into the mitochondrial matrix by the classical pathway involving cleavable amino-terminal targeting presequences
GO:0005829 cytosol
TAS
Reactome:R-HSA-3323111 		MARK AS OVER ANNOTATED
Summary: Reactome cytosolic annotation reflecting the pre-import translocation step (cytosolic carboxylases translocate to mitochondrial matrix), not a functional steady-state cytosolic location.
Reason: Transient pre-import intermediate; MCCC1's mature functional compartment is the mitochondrial matrix.
Supporting Evidence:
PMID:16023992
are imported into the mitochondrial matrix by the classical pathway involving cleavable amino-terminal targeting presequences
GO:0005829 cytosol
TAS
Reactome:R-HSA-9035987 		MARK AS OVER ANNOTATED
Summary: Reactome cytosolic annotation from the defective-HLCS biotinylation reaction, representing the transient pre-import state rather than a functional cytosolic localization.
Reason: Transient pre-import intermediate; MCCC1's mature functional compartment is the mitochondrial matrix.
Supporting Evidence:
PMID:16023992
are imported into the mitochondrial matrix by the classical pathway involving cleavable amino-terminal targeting presequences
GO:0005759 mitochondrial matrix
NAS
PMID:11170888
The molecular basis of 3-methylcrotonylglycinuria, a disorde... 		ACCEPT
Summary: Non-traceable assertion of mitochondrial matrix localization from the primary MCCA characterization.
Reason: Core cellular location, consistent with direct experimental import studies.
Supporting Evidence:
PMID:16023992
are imported into the mitochondrial matrix by the classical pathway involving cleavable amino-terminal targeting presequences
GO:0006552 L-leucine catabolic process
NAS
PMID:11170888
The molecular basis of 3-methylcrotonylglycinuria, a disorde... 		ACCEPT
Summary: Non-traceable assertion of the core leucine catabolic process, supported by the mccA-null fungal complementation model in the same paper.
Reason: Core biological process; MCC catalyses the committed carboxylation step of leucine degradation.
Supporting Evidence:
PMID:11170888
to demonstrate, in vivo, the involvement of MCC in leucine catabolism
GO:0006768 biotin metabolic process
NAS
PMID:11401427
Human biotin-containing subunit of 3-methylcrotonyl-CoA carb... 		MARK AS OVER ANNOTATED
Summary: MCCC1 requires biotin as a covalently attached cofactor but does not participate in biotin biosynthesis or turnover; the biotin metabolic process annotation conflates cofactor usage with biotin metabolism.
Reason: MCCC1's biological process is leucine (and isovalerate) catabolism; being a biotin-dependent enzyme does not make it a participant in biotin metabolism.
Supporting Evidence:
PMID:11401427
plays an essential role in the catabolism of leucine and isovalerate
GO:0009374 biotin binding
NAS
PMID:11401427
Human biotin-containing subunit of 3-methylcrotonyl-CoA carb... 		ACCEPT
Summary: MCCC1 carries a biotinyl (biotin-carrier) domain and holds the covalently attached biotin cofactor on a conserved lysine (Lys681), consistent with a biotin-binding molecular function.
Reason: MCCC1 is the biotin-containing subunit; biotin binding/carriage is a genuine, structurally supported molecular function of the biotinyl-binding domain.
Supporting Evidence:
PMID:11401427
biotin carboxylase, and biotin-carrier domains

Core Functions

MCC alpha subunit contributes the biotin carboxylase and biotin-carrier activities to the mitochondrial 3-methylcrotonyl-CoA carboxylase holoenzyme, which catalyses the ATP-dependent carboxylation of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA.

Molecular Function:
methylcrotonoyl-CoA carboxylase activity
Directly Involved In:
L-leucine catabolic process
Cellular Locations:
mitochondrial matrix
In Complex:
methylcrotonoyl-CoA carboxylase complex
Supporting Evidence:
  • PMID:17360195
    a heteromultimeric complex that is composed of alpha and beta subunits which are encoded by distinct genes
  • PMID:11401427
    plays an essential role in the catabolism of leucine and isovalerate

Binds the biotin cofactor via the C-terminal biotinyl-binding domain, covalently attaching biotin on a conserved lysine to enable the carboxyl-transfer steps of the carboxylase reaction.

Molecular Function:
biotin binding
Cellular Locations:
mitochondrial matrix
Supporting Evidence:

Binds ATP through its ATP-grasp biotin carboxylase domain, providing the energy for carboxylation of the biotin cofactor.

Molecular Function:
ATP binding
Cellular Locations:
mitochondrial matrix
Supporting Evidence:
  • PMID:17360195
    possesses K(m) values (ATP: 45+/-11microM; 3-methylcrotonyl-CoA: 74+/-7microM) similar to those reported for the native enzyme

