MUTA_HUMAN
ID MUTA_HUMAN Reviewed; 750 AA.
AC P22033; A8K953; Q5SYZ3; Q96B11; Q9UD64;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 4.
DT 03-AUG-2022, entry version 221.
DE RecName: Full=Methylmalonyl-CoA mutase, mitochondrial {ECO:0000305};
DE Short=MCM;
DE EC=5.4.99.2 {ECO:0000269|PubMed:1346616, ECO:0000269|PubMed:21138732, ECO:0000269|PubMed:2453061, ECO:0000269|PubMed:25125334, ECO:0000269|PubMed:27167370, ECO:0000269|PubMed:28101778, ECO:0000269|PubMed:28943303};
DE AltName: Full=Methylmalonyl-CoA isomerase;
DE Flags: Precursor;
GN Name=MMUT {ECO:0000312|HGNC:HGNC:7526};
GN Synonyms=MUT {ECO:0000312|HGNC:HGNC:7526};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=2453061; DOI=10.1073/pnas.85.10.3518;
RA Ledley F.D., Lumetta M., Nguyen P.N., Kolhouse J.F., Allen R.H.;
RT "Molecular cloning of L-methylmalonyl-CoA mutase: gene transfer and
RT analysis of mut cell lines.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:3518-3521(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF N-TERMINUS, PARTIAL PROTEIN
RP SEQUENCE, AND VARIANTS HIS-532 AND VAL-671.
RC TISSUE=Liver;
RX PubMed=2567699; DOI=10.1016/0888-7543(89)90300-5;
RA Jansen R., Kalousek F., Fenton W.A., Rosenberg L.E., Ledley F.D.;
RT "Cloning of full-length methylmalonyl-CoA mutase from a cDNA library using
RT the polymerase chain reaction.";
RL Genomics 4:198-205(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-532 AND VAL-671, AND
RP VARIANT MMAM THR-505.
RX PubMed=1980486; DOI=10.1016/0888-7543(90)90259-w;
RA Nham S.U., Wilkemeyer M.F., Ledley F.D.;
RT "Structure of the human methylmalonyl-CoA mutase (MUT) locus.";
RL Genomics 8:710-716(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-671.
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS THR-499 AND VAL-671.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS THR-499 AND VAL-671.
RC TISSUE=Uterus;
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 [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=24458; DOI=10.1111/j.1365-2141.1975.tb00885.x;
RA Frenkel E.P., Kitchens R.L.;
RT "Intracellular localization of hepatic propionyl-CoA carboxylase and
RT methylmalonyl-CoA mutase in humans and normal and vitamin B12 deficient
RT rats.";
RL Br. J. Haematol. 31:501-513(1975).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND COFACTOR.
RC TISSUE=Liver;
RX PubMed=1978672; DOI=10.1042/bj2710449;
RA Wilkemeyer M.F., Crane A.M., Ledley F.D.;
RT "Primary structure and activity of mouse methylmalonyl-CoA mutase.";
RL Biochem. J. 271:449-455(1990).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH MMAA, ACTIVITY REGULATION,
RP AND COFACTOR.
RX PubMed=21138732; DOI=10.1016/j.bbrc.2010.11.141;
RA Takahashi-Iniguez T., Garcia-Arellano H., Trujillo-Roldan M.A.,
RA Flores M.E.;
RT "Protection and reactivation of human methylmalonyl-CoA mutase by MMAA
RT protein.";
RL Biochem. Biophys. Res. Commun. 404:443-447(2011).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, INTERACTION WITH MMAA, COFACTOR, AND ACTIVITY REGULATION.
RX PubMed=28943303; DOI=10.1016/j.biochi.2017.09.012;
RA Takahashi-Iniguez T., Gonzalez-Noriega A., Michalak C., Flores M.E.;
RT "Human MMAA induces the release of inactive cofactor and restores
RT methylmalonyl-CoA mutase activity through their complex formation.";
RL Biochimie 142:191-196(2017).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND ACTIVITY REGULATION.
RX PubMed=29056341; DOI=10.1016/j.cell.2017.09.051;
RA Shen H., Campanello G.C., Flicker D., Grabarek Z., Hu J., Luo C.,
RA Banerjee R., Mootha V.K.;
RT "The human knockout gene CLYBL connects itaconate to vitamin B12.";
RL Cell 171:771-782(2017).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 12-750 IN COMPLEX WITH
RP ADENOSYLCOBALAMIN AND MALONYL-COA, SUBUNIT, AND INTERACTION WITH MMAA.
RX PubMed=20876572; DOI=10.1074/jbc.m110.177717;
RA Froese D.S., Kochan G., Muniz J.R., Wu X., Gileadi C., Ugochukwu E.,
RA Krysztofinska E., Gravel R.A., Oppermann U., Yue W.W.;
RT "Structures of the human GTPase MMAA and vitamin B12-dependent
RT methylmalonyl-CoA mutase and insight into their complex formation.";
RL J. Biol. Chem. 285:38204-38213(2010).
RN [16]
RP VARIANTS MMAM ARG-105 AND GLU-377, AND INVOLVEMENT IN MMAM.
RX PubMed=1977311;
RA Jansen R., Ledley F.D.;
RT "Heterozygous mutations at the mut locus in fibroblasts with mut0
RT methylmalonic acidemia identified by polymerase-chain-reaction cDNA
RT cloning.";
RL Am. J. Hum. Genet. 47:808-814(1990).
RN [17]
RP VARIANT MMAM HIS-93.
RX PubMed=1670635; DOI=10.1172/jci114972;
RA Raff M.L., Crane A.M., Jansen R., Ledley F.D., Rosenblatt D.S.;
RT "Genetic characterization of a MUT locus mutation discriminating
RT heterogeneity in mut0 and mut- methylmalonic aciduria by interallelic
RT complementation.";
RL J. Clin. Invest. 87:203-207(1991).
RN [18]
RP VARIANT MMAM VAL-717, AND VARIANT VAL-671.
RX PubMed=1351030; DOI=10.1007/bf00220536;
RA Crane A.M., Martin L.S., Valle D., Ledley F.D.;
RT "Phenotype of disease in three patients with identical mutations in
RT methylmalonyl CoA mutase.";
RL Hum. Genet. 89:259-264(1992).
RN [19]
RP VARIANT MMAM VAL-717, VARIANT VAL-671, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=1346616; DOI=10.1172/jci115597;
RA Crane A.M., Jansen R., Andrews E.R., Ledley F.D.;
RT "Cloning and expression of a mutant methylmalonyl coenzyme A mutase with
RT altered cobalamin affinity that causes mut- methylmalonic aciduria.";
RL J. Clin. Invest. 89:385-391(1992).
RN [20]
RP VARIANTS MMAM CYS-626; GLU-630; ASP-648 AND TRP-694, AND VARIANT HIS-532.
RX PubMed=7912889;
RA Crane A.M., Ledley F.D.;
RT "Clustering of mutations in methylmalonyl CoA mutase associated with mut-
RT methylmalonic acidemia.";
RL Am. J. Hum. Genet. 55:42-50(1994).
RN [21]
RP VARIANTS MMAM ARG-623 AND ARG-703.
RX PubMed=7909321; DOI=10.1172/jci117166;
RA Qureshi A.A., Crane A.M., Matiaszuk N.V., Resvani I., Ledley F.D.,
RA Rosenblatt D.S.;
RT "Cloning and expression of mutations demonstrating intragenic
RT complementation in mut0 methylmalonic aciduria.";
RL J. Clin. Invest. 93:1812-1819(1994).
RN [22]
RP VARIANTS MMAM VAL-94; ASN-231; HIS-369; ARG-623; ARG-678; TRP-694 AND
RP VAL-717.
RX PubMed=9285782; DOI=10.1093/hmg/6.9.1457;
RA Janata J., Kogekar N., Fenton W.A.;
RT "Expression and kinetic characterization of methylmalonyl-CoA mutase from
RT patients with the mut- phenotype: evidence for naturally occurring
RT interallelic complementation.";
RL Hum. Mol. Genet. 6:1457-1464(1997).
RN [23]
RP REVIEW ON VARIANTS.
RX PubMed=8990001;
RX DOI=10.1002/(sici)1098-1004(1997)9:1<1::aid-humu1>3.0.co;2-e;
RA Ledley F.D., Rosenblatt D.S.;
RT "Mutations in mut methylmalonic acidemia: clinical and enzymatic
RT correlations.";
RL Hum. Mutat. 9:1-6(1997).
RN [24]
RP VARIANT MMAM VAL-717, AND VARIANT VAL-671.
RX PubMed=9452100; DOI=10.1002/humu.1380110179;
RA Adjalla C.E., Hosack A.R., Matiaszuk N.V., Rosenblatt D.S.;
RT "A common mutation among blacks with mut- methylmalonic aciduria.";
RL Hum. Mutat. Suppl. 1:S248-S250(1998).
RN [25]
RP VARIANTS MMAM GLU-191; GLN-228; VAL-312; LEU-346 DEL; GLY-633; LEU-684 INS
RP AND ARG-685.
RX PubMed=9554742;
RX DOI=10.1002/(sici)1098-1004(1998)11:4<270::aid-humu3>3.0.co;2-t;
RA Adjalla C.E., Hosack A.R., Gilfix B.M., Lamothe E., Sun S., Chan A.,
RA Evans S., Matiaszuk N.V., Rosenblatt D.S.;
RT "Seven novel mutations in mut methylmalonic aciduria.";
RL Hum. Mutat. 11:270-274(1998).
