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Q8IVH4

- MMAA_HUMAN

UniProt

Q8IVH4 - MMAA_HUMAN

Protein

Methylmalonic aciduria type A protein, mitochondrial

Gene

MMAA

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 107 (01 Oct 2014)
      Sequence version 1 (01 Mar 2003)
      Previous versions | rss
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    Functioni

    Probable GTPase. May function as chaperone. May be involved in the transport of cobalamin (Cbl) into mitochondria for the final steps of adenosylcobalamin (AdoCbl) synthesis.

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei292 – 2921GTP

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi150 – 1589GTP
    Nucleotide bindingi328 – 3303GTP

    GO - Molecular functioni

    1. GTP binding Source: UniProtKB-KW
    2. nucleoside-triphosphatase activity Source: InterPro

    GO - Biological processi

    1. cellular lipid metabolic process Source: Reactome
    2. cobalamin biosynthetic process Source: UniProtKB-UniPathway
    3. cobalamin metabolic process Source: Reactome
    4. fatty acid beta-oxidation Source: Reactome
    5. short-chain fatty acid catabolic process Source: Reactome
    6. small molecule metabolic process Source: Reactome
    7. vitamin metabolic process Source: Reactome
    8. water-soluble vitamin metabolic process Source: Reactome

    Keywords - Molecular functioni

    Chaperone, Hydrolase

    Keywords - Ligandi

    GTP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_163862. Cobalamin (Cbl, vitamin B12) transport and metabolism.
    REACT_169313. Defective MUT causes methylmalonic aciduria mut type.
    REACT_169316. Defective MMAA causes methylmalonic aciduria type cblA.
    REACT_993. Propionyl-CoA catabolism.
    UniPathwayiUPA00148.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Methylmalonic aciduria type A protein, mitochondrial (EC:3.6.-.-)
    Gene namesi
    Name:MMAA
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:18871. MMAA.

    Subcellular locationi

    GO - Cellular componenti

    1. mitochondrial matrix Source: Reactome

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Involvement in diseasei

    Methylmalonic aciduria type cblA (MMAA) [MIM:251100]: A disorder of methylmalonate and cobalamin metabolism due to defective synthesis of adenosylcobalamin.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti89 – 891L → P in MMAA. 1 Publication
    VAR_020835
    Natural varianti145 – 1451R → Q in MMAA. 1 Publication
    Corresponds to variant rs200577967 [ dbSNP | Ensembl ].
    VAR_020836
    Natural varianti207 – 2071Y → C in MMAA. 2 Publications
    VAR_017202
    Natural varianti218 – 2181G → E in MMAA. 1 Publication
    VAR_020837
    Natural varianti359 – 3591R → G in MMAA. 1 Publication
    VAR_038804
    Natural varianti359 – 3591R → Q in MMAA. 1 Publication
    VAR_020838

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi251100. phenotype.
    Orphaneti79310. Vitamin B12-responsive methylmalonic acidemia type cblA.
    PharmGKBiPA134912808.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 6565MitochondrionSequence AnalysisAdd
    BLAST
    Chaini66 – 418353Methylmalonic aciduria type A protein, mitochondrialPRO_0000002285Add
    BLAST

    Proteomic databases

    MaxQBiQ8IVH4.
    PaxDbiQ8IVH4.
    PRIDEiQ8IVH4.

    PTM databases

    PhosphoSiteiQ8IVH4.

    Expressioni

    Tissue specificityi

    Widely expressed. Highest expression is observed in liver and skeletal muscle.

    Gene expression databases

    ArrayExpressiQ8IVH4.
    BgeeiQ8IVH4.
    CleanExiHS_MMAA.
    GenevestigatoriQ8IVH4.

    Organism-specific databases

    HPAiHPA037361.

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    Protein-protein interaction databases

    BioGridi127933. 3 interactions.
    STRINGi9606.ENSP00000281317.

    Structurei

    Secondary structure

    1
    418
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi80 – 9415
    Helixi98 – 10912
    Helixi113 – 13523
    Turni136 – 1394
    Beta strandi144 – 1496
    Helixi156 – 16914
    Beta strandi174 – 1785
    Beta strandi206 – 2094
    Helixi224 – 23310
    Beta strandi237 – 2426
    Helixi250 – 2545
    Beta strandi258 – 2647
    Beta strandi284 – 2885
    Helixi293 – 2953
    Helixi296 – 31015
    Beta strandi323 – 3264
    Turni329 – 3313
    Helixi335 – 35218
    Helixi354 – 38128
    Helixi383 – 39715
    Helixi403 – 41513

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2WWWX-ray2.64A/B/C/D72-418[»]
    ProteinModelPortaliQ8IVH4.
    SMRiQ8IVH4. Positions 73-416.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ8IVH4.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the ArgK family.Curated

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG1703.
    HOVERGENiHBG045588.
    InParanoidiQ8IVH4.
    KOiK07588.
    OMAiWMLLSNG.
    OrthoDBiEOG7BCNBZ.
    PhylomeDBiQ8IVH4.
    TreeFamiTF313243.

