Q96RQ3 · MCCA_HUMAN
- ProteinMethylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial
- GeneMCCC1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids725 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Biotin-attachment subunit of the 3-methylcrotonyl-CoA carboxylase, an enzyme that catalyzes the conversion of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA, a critical step for leucine and isovaleric acid catabolism.
Catalytic activity
- 3-methyl-(2E)-butenoyl-CoA + ATP + hydrogencarbonate = 3-methyl-(2E)-glutaconyl-CoA + ADP + H+ + phosphate
Cofactor
Pathway
Amino-acid degradation; L-leucine degradation; (S)-3-hydroxy-3-methylglutaryl-CoA from 3-isovaleryl-CoA: step 2/3.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 163 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 205 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 211-212 | ATP (UniProtKB | ChEBI) | ||||
Sequence: GG | ||||||
Binding site | 255 | ATP (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 282 | ATP (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 322 | ATP (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Active site | 339 | |||||
Sequence: R |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | 3-methylcrotonyl-CoA carboxylase complex, mitochondrial | |
Cellular Component | cytosol | |
Cellular Component | methylcrotonoyl-CoA carboxylase complex | |
Cellular Component | mitochondrial matrix | |
Cellular Component | mitochondrion | |
Molecular Function | ATP binding | |
Molecular Function | biotin binding | |
Molecular Function | biotin carboxylase activity | |
Molecular Function | metal ion binding | |
Molecular Function | methylcrotonoyl-CoA carboxylase activity | |
Biological Process | biotin metabolic process | |
Biological Process | branched-chain amino acid catabolic process | |
Biological Process | L-leucine catabolic process |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMethylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial
- EC number
- Short namesMCCase subunit alpha
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ96RQ3
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
3-methylcrotonoyl-CoA carboxylase 1 deficiency (MCC1D)
- Note
- DescriptionAn autosomal recessive disorder of leucine catabolism. The phenotype is variable, ranging from neonatal onset with severe neurological involvement to asymptomatic adults. There is a characteristic organic aciduria with massive excretion of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine, usually in combination with a severe secondary carnitine deficiency.
- See alsoMIM:210200
Natural variants in MCC1D
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_072486 | 46 | G>E | in MCC1D; dbSNP:rs199517715 | |
VAR_072487 | 56 | N>K | in MCC1D; dbSNP:rs1057520695 | |
VAR_072488 | 65 | M>L | in MCC1D; dbSNP:rs1718436080 | |
VAR_077284 | 79 | Y>C | in MCC1D | |
VAR_077285 | 120 | S>F | in MCC1D; dbSNP:rs1307589698 | |
VAR_072489 | 123 | Q>H | in MCC1D | |
VAR_072490 | 125 | I>M | in MCC1D | |
VAR_077286 | 130 | G>S | in MCC1D; clinically asymptomatic form; dbSNP:rs202197951 | |
VAR_072491 | 134 | E>K | in MCC1D; dbSNP:rs1229069160 | |
VAR_072492 | 160 | M>R | in MCC1D | |
VAR_072493 | 180 | G>V | in MCC1D; dbSNP:rs748201122 | |
VAR_072494 | 187 | S>P | in MCC1D; dbSNP:rs757362635 | |
VAR_077287 | 209 | G>V | in MCC1D; dbSNP:rs186209189 | |
VAR_072495 | 232 | R>W | in MCC1D; dbSNP:rs727504004 | |
VAR_072496 | 268 | A>D | in MCC1D | |
