MMAA_MOUSE
ID MMAA_MOUSE Reviewed; 415 AA.
AC Q8C7H1; Q8R2N3; Q8VC22;
DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Methylmalonic aciduria type A homolog, mitochondrial {ECO:0000305};
DE EC=3.6.-.- {ECO:0000250|UniProtKB:Q8IVH4};
DE Flags: Precursor;
GN Name=Mmaa {ECO:0000312|MGI:MGI:1923805};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: GTPase, binds and hydrolyzes GTP (By similarity). Involved in
CC intracellular vitamin B12 metabolism, mediates the transport of
CC cobalamin (Cbl) into mitochondria for the final steps of
CC adenosylcobalamin (AdoCbl) synthesis (By similarity). Functions as a G-
CC protein chaperone that assists AdoCbl cofactor delivery from MMAB to
CC the methylmalonyl-CoA mutase (MMUT) (By similarity). Plays a dual role
CC as both a protectase and a reactivase for MMUT (By similarity).
CC Protects MMUT from progressive inactivation by oxidation by decreasing
CC the rate of the formation of the oxidized inactive cofactor
CC hydroxocobalamin (OH2Cbl) (By similarity). Additionally acts a
CC reactivase by promoting the replacement of OH2Cbl by the active
CC cofactor AdoCbl, restoring the activity of MMUT in the presence and
CC hydrolysis of GTP (By similarity). {ECO:0000250|UniProtKB:Q8IVH4}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189;
CC Evidence={ECO:0000250|UniProtKB:Q8IVH4};
CC -!- ACTIVITY REGULATION: GTPase activity is stimulated by MMUT.
CC {ECO:0000250|UniProtKB:Q8IVH4}.
CC -!- SUBUNIT: Homodimer. Interacts with MMUT (the apoenzyme form); the
CC interaction is GTP dependent. {ECO:0000250|UniProtKB:Q8IVH4}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q8IVH4}.
CC Cytoplasm {ECO:0000250|UniProtKB:Q8IVH4}.
CC -!- SIMILARITY: Belongs to the SIMIBI class G3E GTPase family. ArgK/MeaB
CC subfamily. {ECO:0000305}.
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DR EMBL; AK050255; BAC34149.1; -; mRNA.
DR EMBL; BC021954; AAH21954.1; -; mRNA.
DR EMBL; BC027398; AAH27398.1; -; mRNA.
DR CCDS; CCDS22436.1; -.
DR RefSeq; NP_598584.2; NM_133823.4.
DR RefSeq; XP_006530625.1; XM_006530562.3.
DR RefSeq; XP_006530626.1; XM_006530563.3.
DR RefSeq; XP_006530627.1; XM_006530564.3.
DR RefSeq; XP_011246563.1; XM_011248261.2.
DR RefSeq; XP_011246564.1; XM_011248262.2.
DR RefSeq; XP_011246565.1; XM_011248263.2.
DR RefSeq; XP_011246566.1; XM_011248264.2.
DR RefSeq; XP_011246567.1; XM_011248265.2.
DR RefSeq; XP_011246568.1; XM_011248266.2.
DR RefSeq; XP_011246569.1; XM_011248267.2.
DR RefSeq; XP_011246570.1; XM_011248268.2.
DR RefSeq; XP_011246571.1; XM_011248269.2.
DR RefSeq; XP_011246572.1; XM_011248270.2.
DR RefSeq; XP_017167993.1; XM_017312504.1.
DR RefSeq; XP_017167994.1; XM_017312505.1.
DR AlphaFoldDB; Q8C7H1; -.
DR SMR; Q8C7H1; -.
DR BioGRID; 224569; 1.
DR STRING; 10090.ENSMUSP00000048826; -.
DR iPTMnet; Q8C7H1; -.
DR PhosphoSitePlus; Q8C7H1; -.
DR SwissPalm; Q8C7H1; -.
DR EPD; Q8C7H1; -.
DR jPOST; Q8C7H1; -.
DR MaxQB; Q8C7H1; -.
DR PaxDb; Q8C7H1; -.
DR PeptideAtlas; Q8C7H1; -.
DR PRIDE; Q8C7H1; -.
DR ProteomicsDB; 295957; -.
DR Antibodypedia; 27481; 159 antibodies from 20 providers.
DR DNASU; 109136; -.
DR Ensembl; ENSMUST00000048718; ENSMUSP00000048826; ENSMUSG00000037022.
DR GeneID; 109136; -.
DR KEGG; mmu:109136; -.
DR UCSC; uc009mim.1; mouse.
DR CTD; 166785; -.
DR MGI; MGI:1923805; Mmaa.
DR VEuPathDB; HostDB:ENSMUSG00000037022; -.
DR eggNOG; ENOG502QR2W; Eukaryota.
DR GeneTree; ENSGT00390000009908; -.
DR HOGENOM; CLU_043725_2_2_1; -.
DR InParanoid; Q8C7H1; -.
DR OMA; WMWERID; -.
DR OrthoDB; 817699at2759; -.
DR PhylomeDB; Q8C7H1; -.
DR TreeFam; TF313243; -.
DR Reactome; R-MMU-71032; Propionyl-CoA catabolism.
DR Reactome; R-MMU-9759218; Cobalamin (Cbl) metabolism.
DR BioGRID-ORCS; 109136; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Mmaa; mouse.
DR PRO; PR:Q8C7H1; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q8C7H1; protein.
DR Bgee; ENSMUSG00000037022; Expressed in interventricular septum and 238 other tissues.
DR ExpressionAtlas; Q8C7H1; baseline and differential.
DR Genevisible; Q8C7H1; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; ISS:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0009235; P:cobalamin metabolic process; ISO:MGI.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR005129; GTPase_ArgK.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR23408; PTHR23408; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00750; lao; 1.
PE 1: Evidence at protein level;
KW Chaperone; Cytoplasm; GTP-binding; Hydrolase; Mitochondrion;
KW Nucleotide-binding; Reference proteome; Transit peptide.
FT TRANSIT 1..62
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 63..415
FT /note="Methylmalonic aciduria type A homolog,
FT mitochondrial"
FT /id="PRO_0000002286"
FT BINDING 147..155
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8IVH4"
FT BINDING 289
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8IVH4"
FT BINDING 325..327
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8IVH4"
FT CONFLICT 31
FT /note="H -> P (in Ref. 2; AAH21954)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 415 AA; 45932 MW; A46967424CC4CC06 CRC64;
MTISTLLLSP NRRLLTCLSR VPSPWLLHSS HPAPGPPGAL PNCFGHHCTK RVLLSDGFRR
TLCVQATLKD HTEGLSDKEQ RFVDRLYTGL VKGQRACLAE AITLVESTHT RKRELAQVLL
QRVLALQREQ ELRNQGKPLT FRVGLSGPPG AGKSTFIECF GKMLTEQGHR LSVLAVDPSS
CTSGGSLLGD KTRMIELSRD MNAYIRPSPT SGTLGGVTRT TNEAIVLCEG GGYDIILIET
VGVGQSEFAV ADMVDMFVLL LPPAGGDELQ GIKRGIIEMA DLVVITKSDG DLIVPARRIQ
AEYVSALKLL RRRSEVWRPK VIRISARSGE GITEMWDTMR EFQHQMLASG ELAAKRQTQH
KVWMWNLIQE NVLEHFKTHP SIREQIPLME RKVLSGALSP GRAADLLLKA FKSRH