RN [26]
RP VARIANTS MMAM VAL-137; SER-174; ARG-203; HIS-218; PRO-535 AND ARG-627.
RX PubMed=10923046;
RX DOI=10.1002/1098-1004(200008)16:2<179::aid-humu17>3.0.co;2-r;
RA Fuchshuber A., Mucha B., Baumgartner E.R., Vollmer M., Hildebrandt F.;
RT "mut0 methylmalonic acidemia: eleven novel mutations of the methylmalonyl
RT CoA mutase including a deletion-insertion mutation.";
RL Hum. Mutat. 16:179-179(2000).
RN [27]
RP VARIANT MMAM TYR-219, AND VARIANTS THR-499 AND VAL-671.
RX PubMed=11350191; DOI=10.1006/mgme.2001.3166;
RA Berger I., Shaag A., Anikster Y., Baumgartner E.R., Bar-Meir M., Joseph A.,
RA Elpeleg O.N.;
RT "Mutation analysis of the MCM gene in Israeli patients with mut(0)
RT disease.";
RL Mol. Genet. Metab. 73:107-110(2001).
RN [28]
RP VARIANTS MMAM HIS-108; LEU-148; ASN-156; VAL-158; GLU-191; ARG-203;
RP SER-215; TYR-219; ASN-262; PRO-293; PHE-328; CYS-587; THR-615; ASN-621;
RP ARG-623; ARG-624; ARG-627; GLU-637; ILE-638; TYR-640; ARG-642; TRP-694 AND
RP LYS-700.
RX PubMed=15643616; DOI=10.1002/humu.20128;
RA Acquaviva C., Benoist J.-F., Pereira S., Callebaut I., Koskas T.,
RA Porquet D., Elion J.;
RT "Molecular basis of methylmalonyl-CoA mutase apoenzyme defect in 40
RT European patients affected by mut(o) and mut- forms of methylmalonic
RT acidemia: identification of 29 novel mutations in the MUT gene.";
RL Hum. Mutat. 25:167-176(2005).
RN [29]
RP VARIANTS MMAM ARG-109; GLU-191; TYR-219; THR-324; PRO-328; CYS-616 AND
RP ARG-617, AND VARIANT VAL-69.
RX PubMed=15781192; DOI=10.1016/j.ymgme.2004.11.011;
RA Martinez M.A., Rincon A., Desviat L.R., Merinero B., Ugarte M., Perez B.;
RT "Genetic analysis of three genes causing isolated methylmalonic acidemia:
RT identification of 21 novel allelic variants.";
RL Mol. Genet. Metab. 84:317-325(2005).
RN [30]
RP VARIANTS MMAM LEU-86; GLU-87; HIS-93; ARG-94; VAL-94; ARG-95; ARG-105;
RP CYS-108; GLY-108; HIS-108; SER-145; SER-174; VAL-186; LYS-189; GLU-191;
RP GLU-197; ARG-203; CYS-215; SER-215; HIS-218; TYR-219; GLN-228; ILE-230;
RP ASN-231; ASN-262; TYR-265; SER-281; GLU-291; SER-305; PHE-306; VAL-312;
RP CYS-316; THR-324; LEU-346 DEL; ARG-347; TYR-350; CYS-369; HIS-369; PRO-370;
RP GLU-377; HIS-383; PRO-383; ARG-386; ASN-386; HIS-388; SER-389 DEL; ILE-412
RP DEL; ARG-426; ASP-427; PRO-518; TYR-560; ARG-566; SER-573; ARG-615;
RP CYS-616; ARG-623; GLU-630; GLY-633; ARG-637; ARG-642; ARG-678; ARG-685;
RP TRP-694; LYS-700; ARG-703 AND VAL-717, AND VARIANTS VAL-69; THR-499;
RP HIS-532 AND VAL-671.
RX PubMed=16281286; DOI=10.1002/humu.20258;
RA Worgan L.C., Niles K., Tirone J.C., Hofmann A., Verner A., Sammak A.,
RA Kucic T., Lepage P., Rosenblatt D.S.;
RT "Spectrum of mutations in mut methylmalonic acidemia and identification of
RT a common Hispanic mutation and haplotype.";
RL Hum. Mutat. 27:31-43(2006).
RN [31]
RP VARIANTS MMAM CYS-100; HIS-108; VAL-137; TYR-143; LEU-148; GLU-191;
RP ARG-203; HIS-218; TYR-219; ASN-231; PRO-288; PHE-328; PHE-344; SER-366;
RP HIS-369; GLU-454; THR-615; GLU-630; GLY-633; LEU-694; TRP-694 AND LYS-700.
RX PubMed=17113806; DOI=10.1016/j.ymgme.2006.10.002;
RA Lempp T.J., Suormala T., Siegenthaler R., Baumgartner E.R., Fowler B.,
RA Steinmann B., Baumgartner M.R.;
RT "Mutation and biochemical analysis of 19 probands with mut0 and 13 with
RT mut- methylmalonic aciduria: identification of seven novel mutations.";
RL Mol. Genet. Metab. 90:284-290(2007).
RN [32]
RP VARIANTS MMAM 7-GLN--VAL-750 DEL; VAL-69; ARG-109; 152-ARG--VAL-750 DEL;
RP GLU-191; ARG-203; TYR-219; 228-ARG--VAL-750 DEL; ASN-231; THR-324; PRO-328;
RP PRO-358; CYS-369; CYS-616; ARG-617 AND TRP-694.
RX PubMed=17957493; DOI=10.1007/s10545-007-0667-y;
RA Merinero B., Perez B., Perez-Cerda C., Rincon A., Desviat L.R.,
RA Martinez M.A., Sala P.R., Garcia M.J., Aldamiz-Echevarria L., Campos J.,
RA Cornejo V., Del Toro M., Mahfoud A., Martinez-Pardo M., Parini R.,
RA Pedron C., Pena-Quintana L., Perez M., Pourfarzam M., Ugarte M.;
RT "Methylmalonic acidaemia: examination of genotype and biochemical data in
RT 32 patients belonging to mut, cblA or cblB complementation group.";
RL J. Inherit. Metab. Dis. 31:55-66(2008).
RN [33]
RP VARIANT MMAM ARG-161.
RX PubMed=19588269; DOI=10.1007/s10545-009-1141-9;
RA Filippi L., Gozzini E., Cavicchi C., Morrone A., Fiorini P., Donzelli G.,
RA Malvagia S., la Marca G.;
RT "Insulin-resistant hyperglycaemia complicating neonatal onset of
RT methylmalonic and propionic acidaemias.";
RL J. Inherit. Metab. Dis. 32:S179-S186(2009).
RN [34]
RP VARIANT [LARGE SCALE ANALYSIS] VAL-671, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [35]
RP VARIANTS MMAM GLY-137; TYR-219; SER-305; PHE-328; ILE-387; GLU-454;
RP GLU-514; LEU-615; THR-615; VAL-625 AND PHE-674, AND VARIANTS THR-499;
RP HIS-532 AND VAL-671.
RX PubMed=22727635; DOI=10.1016/j.ymgme.2012.05.014;
RA Duendar H., Oezguel R.K., Guezel-Ozantuerk A., Dursun A., Sivri S.,
RA Aliefendioglu D., Coskun T., Tokatli A.;
RT "Microarray based mutational analysis of patients with methylmalonic
RT acidemia: identification of 10 no vel mutations.";
RL Mol. Genet. Metab. 106:419-423(2012).
RN [36]
RP CHARACTERIZATION OF VARIANTS MMAM LEU-86; CYS-100; GLU-191; HIS-218;
RP TYR-219; ASN-231; CYS-316; PHE-328; PHE-344; SER-366; HIS-369; ILE-387;
RP ARG-426; SER-573; LEU-615; THR-615; GLY-633; ASP-648; LEU-694; TRP-694;
RP LYS-700; VAL-717 AND PHE-736, FUNCTION, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=25125334; DOI=10.1002/humu.22633;
RA Forny P., Froese D.S., Suormala T., Yue W.W., Baumgartner M.R.;
RT "Functional characterization and categorization of missense mutations that
RT cause methylmalonyl-CoA mutase (MUT) deficiency.";
RL Hum. Mutat. 35:1449-1458(2014).
RN [37]
RP VARIANTS MMAM LYS-126; ARG-133; ASN-139; VAL-156; ARG-161; SER-187;
RP ILE-189; GLU-205 DEL; ARG-230; ASP-276; ARG-284; GLU-284; ASP-325; LYS-326;
RP LYS-388; LEU-424; GLU-426; VAL-552; PRO-618 AND GLY-625, CHARACTERIZATION
RP OF VARIANTS MMAM HIS-93; ARG-133; ARG-161; ILE-189; GLU-191; ARG-203;
RP ARG-230; PRO-288; SER-305; GLU-377; LYS-388; LEU-424; GLU-426; LEU-615;
RP THR-615; ARG-624; VAL-625; GLY-625; PHE-674 AND TRP-694, FUNCTION, AND
RP CATALYTIC ACTIVITY.
RX PubMed=27167370; DOI=10.1002/humu.23013;
RA Forny P., Schnellmann A.S., Buerer C., Lutz S., Fowler B., Froese D.S.,
RA Baumgartner M.R.;
RT "Molecular genetic characterization of 151 mut-type methylmalonic aciduria
RT patients and identification of 41 novel mutations in MUT.";
RL Hum. Mutat. 37:745-754(2016).