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:11170888
The molecular basis of 3-methylcrotonylglycinuria, a disorder of leucine catabolism.
  • MCC is a heteromeric biotin-dependent enzyme with a biotin-containing alpha subunit (MCCC1) and a beta subunit; a fungal mccA-null model established the in vivo involvement of MCC in leucine catabolism.
PMID:11181649
The molecular basis of human 3-methylcrotonyl-CoA carboxylase deficiency.
  • MCC is a heteromeric mitochondrial enzyme composed of biotin-containing alpha subunits and smaller beta subunits; MCCA missense mutations cause loss of function.
PMID:11401427
Human biotin-containing subunit of 3-methylcrotonyl-CoA carboxylase gene (MCCA): cDNA sequence, genomic organization, localization to chromosomal band 3q27, and expression.
  • The MCCA cDNA encodes a 725-residue protein with a mitochondrial signal peptide, biotin carboxylase, and biotin-carrier domains; MCCase is a mitochondrial biotin enzyme essential for leucine and isovalerate catabolism, abundantly expressed in mitochondria-rich organs.
PMID:16023992
Mitochondrial targeting signals and mature peptides of 3-methylcrotonyl-CoA carboxylase.
  • Both MCC subunits are imported into the mitochondrial matrix by the classical presequence pathway; the MCCalpha cleavage site is Tyr41/Thr42.
PMID:17360195
Expression, purification, characterization of human 3-methylcrotonyl-CoA carboxylase (MCCC).
  • Recombinant human MCCC is a heteromultimeric alpha/beta complex (~500-800 kDa) with a 1:1 alpha:beta stoichiometry and measurable carboxylase kinetics (kcat ~4 s-1; Km ATP 45 uM, 3-methylcrotonyl-CoA 74 uM).
PMID:22869039
Structure and function of biotin-dependent carboxylases.
  • Biotin-dependent carboxylases (including MCC) contain biotin carboxylase (BC), carboxyltransferase (CT), and biotin-carboxyl carrier protein components; MCC deficiency is linked to human disease.
PMID:27499296
Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function.
PMID:28514442
Architecture of the human interactome defines protein communities and disease networks.
PMID:32561715
Leucine regulates autophagy via acetylation of the mTORC1 component raptor.
  • MCCC1 is described as a key enzyme in the leucine metabolic pathway; siRNA knockdown of MCCC1 perturbs leucine metabolism and thereby modulates mTORC1 activity and autophagy.
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
PMID:34800366
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
  • MCCC1 is detected as part of a quantitative high-confidence human mitochondrial proteome.
PMID:40205054
Multimodal cell maps as a foundation for structural and functional genomics.
Reactome:R-HSA-2993799
HLCS biotinylates 6xMCCC1:6xMCCC2
Reactome:R-HSA-3065959
An unknown protease degrades hCBXs
Reactome:R-HSA-3323111
Cytosolic carboxylases translocate to mitochondrial matrix
Reactome:R-HSA-508308
beta-methylglutaconyl-CoA + ADP + orthophosphate <=> beta-methylcrotonyl-CoA + ATP + HCO3- (MCCA)
Reactome:R-HSA-70773
beta-methylcrotonyl-CoA + ATP + HCO3- <=> beta-methylglutaconyl-CoA + ADP + orthophosphate + H2O (MCCA)
Reactome:R-HSA-9035987
Defective HLCS does not biotinylate 6xMCCC1:6xMCCC2
Reactome:R-HSA-9909466
MCCC mutants don't synthesize beta-methylglutaconyl-CoA

📚 Additional Documentation

Notes

(MCCC1-notes.md)

MCCC1 (Q96RQ3) review notes

Deep research status

just deep-research-falcon human Q96RQ3 fails in this worktree: scripts/deep_research_wrapper.py
is executed under system Python 3.9.5, which cannot evaluate the dict | None annotation at import
time (TypeError: unsupported operand type(s) for |: 'type' and 'NoneType'). This is a pre-existing
environment/venv-selection issue, not a content problem. No -deep-research-falcon.md was produced;
I did NOT fabricate one. Review grounded in UniProt (Q96RQ3), the seeded GOA TSV, the dismech disorder
KB (3-Methylcrotonyl-CoA_Carboxylase_Deficiency.yaml), and cached publications/PMID_*.md.

Verified biology

MCCC1 = biotin-containing alpha subunit of mitochondrial 3-methylcrotonyl-CoA carboxylase (MCC),
a biotin-dependent carboxylase (EC 6.4.1.4). MCC catalyses the ATP-dependent carboxylation of
3-methylcrotonyl-CoA -> 3-methylglutaconyl-CoA, the committed carboxylation step of leucine catabolism
(downstream of isovaleryl-CoA dehydrogenase / IVD; L-leucine degradation UniPathway UPA00363, step 2/3
to HMG-CoA). Holoenzyme is an alpha6-beta6 dodecamer of MCCC1 (biotin carboxylase + biotinyl/BCCP
domain, carries biotin at Lys681, binds ATP) and MCCC2 (carboxyltransferase). Mitochondrial matrix
(N-terminal transit peptide 1-41, cleaved at Tyr41/Thr42; PMID:16023992). Deficiency of MCCC1 or MCCC2 =
3-methylcrotonyl-CoA carboxylase deficiency (3-MCC / MCC1D, MIM:210200), a common newborn-screening
finding, often benign/asymptomatic.

Key supporting quotes (verbatim, grep-verified in cache)

  • PMID:17360195 (abstract-only cache): "a heteromultimeric complex that is composed of alpha and beta
    subunits which are encoded by distinct genes"; "the stoichiometry of alpha and beta subunits are at
    a one:one ratio"; Km ATP 45 uM, 3-methylcrotonyl-CoA 74 uM. -> FUNCTION, CATALYTIC ACTIVITY, SUBUNIT,
    ComplexPortal complex. (Chu & Cheng 2007.)
  • PMID:11170888 full text: "MCC, an heteromeric enzyme consisting of α (biotin-containing) and β
    subunits"; "725-residue protein with a biotin attachment site"; fungal mccA null used to demonstrate
    "the involvement of MCC in leucine catabolism".
  • PMID:11181649 abstract: "MCC is a heteromeric mitochondrial enzyme composed of biotin-containing
    alpha subunits and smaller beta subunits."
  • PMID:11401427 abstract: "mitochondrial biotin enzyme and plays an essential role in the catabolism of
    leucine and isovalerate"; "biotin carboxylase, and biotin-carrier domains"; "abundantly expressed in
    mitochondria-rich organs".
  • PMID:16023992 abstract: two subunits "are imported into the mitochondrial matrix by the classical
    pathway"; cleavage site "Tyr41/Thr42 ... for MCCalpha".
  • PMID:22869039 (Tong review): "Biotin-dependent carboxylases include ... 3-methylcrotonyl-CoA
    carboxylase (MCC) ... They contain biotin carboxylase (BC), carboxyltransferase (CT), and
    biotin-carboxyl carrier protein components." Family-level (review), NAS/TAS -> mark biotin
    carboxylase activity / biotin metabolic process as over-annotated (component activities of one
    domain, not the holoenzyme's committed MF).
  • PMID:32561715 (Son 2020, full text): "MCCC1, a key enzyme in the Leu metabolic pathway"; "the
    Leu-metabolizing enzyme MCCC1"; siRNA knockdown -> autophagy/mTORC1. This is a knockdown/autophagy
    study, NOT a direct carboxylase-activity assay; UniProt attaches the ECO:0000269 catalytic-activity
    to it alongside 17360195. Accept the enzyme/leucine-metabolism role; note the catalytic MF is more
    directly supported by 17360195.
  • UniProt INTERACTION: MCCC1–MCCC2 (Q9HCC0, NbExp=8) and MCCC1–OXCT2 (Q9BYC2, NbExp=3). The GOA
    protein binding IPIs point to exactly Q9HCC0 (MCCC2, the obligate partner) and Q9BYC2 (OXCT2).

