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Entry version 151 (29 Sep 2021)
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_section">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_section">'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_section">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

BRENDA Comprehensive Enzyme Information System

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BRENDAi
2.5.1.151, 2681

Pathway Commons web resource for biological pathway data

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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_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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_manual">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

Human Gene Nomenclature Database

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HGNCi
HGNC:24525, MMACHC

Online Mendelian Inheritance in Man (OMIM)

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MIMi
609831, gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_Q9Y4U1

Eukaryotic Pathogen, Vector and Host Database Resources

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VEuPathDBi
HostDB:ENSG00000132763

<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

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 variants 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_and_biotech_section">'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 variant

Organism-specific databases

DisGeNET

More...
DisGeNETi
25974

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

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GeneReviewsi
MMACHC

MalaCards human disease database

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MalaCardsi
MMACHC
MIMi277400, phenotype

Open Targets

More...
OpenTargetsi
ENSG00000132763

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

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Orphaneti
79282, Methylmalonic acidemia with homocystinuria, type cblC

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA142671348

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...
Pharosi
Q9Y4U1, Tbio

Chemistry databases

Drug and drug target database

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DrugBanki
DB00115, Cyanocobalamin
DB00200, Hydroxocobalamin

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

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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

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EPDi
Q9Y4U1

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
Q9Y4U1

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
Q9Y4U1

MaxQB - The MaxQuant DataBase

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MaxQBi
Q9Y4U1

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

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PaxDbi
Q9Y4U1

PeptideAtlas

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PeptideAtlasi
Q9Y4U1

PRoteomics IDEntifications database

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PRIDEi
Q9Y4U1

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
86249

Consortium for Top Down Proteomics

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TopDownProteomicsi
Q9Y4U1

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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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 149 other tissues

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q9Y4U1, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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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_section">'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_section">'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_section">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)

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BioGRIDi
117458, 7 interactors

Protein interaction database and analysis system

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IntActi
Q9Y4U1, 2 interactors

STRING: functional protein association networks

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STRINGi
9606.ENSP00000383840

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

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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

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SMRi
Q9Y4U1

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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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
Regioni234 – 282DisorderedSequence analysisAdd BLAST49

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes the position of regions of compositional bias within the protein and the particular type of amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi244 – 258Pro residuesSequence analysisAdd BLAST15

<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

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eggNOGi
KOG4552, Eukaryota

Ensembl GeneTree

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GeneTreei
ENSGT00390000003464

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
CLU_095722_0_0_1

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q9Y4U1

Identification of Orthologs from Complete Genome Data

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OMAi
QMEVIAD

Database of Orthologous Groups

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OrthoDBi
1375709at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
Q9Y4U1

TreeFam database of animal gene trees

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TreeFami
TF332476

Family and domain databases

Conserved Domains Database

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CDDi
cd12959, MMACHC-like, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR032037, MMACHC

The PANTHER Classification System

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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_length">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_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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
        10         20         30         40         50
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

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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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

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CCDSi
CCDS41324.1

Protein sequence database of the Protein Information Resource

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PIRi
T12462

NCBI Reference Sequences

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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

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GeneIDi
25974

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:25974

UCSC genome browser

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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

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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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

Genetic variation 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

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Antibodypediai
32641, 380 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

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
VEuPathDBiHostDB:ENSG00000132763

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG4552, Eukaryota
GeneTreeiENSGT00390000003464
HOGENOMiCLU_095722_0_0_1
InParanoidiQ9Y4U1
OMAiQMEVIAD
OrthoDBi1375709at2759
PhylomeDBiQ9Y4U1
TreeFamiTF332476

Enzyme and pathway databases

UniPathwayiUPA00148
BioCyciMetaCyc:ENSG00000132763-MONOMER
BRENDAi2.5.1.151, 2681
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, 55 hits in 1024 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 149 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

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_and_isoforms">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: September 29, 2021
This is version 151 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 chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with genetic variants
    List of human entries with genetic variants
  3. Human variants curated from literature reports
    Index of human variants curated from literature reports
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families
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