Reviewed, UniProtKB/Swiss-Prot O96553 (C1TC_DROME)

Names and origin

Protein names

Recommended name:
    C-1-tetrahydrofolate synthase, cytoplasmic
      Short name=C1-THF synthase
Including the following 3 domains:
    1- Recommended name:
            Methylenetetrahydrofolate dehydrogenase
              EC=1.5.1.5
    2- Recommended name:
            Methenyltetrahydrofolate cyclohydrolase
              EC=3.5.4.9
    3- Recommended name:
            Formyltetrahydrofolate synthetase
              EC=6.3.4.3

Gene names

Name:	pug
ORF Names:	CG4067

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	968 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	5,10-methylenetetrahydrofolate + NADP+ = 5,10-methenyltetrahydrofolate + NADPH. UniProtKB P11586 5,10-methenyltetrahydrofolate + H2O = 10-formyltetrahydrofolate. UniProtKB P11586 ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate. UniProtKB P11586
Pathway	One-carbon metabolism; tetrahydrofolate pathway.
Subunit structure	Homodimer. UniProtKB P11586
Subcellular location	Cytoplasm. UniProtKB P11586
Tissue specificity	Present in all tissues. Ref.1
Domain	This trifunctional enzyme consists of two major domains: a N-terminal part, containing the methylene-THF dehydrogenase and the methenyl-THF cyclohydrolase activities and a larger formyl-THF synthetase domain.
Sequence similarities	In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family. In the C-terminal section; belongs to the formate--tetrahydrofolate ligase family.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Histidine biosynthesis Methionine biosynthesis One-carbon metabolism Purine biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding NADP Nucleotide-binding
Molecular function	Hydrolase Ligase Oxidoreductase
Technical term	Complete proteome Multifunctional enzyme
Gene Ontology (GO)
Biological process	folic acid and derivative biosynthetic process Inferred from electronic annotation. Source: InterPro histidine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW methionine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW one-carbon compound metabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW purine nucleotide biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Ref.1 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW formate-tetrahydrofolate ligase activity Ref.1 Non-traceable author statement. Source: UniProtKB methenyltetrahydrofolate cyclohydrolase activity Ref.1 Non-traceable author statement. Source: UniProtKB methylenetetrahydrofolate dehydrogenase (NADP+) activity Ref.1 Non-traceable author statement. Source: UniProtKB protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Keap1	Q9VEN5	1	EBI-118733,EBI-181742

Alternative products

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

Isoform B (identifier: O96553-1)

Also known as: D;

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.

Note: No experimental confirmation available.

Isoform A (identifier: O96553-2)

Also known as: C;

