Rv2780 (ald)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: alanine dehydrogenase
- REFSEQ: secreted L-alanine dehydrogenase ALD (40 kDa antigen) (TB43)
- PATRIC: Alanine dehydrogenase (EC 1.4.1.1)
- TUBERCULIST: Secreted L-alanine dehydrogenase Ald (40 kDa antigen) (TB43)
- NCBI: Secreted L-alanine dehydrogenase Ald (40 kDa antigen) (TB43)
- updated information (H37Rv4):
  - gene name: ald
  - function:
  - reference:
Type: Not Target
Start: 3086820
End: 3087935
Operon:

Trans-membrane region:
Role: I.A.2 - Amino acids and amines
GO terms:
- GO:0055114 - oxidation-reduction process (Uniprot)
- GO:0046872 - metal ion binding (Uniprot)
- GO:0042853 - L-alanine catabolic process (Uniprot)
- GO:0016491 - oxidoreductase activity (Uniprot)
- GO:0006524 - alanine catabolic process (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0005618 - cell wall (Uniprot)
- GO:0005576 - extracellular region (Uniprot)
- GO:0001666 - response to hypoxia (Uniprot)
- GO:0000286 - alanine dehydrogenase activity (Uniprot)
- GO:0000166 - nucleotide binding (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- NADH[c] + PYR[c] + NH3[c] <=> NAD[c] + ALA[c]
Gene Expression Profile (Transcriptional Responses to Drugs; Boshoff et al, 2004)
Gene Modules extracted from cluster analysis of 249 transcriptomic datasets using ICA
Orthologs among selected mycobacteria
Protein structure: 2voe, 2vhw, 2vhv, 2vhz, 2vhy, 2vhx, 2voj
Search for Homologs in PDB

Top 10 Homologs in PDB (as of Nov 2020):

PDB	aa ident	species	PDB title
6O7F	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Mycobacterium tuberculosis L-alanine dehydrogenase x-ray structure in complex with N6-isobutyl adenosine
4LMP	100%	Mycobacterium tuberculosis	Mycobacterium tuberculosis L-alanine dehydrogenase x-ray structure in complex with N6-methyl adenosine
2VOJ	100%	MYCOBACTERIUM TUBERCULOSIS	Ternary complex of M. tuberculosis Rv2780 with NAD and pyruvate
2VOE	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of Rv2780 from M. tuberculosis H37Rv
2VHZ	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of holo L-alanine dehydrogenase from Mycobacterium tuberculosis in the closed conformation
2VHY	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of apo L-alanine dehydrogenase from Mycobacterium tuberculosis
2VHX	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of the ternary complex of L-alanine dehydrogenase from Mycobacterium tuberculosis with NAD+ and pyruvate
2VHW	100%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of holo L-alanine dehydrogenase from Mycobacterium tuberculosis in the open and closed conformation
2VHV	99%	MYCOBACTERIUM TUBERCULOSIS	Crystal structure of the D270A mutant of L-alanine dehydrogenase from Mycobacterium tuberculosis in complex with NADH.
2EEZ	56%	Thermus thermophilus	Crystal structure of alanine dehydrogenase from themus thermophilus

Links to additional information on ald:
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.363 (from Jeremy Rock's lab)

Amino Acid Sequence

MRVGIPTETKNNEFRVAITPAGVAELTRRGHEVLIQAGAGEGSAITDADFKAAGAQLVGTADQVWADADLLLKVKEPIAAEYGRLRHGQILFTFLHLAAS
RACTDALLDSGTTSIAYETVQTADGALPLLAPMSEVAGRLAAQVGAYHLMRTQGGRGVLMGGVPGVEPADVVVIGAGTAGYNAARIANGMGATVTVLDIN
IDKLRQLDAEFCGRIHTRYSSAYELEGAVKRADLVIGAVLVPGAKAPKLVSNSLVAHMKPGAVLVDIAIDQGGCFEGSRPTTYDHPTFAVHDTLFYCVAN
MPASVPKTSTYALTNATMPYVLELADHGWRAACRSNPALAKGLSTHEGALLSERVATDLGVPFTEPASVLA

(Nucleotide sequence available on KEGG)

Additional Information

ESSENTIALITY

MtbTnDB - interactive tool for exploring a database of published TnSeq datasets for Mtb

TnSeqCorr - genes with correlated TnSeq profiles across >100 conditions *new*

Classification	Condition	Strain	Method	Reference	Notes
Non-Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 5 non-insertions in a row out of 25 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 25 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 25 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 4 non-insertions in a row out of 25 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 4 non-insertions in a row out of 25 sites
Non-Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Non-Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.91
Non-Essential	7H09/7H10 + rich media	H37RvMA	MotifHMM	DeJesus et al. (2017)	Fully saturated (14 reps).

