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Entry version 146 (12 Aug 2020)
Sequence version 3 (10 Jan 2006)
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Protein

Cyanocobalamin reductase / alkylcobalamin dealkylase

Gene

MMACHC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Cobalamin (vitamin B12) cytosolic chaperone that catalyzes the reductive decyanation of cyanocob(III)alamin (cyanocobalamin, CNCbl) to yield cob(II)alamin and cyanide, using FAD or FMN as cofactors and NADPH as cosubstrate (PubMed:18779575, PubMed:19700356, PubMed:21697092, PubMed:25809485). Cyanocobalamin constitutes the inactive form of vitamin B12 introduced from the diet, and is converted into the active cofactors methylcobalamin (MeCbl) involved in methionine biosynthesis, and 5'-deoxyadenosylcobalamin (AdoCbl) involved in the TCA cycle (PubMed:19801555). Forms a complex with the lysosomal transporter ABCD4 and its chaperone LMBRD1, to transport cobalamin across the lysosomal membrane into the cytosol (PubMed:25535791). The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR (methionine synthase) which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine (PubMed:21071249, PubMed:27771510). Also acts as a glutathione transferase by catalyzing the dealkylation of the alkylcob(III)alamins MeCbl and AdoCbl, using the thiolate of glutathione for nucleophilic displacement to generate cob(I)alamin and the corresponding glutathione thioether (PubMed:19801555, PubMed:21697092, PubMed:22642810, PubMed:25809485). The conversion of incoming MeCbl or AdoCbl into a common intermediate cob(I)alamin is necessary to meet the cellular needs for both cofactors (PubMed:19801555). Cysteine and homocysteine cannot substitute for glutathione in this reaction (PubMed:19801555).2 Publications8 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

FAD2 Publications, FMN2 PublicationsNote: Can utilize both FAD and FMN.2 Publications

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

kcat is 11.7 h(-1) for the dealkylation of methylcobalamin (MeCbl) (PubMed:19801555). kcat is 0.006 h(-1) for the dealkylation of 5'-deoxyadenosylcobalamin (AdoCbl) (PubMed:19801555).1 Publication
  1. KM=27.7 µM for glutathione1 Publication

    <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: adenosylcobalamin biosynthesis

    This protein is involved in the pathway adenosylcobalamin biosynthesis, which is part of Cofactor biosynthesis.3 Publications
    View all proteins of this organism that are known to be involved in the pathway adenosylcobalamin biosynthesis and in Cofactor biosynthesis.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei104SubstrateCombined sources2 Publications1
    Binding sitei149Substrate; via amide nitrogenCombined sources2 Publications1
    Binding sitei160Substrate; via amide nitrogen and carbonyl oxygenCombined sources2 Publications1

    <p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

    GO - Biological processi

    <p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

    Molecular functionOxidoreductase, Transferase
    LigandCobalamin, Cobalt, FAD, Flavoprotein, FMN, NADP

    Enzyme and pathway databases

    BioCyc Collection of Pathway/Genome Databases

    More...
    BioCyci
    MetaCyc:ENSG00000132763-MONOMER

    Pathway Commons web resource for biological pathway data

    More...
    PathwayCommonsi
    Q9Y4U1

    Reactome - a knowledgebase of biological pathways and processes

    More...
    Reactomei
    R-HSA-196741, Cobalamin (Cbl, vitamin B12) transport and metabolism
    R-HSA-3359473, Defective MMADHC causes methylmalonic aciduria and homocystinuria type cblD
    R-HSA-3359474, Defective MMACHC causes methylmalonic aciduria and homocystinuria type cblC

    UniPathway: a resource for the exploration and annotation of metabolic pathways

    More...
    UniPathwayi
    UPA00148

    <p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
    Recommended name:
    Cyanocobalamin reductase / alkylcobalamin dealkylase
    Alternative name(s):
    Alkylcobalamin:glutathione S-alkyltransferase (EC:2.5.1.1514 Publications)
    CblC2 Publications
    Cyanocobalamin reductase (cyanide-eliminating) (EC:1.16.1.64 Publications)
    Methylmalonic aciduria and homocystinuria type C protein1 Publication
    Short name:
    MMACHC
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
    Name:MMACHCImported
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
    • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 1