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 968	968	C-1-tetrahydrofolate synthase, cytoplasmic		PRO_0000199324
Regions
	Nucleotide binding	205 – 207	3	NADP By similarity
	Nucleotide binding	413 – 420	8	ATP By similarity
	Region	1 – 338	338	Methylenetetrahydrofolate dehydrogenase and cyclohydrolase
	Region	86 – 90	5	Substrate binding By similarity
	Region	133 – 135	3	Substrate binding By similarity
	Region	305 – 309	5	Substrate binding By similarity
	Region	339 – 968	630	Formyltetrahydrofolate synthetase
Sites
	Binding site	230	1	NADP By similarity
Natural variations
	Alternative sequence	1 – 34	34	Missing in isoform A.		VSP_010883
Experimental info
	Sequence conflict	879	1	E → K in AAX33426. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform B (D) [UniParc]. Last modified July 19, 2004. Version 4. Checksum: D65EC8455DD8AF2C	FASTA	968	103,504
	10 20 30 40 50 60 MSAQYQRFLK VLEKWPAEKS KVGSGEWTAE PAIKMSGAKI ISGTAVAKSI REELRNEVTA 70 80 90 100 110 120 MSKQLADFVP GLRIVQVGGR EDSNVYIRMK IKAATEIGID AAHVQLPRSI TEVELLDKIN 130 140 150 160 170 180 DLNEDPRVHG IIVQMPLDCD TPIDSHRITD AVSPEKDVDG LHTVNEGRLA IGDLGGFLPC 190 200 210 220 230 240 TPWGCLELIR RSGVEIAGAR AVVLGRSKIV GTPAAELLKW ANATVTVCHS KTRNLEEITR 250 260 270 280 290 300 SADILVVGIG VAEMVKGSWI KPGAVVIDCG INVKPDASKA SGSKLVGDVD YAEALQVAGH 310 320 330 340 350 360 LTPVPGGVGP MTVAMLMKNT VRSAARFLER LAKSQWALQT LPLKPQRPVP SDIVIARAQK 370 380 390 400 410 420 PKDIAVLAKE IGLEAREVSL YGNKKAKISL SVLERLKDKE VGHYVVVAGM TPTPLGEGKT 430 440 450 460 470 480 TTLMGLVQAL GAHKLRNTMA ALRQPSQGPT FGIKGGAAGG GYAQVIPMEE FNLHLTGDIH 490 500 510 520 530 540 AVSAANNLLA AQLDTRIFHE NTQKDKALYD RLVPAIKGQR KFSPIQLRRL QKLGITKTDP 550 560 570 580 590 600 DTLTADEYGP FARLDIDPDT IMWERVVDIN DRYLRTITVG QSPTEKGISR ETRFSISVAS 610 620 630 640 650 660 EIMAVLALSR SLEDMKQRLA DMVVAFDKRG KPVTADDLGV TGALAVLLKD ALEPNLMQSL 670 680 690 700 710 720 EGTPVLVHAG PFANIAHGCN SIIADEVGLK LVGKNGFVCT EAGFGSDIGM EKFCNIKCRT 730 740 750 760 770 780 SGRKPNAMVL VATVRAIKMH GGGAPVTPGA PLNKQYTEEN LELVQKGLPN LLQHIENGKA 790 800 810 820 830 840 FGMPVVVSLN AHSADTPAEH ELVKKAALEA GAFAAVVSTH WADGGAGAVQ LADAVIKACE 850 860 870 880 890 900 QGNQFRLLYD LELPLVDKMN KIATTMYGAG KVVLSPAAEE KVKRLTDAGF GNLPICMSKV 910 920 930 940 950 960 SGSFTGDAKI KGAPKGFTLD VEDVYVSAGA GFVVAMCGEV TKMPGLPTRP AIYDIDLNTE TGEIEGLF
	Isoform A (C). Checksum: 42CC88A69A4D5345	FASTA	934	99,627
	10 20 30 40 50 60 MSGAKIISGT AVAKSIREEL RNEVTAMSKQ LADFVPGLRI VQVGGREDSN VYIRMKIKAA 70 80 90 100 110 120 TEIGIDAAHV QLPRSITEVE LLDKINDLNE DPRVHGIIVQ MPLDCDTPID SHRITDAVSP 130 140 150 160 170 180 EKDVDGLHTV NEGRLAIGDL GGFLPCTPWG CLELIRRSGV EIAGARAVVL GRSKIVGTPA 190 200 210 220 230 240 AELLKWANAT VTVCHSKTRN LEEITRSADI LVVGIGVAEM VKGSWIKPGA VVIDCGINVK 250 260 270 280 290 300 PDASKASGSK LVGDVDYAEA LQVAGHLTPV PGGVGPMTVA MLMKNTVRSA ARFLERLAKS 310 320 330 340 350 360 QWALQTLPLK PQRPVPSDIV IARAQKPKDI AVLAKEIGLE AREVSLYGNK KAKISLSVLE 370 380 390 400 410 420 RLKDKEVGHY VVVAGMTPTP LGEGKTTTLM GLVQALGAHK LRNTMAALRQ PSQGPTFGIK 430 440 450 460 470 480 GGAAGGGYAQ VIPMEEFNLH LTGDIHAVSA ANNLLAAQLD TRIFHENTQK DKALYDRLVP 490 500 510 520 530 540 AIKGQRKFSP IQLRRLQKLG ITKTDPDTLT ADEYGPFARL DIDPDTIMWE RVVDINDRYL 550 560 570 580 590 600 RTITVGQSPT EKGISRETRF SISVASEIMA VLALSRSLED