MMAD_HUMAN
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 03-AUG-2022, entry version 141.
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};
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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 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; Q9H3L0; -.
DR PeptideAtlas; Q9H3L0; -.
DR PRIDE; Q9H3L0; -.
DR ProteomicsDB; 80728; -.
DR Antibodypedia; 33644; 218 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 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; 1363001at2759; -.
DR PhylomeDB; Q9H3L0; -.
DR TreeFam; TF314208; -.
DR BioCyc; MetaCyc:ENSG00000168288-MON; -.
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; 15 hits in 1074 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 207 other 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; PTHR13192; 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
