DOP_MYCTU
ID DOP_MYCTU Reviewed; 505 AA.
AC P9WNU9; L0TBE2; O33247; Q8VJQ0;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 46.
DE RecName: Full=Pup deamidase/depupylase;
DE EC=3.4.-.-;
DE EC=3.5.1.119 {ECO:0000269|PubMed:19448618, ECO:0000269|PubMed:20705495};
DE AltName: Full=Deamidase of protein Pup;
GN Name=dop; Synonyms=pafD; OrderedLocusNames=Rv2112c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP FUNCTION AS PUP DEAMIDASE, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH
RP PUP, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19448618; DOI=10.1038/nsmb.1597;
RA Striebel F., Imkamp F., Sutter M., Steiner M., Mamedov A., Weber-Ban E.;
RT "Bacterial ubiquitin-like modifier Pup is deamidated and conjugated to
RT substrates by distinct but homologous enzymes.";
RL Nat. Struct. Mol. Biol. 16:647-651(2009).
RN [3]
RP FUNCTION AS DEPUPYLASE, CATALYTIC ACTIVITY, COFACTOR, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF GLU-10.
RX PubMed=20705495; DOI=10.1016/j.molcel.2010.07.019;
RA Burns K.E., Cerda-Maira F.A., Wang T., Li H., Bishai W.R., Darwin K.H.;
RT "'Depupylation' of prokaryotic ubiquitin-like protein from mycobacterial
RT proteasome substrates.";
RL Mol. Cell 39:821-827(2010).
RN [4]
RP FUNCTION IN PUP RECYCLING, ROLE IN PUPYLATION; RESISTANCE TO RNI AND
RP VIRULENCE, DISRUPTION PHENOTYPE, INTERACTION WITH PUP, AND MUTAGENESIS OF
RP GLU-8; GLU-10; ASP-95; HIS-96; GLU-100; ARG-206 AND ARG-222.
RX PubMed=20636328; DOI=10.1111/j.1365-2958.2010.07276.x;
RA Cerda-Maira F.A., Pearce M.J., Fuortes M., Bishai W.R., Hubbard S.R.,
RA Darwin K.H.;
RT "Molecular analysis of the prokaryotic ubiquitin-like protein (Pup)
RT conjugation pathway in Mycobacterium tuberculosis.";
RL Mol. Microbiol. 77:1123-1135(2010).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
CC -!- FUNCTION: Specifically catalyzes the deamidation of the C-terminal
CC glutamine of the prokaryotic ubiquitin-like protein Pup to glutamate,
CC thereby rendering Pup competent for conjugation. Also displays
CC depupylase (DPUP) activity, removing conjugated Pup from target
CC proteins; is thus involved in the recycling of Pup and may function
CC similarly to deubiquitinases (DUBs) in eukaryotes to prevent or promote
CC proteasomal degradation of certain proteins.
CC {ECO:0000269|PubMed:19448618, ECO:0000269|PubMed:20636328,
CC ECO:0000269|PubMed:20705495}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[prokaryotic ubiquitin-like protein]-C-terminal-L-glutamine +
CC H2O = [prokaryotic ubiquitin-like protein]-C-terminal-L-glutamate +
CC NH4(+); Xref=Rhea:RHEA:47952, Rhea:RHEA-COMP:11959, Rhea:RHEA-
CC COMP:11960, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938, ChEBI:CHEBI:78525,
CC ChEBI:CHEBI:88115; EC=3.5.1.119;
CC Evidence={ECO:0000269|PubMed:19448618, ECO:0000269|PubMed:20705495};
CC -!- COFACTOR:
CC Name=ATP; Xref=ChEBI:CHEBI:30616;
CC Evidence={ECO:0000269|PubMed:19448618, ECO:0000269|PubMed:20705495};
CC Note=ATP is required for the deamidation and depupylation reactions but
CC is not hydrolyzed during the reactions. {ECO:0000269|PubMed:19448618,
CC ECO:0000269|PubMed:20705495};
CC -!- PATHWAY: Protein degradation; proteasomal Pup-dependent pathway.
CC -!- SUBUNIT: Interacts with the prokaryotic ubiquitin-like protein Pup.
CC {ECO:0000269|PubMed:19448618, ECO:0000269|PubMed:20636328}.
CC -!- DISRUPTION PHENOTYPE: Disruption of dop abolishes pupylation. Cells
CC lacking this gene also become hypersensitive to reactive nitrogen
CC intermediates (RNI) and are severely attenuated for survival and growth
CC in mice. They also cannot depupylate proteasome substrates.
