PAFA_MYCS2
ID PAFA_MYCS2 Reviewed; 452 AA.
AC A0QZ42; I7FNH9;
DT 10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Pup--protein ligase;
DE EC=6.3.1.19 {ECO:0000269|PubMed:20025664};
DE AltName: Full=Proteasome accessory factor A;
DE AltName: Full=Pup-conjugating enzyme;
GN Name=pafA; OrderedLocusNames=MSMEG_3890, MSMEI_3800;
OS Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (Mycobacterium
OS smegmatis).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycolicibacterium.
OX NCBI_TaxID=246196;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RA Fleischmann R.D., Dodson R.J., Haft D.H., Merkel J.S., Nelson W.C.,
RA Fraser C.M.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=17295914; DOI=10.1186/gb-2007-8-2-r20;
RA Deshayes C., Perrodou E., Gallien S., Euphrasie D., Schaeffer C.,
RA Van-Dorsselaer A., Poch O., Lecompte O., Reyrat J.-M.;
RT "Interrupted coding sequences in Mycobacterium smegmatis: authentic
RT mutations or sequencing errors?";
RL Genome Biol. 8:R20.1-R20.9(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=18955433; DOI=10.1101/gr.081901.108;
RA Gallien S., Perrodou E., Carapito C., Deshayes C., Reyrat J.-M.,
RA Van Dorsselaer A., Poch O., Schaeffer C., Lecompte O.;
RT "Ortho-proteogenomics: multiple proteomes investigation through orthology
RT and a new MS-based protocol.";
RL Genome Res. 19:128-135(2009).
RN [4]
RP FUNCTION AS A PUP LIGASE, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLU-11.
RX PubMed=20025664; DOI=10.1111/j.1365-2958.2009.07013.x;
RA Imkamp F., Rosenberger T., Striebel F., Keller P.M., Amstutz B., Sander P.,
RA Weber-Ban E.;
RT "Deletion of dop in Mycobacterium smegmatis abolishes pupylation of protein
RT substrates in vivo.";
RL Mol. Microbiol. 75:744-754(2010).
RN [5]
RP PUPYLATION.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=24986881; DOI=10.15252/embj.201387076;
RA Elharar Y., Roth Z., Hermelin I., Moon A., Peretz G., Shenkerman Y.,
RA Vishkautzan M., Khalaila I., Gur E.;
RT "Survival of mycobacteria depends on proteasome-mediated amino acid
RT recycling under nutrient limitation.";
RL EMBO J. 33:1802-1814(2014).
CC -!- FUNCTION: Catalyzes the covalent attachment of the prokaryotic
CC ubiquitin-like protein modifier Pup to the proteasomal substrate
CC proteins, thereby targeting them for proteasomal degradation. This
CC tagging system is termed pupylation. The ligation reaction likely
CC involves the side-chain carboxylate of the C-terminal glutamate of Pup
CC and the side-chain amino group of a substrate lysine.
CC {ECO:0000269|PubMed:20025664}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + [prokaryotic ubiquitin-like protein]-L-glutamate +
CC [protein]-L-lysine = ADP + phosphate + N(6)-([prokaryotic ubiquitin-
CC like protein]-gamma-L-glutamyl)-[protein]-L-lysine.; EC=6.3.1.19;
CC Evidence={ECO:0000269|PubMed:20025664};
CC -!- PATHWAY: Protein degradation; proteasomal Pup-dependent pathway.
CC -!- PATHWAY: Protein modification; protein pupylation.
CC -!- PTM: Pupylated at an undetermined lysine residue by the prokaryotic
CC ubiquitin-like protein Pup, which leads to its degradation by the
CC proteasome and thereby constitutes a negative auto-regulation.
CC {ECO:0000269|PubMed:24986881}.
