Reviewed, UniProtKB/Swiss-Prot Q04448 (MTDC_DROME)

Names and origin

Protein names

Recommended name:
    Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial
      Short name=DNMDMC
Including the following 2 domains:
    1- Recommended name:
            NAD-dependent methylenetetrahydrofolate dehydrogenase
              EC=1.5.1.15
    2- Recommended name:
            Methenyltetrahydrofolate cyclohydrolase
              EC=3.5.4.9

Gene names

Name:	Nmdmc
ORF Names:	CG18466

Organism

Drosophila melanogaster (Fruit fly) [Complete proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	309 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	May play a role in spermatogenesis.
Catalytic activity	5,10-methylenetetrahydrofolate + NAD+ = 5,10-methenyltetrahydrofolate + NADH. 5,10-methenyltetrahydrofolate + H2O = 10-formyltetrahydrofolate.
Cofactor	Magnesium.
Subunit structure	Homodimer.
Subcellular location	Mitochondrion.
Developmental stage	Expressed in developing tissues and at high levels in adult tissues. Isoform A shows male-specific expression. Ref.1
Miscellaneous	This NAD-dependent bifunctional enzyme has very different kinetic properties than the larger NADP-dependent trifunctional enzyme and is unique in that it requires formation of an enzyme-magnesium complex to allow binding of NAD.
Sequence similarities	Belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.

Ontologies

Keywords
Biological process	One-carbon metabolism
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing
Domain	Transit peptide
Ligand	Magnesium NAD
Molecular function	Hydrolase Oxidoreductase
Technical term	Complete proteome Multifunctional enzyme
Gene Ontology (GO)
Biological process	folic acid and derivative biosynthetic process Inferred from electronic annotation. Source: InterPro one-carbon metabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW tetrahydrofolate metabolic process Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	mitochondrion Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	magnesium ion binding Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB methenyltetrahydrofolate cyclohydrolase activity Inferred from sequence or structural similarity. Source: UniProtKB methylenetetrahydrofolate dehydrogenase (NAD+) activity Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB methylenetetrahydrofolate dehydrogenase (NADP+) activity Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB phosphate binding Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform B (identifier: Q04448-1)

Also known as: Hedengren-A;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform A (identifier: Q04448-2)

Also known as: Hedengren-B;

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – ?		Mitochondrion Potential
	Chain	? – 309		Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial		PRO_0000034051
Natural variations
	Alternative sequence	1 – 6	6	Missing in isoform A.		VSP_016458
Experimental info
	Sequence conflict	1 – 4	4	MRFT → MATVMGPTPPGTGVMWPAIW RTSSKAIGIRQSVQFEFSTR KISQKPQKEVTI Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform B (Hedengren-A) [UniParc]. Last modified November 22, 2005. Version 2. Checksum: 9E6846282570F457	FASTA	309	33,551
	10 20 30 40 50 60 MRFTSNMAQI IDGKAIAQEV RTQLAHELKG MEAAGYPKPH LTAVIVGEDP ASEKYVANKM 70 80 90 100 110 120 VACREVGISS ETKRLPASTT QEELLQLIAD LNKDPQVTGI LVQLPVPEHI NERTICNAVD 130 140 150 160 170 180 VDKDVDGFNE VNIGRTALDM EANIPATPLG VKRLLEHMKI ETLGRNAVVV GRSKNVSLPM 190 200 210 220 230 240 AILLHADGKY ATKAMDATVT ICHRYTPPKE LARHCRQADI IVVAVGKPGL ITKDMVKPGA 250 260 270 280 290 300 CVIDVGINRI KDESTGQFKL VGDVDFEEVR QVAGHITPVP GGVGPMTVAM LMHNTLKAAR KQFDDRKSS
	Isoform A (Hedengren-B). Checksum: C925101D096B1358	FASTA	303	32,814
	10 20 30 40 50 60 MAQIIDGKAI AQEVRTQLAH ELKGMEAAGY PKPHLTAVIV GEDPASEKYV ANKMVACREV 70 80 90 100 110 120 GISSETKRLP ASTTQEELLQ LIADLNKDPQ VTGILVQLPV PEHINERTIC NAVDVDKDVD 130 140 150 160 170 180 GFNEVNIGRT ALDMEANIPA TPLGVKRLLE HMKIETLGRN AVVVGRSKNV SLPMAILLHA 190 200 210 220 230 240 DGKYATKAMD ATVTICHRYT PPKELARHCR QADIIVVAVG KPGLITKDMV KPGACVIDVG 250 260 270 280 290 300 INRIKDESTG QFKLVGDVDF EEVRQVAGHI TPVPGGVGPM TVAMLMHNTL KAARKQFDDR KSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The isolation and characterization of a Drosophila gene encoding a putative NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase." Price B.D., Laughon A. Biochim. Biophys. Acta 1173:94-98(1993) [PubMed: 8485162] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE.
[2]	"Relish, a central factor in the control of humoral, but not cellular immunity in Drosophila." Hedengren M., Asling B., Dushay M.S., Ando I., Ekengren S., Wihlborg M., Hultmark D. Mol. Cell 4:827-837(1999) [PubMed: 10619029] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING.
[3]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[4]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING.
[5]	"A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed: 12537569] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B). Strain: Berkeley. Tissue: Head.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L07958 mRNA. Translation: AAB41352.1. AF186073 Genomic DNA. Translation: AAF07929.1. AF186073 Genomic DNA. Translation: AAF07930.1. AE014297 Genomic DNA. Translation: AAF54332.1. AE014297 Genomic DNA. Translation: AAN13408.1. AY047498 mRNA. Translation: AAK77230.1.
PIR	S32562.
RefSeq	NP_476929.1. NP_476930.1.
UniGene	Dm.33471
3D structure databases
SMR	Q04448. Positions 8-306.
ModBase	Search...
Protein-protein interaction databases
STRING	Q04448.
Genome annotation databases
Ensembl	FBtr0081996; FBpp0081476; FBgn0010222; Drosophila melanogaster. [Genome view] FBtr0081997; FBpp0081477; FBgn0010222; Drosophila melanogaster. [Genome view]
GeneID	47895.
KEGG	dme:Dmel_CG18466.
Organism-specific databases
CTD	47895.
FlyBase	FBgn0010222. Nmdmc.
Phylogenomic databases
eggNOG	inNOG04050.
InParanoid	Q04448.
OMA	HSVLEKY.
OrthoDB	EOG9MKNP8.
PhylomeDB	Q04448.
Enzyme and pathway databases
BRENDA	1.5.1.15. 48. 3.5.4.9. 48.
Gene expression databases
Bgee	Q04448.
GermOnline	CG18466. Drosophila melanogaster.
Family and domain databases
InterPro	IPR016040. NAD(P)-bd_dom. IPR000672. THF_DH/CycHdrlase. IPR020630. THF_DH/CycHdrlase_cat_dom. IPR020867. THF_DH/CycHdrlase_CS. IPR020631. THF_DH/CycHdrlase_NAD-bd_dom. [Graphical view]
Gene3D	G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.
Pfam	PF00763. THF_DHG_CYH. 1 hit. PF02882. THF_DHG_CYH_C. 1 hit. [Graphical view]
PRINTS	PR00085. THFDHDRGNASE.
PROSITE	PS00766. THF_DHG_CYH_1. 1 hit. PS00767. THF_DHG_CYH_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	839208.

Entry information

Entry name

MTDC_DROME

Accession

Primary (citable) accession number: Q04448
Secondary accession number(s): Q7KSU1, Q9U6H6, Q9V3H4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	November 22, 2005
Last modified:	January 19, 2010
This is version 82 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project