Rv2122c (hisE)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: phosphoribosyl-ATP pyrophosphatase
- REFSEQ: phosphoribosyl-ATP pyrophosphatase
- PATRIC: Phosphoribosyl-ATP pyrophosphatase (EC 3.6.1.31)
- TUBERCULIST: Phosphoribosyl-AMP pyrophosphatase HisE
- NCBI: Phosphoribosyl-AMP pyrophosphatase HisE
- updated information (H37Rv4):
  - gene name: hisE
  - function:
  - reference:
Type: Not Target
Start: 2380663
End: 2380944
Operon:

Trans-membrane region:
Role: I.D.5 - Histidine
GO terms:
- GO:0075139 - response to host iron concentration (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0016787 - hydrolase activity (Uniprot)
- GO:0008652 - cellular amino acid biosynthetic process (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
- GO:0005618 - cell wall (Uniprot)
- GO:0005524 - ATP binding (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0004636 - phosphoribosyl-ATP diphosphatase activity (Uniprot)
- GO:0000287 - magnesium ion binding (Uniprot)
- GO:0000166 - nucleotide binding (Uniprot)
- GO:0000105 - histidine biosynthetic process (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- PRBATP[c] -> PPI[c] + PRBAMP[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: 1y6x, 3c90
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
3C90	100%	Mycobacterium tuberculosis	The 1.25 A Resolution Structure of Phosphoribosyl-ATP Pyrophosphohydrolase from Mycobacterium tuberculosis, crystal form II
1Y6X	98%	Mycobacterium tuberculosis	The 1.25 A resolution structure of phosphoribosyl-ATP pyrophosphohydrolase from Mycobacterium tuberculosis
1YXB	60%	Streptomyces coelicolor	Crystal structure of Phosphoribosyl-ATP pyrophosphatase from Streptomyces coelicolor. NESG target RR8.

Links to additional information on hisE:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -9.023 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VQQSLAVKTFEDLFAELGDRARTRPADSTTVAALDGGVHALGKKLLEEAGEVWLAAEHESNDALAEEISQLLYWTQVLMISRGLSLDDVYRKL

(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
Too-Short	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: -1.000000; 3 non-insertions in a row out of 3 sites
Too-Short	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: -1.000000; 3 non-insertions in a row out of 3 sites
Too-Short	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: -1.000000; 3 non-insertions in a row out of 3 sites
Too-Short	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: -1.000000; 3 non-insertions in a row out of 3 sites
Too-Short	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: -1.000000; 3 non-insertions in a row out of 3 sites
Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.05
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

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

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

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

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv0023 (-)
- Rv0081 (-)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Regulatory Rv2123	ahal4789	IDA		Footprinting GM. Rodriguez, MI. Voskuil et al. ideR, An essential gene in mycobacterium tuberculosis: role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. Infect. Immun. 2002
Interaction	Regulatory Rv2123	sourish10	IDA		Footprinting P. Prakash, S. Yellaboina et al. Computational prediction and experimental verification of novel IdeR binding sites in the upstream sequences of Mycobacterium tuberculosis open reading frames. Bioinformatics 2005
Interaction	Regulatory Rv2123	sourish10	IDA		Footprinting GM. Rodriguez, MI. Voskuil et al. ideR, An essential gene in mycobacterium tuberculosis: role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. Infect. Immun. 2002
Citation	The 1.25 A resolution structure of phosphoribosyl-ATP pyrophosphohydrolase from Mycobacterium tuberculosis. F. Javid-Majd, D. Yang et al. Acta Crystallogr. D Biol. Crystallogr. 2008	ashwinigbhat	NAS	18560150	operon
Interaction	Operon Rv2121c	ashwinigbhat	NAS		operon F. Javid-Majd, D. Yang et al. The 1.25 A resolution structure of phosphoribosyl-ATP pyrophosphohydrolase from Mycobacterium tuberculosis. Acta Crystallogr. D Biol. Crystallogr. 2008
Citation	Identification and characterization of two divergently transcribed iron regulated genes in Mycobacterium tuberculosis. GM. Rodriguez, B. Gold et al. Tuber. Lung Dis. 1999	ashwinigbhat	NAS	10707257	operon
Interaction	Operon Rv2121c	ashwinigbhat	NAS		operon GM. Rodriguez, B. Gold et al. Identification and characterization of two divergently transcribed iron regulated genes in Mycobacterium tuberculosis. Tuber. Lung Dis. 1999
Interaction	Regulatory Rv2123	ahal4789	IDA		Footprinting P. Prakash, S. Yellaboina et al. Computational prediction and experimental verification of novel IdeR binding sites in the upstream sequences of Mycobacterium tuberculosis open reading frames. Bioinformatics 2005
Interaction	Operon Rv2121c	priti.priety	NAS		operon F. Javid-Majd, D. Yang et al. The 1.25 A resolution structure of phosphoribosyl-ATP pyrophosphohydrolase from Mycobacterium tuberculosis. Acta Crystallogr. D Biol. Crystallogr. 2008
Interaction	Operon Rv2121c	priti.priety	NAS		operon GM. Rodriguez, B. Gold et al. Identification and characterization of two divergently transcribed iron regulated genes in Mycobacterium tuberculosis. Tuber. Lung Dis. 1999
Interaction	Operon Rv2121c	ashwinigbhat	NAS		operon F. Javid-Majd, D. Yang et al. The 1.25 A resolution structure of phosphoribosyl-ATP pyrophosphohydrolase from Mycobacterium tuberculosis. Acta Crystallogr. D Biol. Crystallogr. 2008
Interaction	Operon Rv2121c	ashwinigbhat	NAS		operon GM. Rodriguez, B. Gold et al. Identification and characterization of two divergently transcribed iron regulated genes in Mycobacterium tuberculosis. Tuber. Lung Dis. 1999
Citation	The 1.25 A resolution structure of phosphoribosyl-ATP pyrophosphohydrolase from Mycobacterium tuberculosis. F. Javid-Majd, D. Yang et al. Acta Crystallogr. D Biol. Crystallogr. 2008	priti.priety	NAS	18560150	operon
Interaction	Operon Rv2121c	priti.priety	NAS		operon F. Javid-Majd, D. Yang et al. The 1.25 A resolution structure of phosphoribosyl-ATP pyrophosphohydrolase from Mycobacterium tuberculosis. Acta Crystallogr. D Biol. Crystallogr. 2008
Citation	Identification and characterization of two divergently transcribed iron regulated genes in Mycobacterium tuberculosis. GM. Rodriguez, B. Gold et al. Tuber. Lung Dis. 1999	priti.priety	NAS	10707257	operon
Interaction	Operon Rv2121c	priti.priety	NAS		operon GM. Rodriguez, B. Gold et al. Identification and characterization of two divergently transcribed iron regulated genes in Mycobacterium tuberculosis. Tuber. Lung Dis. 1999
Interaction	RegulatedBy Rv2711	yamir.moreno	TAS		Literature previously reported link (from Balazsi et al. 2008). Traceable author statement to experimental support. G. Balzsi, AP. Heath et al. The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. Mol. Syst. Biol. 2008

TB Genome Annotation Portal