MMAB_HUMAN
ID MMAB_HUMAN Reviewed; 250 AA.
AC Q96EY8; C5HU05; Q9BSH0;
DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Corrinoid adenosyltransferase MMAB {ECO:0000305};
DE EC=2.5.1.- {ECO:0000269|PubMed:12514191};
DE AltName: Full=ATP:co(I)rrinoid adenosyltransferase MMAB;
DE AltName: Full=Methylmalonic aciduria type B protein;
DE Flags: Precursor;
GN Name=MMAB {ECO:0000312|HGNC:HGNC:19331};
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 [GENOMIC DNA], VARIANTS MMAB THR-135; TRP-191 AND
RP LYS-193, AND VARIANTS GLN-19; TRP-186 AND LYS-239.
RX PubMed=12471062; DOI=10.1093/hmg/11.26.3361;
RA Dobson C.M., Wai T., Leclerc D., Kadir H., Narang M., Lerner-Ellis J.P.,
RA Hudson T.J., Rosenblatt D.S., Gravel R.A.;
RT "Identification of the gene responsible for the cblB complementation group
RT of vitamin B(12)-dependent methylmalonic aciduria.";
RL Hum. Mol. Genet. 11:3361-3369(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, VARIANTS GLN-19
RP AND LYS-239, AND INVOLVEMENT IN DISEASE.
RX PubMed=12514191; DOI=10.1074/jbc.m212739200;
RA Leal N.A., Park S.D., Kima P.E., Bobik T.A.;
RT "Identification of the human and bovine ATP:Cob(I)alamin
RT adenosyltransferase cDNAs based on complementation of a bacterial mutant.";
RL J. Biol. Chem. 278:9227-9234(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS GLN-19 AND LYS-239.
RC TISSUE=Lung;
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 [5]
RP IDENTIFICATION BY MASS 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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-134, 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 [7]
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 [8]
RP FUNCTION, AND ADENOSYLCOBALAMIN-BINDING.
RX PubMed=28497574; DOI=10.1002/humu.23251;
RA Plessl T., Buerer C., Lutz S., Yue W.W., Baumgartner M.R., Froese D.S.;
RT "Protein destabilization and loss of protein-protein interaction are
RT fundamental mechanisms in cblA-type methylmalonic aciduria.";
RL Hum. Mutat. 38:988-1001(2017).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 55-250 IN COMPLEX WITH ATP, AND
RP SUBUNIT.
RX PubMed=17176040; DOI=10.1021/bi061396f;
RA Schubert H.L., Hill C.P.;
RT "Structure of ATP-bound human ATP:cobalamin adenosyltransferase.";
RL Biochemistry 45:15188-15196(2006).
RN [10]
RP VARIANTS MMAB THR-96 AND TRP-191.
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 [11]
RP VARIANTS MMAB THR-96; TRP-186 AND TRP-191.
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).
CC -!- FUNCTION: Converts cob(I)alamin to adenosylcobalamin
CC (adenosylcob(III)alamin), a coenzyme for methylmalonyl-CoA mutase,
CC therefore participates in the final step of the vitamin B12 conversion
CC (PubMed:12514191). Generates adenosylcobalamin (AdoCbl) and directly
CC delivers the cofactor to MUT in a transfer that is stimulated by ATP-
CC binding to MMAB and gated by MMAA (Probable).
CC {ECO:0000269|PubMed:12514191, ECO:0000305|PubMed:28497574}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + cob(I)alamin-[corrinoid adenosyltransferase] =
CC adenosylcob(III)alamin + apo-[corrinoid adenosyltransferase] +
CC triphosphate; Xref=Rhea:RHEA:56796, Rhea:RHEA-COMP:14743, Rhea:RHEA-
CC COMP:14744, ChEBI:CHEBI:18036, ChEBI:CHEBI:18408, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:60488, ChEBI:CHEBI:83228;
CC Evidence={ECO:0000269|PubMed:12514191};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56797;
CC Evidence={ECO:0000305|PubMed:12514191};
CC -!- SUBUNIT: Homotrimer. {ECO:0000269|PubMed:17176040}.
