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Entry version 30 (16 Oct 2019)
Sequence version 1 (16 Apr 2014)
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Protein

2-isopropylmalate synthase

Gene

leuA

Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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).UniRule annotation

Miscellaneous

Was identified as a high-confidence drug target.

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: L-leucine biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes L-leucine from 3-methyl-2-oxobutanoate.UniRule annotation
Proteins known to be involved in the 4 steps of the subpathway in this organism are:
  1. 2-isopropylmalate synthase (leuA)
  2. 3-isopropylmalate dehydratase large subunit (leuC), 3-isopropylmalate dehydratase small subunit (leuD)
  3. 3-isopropylmalate dehydrogenase (leuB)
  4. Branched-chain-amino-acid aminotransferase (ilvE)
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.

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionTransferase
Biological processAmino-acid biosynthesis, Branched-chain amino acid biosynthesis, Leucine biosynthesis

Enzyme and pathway databases

BioCyc Collection of Pathway/Genome Databases

More...
BioCyci
MTBH37RV:G185E-7997-MONOMER

UniPathway: a resource for the exploration and annotation of metabolic pathways

More...
UniPathwayi
UPA00048;UER00070

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
2-isopropylmalate synthaseUniRule annotation (EC:2.3.3.13UniRule annotation)
Alternative name(s):
Alpha-IPM synthaseUniRule annotation
Alpha-isopropylmalate synthaseUniRule annotation
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:leuAUniRule annotation
Ordered Locus Names:Rv3710
ORF Names:MTV025.058
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri83332 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000001584 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome

Organism-specific databases

Mycobacterium tuberculosis strain H37Rv genome database

More...
TubercuListi
Rv3710

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

GO - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Chemistry databases

Drug and drug target database

More...
DrugBanki
DB04074 alpha-Ketoisovalerate

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001404361 – 6442-isopropylmalate synthaseAdd BLAST644

Proteomic databases

PaxDb, a database of protein abundance averages across all three domains of life

More...
PaxDbi
P9WQB3

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homotetramer.

UniRule annotation

Protein-protein interaction databases

STRING: functional protein association networks

More...
STRINGi
83332.Rv3710

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1644
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...
SMRi
P9WQB3

Database of comparative protein structure models

More...
ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

More...
PDBe-KBi
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini72 – 346Pyruvate carboxyltransferasePROSITE-ProRule annotationAdd BLAST275

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni577 – 614InsertAdd BLAST38

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the alpha-IPM synthase/homocitrate synthase family. LeuA type 2 subfamily.UniRule annotation

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
ENOG4105CYQ Bacteria
COG0119 LUCA

KEGG Orthology (KO)

More...
KOi
K01649

Identification of Orthologs from Complete Genome Data

More...
OMAi
WPDKVID

Family and domain databases

Conserved Domains Database

More...
CDDi
cd07942 DRE_TIM_LeuA, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
3.20.20.70, 1 hit

HAMAP database of protein families

More...
HAMAPi
MF_00572 LeuA_type2, 1 hit

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR013709 2-isopropylmalate_synth_dimer
IPR002034 AIPM/Hcit_synth_CS
IPR013785 Aldolase_TIM
IPR005668 IPM_Synthase
IPR036230 LeuA_allosteric_dom_sf
IPR039371 LeuA_N_DRE-TIM
IPR000891 PYR_CT

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF00682 HMGL-like, 1 hit
PF08502 LeuA_dimer, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...
SMARTi
View protein in SMART
SM00917 LeuA_dimer, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF110921 SSF110921, 1 hit

TIGRFAMs; a protein family database

More...
TIGRFAMsi
TIGR00970 leuA_yeast, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS00815 AIPM_HOMOCIT_SYNTH_1, 1 hit
PS00816 AIPM_HOMOCIT_SYNTH_2, 1 hit
PS50991 PYR_CT, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