Annotation strategy

  • Core MF: GO:0004485 methylcrotonoyl-CoA carboxylase activity (holoenzyme MF; MCCC1 contributes the
    BC + BCCP half). Accept the contributes_to IDA/IBA/EXP/NAS/EC copies; these are the core function.
  • GO:0004075 biotin carboxylase activity (NAS, review) and GO:0006768 biotin metabolic process (NAS):
    MARK_AS_OVER_ANNOTATED — biotin carboxylase is a partial-reaction/domain activity of the alpha
    subunit, not the committed cellular MF; biotin metabolic process conflates the biotin cofactor
    requirement with actual biotin biosynthesis/utilisation metabolism.
  • GO:0009374 biotin binding (NAS) and GO:0005524 ATP binding (IEA), GO:0046872 metal ion binding (IEA):
    cofactor/substrate binding, real (biotin at Lys681, ATP-grasp domain). Accept binding; metal ion
    binding is a generic InterPro ATP-grasp Mg2+ inference — keep as accept (plausible for ATP-grasp).
  • Localization: mitochondrial matrix (multiple IDA/IEA/TAS) ACCEPT (core). mitochondrion (IBA/IDA/HTP)
    accept as correct-but-less-specific. cytosol (Reactome TAS, R-HSA transit-of-cytosolic-carboxylases
    reactions) = transient import intermediate only -> MARK_AS_OVER_ANNOTATED (steady-state is matrix).
  • Complex: GO:1905202 methylcrotonoyl-CoA carboxylase complex ACCEPT (core CC).
  • BP: GO:0006552 L-leucine catabolic process ACCEPT (core BP). GO:0009083 branched-chain amino acid
    catabolic process (NAS) — parent of leucine catabolism, correct but less specific -> KEEP_AS_NON_CORE.
  • protein binding IPIs (bare GO:0005515): MARK_AS_OVER_ANNOTATED per policy (do not REMOVE). The
    MCCC2 partner is captured by the complex term; OXCT2 is a proteomic co-purification.