TnSeq Data No data currently available.

No TnSeq data currently available for this Target.

RNASeq Data No data currently available.

No RNA-Seq data currently available for this Target.

Metabolomic Profiles No data currently available.

No Metabolomic data currently available for this Target.

Proteomic Data No data currently available.

No Proteomic data currently available for this Target.

Regulatory Relationships from Systems Biology

BioCyc

Gene interactions based on ChIPSeq and Transcription Factor Over-Expression (TFOE) (Systems Biology)

NOTE: Green edges represent the connected genes being classified as differentially essential as a result of the middle gene being knocked out. These interactions are inferred based on RNASeq.

Interactions based on ChIPSeq data

RNA processing and modification

Energy production and conversion

Chromatin structure and dynamics

Amino acid transport and metabolism

Cell cycle control, cell division, chromosome partitioning

Carbohydrate transport and metabolism

Nucleotide transport and metabolism

Lipid transport and metabolism

Coenzyme transport and metabolism

Transcription

Translation, ribosomal structure and biogenesis

Cell wall/membrane/envelope biogenesis

Replication, recombination and repair

Posttranslational modification, protein turnover, chaperones

Cell motility

Secondary metabolites biosynthesis, transport and catabolism

Inorganic ion transport and metabolism

Function unknown

General function prediction only

Intracellular trafficking, secretion, and vesicular transport

Signal transduction mechanisms

Extracellular structures

Defense mechanisms

Nuclear structure

Cytoskeleton

BioCyc Co-regulated genes based on gene expression profiling (Systems Biology, Inferelator Network)

Differentially expressed as result of RNASeq in glycerol environment (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

Conditionally essential as result of TNSeq (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

BioCyc Transcription factor binding based on ChIP-Seq (Systems Biology)

Binds To:
- No bindings to other targets were found.
Bound By:
- No bindings from other targets were found.

Interactions based on ChIPSeq data (Minch et al. 2014)

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0023 (-) (Direct binding)
- Rv0081 (-) (Direct binding)
- Rv0324 (-) (Direct binding)
- Rv0602c (tcrA) (Direct binding)
- Rv0678 (-) (Direct binding)
- Rv0757 (phoP) (Direct binding)
- Rv1255c (-) (Direct binding)
- Rv1353c (-) (Direct binding)
- Rv1985c (-) (Direct binding)
- Rv2779c (-) (Direct binding)
- Rv2989 (-) (Direct binding)
- Rv3133c (devR) (Direct binding)
- Rv3291c (lrpA) (Direct binding)
- Rv3488 (-) (Direct binding)
- Rv3597c (lsr2) (Direct binding)
- Rv3681c (whiB4) (Direct binding)
- Rv3765c (tcrX) (Direct binding)
- Rv3855 (ethR) (Direct binding)

Interactions based on TFOE data (Rustad et al. 2014)