CC {ECO:0000269|PubMed:20636328, ECO:0000269|PubMed:20705495}.
CC -!- SIMILARITY: Belongs to the Pup ligase/Pup deamidase family. Pup
CC deamidase subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CCP44887.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL123456; CCP44887.1; ALT_INIT; Genomic_DNA.
DR PIR; C70512; C70512.
DR RefSeq; NP_216628.1; NC_000962.3.
DR RefSeq; WP_003411029.1; NC_018143.2.
DR AlphaFoldDB; P9WNU9; -.
DR SMR; P9WNU9; -.
DR STRING; 83332.Rv2112c; -.
DR PaxDb; P9WNU9; -.
DR GeneID; 888290; -.
DR KEGG; mtu:Rv2112c; -.
DR PATRIC; fig|83332.12.peg.2359; -.
DR TubercuList; Rv2112c; -.
DR eggNOG; COG4122; Bacteria.
DR OMA; YFRGRCL; -.
DR BioCyc; MetaCyc:G185E-6318-MON; -.
DR BRENDA; 3.5.1.119; 3445.
DR UniPathway; UPA00997; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0016811; F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008233; F:peptidase activity; IDA:MTBBASE.
DR GO; GO:0019941; P:modification-dependent protein catabolic process; IDA:MTBBASE.
DR GO; GO:0010498; P:proteasomal protein catabolic process; IDA:MTBBASE.
DR GO; GO:0070490; P:protein pupylation; IDA:UniProtKB.
DR InterPro; IPR022366; Pup_deamidase.
DR InterPro; IPR004347; Pup_ligase/deamidase.
DR PANTHER; PTHR42307; PTHR42307; 1.
DR Pfam; PF03136; Pup_ligase; 1.
DR PIRSF; PIRSF018077; UCP018077; 1.
DR TIGRFAMs; TIGR03688; pupylate_PafA2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Hydrolase; Magnesium; Metal-binding; Nucleotide-binding;
KW Reference proteome; Virulence.
FT CHAIN 1..505
FT /note="Pup deamidase/depupylase"
FT /id="PRO_0000383480"
FT ACT_SITE 95
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 6..10
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 8
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 8
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 93
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 100
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 102..103
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 156
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 158
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 240
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 242
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MUTAGEN 8
FT /note="E->A: Abolishes pupylation."
FT /evidence="ECO:0000269|PubMed:20636328"
FT MUTAGEN 10
FT /note="E->A: Abolishes pupylation and depupylase activity."
FT /evidence="ECO:0000269|PubMed:20636328,
FT ECO:0000269|PubMed:20705495"
FT MUTAGEN 95
FT /note="D->N: Abolishes pupylation."
FT /evidence="ECO:0000269|PubMed:20636328"
FT MUTAGEN 96
FT /note="H->V: Abolishes pupylation."
FT /evidence="ECO:0000269|PubMed:20636328"
FT MUTAGEN 100
FT /note="E->A: Abolishes pupylation."
FT /evidence="ECO:0000269|PubMed:20636328"
FT MUTAGEN 206
FT /note="R->A: Abolishes pupylation."
FT /evidence="ECO:0000269|PubMed:20636328"
FT MUTAGEN 222
FT /note="R->A: Abolishes pupylation."
FT /evidence="ECO:0000269|PubMed:20636328"
SQ SEQUENCE 505 AA; 55179 MW; 963CF8592FC182EB CRC64;
MQRIIGTEVE YGISSPSDPT ANPILTSTQA VLAYAAAAGI QRAKRTRWDY EVESPLRDAR
GFDLSRSAGP PPVVDADEVG AANMILTNGA RLYVDHAHPE YSAPECTDPL DAVIWDKAGE
RVMEAAARHV ASVPGAAKLQ LYKNNVDGKG ASYGSHENYL MSRQTPFSAI ITGLTPFLVS
RQVVTGSGRV GIGPSGDEPG FQLSQRSDYI EVEVGLETTL KRGIINTRDE PHADADRYRR
LHVIIGDANL AETSTYLKLG TTALVLDLIE EGPAHAIDLT DLALARPVHA VHAISRDPSL
RATVALADGR ELTGLALQRI YLDRVAKLVD SRDPDPRAAD IVETWAHVLD QLERDPMDCA
ELLDWPAKLR LLDGFRQREN LSWSAPRLHL VDLQYSDVRL DKGLYNRLVA RGSMKRLVTE
HQVLSAVENP PTDTRAYFRG ECLRRFGADI AAASWDSVIF DLGGDSLVRI PTLEPLRGSK
AHVGALLDSV DSAVELVEQL TAEPR
