MMACHC

Protein identityUniProt · HPA

UniProt accession

Q9Y4U1

Gene

MMACHC

Ensembl

ENSG00000132763

Chromosome

1

Canonical length

282 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Plasma membrane,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

The exact function of the protein encoded by this gene is not known, however, its C-terminal region shows similarity to TonB, a bacterial protein involved in energy transduction for cobalamin (vitamin B12) uptake. Hence, it is postulated that this protein may have a role in the binding and intracellular trafficking of cobalamin. Mutations in this gene are associated with methylmalonic aciduria and homocystinuria type cblC. [provided by RefSeq, Oct 2009]

Canonical amino-acid sequenceUniProt

282 residues, UniProt reviewed canonical sequence.

>Q9Y4U1|MMACHC
     1  MEPKVAELKQ KIEDTLCPFG FEVYPFQVAW YNELLPPAFH LPLPGPTLAF LVLSTPAMFD
    61  RALKPFLQSC HLRMLTDPVD QCVAYHLGRV RESLPELQIE IIADYEVHPN RRPKILAQTA
   121  AHVAGAAYYY QRQDVEADPW GNQRISGVCI HPRFGGWFAI RGVVLLPGIE VPDLPPRKPH
   181  DCVPTRADRI ALLEGFNFHW RDWTYRDAVT PQERYSEEQK AYFSTPPAQR LALLGLAQPS
   241  EKPSSPSPDL PFTTPAPKKP GNPSRARSWL SPRVSPPASP GP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MMACHC can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.33

Highest tissue expression

16 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MMACHC.

Disease | AllUniProt

Conditions MMACHC is implicated in, by any mechanism.

• Methylmalonic aciduria and homocystinuria, cblC type (MAHCC) MIM:277400

Disease | GeneticClinVar

179 pathogenic / likely-pathogenic of 661 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Cobalamin C disease
• MMACHC-related disorder
• Disorders of Intracellular Cobalamin Metabolism
• Inborn genetic diseases
• METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, cblC TYPE, DIGENIC

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.76

gnomAD pLI

0

gnomAD missense Z

-1.08

DepMap mean gene effect

-0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cobalamin metabolic process
• demethylation
• glutathione metabolic process

Molecular functions

• cobalamin binding
• demethylase activity
• FAD binding
• glutathione binding
• oxidoreductase activity
• protein homodimerization activity
• transferase activity, transferring alkyl or aryl (other than methyl) groups
• cyanocobalamin reductase (cyanide-eliminating) (NADP+) activity

Cellular components

• cytoplasm
• cytosol

Protein domainsUniProt · Pfam · InterPro

• Methylmalonic aciduria and homocystinuria type C family
• Methylmalonic aciduria and homocystinuria type C family

KeywordsUniProt

• Cobalamin
• Cobalt
• Cytoplasm
• FAD
• Flavoprotein
• FMN
• NADP
• Oxidoreductase
• Phosphoprotein
• Transferase

InteractionsUniProt · HPA

Protein binding partners of MMACHC in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ABCD4
• LMBRD1