RN [38]
RP VARIANTS MMAM HIS-93; CYS-108; CYS-110; SER-174; SER-215; SER-364; ILE-387;
RP PRO-692 AND TRP-694.
RX PubMed=26615597; DOI=10.1007/8904_2014_297;
RA Imtiaz F., Al-Mubarak B.M., Al-Mostafa A., Al-Hamed M., Allam R.,
RA Al-Hassnan Z., Al-Owain M., Al-Zaidan H., Rahbeeni Z., Qari A.,
RA Faqeih E.A., Alasmari A., Al-Mutairi F., Alfadhel M., Eyaid W.M.,
RA Rashed M.S., Al-Sayed M.;
RT "Spectrum of mutations in 60 Saudi patients with Mut methylmalonic
RT acidemia.";
RL JIMD Rep. 29:39-46(2016).
RN [39]
RP VARIANTS MMAM PRO-140; THR-141; VAL-161; GLY-309; THR-505; LYS-514; ARG-597
RP AND ASP-723, CHARACTERIZATION OF VARIANTS MMAM PRO-140; THR-141; VAL-161;
RP GLY-309; THR-505; LYS-514; ARG-597 AND ASP-723, FUNCTION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=28101778; DOI=10.1007/s12519-016-0085-z;
RA Han L.S., Huang Z., Han F., Wang Y., Gong Z.W., Gu X.F.;
RT "Eight novel MUT loss-of-function missense mutations in Chinese patients
RT with isolated methylmalonic academia.";
RL World J. Pediatr. 13:381-386(2017).
CC -!- FUNCTION: Catalyzes the reversible isomerization of methylmalonyl-CoA
CC (MMCoA) (generated from branched-chain amino acid metabolism and
CC degradation of dietary odd chain fatty acids and cholesterol) to
CC succinyl-CoA (3-carboxypropionyl-CoA), a key intermediate of the
CC tricarboxylic acid cycle. {ECO:0000269|PubMed:1346616,
CC ECO:0000269|PubMed:1978672, ECO:0000269|PubMed:21138732,
CC ECO:0000269|PubMed:24458, ECO:0000269|PubMed:2453061,
CC ECO:0000269|PubMed:25125334, ECO:0000269|PubMed:27167370,
CC ECO:0000269|PubMed:28101778, ECO:0000269|PubMed:28943303,
CC ECO:0000269|PubMed:29056341}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-methylmalonyl-CoA = succinyl-CoA; Xref=Rhea:RHEA:22888,
CC ChEBI:CHEBI:57292, ChEBI:CHEBI:57326; EC=5.4.99.2;
CC Evidence={ECO:0000269|PubMed:1346616, ECO:0000269|PubMed:1978672,
CC ECO:0000269|PubMed:21138732, ECO:0000269|PubMed:24458,
CC ECO:0000269|PubMed:2453061, ECO:0000269|PubMed:25125334,
CC ECO:0000269|PubMed:27167370, ECO:0000269|PubMed:28101778,
CC ECO:0000269|PubMed:28943303, ECO:0000269|PubMed:29056341};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22889;
CC Evidence={ECO:0000305|PubMed:2453061};
CC -!- COFACTOR:
CC Name=adenosylcob(III)alamin; Xref=ChEBI:CHEBI:18408;
CC Evidence={ECO:0000269|PubMed:1978672, ECO:0000269|PubMed:21138732,
CC ECO:0000269|PubMed:28943303, ECO:0000269|PubMed:29056341};
CC -!- ACTIVITY REGULATION: During catalysis, accumulation of oxidized
CC inactive cofactor hydroxocobalamin (OH2Cbl) leads to loss of MMUT
CC activity (PubMed:21138732, PubMed:28943303). Interaction with MMAA
CC decreases the rate of OH2Cbl formation and promotes the replacement of
CC OH2Cbl by the active cofactor adenosylcobalamin (AdoCbl), thereby
CC restoring MMUT activity (PubMed:21138732, PubMed:28943303). Inhibited
CC by itaconyl-CoA, a metabolite that inactivates the coenzyme B12
CC cofactor (PubMed:29056341). Inhibited at high concentration of
CC substrate (PubMed:28943303). {ECO:0000269|PubMed:28943303,
CC ECO:0000269|PubMed:29056341}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.7 nM for adenosylcob(III)alamin {ECO:0000269|PubMed:25125334};
CC KM=0.24 uM for adenosylcob(III)alamin {ECO:0000269|PubMed:1978672};
CC KM=0.35 mM for methylmalonyl-CoA {ECO:0000269|PubMed:1978672};
CC KM=76.15 uM for methylmalonyl-CoA {ECO:0000269|PubMed:28943303};
CC KM=23.19 uM for methylmalonyl-CoA (in the presence of methylmalonic
CC aciduria type A protein/MMAA and GTP) {ECO:0000269|PubMed:28943303};
CC Vmax=9.06 umol/min/mg enzyme for methylmalonyl-CoA
CC {ECO:0000269|PubMed:28943303};
CC Vmax=4.83 umol/min/mg enzyme for methylmalonyl-CoA in the presence of
CC methylmalonic aciduria type A protein/MMAA and GTP
CC {ECO:0000269|PubMed:28943303};
CC -!- SUBUNIT: Homodimer (PubMed:20876572). Interacts (the apoenzyme form)
CC with MMAA; the interaction is GTP dependent (PubMed:20876572,
CC PubMed:21138732, PubMed:28943303). {ECO:0000269|PubMed:20876572,
CC ECO:0000269|PubMed:21138732, ECO:0000269|PubMed:28943303}.
CC -!- INTERACTION:
CC P22033; P42858: HTT; NbExp=12; IntAct=EBI-2690467, EBI-466029;
CC P22033; Q8IVH4: MMAA; NbExp=3; IntAct=EBI-2690467, EBI-10714945;
CC P22033; P22033: MMUT; NbExp=2; IntAct=EBI-2690467, EBI-2690467;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000269|PubMed:24458}.
CC Mitochondrion {ECO:0000269|PubMed:28943303}. Cytoplasm
CC {ECO:0000269|PubMed:28943303}.
CC -!- DISEASE: Methylmalonic aciduria due to methylmalonyl-CoA mutase
CC deficiency (MMAM) [MIM:251000]: An often fatal disorder of organic acid
CC metabolism. Common clinical features include lethargy, vomiting,
CC failure to thrive, hypotonia, neurological deficit and early death. Two
CC forms of the disease are distinguished by the presence (mut-) or
CC absence (mut0) of residual enzyme activity. Mut0 patients have more
CC severe neurological manifestations of the disease than do
CC MUT- patients. MMAM is unresponsive to vitamin B12 therapy.
CC {ECO:0000269|PubMed:10923046, ECO:0000269|PubMed:11350191,
CC ECO:0000269|PubMed:1346616, ECO:0000269|PubMed:1351030,
CC ECO:0000269|PubMed:15643616, ECO:0000269|PubMed:15781192,
CC ECO:0000269|PubMed:16281286, ECO:0000269|PubMed:1670635,
CC ECO:0000269|PubMed:17113806, ECO:0000269|PubMed:17957493,
CC ECO:0000269|PubMed:19588269, ECO:0000269|PubMed:1977311,
CC ECO:0000269|PubMed:1980486, ECO:0000269|PubMed:22727635,
CC ECO:0000269|PubMed:25125334, ECO:0000269|PubMed:26615597,
CC ECO:0000269|PubMed:27167370, ECO:0000269|PubMed:28101778,
CC ECO:0000269|PubMed:7909321, ECO:0000269|PubMed:7912889,
CC ECO:0000269|PubMed:9285782, ECO:0000269|PubMed:9452100,
CC ECO:0000269|PubMed:9554742}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the methylmalonyl-CoA mutase family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Methylmalonyl coenzyme A mutase
CC entry;
CC URL="https://en.wikipedia.org/wiki/Methylmalonyl_Coenzyme_A_mutase";
CC ---------------------------------------------------------------------------
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DR EMBL; M65131; AAA59569.1; -; mRNA.
DR EMBL; M37510; AAA99226.1; -; Genomic_DNA.
DR EMBL; M37499; AAA99226.1; JOINED; Genomic_DNA.
DR EMBL; M37500; AAA99226.1; JOINED; Genomic_DNA.
DR EMBL; M37501; AAA99226.1; JOINED; Genomic_DNA.
DR EMBL; M37503; AAA99226.1; JOINED; Genomic_DNA.
DR EMBL; M37504; AAA99226.1; JOINED; Genomic_DNA.
DR EMBL; M37505; AAA99226.1; JOINED; Genomic_DNA.
DR EMBL; M37506; AAA99226.1; JOINED; Genomic_DNA.
DR EMBL; M37507; AAA99226.1; JOINED; Genomic_DNA.
DR EMBL; M37508; AAA99226.1; JOINED; Genomic_DNA.
DR EMBL; M37509; AAA99226.1; JOINED; Genomic_DNA.
DR EMBL; AK292568; BAF85257.1; -; mRNA.
DR EMBL; BT007434; AAP36102.1; -; mRNA.
DR EMBL; AL590668; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC016282; AAH16282.1; -; mRNA.
DR CCDS; CCDS4924.1; -.
DR PIR; A59145; A59145.
DR RefSeq; NP_000246.2; NM_000255.3.
DR RefSeq; XP_005249200.1; XM_005249143.3.
