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Details on Person UniProt:Q8IVH4 MMAA

Class:IdReferenceGeneProduct:95395
_chainChangeLogtransit peptide:1-65 added on Fri February 6 2015;chain:66-418 added on Fri February 6 2015
_displayNameUniProt:Q8IVH4 MMAA
_timestamp2025-02-21 20:01:10
chaintransit peptide:1-65
chain:66-418
checksumAD9EA19DDB8DEEF8
commentFUNCTION GTPase, binds and hydrolyzes GTP (PubMed:20876572, PubMed:21138732, PubMed:28497574, PubMed:28943303). Involved in intracellular vitamin B12 metabolism, mediates the transport of cobalamin (Cbl) into mitochondria for the final steps of adenosylcobalamin (AdoCbl) synthesis (PubMed:20876572, PubMed:28497574). Functions as a G-protein chaperone that assists AdoCbl cofactor delivery from MMAB to the methylmalonyl-CoA mutase (MMUT) (PubMed:20876572, PubMed:28497574). Plays a dual role as both a protectase and a reactivase for MMUT (PubMed:21138732, PubMed:28943303). Protects MMUT from progressive inactivation by oxidation by decreasing the rate of the formation of the oxidized inactive cofactor hydroxocobalamin (OH2Cbl) (PubMed:21138732, PubMed:28943303). Additionally acts a reactivase by promoting the replacement of OH2Cbl by the active cofactor AdoCbl, restoring the activity of MMUT in the presence and hydrolysis of GTP (PubMed:21138732, PubMed:28943303).CATALYTIC ACTIVITY GTP + H2O = GDP + phosphate + H(+)ACTIVITY REGULATION GTPase activity is stimulated by MMUT.BIOPHYSICOCHEMICAL PROPERTIES kcat is 0.201 min(-1) for GTP hydrolysis (PubMed:28497574). kcat is 0.03 min(-1) for GTP hydrolysis (PubMed:20876572).SUBUNIT Homodimer (PubMed:20876572). Interacts with MMUT (the apoenzyme form); the interaction is GTP dependent (PubMed:20876572, PubMed:21138732, PubMed:28497574, PubMed:28943303).INTERACTION Widely expressed. Highest expression is observed in liver and skeletal muscle.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the SIMIBI class G3E GTPase family. ArgK/MeaB subfamily.
descriptionrecommendedName: fullName evidence="11"Methylmalonic aciduria type A protein, mitochondrial ecNumber evidence="6 7 9 10"3.6.-.-
geneNameMMAA
identifierQ8IVH4
isSequenceChangedFALSE
keyword3D-structure
Chaperone
Cytoplasm
Disease variant
GTP-binding
Hydrolase
Mitochondrion
Nucleotide-binding
Proteomics identification
Reference proteome
Transit peptide
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
nameMMAA
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8990832] ENSEMBL:ENSG00000151611 MMAA [Homo sapiens]
secondaryIdentifierMMAA_HUMAN
B3KX40
Q495G7
sequenceLength418
species[Species:48887] Homo sapiens
(referenceEntity)[EntityWithAccessionedSequence:2980907] MMAA [mitochondrial matrix] [Homo sapiens]
[EntityWithAccessionedSequence:3322133] MMAA Y207C [mitochondrial matrix] [Homo sapiens]
[EntityWithAccessionedSequence:3322136] MMAA R145* [mitochondrial matrix] [Homo sapiens]
[EntityWithAccessionedSequence:3322137] MMAA Q95* [mitochondrial matrix] [Homo sapiens]
[EntityWithAccessionedSequence:3322147] MMAA K88Ifs*9 [mitochondrial matrix] [Homo sapiens]
(referenceSequence)[NonsenseMutation:3322113] Nonsense mutation at L-arginine 145
[ReplacedResidue:3322115] L-isoleucine 94 replaced with L-leucine
[ReplacedResidue:3322118] L-glutamine 95 replaced with L-valine
[NonsenseMutation:3322119] Nonsense mutation at L-glutamine 95
[ReplacedResidue:3322123] glycine 96 replaced with unknown
[ReplacedResidue:3322124] L-aspartic acid 87 replaced with L-isoleucine
[ReplacedResidue:3322126] glycine 92 replaced with L-phenylalanine
[ReplacedResidue:3322129] L-threonine 91 replaced with L-asparagine
[ReplacedResidue:3322139] L-lysine 93 replaced with L-isoleucine
[ReplacedResidue:3322144] L-tyrosine 207 replaced with L-cysteine
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No pathways have been reviewed or authored by UniProt:Q8IVH4 MMAA (95395)