Rv2111c (pup)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: prokaryotic ubiquitin-like protein Pup
- REFSEQ: hypothetical protein
- PATRIC: Prokaryotic ubiquitin-like protein Pup
- TUBERCULIST: Prokaryotic ubiquitin-like protein Pup
- NCBI: Prokaryotic ubiquitin-like protein Pup
- updated information (H37Rv4):
  - gene name: pup
  - function:
  - reference:
Type: Not Target
Start: 2370598
End: 2370792
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0070628 - proteasome binding (Uniprot)
- GO:0070490 - protein pupylation (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0031386 - protein tag (Uniprot)
- GO:0019941 - modification-dependent protein catabolic process (Uniprot)
- GO:0010498 - proteasomal protein catabolic process (Uniprot)
- GO:0005515 - protein binding (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: 3m9d, 3m91
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
3M9D	98%	Mycobacterium tuberculosis	Crystal structure of the prokaryotic ubiquintin-like protein Pup complexed with the hexameric proteasomal ATPase Mpa which includes the amino terminal coiled coil domain and the inter domain
3M91	97%	Mycobacterium tuberculosis	Crystal structure of the prokaryotic ubiquitin-like protein (Pup) complexed with the amino terminal coiled coil of the Mycobacterium tuberculosis proteasomal ATPase Mpa
4BJR	76%	CORYNEBACTERIUM GLUTAMICUM	Crystal structure of the complex between Prokaryotic Ubiquitin-like Protein Pup and its Ligase PafA

Links to additional information on pup:
- KEGG - nucleotide and amino acid sequences of gene
- BioCyc
- Systems Biology
- Mycobrowser
- PATRIC
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -4.791 (from Jeremy Rock's lab)

Amino Acid Sequence

MAQEQTKRGGGGGDDDDIAGSTAAGQERREKLTEETDDLLDEIDDVLEENAEDFVRAYVQKGGQ

(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; 1 non-insertions in a row out of 1 sites
Too-Short	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: -1.000000; 1 non-insertions in a row out of 1 sites
Too-Short	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: -1.000000; 1 non-insertions in a row out of 1 sites
Too-Short	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: -1.000000; 1 non-insertions in a row out of 1 sites
Too-Short	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: -1.000000; 1 non-insertions in a row out of 1 sites
Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.09
Uncertain	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:
- Rv0260c (-)

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:
- Not upregulated by other genes.
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Rv0260c (-)