DR PDB; 2XIJ; X-ray; 1.95 A; A=12-750.
DR PDB; 2XIQ; X-ray; 1.95 A; A/B=12-750.
DR PDB; 3BIC; X-ray; 2.60 A; A/B=12-750.
DR PDBsum; 2XIJ; -.
DR PDBsum; 2XIQ; -.
DR PDBsum; 3BIC; -.
DR AlphaFoldDB; P22033; -.
DR SMR; P22033; -.
DR BioGRID; 110680; 55.
DR CORUM; P22033; -.
DR IntAct; P22033; 11.
DR MINT; P22033; -.
DR STRING; 9606.ENSP00000274813; -.
DR DrugBank; DB00115; Cyanocobalamin.
DR DrugBank; DB00200; Hydroxocobalamin.
DR SwissLipids; SLP:000001254; -.
DR GlyGen; P22033; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P22033; -.
DR MetOSite; P22033; -.
DR PhosphoSitePlus; P22033; -.
DR BioMuta; MUT; -.
DR DMDM; 317373575; -.
DR EPD; P22033; -.
DR jPOST; P22033; -.
DR MassIVE; P22033; -.
DR MaxQB; P22033; -.
DR PaxDb; P22033; -.
DR PeptideAtlas; P22033; -.
DR PRIDE; P22033; -.
DR ProteomicsDB; 53953; -.
DR Antibodypedia; 30809; 187 antibodies from 27 providers.
DR DNASU; 4594; -.
DR Ensembl; ENST00000274813.4; ENSP00000274813.3; ENSG00000146085.8.
DR GeneID; 4594; -.
DR KEGG; hsa:4594; -.
DR MANE-Select; ENST00000274813.4; ENSP00000274813.3; NM_000255.4; NP_000246.2.
DR UCSC; uc003ozg.5; human.
DR CTD; 4594; -.
DR DisGeNET; 4594; -.
DR GeneCards; MMUT; -.
DR GeneReviews; MMUT; -.
DR HGNC; HGNC:7526; MMUT.
DR HPA; ENSG00000146085; Tissue enhanced (liver).
DR MalaCards; MMUT; -.
DR MIM; 251000; phenotype.
DR MIM; 609058; gene.
DR neXtProt; NX_P22033; -.
DR OpenTargets; ENSG00000146085; -.
DR Orphanet; 79312; Vitamin B12-unresponsive methylmalonic acidemia type mut-.
DR Orphanet; 289916; Vitamin B12-unresponsive methylmalonic acidemia type mut0.
DR PharmGKB; PA31327; -.
DR VEuPathDB; HostDB:ENSG00000146085; -.
DR eggNOG; ENOG502QQ7X; Eukaryota.
DR GeneTree; ENSGT00390000011892; -.
DR HOGENOM; CLU_009523_3_1_1; -.
DR InParanoid; P22033; -.
DR OMA; PWGGSAY; -.
DR OrthoDB; 347581at2759; -.
DR PhylomeDB; P22033; -.
DR TreeFam; TF313557; -.
DR BioCyc; MetaCyc:HS07322-MON; -.
DR BRENDA; 5.4.99.2; 2681.
DR PathwayCommons; P22033; -.
DR Reactome; R-HSA-3359475; Defective MMAA causes MMA, cblA type.
DR Reactome; R-HSA-3359478; Defective MUT causes MMAM.
DR Reactome; R-HSA-71032; Propionyl-CoA catabolism.
DR Reactome; R-HSA-9759218; Cobalamin (Cbl) metabolism.
DR SABIO-RK; P22033; -.
DR SignaLink; P22033; -.
DR BioGRID-ORCS; 4594; 13 hits in 1085 CRISPR screens.
DR ChiTaRS; MUT; human.
DR EvolutionaryTrace; P22033; -.
DR GeneWiki; Methylmalonyl-CoA_mutase; -.
DR GenomeRNAi; 4594; -.
DR Pharos; P22033; Tbio.
DR PRO; PR:P22033; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P22033; protein.
DR Bgee; ENSG00000146085; Expressed in choroid plexus epithelium and 206 other tissues.
DR ExpressionAtlas; P22033; baseline and differential.
DR Genevisible; P22033; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0031419; F:cobalamin binding; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004494; F:methylmalonyl-CoA mutase activity; IDA:UniProtKB.
DR GO; GO:0072341; F:modified amino acid binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0050667; P:homocysteine metabolic process; IDA:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0019678; P:propionate metabolic process, methylmalonyl pathway; IBA:GO_Central.
DR InterPro; IPR006159; Acid_CoA_mut_C.
DR InterPro; IPR016176; Cbl-dep_enz_cat.
DR InterPro; IPR006158; Cobalamin-bd.
DR InterPro; IPR036724; Cobalamin-bd_sf.
DR InterPro; IPR006099; MeMalonylCoA_mutase_a/b_cat.
DR InterPro; IPR006098; MMCoA_mutase_a_cat.
DR Pfam; PF02310; B12-binding; 1.
DR Pfam; PF01642; MM_CoA_mutase; 1.
DR SUPFAM; SSF51703; SSF51703; 1.
DR SUPFAM; SSF52242; SSF52242; 1.
DR TIGRFAMs; TIGR00640; acid_CoA_mut_C; 1.
DR TIGRFAMs; TIGR00641; acid_CoA_mut_N; 1.
DR PROSITE; PS51332; B12_BINDING; 1.
DR PROSITE; PS00544; METMALONYL_COA_MUTASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cobalamin; Cobalt; Cytoplasm;
KW Direct protein sequencing; Disease variant; Isomerase; Metal-binding;
KW Mitochondrion; Phosphoprotein; Reference proteome; Transit peptide.
FT TRANSIT 1..32
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:2567699"
FT CHAIN 33..750
FT /note="Methylmalonyl-CoA mutase, mitochondrial"
FT /id="PRO_0000019293"
FT DOMAIN 614..746
FT /note="B12-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00666"
FT BINDING 50
FT /ligand="malonyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57384"
FT /evidence="ECO:0000269|PubMed:20876572"
FT BINDING 96..99
FT /ligand="malonyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57384"
FT /evidence="ECO:0000269|PubMed:20876572"
FT BINDING 106..110
FT /ligand="malonyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57384"
FT /evidence="ECO:0000269|PubMed:20876572"
FT BINDING 216..218
FT /ligand="malonyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57384"
FT /evidence="ECO:0000269|PubMed:20876572"
FT BINDING 228
FT /ligand="malonyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57384"
FT /evidence="ECO:0000269|PubMed:20876572"
FT BINDING 255
FT /ligand="malonyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57384"
FT /evidence="ECO:0000269|PubMed:20876572"
FT BINDING 265
FT /ligand="malonyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57384"
FT /evidence="ECO:0000269|PubMed:20876572"
FT BINDING 304..306
FT /ligand="malonyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57384"
FT /evidence="ECO:0000269|PubMed:20876572"
FT BINDING 627
FT /ligand="adenosylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:18408"
FT /ligand_part="Co"
FT /ligand_part_id="ChEBI:CHEBI:27638"
FT /note="axial binding residue"
FT /evidence="ECO:0000269|PubMed:20876572"
FT MOD_RES 89
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P16332"
FT MOD_RES 212
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P16332"
FT MOD_RES 335
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P16332"
FT MOD_RES 343
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P16332"
FT MOD_RES 481
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 595
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P16332"
FT MOD_RES 602
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P16332"
FT VARIANT 7..750
FT /note="Missing (in MMAM; mut-)"
FT /evidence="ECO:0000269|PubMed:17957493"
FT /id="VAR_080031"
FT VARIANT 69
FT /note="I -> V (in MMAM; likely benign variant;
FT dbSNP:rs115923556)"
FT /evidence="ECO:0000269|PubMed:15781192,
FT ECO:0000269|PubMed:16281286, ECO:0000269|PubMed:17957493"
FT /id="VAR_023472"
FT VARIANT 86
FT /note="P -> L (in MMAM; mut0 and mut-; no effect on protein
FT abundance; decreased methylmalonyl-CoA mutase activity;
FT decreased affinity for adenosylcob(III)alamin; alters
FT thermodynamic stability; dbSNP:rs769348060)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:25125334"
FT /id="VAR_026592"
FT VARIANT 87
FT /note="G -> E (in MMAM; mut0; dbSNP:rs1554160986)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026593"
FT VARIANT 93
FT /note="R -> H (in MMAM; mut0; decreased methylmalonyl-CoA
FT mutase activity; dbSNP:rs121918251)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:1670635, ECO:0000269|PubMed:26615597,
FT ECO:0000269|PubMed:27167370"
FT /id="VAR_004409"
FT VARIANT 94
FT /note="G -> R (in MMAM; mut0; dbSNP:rs727504022)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026594"
FT VARIANT 94
FT /note="G -> V (in MMAM; mut- and mut0; dbSNP:rs535411418)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:9285782"
FT /id="VAR_022393"
FT VARIANT 95
FT /note="P -> R (in MMAM; mut0; dbSNP:rs190834116)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026595"
FT VARIANT 100
