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Protein

Methylmalonic aciduria and homocystinuria type C protein

Gene

MMACHC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May be involved in the binding and intracellular trafficking of cobalamin (vitamin B12).

Pathway: adenosylcobalamin biosynthesis

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

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

Cobalamin, Cobalt

Enzyme and pathway databases

ReactomeiREACT_163862. Cobalamin (Cbl, vitamin B12) transport and metabolism.
REACT_169169. Defective MMACHC causes methylmalonic aciduria and homocystinuria type cblC.
REACT_169256. Defective MMADHC causes methylmalonic aciduria and homocystinuria type cblD.
UniPathwayiUPA00148.

Names & Taxonomyi

Protein namesi
Recommended name:
Methylmalonic aciduria and homocystinuria type C protein
Gene namesi
Name:MMACHC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:24525. MMACHC.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Methylmalonic aciduria and homocystinuria type cblC (MMAHCC)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:277400
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti27 – 271Q → R in MMAHCC. 1 Publication
VAR_024770
Natural varianti116 – 1161L → P in MMAHCC. 1 Publication
VAR_024771
Natural varianti122 – 1221H → R in MMAHCC. 1 Publication
VAR_024772
Natural varianti130 – 1301Y → H in MMAHCC. 1 Publication
VAR_024773
Natural varianti147 – 1471G → A in MMAHCC. 1 Publication
Corresponds to variant rs140522266 [ dbSNP | Ensembl ].
VAR_024774
Natural varianti147 – 1471G → D in MMAHCC. 1 Publication
VAR_024775
Natural varianti156 – 1561G → D in MMAHCC. 1 Publication
VAR_024776
Natural varianti157 – 1571W → C in MMAHCC. 1 Publication
VAR_024777
Natural varianti161 – 1611R → G in MMAHCC. 1 Publication
VAR_024778
Natural varianti161 – 1611R → Q in MMAHCC. 1 Publication
VAR_024779
Natural varianti189 – 1891R → S in MMAHCC. 1 Publication
VAR_024780
Natural varianti193 – 1931L → P in MMAHCC. 1 Publication
VAR_024781
Natural varianti206 – 2061R → P in MMAHCC. 1 Publication
VAR_024782
Natural varianti206 – 2061R → W in MMAHCC. 1 Publication
VAR_024783

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi277400. phenotype.
603174. phenotype.
Orphaneti79282. Methylmalonic acidemia with homocystinuria, type cblC.
PharmGKBiPA142671348.

Chemistry

DrugBankiDB00115. Cyanocobalamin.
DB00200. Hydroxocobalamin.

Polymorphism and mutation databases

BioMutaiMMACHC.
DMDMi85681045.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 282282Methylmalonic aciduria and homocystinuria type C proteinPRO_0000076258Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei245 – 2451Phosphoserine1 Publication
Modified residuei247 – 2471Phosphoserine1 Publication
Modified residuei275 – 2751Phosphoserine2 Publications
Modified residuei279 – 2791Phosphoserine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9Y4U1.
PaxDbiQ9Y4U1.
PRIDEiQ9Y4U1.

PTM databases

PhosphoSiteiQ9Y4U1.

Expressioni

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

BgeeiQ9Y4U1.
CleanExiHS_MMACHC.
GenevisibleiQ9Y4U1. HS.

Organism-specific databases

HPAiHPA027394.
HPA027399.
HPA027402.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
MTRQ997073EBI-9775184,EBI-1045782

Protein-protein interaction databases

BioGridi117458. 3 interactions.
IntActiQ9Y4U1. 1 interaction.
STRINGi9606.ENSP00000383840.

Structurei

Secondary structure

1
282
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi3 – 1614Combined sources
Helixi17 – 193Combined sources
Beta strandi21 – 277Combined sources
Helixi28 – 325Combined sources
Helixi37 – 393Combined sources
Beta strandi47 – 548Combined sources
Helixi58 – 614Combined sources
Helixi63 – 664Combined sources
Beta strandi74 – 763Combined sources
Helixi78 – 9316Combined sources
Beta strandi100 – 1034Combined sources
Helixi104 – 1063Combined sources
Beta strandi113 – 1153Combined sources
Helixi117 – 1237Combined sources
Beta strandi126 – 1305Combined sources
Helixi132 – 1343Combined sources
Beta strandi135 – 1373Combined sources
Turni139 – 1424Combined sources
Beta strandi148 – 1514Combined sources
Turni152 – 1543Combined sources
Beta strandi159 – 17012Combined sources
Helixi186 – 19813Combined sources
Helixi200 – 2023Combined sources
Helixi204 – 2074Combined sources
Helixi217 – 2226Combined sources
Helixi226 – 2294Combined sources
Turni235 – 2373Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliQ9Y4U1.
SMRiQ9Y4U1. Positions 2-238.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y4U1.

Family & Domainsi

Sequence similaritiesi

Belongs to the MMACHC family.Curated

Phylogenomic databases

eggNOGiNOG80998.
GeneTreeiENSGT00390000003464.
HOGENOMiHOG000231413.
HOVERGENiHBG080267.
InParanoidiQ9Y4U1.
KOiK14618.
OMAiWYNELLP.
PhylomeDBiQ9Y4U1.
TreeFamiTF332476.

Sequencei

Sequence statusi: Complete.

