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Protein

2-isopropylmalate synthase

Gene

LEU4

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-hydroxy-4-methylpentanoate (2-isopropylmalate).

Catalytic activityi

Acetyl-CoA + 3-methyl-2-oxobutanoate + H2O = (2S)-2-isopropylmalate + CoA.

Pathwayi: L-leucine biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes L-leucine from 3-methyl-2-oxobutanoate.
Proteins known to be involved in the 4 steps of the subpathway in this organism are:
  1. 2-isopropylmalate synthase (LEU4), 2-isopropylmalate synthase 2, mitochondrial (LEU9)
  2. 3-isopropylmalate dehydratase (LEU1)
  3. 3-isopropylmalate dehydrogenase (LEU2)
  4. Branched-chain-amino-acid aminotransferase, cytosolic (BAT2), Branched-chain-amino-acid aminotransferase, mitochondrial (BAT1)
This subpathway is part of the pathway L-leucine biosynthesis, which is itself part of Amino-acid biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-leucine from 3-methyl-2-oxobutanoate, the pathway L-leucine biosynthesis and in Amino-acid biosynthesis.

GO - Molecular functioni

  • 2-isopropylmalate synthase activity Source: SGD

GO - Biological processi

  • leucine biosynthetic process Source: SGD
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Amino-acid biosynthesis, Branched-chain amino acid biosynthesis, Leucine biosynthesis

Enzyme and pathway databases

BioCyciYEAST:YNL104C-MONOMER.
UniPathwayiUPA00048; UER00070.

Names & Taxonomyi

Protein namesi
Recommended name:
2-isopropylmalate synthase (EC:2.3.3.13)
Alternative name(s):
Alpha-IPM synthase
Alpha-isopropylmalate synthase
Gene namesi
Name:LEU4
Ordered Locus Names:YNL104C
ORF Names:N2173
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
Proteomesi
  • UP000002311 Componenti: Chromosome XIV

Organism-specific databases

EuPathDBiFungiDB:YNL104C.
SGDiS000005048. LEU4.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: SGD
  • mitochondrion Source: SGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 6196192-isopropylmalate synthasePRO_0000001046Add
BLAST

Proteomic databases

MaxQBiP06208.
PeptideAtlasiP06208.

PTM databases

iPTMnetiP06208.

Interactioni

Subunit structurei

Homodimer.

Binary interactionsi

WithEntry#Exp.IntActNotes
LEU9Q121663EBI-10116,EBI-37359

Protein-protein interaction databases

BioGridi35719. 35 interactions.
DIPiDIP-1412N.
IntActiP06208. 4 interactions.
MINTiMINT-392669.

Structurei

3D structure databases

ProteinModelPortaliP06208.
SMRiP06208. Positions 35-592.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

GeneTreeiENSGT00390000018527.
HOGENOMiHOG000110941.
InParanoidiP06208.
KOiK01649.
OMAiNYTEHSL.
OrthoDBiEOG73NGC6.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
HAMAPiMF_00572. LeuA_type2.
InterProiIPR013709. 2-isopropylmalate_synth_dimer.
IPR002034. AIPM/Hcit_synth_CS.
IPR013785. Aldolase_TIM.
IPR005668. IPM_Synthase.
IPR000891. PYR_CT.
[Graphical view]
PfamiPF00682. HMGL-like. 1 hit.
PF08502. LeuA_dimer. 1 hit.
[Graphical view]
SMARTiSM00917. LeuA_dimer. 1 hit.
[Graphical view]
SUPFAMiSSF110921. SSF110921. 1 hit.
TIGRFAMsiTIGR00970. leuA_yeast. 1 hit.
PROSITEiPS00815. AIPM_HOMOCIT_SYNTH_1. 1 hit.
PS00816. AIPM_HOMOCIT_SYNTH_2. 1 hit.
PS50991. PYR_CT. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform Mitochondrial (identifier: P06208-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MVKESIIALA EHAASRASRV IPPVKLAYKN MLKDPSSKYK PFNAPKLSNR
60 70 80 90 100
KWPDNRITRA PRWLSTDLRD GNQSLPDPMS VEQKKEYFHK LVNIGFKEIE
110 120 130 140 150
VSFPSASQTD FDFTRYAVEN APDDVSIQCL VQSREHLIKR TVEALTGAKK
160 170 180 190 200
ATIHTYLATS DMFREIVFNM SREEAISKAV EATKLVRKLT KDDPSQQATR
210 220 230 240 250
WSYEFSPECF SDTPGEFAVE ICEAVKKAWE PTEENPIIFN LPATVEVASP
260 270 280 290 300
NVYADQIEYF ATHITEREKV CISTHCHNDR GCGVAATELG MLAGADRVEG
310 320 330 340 350
CLFGNGERTG NVDLVTVAMN MYTQGVSPNL DFSDLTSVLD VVERCNKIPV
360 370 380 390 400
SQRAPYGGDL VVCAFSGSHQ DAIKKGFNLQ NKKRAQGETQ WRIPYLPLDP
410 420 430 440 450
KDIGRDYEAV IRVNSQSGKG GAAWVILRSL GLDLPRNMQI EFSSAVQDHA
460 470 480 490 500
DSLGRELKSD EISKLFKEAY NYNDEQYQAI SLVNYNVEKF GTERRVFTGQ
510 520 530 540 550
VKVGDQIVDI EGTGNGPISS LVDALSNLLN VRFAVANYTE HSLGSGSSTQ
560 570 580 590 600
AASYIHLSYR RNADNEKAYK WGVGVSEDVG DSSVRAIFAT INNIIHSGDV
610
SIPSLAEVEG KNAAASGSA
Length:619
Mass (Da):68,409
Last modified:January 1, 1988 - v1
Checksum:i6886E76C5DD89CE2
GO
Isoform Cytoplasmic (identifier: P06208-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-30: Missing.