P9WQB3-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MTTSESPDAY TESFGAHTIV KPAGPPRVGQ PSWNPQRASS MPVNRYRPFA
60 70 80 90 100
EEVEPIRLRN RTWPDRVIDR APLWCAVDLR DGNQALIDPM SPARKRRMFD
110 120 130 140 150
LLVRMGYKEI EVGFPSASQT DFDFVREIIE QGAIPDDVTI QVLTQCRPEL
160 170 180 190 200
IERTFQACSG APRAIVHFYN STSILQRRVV FRANRAEVQA IATDGARKCV
210 220 230 240 250
EQAAKYPGTQ WRFEYSPESY TGTELEYAKQ VCDAVGEVIA PTPERPIIFN
260 270 280 290 300
LPATVEMTTP NVYADSIEWM SRNLANRESV ILSLHPHNDR GTAVAAAELG
310 320 330 340 350
FAAGADRIEG CLFGNGERTG NVCLVTLGLN LFSRGVDPQI DFSNIDEIRR
360 370 380 390 400
TVEYCNQLPV HERHPYGGDL VYTAFSGSHQ DAINKGLDAM KLDADAADCD
410 420 430 440 450
VDDMLWQVPY LPIDPRDVGR TYEAVIRVNS QSGKGGVAYI MKTDHGLSLP
460 470 480 490 500
RRLQIEFSQV IQKIAEGTAG EGGEVSPKEM WDAFAEEYLA PVRPLERIRQ
510 520 530 540 550
HVDAADDDGG TTSITATVKI NGVETEISGS GNGPLAAFVH ALADVGFDVA
560 570 580 590 600
VLDYYEHAMS AGDDAQAAAY VEASVTIASP AQPGEAGRHA SDPVTIASPA
610 620 630 640
QPGEAGRHAS DPVTSKTVWG VGIAPSITTA SLRAVVSAVN RAAR
Length:644
Mass (Da):70,114
Last modified:April 16, 2014 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i881A9AAEA7F8FB71
GO

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence AAB48096 differs from that shown. Reason: Frameshift.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti628 – 633TTASLR → NRPA in AAB48096 (PubMed:11914056).Curated6
Sequence conflicti642 – 644AAR → RHARTALN in AAB48096 (PubMed:11914056).Curated3

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
U88526 Genomic DNA Translation: AAB48096.1 Frameshift.
AL123456 Genomic DNA Translation: CCP46536.1

Protein sequence database of the Protein Information Resource

More...
PIRi
G70794

NCBI Reference Sequences

More...
RefSeqi
NP_218227.3, NC_000962.3
WP_003902547.1, NZ_NVQJ01000009.1

Genome annotation databases

Ensembl bacterial and archaeal genome annotation project

More...
EnsemblBacteriai
CCP46536; CCP46536; Rv3710

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
885092

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
mtu:Rv3710
mtv:RVBD_3710

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U88526 Genomic DNA Translation: AAB48096.1 Frameshift.
AL123456 Genomic DNA Translation: CCP46536.1
PIRiG70794
RefSeqiNP_218227.3, NC_000962.3
WP_003902547.1, NZ_NVQJ01000009.1

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1SR9X-ray2.00A/B1-644[»]
3FIGX-ray2.30A/B3-644[»]
3HPSX-ray1.80A/B1-644[»]
3HPXX-ray2.03A/B1-425[»]
3HPZX-ray2.20A/B1-644[»]
3HQ1X-ray1.70A/B1-644[»]
3U6WX-ray2.21A/B1-425[»]
SMRiP9WQB3
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

STRINGi83332.Rv3710

Chemistry databases

DrugBankiDB04074 alpha-Ketoisovalerate

Proteomic databases

PaxDbiP9WQB3

Genome annotation databases

EnsemblBacteriaiCCP46536; CCP46536; Rv3710
GeneIDi885092
KEGGimtu:Rv3710
mtv:RVBD_3710

Organism-specific databases

TubercuListiRv3710

Phylogenomic databases

eggNOGiENOG4105CYQ Bacteria
COG0119 LUCA
KOiK01649
OMAiWPDKVID

Enzyme and pathway databases

UniPathwayiUPA00048;UER00070
BioCyciMTBH37RV:G185E-7997-MONOMER

Family and domain databases

CDDicd07942 DRE_TIM_LeuA, 1 hit
Gene3Di3.20.20.70, 1 hit
HAMAPiMF_00572 LeuA_type2, 1 hit
InterProiView protein in InterPro
IPR013709 2-isopropylmalate_synth_dimer
IPR002034 AIPM/Hcit_synth_CS
IPR013785 Aldolase_TIM
IPR005668 IPM_Synthase
IPR036230 LeuA_allosteric_dom_sf
IPR039371 LeuA_N_DRE-TIM
IPR000891 PYR_CT
PfamiView protein in Pfam
PF00682 HMGL-like, 1 hit
PF08502 LeuA_dimer, 1 hit
SMARTiView protein in SMART
SM00917 LeuA_dimer, 1 hit
SUPFAMiSSF110921 SSF110921, 1 hit
TIGRFAMsiTIGR00970 leuA_yeast, 1 hit
PROSITEiView protein in PROSITE
PS00815 AIPM_HOMOCIT_SYNTH_1, 1 hit
PS00816 AIPM_HOMOCIT_SYNTH_2, 1 hit
PS50991 PYR_CT, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiLEU1_MYCTU
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P9WQB3
Secondary accession number(s): L0TGA3, O69677, P96420
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 16, 2014
Last sequence update: April 16, 2014
Last modified: October 16, 2019
This is version 30 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh
    Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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