    Organism-specific databases

    Eukaryotic Pathogen Database Resources

    More...
    EuPathDBi
    HostDB:ENSG00000132763.14

    Human Gene Nomenclature Database

    More...
    HGNCi
    HGNC:24525, MMACHC

    Online Mendelian Inheritance in Man (OMIM)

    More...
    MIMi
    609831, gene

    neXtProt; the human protein knowledge platform

    More...
    neXtProti
    NX_Q9Y4U1

    <p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm

    <p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

    <p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

    Methylmalonic aciduria and homocystinuria, cblC type (MAHCC)5 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionAn autosomal recessive disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Affected individuals may have developmental, hematologic, neurologic, metabolic, ophthalmologic, and dermatologic clinical findings. Although considered a disease of infancy or childhood, some individuals develop symptoms in adulthood.
    Related information in OMIM
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_02477027Q → R in MAHCC. 1 PublicationCorresponds to variant dbSNP:rs546099787EnsemblClinVar.1
    Natural variantiVAR_024771116L → P in MAHCC. 1 PublicationCorresponds to variant dbSNP:rs121918240EnsemblClinVar.1
    Natural variantiVAR_024772122H → R in MAHCC. 1 Publication1
    Natural variantiVAR_024773130Y → H in MAHCC. 1 PublicationCorresponds to variant dbSNP:rs372670428EnsemblClinVar.1
    Natural variantiVAR_024774147G → A in MAHCC. 1 PublicationCorresponds to variant dbSNP:rs140522266EnsemblClinVar.1
    Natural variantiVAR_024775147G → D in MAHCC; loss of cyanocobalamin binding. 2 PublicationsCorresponds to variant dbSNP:rs140522266EnsemblClinVar.1
    Natural variantiVAR_024776156G → D in MAHCC. 1 PublicationCorresponds to variant dbSNP:rs1553162910EnsemblClinVar.1
    Natural variantiVAR_024777157W → C in MAHCC. 1 PublicationCorresponds to variant dbSNP:rs1002571805Ensembl.1
    Natural variantiVAR_024778161R → G in MAHCC; results in decreased stability and decreased methylcobalamin dealkylation activity. 2 PublicationsCorresponds to variant dbSNP:rs370596113EnsemblClinVar.1
    Natural variantiVAR_024779161R → Q in MAHCC; results in decreased stability and reduced stabilization induced by cobalamin binding; has reduced affinity for cyanocobalamin and reduced activity in dealkylation of methylcobalamin. 5 PublicationsCorresponds to variant dbSNP:rs121918243EnsemblClinVar.1
    Natural variantiVAR_024780189R → S in MAHCC. 1 PublicationCorresponds to variant dbSNP:rs200895671EnsemblClinVar.1
    Natural variantiVAR_024781193L → P in MAHCC. 1 PublicationCorresponds to variant dbSNP:rs1233135084EnsemblClinVar.1
    Natural variantiVAR_024782206R → P in MAHCC. 1 PublicationCorresponds to variant dbSNP:rs371753672EnsemblClinVar.1
    Natural variantiVAR_024783206R → W in MAHCC. 1 PublicationCorresponds to variant dbSNP:rs538023671EnsemblClinVar.1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi122H → A: Reduced affinity for cyanocobalamin. 1 Publication1
    Mutagenesisi206R → Q: Impairs protein folding. 1 Publication1
    Mutagenesisi230R → Q: Reduced activity in dealkylation of methylcobalamin. 1 Publication1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNET

    More...
    DisGeNETi
    25974

    GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

    More...
    GeneReviewsi
    MMACHC

    MalaCards human disease database

    More...
    MalaCardsi
    MMACHC
    MIMi277400, phenotype

    Open Targets

    More...
    OpenTargetsi
    ENSG00000132763

    Orphanet; a database dedicated to information on rare diseases and orphan drugs

    More...
    Orphaneti
    79282, Methylmalonic acidemia with homocystinuria, type cblC

    The Pharmacogenetics and Pharmacogenomics Knowledge Base

    More...
    PharmGKBi
    PA142671348

    Miscellaneous databases

    Pharos NIH Druggable Genome Knowledgebase

    More...
    Pharosi
    Q9Y4U1, Tbio

    Chemistry databases

    Drug and drug target database

    More...
    DrugBanki
    DB00115, Cyanocobalamin
    DB00200, Hydroxocobalamin

    Polymorphism and mutation databases

    BioMuta curated single-nucleotide variation and disease association database

    More...
    BioMutai
    MMACHC

    Domain mapping of disease mutations (DMDM)