VAR_067197 | 276 | C>R | in MCC1D; dbSNP:rs773433541 | |
VAR_067198 | 281 | R>Q | in MCC1D; dbSNP:rs754437245 | |
VAR_072497 | 288 | E>G | in MCC1D; shows no residual activity; dbSNP:rs746500530 | |
VAR_012785 | 289 | A>V | in MCC1D; mild form; dbSNP:rs1326114075 | |
VAR_072498 | 291 | A>V | in MCC1D; associated with a reduction of wild-type residual activity; dbSNP:rs201041864 | |
VAR_012786 | 325 | M>R | in MCC1D; dbSNP:rs119103212 | |
VAR_077288 | 366 | E>K | in MCC1D; uncertain significance; dbSNP:rs201386261 | |
VAR_072499 | 372 | Q>P | in MCC1D; dbSNP:rs755328329 | |
VAR_072500 | 379 | G>D | in MCC1D | |
VAR_072501 | 379 | G>S | in MCC1D; dbSNP:rs887877405 | |
VAR_072502 | 380 | H>P | in MCC1D; dbSNP:rs794727036 | |
VAR_077289 | 383 | E>K | in MCC1D; uncertain significance; dbSNP:rs1333357031 | |
VAR_012787 | 385 | R>S | in MCC1D; severe form; dbSNP:rs119103213 | |
VAR_072503 | 434 | I>M | in MCC1D; shows some wild-type residual activity; dbSNP:rs376289130 | |
VAR_012788 | 437 | L>P | in MCC1D; severe form; dbSNP:rs119103215 | |
VAR_072504 | 439 | V>M | in MCC1D; dbSNP:rs398124352 | |
VAR_077290 | 444 | R>H | in MCC1D; dbSNP:rs768785753 | |
VAR_072505 | 460 | I>M | in MCC1D; dbSNP:rs119103218 | |
VAR_012790 | 532 | D>H | in MCC1D; severe form; dbSNP:rs119103214 | |
VAR_012791 | 535 | S>F | in MCC1D; asymptomatic form; dbSNP:rs119103216 | |
VAR_072506 | 566-567 | missing | in MCC1D |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_072486 | 46 | in MCC1D; dbSNP:rs199517715 | |||
Sequence: G → E | ||||||
Natural variant | VAR_072487 | 56 | in MCC1D; dbSNP:rs1057520695 | |||
Sequence: N → K | ||||||
Natural variant | VAR_072488 | 65 | in MCC1D; dbSNP:rs1718436080 | |||
Sequence: M → L | ||||||
Natural variant | VAR_077284 | 79 | in MCC1D | |||
Sequence: Y → C | ||||||
Natural variant | VAR_077285 | 120 | in MCC1D; dbSNP:rs1307589698 | |||
Sequence: S → F | ||||||
Natural variant | VAR_072489 | 123 | in MCC1D | |||
Sequence: Q → H | ||||||
Natural variant | VAR_072490 | 125 | in MCC1D | |||
Sequence: I → M | ||||||
Natural variant | VAR_077286 | 130 | in MCC1D; clinically asymptomatic form; dbSNP:rs202197951 | |||
Sequence: G → S | ||||||
Natural variant | VAR_072491 | 134 | in MCC1D; dbSNP:rs1229069160 | |||
Sequence: E → K | ||||||
Natural variant | VAR_072492 | 160 | in MCC1D | |||
Sequence: M → R | ||||||
Natural variant | VAR_072493 | 180 | in MCC1D; dbSNP:rs748201122 | |||
Sequence: G → V | ||||||
Natural variant | VAR_072494 | 187 | in MCC1D; dbSNP:rs757362635 | |||
Sequence: S → P | ||||||
Natural variant | VAR_077287 | 209 | in MCC1D; dbSNP:rs186209189 | |||
Sequence: G → V | ||||||
Natural variant | VAR_072495 | 232 | in MCC1D; dbSNP:rs727504004 | |||
Sequence: R → W | ||||||
Natural variant | VAR_072496 | 268 | in MCC1D | |||
Sequence: A → D | ||||||
Natural variant | VAR_067197 | 276 | in MCC1D; dbSNP:rs773433541 | |||
Sequence: C → R | ||||||
Natural variant | VAR_067198 | 281 | in MCC1D; dbSNP:rs754437245 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_072497 | 288 | in MCC1D; shows no residual activity; dbSNP:rs746500530 | |||
Sequence: E → G | ||||||
Natural variant | VAR_012785 | 289 | in MCC1D; mild form; dbSNP:rs1326114075 | |||
Sequence: A → V | ||||||
Natural variant | VAR_072498 | 291 | in MCC1D; associated with a reduction of wild-type residual activity; dbSNP:rs201041864 | |||
Sequence: A → V | ||||||
Natural variant | VAR_012786 | 325 | in MCC1D; dbSNP:rs119103212 | |||
Sequence: M → R | ||||||
