ID MMAD_HUMAN Reviewed; 296 AA. AC Q9H3L0; B2R895; D3DP91; O95891; DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2005, sequence version 2. DT 24-JAN-2024, entry version 148. DE RecName: Full=Cobalamin trafficking protein CblD {ECO:0000303|PubMed:26364851}; DE AltName: Full=CblD {ECO:0000303|PubMed:23415655, ECO:0000303|PubMed:24722857, ECO:0000303|PubMed:26364851}; DE AltName: Full=Methylmalonic aciduria and homocystinuria type D protein, mitochondrial; DE Flags: Precursor; GN Name=MMADHC {ECO:0000312|HGNC:HGNC:25221}; Synonyms=C2orf25, CL25022; GN ORFNames=HSPC161, My011; 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 [LARGE SCALE MRNA]. RC TISSUE=Fetal brain; RA Mao Y.M., Xie Y., Zheng Z.H., Gu S.H., Ying K., Lin Q., Dai J.L., Tang R., RA Dong H., Wu X.Z.; RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RA Mei G., Yu W., Gibbs R.A.; RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for 300 RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor RT cells."; RL Genome Res. 10:1546-1560(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skeletal muscle; 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 GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain, Kidney, Placenta, and Skeletal muscle; 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, TISSUE SPECIFICITY, AND VARIANTS MAHCD RP LEU-ALA-GLU-PRO-LEU-SER-108 INS; ASN-182; 204-PHE--ALA-232 DEL; CYS-249 AND RP PRO-259. RX PubMed=18385497; DOI=10.1056/nejmoa072200; RA Coelho D., Suormala T., Stucki M., Lerner-Ellis J.P., Rosenblatt D.S., RA Newbold R.F., Baumgartner M.R., Fowler B.; RT "Gene identification for the cblD defect of vitamin B12 metabolism."; RL N. Engl. J. Med. 358:1454-1464(2008). RN [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-203, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [10] RP INTERACTION WITH MMACHC. RX PubMed=21071249; DOI=10.1016/j.ymgme.2010.10.011; RA Plesa M., Kim J., Paquette S.G., Gagnon H., Ng-Thow-Hing C., Gibbs B.F., RA Hancock M.A., Rosenblatt D.S., Coulton J.W.; RT "Interaction between MMACHC and MMADHC, two human proteins participating in RT intracellular vitamin B(1)(2) metabolism."; RL Mol. Genet. Metab. 102:139-148(2011). RN [11] RP FUNCTION, AND INTERACTION WITH MMACHC. RX PubMed=23415655; DOI=10.1016/j.biochi.2013.02.003; RA Gherasim C., Hannibal L., Rajagopalan D., Jacobsen D.W., Banerjee R.; RT "The C-terminal domain of CblD interacts with CblC and influences RT intracellular cobalamin partitioning."; RL Biochimie 95:1023-1032(2013). RN [12] RP SUBCELLULAR LOCATION. RX PubMed=23270877; DOI=10.1016/j.ymgme.2012.11.284; RA Mah W., Deme J.C., Watkins D., Fung S., Janer A., Shoubridge E.A., RA Rosenblatt D.S., Coulton J.W.; RT "Subcellular location of MMACHC and MMADHC, two human proteins central to RT intracellular vitamin B(12) metabolism."; RL Mol. Genet. Metab. 