📄 View Raw YAML

 
id: Q96RQ3
gene_symbol: MCCC1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  MCCC1 is the biotin-containing alpha subunit of mitochondrial 3-methylcrotonyl-CoA
  carboxylase (MCC), a biotin-dependent carboxylase (EC 6.4.1.4). MCC catalyses the
  ATP-dependent carboxylation of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA, the
  committed carboxylation step of the leucine (and isovalerate) catabolic pathway,
  downstream of isovaleryl-CoA dehydrogenase. The holoenzyme is an alpha6-beta6 dodecamer
  assembled from six MCCC1 subunits and six MCCC2 subunits: MCCC1 carries the biotin
  carboxylase and biotinyl (biotin-carboxyl-carrier) domains, holds the covalently
  attached biotin cofactor (on a conserved lysine) and binds ATP, while MCCC2 provides
  the carboxyltransferase activity. The protein is synthesized with an N-terminal
  mitochondrial transit peptide and functions in the mitochondrial matrix. Loss of
  MCC activity due to biallelic variants in MCCC1 (or its partner MCCC2) causes
  3-methylcrotonyl-CoA carboxylase deficiency, an autosomal recessive organic aciduria
  that is one of the most common findings on newborn tandem mass spectrometry
  screening and is frequently benign or asymptomatic.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:11170888
  title: The molecular basis of 3-methylcrotonylglycinuria, a disorder of leucine
    catabolism.
  findings:
  - statement: MCC is a heteromeric biotin-dependent enzyme with a biotin-containing
      alpha subunit (MCCC1) and a beta subunit; a fungal mccA-null model established
      the in vivo involvement of MCC in leucine catabolism.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Primary molecular characterization of the human MCCA (MCCC1) gene;
      PubMed-verified. Establishes the alpha subunit as biotin-containing and the
      leucine-catabolic role of MCC.
- id: PMID:11181649
  title: The molecular basis of human 3-methylcrotonyl-CoA carboxylase deficiency.
  findings:
  - statement: MCC is a heteromeric mitochondrial enzyme composed of biotin-containing
      alpha subunits and smaller beta subunits; MCCA missense mutations cause loss
      of function.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Independent primary characterization of MCCA/MCCB and disease-causing
      mutations; PubMed-verified.
- id: PMID:11401427
  title: 'Human biotin-containing subunit of 3-methylcrotonyl-CoA carboxylase gene
    (MCCA): cDNA sequence, genomic organization, localization to chromosomal band
    3q27, and expression.'
  findings:
  - statement: The MCCA cDNA encodes a 725-residue protein with a mitochondrial signal
      peptide, biotin carboxylase, and biotin-carrier domains; MCCase is a mitochondrial
      biotin enzyme essential for leucine and isovalerate catabolism, abundantly expressed
      in mitochondria-rich organs.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Defines the domain architecture (biotin carboxylase + biotin-carrier)
      and mitochondrial localization of MCCC1; PubMed-verified.
- id: PMID:16023992
  title: Mitochondrial targeting signals and mature peptides of 3-methylcrotonyl-CoA
    carboxylase.
  findings:
  - statement: Both MCC subunits are imported into the mitochondrial matrix by the
      classical presequence pathway; the MCCalpha cleavage site is Tyr41/Thr42.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Direct experimental evidence for mitochondrial matrix localization
      and transit peptide cleavage; PubMed-verified.
- id: PMID:17360195
  title: Expression, purification, characterization of human 3-methylcrotonyl-CoA
    carboxylase (MCCC).
  findings:
  - statement: Recombinant human MCCC is a heteromultimeric alpha/beta complex (~500-800
      kDa) with a 1:1 alpha:beta stoichiometry and measurable carboxylase kinetics
      (kcat ~4 s-1; Km ATP 45 uM, 3-methylcrotonyl-CoA 74 uM).
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Biochemical characterization of the assembled MCC holoenzyme; basis
      for the IDA carboxylase-activity, complex, and matrix-localization annotations.
      PubMed-verified.
- id: PMID:22869039
  title: Structure and function of biotin-dependent carboxylases.
  findings:
  - statement: Biotin-dependent carboxylases (including MCC) contain biotin carboxylase
      (BC), carboxyltransferase (CT), and biotin-carboxyl carrier protein components;
      MCC deficiency is linked to human disease.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Family-level structure/function review; supports the modular BC/CT/BCCP
      architecture but is not gene-specific experimental evidence for MCCC1.
- id: PMID:27499296
  title: Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory
    Chain Function.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Large-scale mitochondrial protein-interaction mapping; source of
      an IntAct protein-binding IPI. MCCC1 is one node in a high-throughput dataset;
      not gene-specific functional evidence.
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: BioPlex high-throughput AP-MS interactome; source of an IntAct protein-binding
      IPI (partner OXCT2). Not gene-specific functional evidence.
- id: PMID:32561715
  title: Leucine regulates autophagy via acetylation of the mTORC1 component raptor.
  findings:
  - statement: MCCC1 is described as a key enzyme in the leucine metabolic pathway;
      siRNA knockdown of MCCC1 perturbs leucine metabolism and thereby modulates mTORC1
      activity and autophagy.
    reference_section_type: RESULTS
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Knockdown/autophagy study confirming MCCC1's role as the leucine-metabolizing
      enzyme; it does not itself assay carboxylase catalytic activity (UniProt attaches
      the ECO:0000269 catalytic-activity claim to this paper alongside PMID:17360195).
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: BioPlex 3.0 dual proteome-scale interactome; source of IntAct protein-binding
      IPIs (partners OXCT2, MCCC2). High-throughput, not gene-specific functional
      evidence.
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics
    in cellular context.
  findings:
  - statement: MCCC1 is detected as part of a quantitative high-confidence human mitochondrial
      proteome.
    reference_section_type: RESULTS
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: High-throughput mitochondrial proteomics; supports mitochondrial
      localization at proteome scale (HTP evidence code).
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Multimodal cell-mapping resource; source of an IntAct protein-binding
      IPI (partner MCCC2). Not gene-specific functional evidence.
- id: Reactome:R-HSA-2993799
  title: HLCS biotinylates 6xMCCC1:6xMCCC2
  findings: []
- id: Reactome:R-HSA-3065959
  title: An unknown protease degrades hCBXs
  findings: []
- id: Reactome:R-HSA-3323111
  title: Cytosolic carboxylases translocate to mitochondrial matrix
  findings: []
- id: Reactome:R-HSA-508308
  title: beta-methylglutaconyl-CoA + ADP + orthophosphate <=> beta-methylcrotonyl-CoA
    + ATP + HCO3- (MCCA)
  findings: []
- id: Reactome:R-HSA-70773
  title: beta-methylcrotonyl-CoA + ATP + HCO3- <=> beta-methylglutaconyl-CoA + ADP
    + orthophosphate + H2O (MCCA)
  findings: []
- id: Reactome:R-HSA-9035987
  title: Defective HLCS does not biotinylate 6xMCCC1:6xMCCC2
  findings: []
- id: Reactome:R-HSA-9909466