Natural variant | VAR_077288 | 366 | in MCC1D; uncertain significance; dbSNP:rs201386261 | |||
Sequence: E → K | ||||||
Natural variant | VAR_072499 | 372 | in MCC1D; dbSNP:rs755328329 | |||
Sequence: Q → P | ||||||
Natural variant | VAR_072500 | 379 | in MCC1D | |||
Sequence: G → D | ||||||
Natural variant | VAR_072501 | 379 | in MCC1D; dbSNP:rs887877405 | |||
Sequence: G → S | ||||||
Natural variant | VAR_072502 | 380 | in MCC1D; dbSNP:rs794727036 | |||
Sequence: H → P | ||||||
Natural variant | VAR_077289 | 383 | in MCC1D; uncertain significance; dbSNP:rs1333357031 | |||
Sequence: E → K | ||||||
Natural variant | VAR_012787 | 385 | in MCC1D; severe form; dbSNP:rs119103213 | |||
Sequence: R → S | ||||||
Natural variant | VAR_072503 | 434 | in MCC1D; shows some wild-type residual activity; dbSNP:rs376289130 | |||
Sequence: I → M | ||||||
Natural variant | VAR_012788 | 437 | in MCC1D; severe form; dbSNP:rs119103215 | |||
Sequence: L → P | ||||||
Natural variant | VAR_072504 | 439 | in MCC1D; dbSNP:rs398124352 | |||
Sequence: V → M | ||||||
Natural variant | VAR_077290 | 444 | in MCC1D; dbSNP:rs768785753 | |||
Sequence: R → H | ||||||
Natural variant | VAR_072505 | 460 | in MCC1D; dbSNP:rs119103218 | |||
Sequence: I → M | ||||||
Natural variant | VAR_012789 | 464 | in dbSNP:rs2270968 | |||
Sequence: H → P | ||||||
Natural variant | VAR_012790 | 532 | in MCC1D; severe form; dbSNP:rs119103214 | |||
Sequence: D → H | ||||||
Natural variant | VAR_012791 | 535 | in MCC1D; asymptomatic form; dbSNP:rs119103216 | |||
Sequence: S → F | ||||||
Natural variant | VAR_038631 | 560 | in dbSNP:rs35219417 | |||
Sequence: N → T | ||||||
Natural variant | VAR_072506 | 566-567 | in MCC1D | |||
Sequence: Missing | ||||||
Natural variant | VAR_079752 | 632 | in dbSNP:rs142867987 | |||
Sequence: P → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 907 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Transit peptide | 1-41 | UniProt | Mitochondrion | ||||
Sequence: MAAASAVSVLLVAAERNRWHRLPSLLLPPRTWVWRQRTMKY | |||||||
Chain | PRO_0000002833 | 42-725 | UniProt | Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial | |||
Sequence: TTATGRNITKVLIANRGEIACRVMRTAKKLGVQTVAVYSEADRNSMHVDMADEAYSIGPAPSQQSYLSMEKIIQVAKTSAAQAIHPGCGFLSENMEFAELCKQEGIIFIGPPPSAIRDMGIKSTSKSIMAAAGVPVVEGYHGEDQSDQCLKEHARRIGYPVMIKAVRGGGGKGMRIVRSEQEFQEQLESARREAKKSFNDDAMLIEKFVDTPRHVEVQVFGDHHGNAVYLFERDCSVQRRHQKIIEEAPAPGIKSEVRKKLGEAAVRAAKAVNYVGAGTVEFIMDSKHNFCFMEMNTRLQVEHPVTEMITGTDLVEWQLRIAAGEKIPLSQEEITLQGHAFEARIYAEDPSNNFMPVAGPLVHLSTPRADPSTRIETGVRQGDEVSVHYDPMIAKLVVWAADRQAALTKLRYSLRQYNIVGLHTNIDFLLNLSGHPEFEAGNVHTDFIPQHHKQLLLSRKAAAKESLCQAALGLILKEKAMTDTFTLQAHDQFSPFSSSSGRRLNISYTRNMTLKDGKNNVAIAVTYNHDGSYSMQIEDKTFQVLGNLYSEGDCTYLKCSVNGVASKAKLIILENTIYLFSKEGSIEIDIPVPKYLSSVSSQETQGGPLAPMTGTIEKVFVKAGDKVKAGDSLMVMIAMKMEHTIKSPKDGTVKKVFYREGAQANRHTPLVEFEEEESDKRESE | |||||||
Modified residue | 237 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 494 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 581 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 581 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 681 | UniProt | N6-biotinyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 719 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 724 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Acetylated.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Probably a dodecamer composed of six biotin-containing alpha subunits (MCCC1) and six beta (MCCC2) subunits (PubMed:17360195).
Interacts (via the biotin carboxylation domain) with SIRT4 (PubMed:23438705).
Interacts (via the biotin carboxylation domain) with SIRT4 (PubMed:23438705).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q96RQ3 | MCCC2 Q9HCC0 | 7 | EBI-2211703, EBI-2211296 | |
BINARY | Q96RQ3 | OXCT2 Q9BYC2 | 3 | EBI-2211703, EBI-21843684 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 48-494 | Biotin carboxylation | ||||
Sequence: NITKVLIANRGEIACRVMRTAKKLGVQTVAVYSEADRNSMHVDMADEAYSIGPAPSQQSYLSMEKIIQVAKTSAAQAIHPGCGFLSENMEFAELCKQEGIIFIGPPPSAIRDMGIKSTSKSIMAAAGVPVVEGYHGEDQSDQCLKEHARRIGYPVMIKAVRGGGGKGMRIVRSEQEFQEQLESARREAKKSFNDDAMLIEKFVDTPRHVEVQVFGDHHGNAVYLFERDCSVQRRHQKIIEEAPAPGIKSEVRKKLGEAAVRAAKAVNYVGAGTVEFIMDSKHNFCFMEMNTRLQVEHPVTEMITGTDLVEWQLRIAAGEKIPLSQEEITLQGHAFEARIYAEDPSNNFMPVAGPLVHLSTPRADPSTRIETGVRQGDEVSVHYDPMIAKLVVWAADRQAALTKLRYSLRQYNIVGLHTNIDFLLNLSGHPEFEAGNVHTDFIPQHHK | ||||||
Domain | 167-364 | ATP-grasp | ||||
Sequence: KSIMAAAGVPVVEGYHGEDQSDQCLKEHARRIGYPVMIKAVRGGGGKGMRIVRSEQEFQEQLESARREAKKSFNDDAMLIEKFVDTPRHVEVQVFGDHHGNAVYLFERDCSVQRRHQKIIEEAPAPGIKSEVRKKLGEAAVRAAKAVNYVGAGTVEFIMDSKHNFCFMEMNTRLQVEHPVTEMITGTDLVEWQLRIAA | ||||||
Domain | 643-715 | Biotinyl-binding | ||||
Sequence: QETQGGPLAPMTGTIEKVFVKAGDKVKAGDSLMVMIAMKMEHTIKSPKDGTVKKVFYREGAQANRHTPLVEFE |
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length725
- Mass (Da)80,473
- Last updated2006-05-30 v3
- ChecksumB84AD23806035A40
Computationally mapped potential isoform sequences
There are 7 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 469 | in Ref. 3; AAK67986 | ||||
Sequence: F → L |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF310972 EMBL· GenBank· DDBJ | AAG53095.1 EMBL· GenBank· DDBJ | mRNA | ||
AB029826 EMBL· GenBank· DDBJ | BAA99407.1 EMBL· GenBank· DDBJ | mRNA | ||
AF297332 EMBL· GenBank· DDBJ | AAK67986.1 EMBL· GenBank· DDBJ | mRNA | ||
AF310339 EMBL· GenBank· DDBJ | AAG50245.1 EMBL· GenBank· DDBJ | mRNA | ||
AK023051 EMBL· GenBank· DDBJ | BAB14377.1 EMBL· GenBank· DDBJ | mRNA | ||
AB209737 EMBL· GenBank· DDBJ | BAD92974.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC004214 EMBL· GenBank· DDBJ | AAH04214.1 EMBL· GenBank· DDBJ | mRNA | ||
BC004187 EMBL· GenBank· DDBJ | AAH04187.1 EMBL· GenBank· DDBJ | mRNA |