108:112-118(2013). RN [13] RP FUNCTION, CHARACTERIZATION OF VARIANT MAHCD PRO-259, AND MUTAGENESIS OF RP PHE-165; MET-186; TRP-189; ARG-197; PHE-204; CYS-212; ASP-226; TYR-237; RP ARG-266; TRP-270; SER-278 AND PHE-280. RX PubMed=24722857; DOI=10.1007/s10545-014-9709-4; RA Jusufi J., Suormala T., Burda P., Fowler B., Froese D.S., Baumgartner M.R.; RT "Characterization of functional domains of the cblD (MMADHC) gene RT product."; RL J. Inherit. Metab. Dis. 37:841-849(2014). RN [14] RP INTERACTION WITH MMACHC, CHARACTERIZATION OF VARIANTS MAHCD ASN-182 AND RP PRO-259, AND MUTAGENESIS OF TRP-189 AND ASP-226. RX PubMed=26483544; DOI=10.1074/jbc.m115.683268; RA Froese D.S., Kopec J., Fitzpatrick F., Schuller M., McCorvie T.J., RA Chalk R., Plessl T., Fettelschoss V., Fowler B., Baumgartner M.R., RA Yue W.W.; RT "Structural insights into the MMACHC-MMADHC protein complex involved in RT vitamin B12 trafficking."; RL J. Biol. Chem. 290:29167-29177(2015). RN [15] RP FUNCTION, AND INTERACTION WITH MMADHC; MTR AND MTRR. RX PubMed=27771510; DOI=10.1016/j.bbadis.2016.10.016; RA Bassila C., Ghemrawi R., Flayac J., Froese D.S., Baumgartner M.R., RA Gueant J.L., Coelho D.; RT "Methionine synthase and methionine synthase reductase interact with MMACHC RT and with MMADHC."; RL Biochim. Biophys. Acta 1863:103-112(2017). RN [16] {ECO:0007744|PDB:5CUZ, ECO:0007744|PDB:5CV0} RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 108-296, AND FUNCTION. RX PubMed=26364851; DOI=10.1074/jbc.m115.682435; RA Yamada K., Gherasim C., Banerjee R., Koutmos M.; RT "Structure of human B12 trafficking protein CblD reveals molecular mimicry RT and identifies a new subfamily of nitro-FMN reductases."; RL J. Biol. Chem. 290:29155-29166(2015). CC -!- FUNCTION: Involved in cobalamin metabolism and trafficking CC (PubMed:18385497, PubMed:23415655, PubMed:24722857, PubMed:26364851). CC Plays a role in regulating the biosynthesis and the proportion of two CC coenzymes, methylcob(III)alamin (MeCbl) and 5'-deoxyadenosylcobalamin CC (AdoCbl) (PubMed:18385497, PubMed:23415655, PubMed:24722857). Promotes CC oxidation of cob(II)alamin bound to MMACHC (PubMed:26364851). The CC processing of cobalamin in the cytosol occurs in a multiprotein complex CC composed of at least MMACHC, MMADHC, MTRR (methionine synthase CC reductase) and MTR (methionine synthase) which may contribute to CC shuttle safely and efficiently cobalamin towards MTR in order to CC produce methionine (PubMed:27771510). {ECO:0000269|PubMed:18385497, CC ECO:0000269|PubMed:23415655, ECO:0000269|PubMed:24722857, CC ECO:0000269|PubMed:26364851, ECO:0000269|PubMed:27771510}. CC -!- SUBUNIT: Heterodimer with MMACHC. Forms a multiprotein complex with CC MMACHC, MTR and MTRR (PubMed:27771510). {ECO:0000269|PubMed:21071249, CC ECO:0000269|PubMed:23415655, ECO:0000269|PubMed:26483544, CC ECO:0000269|PubMed:27771510}. CC -!- INTERACTION: CC Q9H3L0; Q9BW66: CINP; NbExp=3; IntAct=EBI-11111575, EBI-739784; CC Q9H3L0; Q02930-3: CREB5; NbExp=5; IntAct=EBI-11111575, EBI-10192698; CC Q9H3L0; Q12837: POU4F2; NbExp=3; IntAct=EBI-11111575, EBI-17236143; CC Q9H3L0; Q9P0N9: TBC1D7; NbExp=3; IntAct=EBI-11111575, EBI-3258000; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23270877}. CC Mitochondrion {ECO:0000269|PubMed:23270877}. CC -!