CC -!- INTERACTION:
CC Q96EY8; P27797: CALR; NbExp=3; IntAct=EBI-7825413, EBI-1049597;
CC Q96EY8; Q8NA61-2: CBY2; NbExp=3; IntAct=EBI-7825413, EBI-11524851;
CC Q96EY8; P36957: DLST; NbExp=3; IntAct=EBI-7825413, EBI-351007;
CC Q96EY8; Q8TDX7: NEK7; NbExp=3; IntAct=EBI-7825413, EBI-1055945;
CC Q96EY8; Q96CV9: OPTN; NbExp=3; IntAct=EBI-7825413, EBI-748974;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in liver and skeletal muscle.
CC -!- DISEASE: Methylmalonic aciduria type cblB (MMAB) [MIM:251110]: A
CC disorder of methylmalonate and cobalamin metabolism due to defective
CC synthesis of adenosylcobalamin. {ECO:0000269|PubMed:12471062,
CC ECO:0000269|PubMed:15781192, ECO:0000269|PubMed:17957493}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the Cob(I)alamin adenosyltransferase family.
CC {ECO:0000305}.
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DR EMBL; AF550404; AAN85091.1; -; Genomic_DNA.
DR EMBL; AF550396; AAN85091.1; JOINED; Genomic_DNA.
DR EMBL; AF550397; AAN85091.1; JOINED; Genomic_DNA.
DR EMBL; AF550398; AAN85091.1; JOINED; Genomic_DNA.
DR EMBL; AF550399; AAN85091.1; JOINED; Genomic_DNA.
DR EMBL; AF550400; AAN85091.1; JOINED; Genomic_DNA.
DR EMBL; AF550401; AAN85091.1; JOINED; Genomic_DNA.
DR EMBL; AF550402; AAN85091.1; JOINED; Genomic_DNA.
DR EMBL; AF550403; AAN85091.1; JOINED; Genomic_DNA.
DR EMBL; FJ515859; ACS13749.1; -; Genomic_DNA.
DR EMBL; BC005054; AAH05054.2; -; mRNA.
DR EMBL; BC011831; AAH11831.1; -; mRNA.
DR CCDS; CCDS9131.1; -.
DR RefSeq; NP_443077.1; NM_052845.3.
DR PDB; 2IDX; X-ray; 2.50 A; A/B/C=56-250.
DR PDB; 6D5K; X-ray; 2.85 A; A/B/C=55-250.
DR PDB; 6D5X; X-ray; 2.40 A; A/B/C=55-250.
DR PDB; 7RUT; X-ray; 1.50 A; A/B/C/D/E/F=55-250.
DR PDB; 7RUU; X-ray; 1.85 A; A/B/C/D=55-250.
DR PDB; 7RUV; X-ray; 2.10 A; A/B/C/D=55-250.
DR PDBsum; 2IDX; -.
DR PDBsum; 6D5K; -.
DR PDBsum; 6D5X; -.
DR PDBsum; 7RUT; -.
DR PDBsum; 7RUU; -.
DR PDBsum; 7RUV; -.
DR AlphaFoldDB; Q96EY8; -.
DR SMR; Q96EY8; -.
DR BioGRID; 130605; 118.
DR IntAct; Q96EY8; 27.
DR MINT; Q96EY8; -.
DR STRING; 9606.ENSP00000445920; -.
DR DrugBank; DB00115; Cyanocobalamin.
DR DrugCentral; Q96EY8; -.
DR GlyGen; Q96EY8; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96EY8; -.
DR MetOSite; Q96EY8; -.
DR PhosphoSitePlus; Q96EY8; -.
DR BioMuta; MMAB; -.
DR DMDM; 38258221; -.
DR EPD; Q96EY8; -.
