Rv2031c (hspX)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: heat shock protein hspX
- REFSEQ: heat shock protein hspX
- PATRIC: 14 kDa antigen (16 kDa antigen) (HSP 16.3)
- TUBERCULIST: Heat shock protein HspX (alpha-crystallin homolog) (14 kDa antigen) (HSP16.3)
- NCBI: Heat shock protein HspX (alpha-crystallin homolog) (14 kDa antigen) (HSP16.3)
- updated information (H37Rv4):
  - gene name: acr/hspX
  - function: alpha crystallin; highly up-regulated in hypoxia (in dosR regulon)
  - reference:
Type: Not Target
Start: 2278498
End: 2278932
Operon:

Trans-membrane region:
Role: III.B - Chaperones/Heat shock
GO terms:
- GO:0075136 - response to host (Uniprot)
- GO:0071456 - cellular response to hypoxia (Uniprot)
- GO:0052572 - response to host immune response (Uniprot)
- GO:0051409 - response to nitrosative stress (Uniprot)
- GO:0046777 - protein autophosphorylation (Uniprot)
- GO:0045926 - negative regulation of growth (Uniprot)
- GO:0044183 - protein binding involved in protein folding (Uniprot)
- GO:0044121 - growth of symbiont in host organelle (Uniprot)
- GO:0010039 - response to iron ion (Uniprot)
- GO:0009408 - response to heat (Uniprot)
- GO:0009267 - cellular response to starvation (Uniprot)
- GO:0006457 - protein folding (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
- GO:0005618 - cell wall (Uniprot)
- GO:0005576 - extracellular region (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0001666 - response to hypoxia (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
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:
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
2BYU	38%	TRITICUM AESTIVUM	Negative stain EM reconstruction of M.tuberculosis Acr1(Hsp 16.3) fitted with wheat sHSP dimer
6EWN	37%	Thermosynechococcus vulcanus	HspA from Thermosynechococcus vulcanus in the presence of 2M urea with initial stages of denaturation
5DS2	35%	Pisum sativum	Core domain of the class I small heat-shock protein HSP 18.1 from Pisum sativum

Links to additional information on hspX:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.924 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MATTLPVQRHPRSLFPEFSELFAAFPSFAGLRPTFDTRLMRLEDEMKEGRYEVRAELPGVDPDKDVDIMVRDGQLTIKAERTEQKDFDGRSEFAYGSFVR
TVSLPVGADEDDIKATYDKGILTVSVAVSEGKPTEKHIQIRSTN

(Nucleotide sequence available on KEGG)

Additional Information

also known as acr (alpha-crystallin), highly up-regulated in hypoxia (in dos regulon)

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; 3 non-insertions in a row out of 8 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 8 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 8 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 8 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 1 non-insertions in a row out of 8 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: 1.07
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

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv1985c (-) (Direct binding)
- Rv2745c (clgR) (Direct binding)
- Rv3133c (devR) (Direct binding)

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

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv0081 (-)
- Rv3133c (devR)
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv0576 (-)

TBCAP

Tubculosis Community Annotation Project (

Slayden et al., 2013

Rv2031c (hspX)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Regulatory Rv2069	ashwinigbhat	IEP		Co-expression (Functional linkage) R. Sun, PJ. Converse et al. Mycobacterium tuberculosis ECF sigma factor sigC is required for lethality in mice and for the conditional expression of a defined gene set. Mol. Microbiol. 2004
Interaction	Regulatory Rv2069	priti.priety	IEP		Co-expression (Functional linkage) R. Sun, PJ. Converse et al. Mycobacterium tuberculosis ECF sigma factor sigC is required for lethality in mice and for the conditional expression of a defined gene set. Mol. Microbiol. 2004
Citation	Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. M. Guo, H. Feng et al. Genome Res. 2009	priti.priety	IDA	19228590	affinity purification
Interaction	Signaling Rv3133c	priti.priety	IDA		affinity purification M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Citation	Recognition of stage-specific mycobacterial antigens differentiates between acute and latent infections with Mycobacterium tuberculosis. A. Demissie, EM. Leyten et al. Clin. Vaccine Immunol. 2006	priti.priety	IDA	16467323	affinity purification
Interaction	Signaling Rv3133c	priti.priety	IDA		affinity purification A. Demissie, EM. Leyten et al. Recognition of stage-specific mycobacterial antigens differentiates between acute and latent infections with Mycobacterium tuberculosis. Clin. Vaccine Immunol. 2006
Interaction	Regulatory Rv2032	priti.priety	IDA		Spectrophotometric analysis A. Purkayastha, LA. McCue et al. Identification of a Mycobacterium tuberculosis putative classical nitroreductase gene whose expression is coregulated with that of the acr aene within macrophages, in standing versus shaking cultures, and under low oxygen conditions. Infect. Immun. 2002
Interaction	Regulatory Rv2034	priti.priety	IDA		Bacterial one-hybrid system M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction	Regulatory Rv2007c	akankshajain.21	IEP		co-expression(Functional linkage) A. Kumar,JC. Toledo,RP. Patel,JR. Lancaster,AJ. Steyn Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor. Proc. Natl. Acad. Sci. U.S.A. 2007
Interaction	Regulatory Rv2007c	prabhakarsmail	IEP		co-expression(Functional linkage) A. Kumar,JC. Toledo,RP. Patel,JR. Lancaster,AJ. Steyn Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor. Proc. Natl. Acad. Sci. U.S.A. 2007
Interaction	Regulatory Rv1996	priyadarshinipriyanka2001	IEP		Co-expression (Functional linkage) MA. Florczyk, LA. McCue et al. A family of acr-coregulated Mycobacterium tuberculosis genes shares a common DNA motif and requires Rv3133c (dosR or devR) for expression. Infect. Immun. 2003
Interaction	Regulatory Rv1996	priyadarshinipriyanka2001	IEP		Co-expression (Functional linkage) authors,SM. Hingley-Wilson,KE. Lougheed,K. Ferguson,S. Leiva,HD. Williams Individual Mycobacterium tuberculosis universal stress protein homologues are dispensable in vitro. Tuberculosis (Edinb) 2010
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Structural Analysis J. Gonzalo-Asensio, S. Mostowy et al. PhoP: a missing piece in the intricate puzzle of Mycobacterium tuberculosis virulence. PLoS ONE 2008
Interaction	Regulatory Rv0757	singhpankaj2116	IEP		Spectrophotometric 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 Rv3416	yamir.moreno	IDA		One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction	RegulatedBy Rv3678c	yamir.moreno	IDA		One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction	RegulatedBy Rv3681c	yamir.moreno	IDA		One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction	RegulatedBy Rv3133c	yamir.moreno	IDA		One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction	RegulatedBy Rv0445c	yamir.moreno	IDA		One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction	RegulatedBy Rv2034	yamir.moreno	IDA		One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction	RegulatedBy Rv3133c	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
Interaction	RegulatedBy Rv2069	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