  title: MCCC mutants don't synthesize beta-methylglutaconyl-CoA
  findings: []
existing_annotations:
- term:
    id: GO:0004485
    label: methylcrotonoyl-CoA carboxylase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: contributes_to
  review:
    summary: Phylogenetically inferred core molecular function of the MCC alpha subunit.
      The contributes_to qualifier correctly reflects that the full carboxylase activity
      is a property of the assembled alpha6-beta6 holoenzyme to which MCCC1 contributes.
    action: ACCEPT
    reason: This is the core molecular function of MCCC1. The IBA is consistent with
      the biochemically characterized activity of the human enzyme.
    supported_by:
    - reference_id: PMID:17360195
      supporting_text: a heteromultimeric complex that is composed of alpha and beta
        subunits which are encoded by distinct genes
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic inference of mitochondrial localization. Correct but less
      specific than the mitochondrial matrix localization supported by direct evidence.
    action: ACCEPT
    reason: MCCC1 is a mitochondrial matrix protein; the mitochondrion annotation
      is correct though the matrix term is more informative.
    supported_by:
    - reference_id: PMID:16023992
      supporting_text: are imported into the mitochondrial matrix by the classical
        pathway involving cleavable amino-terminal targeting presequences
- term:
    id: GO:0004485
    label: methylcrotonoyl-CoA carboxylase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic inference (RHEA:13589 / EC 6.4.1.4) of the core carboxylase
      activity, consistent with the curated catalytic activity in UniProt.
    action: ACCEPT
    reason: Correctly maps the EC 6.4.1.4 / RHEA:13589 reaction to the core MCC activity.
    supported_by:
    - reference_id: PMID:17360195
      supporting_text: a heteromultimeric complex that is composed of alpha and beta
        subunits which are encoded by distinct genes
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based inference of ATP binding, consistent with the ATP-grasp
      domain of the biotin carboxylase module that binds ATP during the carboxylation
      reaction.
    action: ACCEPT
    reason: MCCC1 contains an ATP-grasp domain and binds ATP as part of the biotin
      carboxylation half-reaction (curated ATP-binding residues in UniProt).
    supported_by:
    - reference_id: PMID:11401427
      supporting_text: biotin carboxylase, and biotin-carrier domains
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Electronic inference of mitochondrial matrix localization (UniProt-SubCell
      SL-0170), matching direct experimental evidence.
    action: ACCEPT
    reason: MCCC1 is imported into and functions in the mitochondrial matrix.
    supported_by:
    - reference_id: PMID:16023992
      supporting_text: are imported into the mitochondrial matrix by the classical
        pathway involving cleavable amino-terminal targeting presequences
- term:
    id: GO:0046872
    label: metal ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro (ATP-grasp) inference of metal ion binding. ATP-grasp carboxylase
      domains use a divalent metal (Mg2+) for ATP-dependent catalysis, so a generic
      metal-ion-binding inference is biologically plausible but uninformative.
    action: ACCEPT
    reason: Divalent metal (Mg2+) coordination is expected for the ATP-grasp biotin
      carboxylase reaction; the generic term is a reasonable, if low-information, InterPro
      inference and is not contradicted by evidence.
    supported_by:
    - reference_id: PMID:22869039
      supporting_text: biotin carboxylase (BC), carboxyltransferase (CT), and biotin-carboxyl
        carrier protein components
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17360195
  qualifier: enables
  review:
    summary: IntAct protein-binding annotation capturing the MCCC1-MCCC2 (Q9HCC0)
      interaction, i.e. assembly of the MCC holoenzyme. The bare protein binding term
      is uninformative; the biologically meaningful interaction is captured by the
      methylcrotonoyl-CoA carboxylase complex annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare GO:0005515 provides no functional information beyond the fact of
      an interaction. The relevant partner here is the obligate holoenzyme subunit
      MCCC2, already captured by GO:1905202 (methylcrotonoyl-CoA carboxylase complex).
      Retained (not removed) per curation policy on protein-binding IPIs.
    supported_by:
    - reference_id: PMID:17360195
      supporting_text: stoichiometry of alpha and beta subunits are at a one:one ratio
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27499296
  qualifier: enables
  review:
    summary: IntAct protein-binding annotation from a high-throughput mitochondrial
      interaction mapping study (partner MCCC2/Q9HCC0). Uninformative bare-binding
      term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare GO:0005515 from a high-throughput screen; the meaningful holoenzyme
      partnership with MCCC2 is captured by GO:1905202. Retained per policy on protein-binding
      IPIs.
    supported_by:
    - reference_id: PMID:27499296
      supporting_text: Mitochondrial Protein Interaction Mapping Identifies Regulators
        of Respiratory Chain Function
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: IntAct protein-binding annotation from the BioPlex human interactome
      (partner OXCT2/Q9BYC2). Bare-binding term with no functional content.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare GO:0005515 from high-throughput AP-MS. The OXCT2 co-purification
      is a mitochondrial-matrix proximity/co-complex observation without established
      functional meaning for MCCC1. Retained per policy on protein-binding IPIs.
    supported_by:
    - reference_id: PMID:28514442
      supporting_text: Architecture of the human interactome defines protein communities
        and disease networks
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: IntAct protein-binding annotation from BioPlex 3.0 (partner OXCT2/Q9BYC2).
      Bare-binding term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare GO:0005515 from high-throughput interactome data; no specific molecular
      function conveyed. Retained per policy on protein-binding IPIs.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: Dual proteome-scale networks reveal cell-specific remodeling
        of the human interactome
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Second IntAct protein-binding annotation from BioPlex 3.0 for the same
      paper, capturing the MCCC1-MCCC2 (Q9HCC0) holoenzyme interaction. Bare-binding
      term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare GO:0005515 from a high-throughput screen; the MCCC2 partnership is
      already represented by GO:1905202. Retained per policy on protein-binding IPIs.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: Dual proteome-scale networks reveal cell-specific remodeling
        of the human interactome
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: IntAct protein-binding annotation from a multimodal cell-mapping resource
      (partner MCCC2/Q9HCC0). Bare-binding term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare GO:0005515 from a high-throughput mapping study; the MCCC2 holoenzyme
      partnership is captured by GO:1905202. Retained per policy on protein-binding