FT /note="Y -> C (in MMAM; mut-; no effect on protein
FT abundance; decreased methylmalonyl-CoA mutase activity;
FT decreased affinity for adenosylcob(III)alamin; alters
FT thermodynamic stability; dbSNP:rs864309735)"
FT /evidence="ECO:0000269|PubMed:17113806,
FT ECO:0000269|PubMed:25125334"
FT /id="VAR_075379"
FT VARIANT 105
FT /note="W -> R (in MMAM; mut0; dbSNP:rs121918249)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:1977311"
FT /id="VAR_004410"
FT VARIANT 108
FT /note="R -> C (in MMAM; mut0; dbSNP:rs121918257)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:26615597"
FT /id="VAR_026596"
FT VARIANT 108
FT /note="R -> G (in MMAM; mut-)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026597"
FT VARIANT 108
FT /note="R -> H (in MMAM; mut0; dbSNP:rs483352778)"
FT /evidence="ECO:0000269|PubMed:15643616,
FT ECO:0000269|PubMed:16281286, ECO:0000269|PubMed:17113806"
FT /id="VAR_022394"
FT VARIANT 109
FT /note="Q -> R (in MMAM; mut0; dbSNP:rs1461110052)"
FT /evidence="ECO:0000269|PubMed:15781192,
FT ECO:0000269|PubMed:17957493"
FT /id="VAR_023473"
FT VARIANT 110
FT /note="Y -> C (in MMAM; dbSNP:rs796052005)"
FT /evidence="ECO:0000269|PubMed:26615597"
FT /id="VAR_075380"
FT VARIANT 126
FT /note="N -> K (in MMAM; dbSNP:rs879253827)"
FT /evidence="ECO:0000269|PubMed:27167370"
FT /id="VAR_077210"
FT VARIANT 133
FT /note="G -> R (in MMAM; mut0; decreased protein abundance;
FT decreased methylmalonyl-CoA mutase activity;
FT dbSNP:rs879253828)"
FT /evidence="ECO:0000269|PubMed:27167370"
FT /id="VAR_077211"
FT VARIANT 137
FT /note="A -> G (in MMAM; dbSNP:rs941483851)"
FT /evidence="ECO:0000269|PubMed:22727635"
FT /id="VAR_075381"
FT VARIANT 137
FT /note="A -> V (in MMAM; mut0; dbSNP:rs941483851)"
FT /evidence="ECO:0000269|PubMed:10923046,
FT ECO:0000269|PubMed:17113806"
FT /id="VAR_022395"
FT VARIANT 139
FT /note="D -> N (in MMAM; unknown pathological significance;
FT dbSNP:rs879253829)"
FT /evidence="ECO:0000269|PubMed:27167370"
FT /id="VAR_077212"
FT VARIANT 140
FT /note="L -> P (in MMAM; decreased protein expression;
FT decreased methylmalonyl-CoA mutase activity)"
FT /evidence="ECO:0000269|PubMed:1980486,
FT ECO:0000269|PubMed:28101778"
FT /id="VAR_078342"
FT VARIANT 141
FT /note="A -> T (in MMAM; decreased protein expression;
FT dbSNP:rs1554160730)"
FT /evidence="ECO:0000269|PubMed:28101778"
FT /id="VAR_078343"
FT VARIANT 143
FT /note="H -> Y (in MMAM; mut0)"
FT /evidence="ECO:0000269|PubMed:17113806"
FT /id="VAR_075382"
FT VARIANT 145
FT /note="G -> S (in MMAM; mut0)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026598"
FT VARIANT 148
FT /note="S -> L (in MMAM; mut0; dbSNP:rs1300547552)"
FT /evidence="ECO:0000269|PubMed:15643616,
FT ECO:0000269|PubMed:17113806"
FT /id="VAR_022396"
FT VARIANT 152..750
FT /note="Missing (in MMAM; mut0)"
FT /evidence="ECO:0000269|PubMed:17957493"
FT /id="VAR_080032"
FT VARIANT 156
FT /note="D -> N (in MMAM; mut-)"
FT /evidence="ECO:0000269|PubMed:15643616"
FT /id="VAR_022397"
FT VARIANT 156
FT /note="D -> V (in MMAM; dbSNP:rs757000253)"
FT /evidence="ECO:0000269|PubMed:27167370"
FT /id="VAR_077213"
FT VARIANT 158
FT /note="G -> V (in MMAM; mut0)"
FT /evidence="ECO:0000269|PubMed:15643616"
FT /id="VAR_022398"
FT VARIANT 161
FT /note="G -> R (in MMAM; mut0; decreased protein abundance;
FT decreased methylmalonyl-CoA mutase activity)"
FT /evidence="ECO:0000269|PubMed:19588269,
FT ECO:0000269|PubMed:27167370"
FT /id="VAR_077214"
FT VARIANT 161
FT /note="G -> V (in MMAM; decreased protein expression)"
FT /evidence="ECO:0000269|PubMed:28101778"
FT /id="VAR_078344"
FT VARIANT 174
FT /note="F -> S (in MMAM; mut0; dbSNP:rs864309733)"
FT /evidence="ECO:0000269|PubMed:10923046,
FT ECO:0000269|PubMed:16281286, ECO:0000269|PubMed:26615597"
FT /id="VAR_022399"
FT VARIANT 186
FT /note="M -> V (in MMAM; mut-; dbSNP:rs148331800)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026599"
FT VARIANT 187
FT /note="T -> S (in MMAM; mut0; dbSNP:rs879253830)"
FT /evidence="ECO:0000269|PubMed:27167370"
FT /id="VAR_077215"
FT VARIANT 189
FT /note="N -> I (in MMAM; mut-; decreased protein abundance;
FT decreased methylmalonyl-CoA mutase activity;
FT dbSNP:rs200908035)"
FT /evidence="ECO:0000269|PubMed:27167370"
FT /id="VAR_077216"
FT VARIANT 189
FT /note="N -> K (in MMAM; mut-; dbSNP:rs1561959114)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026600"
FT VARIANT 191
FT /note="A -> E (in MMAM; mut- and mut0; affects proper
FT folding; reduced protein level; decreased methylmalonyl-CoA
FT mutase activity; dbSNP:rs760782399)"
FT /evidence="ECO:0000269|PubMed:15643616,
FT ECO:0000269|PubMed:15781192, ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:17113806, ECO:0000269|PubMed:17957493,
FT ECO:0000269|PubMed:25125334, ECO:0000269|PubMed:27167370,
FT ECO:0000269|PubMed:9554742"
FT /id="VAR_004411"
FT VARIANT 197
FT /note="A -> E (in MMAM; mut0)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026601"
FT VARIANT 203
FT /note="G -> R (in MMAM; mut0; decreased protein abundance;
FT decreased methylmalonyl-CoA mutase activity;
FT dbSNP:rs778702777)"
FT /evidence="ECO:0000269|PubMed:10923046,
FT ECO:0000269|PubMed:15643616, ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:17113806, ECO:0000269|PubMed:17957493,
FT ECO:0000269|PubMed:27167370"
FT /id="VAR_022400"
FT VARIANT 205
FT /note="Missing (in MMAM; mut0; dbSNP:rs879253831)"
FT /evidence="ECO:0000269|PubMed:27167370"
FT /id="VAR_077217"
FT VARIANT 215
FT /note="G -> C (in MMAM; mut- and mut0; dbSNP:rs121918258)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026602"
FT VARIANT 215
FT /note="G -> S (in MMAM; mut0; dbSNP:rs121918258)"
FT /evidence="ECO:0000269|PubMed:15643616,
FT ECO:0000269|PubMed:16281286, ECO:0000269|PubMed:26615597"
FT /id="VAR_022401"
FT VARIANT 218
FT /note="Q -> H (in MMAM; mut0 and mut-; no effect on protein
FT abundance; loss of methylmalonyl-CoA mutase activity;
FT alters thermodynamic stability; dbSNP:rs1446389693)"
FT /evidence="ECO:0000269|PubMed:10923046,
FT ECO:0000269|PubMed:16281286, ECO:0000269|PubMed:17113806,
FT ECO:0000269|PubMed:25125334"
FT /id="VAR_022402"
FT VARIANT 219
FT /note="N -> Y (in MMAM; mut0; no effect on protein
FT abundance; loss of methylmalonyl-CoA mutase activity;
FT dbSNP:rs121918256)"
FT /evidence="ECO:0000269|PubMed:11350191,
FT ECO:0000269|PubMed:15643616, ECO:0000269|PubMed:15781192,
FT ECO:0000269|PubMed:16281286, ECO:0000269|PubMed:17113806,
FT ECO:0000269|PubMed:17957493, ECO:0000269|PubMed:22727635,
FT ECO:0000269|PubMed:25125334"
FT /id="VAR_022403"
FT VARIANT 228..750
FT /note="Missing (in MMAM; mut0)"
FT /evidence="ECO:0000269|PubMed:17957493"
FT /id="VAR_080033"
FT VARIANT 228
FT /note="R -> Q (in MMAM; mut0; dbSNP:rs770810987)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:9554742"
FT /id="VAR_004412"
FT VARIANT 230
FT /note="T -> I (in MMAM; mut-)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026603"
FT VARIANT 230
FT /note="T -> R (in MMAM; mut0; decreased protein abundance;
FT decreased methylmalonyl-CoA mutase activity;
FT dbSNP:rs879253833)"
FT /evidence="ECO:0000269|PubMed:27167370"
FT /id="VAR_077218"
FT VARIANT 231
FT /note="Y -> N (in MMAM; mut-; no effect on protein
FT abundance; decreased methylmalonyl-CoA mutase activity;
FT strong decreased affinity for adenosylcob(III)alamin;
FT alters thermodynamic stability; dbSNP:rs864309736)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:17113806, ECO:0000269|PubMed:17957493,
FT ECO:0000269|PubMed:25125334, ECO:0000269|PubMed:9285782"
FT /id="VAR_004413"