Property

Value

Creator

Evidence

PMID

Comment

Interaction

Regulatory Rv2069

ashwinigbhat

IEP

Co-expression (Functional linkage)
R. Sun, PJ. Converse et al. Mycobacterium tuberculosis ECF sigma factor sigC is required for lethality in mice and for the conditional expression of a defined gene set. Mol. Microbiol. 2004

Interaction

Regulatory Rv2069

priti.priety

IEP

Citation

Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. M. Guo, H. Feng et al. Genome Res. 2009

priti.priety

IDA

19228590

affinity purification

Interaction

Signaling Rv3133c

priti.priety

IDA

affinity purification
M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009

Citation

Recognition of stage-specific mycobacterial antigens differentiates between acute and latent infections with Mycobacterium tuberculosis. A. Demissie, EM. Leyten et al. Clin. Vaccine Immunol. 2006

priti.priety

IDA

16467323

affinity purification

Interaction

Signaling Rv3133c

priti.priety

IDA

affinity purification
A. Demissie, EM. Leyten et al. Recognition of stage-specific mycobacterial antigens differentiates between acute and latent infections with Mycobacterium tuberculosis. Clin. Vaccine Immunol. 2006

Interaction

Regulatory Rv2032

priti.priety

IDA

Spectrophotometric analysis
A. Purkayastha, LA. McCue et al. Identification of a Mycobacterium tuberculosis putative classical nitroreductase gene whose expression is coregulated with that of the acr aene within macrophages, in standing versus shaking cultures, and under low oxygen conditions. Infect. Immun. 2002

Interaction

Regulatory Rv2034

priti.priety

IDA

Bacterial one-hybrid system
M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009

Interaction

Regulatory Rv2007c

akankshajain.21

IEP

co-expression(Functional linkage)
A. Kumar,JC. Toledo,RP. Patel,JR. Lancaster,AJ. Steyn Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor. Proc. Natl. Acad. Sci. U.S.A. 2007

Interaction

Regulatory Rv2007c

prabhakarsmail

IEP

Interaction

Regulatory Rv1996

priyadarshinipriyanka2001

IEP

Co-expression (Functional linkage)
MA. Florczyk, LA. McCue et al. A family of acr-coregulated Mycobacterium tuberculosis genes shares a common DNA motif and requires Rv3133c (dosR or devR) for expression. Infect. Immun. 2003

Interaction

Regulatory Rv1996

priyadarshinipriyanka2001

IEP

Co-expression (Functional linkage)
authors,SM. Hingley-Wilson,KE. Lougheed,K. Ferguson,S. Leiva,HD. Williams Individual Mycobacterium tuberculosis universal stress protein homologues are dispensable in vitro. Tuberculosis (Edinb) 2010

Interaction

Regulatory Rv0757

singhpankaj2116

IEP

Structural Analysis
J. Gonzalo-Asensio, S. Mostowy et al. PhoP: a missing piece in the intricate puzzle of Mycobacterium tuberculosis virulence. PLoS ONE 2008

Interaction

Regulatory Rv0757

singhpankaj2116

IEP

Spectrophotometric
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 Rv3416

yamir.moreno

IDA

One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. .
M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009

Interaction

RegulatedBy Rv3678c

yamir.moreno

IDA

Interaction

RegulatedBy Rv3681c

yamir.moreno

IDA

Interaction

RegulatedBy Rv3133c

yamir.moreno

IDA

Interaction

RegulatedBy Rv0445c

yamir.moreno

IDA

Interaction

RegulatedBy Rv2034

yamir.moreno

IDA

Interaction

RegulatedBy Rv3133c

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

Interaction

RegulatedBy Rv2069

yamir.moreno

TAS

Comments