      IPIs.
    supported_by:
    - reference_id: PMID:40205054
      supporting_text: Multimodal cell maps as a foundation for structural and functional
        genomics
- term:
    id: GO:0006552
    label: L-leucine catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Electronic inference (UniPathway UPA00363, L-leucine degradation) of
      the core biological process in which MCC acts.
    action: ACCEPT
    reason: MCC catalyses the committed carboxylation step of leucine catabolism;
      this is the core biological process.
    supported_by:
    - reference_id: PMID:11401427
      supporting_text: plays an essential role in the catabolism of leucine and isovalerate
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: IDA
  original_reference_id: PMID:17360195
  qualifier: located_in
  review:
    summary: Direct assignment (ComplexPortal) of mitochondrial matrix localization
      for the MCC complex, consistent with import studies.
    action: ACCEPT
    reason: MCCC1 is a mitochondrial matrix protein; this is the core cellular location.
    supported_by:
    - reference_id: PMID:16023992
      supporting_text: are imported into the mitochondrial matrix by the classical
        pathway involving cleavable amino-terminal targeting presequences
- term:
    id: GO:0009083
    label: branched-chain amino acid catabolic process
  evidence_type: NAS
  original_reference_id: PMID:17360195
  qualifier: involved_in
  review:
    summary: Leucine is a branched-chain amino acid, so MCC participation in leucine
      catabolism is subsumed by branched-chain amino acid catabolism. This parent
      term is correct but less specific than L-leucine catabolic process.
    action: KEEP_AS_NON_CORE
    reason: Biologically correct but a generalization of the more precise leucine-catabolism
      annotation; MCC specifically acts on the leucine branch, not other BCAAs (valine/isoleucine).
    supported_by:
    - reference_id: PMID:11401427
      supporting_text: plays an essential role in the catabolism of leucine and isovalerate
- term:
    id: GO:1905202
    label: methylcrotonoyl-CoA carboxylase complex
  evidence_type: IPI
  original_reference_id: PMID:17360195
  qualifier: part_of
  review:
    summary: MCCC1 is a subunit of the alpha6-beta6 methylcrotonoyl-CoA carboxylase
      holoenzyme, directly demonstrated by expression, purification and characterization
      of the assembled human complex.
    action: ACCEPT
    reason: Core cellular-component annotation; MCCC1 is an integral subunit of the
      MCC complex.
    supported_by:
    - reference_id: PMID:17360195
      supporting_text: a heteromultimeric complex that is composed of alpha and beta
        subunits which are encoded by distinct genes
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Immunofluorescence-based (HPA) mitochondrial localization. Correct but
      less specific than the mitochondrial matrix.
    action: ACCEPT
    reason: Consistent with the established mitochondrial matrix localization; the
      matrix term is more informative.
    supported_by:
    - reference_id: PMID:16023992
      supporting_text: are imported into the mitochondrial matrix by the classical
        pathway involving cleavable amino-terminal targeting presequences
- term:
    id: GO:0004485
    label: methylcrotonoyl-CoA carboxylase activity
  evidence_type: EXP
  original_reference_id: PMID:32561715
  qualifier: enables
  review:
    summary: Experimental-code annotation of the core carboxylase activity. UniProt
      attaches the catalytic-activity claim to this paper, which studies MCCC1 as
      the leucine-metabolizing enzyme via knockdown; the enzymatic function itself
      is most directly supported by the biochemical characterization in PMID:17360195.
    action: ACCEPT
    reason: The core molecular function of MCCC1. The annotated activity is well established
      biochemically for the assembled MCC enzyme.
    supported_by:
    - reference_id: PMID:32561715
      supporting_text: the Leu-metabolizing enzyme MCCC1
    - reference_id: PMID:17360195
      supporting_text: a heteromultimeric complex that is composed of alpha and beta
        subunits which are encoded by distinct genes
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    summary: High-throughput mitochondrial proteomics detection. Correct but less
      specific than the mitochondrial matrix.
    action: ACCEPT
    reason: Consistent with the established mitochondrial localization of MCCC1.
    supported_by:
    - reference_id: PMID:34800366
      supporting_text: Quantitative high-confidence human mitochondrial proteome and
        its dynamics in cellular context
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9909466
  qualifier: located_in
  review:
    summary: Reactome traceable-author-statement placing MCCC1 in the mitochondrial
      matrix, consistent with all other localization evidence.
    action: ACCEPT
    reason: Core cellular location, consistent with direct import/localization studies.
    supported_by:
    - reference_id: PMID:16023992
      supporting_text: are imported into the mitochondrial matrix by the classical
        pathway involving cleavable amino-terminal targeting presequences
- term:
    id: GO:1905202
    label: methylcrotonoyl-CoA carboxylase complex
  evidence_type: IDA
  original_reference_id: PMID:17360195
  qualifier: part_of
  review:
    summary: Direct-assignment (UniProt) membership in the MCC holoenzyme complex,
      duplicate of the ComplexPortal IPI annotation.
    action: ACCEPT
    reason: Core cellular-component annotation; MCCC1 is an integral subunit of the
      MCC complex.
    supported_by:
    - reference_id: PMID:17360195
      supporting_text: a heteromultimeric complex that is composed of alpha and beta
        subunits which are encoded by distinct genes
- term:
    id: GO:0004485
    label: methylcrotonoyl-CoA carboxylase activity
  evidence_type: IDA
  original_reference_id: PMID:17360195
  qualifier: contributes_to
  review:
    summary: Direct assay of the recombinant human MCC holoenzyme with measurable
      carboxylase kinetics; MCCC1 contributes the biotin carboxylase and biotinyl
      components of the activity.
    action: ACCEPT
    reason: This is the primary experimental evidence for the core molecular function
      of MCC and is the best-supported carboxylase-activity annotation.
    supported_by:
    - reference_id: PMID:17360195
      supporting_text: 'possesses K(m) values (ATP: 45+/-11microM; 3-methylcrotonyl-CoA:
        74+/-7microM) similar to those reported for the native enzyme'
- term:
    id: GO:0004075
    label: biotin carboxylase activity
  evidence_type: NAS
  original_reference_id: PMID:22869039
  qualifier: enables
  review:
    summary: Biotin carboxylase (BC) is a component activity of the biotin carboxylase
      domain that MCCC1 contributes to the holoenzyme; it is a partial reaction, not
      the committed cellular molecular function of MCC (methylcrotonoyl-CoA carboxylase
      activity).
    action: MARK_AS_OVER_ANNOTATED
    reason: The BC half-reaction is a mechanistic sub-step shared by all biotin-dependent
      carboxylases and is captured within GO:0004485; asserting a standalone biotin
      carboxylase activity for MCCC1 over-annotates a domain-level partial reaction.
      Sourced from a family-level review (NAS).
    supported_by:
    - reference_id: PMID:22869039
