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Q9Y4U1

- MMAC_HUMAN

UniProt

Q9Y4U1 - MMAC_HUMAN

Protein

Methylmalonic aciduria and homocystinuria type C protein

Gene

MMACHC

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 102 (01 Oct 2014)
      Sequence version 3 (10 Jan 2006)
      Previous versions | rss
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    Functioni

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

    Pathwayi

    GO - Molecular functioni

    1. cobalamin binding Source: UniProtKB-KW

    GO - Biological processi

    1. cobalamin biosynthetic process Source: UniProtKB-UniPathway
    2. cobalamin metabolic process Source: Reactome
    3. small molecule metabolic process Source: Reactome
    4. vitamin metabolic process Source: Reactome
    5. water-soluble vitamin metabolic process Source: Reactome

    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: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:24525. MMACHC.

    Subcellular locationi

    Cytoplasm 1 Publication

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. mitochondrion Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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.

    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.
    GenevestigatoriQ9Y4U1.

    Organism-specific databases

    HPAiHPA027394.
    HPA027399.
    HPA027402.

    Interactioni

    Protein-protein interaction databases

    BioGridi117458. 2 interactions.
    STRINGi9606.ENSP00000361154.

    Structurei

    Secondary structure

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

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.
    HOGENOMiHOG000231413.
    HOVERGENiHBG080267.
    InParanoidiQ9Y4U1.
    KOiK14618.
    OMAiWYNELLP.
    PhylomeDBiQ9Y4U1.
    TreeFamiTF332476.

    Sequencei

    Sequence statusi: Complete.

    Q9Y4U1-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEPKVAELKQ KIEDTLCPFG FEVYPFQVAW YNELLPPAFH LPLPGPTLAF    50
    LVLSTPAMFD RALKPFLQSC HLRMLTDPVD QCVAYHLGRV RESLPELQIE 100
    IIADYEVHPN RRPKILAQTA AHVAGAAYYY QRQDVEADPW GNQRISGVCI 150
    HPRFGGWFAI RGVVLLPGIE VPDLPPRKPH DCVPTRADRI ALLEGFNFHW 200
    RDWTYRDAVT PQERYSEEQK AYFSTPPAQR LALLGLAQPS EKPSSPSPDL 250
    PFTTPAPKKP GNPSRARSWL SPRVSPPASP GP 282
    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.

    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:
    EMBL
    GenBank
    DDBJ
    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.

    Polymorphism databases

    DMDMi85681045.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AL080062 mRNA. Translation: CAB45693.2 .
    AL451136 Genomic DNA. Translation: CAI13094.1 .
    BC006122 mRNA. Translation: AAH06122.3 . Different initiation.
    CCDSi CCDS41324.1.
    PIRi T12462.
    RefSeqi NP_056321.2. NM_015506.2.
    UniGenei Hs.13024.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3SBY X-ray 2.71 A/B 1-244 [» ]
    3SBZ X-ray 2.00 A 1-244 [» ]
    3SC0 X-ray 1.95 A 1-238 [» ]
    3SOM X-ray 2.40 A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P 1-282 [» ]
    ProteinModelPortali Q9Y4U1.
    SMRi Q9Y4U1. Positions 2-238.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 117458. 2 interactions.
    STRINGi 9606.ENSP00000361154.

    Chemistry

    DrugBanki DB00115. Cyanocobalamin.
    DB00200. Hydroxocobalamin.

    PTM databases

    PhosphoSitei Q9Y4U1.

    Polymorphism databases

    DMDMi 85681045.

    Proteomic databases

    MaxQBi Q9Y4U1.
    PaxDbi Q9Y4U1.
    PRIDEi Q9Y4U1.

    Protocols and materials databases

    DNASUi 25974.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000401061 ; ENSP00000383840 ; ENSG00000132763 .
    GeneIDi 25974.
    KEGGi hsa:25974.
    UCSCi uc009vxv.3. human.

    Organism-specific databases

    CTDi 25974.
    GeneCardsi GC01P045965.
    GeneReviewsi MMACHC.
    H-InvDB HIX0000532.
    HGNCi HGNC:24525. MMACHC.
    HPAi HPA027394.
    HPA027399.
    HPA027402.
    MIMi 277400. phenotype.
    603174. phenotype.
    609831. gene.
    neXtProti NX_Q9Y4U1.
    Orphaneti 79282. Methylmalonic acidemia with homocystinuria, type cblC.
    PharmGKBi PA142671348.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG80998.
    HOGENOMi HOG000231413.
    HOVERGENi HBG080267.
    InParanoidi Q9Y4U1.
    KOi K14618.
    OMAi WYNELLP.
    PhylomeDBi Q9Y4U1.
    TreeFami TF332476.

    Enzyme and pathway databases

    UniPathwayi UPA00148 .
    Reactomei REACT_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

    ChiTaRSi MMACHC. human.
    EvolutionaryTracei Q9Y4U1.
    GeneWikii MMACHC.
    GenomeRNAii 25974.
    NextBioi 47614.
    PROi Q9Y4U1.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9Y4U1.
    CleanExi HS_MMACHC.
    Genevestigatori Q9Y4U1.

    Family and domain databases

    ProtoNeti Search...

    Publicationsi

    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. 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: October 1, 2014
    This is version 102 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