- TISSUE SPECIFICITY: Widely expressed at high levels. CC {ECO:0000269|PubMed:18385497}. CC -!- DISEASE: Methylmalonic aciduria and homocystinuria, cblD type (MAHCD) CC [MIM:277410]: An autosomal recessive disorder of cobalamin metabolism CC characterized by decreased levels of the coenzymes adenosylcobalamin CC (AdoCbl) and methylcobalamin (MeCbl). Clinical features include CC developmental delay, hyotonia, intellectual disability, seizures, CC megaloblastic anemia. Some patients manifest combined methylmalonic CC aciduria and homocystinuria (referred to as cblD original), some have CC only isolated homocystinuria (cblD variant 1), and others have only CC methylmalonic aciduria (cblD variant 2). {ECO:0000269|PubMed:18385497, CC ECO:0000269|PubMed:24722857, ECO:0000269|PubMed:26483544}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SEQUENCE CAUTION: CC Sequence=AAG43124.1; Type=Frameshift; Evidence={ECO:0000305}; 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; AF060224; AAG43124.1; ALT_FRAME; mRNA. DR EMBL; AF131802; AAD20048.1; -; mRNA. DR EMBL; AF161510; AAF29125.1; -; mRNA. DR EMBL; AK313284; BAG36092.1; -; mRNA. DR EMBL; AC110782; AAY14891.1; -; Genomic_DNA. DR EMBL; CH471058; EAX11533.1; -; Genomic_DNA. DR EMBL; CH471058; EAX11534.1; -; Genomic_DNA. DR EMBL; CH471058; EAX11535.1; -; Genomic_DNA. DR EMBL; CH471058; EAX11537.1; -; Genomic_DNA. DR EMBL; BC000932; AAH00932.1; -; mRNA. DR EMBL; BC010894; AAH10894.1; -; mRNA. DR EMBL; BC022859; AAH22859.1; -; mRNA. DR EMBL; BC023995; AAH23995.1; -; mRNA. DR CCDS; CCDS2189.1; -. DR RefSeq; NP_056517.1; NM_015702.2. DR PDB; 5CUZ; X-ray; 2.31 A; A=108-296. DR PDB; 5CV0; X-ray; 1.90 A; A/B=108-296. DR PDB; 6X8Z; X-ray; 2.50 A; A/B=108-296. DR PDBsum; 5CUZ; -. DR PDBsum; 5CV0; -. DR PDBsum; 6X8Z; -. DR AlphaFoldDB; Q9H3L0; -. DR SMR; Q9H3L0; -. DR BioGRID; 118097; 36. DR IntAct; Q9H3L0; 18. DR STRING; 9606.ENSP00000389060; -. DR ChEMBL; CHEMBL4879517; -. DR iPTMnet; Q9H3L0; -. DR PhosphoSitePlus; Q9H3L0; -. DR BioMuta; MMADHC; -. DR DMDM; 68565296; -. DR EPD; Q9H3L0; -. DR jPOST; Q9H3L0; -. DR MassIVE; Q9H3L0; -. DR MaxQB; Q9H3L0; -. DR PaxDb; 9606-ENSP00000389060; -. DR PeptideAtlas; Q9H3L0; -. DR ProteomicsDB; 80728; -. DR Pumba; Q9H3L0; -. DR Antibodypedia; 33644; 245 antibodies from 21 providers. DR DNASU; 27249; -. DR Ensembl; ENST00000303319.10; ENSP00000301920.5; ENSG00000168288.13. DR Ensembl; ENST00000428879.5; ENSP00000389060.1; ENSG00000168288.13. DR GeneID; 27249; -. DR KEGG; hsa:27249; -. DR MANE-Select; ENST00000303319.10; ENSP00000301920.5; NM_015702.3; NP_056517.1. DR UCSC; uc002txc.4; human. DR AGR; HGNC:25221; -. DR CTD; 27249; -. DR DisGeNET; 27249; -. DR GeneCards; MMADHC; -. DR GeneReviews; MMADHC; -. DR HGNC; HGNC:25221; MMADHC. DR HPA; ENSG00000168288; Low tissue specificity. DR MalaCards; MMADHC; -. DR MIM; 277410; phenotype. DR MIM; 