    More...
    DMDMi
    85681045

    <p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000762581 – 282Cyanocobalamin reductase / alkylcobalamin dealkylaseAdd BLAST282

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei245PhosphoserineCombined sources1
    Modified residuei247PhosphoserineCombined sources1
    Modified residuei275PhosphoserineCombined sources1
    Modified residuei279PhosphoserineCombined sources1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    Encyclopedia of Proteome Dynamics

    More...
    EPDi
    Q9Y4U1

    jPOST - Japan Proteome Standard Repository/Database

    More...
    jPOSTi
    Q9Y4U1

    MassIVE - Mass Spectrometry Interactive Virtual Environment

    More...
    MassIVEi
    Q9Y4U1

    MaxQB - The MaxQuant DataBase

    More...
    MaxQBi
    Q9Y4U1

    PaxDb, a database of protein abundance averages across all three domains of life

    More...
    PaxDbi
    Q9Y4U1

    PeptideAtlas

    More...
    PeptideAtlasi
    Q9Y4U1

    PRoteomics IDEntifications database

    More...
    PRIDEi
    Q9Y4U1

    ProteomicsDB: a multi-organism proteome resource

    More...
    ProteomicsDBi
    86249

    Consortium for Top Down Proteomics

    More...
    TopDownProteomicsi
    Q9Y4U1

    PTM databases

    iPTMnet integrated resource for PTMs in systems biology context

    More...
    iPTMneti
    Q9Y4U1

    Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

    More...
    PhosphoSitePlusi
    Q9Y4U1

    <p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

    <p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

    Widely expressed. Expressed at higher level in fetal liver. Also expressed in spleen, lymph node, thymus and bone marrow. Weakly or not expressed in peripheral blood leukocytes.1 Publication

    Gene expression databases

    Bgee dataBase for Gene Expression Evolution

    More...
    Bgeei
    ENSG00000132763, Expressed in liver and 148 other tissues

    ExpressionAtlas, Differential and Baseline Expression

    More...
    ExpressionAtlasi
    Q9Y4U1, baseline and differential

    Genevisible search portal to normalized and curated expression data from Genevestigator

    More...
    Genevisiblei
    Q9Y4U1, HS

    Organism-specific databases

    Human Protein Atlas

    More...
    HPAi
    ENSG00000132763, Tissue enhanced (liver)

    <p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

    <p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

    Monomer in the absence of bound substrate (PubMed:21697092, PubMed:22642810). Homodimer; dimerization is triggered by binding to FMN or adenosylcobalamin (PubMed:22642810).

    Interacts with LMBRD1 and ABCD4; the interaction ensures the transport of cobalamin from the lysosome to the cytoplasm (PubMed:25535791).

    Forms a multiprotein complex with MMADHC, MTR and MTRR; the interaction with MTR could modulate MMACHC-dependent processing of cobalamin (PubMed:27771510). Heterodimer with MMADHC; the interaction might play a role in the regulation of the balance between AdoCbl and MeCbl synthesis (PubMed:21071249, PubMed:23415655, PubMed:26483544).

    7 Publications

    <p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

    GO - Molecular functioni

    Protein-protein interaction databases

    The Biological General Repository for Interaction Datasets (BioGRID)

    More...
    BioGRIDi
    117458, 7 interactors

    Protein interaction database and analysis system

    More...
    IntActi
    Q9Y4U1, 2 interactors

    STRING: functional protein association networks

    More...
    STRINGi
    9606.ENSP00000383840

    Miscellaneous databases

    RNAct, Protein-RNA interaction predictions for model organisms.

    More...
    RNActi
    Q9Y4U1, protein

    <p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

    Secondary structure

    1282
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    SWISS-MODEL Repository - a database of annotated 3D protein structure models

    More...
    SMRi
    Q9Y4U1

    Database of comparative protein structure models

    More...
    ModBasei
    Search...

    Protein Data Bank in Europe - Knowledge Base

    More...
    PDBe-KBi
    Search...

    Miscellaneous databases

    Relative evolutionary importance of amino acids within a protein sequence

    More...
    EvolutionaryTracei
    Q9Y4U1

    <p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni115 – 118Substrate bindingCombined sources2 Publications4
    Regioni129 – 131Substrate bindingCombined sources2 Publications3

    <p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

    Belongs to the MMACHC family.Curated

    Phylogenomic databases

    evolutionary genealogy of genes: Non-supervised Orthologous Groups

    More...
    eggNOGi
    KOG4552, Eukaryota

    Ensembl GeneTree

    More...
    GeneTreei
    ENSGT00390000003464

    The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

    More...
    HOGENOMi
    CLU_095722_0_0_1

    InParanoid: Eukaryotic Ortholog Groups

    More...
    InParanoidi
    Q9Y4U1

    KEGG Orthology (KO)

    More...
    KOi
    K14618

    Identification of Orthologs from Complete Genome Data

    More...
    OMAi
    WQDWTYR

    Database of Orthologous Groups

    More...
    OrthoDBi
    1375709at2759

    Database for complete collections of gene phylogenies

    More...
    PhylomeDBi
    Q9Y4U1

    TreeFam database of animal gene trees

    More...
    TreeFami
    TF332476

    Family and domain databases

    Conserved Domains Database

    More...
    CDDi
    cd12959, MMACHC-like, 1 hit

    Integrated resource of protein families, domains and functional sites

    More...
    InterProi
    View protein in InterPro
    IPR032037, MMACHC

    The PANTHER Classification System

    More...
    PANTHERi
    PTHR31457, PTHR31457, 1 hit

    Pfam protein domain database

    More...
    Pfami
    View protein in Pfam
    PF16690, MMACHC, 1 hit

    <p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

    <p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

    This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

    Q9Y4U1-1 [UniParc]FASTAAdd to basket
    « Hide
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    MEPKVAELKQ KIEDTLCPFG FEVYPFQVAW YNELLPPAFH LPLPGPTLAF
    60 70 80 90 100
    LVLSTPAMFD RALKPFLQSC HLRMLTDPVD QCVAYHLGRV RESLPELQIE
    110 120 130 140 150
    IIADYEVHPN RRPKILAQTA AHVAGAAYYY QRQDVEADPW GNQRISGVCI
    160 170 180 190 200
    HPRFGGWFAI RGVVLLPGIE VPDLPPRKPH DCVPTRADRI ALLEGFNFHW
    210 220 230 240 250
    RDWTYRDAVT PQERYSEEQK AYFSTPPAQR LALLGLAQPS EKPSSPSPDL
    260 270 280
    PFTTPAPKKP GNPSRARSWL SPRVSPPASP GP
    Length:282
    Mass (Da):31,728
    Last modified:January 10, 2006 - v3
    <p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i3A7E6BC774CB5D17
    GO

    <p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

    There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    A0A0C4DGU2A0A0C4DGU2_HUMAN
    Alkylcobalamin:glutathione S-alkylt...
    MMACHC
    225Annotation score:

    Annotation score:3 out of 5

    <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

    <p>This subsection of the 'Sequence' section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

    The sequence AAH06122 differs from that shown. Reason: Erroneous initiation.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti100E → G in CAB45693 (PubMed:17974005).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_02477027Q → R in MAHCC. 1 PublicationCorresponds to variant dbSNP:rs546099787EnsemblClinVar.1
    Natural variantiVAR_024771116L → P in MAHCC. 1 PublicationCorresponds to variant dbSNP:rs121918240EnsemblClinVar.1
    Natural variantiVAR_024772122H → R in MAHCC. 1 Publication1
    Natural variantiVAR_024773130Y → H in MAHCC. 1 PublicationCorresponds to variant dbSNP:rs372670428EnsemblClinVar.1
    Natural variantiVAR_024774147G → A in MAHCC. 1 PublicationCorresponds to variant dbSNP:rs140522266EnsemblClinVar.1
    Natural variantiVAR_024775147G → D in MAHCC; loss of cyanocobalamin binding. 2 PublicationsCorresponds to variant dbSNP:rs140522266EnsemblClinVar.1
    Natural variantiVAR_024776156G → D in MAHCC. 1 PublicationCorresponds to variant dbSNP:rs1553162910EnsemblClinVar.1
    Natural variantiVAR_024777157W → C in MAHCC. 1 PublicationCorresponds to variant dbSNP:rs1002571805Ensembl.1
    Natural variantiVAR_024778161R → G in MAHCC; results in decreased stability and decreased methylcobalamin dealkylation activity. 2 PublicationsCorresponds to variant dbSNP:rs370596113EnsemblClinVar.1
    Natural variantiVAR_024779161R → Q in MAHCC; results in decreased stability and reduced stabilization induced by cobalamin binding; has reduced affinity for cyanocobalamin and reduced activity in dealkylation of methylcobalamin. 5 PublicationsCorresponds to variant dbSNP:rs121918243EnsemblClinVar.1
    Natural variantiVAR_024780189R → S in MAHCC. 1 PublicationCorresponds to variant dbSNP:rs200895671EnsemblClinVar.1
    Natural variantiVAR_024781193L → P in MAHCC. 1 PublicationCorresponds to variant dbSNP:rs1233135084EnsemblClinVar.1
    Natural variantiVAR_024782206R → P in MAHCC. 1 PublicationCorresponds to variant dbSNP:rs371753672EnsemblClinVar.1
    Natural variantiVAR_024783206R → W in MAHCC. 1 PublicationCorresponds to variant dbSNP:rs538023671EnsemblClinVar.1
    Natural variantiVAR_038805271S → G. Corresponds to variant dbSNP:rs35219601EnsemblClinVar.1

