P09440 (C1TM_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
C-1-tetrahydrofolate synthase, mitochondrial
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:	MIS1
Ordered Locus Names:	YBR084W
ORF Names:	YBR0751

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	975 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	5,10-methylenetetrahydrofolate + NADP+ = 5,10-methenyltetrahydrofolate + NADPH. 5,10-methenyltetrahydrofolate + H2O = 10-formyltetrahydrofolate. ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate.
Pathway	One-carbon metabolism; tetrahydrofolate interconversion.
Subunit structure	Homodimer. Ref.4
Subcellular location	Mitochondrion Ref.4 Ref.5 Ref.7.
Domain	This trifunctional enzyme consists of two major domains: an N-terminal part containing the methylene-THF dehydrogenase and cyclohydrolase activities and a larger C-terminal part containing formyl-THF synthetase activity.
Miscellaneous	Present with 11400 molecules/cell in log phase SD medium.
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	Mitochondrion
Domain	Transit peptide
Ligand	ATP-binding NADP Nucleotide-binding
Molecular function	Hydrolase Ligase Oxidoreductase
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	folic acid biosynthetic process Inferred from direct assay Ref.4. Source: SGD histidine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW methionine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW nucleobase-containing compound metabolic process Inferred from mutant phenotype PubMed 10781559. Source: SGD purine nucleotide biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW tetrahydrofolate interconversion Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	mitochondrion Inferred from direct assay Ref.7PubMed 16823961Ref.4. Source: SGD
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW formate-tetrahydrofolate ligase activity Inferred from direct assay Ref.4. Source: SGD methenyltetrahydrofolate cyclohydrolase activity Inferred from direct assay Ref.4. Source: SGD methylenetetrahydrofolate dehydrogenase (NADP+) activity Inferred from direct assay Ref.4. Source: SGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RPB5	P20434	1	EBI-3903,EBI-15781
SAT4	P25333	1	EBI-3903,EBI-16492
YHR080C	P38800	1	EBI-3903,EBI-24597

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 34	34	Mitochondrion Ref.4
	Chain	35 – 975	941	C-1-tetrahydrofolate synthase, mitochondrial		PRO_0000034052
Regions
	Nucleotide binding	201 – 203	3	NADP By similarity
	Nucleotide binding	408 – 415	8	ATP By similarity
	Region	35 – 343	309	Methylenetetrahydrofolate dehydrogenase and cyclohydrolase
	Region	83 – 87	5	Substrate binding By similarity
	Region	130 – 132	3	Substrate binding By similarity
	Region	301 – 305	5	Substrate binding By similarity
	Region	344 – 975	632	Formyltetrahydrofolate synthetase
Sites
	Binding site	226	1	NADP By similarity
Amino acid modifications
	Modified residue	521	1	Phosphoserine Ref.8