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Not upregulated by other genes.
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Regulatory Rv2779c	sumaavasthi	ISO		Operon (Functional linkage) authors,Z. Feng,NE. Cceres,G. Sarath,RG. Barletta Mycobacterium smegmatis L-alanine dehydrogenase (Ald) is required for proficient utilization of alanine as a sole nitrogen source and sustained anaerobic growth. J. Bacteriol. 2002
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) ML. Chesne-Seck, N. Barilone et al. A point mutation in the two-component regulator PhoP-PhoR accounts for the absence of polyketide-derived acyltrehaloses but not that of phthiocerol dimycocerosates in Mycobacterium tuberculosis H37Ra. J. Bacteriol. 2008
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) authors,A. Sola-Landa,RS. Moura,JF. Martn The two-component PhoR-PhoP system controls both primary metabolism and secondary metabolite biosynthesis in Streptomyces lividans. Proc. Natl. Acad. Sci. U.S.A. 2003
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) J. Gonzalo Asensio, C. Maia et al. The virulence-associated two-component PhoP-PhoR system controls the biosynthesis of polyketide-derived lipids in Mycobacterium tuberculosis. J. Biol. Chem. 2006
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) J. Gonzalo-Asensio, CY. Soto et al. The Mycobacterium tuberculosis phoPR operon is positively autoregulated in the virulent strain H37Rv. J. Bacteriol. 2008
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) A. Sinha, S. Gupta et al. PhoP-PhoP interaction at adjacent PhoP binding sites is influenced by protein phosphorylation. J. Bacteriol. 2008
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) J. Gonzalo Asensio, C. Maia et al. The virulence-associated two-component PhoP-PhoR system controls the biosynthesis of polyketide-derived lipids in Mycobacterium tuberculosis. J. Biol. Chem. 2006
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) M. Ryndak, S. Wang et al. PhoP, a key player in Mycobacterium tuberculosis virulence. Trends Microbiol. 2008
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) JA. Asensio, A. Arbus et al. Live tuberculosis vaccines based on phoP mutants: a step towards clinical trials. Expert opinion on biological therapy 2008
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) SB. Walters, E. Dubnau et al. The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol. Microbiol. 2006
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Co-expression (Functional linkage) J. Gonzalo-Asensio, S. Mostowy et al. PhoP: a missing piece in the intricate puzzle of Mycobacterium tuberculosis virulence. PLoS ONE 2008
Interaction	RegulatedBy Rv0348	yamir.moreno	IEP		Microarrays. mRNA levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using microarray (or macroarray) experiments.. B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009
Interaction	RegulatedBy Rv0757	yamir.moreno	IEP		Microarrays. mRNA levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using microarray (or macroarray) experiments.. J. Gonzalo Asensio, C. Maia et al. The virulence-associated two-component PhoP-PhoR system controls the biosynthesis of polyketide-derived lipids in Mycobacterium tuberculosis. J. Biol. Chem. 2006
Interaction	RegulatedBy Rv0491	yamir.moreno	IEP		Microarrays. mRNA levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using microarray (or macroarray) experiments.. T. Parish, DA. Smith et al. The senX3-regX3 two-component regulatory system of Mycobacterium tuberculosis is required for virulence. Microbiology (Reading, Engl.) 2003
Citation	Glutamate synthesis in Streptomyces coelicolor. authors,SH. Fisher J. Bacteriol. 1989	jjmcfadden		2708309	Inferred from direct assay
Term	EC:1.4.1.1 Alanine dehydrogenase. - NR	jjmcfadden	NR		Inferred from direct assay authors,SH. Fisher Glutamate synthesis in Streptomyces coelicolor. J. Bacteriol. 1989
Citation	Glycine and alanine dehydrogenase activities are catalyzed by the same protein in Mycobacterium smegmatis: upregulation of both activities under microaerophilic adaptation. authors,V. Usha,R. Jayaraman,JC. Toro,SE. Hoffner,KS. Das Can. J. Microbiol. 2002	extern:JZUCKER		11888165	Assay of protein purified to homogeneity
Term	EC:1.4.1.10 Glycine dehydrogenase. - NR	extern:JZUCKER	NR		Assay of protein purified to homogeneity authors,V. Usha,R. Jayaraman,JC. Toro,SE. Hoffner,KS. Das Glycine and alanine dehydrogenase activities are catalyzed by the same protein in Mycobacterium smegmatis: upregulation of both activities under microaerophilic adaptation. Can. J. Microbiol. 2002
Term	EC:1.4.1.1 Alanine dehydrogenase. - NR	extern:JZUCKER	NR		Assay of protein purified to homogeneity authors,V. Usha,R. Jayaraman,JC. Toro,SE. Hoffner,KS. Das Glycine and alanine dehydrogenase activities are catalyzed by the same protein in Mycobacterium smegmatis: upregulation of both activities under microaerophilic adaptation. Can. J. Microbiol. 2002
Term	EC:1.5.1.7 Saccharopine dehydrogenase (NAD(+), L-lysine-forming). - NR	extern:JZUCKER	NR		Assay of protein purified to homogeneity authors,V. Usha,R. Jayaraman,JC. Toro,SE. Hoffner,KS. Das Glycine and alanine dehydrogenase activities are catalyzed by the same protein in Mycobacterium smegmatis: upregulation of both activities under microaerophilic adaptation. Can. J. Microbiol. 2002

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