611935; gene. DR neXtProt; NX_Q9H3L0; -. DR OpenTargets; ENSG00000168288; -. DR Orphanet; 308380; Methylcobalamin deficiency type cblDv1. DR Orphanet; 79283; Methylmalonic acidemia with homocystinuria, type cblD. DR Orphanet; 308442; Vitamin B12-responsive methylmalonic acidemia, type cblDv2. DR PharmGKB; PA164723053; -. DR VEuPathDB; HostDB:ENSG00000168288; -. DR eggNOG; KOG3994; Eukaryota. DR GeneTree; ENSGT00390000015050; -. DR HOGENOM; CLU_066240_0_0_1; -. DR InParanoid; Q9H3L0; -. DR OrthoDB; 8004at2759; -. DR PhylomeDB; Q9H3L0; -. DR TreeFam; TF314208; -. DR BioCyc; MetaCyc:ENSG00000168288-MONOMER; -. DR PathwayCommons; Q9H3L0; -. DR Reactome; R-HSA-3359473; Defective MMADHC causes MMAHCD. DR Reactome; R-HSA-9759218; Cobalamin (Cbl) metabolism. DR SignaLink; Q9H3L0; -. DR BioGRID-ORCS; 27249; 16 hits in 1153 CRISPR screens. DR ChiTaRS; MMADHC; human. DR GeneWiki; MMADHC; -. DR GenomeRNAi; 27249; -. DR Pharos; Q9H3L0; Tbio. DR PRO; PR:Q9H3L0; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q9H3L0; Protein. DR Bgee; ENSG00000168288; Expressed in palpebral conjunctiva and 209 other cell types or tissues. DR ExpressionAtlas; Q9H3L0; baseline and differential. DR Genevisible; Q9H3L0; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:MGI. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0009235; P:cobalamin metabolic process; IDA:UniProtKB. DR InterPro; IPR019362; MMADHC. DR PANTHER; PTHR13192:SF3; COBALAMIN TRAFFICKING PROTEIN CBLD; 1. DR PANTHER; PTHR13192; MY011 PROTEIN; 1. DR Pfam; PF10229; MMADHC; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cytoplasm; Disease variant; Mitochondrion; KW Reference proteome; Transit peptide. FT TRANSIT 1..38 FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN 39..296 FT /note="Cobalamin trafficking protein CblD" FT /id="PRO_0000019534" FT MOD_RES 203 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT VARIANT 108 FT /note="S -> SLAEPLS (in MAHCD; cblD variant 2)" FT /id="VAR_043843" FT VARIANT 182 FT /note="T -> N (in MAHCD; cblD variant 1; impairs FT interaction with MMACHC; dbSNP:rs118204045)" FT /evidence="ECO:0000269|PubMed:18385497, FT ECO:0000269|PubMed:24722857, ECO:0000269|PubMed:26483544" FT /id="VAR_043844" FT VARIANT 204..232 FT /note="Missing (in MAHCD; cblD original)" FT /evidence="ECO:0000269|PubMed:18385497" FT /id="VAR_043845" FT VARIANT 249 FT /note="Y -> C (in MAHCD; cblD variant 1; FT dbSNP:rs118204046)" FT /evidence="ECO:0000269|PubMed:18385497" FT /id="VAR_043846" FT VARIANT 259 FT /note="L -> P (in MAHCD; cblD variant 1; decreases FT methylcobalamin levels and increases adenosylcobalamin FT levels; no effect on interaction with MMACHC; FT dbSNP:rs118204044)" FT /evidence="ECO:0000269|PubMed:18385497, FT ECO:0000269|PubMed:24722857, ECO:0000269|PubMed:26483544" FT /id="VAR_043847" FT MUTAGEN 165 FT /note="F->A: Mildly decreases methylcobalamin levels and FT strongly increases adenosylcobalamin levels." FT /evidence="ECO:0000269|PubMed:24722857" FT MUTAGEN 186 FT /note="M->A: Decreases methylcobalamin levels. No effect on FT interaction with MMACHC." FT /evidence="ECO:0000269|PubMed:24722857, FT ECO:0000269|PubMed:26483544" FT MUTAGEN 189 FT /note="W->A: Decreases methylcobalamin levels. Impairs FT interaction with MMACHC." FT /evidence="ECO:0000269|PubMed:24722857, FT ECO:0000269|PubMed:26483544" FT MUTAGEN 197 FT /note="R->A: Decreases methylcobalamin levels, but FT increases adenosylcobalamin levels." FT /evidence="ECO:0000269|PubMed:24722857" FT MUTAGEN 204 FT /note="F->A: Decreases methylcobalamin levels and mildly FT increases adenosylcobalamin levels." FT /evidence="ECO:0000269|PubMed:24722857" FT MUTAGEN 212 FT /note="C->A: No effect on cobalamin levels." FT /evidence="ECO:0000269|PubMed:24722857" FT MUTAGEN 226 FT /note="D->A: Decreases methylcobalamin levels, but FT increases adenosylcobalamin levels. No effect on FT interaction with MMACHC." FT /evidence="ECO:0000269|PubMed:24722857, FT ECO:0000269|PubMed:26483544" FT MUTAGEN 237 FT /note="Y->A: Mildly decreases methylcobalamin levels and FT strongly increases adenosylcobalamin levels." FT /evidence="ECO:0000269|PubMed:24722857" FT MUTAGEN 266 FT /note="R->A: Mildly decreases methylcobalamin levels and FT strongly increases adenosylcobalamin levels." FT /evidence="ECO:0000269|PubMed:24722857" FT MUTAGEN 270 FT /note="W->A: Decreases methylcobalamin levels." FT /evidence="ECO:0000269|PubMed:24722857" FT MUTAGEN 278 FT /note="S->A: Marginally decreases methylcobalamin levels FT and strongly increases adenosylcobalamin levels." FT /evidence="ECO:0000269|PubMed:24722857" FT MUTAGEN 280 FT /note="F->A: No effect on cobalamin levels." FT /evidence="ECO:0000269|PubMed:24722857" FT CONFLICT 204 FT /note="F -> S (in Ref. 1; AAG43124)" FT /evidence="ECO:0000305" FT CONFLICT 211 FT /note="I -> N (in Ref. 1; AAG43124)" FT /evidence="ECO:0000305" FT HELIX 137..140 FT /evidence="ECO:0007829|PDB:5CV0" FT STRAND 146..152 FT /evidence="ECO:0007829|PDB:5CV0" FT HELIX 155..162 FT /evidence="ECO:0007829|PDB:5CV0" FT STRAND 174..181 FT /evidence="ECO:0007829|PDB:5CV0" FT HELIX 191..217 FT /evidence="ECO:0007829|PDB:5CV0" FT STRAND 222..225 FT /evidence="ECO:0007829|PDB:5CV0" FT TURN 227..229 FT /evidence="ECO:0007829|PDB:5CV0" FT STRAND 231..235 FT /evidence="ECO:0007829|PDB:5CV0" FT HELIX 247..251 FT /evidence="ECO:0007829|PDB:5CV0" FT STRAND 255..258 FT /evidence="ECO:0007829|PDB:5CV0" FT STRAND 263..267 FT /evidence="ECO:0007829|PDB:5CV0" FT TURN 268..270 FT /evidence="ECO:0007829|PDB:5CV0" FT STRAND 273..281 FT /evidence="ECO:0007829|PDB:5CV0" FT HELIX 288..293 FT /evidence="ECO:0007829|PDB:5CV0" SQ SEQUENCE 296 AA; 32940 MW; 749C2A91D7E6C95D CRC64; MANVLCNRAR LVSYLPGFCS LVKRVVNPKA FSTAGSSGSD ESHVAAAPPD ICSRTVWPDE TMGPFGPQDQ RFQLPGNIGF DCHLNGTASQ KKSLVHKTLP DVLAEPLSSE RHEFVMAQYV NEFQGNDAPV EQEINSAETY FESARVECAI QTCPELLRKD FESLFPEVAN GKLMILTVTQ KTKNDMTVWS EEVEIEREVL LEKFINGAKE ICYALRAEGY WADFIDPSSG LAFFGPYTNN TLFETDERYR HLGFSVDDLG CCKVIRHSLW GTHVVVGSIF TNATPDSHIM KKLSGN //