Sequences

	Sequence		Length	Mass (Da)
	P09440 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: B9421D4F8981531F	FASTA	975	106,217
	10 20 30 40 50 60 MLSRLSLLSN SRAFQQARWR IYRLKVSPTV HASQYHILSG RKLAQSIREK ANDEIQAIKL 70 80 90 100 110 120 KHPNFKPTLK IIQVGARPDS STYVRMKLKA SKDSNVDCII EKLPAEITEV ELLKKISDIN 130 140 150 160 170 180 DDDSIHGLLI QLPLPRHLDE TTITNAVDFK KDVDGFHRYN AGELAKKGGK PYFIPCTPYG 190 200 210 220 230 240 CMKLLEEAHV KLDGKNAVVL GRSSIVGNPI ASLLKNANAT VTVCHSHTRN IAEVVSQADI 250 260 270 280 290 300 VIAACGIPQY VKSDWIKEGA VVIDVGINYV PDISKKSGQK LVGDVDFDSV KEKTSYITPV 310 320 330 340 350 360 PGGVGPMTVA MLVSNVLLAA KRQFVESEKL PVIKPLPLHL ESPVPSDIDI SRAQSPKHIK 370 380 390 400 410 420 QVAEELGIHS HELELYGHYK AKISPNIFKR LESRENGKYV LVAGITPTPL GEGKSTTTMG 430 440 450 460 470 480 LVQALSAHLG KPSIANVRQP SLGPTLGVKG GAAGGGYAQV IPMDEFNLHL TGDIHAISAA 490 500 510 520 530 540 NNLLAAAIDT RMFHEATQKN DSTFYKRLVP RKKGIRKFTP SMQRRLKRLD IEKEDPDALT 550 560 570 580 590 600 PEEVKRFARL NINPDTITIR RVVDINDRML RQITIGEAAT EKGFTRTTGF DITVASELMA 610 620 630 640 650 660 ILALSKSLHE MKERIGRMVI GADYDNKPVT VEDIGCTGAL TALLRDAIKP NLMQTLEGTP 670 680 690 700 710 720 VMVHAGPFAN ISIGASSVIA DLMALKLVGS EKNPLNDKNI HEPGYVVTEA GFDFAMGGER 730 740 750 760 770 780 FFDIKCRSSG LVPDAVVLVA TVRALKSHGG APNVKPGQSL PKEYTEENID FVAKGVSNLV 790 800 810 820 830 840 KQIENIKTFG IPVVVAINRF ETDSQAEIEV IKKAALNAGA SHAVTSNHWM EGGKGAVELA 850 860 870 880 890 900 HAVVDATKEP KNFNFLYDVN SSIEDKLTSI VQKMYGGAKI EVSPEAQKKI DTYKKQGFGN 910 920 930 940 950 960 LPICIAKTQY SLSHDPSLKG VPRGFTFPIR DVRASIGAGY LYALAAEIQT IPGLSTYAGY 970 MAVEVDDDGE IEGLF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of the Saccharomyces cerevisiae MIS1 gene encoding mitochondrial C1-tetrahydrofolate synthase." Shannon K.W., Rabinowitz J.C. J. Biol. Chem. 263:7717-7725(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Complete DNA sequence of yeast chromosome II." Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C., Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M., Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M., Cziepluch C. , Demolis N., Delaveau T., Doignon F., Domdey H., Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D., Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N., Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J., Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C., Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P., Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y., Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F., Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E., Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M., Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B., Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L., Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M., Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S., Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K., Mewes H.-W., Kleine K. EMBO J. 13:5795-5809(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[3]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[4]	"Purification and characterization of a mitochondrial isozyme of C1-tetrahydrofolate synthase from Saccharomyces cerevisiae." Shannon K.W., Rabinowitz J.C. J. Biol. Chem. 261:12266-12271(1986) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 35-74, CHARACTERIZATION, SUBCELLULAR LOCATION, SUBUNIT.
[5]	"Global analysis of protein localization in budding yeast." Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K. Nature 425:686-691(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[6]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[7]	"The proteome of Saccharomyces cerevisiae mitochondria." Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R.P., Meyer H.E., Schoenfisch B., Perschil I., Chacinska A., Guiard B., Rehling P., Pfanner N., Meisinger C. Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Strain: ATCC 76625 / YPH499.
[8]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-521, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z35953 Genomic DNA. Translation: CAA85029.1. J03724 Genomic DNA. Translation: AAA34781.1. BK006936 Genomic DNA. Translation: DAA07203.1.
PIR	A28174.
RefSeq	NP_009640.1. NM_001178432.1.
3D structure databases
ProteinModelPortal	P09440.
SMR	P09440. Positions 37-326, 346-973.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-6724N.
IntAct	P09440. 48 interactions.
MINT	MINT-660665.
STRING	4932.YBR084W.
Proteomic databases
PaxDb	P09440.
PeptideAtlas	P09440.
PRIDE	P09440.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	YBR084W; YBR084W; YBR084W.
GeneID	852378.
KEGG	sce:YBR084W.
Organism-specific databases
CYGD	YBR084w.
SGD	S000000288. MIS1.
Phylogenomic databases
eggNOG	COG0190.
GeneTree	ENSGT00630000089834.
HOGENOM	HOG000040280.
KO	K00288.
OMA	LPTHAGF.
OrthoDB	EOG4TF3TC.
Enzyme and pathway databases
UniPathway	UPA00193.
Gene expression databases
Genevestigator	P09440.
GermOnline	YBR084W. Saccharomyces cerevisiae.
Family and domain databases
Gene3D	3.40.50.720. 1 hit.
InterPro	IPR000559. Formate_THF_ligase. IPR020628. Formate_THF_ligase_CS. 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]
Pfam	PF01268. FTHFS. 1 hit. PF00763. THF_DHG_CYH. 1 hit. PF02882. THF_DHG_CYH_C. 1 hit. [Graphical view]
PRINTS	PR00085. THFDHDRGNASE.
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
NextBio	971174.

Entry information

Entry name

C1TM_YEAST

Accession

Primary (citable) accession number: P09440
Secondary accession number(s): D6VQ83

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	May 1, 2013
This is version 133 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program