FT VARIANT 262
FT /note="S -> N (in MMAM; mut0)"
FT /evidence="ECO:0000269|PubMed:15643616,
FT ECO:0000269|PubMed:16281286"
FT /id="VAR_022404"
FT VARIANT 265
FT /note="H -> Y (in MMAM; mut-)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026604"
FT VARIANT 276
FT /note="E -> D (in MMAM; mut-; unknown pathological
FT significance; dbSNP:rs12175488)"
FT /evidence="ECO:0000269|PubMed:27167370"
FT /id="VAR_077219"
FT VARIANT 281
FT /note="L -> S (in MMAM; mut0; dbSNP:rs796052007)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026605"
FT VARIANT 284
FT /note="G -> E (in MMAM; mut0; dbSNP:rs879253835)"
FT /evidence="ECO:0000269|PubMed:27167370"
FT /id="VAR_077220"
FT VARIANT 284
FT /note="G -> R (in MMAM; mut0; dbSNP:rs761477436)"
FT /evidence="ECO:0000269|PubMed:27167370"
FT /id="VAR_077221"
FT VARIANT 288
FT /note="S -> P (in MMAM; mut0; decreased protein abundance;
FT decreased methylmalonyl-CoA mutase activity;
FT dbSNP:rs1179778233)"
FT /evidence="ECO:0000269|PubMed:17113806,
FT ECO:0000269|PubMed:27167370"
FT /id="VAR_075383"
FT VARIANT 291
FT /note="G -> E (in MMAM; mut0)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026606"
FT VARIANT 293
FT /note="Q -> P (in MMAM; mut0)"
FT /evidence="ECO:0000269|PubMed:15643616"
FT /id="VAR_022405"
FT VARIANT 305
FT /note="L -> S (in MMAM; mut0; decreased protein abundance;
FT decreased methylmalonyl-CoA mutase activity;
FT dbSNP:rs1554160246)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:22727635, ECO:0000269|PubMed:27167370"
FT /id="VAR_026607"
FT VARIANT 306
FT /note="S -> F (in MMAM; mut0; dbSNP:rs1085307929)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026608"
FT VARIANT 309
FT /note="W -> G (in MMAM; decreased protein expression)"
FT /evidence="ECO:0000269|PubMed:28101778"
FT /id="VAR_078345"
FT VARIANT 312
FT /note="G -> V (in MMAM; mut0; dbSNP:rs864309734)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:9554742"
FT /id="VAR_004414"
FT VARIANT 316
FT /note="Y -> C (in MMAM; mut-; no effect on protein
FT abundance; decreased methylmalonyl-CoA mutase activity; no
FT decreased affinity for adenosylcob(III)alamin;
FT dbSNP:rs781474200)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:25125334"
FT /id="VAR_026609"
FT VARIANT 324
FT /note="A -> T (in MMAM; mut-; dbSNP:rs780387525)"
FT /evidence="ECO:0000269|PubMed:15781192,
FT ECO:0000269|PubMed:16281286, ECO:0000269|PubMed:17957493"
FT /id="VAR_023474"
FT VARIANT 325
FT /note="G -> D (in MMAM; dbSNP:rs879253837)"
FT /evidence="ECO:0000269|PubMed:27167370"
FT /id="VAR_077222"
FT VARIANT 326
FT /note="R -> K (in MMAM; unknown pathological significance;
FT dbSNP:rs758577372)"
FT /evidence="ECO:0000269|PubMed:27167370"
FT /id="VAR_077223"
FT VARIANT 328
FT /note="L -> F (in MMAM; mut0; affects proper folding; no
FT effect on protein abundance; loss of methylmalonyl-CoA
FT mutase activity; dbSNP:rs796052002)"
FT /evidence="ECO:0000269|PubMed:15643616,
FT ECO:0000269|PubMed:17113806, ECO:0000269|PubMed:22727635,
FT ECO:0000269|PubMed:25125334"
FT /id="VAR_022406"
FT VARIANT 328
FT /note="L -> P (in MMAM; mut0; dbSNP:rs965316043)"
FT /evidence="ECO:0000269|PubMed:15781192,
FT ECO:0000269|PubMed:17957493"
FT /id="VAR_023475"
FT VARIANT 344
FT /note="S -> F (in MMAM; mut-; affects proper folding; no
FT effect on protein abundance; loss of methylmalonyl-CoA
FT mutase activity; decreased affinity for
FT adenosylcob(III)alamin)"
FT /evidence="ECO:0000269|PubMed:17113806,
FT ECO:0000269|PubMed:25125334"
FT /id="VAR_075384"
FT VARIANT 346
FT /note="Missing (in MMAM; mut0)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:9554742"
FT /id="VAR_004415"
FT VARIANT 347
FT /note="L -> R (in MMAM; mut0; dbSNP:rs1026703654)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026610"
FT VARIANT 350
FT /note="H -> Y (in MMAM; mut0; dbSNP:rs1407914109)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026611"
FT VARIANT 358
FT /note="L -> P (in MMAM; mut0)"
FT /evidence="ECO:0000269|PubMed:17957493"
FT /id="VAR_077224"
FT VARIANT 364
FT /note="Y -> S (in MMAM; dbSNP:rs563776413)"
FT /evidence="ECO:0000269|PubMed:26615597"
FT /id="VAR_075385"
FT VARIANT 366
FT /note="N -> S (in MMAM; mut-; no effect on protein
FT abundance; loss of methylmalonyl-CoA mutase activity;
FT decreased affinity for adenosylcob(III)alamin; alters
FT thermodynamic stability; dbSNP:rs864309737)"
FT /evidence="ECO:0000269|PubMed:17113806,
FT ECO:0000269|PubMed:25125334"
FT /id="VAR_075386"
FT VARIANT 368
FT /note="V -> D (in MMAM)"
FT /id="VAR_004416"
FT VARIANT 369
FT /note="R -> C (in MMAM; mut0; dbSNP:rs772552898)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:17957493"
FT /id="VAR_026612"
FT VARIANT 369
FT /note="R -> H (in MMAM; mut- and mut0; no effect on protein
FT abundance; loss of methylmalonyl-CoA mutase activity;
FT alters thermodynamic stability; dbSNP:rs564069299)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:17113806, ECO:0000269|PubMed:25125334,
FT ECO:0000269|PubMed:9285782"
FT /id="VAR_004417"
FT VARIANT 370
FT /note="T -> P (in MMAM; mut0; dbSNP:rs368790885)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026613"
FT VARIANT 377
FT /note="A -> E (in MMAM; mut0; decreased protein abundance;
FT decreased methylmalonyl-CoA mutase activity;
FT dbSNP:rs121918250)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:1977311, ECO:0000269|PubMed:27167370"
FT /id="VAR_004418"
FT VARIANT 383
FT /note="Q -> H (in MMAM; mut0)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026614"
FT VARIANT 383
FT /note="Q -> P (in MMAM; mut0)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026615"
FT VARIANT 386
FT /note="H -> N (in MMAM; mut0; dbSNP:rs1554159937)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026616"
FT VARIANT 386
FT /note="H -> R (in MMAM; mut0; dbSNP:rs866933356)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_077225"
FT VARIANT 387
FT /note="T -> I (in MMAM; mut-; no effect on protein
FT abundance; decreased methylmalonyl-CoA mutase activity;
FT decreased affinity for adenosylcob(III)alamin; alters
FT thermodynamic stability)"
FT /evidence="ECO:0000269|PubMed:22727635,
FT ECO:0000269|PubMed:25125334, ECO:0000269|PubMed:26615597"
FT /id="VAR_075387"
FT VARIANT 388
FT /note="N -> H (in MMAM; mut0; dbSNP:rs766010704)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026617"
FT VARIANT 388
FT /note="N -> K (in MMAM; mut0; decreased protein abundance;
FT decreased methylmalonyl-CoA mutase activity;
FT dbSNP:rs879253840)"
FT /evidence="ECO:0000269|PubMed:27167370"
FT /id="VAR_077226"
FT VARIANT 389
FT /note="Missing (in MMAM; mut0)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026618"
FT VARIANT 412
FT /note="Missing (in MMAM; mut0)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026619"
FT VARIANT 424
FT /note="P -> L (in MMAM; mut0; decreased protein abundance;
FT decreased methylmalonyl-CoA mutase activity;
FT dbSNP:rs879253842)"
FT /evidence="ECO:0000269|PubMed:27167370"
FT /id="VAR_077227"
FT VARIANT 426
FT /note="G -> E (in MMAM; mut-; decreased protein abundance;
FT decreased methylmalonyl-CoA mutase activity;
FT dbSNP:rs533755473)"
FT /evidence="ECO:0000269|PubMed:27167370"
FT /id="VAR_077228"
FT VARIANT 426
FT /note="G -> R (in MMAM; mut-; no effect on protein
FT abundance; decreased methylmalonyl-CoA mutase activity;
FT strong decreased affinity for adenosylcob(III)alamin;
FT alters thermodynamic stability; dbSNP:rs769922244)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:25125334"
FT /id="VAR_026620"
FT VARIANT 427
