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Q8IVH4 (MMAA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 105. 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 type A protein, mitochondrial

EC=3.6.-.-
Gene names
Name:MMAA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length418 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Pathway

Cofactor biosynthesis; adenosylcobalamin biosynthesis.

Subunit structure

Homodimer. Ref.5

Subcellular location

Mitochondrion Probable.

Tissue specificity

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

Involvement in disease

Methylmalonic aciduria type cblA (MMAA) [MIM:251100]: A disorder of methylmalonate and cobalamin metabolism due to defective synthesis of adenosylcobalamin.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.6 Ref.7

Sequence similarities

Belongs to the ArgK family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 6565Mitochondrion Potential
Chain66 – 418353Methylmalonic aciduria type A protein, mitochondrial
PRO_0000002285

Regions

Nucleotide binding150 – 1589GTP
Nucleotide binding328 – 3303GTP

Sites

Binding site2921GTP

Natural variations

Natural variant891L → P in MMAA. Ref.6
VAR_020835
Natural variant1451R → Q in MMAA. Ref.6
Corresponds to variant rs200577967 [ dbSNP | Ensembl ].
VAR_020836
Natural variant2071Y → C in MMAA. Ref.1 Ref.6
VAR_017202
Natural variant2181G → E in MMAA. Ref.6
VAR_020837
Natural variant3591R → G in MMAA. Ref.7
VAR_038804
Natural variant3591R → Q in MMAA. Ref.6
VAR_020838
Natural variant3631Q → H. Ref.6
Corresponds to variant rs2270655 [ dbSNP | Ensembl ].
VAR_020423

Secondary structure

......................................... 418
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q8IVH4 [UniParc].

Last modified March 1, 2003. Version 1.
Checksum: AD9EA19DDB8DEEF8

FASTA41846,538
        10         20         30         40         50         60 
MPMLLPHPHQ HFLKGLLRAP FRCYHFIFHS STHLGSGIPC AQPFNSLGLH CTKWMLLSDG 

        70         80         90        100        110        120 
LKRKLCVQTT LKDHTEGLSD KEQRFVDKLY TGLIQGQRAC LAEAITLVES THSRKKELAQ 

       130        140        150        160        170        180 
VLLQKVLLYH REQEQSNKGK PLAFRVGLSG PPGAGKSTFI EYFGKMLTER GHKLSVLAVD 

       190        200        210        220        230        240 
PSSCTSGGSL LGDKTRMTEL SRDMNAYIRP SPTRGTLGGV TRTTNEAILL CEGAGYDIIL 

       250        260        270        280        290        300 
IETVGVGQSE FAVADMVDMF VLLLPPAGGD ELQGIKRGII EMADLVAVTK SDGDLIVPAR 

       310        320        330        340        350        360 
RIQAEYVSAL KLLRKRSQVW KPKVIRISAR SGEGISEMWD KMKDFQDLML ASGELTAKRR 

       370        380        390        400        410 
KQQKVWMWNL IQESVLEHFR THPTVREQIP LLEQKVLIGA LSPGLAADFL LKAFKSRD 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF524846 expand/collapse EMBL AC list , 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.
CCDSCCDS3766.1.
RefSeqNP_758454.1. NM_172250.2.
XP_006714181.1. XM_006714118.1.
UniGeneHs.452864.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2WWWX-ray2.64A/B/C/D72-418[»]
ProteinModelPortalQ8IVH4.
SMRQ8IVH4. Positions 73-416.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid127933. 3 interactions.
STRING9606.ENSP00000281317.

Chemistry

DrugBankDB00115. Cyanocobalamin.
DB00200. Hydroxocobalamin.

PTM databases

PhosphoSiteQ8IVH4.

Polymorphism databases

DMDM38258173.

Proteomic databases

MaxQBQ8IVH4.
PaxDbQ8IVH4.
PRIDEQ8IVH4.

Protocols and materials databases

DNASU166785.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000281317; ENSP00000281317; ENSG00000151611.
GeneID166785.
KEGGhsa:166785.
UCSCuc003ikh.4. human.

Organism-specific databases

CTD166785.
GeneCardsGC04P146540.
GeneReviewsMMAA.
HGNCHGNC:18871. MMAA.
HPAHPA037361.
MIM251100. phenotype.
607481. gene.
neXtProtNX_Q8IVH4.
Orphanet79310. Vitamin B12-responsive methylmalonic acidemia type cblA.
PharmGKBPA134912808.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1703.
HOVERGENHBG045588.
InParanoidQ8IVH4.
KOK07588.
OMAWMLLSNG.
OrthoDBEOG7BCNBZ.
PhylomeDBQ8IVH4.
TreeFamTF313243.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
UniPathwayUPA00148.

Gene expression databases

ArrayExpressQ8IVH4.
BgeeQ8IVH4.
CleanExHS_MMAA.
GenevestigatorQ8IVH4.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR003593. AAA+_ATPase.
IPR005129. ArgK.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamPF03308. ArgK. 1 hit.
[Graphical view]
SMARTSM00382. AAA. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
TIGRFAMsTIGR00750. lao. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ8IVH4.
GeneWikiMMAA.
GenomeRNAi166785.
NextBio88619.
PROQ8IVH4.
SOURCESearch...

Entry information

Entry nameMMAA_HUMAN
AccessionPrimary (citable) accession number: Q8IVH4
Secondary accession number(s): B3KX40, Q495G7
Entry history
Integrated into UniProtKB/Swiss-Prot: November 7, 2003
Last sequence update: March 1, 2003
Last modified: July 9, 2014
This is version 105 of the entry and version 1 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 4

Human chromosome 4: entries, gene names and cross-references to MIM