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 24-JAN-2024, entry version 229. 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 VARIANTS MMAM ASP-368 AND GLU-669. 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:8990001, ECO:0000269|PubMed:9285782, CC ECO:0000269|PubMed:9452100, ECO:0000269|PubMed:9554742}. Note=The CC disease is caused by variants affecting the gene represented in this CC 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 8DYJ; X-ray; 2.20 A; B=11-750. DR PDB; 8DYL; X-ray; 1.90 A; B=11-750. DR PDBsum; 2XIJ; -. DR PDBsum; 2XIQ; -. DR PDBsum; 3BIC; -. DR PDBsum; 8DYJ; -. DR PDBsum; 8DYL; -. DR AlphaFoldDB; P22033; -. DR SMR; P22033; -. DR BioGRID; 110680; 70. 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 SwissPalm; P22033; -. DR BioMuta; MUT; -. DR DMDM; 317373575; -. DR EPD; P22033; -. DR jPOST; P22033; -. DR MassIVE; P22033; -. DR MaxQB; P22033; -. DR PaxDb; 9606-ENSP00000274813; -. DR PeptideAtlas; P22033; -. DR ProteomicsDB; 53953; -. DR Pumba; P22033; -. DR Antibodypedia; 30809; 225 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 AGR; HGNC:7526; -. 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; IQEETHI; -. DR OrthoDB; 304517at2759; -. DR PhylomeDB; P22033; -. DR TreeFam; TF313557; -. DR BioCyc; MetaCyc:HS07322-MONOMER; -. 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 SIGNOR; P22033; -. DR BioGRID-ORCS; 4594; 14 hits in 1168 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 208 other cell types or tissues. DR ExpressionAtlas; P22033; baseline and differential. 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 GO; GO:1901290; P:succinyl-CoA biosynthetic process; IEA:Ensembl. DR CDD; cd02071; MM_CoA_mut_B12_BD; 1. DR CDD; cd03679; MM_CoA_mutase_alpha_like; 1. DR Gene3D; 3.40.50.280; Cobalamin-binding domain; 1. DR Gene3D; 3.20.20.240; Methylmalonyl-CoA mutase; 1. 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 NCBIfam; TIGR00640; acid_CoA_mut_C; 1. DR NCBIfam; TIGR00641; acid_CoA_mut_N; 1. DR PANTHER; PTHR48101:SF4; METHYLMALONYL-COA MUTASE, MITOCHONDRIAL; 1. DR PANTHER; PTHR48101; METHYLMALONYL-COA MUTASE, MITOCHONDRIAL-RELATED; 1. DR Pfam; PF02310; B12-binding; 1. DR Pfam; PF01642; MM_CoA_mutase; 1. DR SUPFAM; SSF52242; Cobalamin (vitamin B12)-binding domain; 1. DR SUPFAM; SSF51703; Cobalamin (vitamin B12)-dependent enzymes; 1. DR PROSITE; PS51332; B12_BINDING; 1. DR PROSITE; PS00544; METMALONYL_COA_MUTASE; 1. DR Genevisible; P22033; HS. 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; 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; uncertain 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; uncertain significance; mut-; FT 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; uncertain 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 /evidence="ECO:0000269|PubMed:8990001" 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; uncertain 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; uncertain 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 /evidence="ECO:0000269|PubMed:8990001" 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; interferes 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:8DYL" FT TURN 51..53 FT /evidence="ECO:0007829|PDB:2XIQ" FT HELIX 56..59 FT /evidence="ECO:0007829|PDB:8DYL" FT STRAND 60..62 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 75..77 FT /evidence="ECO:0007829|PDB:8DYL" FT STRAND 95..98 FT /evidence="ECO:0007829|PDB:8DYL" FT STRAND 101..103 FT /evidence="ECO:0007829|PDB:8DYL" FT STRAND 106..111 FT /evidence="ECO:0007829|PDB:2XIQ" FT HELIX 116..128 FT /evidence="ECO:0007829|PDB:8DYL" FT STRAND 133..136 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 140..143 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 151..153 FT /evidence="ECO:0007829|PDB:8DYL" FT TURN 154..159 FT /evidence="ECO:0007829|PDB:8DYL" FT STRAND 160..162 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 167..173 FT /evidence="ECO:0007829|PDB:8DYL" FT TURN 174..176 FT /evidence="ECO:0007829|PDB:8DYL" FT TURN 179..181 FT /evidence="ECO:0007829|PDB:8DYL" FT STRAND 183..186 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 192..205 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 210..212 FT /evidence="ECO:0007829|PDB:8DYL" FT STRAND 214..217 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 221..226 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 235..252 FT /evidence="ECO:0007829|PDB:8DYL" FT STRAND 259..262 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 264..268 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 273..293 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 298..301 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 302..304 FT /evidence="ECO:0007829|PDB:8DYL" FT STRAND 305..311 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 315..337 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 342..345 FT /evidence="ECO:0007829|PDB:8DYL" FT STRAND 349..353 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 355..357 FT /evidence="ECO:0007829|PDB:8DYJ" FT STRAND 360..362 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 365..379 FT /evidence="ECO:0007829|PDB:8DYL" FT STRAND 383..386 FT /evidence="ECO:0007829|PDB:8DYL" FT TURN 390..394 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 399..414 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 418..420 FT /evidence="ECO:0007829|PDB:8DYL" FT STRAND 421..423 FT /evidence="ECO:0007829|PDB:8DYL" FT TURN 424..427 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 429..451 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 455..461 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 463..480 FT /evidence="ECO:0007829|PDB:8DYL" FT STRAND 482..484 FT /evidence="ECO:0007829|PDB:2XIJ" FT TURN 487..489 FT /evidence="ECO:0007829|PDB:8DYL" FT STRAND 490..492 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 508..524 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 527..543 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 548..557 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 562..573 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 586..591 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 595..611 FT /evidence="ECO:0007829|PDB:8DYL" FT STRAND 616..620 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 629..640 FT /evidence="ECO:0007829|PDB:8DYL" FT STRAND 644..647 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 654..663 FT /evidence="ECO:0007829|PDB:8DYL" FT STRAND 667..673 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 678..691 FT /evidence="ECO:0007829|PDB:8DYL" FT STRAND 697..704 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 707..709 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 710..716 FT /evidence="ECO:0007829|PDB:8DYL" FT STRAND 720..722 FT /evidence="ECO:0007829|PDB:8DYL" FT HELIX 728..745 FT /evidence="ECO:0007829|PDB:8DYL" 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 //