      supporting_text: biotin carboxylase (BC), carboxyltransferase (CT), and biotin-carboxyl
        carrier protein components
- term:
    id: GO:0004485
    label: methylcrotonoyl-CoA carboxylase activity
  evidence_type: NAS
  original_reference_id: PMID:11170888
  qualifier: contributes_to
  review:
    summary: Non-traceable assertion of the core carboxylase activity from the primary
      MCCA characterization paper.
    action: ACCEPT
    reason: Core molecular function; consistent with all experimental and inferred
      evidence.
    supported_by:
    - reference_id: PMID:11170888
      supporting_text: MCC, an heteromeric enzyme consisting of alpha (biotin-containing)
        and beta subunits
- term:
    id: GO:0004485
    label: methylcrotonoyl-CoA carboxylase activity
  evidence_type: NAS
  original_reference_id: PMID:11181649
  qualifier: contributes_to
  review:
    summary: Non-traceable assertion of the core carboxylase activity from an independent
      primary characterization of MCC deficiency.
    action: ACCEPT
    reason: Core molecular function; consistent with all other evidence.
    supported_by:
    - reference_id: PMID:11181649
      supporting_text: MCC is a heteromeric mitochondrial enzyme composed of biotin-containing
        alpha subunits and smaller beta subunits
- term:
    id: GO:0004485
    label: methylcrotonoyl-CoA carboxylase activity
  evidence_type: NAS
  original_reference_id: PMID:11401427
  qualifier: contributes_to
  review:
    summary: Non-traceable assertion of the core carboxylase activity from the MCCA
      cDNA/genomic characterization paper.
    action: ACCEPT
    reason: Core molecular function; consistent with all other evidence.
    supported_by:
    - reference_id: PMID:11401427
      supporting_text: plays an essential role in the catabolism of leucine and isovalerate
- term:
    id: GO:0006768
    label: biotin metabolic process
  evidence_type: NAS
  original_reference_id: PMID:22869039
  qualifier: involved_in
  review:
    summary: MCCC1 uses biotin as a covalently attached cofactor but does not participate
      in biotin biosynthesis or turnover. Annotating a biotin metabolic process conflates
      the requirement for the biotin cofactor with actual biotin metabolism.
    action: MARK_AS_OVER_ANNOTATED
    reason: MCCC1's biological process is leucine catabolism; its dependence on the
      biotin cofactor does not make it a participant in biotin metabolism. Sourced
      from a family-level review (NAS).
    supported_by:
    - reference_id: PMID:22869039
      supporting_text: Biotin-dependent carboxylases include acetyl-CoA carboxylase
        (ACC),
- term:
    id: GO:1905202
    label: methylcrotonoyl-CoA carboxylase complex
  evidence_type: NAS
  original_reference_id: PMID:11170888
  qualifier: part_of
  review:
    summary: Non-traceable assertion of MCC complex membership from the primary MCCA
      characterization.
    action: ACCEPT
    reason: Core cellular-component annotation; MCCC1 is an integral subunit of the
      MCC holoenzyme.
    supported_by:
    - reference_id: PMID:11170888
      supporting_text: MCC, an heteromeric enzyme consisting of alpha (biotin-containing)
        and beta subunits
- term:
    id: GO:1905202
    label: methylcrotonoyl-CoA carboxylase complex
  evidence_type: NAS
  original_reference_id: PMID:11181649
  qualifier: part_of
  review:
    summary: Non-traceable assertion of MCC complex membership from an independent
      primary study.
    action: ACCEPT
    reason: Core cellular-component annotation; MCCC1 is an integral subunit of the
      MCC holoenzyme.
    supported_by:
    - reference_id: PMID:11181649
      supporting_text: MCC is a heteromeric mitochondrial enzyme composed of biotin-containing
        alpha subunits and smaller beta subunits
- term:
    id: GO:1905202
    label: methylcrotonoyl-CoA carboxylase complex
  evidence_type: NAS
  original_reference_id: PMID:11401427
  qualifier: part_of
  review:
    summary: Non-traceable assertion of MCC complex membership from the MCCA cDNA
      characterization paper.
    action: ACCEPT
    reason: Core cellular-component annotation; MCCC1 is an integral subunit of the
      MCC holoenzyme.
    supported_by:
    - reference_id: PMID:11401427
      supporting_text: MCCase consists of two subunits,
- term:
    id: GO:1905202
    label: methylcrotonoyl-CoA carboxylase complex
  evidence_type: TAS
  original_reference_id: PMID:22869039
  qualifier: part_of
  review:
    summary: Traceable-author-statement membership in the MCC complex, from the biotin-dependent
      carboxylase structure/function review.
    action: ACCEPT
    reason: Core cellular-component annotation; MCC assembles into a defined holoenzyme.
    supported_by:
    - reference_id: PMID:22869039
      supporting_text: biotin carboxylase (BC), carboxyltransferase (CT), and biotin-carboxyl
        carrier protein components
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: IDA
  original_reference_id: PMID:16023992
  qualifier: located_in
  review:
    summary: Direct experimental evidence (protein import and presequence-cleavage
      analysis) that MCCC1 localizes to the mitochondrial matrix.
    action: ACCEPT
    reason: Primary experimental support for the core mitochondrial matrix location.
    supported_by:
    - reference_id: PMID:16023992
      supporting_text: are imported into the mitochondrial matrix by the classical
        pathway involving cleavable amino-terminal targeting presequences
- term:
    id: GO:0006552
    label: L-leucine catabolic process
  evidence_type: ISS
  original_reference_id: PMID:11170888
  qualifier: involved_in
  review:
    summary: Sequence-similarity-based assignment of the core leucine catabolic process,
      supported in the same work by an mccA-null fungal model demonstrating the in
      vivo role of MCC in leucine catabolism.
    action: ACCEPT
    reason: Core biological process; MCC catalyses the committed carboxylation step
      of leucine degradation.
    supported_by:
    - reference_id: PMID:11170888
      supporting_text: to demonstrate, in vivo, the involvement of MCC in leucine
        catabolism
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3065959
  qualifier: located_in
  review:
    summary: Reactome traceable-author-statement placing MCCC1 in the mitochondrial
      matrix (protein degradation reaction context).
    action: ACCEPT
    reason: Core cellular location, consistent with all other evidence.
    supported_by:
    - reference_id: PMID:16023992
      supporting_text: are imported into the mitochondrial matrix by the classical
        pathway involving cleavable amino-terminal targeting presequences
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3323111
  qualifier: located_in
  review:
    summary: Reactome traceable-author-statement placing MCCC1 in the mitochondrial
      matrix.
    action: ACCEPT
    reason: Core cellular location, consistent with all other evidence.
    supported_by:
    - reference_id: PMID:16023992
      supporting_text: are imported into the mitochondrial matrix by the classical
        pathway involving cleavable amino-terminal targeting presequences
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-508308
  qualifier: located_in
  review:
    summary: Reactome traceable-author-statement placing MCCC1 in the mitochondrial
      matrix (carboxylation reaction context).
    action: ACCEPT