DR jPOST; Q96EY8; -.
DR MassIVE; Q96EY8; -.
DR MaxQB; Q96EY8; -.
DR PaxDb; Q96EY8; -.
DR PeptideAtlas; Q96EY8; -.
DR PRIDE; Q96EY8; -.
DR ProteomicsDB; 76474; -.
DR Antibodypedia; 30891; 193 antibodies from 27 providers.
DR DNASU; 326625; -.
DR Ensembl; ENST00000545712.7; ENSP00000445920.1; ENSG00000139428.12.
DR GeneID; 326625; -.
DR KEGG; hsa:326625; -.
DR MANE-Select; ENST00000545712.7; ENSP00000445920.1; NM_052845.4; NP_443077.1.
DR UCSC; uc001tou.4; human.
DR CTD; 326625; -.
DR DisGeNET; 326625; -.
DR GeneCards; MMAB; -.
DR GeneReviews; MMAB; -.
DR HGNC; HGNC:19331; MMAB.
DR HPA; ENSG00000139428; Tissue enhanced (liver).
DR MalaCards; MMAB; -.
DR MIM; 251110; phenotype.
DR MIM; 607568; gene.
DR neXtProt; NX_Q96EY8; -.
DR OpenTargets; ENSG00000139428; -.
DR Orphanet; 79311; Vitamin B12-responsive methylmalonic acidemia type cblB.
DR PharmGKB; PA134864025; -.
DR VEuPathDB; HostDB:ENSG00000139428; -.
DR eggNOG; ENOG502QS64; Eukaryota.
DR GeneTree; ENSGT00390000008432; -.
DR HOGENOM; CLU_083486_1_0_1; -.
DR InParanoid; Q96EY8; -.
DR OMA; HQACTVV; -.
DR OrthoDB; 788789at2759; -.
DR PhylomeDB; Q96EY8; -.
DR TreeFam; TF312942; -.
DR BioCyc; MetaCyc:HS13779-MON; -.
DR BRENDA; 2.5.1.17; 2681.
DR PathwayCommons; Q96EY8; -.
DR Reactome; R-HSA-3359471; Defective MMAB causes MMA, cblB type.
DR Reactome; R-HSA-9759218; Cobalamin (Cbl) metabolism.
DR SignaLink; Q96EY8; -.
DR BioGRID-ORCS; 326625; 17 hits in 1084 CRISPR screens.
DR ChiTaRS; MMAB; human.
DR EvolutionaryTrace; Q96EY8; -.
DR GeneWiki; MMAB; -.
DR GenomeRNAi; 326625; -.
DR Pharos; Q96EY8; Tbio.
DR PRO; PR:Q96EY8; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q96EY8; protein.
DR Bgee; ENSG00000139428; Expressed in right lobe of liver and 162 other tissues.
DR ExpressionAtlas; Q96EY8; baseline and differential.
DR Genevisible; Q96EY8; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008817; F:cob(I)yrinic acid a,c-diamide adenosyltransferase activity; IDA:MGI.
DR GO; GO:0031419; F:cobalamin binding; IDA:UniProtKB.
DR GO; GO:0016765; F:transferase activity, transferring alkyl or aryl (other than methyl) groups; IDA:UniProtKB.
DR GO; GO:0009235; P:cobalamin metabolic process; IDA:UniProtKB.
DR Gene3D; 1.20.1200.10; -; 1.
DR InterPro; IPR016030; CblAdoTrfase-like.
DR InterPro; IPR036451; CblAdoTrfase-like_sf.
DR InterPro; IPR029499; PduO-typ.
DR PANTHER; PTHR12213; PTHR12213; 1.
DR Pfam; PF01923; Cob_adeno_trans; 1.
DR SUPFAM; SSF89028; SSF89028; 1.
DR TIGRFAMs; TIGR00636; PduO_Nterm; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Disease variant; Mitochondrion;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase;
KW Transit peptide.
FT TRANSIT 1..32
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 33..250
FT /note="Corrinoid adenosyltransferase MMAB"
FT /id="PRO_0000005568"
FT REGION 34..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 60..63
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:17176040"
FT BINDING 68..69
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:17176040"
FT BINDING 78
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:17176040"
FT BINDING 190..194
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:17176040"
FT BINDING 214
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:17176040"
FT MOD_RES 134
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 211
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9D273"
FT MOD_RES 230
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9D273"
FT MOD_RES 230
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9D273"
FT VARIANT 19
FT /note="R -> H (in dbSNP:rs10774775)"
FT /id="VAR_038803"
FT VARIANT 19
FT /note="R -> Q (in dbSNP:rs36013132)"
FT /evidence="ECO:0000269|PubMed:12471062,
FT ECO:0000269|PubMed:12514191, ECO:0000269|PubMed:15489334"
FT /id="VAR_017203"
FT VARIANT 96
FT /note="I -> T (in MMAB; dbSNP:rs864309509)"
FT /evidence="ECO:0000269|PubMed:15781192,
FT ECO:0000269|PubMed:17957493"
FT /id="VAR_023471"
FT VARIANT 135
FT /note="A -> T (in MMAB; dbSNP:rs35648932)"
FT /evidence="ECO:0000269|PubMed:12471062"
FT /id="VAR_017204"
FT VARIANT 186
FT /note="R -> W (in MMAB; dbSNP:rs28941784)"
FT /evidence="ECO:0000269|PubMed:12471062,
FT ECO:0000269|PubMed:17957493"
FT /id="VAR_017205"
FT VARIANT 191
FT /note="R -> W (in MMAB; dbSNP:rs376128990)"
FT /evidence="ECO:0000269|PubMed:12471062,
FT ECO:0000269|PubMed:15781192, ECO:0000269|PubMed:17957493"
FT /id="VAR_017206"
FT VARIANT 193
FT /note="E -> K (in MMAB; dbSNP:rs749758687)"
FT /evidence="ECO:0000269|PubMed:12471062"
FT /id="VAR_017207"
FT VARIANT 239
FT /note="M -> K (in dbSNP:rs9593)"
FT /evidence="ECO:0000269|PubMed:12471062,
FT ECO:0000269|PubMed:12514191, ECO:0000269|PubMed:15489334"
FT /id="VAR_017208"
FT TURN 62..65
FT /evidence="ECO:0007829|PDB:7RUT"
FT STRAND 66..69
FT /evidence="ECO:0007829|PDB:7RUT"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:7RUT"
FT HELIX 81..106
FT /evidence="ECO:0007829|PDB:7RUT"
FT HELIX 111..128
FT /evidence="ECO:0007829|PDB:7RUT"
FT TURN 132..134
FT /evidence="ECO:0007829|PDB:7RUT"
FT HELIX 137..140
FT /evidence="ECO:0007829|PDB:7RUT"
FT HELIX 148..161
FT /evidence="ECO:0007829|PDB:7RUT"
FT HELIX 177..201
FT /evidence="ECO:0007829|PDB:7RUT"
FT HELIX 207..231
FT /evidence="ECO:0007829|PDB:7RUT"
SQ SEQUENCE 250 AA; 27388 MW; AEFC4E487C9FA5AB CRC64;
MAVCGLGSRL GLGSRLGLRG CFGAARLLYP RFQSRGPQGV EDGDRPQPSS KTPRIPKIYT
KTGDKGFSST FTGERRPKDD QVFEAVGTTD ELSSAIGFAL ELVTEKGHTF AEELQKIQCT
LQDVGSALAT PCSSAREAHL KYTTFKAGPI LELEQWIDKY TSQLPPLTAF ILPSGGKISS
ALHFCRAVCR RAERRVVPLV QMGETDANVA KFLNRLSDYL FTLARYAAMK EGNQEKIYMK
NDPSAESEGL