    Family and domain databases

    Gene3Di3.40.50.300. 1 hit.
    InterProiIPR003593. AAA+_ATPase.
    IPR005129. ArgK.
    IPR027417. P-loop_NTPase.
    [Graphical view]
    PfamiPF03308. ArgK. 1 hit.
    [Graphical view]
    SMARTiSM00382. AAA. 1 hit.
    [Graphical view]
    SUPFAMiSSF52540. SSF52540. 1 hit.
    TIGRFAMsiTIGR00750. lao. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q8IVH4-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPMLLPHPHQ HFLKGLLRAP FRCYHFIFHS STHLGSGIPC AQPFNSLGLH    50
    CTKWMLLSDG LKRKLCVQTT LKDHTEGLSD KEQRFVDKLY TGLIQGQRAC 100
    LAEAITLVES THSRKKELAQ VLLQKVLLYH REQEQSNKGK PLAFRVGLSG 150
    PPGAGKSTFI EYFGKMLTER GHKLSVLAVD PSSCTSGGSL LGDKTRMTEL 200
    SRDMNAYIRP SPTRGTLGGV TRTTNEAILL CEGAGYDIIL IETVGVGQSE 250
    FAVADMVDMF VLLLPPAGGD ELQGIKRGII EMADLVAVTK SDGDLIVPAR 300
    RIQAEYVSAL KLLRKRSQVW KPKVIRISAR SGEGISEMWD KMKDFQDLML 350
    ASGELTAKRR KQQKVWMWNL IQESVLEHFR THPTVREQIP LLEQKVLIGA 400
    LSPGLAADFL LKAFKSRD 418
    Length:418
    Mass (Da):46,538
    Last modified:March 1, 2003 - v1
    Checksum:iAD9EA19DDB8DEEF8
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti89 – 891L → P in MMAA. 1 Publication
    VAR_020835
    Natural varianti145 – 1451R → Q in MMAA. 1 Publication
    Corresponds to variant rs200577967 [ dbSNP | Ensembl ].
    VAR_020836
    Natural varianti207 – 2071Y → C in MMAA. 2 Publications
    VAR_017202
    Natural varianti218 – 2181G → E in MMAA. 1 Publication
    VAR_020837
    Natural varianti359 – 3591R → G in MMAA. 1 Publication
    VAR_038804
    Natural varianti359 – 3591R → Q in MMAA. 1 Publication
    VAR_020838
    Natural varianti363 – 3631Q → H.1 Publication
    Corresponds to variant rs2270655 [ dbSNP | Ensembl ].
    VAR_020423

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF524846
    , AF524841, AF524842, AF524843, AF524844, AF524845 Genomic DNA. Translation: AAN77287.1.
    AK126662 mRNA. Translation: BAG54352.1.
    CH471056 Genomic DNA. Translation: EAX05036.1.
    BC101178 mRNA. Translation: AAI01179.1.
    BC101179 mRNA. Translation: AAI01180.1.
    CCDSiCCDS3766.1.
    RefSeqiNP_758454.1. NM_172250.2.
    XP_006714181.1. XM_006714118.1.
    UniGeneiHs.452864.

    Genome annotation databases

    EnsembliENST00000281317; ENSP00000281317; ENSG00000151611.
    GeneIDi166785.
    KEGGihsa:166785.
    UCSCiuc003ikh.4. human.

    Polymorphism databases

    DMDMi38258173.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF524846
    , AF524841 , AF524842 , AF524843 , AF524844 , AF524845 Genomic DNA. Translation: AAN77287.1 .
    AK126662 mRNA. Translation: BAG54352.1 .
    CH471056 Genomic DNA. Translation: EAX05036.1 .
    BC101178 mRNA. Translation: AAI01179.1 .
    BC101179 mRNA. Translation: AAI01180.1 .
    CCDSi CCDS3766.1.
    RefSeqi NP_758454.1. NM_172250.2.
    XP_006714181.1. XM_006714118.1.
    UniGenei Hs.452864.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2WWW X-ray 2.64 A/B/C/D 72-418 [» ]
    ProteinModelPortali Q8IVH4.
    SMRi Q8IVH4. Positions 73-416.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 127933. 3 interactions.
    STRINGi 9606.ENSP00000281317.