CC -!- MISCELLANEOUS: The reaction mechanism probably proceeds via the
CC activation of Pup by phosphorylation of its C-terminal glutamate, which
CC is then subject to nucleophilic attack by the substrate lysine,
CC resulting in an isopeptide bond and the release of phosphate as a good
CC leaving group. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the Pup ligase/Pup deamidase family. Pup-
CC conjugating enzyme subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CP000480; ABK72318.1; -; Genomic_DNA.
DR EMBL; CP001663; AFP40258.1; -; Genomic_DNA.
DR RefSeq; WP_011729397.1; NC_018289.1.
DR RefSeq; YP_888180.1; NC_008596.1.
DR AlphaFoldDB; A0QZ42; -.
DR SMR; A0QZ42; -.
DR STRING; 246196.MSMEI_3800; -.
DR PRIDE; A0QZ42; -.
DR EnsemblBacteria; ABK72318; ABK72318; MSMEG_3890.
DR EnsemblBacteria; AFP40258; AFP40258; MSMEI_3800.
DR GeneID; 66735257; -.
DR KEGG; msg:MSMEI_3800; -.
DR KEGG; msm:MSMEG_3890; -.
DR PATRIC; fig|246196.19.peg.3830; -.
DR eggNOG; COG0638; Bacteria.
DR OMA; CVSQRAE; -.
DR BRENDA; 6.3.1.19; 3512.
DR UniPathway; UPA00997; -.
DR UniPathway; UPA00998; -.
DR Proteomes; UP000000757; Chromosome.
DR Proteomes; UP000006158; Chromosome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0016879; F:ligase activity, forming carbon-nitrogen bonds; IEA:InterPro.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0019787; F:ubiquitin-like protein transferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0019941; P:modification-dependent protein catabolic process; IEA:UniProtKB-UniRule.
DR GO; GO:0010498; P:proteasomal protein catabolic process; IEA:UniProtKB-UniRule.
DR GO; GO:0070490; P:protein pupylation; IEA:UniProtKB-UniRule.
DR HAMAP; MF_02111; Pup_ligase; 1.
DR InterPro; IPR022279; Pup_ligase.
DR InterPro; IPR004347; Pup_ligase/deamidase.
DR PANTHER; PTHR42307; PTHR42307; 1.
DR Pfam; PF03136; Pup_ligase; 1.
DR PIRSF; PIRSF018077; UCP018077; 1.
DR TIGRFAMs; TIGR03686; pupylate_PafA; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Ligase; Magnesium; Metal-binding; Nucleotide-binding;
KW Reference proteome; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..452
FT /note="Pup--protein ligase"
FT /id="PRO_0000395931"
FT ACT_SITE 57
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 9
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 53
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 55
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 63
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 66
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 419
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MUTAGEN 11
FT /note="E->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:20025664"
SQ SEQUENCE 452 AA; 51373 MW; 4990E431CFA492B8 CRC64;
MQRRIMGIET EFGVTCTFHG HRRLSPDEVA RYLFRRVVSW GRSSNVFLRN GARLYLDVGS
HPEYATAECD NLIQLVTHDR AGERVLEDLL IDAEQRLADE GIGGDIYLFK NNTDSAGNSY
GCHENYLIVR AGEFSRISDV LLPFLVTRQL ICGAGKVLQT PKAATFCLSQ RAEHIWEGVS
SATTRSRPII NTRDEPHADA EKYRRLHVIV GDSNMCEATT MLKVGTASLV LEMIEAGVPF
RDFSLDNPIR AIREVSHDLT GRRPVRLAGG RQASALDIQR EYYSRAVEYL QSREPNTQIE
QVVDLWGRQL DAVESQDFAK VDTEIDWVIK RKLFQRYQDR YNMELSDPKI SQLDLAYHDI
KRGRGVFDLL QRKGLAARIT TDEEIDAAVT TPPQTTRAKL RGEFISAAQE AGRDFTVDWV
HLKLNDQAQR TVLCKDPFRS VDERVKRLIA SM
