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O96553 (C1TC_DROME) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
C-1-tetrahydrofolate synthase, cytoplasmic

Short name=C1-THF synthase

Including the following 3 domains:

  1. Methylenetetrahydrofolate dehydrogenase
    EC=1.5.1.5
  2. Methenyltetrahydrofolate cyclohydrolase
    EC=3.5.4.9
  3. Formyltetrahydrofolate synthetase
    EC=6.3.4.3
Gene names
Name:pug
ORF Names:CG4067
OrganismDrosophila melanogaster (Fruit fly) [Reference proteome]
Taxonomic identifier7227 [NCBI]
Taxonomic lineageEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora

Protein attributes

Sequence length968 AA.
Sequence statusComplete.
Protein existenceEvidence 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 interconversion.

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.

Sequence caution

The sequence AAL39291.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processAmino-acid biosynthesis
Histidine biosynthesis
Methionine biosynthesis
One-carbon metabolism
Purine biosynthesis
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   LigandATP-binding
NADP
Nucleotide-binding
   Molecular functionHydrolase
Ligase
Oxidoreductase
   Technical termComplete proteome
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processcellular amino acid biosynthetic process

Non-traceable author statement Ref.1. Source: UniProtKB

folic acid-containing compound 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 metabolic process

Inferred from Biological aspect of Ancestor. Source: RefGenome

purine nucleotide biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

tetrahydrofolate interconversion

Inferred from electronic annotation. Source: UniProtKB-UniPathway

   Cellular_componentcytoplasm

Inferred from direct assay Ref.1. Source: UniProtKB

cytosol

Inferred from Biological aspect of Ancestor. Source: RefGenome

lipid particle

Inferred from direct assay PubMed 16543254. Source: FlyBase

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

formate-tetrahydrofolate ligase activity

Non-traceable author statement Ref.1. Source: UniProtKB

methenyltetrahydrofolate cyclohydrolase activity

Non-traceable author statement Ref.1. Source: UniProtKB

methylenetetrahydrofolate dehydrogenase (NADP+) activity

Non-traceable author statement Ref.1. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Keap1Q9VEN51EBI-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 968968C-1-tetrahydrofolate synthase, cytoplasmic
PRO_0000199324

Regions

Nucleotide binding205 – 2073NADP By similarity
Nucleotide binding413 – 4208ATP By similarity
Region1 – 338338Methylenetetrahydrofolate dehydrogenase and cyclohydrolase
Region86 – 905Substrate binding By similarity
Region133 – 1353Substrate binding By similarity
Region305 – 3095Substrate binding By similarity
Region339 – 968630Formyltetrahydrofolate synthetase

Sites

Binding site2301NADP By similarity

Natural variations

Alternative sequence1 – 3434Missing in isoform A.
VSP_010883

Experimental info

Sequence conflict8791E → K in AAX33426. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform B (D) [UniParc].

Last modified July 19, 2004. Version 4.
Checksum: D65EC8455DD8AF2C

FASTA968103,504
        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 

« Hide

Isoform A (C) [UniParc].

Checksum: 42CC88A69A4D5345
Show »

FASTA93499,627

References

« Hide '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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING.
Strain: Berkeley.
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 604-968.
Strain: Berkeley.
Tissue: Head.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001014614.1. NM_001014614.2.
NP_477254.1. NM_057906.4.
NP_731489.2. NM_169350.2.
NP_731490.1. NM_169351.2.
UniGeneDm.14326.

3D structure databases

ProteinModelPortalO96553.
SMRO96553. Positions 38-329, 350-968.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid66423. 2 interactions.
IntActO96553. 1 interaction.
MINTMINT-297603.

Proteomic databases

PaxDbO96553.
PRIDEO96553.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaFBtr0082264; FBpp0081741; FBgn0020385. [O96553-1]
FBtr0100144; FBpp0099494; FBgn0020385. [O96553-1]
GeneID41279.
KEGGdme:Dmel_CG4067.
UCSCCG4067-RA. d. melanogaster. [O96553-1]

Organism-specific databases

CTD41279.
FlyBaseFBgn0020385. pug.

Phylogenomic databases

eggNOGCOG0190.
GeneTreeENSGT00750000117401.
InParanoidO96553.
KOK00288.
OMAGFHAYNI.
OrthoDBEOG76T9QN.
PhylomeDBO96553.

Enzyme and pathway databases

UniPathwayUPA00193.

Gene expression databases

BgeeO96553.

Family and domain databases

Gene3D3.40.50.300. 2 hits.
3.40.50.720. 1 hit.
HAMAPMF_01543. FTHFS.
MF_01576. THF_DHG_CYH.
InterProIPR000559. Formate_THF_ligase.
IPR020628. Formate_THF_ligase_CS.
IPR016040. NAD(P)-bd_dom.
IPR027417. P-loop_NTPase.
IPR000672. THF_DH/CycHdrlase.
IPR020630. THF_DH/CycHdrlase_cat_dom.
IPR020867. THF_DH/CycHdrlase_CS.
IPR020631. THF_DH/CycHdrlase_NAD-bd_dom.
[Graphical view]
PfamPF01268. FTHFS. 1 hit.
PF00763. THF_DHG_CYH. 1 hit.
PF02882. THF_DHG_CYH_C. 1 hit.
[Graphical view]
PRINTSPR00085. THFDHDRGNASE.
SUPFAMSSF52540. SSF52540. 2 hits.
PROSITEPS00721. 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]
ProtoNetSearch...

Other

GenomeRNAi41279.
NextBio823064.
PROO96553.

Entry information

Entry nameC1TC_DROME
AccessionPrimary (citable) accession number: O96553
Secondary accession number(s): A4V2N7 expand/collapse secondary AC list , A4V2N9, Q5BIE6, Q8T0P2
Entry history
Integrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: July 19, 2004
Last modified: April 16, 2014
This is version 107 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

Drosophila

Drosophila: entries, gene names and cross-references to FlyBase