Reactome | UniProt:P22033 MMUT

chain	transit peptide:1-32 chain:33-750
checksum	B5909729C08B562F
comment	FUNCTION Catalyzes the reversible isomerization of methylmalonyl-CoA (MMCoA) (generated from branched-chain amino acid metabolism and degradation of dietary odd chain fatty acids and cholesterol) to succinyl-CoA (3-carboxypropionyl-CoA), a key intermediate of the tricarboxylic acid cycle.CATALYTIC ACTIVITY (R)-methylmalonyl-CoA = succinyl-CoACOFACTOR During catalysis, accumulation of oxidized inactive cofactor hydroxocobalamin (OH2Cbl) leads to loss of MMUT activity (PubMed:21138732, PubMed:28943303). Interaction with MMAA decreases the rate of OH2Cbl formation and promotes the replacement of OH2Cbl by the active cofactor adenosylcobalamin (AdoCbl), thereby restoring MMUT activity (PubMed:21138732, PubMed:28943303). Inhibited by itaconyl-CoA, a metabolite that inactivates the coenzyme B12 cofactor (PubMed:29056341). Inhibited at high concentration of substrate (PubMed:28943303).BIOPHYSICOCHEMICAL PROPERTIES Homodimer (PubMed:20876572). Interacts (the apoenzyme form) with MMAA; the interaction is GTP dependent (PubMed:20876572, PubMed:21138732, PubMed:28943303).INTERACTION The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the methylmalonyl-CoA mutase family.ONLINE INFORMATION Methylmalonyl coenzyme A mutase entry
crossReference	[DatabaseIdentifier:10975758] Pharos - Targets:P22033 [DatabaseIdentifier:11071082] OpenTargets:ENSG00000146085 [DatabaseIdentifier:11619720] RefSeq:NP_000246.2 [DatabaseIdentifier:11619723] RefSeq:XP_005249200.1 [DatabaseIdentifier:11712927] PDB:2XIJ [DatabaseIdentifier:11712936] PDB:2XIQ [DatabaseIdentifier:11712943] PDB:3BIC [DatabaseIdentifier:11712951] PDB:8DYJ [DatabaseIdentifier:11712961] PDB:8DYL [DatabaseIdentifier:11821642] PRO:P22033 [DatabaseIdentifier:11850610] GeneCards:P22033 [DatabaseIdentifier:11883944] Orphanet:16489 [DatabaseIdentifier:11889603] HMDB Protein:HMDBP00257 [DatabaseIdentifier:11897788] HPA:ENSG00000146085-MMUT [DatabaseIdentifier:12144116] Ensembl:ENSP00000274813 [DatabaseIdentifier:12144117] Ensembl:ENSG00000146085 [DatabaseIdentifier:12144118] Ensembl:ENST00000274813
databaseName	UniProt
dbId	59719
description	recommendedName: fullName evidence="38"Methylmalonyl-CoA mutase, mitochondrial shortName: MCM ecNumber evidence="5 20 23 24 27 28 29"5.4.99.2 alternativeName: Methylmalonyl-CoA isomerase
displayName	UniProt:P22033 MMUT
geneName	MMUT MUT
identifier	P22033
isSequenceChanged	false
keyword	3D-structure Acetylation Cobalamin Cobalt Cytoplasm Direct protein sequencing Disease variant Isomerase Metal-binding Mitochondrion Phosphoprotein Reference proteome Transit peptide
modified	[InstanceEdit:12187927] Wright, Adam, 2024-03-12
name	MMUT
otherIdentifier	11723652_a_at 11723653_at 11758888_at 17019831 202959_PM_at 202959_at 202960_PM_s_at 202960_s_at 2956439 2956440 2956441 2956442 2956443 2956444 2956445 2956447 2956449 2956451 2956452 2956453 2956454 2956455 2956457 2956458 2956459 2956460 2956461 2956462 2956463 2956465 2956466 2956467 40105_at 4594 62961_at 8126860 A_23_P214273 A_23_P400235 GE58043 GO:0003824 GO:0003924 GO:0004494 GO:0005515 GO:0005737 GO:0005739 GO:0005759 GO:0006520 GO:0006629 GO:0006790 GO:0009791 GO:0016787 GO:0016853 GO:0016866 GO:0019678 GO:0031419 GO:0042802 GO:0042803 GO:0043226 GO:0043547 GO:0046872 GO:0048856 GO:0050667 GO:0055086 GO:0072341 GO:1901135 GO:1901290 HMNXSV003042461 Hs.155212.0.A2_3p_at ILMN_1785113 M65131_rna1_at PH_hs_0009350 TC06001782.hg g4557766_3p_a_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-3323133] MUT A378E [mitochondrial matrix] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-3323099] MUT G703R [mitochondrial matrix] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-70998] MUT [mitochondrial matrix] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-3323138] MUT R93H [mitochondrial matrix] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-3323106] MUT W105R [mitochondrial matrix] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-3323123] MUT G623R [mitochondrial matrix] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-3323139] MUT R108C [mitochondrial matrix] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-3323175] MUT G215S [mitochondrial matrix] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-3323146] MUT N219Y [mitochondrial matrix] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-3323178] MUT Q17* [mitochondrial matrix] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8996725] ENSEMBL:ENSG00000146085 MUT [ReferenceDNASequence:11028491] KEGG Gene (Homo sapiens):4594 MMUT [ReferenceDNASequence:11273368] NCBI Gene:4594 MMUT [ReferenceDNASequence:11273369] BioGPS Gene:4594 MMUT [ReferenceDNASequence:11273370] CTD Gene:4594 MMUT [ReferenceDNASequence:11273371] dbSNP Gene:4594 MMUT [ReferenceDNASequence:11273372] Monarch:4594 MMUT [ReferenceDNASequence:11346078] ENSEMBL_homo_sapiens_GENE:ENSG00000146085.8 MMUT [ReferenceDNASequence:11518056] UCSC:P22033 MMUT [ReferenceDNASequence:11802471] OMIM:609058 MMUT [ReferenceDNASequence:11877956] HGNC:7526 MMUT [ReferenceDNASequence:12198274] COSMIC (genes):MMUT MMUT
referenceTranscript	[ReferenceRNASequence:11443538] RefSeq:NM_000255.3 MMUT [ReferenceRNASequence:11443550] RefSeq:XM_005249143.3 MMUT
schemaClass	ReferenceGeneProduct
secondaryIdentifier	MUTA_HUMAN A8K953 Q5SYZ3 Q96B11 Q9UD64
sequenceLength	750
species	[Species:48887] Homo sapiens
url	https://purl.uniprot.org/uniprot/P22033