    reason: Core cellular location, consistent with all other evidence.
    supported_by:
    - reference_id: PMID:16023992
      supporting_text: are imported into the mitochondrial matrix by the classical
        pathway involving cleavable amino-terminal targeting presequences
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-70773
  qualifier: located_in
  review:
    summary: Reactome traceable-author-statement placing MCCC1 in the mitochondrial
      matrix (carboxylation reaction context).
    action: ACCEPT
    reason: Core cellular location, consistent with all other evidence.
    supported_by:
    - reference_id: PMID:16023992
      supporting_text: are imported into the mitochondrial matrix by the classical
        pathway involving cleavable amino-terminal targeting presequences
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2993799
  qualifier: located_in
  review:
    summary: Reactome models newly translated carboxylase subunits transiently in
      the cytosol before mitochondrial import (HLCS biotinylation / translocation
      reactions). MCCC1 is not a steady-state cytosolic protein; its mature functional
      location is the mitochondrial matrix.
    action: MARK_AS_OVER_ANNOTATED
    reason: The cytosolic annotation reflects a transient pre-import biosynthetic
      intermediate in the Reactome pathway, not a functional cytosolic localization.
      MCCC1 carries a cleavable mitochondrial transit peptide and functions in the
      matrix.
    supported_by:
    - reference_id: PMID:16023992
      supporting_text: are imported into the mitochondrial matrix by the classical
        pathway involving cleavable amino-terminal targeting presequences
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3323111
  qualifier: located_in
  review:
    summary: Reactome cytosolic annotation reflecting the pre-import translocation
      step (cytosolic carboxylases translocate to mitochondrial matrix), not a functional
      steady-state cytosolic location.
    action: MARK_AS_OVER_ANNOTATED
    reason: Transient pre-import intermediate; MCCC1's mature functional compartment
      is the mitochondrial matrix.
    supported_by:
    - reference_id: PMID:16023992
      supporting_text: are imported into the mitochondrial matrix by the classical
        pathway involving cleavable amino-terminal targeting presequences
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9035987
  qualifier: located_in
  review:
    summary: Reactome cytosolic annotation from the defective-HLCS biotinylation reaction,
      representing the transient pre-import state rather than a functional cytosolic
      localization.
    action: MARK_AS_OVER_ANNOTATED
    reason: Transient pre-import intermediate; MCCC1's mature functional compartment
      is the mitochondrial matrix.
    supported_by:
    - reference_id: PMID:16023992
      supporting_text: are imported into the mitochondrial matrix by the classical
        pathway involving cleavable amino-terminal targeting presequences
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: NAS
  original_reference_id: PMID:11170888
  qualifier: located_in
  review:
    summary: Non-traceable assertion of mitochondrial matrix localization from the
      primary MCCA characterization.
    action: ACCEPT
    reason: Core cellular location, consistent with direct experimental import studies.
    supported_by:
    - reference_id: PMID:16023992
      supporting_text: are imported into the mitochondrial matrix by the classical
        pathway involving cleavable amino-terminal targeting presequences
- term:
    id: GO:0006552
    label: L-leucine catabolic process
  evidence_type: NAS
  original_reference_id: PMID:11170888
  qualifier: involved_in
  review:
    summary: Non-traceable assertion of the core leucine catabolic process, supported
      by the mccA-null fungal complementation model in the same paper.
    action: ACCEPT
    reason: Core biological process; MCC catalyses the committed carboxylation step
      of leucine degradation.
    supported_by:
    - reference_id: PMID:11170888
      supporting_text: to demonstrate, in vivo, the involvement of MCC in leucine
        catabolism
- term:
    id: GO:0006768
    label: biotin metabolic process
  evidence_type: NAS
  original_reference_id: PMID:11401427
  qualifier: involved_in
  review:
    summary: MCCC1 requires biotin as a covalently attached cofactor but does not
      participate in biotin biosynthesis or turnover; the biotin metabolic process
      annotation conflates cofactor usage with biotin metabolism.
    action: MARK_AS_OVER_ANNOTATED
    reason: MCCC1's biological process is leucine (and isovalerate) catabolism; being
      a biotin-dependent enzyme does not make it a participant in biotin metabolism.
    supported_by:
    - reference_id: PMID:11401427
      supporting_text: plays an essential role in the catabolism of leucine and isovalerate
- term:
    id: GO:0009374
    label: biotin binding
  evidence_type: NAS
  original_reference_id: PMID:11401427
  qualifier: enables
  review:
    summary: MCCC1 carries a biotinyl (biotin-carrier) domain and holds the covalently
      attached biotin cofactor on a conserved lysine (Lys681), consistent with a biotin-binding
      molecular function.
    action: ACCEPT
    reason: MCCC1 is the biotin-containing subunit; biotin binding/carriage is a genuine,
      structurally supported molecular function of the biotinyl-binding domain.
    supported_by:
    - reference_id: PMID:11401427
      supporting_text: biotin carboxylase, and biotin-carrier domains
core_functions:
- description: MCC alpha subunit contributes the biotin carboxylase and biotin-carrier
    activities to the mitochondrial 3-methylcrotonyl-CoA carboxylase holoenzyme, which
    catalyses the ATP-dependent carboxylation of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA.
  molecular_function:
    id: GO:0004485
    label: methylcrotonoyl-CoA carboxylase activity
  directly_involved_in:
  - id: GO:0006552
    label: L-leucine catabolic process
  locations:
  - id: GO:0005759
    label: mitochondrial matrix
  in_complex:
    id: GO:1905202
    label: methylcrotonoyl-CoA carboxylase complex
  supported_by:
  - reference_id: PMID:17360195
    supporting_text: a heteromultimeric complex that is composed of alpha and beta
      subunits which are encoded by distinct genes
  - reference_id: PMID:11401427
    supporting_text: plays an essential role in the catabolism of leucine and isovalerate
- description: Binds the biotin cofactor via the C-terminal biotinyl-binding domain,
    covalently attaching biotin on a conserved lysine to enable the carboxyl-transfer
    steps of the carboxylase reaction.
  molecular_function:
    id: GO:0009374
    label: biotin binding
  locations:
  - id: GO:0005759
    label: mitochondrial matrix
  supported_by:
  - reference_id: PMID:11401427
    supporting_text: biotin carboxylase, and biotin-carrier domains
- description: Binds ATP through its ATP-grasp biotin carboxylase domain, providing
    the energy for carboxylation of the biotin cofactor.
  molecular_function:
    id: GO:0005524
    label: ATP binding
  locations:
  - id: GO:0005759
    label: mitochondrial matrix
  supported_by:
  - reference_id: PMID:17360195
    supporting_text: 'possesses K(m) values (ATP: 45+/-11microM; 3-methylcrotonyl-CoA:
      74+/-7microM) similar to those reported for the native enzyme'