TBCAP

Tubculosis Community Annotation Project (

Slayden et al., 2013

Rv2111c (pup)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Translation Rv2859c	akvsangli	IPI		Affinity purification (Physical interaction) RA. Festa,F. McAllister,MJ. Pearce,J. Mintseris,KE. Burns,SP. Gygi,KH. Darwin Prokayrotic ubiquitin-like protein (Pup) proteome of Mycobacterium tuberculosis. PLoS ONE 2010
Interaction	Regulatory Rv2115c	sourish10	IEP		Structural Analysis KH. Darwin, S. Ehrt et al. The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide. Science 2003
Interaction	Regulatory Rv2115c	sourish10	IEP		Structural Analysis authors,DM. Ritchie,JN. Sierchio,RJ. Capetola,ME. Rosenthale SRS-A mediated bronchospasm by pharmacologic modification of lung anaphylaxis in vivo. Agents Actions 1981
Interaction	Regulatory Rv2115c	sourish10	IEP		Spectrophotometric Analysis authors,DM. Ritchie,JN. Sierchio,RJ. Capetola,ME. Rosenthale SRS-A mediated bronchospasm by pharmacologic modification of lung anaphylaxis in vivo. Agents Actions 1981
Interaction	Regulatory Rv2115c	sourish10	IEP		Structural Analysis M. Sutter,F. Striebel,FF. Damberger,FH. Allain,E. Weber-Ban A distinct structural region of the prokaryotic ubiquitin-like protein (Pup) is recognized by the N-terminal domain of the proteasomal ATPase Mpa. FEBS Lett. 2009
Interaction	Regulatory Rv2115c	sourish10	IEP		Structural Analysis KH. Darwin, G. Lin et al. Characterization of a Mycobacterium tuberculosis proteasomal ATPase homologue. Mol. Microbiol. 2005
Interaction	Regulatory Rv2115c	sourish10	IEP		Spectrophotometric Analysis M. Sutter,F. Striebel,FF. Damberger,FH. Allain,E. Weber-Ban A distinct structural region of the prokaryotic ubiquitin-like protein (Pup) is recognized by the N-terminal domain of the proteasomal ATPase Mpa. FEBS Lett. 2009
Interaction	Regulatory Rv2115c	sourish10	IEP		Spectrophotometric Analysis KH. Darwin, G. Lin et al. Characterization of a Mycobacterium tuberculosis proteasomal ATPase homologue. Mol. Microbiol. 2005
Interaction	Regulatory Rv2115c	sourish10	IEP		Spectrophotometric Analysis KH. Darwin, S. Ehrt et al. The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide. Science 2003
Interaction	Regulatory Rv2115c	ahal4789	IEP		Structural Analysis KH. Darwin, G. Lin et al. Characterization of a Mycobacterium tuberculosis proteasomal ATPase homologue. Mol. Microbiol. 2005
Interaction	Regulatory Rv2115c	ahal4789	IEP		Structural Analysis KH. Darwin, S. Ehrt et al. The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide. Science 2003
Interaction	Regulatory Rv2115c	ahal4789	IEP		Structural Analysis authors,DM. Ritchie,JN. Sierchio,RJ. Capetola,ME. Rosenthale SRS-A mediated bronchospasm by pharmacologic modification of lung anaphylaxis in vivo. Agents Actions 1981
Interaction	Regulatory Rv2115c	ahal4789	IEP		Spectrophotometric Analysis KH. Darwin, S. Ehrt et al. The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide. Science 2003
Interaction	Regulatory Rv2115c	ahal4789	IEP		Spectrophotometric Analysis authors,DM. Ritchie,JN. Sierchio,RJ. Capetola,ME. Rosenthale SRS-A mediated bronchospasm by pharmacologic modification of lung anaphylaxis in vivo. Agents Actions 1981
Interaction	Regulatory Rv2115c	ahal4789	IEP		Structural Analysis M. Sutter,F. Striebel,FF. Damberger,FH. Allain,E. Weber-Ban A distinct structural region of the prokaryotic ubiquitin-like protein (Pup) is recognized by the N-terminal domain of the proteasomal ATPase Mpa. FEBS Lett. 2009
Interaction	Regulatory Rv2115c	ahal4789	IEP		Spectrophotometric Analysis M. Sutter,F. Striebel,FF. Damberger,FH. Allain,E. Weber-Ban A distinct structural region of the prokaryotic ubiquitin-like protein (Pup) is recognized by the N-terminal domain of the proteasomal ATPase Mpa. FEBS Lett. 2009
Interaction	Regulatory Rv2115c	ahal4789	IEP		Spectrophotometric Analysis KH. Darwin, G. Lin et al. Characterization of a Mycobacterium tuberculosis proteasomal ATPase homologue. Mol. Microbiol. 2005
Interaction	Activation Rv2097c	priyadarshinipriyanka2001	IEP		Affinity purification (Physical interaction) F. Imkamp,T. Rosenberger,F. Striebel,PM. Keller,B. Amstutz,P. Sander,E. Weber-Ban Deletion of dop in Mycobacterium smegmatis abolishes pupylation of protein substrates in vivo. Mol. Microbiol. 2010
Citation	Bacterial ubiquitin-like modifier Pup is deamidated and conjugated to substrates by distinct but homologous enzymes. F. Striebel, F. Imkamp et al. Nat. Struct. Mol. Biol. 2009	priyadarshinipriyanka2001	IEP	19448618	Affinity purification (Physical interaction)
Interaction	Activation Rv2097c	priyadarshinipriyanka2001	IEP		Affinity purification (Physical interaction) F. Striebel, F. Imkamp et al. Bacterial ubiquitin-like modifier Pup is deamidated and conjugated to substrates by distinct but homologous enzymes. Nat. Struct. Mol. Biol. 2009
Citation	Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium tuberculosis. MJ. Pearce, J. Mintseris et al. Science 2008	priyadarshinipriyanka2001	IEP	18832610	Affinity purification (Physical interaction)
Interaction	Activation Rv2097c	priyadarshinipriyanka2001	IEP		Affinity purification (Physical interaction) MJ. Pearce, J. Mintseris et al. Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium tuberculosis. Science 2008
Citation	Roles of SigB and SigF in the Mycobacterium tuberculosis sigma factor network. JH. Lee, PC. Karakousis et al. J. Bacteriol. 2008	priyadarshinipriyanka2001	NAS	17993538	Co-expression (Functional linkage)
Interaction	Regulatory Rv2710	priyadarshinipriyanka2001	NAS		Co-expression (Functional linkage) JH. Lee, PC. Karakousis et al. Roles of SigB and SigF in the Mycobacterium tuberculosis sigma factor network. J. Bacteriol. 2008
Citation	Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium tuberculosis. MJ. Pearce, J. Mintseris et al. Science 2008	priyadarshinipriyanka2001	IEP	18832610	Affinity purification (Physical interaction)
Interaction	PhysicalInteraction Rv2243	priyadarshinipriyanka2001	IEP		Affinity purification (Physical interaction) MJ. Pearce, J. Mintseris et al. Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium tuberculosis. Science 2008
Citation	Deletion of dop in Mycobacterium smegmatis abolishes pupylation of protein substrates in vivo. F. Imkamp,T. Rosenberger,F. Striebel,PM. Keller,B. Amstutz,P. Sander,E. Weber-Ban Mol. Microbiol. 2010	priyadarshinipriyanka2001	IEP	20025664	Affinity purification (Physical interaction)
Interaction	RegulatedBy Rv1221	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.. R. Manganelli, MI. Voskuil et al. The Mycobacterium tuberculosis ECF sigma factor sigmaE: role in global gene expression and survival in macrophages. Mol. Microbiol. 2001

