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Protein

Methylmalonic aciduria type A protein, mitochondrial

Gene

MMAA

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

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. hydrolase activity Source: UniProtKB-KW

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
Complete GO annotation...

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
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Methylmalonic aciduria type cblA4 Publications

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

Disease descriptionA disorder of methylmalonate and cobalamin metabolism due to defective synthesis of adenosylcobalamin.

See also OMIM:251100
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 varianti209 – 2091R → S in MMAA. 1 Publication
VAR_071919
Natural varianti218 – 2181G → E in MMAA. 1 Publication
VAR_020837
Natural varianti250 – 2501E → K in MMAA. 1 Publication
VAR_071920
Natural varianti274 – 2741G → D in MMAA. 1 Publication
VAR_071921
Natural varianti274 – 2741G → S in MMAA. 1 Publication
VAR_071922
Natural varianti276 – 2761K → E in MMAA. 1 Publication
VAR_071923
Natural varianti359 – 3591R → G in MMAA. 1 Publication
VAR_038804
Natural varianti359 – 3591R → Q in MMAA. 2 Publications
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

BgeeiQ8IVH4.
CleanExiHS_MMAA.
ExpressionAtlasiQ8IVH4. baseline and differential.
GenevestigatoriQ8IVH4.

Organism-specific databases

HPAiHPA037361.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

BioGridi127933. 2 interactions.
STRINGi9606.ENSP00000281317.

Structurei

Secondary structure

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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
GeneTreeiENSGT00390000009908.
HOVERGENiHBG045588.
InParanoidiQ8IVH4.
KOiK07588.
OMAiEAMLVCE.
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

        10         20         30         40         50
MPMLLPHPHQ HFLKGLLRAP FRCYHFIFHS STHLGSGIPC AQPFNSLGLH
60 70 80 90 100
CTKWMLLSDG LKRKLCVQTT LKDHTEGLSD KEQRFVDKLY TGLIQGQRAC
110 120 130 140 150
LAEAITLVES THSRKKELAQ VLLQKVLLYH REQEQSNKGK PLAFRVGLSG
160 170 180 190 200
PPGAGKSTFI EYFGKMLTER GHKLSVLAVD PSSCTSGGSL LGDKTRMTEL
210 220 230 240 250
SRDMNAYIRP SPTRGTLGGV TRTTNEAILL CEGAGYDIIL IETVGVGQSE
260 270 280 290 300
FAVADMVDMF VLLLPPAGGD ELQGIKRGII EMADLVAVTK SDGDLIVPAR
310 320 330 340 350
RIQAEYVSAL KLLRKRSQVW KPKVIRISAR SGEGISEMWD KMKDFQDLML
360 370 380 390 400
ASGELTAKRR KQQKVWMWNL IQESVLEHFR THPTVREQIP LLEQKVLIGA
410
LSPGLAADFL LKAFKSRD
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 varianti209 – 2091R → S in MMAA. 1 Publication
VAR_071919
Natural varianti218 – 2181G → E in MMAA. 1 Publication
VAR_020837
Natural varianti250 – 2501E → K in MMAA. 1 Publication
VAR_071920
Natural varianti274 – 2741G → D in MMAA. 1 Publication
VAR_071921
Natural varianti274 – 2741G → S in MMAA. 1 Publication
VAR_071922
Natural varianti276 – 2761K → E in MMAA. 1 Publication
VAR_071923
Natural varianti359 – 3591R → G in MMAA. 1 Publication
VAR_038804
Natural varianti359 – 3591R → Q in MMAA. 2 Publications
VAR_020838
Natural varianti363 – 3631Q → H.1 Publication
Corresponds to variant rs2270655 [ dbSNP | Ensembl ].
VAR_020423

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi127933. 2 interactions.
STRINGi9606.ENSP00000281317.

Chemistry

DrugBankiDB00115. Cyanocobalamin.
DB00200. Hydroxocobalamin.

PTM databases

PhosphoSiteiQ8IVH4.

Polymorphism databases

DMDMi38258173.

Proteomic databases

MaxQBiQ8IVH4.
PaxDbiQ8IVH4.
PRIDEiQ8IVH4.

Protocols and materials databases

DNASUi166785.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi166785.
GeneCardsiGC04P146540.
GeneReviewsiMMAA.
HGNCiHGNC:18871. MMAA.
HPAiHPA037361.
MIMi251100. phenotype.
607481. gene.
neXtProtiNX_Q8IVH4.
Orphaneti79310. Vitamin B12-responsive methylmalonic acidemia type cblA.
PharmGKBiPA134912808.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG1703.
GeneTreeiENSGT00390000009908.
HOVERGENiHBG045588.
InParanoidiQ8IVH4.
KOiK07588.
OMAiEAMLVCE.
OrthoDBiEOG7BCNBZ.
PhylomeDBiQ8IVH4.
TreeFamiTF313243.

Enzyme and pathway databases

UniPathwayiUPA00148.
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.

Miscellaneous databases

EvolutionaryTraceiQ8IVH4.
GeneWikiiMMAA.
GenomeRNAii166785.
NextBioi88619.
PROiQ8IVH4.
SOURCEiSearch...

Gene expression databases

BgeeiQ8IVH4.
CleanExiHS_MMAA.
ExpressionAtlasiQ8IVH4. baseline and differential.
GenevestigatoriQ8IVH4.

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.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
  8. "High resolution melting analysis of the MMAA gene in patients with cblA and in those with undiagnosed methylmalonic aciduria."
    Dempsey-Nunez L., Illson M.L., Kent J., Huang Q., Brebner A., Watkins D., Gilfix B.M., Wittwer C.T., Rosenblatt D.S.
    Mol. Genet. Metab. 107:363-367(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS MMAA SER-209; LYS-250; ASP-274; SER-274; GLU-276 AND GLN-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: February 4, 2015
This is version 111 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

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.