MKQRLADMVV AFDKRGKPVT 610 620 630 640 650 660 ADDLGVTGAL AVLLKDALEP NLMQSLEGTP VLVHAGPFAN IAHGCNSIIA DEVGLKLVGK 670 680 690 700 710 720 NGFVCTEAGF GSDIGMEKFC NIKCRTSGRK PNAMVLVATV RAIKMHGGGA PVTPGAPLNK 730 740 750 760 770 780 QYTEENLELV QKGLPNLLQH IENGKAFGMP VVVSLNAHSA DTPAEHELVK KAALEAGAFA 790 800 810 820 830 840 AVVSTHWADG GAGAVQLADA VIKACEQGNQ FRLLYDLELP LVDKMNKIAT TMYGAGKVVL 850 860 870 880 890 900 SPAAEEKVKR LTDAGFGNLP ICMSKVSGSF TGDAKIKGAP KGFTLDVEDV YVSAGAGFVV 910 920 930 AMCGEVTKMP GLPTRPAIYD IDLNTETGEI EGLF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Dominant defects in Drosophila eye pigmentation resulting from a euchromatin-heterochromatin fusion gene." Rong Y.S., Golic K.G. Genetics 150:1551-1566(1998) [PubMed: 9832531] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
[2]	"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.
[3]	"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.
[4]	Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A., Pacleb J.M., Park S., Wan K.H., Yu C., Rubin G.M., Celniker S.E. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). Strain: Berkeley. Tissue: Embryo.
[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] OF 604-968. Strain: Berkeley. Tissue: Head.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF082097 Genomic DNA. Translation: AAC78847.1. AE014297 Genomic DNA. Translation: AAG22140.2. AE014297 Genomic DNA. Translation: AAN13478.1. AE014297 Genomic DNA. Translation: AAN13479.1. AE014297 Genomic DNA. Translation: AAX52944.1. BT021278 mRNA. Translation: AAX33426.1. AY069146 mRNA. Translation: AAL39291.1. Different initiation.
RefSeq	NP_001014614.1. NP_477254.1. NP_731489.2. NP_731490.1.
UniGene	Dm.14326
3D structure databases
HSSP	HSSP built from PDB template 1A4I based on UniProtKB P11586.
ModBase	Search...
Protein-protein interaction databases
IntAct	O96553. 1 interaction.
Genome annotation databases
Ensembl	FBgn0020385. Drosophila melanogaster. [Contig view]
GeneID	41279.
KEGG	dme:Dmel_CG4067.
Organism-specific databases
FlyBase	FBgn0020385. pug.
Phylogenomic databases
HOGENOM	O96553.
OMA	O96553. KAEVYTK.
Enzyme and pathway databases
BRENDA	1.5.1.5. 48. 3.5.4.9. 48. 6.3.4.3. 48.
Gene expression databases
ArrayExpress	O96553.
GermOnline	CG4067. Drosophila melanogaster.
Family and domain databases
InterPro	IPR000559. For_THF_ligase. IPR016040. NAD(P)-bd_dom. IPR000672. THF_DH/CycHdrlase. [Graphical view]
Gene3D	G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.
Pfam	PF01268. FTHFS. 1 hit. PF00763. THF_DHG_CYH. 1 hit. PF02882. THF_DHG_CYH_C. 1 hit. [Graphical view]
PRINTS	PR00085. THFDHDRGNASE.
ProDom	PD002300. THFDhg/Cyc_hydro. 1 hit. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00721. FTHFS_1. 1 hit. PS00722. FTHFS_2. 1 hit. PS00766. THF_DHG_CYH_1. 1 hit. PS00767. THF_DHG_CYH_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	823064.

Entry information

Entry name

C1TC_DROME

Accession

Primary (citable) accession number: O96553
Secondary accession number(s): A4V2N7 , A4V2N9, Q5BIE6, Q8T0P2

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2003
Last sequence update:	July 19, 2004
Last modified:	June 16, 2009
This is version 69 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project