Property

Value

Creator

Evidence

PMID

Comment

Interaction

Translation Rv2859c

akvsangli

IPI

Affinity purification (Physical interaction)
RA. Festa,F. McAllister,MJ. Pearce,J. Mintseris,KE. Burns,SP. Gygi,KH. Darwin Prokayrotic ubiquitin-like protein (Pup) proteome of Mycobacterium tuberculosis. PLoS ONE 2010

Interaction

Regulatory Rv2115c

sourish10

IEP

Structural Analysis
KH. Darwin, S. Ehrt et al. The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide. Science 2003

Interaction

Regulatory Rv2115c

sourish10

IEP

Structural Analysis
authors,DM. Ritchie,JN. Sierchio,RJ. Capetola,ME. Rosenthale SRS-A mediated bronchospasm by pharmacologic modification of lung anaphylaxis in vivo. Agents Actions 1981

Interaction

Regulatory Rv2115c

sourish10

IEP

Spectrophotometric Analysis
authors,DM. Ritchie,JN. Sierchio,RJ. Capetola,ME. Rosenthale SRS-A mediated bronchospasm by pharmacologic modification of lung anaphylaxis in vivo. Agents Actions 1981

Interaction

Regulatory Rv2115c

sourish10

IEP

Structural Analysis
M. Sutter,F. Striebel,FF. Damberger,FH. Allain,E. Weber-Ban A distinct structural region of the prokaryotic ubiquitin-like protein (Pup) is recognized by the N-terminal domain of the proteasomal ATPase Mpa. FEBS Lett. 2009

Interaction

Regulatory Rv2115c

sourish10

IEP

Structural Analysis
KH. Darwin, G. Lin et al. Characterization of a Mycobacterium tuberculosis proteasomal ATPase homologue. Mol. Microbiol. 2005

Interaction

Regulatory Rv2115c

sourish10

IEP

Spectrophotometric Analysis
M. Sutter,F. Striebel,FF. Damberger,FH. Allain,E. Weber-Ban A distinct structural region of the prokaryotic ubiquitin-like protein (Pup) is recognized by the N-terminal domain of the proteasomal ATPase Mpa. FEBS Lett. 2009

Interaction

Regulatory Rv2115c

sourish10

IEP

Spectrophotometric Analysis
KH. Darwin, G. Lin et al. Characterization of a Mycobacterium tuberculosis proteasomal ATPase homologue. Mol. Microbiol. 2005

Interaction

Regulatory Rv2115c

sourish10

IEP

Spectrophotometric Analysis
KH. Darwin, S. Ehrt et al. The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide. Science 2003

Interaction

Regulatory Rv2115c

ahal4789

IEP

Structural Analysis
KH. Darwin, G. Lin et al. Characterization of a Mycobacterium tuberculosis proteasomal ATPase homologue. Mol. Microbiol. 2005