FT /note="G -> D (in MMAM; mut0; dbSNP:rs753288303)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026621"
FT VARIANT 454
FT /note="G -> E (in MMAM; mut0)"
FT /evidence="ECO:0000269|PubMed:17113806,
FT ECO:0000269|PubMed:22727635"
FT /id="VAR_075388"
FT VARIANT 499
FT /note="A -> T (in dbSNP:rs2229385)"
FT /evidence="ECO:0000269|PubMed:11350191,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:22727635, ECO:0000269|Ref.5"
FT /id="VAR_022407"
FT VARIANT 505
FT /note="I -> T (in MMAM; decreased protein expression;
FT decreased methylmalonyl-CoA mutase activity)"
FT /evidence="ECO:0000269|PubMed:28101778"
FT /id="VAR_078346"
FT VARIANT 514
FT /note="Q -> E (in MMAM; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:22727635"
FT /id="VAR_075389"
FT VARIANT 514
FT /note="Q -> K (in MMAM; decreased protein expression)"
FT /evidence="ECO:0000269|PubMed:28101778"
FT /id="VAR_078347"
FT VARIANT 518
FT /note="L -> P (in MMAM; mut0; dbSNP:rs864309738)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026622"
FT VARIANT 532
FT /note="R -> H (in dbSNP:rs1141321)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:1980486, ECO:0000269|PubMed:22727635,
FT ECO:0000269|PubMed:2567699, ECO:0000269|PubMed:7912889"
FT /id="VAR_004419"
FT VARIANT 535
FT /note="A -> P (in MMAM; mut0; dbSNP:rs760183775)"
FT /evidence="ECO:0000269|PubMed:10923046"
FT /id="VAR_022408"
FT VARIANT 552
FT /note="A -> V (in MMAM; unknown pathological significance;
FT dbSNP:rs879253845)"
FT /evidence="ECO:0000269|PubMed:27167370"
FT /id="VAR_077229"
FT VARIANT 560
FT /note="C -> Y (in MMAM; mut0; dbSNP:rs1238333040)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026623"
FT VARIANT 566
FT /note="T -> R (in MMAM; mut0)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026624"
FT VARIANT 573
FT /note="F -> S (in MMAM; mut-; affects proper folding; no
FT effect on protein abundance; no effect on methylmalonyl-CoA
FT mutase activity; decreased affinity for
FT adenosylcob(III)alamin; does not alter thermodynamic
FT stability; dbSNP:rs775593146)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:25125334"
FT /id="VAR_026625"
FT VARIANT 587
FT /note="Y -> C (in MMAM; mut-)"
FT /evidence="ECO:0000269|PubMed:15643616"
FT /id="VAR_022409"
FT VARIANT 597
FT /note="I -> R (in MMAM; no changed in protein expression;
FT decreased methylmalonyl-CoA mutase activity;
FT dbSNP:rs1554158951)"
FT /evidence="ECO:0000269|PubMed:28101778"
FT /id="VAR_078348"
FT VARIANT 598
FT /note="T -> A (in dbSNP:rs9473556)"
FT /id="VAR_030495"
FT VARIANT 615
FT /note="P -> L (in MMAM; mut0; affects proper folding;
FT reduced strongly protein level)"
FT /evidence="ECO:0000269|PubMed:22727635,
FT ECO:0000269|PubMed:25125334, ECO:0000269|PubMed:27167370"
FT /id="VAR_075390"
FT VARIANT 615
FT /note="P -> R (in MMAM; mut0; dbSNP:rs1554158777)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026626"
FT VARIANT 615
FT /note="P -> T (in MMAM; mut0; affects proper folding;
FT reduced strongly protein level; loss of methylmalonyl-CoA
FT mutase activity; dbSNP:rs1302409621)"
FT /evidence="ECO:0000269|PubMed:15643616,
FT ECO:0000269|PubMed:17113806, ECO:0000269|PubMed:22727635,
FT ECO:0000269|PubMed:25125334, ECO:0000269|PubMed:27167370"
FT /id="VAR_022410"
FT VARIANT 616
FT /note="R -> C (in MMAM; mut0; dbSNP:rs765284825)"
FT /evidence="ECO:0000269|PubMed:15781192,
FT ECO:0000269|PubMed:16281286, ECO:0000269|PubMed:17957493"
FT /id="VAR_023476"
FT VARIANT 617
FT /note="L -> R (in MMAM; mut0; dbSNP:rs1554158775)"
FT /evidence="ECO:0000269|PubMed:15781192,
FT ECO:0000269|PubMed:17957493"
FT /id="VAR_023477"
FT VARIANT 618
FT /note="L -> P (in MMAM; dbSNP:rs879253846)"
FT /evidence="ECO:0000269|PubMed:27167370"
FT /id="VAR_077230"
FT VARIANT 621
FT /note="K -> N (in MMAM; mut0)"
FT /evidence="ECO:0000269|PubMed:15643616"
FT /id="VAR_022411"
FT VARIANT 623
FT /note="G -> R (in MMAM; mut0; dbSNP:rs121918254)"
FT /evidence="ECO:0000269|PubMed:15643616,
FT ECO:0000269|PubMed:16281286, ECO:0000269|PubMed:7909321,
FT ECO:0000269|PubMed:9285782"
FT /id="VAR_004420"
FT VARIANT 624
FT /note="Q -> R (in MMAM; no effect on protein abundance;
FT dbSNP:rs768521956)"
FT /evidence="ECO:0000269|PubMed:15643616,
FT ECO:0000269|PubMed:27167370"
FT /id="VAR_022412"
FT VARIANT 625
FT /note="D -> G (in MMAM; mut0; decreased protein abundance;
FT decreased methylmalonyl-CoA mutase activity;
FT dbSNP:rs879253847)"
FT /evidence="ECO:0000269|PubMed:27167370"
FT /id="VAR_077231"
FT VARIANT 625
FT /note="D -> V (in MMAM; mut0; no effect on protein
FT abundance; decreased methylmalonyl-CoA mutase activity)"
FT /evidence="ECO:0000269|PubMed:22727635,
FT ECO:0000269|PubMed:27167370"
FT /id="VAR_075391"
FT VARIANT 626
FT /note="G -> C (in MMAM; mut-; dbSNP:rs982110849)"
FT /evidence="ECO:0000269|PubMed:7912889"
FT /id="VAR_004421"
FT VARIANT 627
FT /note="H -> R (in MMAM; mut0; dbSNP:rs372486357)"
FT /evidence="ECO:0000269|PubMed:10923046,
FT ECO:0000269|PubMed:15643616"
FT /id="VAR_022413"
FT VARIANT 630
FT /note="G -> E (in MMAM; mut0; dbSNP:rs143023066)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:17113806, ECO:0000269|PubMed:7912889"
FT /id="VAR_004422"
FT VARIANT 633
FT /note="V -> G (in MMAM; mut-; no effect on protein
FT abundance; decreased methylmalonyl-CoA mutase activity;
FT decreased affinity for adenosylcob(III)alamin; does not
FT alter thermodynamic stability; dbSNP:rs200055428)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:17113806, ECO:0000269|PubMed:25125334,
FT ECO:0000269|PubMed:9554742"
FT /id="VAR_004423"
FT VARIANT 637
FT /note="G -> E (in MMAM; mut-)"
FT /evidence="ECO:0000269|PubMed:15643616"
FT /id="VAR_022414"
FT VARIANT 637
FT /note="G -> R (in MMAM; mut0; dbSNP:rs781501004)"
FT /evidence="ECO:0000269|PubMed:16281286"
FT /id="VAR_026627"
FT VARIANT 638
FT /note="F -> I (in MMAM; mut0)"
FT /evidence="ECO:0000269|PubMed:15643616"
FT /id="VAR_022415"
FT VARIANT 640
FT /note="D -> Y (in MMAM; mut0; dbSNP:rs865815395)"
FT /evidence="ECO:0000269|PubMed:15643616"
FT /id="VAR_022416"
FT VARIANT 642
FT /note="G -> R (in MMAM; mut-; dbSNP:rs747897332)"
FT /evidence="ECO:0000269|PubMed:15643616,
FT ECO:0000269|PubMed:16281286"
FT /id="VAR_022417"
FT VARIANT 648
FT /note="G -> D (in MMAM; mut-; no effect on protein
FT abundance; decreased methylmalonyl-CoA mutase activity;
FT strong decreased affinity for adenosylcob(III)alamin;
FT alters thermodynamic stability; dbSNP:rs766721811)"
FT /evidence="ECO:0000269|PubMed:25125334,
FT ECO:0000269|PubMed:7912889"
FT /id="VAR_004424"
FT VARIANT 669
FT /note="V -> E (in MMAM; mut0; dbSNP:rs1360470463)"
FT /id="VAR_004425"
FT VARIANT 671
FT /note="I -> V (in dbSNP:rs8589)"
FT /evidence="ECO:0000269|PubMed:11350191,
FT ECO:0000269|PubMed:1346616, ECO:0000269|PubMed:1351030,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:16281286, ECO:0000269|PubMed:1980486,
FT ECO:0000269|PubMed:22727635, ECO:0000269|PubMed:2567699,
FT ECO:0000269|PubMed:9452100, ECO:0000269|Ref.5,
FT ECO:0007744|PubMed:21269460"
FT /id="VAR_004426"
FT VARIANT 674
FT /note="L -> F (in MMAM; decreased protein abundance;
FT decreased methylmalonyl-CoA mutase activity;
FT dbSNP:rs1164271240)"
FT /evidence="ECO:0000269|PubMed:22727635,
FT ECO:0000269|PubMed:27167370"
FT /id="VAR_075392"
FT VARIANT 678
FT /note="H -> R (in MMAM; mut-; dbSNP:rs147094927)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:9285782"
FT /id="VAR_004427"
FT VARIANT 684
FT /note="E -> EL (in MMAM; mut-)"
FT /evidence="ECO:0000269|PubMed:9554742"
FT /id="VAR_004428"
FT VARIANT 685