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-3323133] MUT A378E [mitochondrial matrix] [EntityWithAccessionedSequence:R-HSA-3323099] MUT G703R [mitochondrial matrix] [EntityWithAccessionedSequence:R-HSA-70998] MUT [mitochondrial matrix] [EntityWithAccessionedSequence:R-HSA-3323138] MUT R93H [mitochondrial matrix] [EntityWithAccessionedSequence:R-HSA-3323106] MUT W105R [mitochondrial matrix] [EntityWithAccessionedSequence:R-HSA-3323123] MUT G623R [mitochondrial matrix] [EntityWithAccessionedSequence:R-HSA-3323139] MUT R108C [mitochondrial matrix] [EntityWithAccessionedSequence:R-HSA-3323175] MUT G215S [mitochondrial matrix] [EntityWithAccessionedSequence:R-HSA-3323146] MUT N219Y [mitochondrial matrix] [EntityWithAccessionedSequence:R-HSA-3323178] MUT Q17* [mitochondrial matrix]
(referenceSequence)	[ReplacedResidue:3323167] L-alanine 378 replaced with L-glutamic acid [ReplacedResidue:9766338] L-arginine 93 replaced with L-histidine [ReplacedResidue:3323103] L-tryptophan 105 replaced with L-arginine [ReplacedResidue:3323187] glycine 623 replaced with L-arginine [ReplacedResidue:3323132] L-arginine 108 replaced with L-cysteine [ReplacedResidue:3323120] glycine 215 replaced with L-serine [ReplacedResidue:3323161] L-asparagine 219 replaced with L-tyrosine [NonsenseMutation:3323124] Nonsense mutation at L-glutamine 17 [ReplacedResidue:3323144] glycine 703 replaced with L-arginine
(interactor)	[UndirectedInteraction:12311957] ChEBI:18408 <-> UniProt:P22033 (IntAct) [UndirectedInteraction:12276497] UniProt:P42858 <-> UniProt:P22033 (IntAct) [UndirectedInteraction:12252117] ChEBI:15996 <-> UniProt:P22033 (IntAct)

UniProt:P22033 MMUT Show undefined attributes

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