    Sequence databases

    Select the link destinations:

    EMBL nucleotide sequence database

    More...
    EMBLi

    GenBank nucleotide sequence database

    More...
    GenBanki

    DNA Data Bank of Japan; a nucleotide sequence database

    More...
    DDBJi
    Links Updated
    AL080062 mRNA Translation: CAB45693.2
    AL451136 Genomic DNA No translation available.
    BC006122 mRNA Translation: AAH06122.3 Different initiation.

    The Consensus CDS (CCDS) project

    More...
    CCDSi
    CCDS41324.1

    Protein sequence database of the Protein Information Resource

    More...
    PIRi
    T12462

    NCBI Reference Sequences

    More...
    RefSeqi
    NP_001317469.1, NM_001330540.1
    NP_056321.2, NM_015506.2

    Genome annotation databases

    Ensembl eukaryotic genome annotation project

    More...
    Ensembli
    ENST00000401061; ENSP00000383840; ENSG00000132763

    Database of genes from NCBI RefSeq genomes

    More...
    GeneIDi
    25974

    KEGG: Kyoto Encyclopedia of Genes and Genomes

    More...
    KEGGi
    hsa:25974

    UCSC genome browser

    More...
    UCSCi
    uc009vxv.4, human

    <p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

    <p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AL080062 mRNA Translation: CAB45693.2
    AL451136 Genomic DNA No translation available.
    BC006122 mRNA Translation: AAH06122.3 Different initiation.
    CCDSiCCDS41324.1
    PIRiT12462
    RefSeqiNP_001317469.1, NM_001330540.1
    NP_056321.2, NM_015506.2

    3D structure databases

    Select the link destinations:

    Protein Data Bank Europe

    More...
    PDBei

    Protein Data Bank RCSB

    More...
    RCSB PDBi

    Protein Data Bank Japan

    More...
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3SBYX-ray2.71A/B1-244[»]
    3SBZX-ray2.00A1-244[»]
    3SC0X-ray1.95A1-238[»]
    3SOMX-ray2.40A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P1-282[»]
    5UOSX-ray2.51A1-238[»]
    SMRiQ9Y4U1
    ModBaseiSearch...
    PDBe-KBiSearch...

    Protein-protein interaction databases

    BioGRIDi117458, 7 interactors
    IntActiQ9Y4U1, 2 interactors
    STRINGi9606.ENSP00000383840

    Chemistry databases

    DrugBankiDB00115, Cyanocobalamin
    DB00200, Hydroxocobalamin

    PTM databases

    iPTMnetiQ9Y4U1
    PhosphoSitePlusiQ9Y4U1

    Polymorphism and mutation databases

    BioMutaiMMACHC
    DMDMi85681045

    Proteomic databases

    EPDiQ9Y4U1
    jPOSTiQ9Y4U1
    MassIVEiQ9Y4U1
    MaxQBiQ9Y4U1
    PaxDbiQ9Y4U1
    PeptideAtlasiQ9Y4U1
    PRIDEiQ9Y4U1
    ProteomicsDBi86249
    TopDownProteomicsiQ9Y4U1