FT /note="L -> R (in MMAM; mut-; dbSNP:rs864309739)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:9554742"
FT /id="VAR_004429"
FT VARIANT 692
FT /note="L -> P (in MMAM)"
FT /evidence="ECO:0000269|PubMed:26615597"
FT /id="VAR_075393"
FT VARIANT 694
FT /note="R -> L (in MMAM; mut-; decreased protein abundance;
FT loss of methylmalonyl-CoA mutase activity; decreased
FT affinity for adenosylcob(III)alamin; alters thermodynamic
FT stability)"
FT /evidence="ECO:0000269|PubMed:17113806,
FT ECO:0000269|PubMed:25125334, ECO:0000269|PubMed:27167370"
FT /id="VAR_075394"
FT VARIANT 694
FT /note="R -> W (in MMAM; mut- and mut0; no effect on protein
FT abundance; loss of methylmalonyl-CoA mutase activity;
FT decreased affinity for adenosylcob(III)alamin; alters
FT thermodynamic stability; dbSNP:rs777758903)"
FT /evidence="ECO:0000269|PubMed:15643616,
FT ECO:0000269|PubMed:16281286, ECO:0000269|PubMed:17113806,
FT ECO:0000269|PubMed:17957493, ECO:0000269|PubMed:25125334,
FT ECO:0000269|PubMed:26615597, ECO:0000269|PubMed:7912889,
FT ECO:0000269|PubMed:9285782"
FT /id="VAR_004430"
FT VARIANT 700
FT /note="M -> K (in MMAM; mut-; no effect on protein
FT abundance; loss of methylmalonyl-CoA mutase activity;
FT decreased affinity for adenosylcob(III)alamin; alters
FT thermodynamic stability; dbSNP:rs140600746)"
FT /evidence="ECO:0000269|PubMed:15643616,
FT ECO:0000269|PubMed:16281286, ECO:0000269|PubMed:17113806,
FT ECO:0000269|PubMed:25125334"
FT /id="VAR_022418"
FT VARIANT 703
FT /note="G -> R (in MMAM; mut0; dbSNP:rs121918255)"
FT /evidence="ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:7909321"
FT /id="VAR_004431"
FT VARIANT 717
FT /note="G -> V (in MMAM; mut-; no effect on protein
FT abundance; interfers with the binding of the cofactor to
FT the apoenzyme; decreased methylmalonyl-CoA mutase activity;
FT strong decreased affinity for adenosylcob(III)alamin;
FT decreased thermodynamic stability; dbSNP:rs121918252)"
FT /evidence="ECO:0000269|PubMed:1346616,
FT ECO:0000269|PubMed:1351030, ECO:0000269|PubMed:16281286,
FT ECO:0000269|PubMed:25125334, ECO:0000269|PubMed:9285782,
FT ECO:0000269|PubMed:9452100"
FT /id="VAR_004432"
FT VARIANT 723
FT /note="G -> D (in MMAM; decreased protein expression;
FT decreased methylmalonyl-CoA mutase activity;
FT dbSNP:rs755077681)"
FT /evidence="ECO:0000269|PubMed:28101778"
FT /id="VAR_078349"
FT VARIANT 736
FT /note="L -> F (in MMAM; dbSNP:rs753461919)"
FT /evidence="ECO:0000269|PubMed:25125334"
FT /id="VAR_077232"
FT CONFLICT 153
FT /note="V -> L (in Ref. 3; AAA99226)"
FT /evidence="ECO:0000305"
FT CONFLICT 236
FT /note="E -> D (in Ref. 3; AAA99226)"
FT /evidence="ECO:0000305"
FT CONFLICT 274..277
FT /note="ILEL -> FWSW (in Ref. 3; AAA99226)"
FT /evidence="ECO:0000305"
FT CONFLICT 316
FT /note="Y -> H (in Ref. 3; AAA99226)"
FT /evidence="ECO:0000305"
FT CONFLICT 516
FT /note="E -> G (in Ref. 3; AAA99226)"
FT /evidence="ECO:0000305"
FT CONFLICT 591
FT /note="F -> Y (in Ref. 3; AAA99226)"
FT /evidence="ECO:0000305"
FT HELIX 30..33
FT /evidence="ECO:0007829|PDB:3BIC"
FT HELIX 41..50
FT /evidence="ECO:0007829|PDB:2XIJ"
FT TURN 51..53
FT /evidence="ECO:0007829|PDB:2XIQ"
FT HELIX 56..59
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 75..78
FT /evidence="ECO:0007829|PDB:2XIJ"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:2XIJ"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:2XIJ"
FT STRAND 106..111
FT /evidence="ECO:0007829|PDB:2XIQ"
FT HELIX 116..128
FT /evidence="ECO:0007829|PDB:2XIJ"
FT STRAND 133..136
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 140..143
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 151..153
FT /evidence="ECO:0007829|PDB:2XIJ"
FT TURN 154..159
FT /evidence="ECO:0007829|PDB:2XIJ"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 167..173
FT /evidence="ECO:0007829|PDB:2XIJ"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:2XIJ"
FT TURN 179..181
FT /evidence="ECO:0007829|PDB:2XIJ"
FT STRAND 183..186
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 192..205
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 210..212
FT /evidence="ECO:0007829|PDB:2XIJ"
FT STRAND 214..217
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 222..226
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 235..252
FT /evidence="ECO:0007829|PDB:2XIJ"
FT STRAND 259..262
FT /evidence="ECO:0007829|PDB:2XIQ"
FT HELIX 264..269
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 273..293
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 298..301
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 302..304
FT /evidence="ECO:0007829|PDB:2XIJ"
FT STRAND 307..311
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 315..337
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 342..345
FT /evidence="ECO:0007829|PDB:2XIJ"
FT STRAND 349..353
FT /evidence="ECO:0007829|PDB:2XIJ"
FT STRAND 360..362
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 365..379
FT /evidence="ECO:0007829|PDB:2XIJ"
FT STRAND 383..386
FT /evidence="ECO:0007829|PDB:2XIJ"
FT TURN 390..394
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 399..415
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 418..420
FT /evidence="ECO:0007829|PDB:2XIJ"
FT STRAND 421..423
FT /evidence="ECO:0007829|PDB:2XIJ"
FT TURN 424..427
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 429..451
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 455..461
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 463..481
FT /evidence="ECO:0007829|PDB:2XIJ"
FT STRAND 482..484
FT /evidence="ECO:0007829|PDB:2XIJ"
FT TURN 487..489
FT /evidence="ECO:0007829|PDB:2XIJ"
FT STRAND 490..492
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 508..524
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 527..543
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 548..557
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 562..573
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 586..591
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 595..611
FT /evidence="ECO:0007829|PDB:2XIJ"
FT STRAND 616..620
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 629..640
FT /evidence="ECO:0007829|PDB:2XIJ"
FT STRAND 644..647
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 654..663
FT /evidence="ECO:0007829|PDB:2XIJ"
FT STRAND 667..673
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 678..691
FT /evidence="ECO:0007829|PDB:2XIJ"
FT STRAND 697..704
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 707..709
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 710..716
FT /evidence="ECO:0007829|PDB:2XIJ"
FT STRAND 720..722
FT /evidence="ECO:0007829|PDB:2XIJ"
FT HELIX 728..744
FT /evidence="ECO:0007829|PDB:2XIJ"
SQ SEQUENCE 750 AA; 83134 MW; B5909729C08B562F CRC64;
MLRAKNQLFL LSPHYLRQVK ESSGSRLIQQ RLLHQQQPLH PEWAALAKKQ LKGKNPEDLI
WHTPEGISIK PLYSKRDTMD LPEELPGVKP FTRGPYPTMY TFRPWTIRQY AGFSTVEESN
KFYKDNIKAG QQGLSVAFDL ATHRGYDSDN PRVRGDVGMA GVAIDTVEDT KILFDGIPLE
KMSVSMTMNG AVIPVLANFI VTGEEQGVPK EKLTGTIQND ILKEFMVRNT YIFPPEPSMK
IIADIFEYTA KHMPKFNSIS ISGYHMQEAG ADAILELAYT LADGLEYSRT GLQAGLTIDE
FAPRLSFFWG IGMNFYMEIA KMRAGRRLWA HLIEKMFQPK NSKSLLLRAH CQTSGWSLTE
QDPYNNIVRT AIEAMAAVFG GTQSLHTNSF DEALGLPTVK SARIARNTQI IIQEESGIPK
VADPWGGSYM MECLTNDVYD AALKLINEIE EMGGMAKAVA EGIPKLRIEE CAARRQARID
SGSEVIVGVN KYQLEKEDAV EVLAIDNTSV RNRQIEKLKK IKSSRDQALA ERCLAALTEC
AASGDGNILA LAVDASRARC TVGEITDALK KVFGEHKAND RMVSGAYRQE FGESKEITSA
IKRVHKFMER EGRRPRLLVA KMGQDGHDRG AKVIATGFAD LGFDVDIGPL FQTPREVAQQ
AVDADVHAVG ISTLAAGHKT LVPELIKELN SLGRPDILVM CGGVIPPQDY EFLFEVGVSN
VFGPGTRIPK AAVQVLDDIE KCLEKKQQSV