Note: Produced by alternative initiation at Met-31 of isoform Mitochondrial.
Show »
Length:589
Mass (Da):65,163
Checksum:iA920218A02F29D99
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 3030Missing in isoform Cytoplasmic. CuratedVSP_018640Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12893 Genomic DNA. Translation: AAA34743.1.
M12893 Genomic DNA. Translation: AAA34744.1.
Z50161 Genomic DNA. Translation: CAA90522.1.
Z71380 Genomic DNA. Translation: CAA95980.1.
Z12126 Genomic DNA. Translation: CAA78110.1.
BK006947 Genomic DNA. Translation: DAA10441.1.
PIRiA23872.
RefSeqiNP_014295.1. NM_001182942.1. [P06208-1]

Genome annotation databases

EnsemblFungiiYNL104C; YNL104C; YNL104C. [P06208-1]
GeneIDi855619.
KEGGisce:YNL104C.

Keywords - Coding sequence diversityi

Alternative initiation

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12893 Genomic DNA. Translation: AAA34743.1.
M12893 Genomic DNA. Translation: AAA34744.1.
Z50161 Genomic DNA. Translation: CAA90522.1.
Z71380 Genomic DNA. Translation: CAA95980.1.
Z12126 Genomic DNA. Translation: CAA78110.1.
BK006947 Genomic DNA. Translation: DAA10441.1.
PIRiA23872.
RefSeqiNP_014295.1. NM_001182942.1. [P06208-1]

3D structure databases

ProteinModelPortaliP06208.
SMRiP06208. Positions 35-592.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi35719. 35 interactions.
DIPiDIP-1412N.
IntActiP06208. 4 interactions.
MINTiMINT-392669.

PTM databases

iPTMnetiP06208.

Proteomic databases

MaxQBiP06208.
PeptideAtlasiP06208.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYNL104C; YNL104C; YNL104C. [P06208-1]
GeneIDi855619.
KEGGisce:YNL104C.

Organism-specific databases

EuPathDBiFungiDB:YNL104C.
SGDiS000005048. LEU4.

Phylogenomic databases

GeneTreeiENSGT00390000018527.
HOGENOMiHOG000110941.
InParanoidiP06208.
KOiK01649.
OMAiNYTEHSL.
OrthoDBiEOG73NGC6.

Enzyme and pathway databases

UniPathwayiUPA00048; UER00070.
BioCyciYEAST:YNL104C-MONOMER.

Miscellaneous databases

NextBioi979807.
PROiP06208.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
HAMAPiMF_00572. LeuA_type2.
InterProiIPR013709. 2-isopropylmalate_synth_dimer.
IPR002034. AIPM/Hcit_synth_CS.
IPR013785. Aldolase_TIM.
IPR005668. IPM_Synthase.
IPR000891. PYR_CT.
[Graphical view]
PfamiPF00682. HMGL-like. 1 hit.
PF08502. LeuA_dimer. 1 hit.
[Graphical view]
SMARTiSM00917. LeuA_dimer. 1 hit.
[Graphical view]
SUPFAMiSSF110921. SSF110921. 1 hit.
TIGRFAMsiTIGR00970. leuA_yeast. 1 hit.
PROSITEiPS00815. AIPM_HOMOCIT_SYNTH_1. 1 hit.
PS00816. AIPM_HOMOCIT_SYNTH_2. 1 hit.
PS50991. PYR_CT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Structure of yeast LEU4. The 5' flanking region contains features that predict two modes of control and two productive translation starts."
    Beltzer J.P., Chang L.-F.L., Hinkkanen A.E., Kohlhaw G.B.
    J. Biol. Chem. 261:5160-5167(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "The sequence of a 21.3 kb DNA fragment from the left arm of yeast chromosome XIV reveals LEU4, MET4, POL1, RAS2, and six new open reading frames."
    Saiz J.E., Buitrago M.J., Soler A., del Rey F., Revuelta J.L.
    Yeast 12:403-409(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: ATCC 96604 / S288c / FY1679.
  3. "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its evolutionary implications."
    Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K., Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K., Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M., Beinhauer J.D., Boskovic J., Buitrago M.J.
    , Bussereau F., Coster F., Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F., Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C., Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A., Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H., Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L., Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R., Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D., Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A., Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C., Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F., Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G., Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M., Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J.
    Nature 387:93-98(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: ATCC 204508 / S288c.
  4. Cited for: GENOME REANNOTATION.
    Strain: ATCC 204508 / S288c.
  5. "The general amino acid control regulates MET4, which encodes a methionine-pathway-specific transcriptional activator of Saccharomyces cerevisiae."
    Mountain H.A., Bystroem A.S., Korch C.
    Mol. Microbiol. 7:215-228(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-23.
    Strain: ATCC 204508 / S288c.
  6. "Yeast LEU4 encodes mitochondrial and nonmitochondrial forms of alpha-isopropylmalate synthase."
    Beltzer J.P., Morris S.R., Kohlhaw G.B.
    J. Biol. Chem. 263:368-374(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: ALTERNATIVE INITIATION.
  7. Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiLEU1_YEAST
AccessioniPrimary (citable) accession number: P06208
Secondary accession number(s): D6W175
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: May 11, 2016
This is version 156 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Miscellaneous

Present with 6630 molecules/cell in log phase SD medium.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families
  3. Yeast
    Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
  4. Yeast chromosome XIV
    Yeast (Saccharomyces cerevisiae) chromosome XIV: entries and gene names

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.