    Chemistry

    DrugBanki DB00115. Cyanocobalamin.
    DB00200. Hydroxocobalamin.

    PTM databases

    PhosphoSitei Q8IVH4.

    Polymorphism databases

    DMDMi 38258173.

    Proteomic databases

    MaxQBi Q8IVH4.
    PaxDbi Q8IVH4.
    PRIDEi Q8IVH4.

    Protocols and materials databases

    DNASUi 166785.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000281317 ; ENSP00000281317 ; ENSG00000151611 .
    GeneIDi 166785.
    KEGGi hsa:166785.
    UCSCi uc003ikh.4. human.

    Organism-specific databases

    CTDi 166785.
    GeneCardsi GC04P146540.
    GeneReviewsi MMAA.
    HGNCi HGNC:18871. MMAA.
    HPAi HPA037361.
    MIMi 251100. phenotype.
    607481. gene.
    neXtProti NX_Q8IVH4.
    Orphaneti 79310. Vitamin B12-responsive methylmalonic acidemia type cblA.
    PharmGKBi PA134912808.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1703.
    HOVERGENi HBG045588.
    InParanoidi Q8IVH4.
    KOi K07588.
    OMAi WMLLSNG.
    OrthoDBi EOG7BCNBZ.
    PhylomeDBi Q8IVH4.
    TreeFami TF313243.

    Enzyme and pathway databases

    UniPathwayi UPA00148 .
    Reactomei REACT_163862. Cobalamin (Cbl, vitamin B12) transport and metabolism.
    REACT_169313. Defective MUT causes methylmalonic aciduria mut type.
    REACT_169316. Defective MMAA causes methylmalonic aciduria type cblA.
    REACT_993. Propionyl-CoA catabolism.

    Miscellaneous databases

    EvolutionaryTracei Q8IVH4.
    GeneWikii MMAA.
    GenomeRNAii 166785.
    NextBioi 88619.
    PROi Q8IVH4.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8IVH4.
    Bgeei Q8IVH4.
    CleanExi HS_MMAA.
    Genevestigatori Q8IVH4.

    Family and domain databases

    Gene3Di 3.40.50.300. 1 hit.
    InterProi IPR003593. AAA+_ATPase.
    IPR005129. ArgK.
    IPR027417. P-loop_NTPase.
    [Graphical view ]
    Pfami PF03308. ArgK. 1 hit.
    [Graphical view ]
    SMARTi SM00382. AAA. 1 hit.
    [Graphical view ]
    SUPFAMi SSF52540. SSF52540. 1 hit.
    TIGRFAMsi TIGR00750. lao. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Identification of the gene responsible for the cblA complementation group of vitamin B12-responsive methylmalonic acidemia based on analysis of prokaryotic gene arrangements."
      Dobson C.M., Wai T., Leclerc D., Wilson A., Wu X., Dore C., Hudson T., Rosenblatt D.S., Gravel R.A.
      Proc. Natl. Acad. Sci. U.S.A. 99:15554-15559(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT MMAA CYS-207.
    2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Cerebellum.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "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].
    5. "Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation."
      Froese D.S., Kochan G., Muniz J.R., Wu X., Gileadi C., Ugochukwu E., Krysztofinska E., Gravel R.A., Oppermann U., Yue W.W.
      J. Biol. Chem. 285:38204-38213(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.64 ANGSTROMS) OF 72-418 IN COMPLEX WITH GDP, SUBUNIT.
    6. "Mutations in the MMAA gene in patients with the cblA disorder of vitamin B(12) metabolism."
      Lerner-Ellis J.P., Dobson C.M., Wai T., Watkins D., Tirone J.C., Leclerc D., Dore C., Lepage P., Gravel R.A., Rosenblatt D.S.
      Hum. Mutat. 24:509-516(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS MMAA PRO-89; GLN-145; CYS-207; GLU-218 AND GLN-359, VARIANT HIS-363.
    7. "Mutation analysis of the MMAA and MMAB genes in Japanese patients with vitamin B(12)-responsive methylmalonic acidemia: identification of a prevalent MMAA mutation."
      Yang X., Sakamoto O., Matsubara Y., Kure S., Suzuki Y., Aoki Y., Suzuki Y., Sakura N., Takayanagi M., Iinuma K., Ohura T.
      Mol. Genet. Metab. 82:329-333(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT MMAA GLY-359.

    Entry informationi

    Entry nameiMMAA_HUMAN
    AccessioniPrimary (citable) accession number: Q8IVH4
    Secondary accession number(s): B3KX40, Q495G7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 7, 2003
    Last sequence update: March 1, 2003
    Last modified: October 1, 2014
    This is version 107 of the entry and version 1 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 4
      Human chromosome 4: 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