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Q9Y4U1 (MMAC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Methylmalonic aciduria and homocystinuria type C protein
Gene names
Name:MMACHC
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length282 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Pathway

Cofactor biosynthesis; adenosylcobalamin biosynthesis.

Subcellular location

Cytoplasm Ref.9.

Tissue specificity

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. Ref.10

Involvement in disease

Methylmalonic aciduria and homocystinuria type cblC (MMAHCC) [MIM:277400]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Sequence similarities

Belongs to the MMACHC family.

Sequence caution

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 282282Methylmalonic aciduria and homocystinuria type C protein
PRO_0000076258

Amino acid modifications

Modified residue2451Phosphoserine Ref.4
Modified residue2471Phosphoserine Ref.7
Modified residue2751Phosphoserine Ref.6 Ref.7
Modified residue2791Phosphoserine Ref.7

Natural variations

Natural variant271Q → R in MMAHCC. Ref.10
VAR_024770
Natural variant1161L → P in MMAHCC. Ref.10
VAR_024771
Natural variant1221H → R in MMAHCC. Ref.10
VAR_024772
Natural variant1301Y → H in MMAHCC. Ref.10
VAR_024773
Natural variant1471G → A in MMAHCC. Ref.10
Corresponds to variant rs140522266 [ dbSNP | Ensembl ].
VAR_024774
Natural variant1471G → D in MMAHCC. Ref.10
VAR_024775
Natural variant1561G → D in MMAHCC. Ref.10
VAR_024776
Natural variant1571W → C in MMAHCC. Ref.10
VAR_024777
Natural variant1611R → G in MMAHCC. Ref.10
VAR_024778
Natural variant1611R → Q in MMAHCC. Ref.10
VAR_024779
Natural variant1891R → S in MMAHCC. Ref.10
VAR_024780
Natural variant1931L → P in MMAHCC. Ref.10
VAR_024781
Natural variant2061R → P in MMAHCC. Ref.10
VAR_024782
Natural variant2061R → W in MMAHCC. Ref.10
VAR_024783
Natural variant2711S → G.
Corresponds to variant rs35219601 [ dbSNP | Ensembl ].
VAR_038805

Experimental info

Sequence conflict1001E → G in CAB45693. Ref.1

Secondary structure

................................................ 282
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9Y4U1 [UniParc].

Last modified January 10, 2006. Version 3.
Checksum: 3A7E6BC774CB5D17

FASTA28231,728
        10         20         30         40         50         60 
MEPKVAELKQ KIEDTLCPFG FEVYPFQVAW YNELLPPAFH LPLPGPTLAF LVLSTPAMFD 

        70         80         90        100        110        120 
RALKPFLQSC HLRMLTDPVD QCVAYHLGRV RESLPELQIE IIADYEVHPN RRPKILAQTA 

       130        140        150        160        170        180 
AHVAGAAYYY QRQDVEADPW GNQRISGVCI HPRFGGWFAI RGVVLLPGIE VPDLPPRKPH 

       190        200        210        220        230        240 
DCVPTRADRI ALLEGFNFHW RDWTYRDAVT PQERYSEEQK AYFSTPPAQR LALLGLAQPS 

       250        260        270        280 
EKPSSPSPDL PFTTPAPKKP GNPSRARSWL SPRVSPPASP GP 

« Hide

References

« Hide 'large scale' references
[1]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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]"Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type."
Lerner-Ellis J.P., Tirone J.C., Pawelek P.D., Dore C., Atkinson J.L., Watkins D., Morel C.F., Fujiwara T.M., Moras E., Hosack A.R., Dunbar G.V., Antonicka H., Forgetta V., Dobson C.M., Leclerc D., Gravel R.A., Shoubridge E.A., Coulton J.W. expand/collapse author list , Lepage P., Rommens J.M., Morgan K., Rosenblatt D.S.
Nat. Genet. 38:93-100(2006) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AL080062 mRNA. Translation: CAB45693.2.
AL451136 Genomic DNA. Translation: CAI13094.1.
BC006122 mRNA. Translation: AAH06122.3. Different initiation.
CCDSCCDS41324.1.
PIRT12462.
RefSeqNP_056321.2. NM_015506.2.
UniGeneHs.13024.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalQ9Y4U1.
SMRQ9Y4U1. Positions 2-238.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117458. 2 interactions.
STRING9606.ENSP00000361154.

Chemistry

DrugBankDB00115. Cyanocobalamin.
DB00200. Hydroxocobalamin.

PTM databases

PhosphoSiteQ9Y4U1.

Polymorphism databases

DMDM85681045.

Proteomic databases

MaxQBQ9Y4U1.
PaxDbQ9Y4U1.
PRIDEQ9Y4U1.

Protocols and materials databases

DNASU25974.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000401061; ENSP00000383840; ENSG00000132763.
GeneID25974.
KEGGhsa:25974.
UCSCuc009vxv.3. human.

Organism-specific databases

CTD25974.
GeneCardsGC01P045965.
GeneReviewsMMACHC.
H-InvDBHIX0000532.
HGNCHGNC:24525. MMACHC.
HPAHPA027394.
HPA027399.
HPA027402.
MIM277400. phenotype.
603174. phenotype.
609831. gene.
neXtProtNX_Q9Y4U1.
Orphanet79282. Methylmalonic acidemia with homocystinuria, type cblC.
PharmGKBPA142671348.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG80998.
HOGENOMHOG000231413.
HOVERGENHBG080267.
InParanoidQ9Y4U1.
KOK14618.
OMAWYNELLP.
PhylomeDBQ9Y4U1.
TreeFamTF332476.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
UniPathwayUPA00148.

Gene expression databases

BgeeQ9Y4U1.
CleanExHS_MMACHC.
GenevestigatorQ9Y4U1.

Family and domain databases

ProtoNetSearch...

Other

ChiTaRSMMACHC. human.
EvolutionaryTraceQ9Y4U1.
GeneWikiMMACHC.
GenomeRNAi25974.
NextBio47614.
PROQ9Y4U1.
SOURCESearch...

Entry information

Entry nameMMAC_HUMAN
AccessionPrimary (citable) accession number: Q9Y4U1
Secondary accession number(s): Q5T157, Q9BRQ7
Entry history
Integrated into UniProtKB/Swiss-Prot: January 10, 2006
Last sequence update: January 10, 2006
Last modified: July 9, 2014
This is version 100 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM