MTDC_DROME
ID MTDC_DROME Reviewed; 309 AA.
AC Q04448; Q7KSU1; Q9U6H6; Q9V3H4;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 22-NOV-2005, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial;
DE Short=DNMDMC;
DE Includes:
DE RecName: Full=NAD-dependent methylenetetrahydrofolate dehydrogenase;
DE EC=1.5.1.15;
DE Includes:
DE RecName: Full=Methenyltetrahydrofolate cyclohydrolase;
DE EC=3.5.4.9;
DE Flags: Precursor;
GN Name=Nmdmc; ORFNames=CG18466;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RX PubMed=8485162; DOI=10.1016/0167-4781(93)90251-8;
RA Price B.D., Laughon A.;
RT "The isolation and characterization of a Drosophila gene encoding a
RT putative NAD-dependent methylenetetrahydrofolate dehydrogenase-
RT methenyltetrahydrofolate cyclohydrolase.";
RL Biochim. Biophys. Acta 1173:94-98(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING.
RX PubMed=10619029; DOI=10.1016/s1097-2765(00)80392-5;
RA Hedengren M., Asling B., Dushay M.S., Ando I., Ekengren S., Wihlborg M.,
RA Hultmark D.;
RT "Relish, a central factor in the control of humoral, but not cellular
RT immunity in Drosophila.";
RL Mol. Cell 4:827-837(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4]
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC STRAIN=Berkeley; TISSUE=Head;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
CC -!- FUNCTION: May play a role in spermatogenesis.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NAD(+) = 5,10-
CC methenyltetrahydrofolate + NADH; Xref=Rhea:RHEA:22892,
CC ChEBI:CHEBI:15636, ChEBI:CHEBI:57455, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.5.1.15;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5,10-methenyltetrahydrofolate + H2O = (6S)-10-
CC formyltetrahydrofolate + H(+); Xref=Rhea:RHEA:23700,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57454,
CC ChEBI:CHEBI:57455; EC=3.5.4.9;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Mitochondrion.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=B; Synonyms=Hedengren-A;
CC IsoId=Q04448-1; Sequence=Displayed;
CC Name=A; Synonyms=Hedengren-B;
CC IsoId=Q04448-2; Sequence=VSP_016458;
CC -!- DEVELOPMENTAL STAGE: Expressed in developing tissues and at high levels
CC in adult tissues. Isoform A shows male-specific expression.
CC {ECO:0000269|PubMed:8485162}.
CC -!- MISCELLANEOUS: This NAD-dependent bifunctional enzyme has very
CC different kinetic properties than the larger NADP-dependent
CC trifunctional enzyme and is unique in that it requires formation of an
CC enzyme-magnesium complex to allow binding of NAD.
CC -!- SIMILARITY: Belongs to the tetrahydrofolate
CC dehydrogenase/cyclohydrolase family. {ECO:0000305}.
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DR EMBL; L07958; AAB41352.1; -; mRNA.
DR EMBL; AF186073; AAF07929.1; -; Genomic_DNA.
DR EMBL; AF186073; AAF07930.1; -; Genomic_DNA.
DR EMBL; AE014297; AAF54332.1; -; Genomic_DNA.
DR EMBL; AE014297; AAN13408.1; -; Genomic_DNA.
DR EMBL; AY047498; AAK77230.1; -; mRNA.
DR PIR; S32562; S32562.
DR RefSeq; NP_001262398.1; NM_001275469.1. [Q04448-2]
DR RefSeq; NP_476929.1; NM_057581.5. [Q04448-1]
DR RefSeq; NP_476930.1; NM_057582.5. [Q04448-2]
DR AlphaFoldDB; Q04448; -.
DR SMR; Q04448; -.
DR BioGRID; 71042; 3.
DR STRING; 7227.FBpp0081476; -.
DR PaxDb; Q04448; -.
DR PRIDE; Q04448; -.
DR EnsemblMetazoa; FBtr0081996; FBpp0081476; FBgn0010222. [Q04448-1]
DR EnsemblMetazoa; FBtr0081997; FBpp0081477; FBgn0010222. [Q04448-2]
DR EnsemblMetazoa; FBtr0336761; FBpp0307737; FBgn0010222. [Q04448-2]
DR GeneID; 47895; -.
DR KEGG; dme:Dmel_CG18466; -.
DR CTD; 47895; -.
DR FlyBase; FBgn0010222; Nmdmc.
DR VEuPathDB; VectorBase:FBgn0010222; -.
DR eggNOG; KOG0089; Eukaryota.
DR GeneTree; ENSGT00940000160901; -.
DR InParanoid; Q04448; -.
DR OMA; HIVGRPM; -.
DR PhylomeDB; Q04448; -.
DR Reactome; R-DME-196757; Metabolism of folate and pterines.
DR BioGRID-ORCS; 47895; 0 hits in 3 CRISPR screens.
DR ChiTaRS; Nmdmc; fly.
DR GenomeRNAi; 47895; -.
DR PRO; PR:Q04448; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0010222; Expressed in capitellum (Drosophila) and 27 other tissues.
DR ExpressionAtlas; Q04448; baseline and differential.
DR Genevisible; Q04448; DM.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0004477; F:methenyltetrahydrofolate cyclohydrolase activity; ISS:UniProtKB.
DR GO; GO:0004487; F:methylenetetrahydrofolate dehydrogenase (NAD+) activity; ISS:UniProtKB.
DR GO; GO:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; ISS:UniProtKB.
DR GO; GO:0042301; F:phosphate ion binding; ISS:UniProtKB.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; IBA:GO_Central.
DR GO; GO:0046653; P:tetrahydrofolate metabolic process; ISS:UniProtKB.
DR CDD; cd01080; NAD_bind_m-THF_DH_Cyclohyd; 1.
DR HAMAP; MF_01576; THF_DHG_CYH; 1.
DR InterPro; IPR046346; Aminiacid_DH-like_N_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR000672; THF_DH/CycHdrlase.
DR InterPro; IPR020630; THF_DH/CycHdrlase_cat_dom.
DR InterPro; IPR020867; THF_DH/CycHdrlase_CS.
DR InterPro; IPR020631; THF_DH/CycHdrlase_NAD-bd_dom.
DR Pfam; PF00763; THF_DHG_CYH; 1.
DR Pfam; PF02882; THF_DHG_CYH_C; 1.
DR PRINTS; PR00085; THFDHDRGNASE.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF53223; SSF53223; 1.
DR PROSITE; PS00766; THF_DHG_CYH_1; 1.
DR PROSITE; PS00767; THF_DHG_CYH_2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Hydrolase; Magnesium; Mitochondrion;
KW Multifunctional enzyme; NAD; One-carbon metabolism; Oxidoreductase;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..309
FT /note="Bifunctional methylenetetrahydrofolate
FT dehydrogenase/cyclohydrolase, mitochondrial"
FT /id="PRO_0000034051"
FT VAR_SEQ 1..6
FT /note="Missing (in isoform A)"
FT /evidence="ECO:0000305"
FT /id="VSP_016458"
FT CONFLICT 1..4
FT /note="MRFT -> MATVMGPTPPGTGVMWPAIWRTSSKAIGIRQSVQFEFSTRKISQ
FT KPQKEVTI (in Ref. 1)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 309 AA; 33551 MW; 9E6846282570F457 CRC64;
MRFTSNMAQI IDGKAIAQEV RTQLAHELKG MEAAGYPKPH LTAVIVGEDP ASEKYVANKM
VACREVGISS ETKRLPASTT QEELLQLIAD LNKDPQVTGI LVQLPVPEHI NERTICNAVD
VDKDVDGFNE VNIGRTALDM EANIPATPLG VKRLLEHMKI ETLGRNAVVV GRSKNVSLPM
AILLHADGKY ATKAMDATVT ICHRYTPPKE LARHCRQADI IVVAVGKPGL ITKDMVKPGA
CVIDVGINRI KDESTGQFKL VGDVDFEEVR QVAGHITPVP GGVGPMTVAM LMHNTLKAAR
KQFDDRKSS