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
Checksum:i3A7E6BC774CB5D17
GO

Sequence cautioni

The sequence AAH06122.3 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti100 – 1001E → G in CAB45693 (PubMed:17974005).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti27 – 271Q → R in MMAHCC. 1 Publication
VAR_024770
Natural varianti116 – 1161L → P in MMAHCC. 1 Publication
VAR_024771
Natural varianti122 – 1221H → R in MMAHCC. 1 Publication
VAR_024772
Natural varianti130 – 1301Y → H in MMAHCC. 1 Publication
VAR_024773
Natural varianti147 – 1471G → A in MMAHCC. 1 Publication
Corresponds to variant rs140522266 [ dbSNP | Ensembl ].
VAR_024774
Natural varianti147 – 1471G → D in MMAHCC. 1 Publication
VAR_024775
Natural varianti156 – 1561G → D in MMAHCC. 1 Publication
VAR_024776
Natural varianti157 – 1571W → C in MMAHCC. 1 Publication
VAR_024777
Natural varianti161 – 1611R → G in MMAHCC. 1 Publication
VAR_024778
Natural varianti161 – 1611R → Q in MMAHCC. 1 Publication
VAR_024779
Natural varianti189 – 1891R → S in MMAHCC. 1 Publication
VAR_024780
Natural varianti193 – 1931L → P in MMAHCC. 1 Publication
VAR_024781
Natural varianti206 – 2061R → P in MMAHCC. 1 Publication
VAR_024782
Natural varianti206 – 2061R → W in MMAHCC. 1 Publication
VAR_024783
Natural varianti271 – 2711S → G.
Corresponds to variant rs35219601 [ dbSNP | Ensembl ].
VAR_038805

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL080062 mRNA. Translation: CAB45693.2.
AL451136 Genomic DNA. Translation: CAI13094.1.
BC006122 mRNA. Translation: AAH06122.3. Different initiation.
CCDSiCCDS41324.1.
PIRiT12462.
RefSeqiNP_056321.2. NM_015506.2.
UniGeneiHs.13024.

Genome annotation databases

EnsembliENST00000401061; ENSP00000383840; ENSG00000132763.
GeneIDi25974.
KEGGihsa:25974.
UCSCiuc009vxv.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL080062 mRNA. Translation: CAB45693.2.
AL451136 Genomic DNA. Translation: CAI13094.1.
BC006122 mRNA. Translation: AAH06122.3. Different initiation.
CCDSiCCDS41324.1.
PIRiT12462.
RefSeqiNP_056321.2. NM_015506.2.
UniGeneiHs.13024.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliQ9Y4U1.
SMRiQ9Y4U1. Positions 2-238.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117458. 3 interactions.
IntActiQ9Y4U1. 1 interaction.
STRINGi9606.ENSP00000383840.

Chemistry

DrugBankiDB00115. Cyanocobalamin.
DB00200. Hydroxocobalamin.

PTM databases

PhosphoSiteiQ9Y4U1.

Polymorphism and mutation databases

BioMutaiMMACHC.
DMDMi85681045.

Proteomic databases

MaxQBiQ9Y4U1.
PaxDbiQ9Y4U1.
PRIDEiQ9Y4U1.

Protocols and materials databases

DNASUi25974.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000401061; ENSP00000383840; ENSG00000132763.
GeneIDi25974.
KEGGihsa:25974.
UCSCiuc009vxv.3. human.

Organism-specific databases

CTDi25974.
GeneCardsiGC01P045965.
GeneReviewsiMMACHC.
H-InvDBHIX0000532.
HGNCiHGNC:24525. MMACHC.
HPAiHPA027394.
HPA027399.
HPA027402.
MIMi277400. phenotype.
603174. phenotype.
609831. gene.
neXtProtiNX_Q9Y4U1.
Orphaneti79282. Methylmalonic acidemia with homocystinuria, type cblC.
PharmGKBiPA142671348.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG80998.
GeneTreeiENSGT00390000003464.
HOGENOMiHOG000231413.
HOVERGENiHBG080267.
InParanoidiQ9Y4U1.
KOiK14618.
OMAiWYNELLP.
PhylomeDBiQ9Y4U1.
TreeFamiTF332476.

Enzyme and pathway databases

UniPathwayiUPA00148.
ReactomeiREACT_163862. Cobalamin (Cbl, vitamin B12) transport and metabolism.
REACT_169169. Defective MMACHC causes methylmalonic aciduria and homocystinuria type cblC.
REACT_169256. Defective MMADHC causes methylmalonic aciduria and homocystinuria type cblD.

Miscellaneous databases

ChiTaRSiMMACHC. human.
EvolutionaryTraceiQ9Y4U1.
GeneWikiiMMACHC.
GenomeRNAii25974.
NextBioi47614.
PROiQ9Y4U1.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y4U1.
CleanExiHS_MMACHC.
GenevisibleiQ9Y4U1. HS.

Family and domain databases

ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  2. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4-282.
    Tissue: Lung.
  4. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-245, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  5. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
    Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  6. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  7. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-247; SER-275 AND SER-279, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. "Subcellular location of MMACHC and MMADHC, two human proteins central to intracellular vitamin B(12) metabolism."
    Mah W., Deme J.C., Watkins D., Fung S., Janer A., Shoubridge E.A., Rosenblatt D.S., Coulton J.W.
    Mol. Genet. Metab. 108:112-118(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  10. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  11. Cited for: VARIANTS MMAHCC ARG-27; PRO-116; ARG-122; HIS-130; ASP-147; ALA-147; ASP-156; CYS-157; GLY-161; GLN-161; SER-189; PRO-193; TRP-206 AND PRO-206, TISSUE SPECIFICITY.

Entry informationi

Entry nameiMMAC_HUMAN
AccessioniPrimary (citable) accession number: Q9Y4U1
Secondary accession number(s): Q5T157, Q9BRQ7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 10, 2006
Last sequence update: January 10, 2006
Last modified: June 24, 2015
This is version 108 of the entry and version 3 of the sequence. [Complete history]
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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  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

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.