Interaction

Regulatory Rv2115c

ahal4789

IEP

Structural Analysis
KH. Darwin, S. Ehrt et al. The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide. Science 2003

Interaction

Regulatory Rv2115c

ahal4789

IEP

Structural Analysis
authors,DM. Ritchie,JN. Sierchio,RJ. Capetola,ME. Rosenthale SRS-A mediated bronchospasm by pharmacologic modification of lung anaphylaxis in vivo. Agents Actions 1981

Interaction

Regulatory Rv2115c

ahal4789

IEP

Spectrophotometric Analysis
KH. Darwin, S. Ehrt et al. The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide. Science 2003

Interaction

Regulatory Rv2115c

ahal4789

IEP

Spectrophotometric Analysis
authors,DM. Ritchie,JN. Sierchio,RJ. Capetola,ME. Rosenthale SRS-A mediated bronchospasm by pharmacologic modification of lung anaphylaxis in vivo. Agents Actions 1981

Interaction

Regulatory Rv2115c

ahal4789

IEP

Interaction

Regulatory Rv2115c

ahal4789

IEP

Interaction

Regulatory Rv2115c

ahal4789

IEP

Spectrophotometric Analysis
KH. Darwin, G. Lin et al. Characterization of a Mycobacterium tuberculosis proteasomal ATPase homologue. Mol. Microbiol. 2005

Interaction

Activation Rv2097c

priyadarshinipriyanka2001

IEP

Affinity purification (Physical interaction)
F. Imkamp,T. Rosenberger,F. Striebel,PM. Keller,B. Amstutz,P. Sander,E. Weber-Ban Deletion of dop in Mycobacterium smegmatis abolishes pupylation of protein substrates in vivo. Mol. Microbiol. 2010

Citation

Bacterial ubiquitin-like modifier Pup is deamidated and conjugated to substrates by distinct but homologous enzymes. F. Striebel, F. Imkamp et al. Nat. Struct. Mol. Biol. 2009

priyadarshinipriyanka2001

IEP

19448618

Affinity purification (Physical interaction)

Interaction

Activation Rv2097c

priyadarshinipriyanka2001

IEP

Affinity purification (Physical interaction)
F. Striebel, F. Imkamp et al. Bacterial ubiquitin-like modifier Pup is deamidated and conjugated to substrates by distinct but homologous enzymes. Nat. Struct. Mol. Biol. 2009

Citation

Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium tuberculosis. MJ. Pearce, J. Mintseris et al. Science 2008

priyadarshinipriyanka2001

IEP

18832610

Affinity purification (Physical interaction)

Interaction

Activation Rv2097c

priyadarshinipriyanka2001

IEP

Affinity purification (Physical interaction)
MJ. Pearce, J. Mintseris et al. Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium tuberculosis. Science 2008

Citation

Roles of SigB and SigF in the Mycobacterium tuberculosis sigma factor network. JH. Lee, PC. Karakousis et al. J. Bacteriol. 2008

priyadarshinipriyanka2001

NAS

17993538

Co-expression (Functional linkage)

Interaction

Regulatory Rv2710

priyadarshinipriyanka2001

NAS

Co-expression (Functional linkage)
JH. Lee, PC. Karakousis et al. Roles of SigB and SigF in the Mycobacterium tuberculosis sigma factor network. J. Bacteriol. 2008

Citation

Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium tuberculosis. MJ. Pearce, J. Mintseris et al. Science 2008

priyadarshinipriyanka2001

IEP

18832610

Affinity purification (Physical interaction)

Interaction

PhysicalInteraction Rv2243

priyadarshinipriyanka2001

IEP

Affinity purification (Physical interaction)
MJ. Pearce, J. Mintseris et al. Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium tuberculosis. Science 2008

Citation

Deletion of dop in Mycobacterium smegmatis abolishes pupylation of protein substrates in vivo. F. Imkamp,T. Rosenberger,F. Striebel,PM. Keller,B. Amstutz,P. Sander,E. Weber-Ban Mol. Microbiol. 2010

priyadarshinipriyanka2001

IEP

20025664

Affinity purification (Physical interaction)

Interaction

RegulatedBy Rv1221

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..
R. Manganelli, MI. Voskuil et al. The Mycobacterium tuberculosis ECF sigma factor sigmaE: role in global gene expression and survival in macrophages. Mol. Microbiol. 2001

Comments