    Protocols and materials databases

    ABCD curated depository of sequenced antibodies

    More...
    ABCDi
    Q9Y4U1, 1 sequenced antibody

    Antibodypedia a portal for validated antibodies

    More...
    Antibodypediai
    32641, 372 antibodies

    The DNASU plasmid repository

    More...
    DNASUi
    25974

    Genome annotation databases

    EnsembliENST00000401061; ENSP00000383840; ENSG00000132763
    GeneIDi25974
    KEGGihsa:25974
    UCSCiuc009vxv.4, human

    Organism-specific databases

    Comparative Toxicogenomics Database

    More...
    CTDi
    25974
    DisGeNETi25974
    EuPathDBiHostDB:ENSG00000132763.14

    GeneCards: human genes, protein and diseases

    More...
    GeneCardsi
    MMACHC
    GeneReviewsiMMACHC
    HGNCiHGNC:24525, MMACHC
    HPAiENSG00000132763, Tissue enhanced (liver)
    MalaCardsiMMACHC
    MIMi277400, phenotype
    609831, gene
    neXtProtiNX_Q9Y4U1
    OpenTargetsiENSG00000132763
    Orphaneti79282, Methylmalonic acidemia with homocystinuria, type cblC
    PharmGKBiPA142671348

    GenAtlas: human gene database

    More...
    GenAtlasi
    Search...

    Phylogenomic databases

    eggNOGiKOG4552, Eukaryota
    GeneTreeiENSGT00390000003464
    HOGENOMiCLU_095722_0_0_1
    InParanoidiQ9Y4U1
    KOiK14618
    OMAiWQDWTYR
    OrthoDBi1375709at2759
    PhylomeDBiQ9Y4U1
    TreeFamiTF332476

    Enzyme and pathway databases

    UniPathwayiUPA00148
    BioCyciMetaCyc:ENSG00000132763-MONOMER
    PathwayCommonsiQ9Y4U1
    ReactomeiR-HSA-196741, Cobalamin (Cbl, vitamin B12) transport and metabolism
    R-HSA-3359473, Defective MMADHC causes methylmalonic aciduria and homocystinuria type cblD
    R-HSA-3359474, Defective MMACHC causes methylmalonic aciduria and homocystinuria type cblC

    Miscellaneous databases

    BioGRID ORCS database of CRISPR phenotype screens

    More...
    BioGRID-ORCSi
    25974, 47 hits in 879 CRISPR screens

    ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

    More...
    ChiTaRSi
    MMACHC, human
    EvolutionaryTraceiQ9Y4U1

    The Gene Wiki collection of pages on human genes and proteins

    More...
    GeneWikii
    MMACHC

    Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

    More...
    GenomeRNAii
    25974
    PharosiQ9Y4U1, Tbio

    Protein Ontology

    More...
    PROi
    PR:Q9Y4U1
    RNActiQ9Y4U1, protein

    The Stanford Online Universal Resource for Clones and ESTs

    More...
    SOURCEi
    Search...

    Gene expression databases

    BgeeiENSG00000132763, Expressed in liver and 148 other tissues
    ExpressionAtlasiQ9Y4U1, baseline and differential
    GenevisibleiQ9Y4U1, HS

    Family and domain databases

    CDDicd12959, MMACHC-like, 1 hit
    InterProiView protein in InterPro
    IPR032037, MMACHC
    PANTHERiPTHR31457, PTHR31457, 1 hit
    PfamiView protein in Pfam
    PF16690, MMACHC, 1 hit

    ProtoNet; Automatic hierarchical classification of proteins

    More...
    ProtoNeti
    Search...

    MobiDB: a database of protein disorder and mobility annotations

    More...
    MobiDBi
    Search...

    <p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

    <p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiMMAC_HUMAN
    <p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q9Y4U1
    Secondary accession number(s): Q5T157, Q9BRQ7
    <p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 10, 2006
    Last sequence update: January 10, 2006
    Last modified: August 12, 2020
    This is version 146 of the entry and version 3 of the sequence. See complete history.
    <p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    <p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

    Keywords - Technical termi

    3D-structure, Reference proteome

    Documents

    1. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    4. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    5. SIMILARITY comments
      Index of protein domains and families
    6. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    7. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
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