PUP_MYCTU
ID PUP_MYCTU Reviewed; 64 AA.
AC P9WHN5; B6DAC1; L0TBK1; O33246; Q7D7I1;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=Prokaryotic ubiquitin-like protein Pup;
DE AltName: Full=Bacterial ubiquitin-like modifier;
GN Name=pup; OrderedLocusNames=Rv2111c;
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 [GENOMIC DNA], FUNCTION, ROLE IN THE PROTEASOME
RP DEGRADATION PATHWAY, CROSS-LINK SITE TO PROTEASOME SUBSTRATES, AND
RP INTERACTION WITH MPA.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18832610; DOI=10.1126/science.1163885;
RA Pearce M.J., Mintseris J., Ferreyra J., Gygi S.P., Darwin K.H.;
RT "Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium
RT tuberculosis.";
RL Science 322:1104-1107(2008).
RN [2]
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 [3]
RP PROTEIN SUBSTRATES.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17082771; DOI=10.1038/sj.emboj.7601405;
RA Pearce M.J., Arora P., Festa R.A., Butler-Wu S.M., Gokhale R.S.,
RA Darwin K.H.;
RT "Identification of substrates of the Mycobacterium tuberculosis
RT proteasome.";
RL EMBO J. 25:5423-5432(2006).
RN [4]
RP INTERACTION WITH MPA, DOMAIN, AND SPECTROSCOPIC STUDIES.
RX PubMed=19580545; DOI=10.1042/bj20090738;
RA Liao S., Shang Q., Zhang X., Zhang J., Xu C., Tu X.;
RT "Pup, a prokaryotic ubiquitin-like protein, is an intrinsically disordered
RT protein.";
RL Biochem. J. 422:207-215(2009).
RN [5]
RP INTERACTION WITH MPA, STOICHIOMETRY OF THE PUP-MPA COMPLEX, AND DOMAIN.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19761766; DOI=10.1016/j.febslet.2009.09.020;
RA Sutter M., Striebel F., Damberger F.F., Allain F.H., Weber-Ban E.;
RT "A distinct structural region of the prokaryotic ubiquitin-like protein
RT (Pup) is recognized by the N-terminal domain of the proteasomal ATPase
RT Mpa.";
RL FEBS Lett. 583:3151-3157(2009).
RN [6]
RP INTERACTION WITH MPA, STOICHIOMETRY OF THE PUP-MPA COMPLEX, DOMAIN, AND
RP SPECTROSCOPIC STUDIES.
RX PubMed=19607839; DOI=10.1016/j.jmb.2009.07.018;
RA Chen X., Solomon W.C., Kang Y., Cerda-Maira F., Darwin K.H., Walters K.J.;
RT "Prokaryotic ubiquitin-like protein Pup is intrinsically disordered.";
RL J. Mol. Biol. 392:208-217(2009).
RN [7]
RP DEAMIDATION AT GLN-64 BY DOP, ROLE IN THE PROTEASOME DEGRADATION PATHWAY,
RP AND INTERACTION WITH MPA; PAFA AND DOP.
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 [8]
RP DOMAIN, AND RECONSTITUTION OF THE PROTEASOME DEGRADATION PATHWAY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20203624; DOI=10.1038/emboj.2010.23;
RA Striebel F., Hunkeler M., Summer H., Weber-Ban E.;
RT "The mycobacterial Mpa-proteasome unfolds and degrades pupylated substrates
RT by engaging Pup's N-terminus.";
RL EMBO J. 29:1262-1271(2010).
RN [9]
RP CROSS-LINK.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20355727; DOI=10.1021/ja910546x;
RA Sutter M., Damberger F.F., Imkamp F., Allain F.H., Weber-Ban E.;
RT "Prokaryotic ubiquitin-like protein (Pup) is coupled to substrates via the
RT side chain of its C-terminal glutamate.";
RL J. Am. Chem. Soc. 132:5610-5612(2010).
RN [10]
RP FUNCTION IN THE PROTEASOME DEGRADATION PATHWAY, AND DOMAIN.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20233925; DOI=10.1128/jb.01639-09;
RA Burns K.E., Pearce M.J., Darwin K.H.;
RT "Prokaryotic ubiquitin-like protein provides a two-part degron to
RT Mycobacterium proteasome substrates.";
RL J. Bacteriol. 192:2933-2935(2010).
RN [11]
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: Protein modifier that is covalently attached to lysine
CC residues of substrate proteins, thereby targeting them for proteasomal
CC degradation. The tagging system is termed pupylation. Among the
CC identified substrates are the FabD, PanB and Mpa proteins.
CC {ECO:0000269|PubMed:18832610, ECO:0000269|PubMed:19448618,
CC ECO:0000269|PubMed:20233925}.
CC -!- PATHWAY: Protein degradation; proteasomal Pup-dependent pathway.
CC -!- SUBUNIT: Strongly interacts with the proteasome-associated ATPase ARC
CC (Mpa) through a hydrophobic interface; the interacting region of Pup
CC lies in its C-terminal half. There is one Pup binding site per Mpa
CC hexamer ring; the K(D) measured is about 3.8 uM.
CC {ECO:0000269|PubMed:18832610, ECO:0000269|PubMed:19448618,
CC ECO:0000269|PubMed:19580545, ECO:0000269|PubMed:19607839,
CC ECO:0000269|PubMed:19761766}.
CC -!- INTERACTION:
CC P9WHN5; P9WQN5: mpa; NbExp=6; IntAct=EBI-7241023, EBI-7241067;
CC -!- DOMAIN: The N-terminal unstructured half of Pup provides a signal
CC required to initiate unfolding and degradation by the proteasome but is
CC not needed for pupylation, while the C-terminal helical half of Pup
CC interacts with Mpa to target proteins to the proteasome.
CC {ECO:0000269|PubMed:19580545, ECO:0000269|PubMed:19607839,
CC ECO:0000269|PubMed:19761766, ECO:0000269|PubMed:20203624,
CC ECO:0000269|PubMed:20233925}.
CC -!- PTM: Is modified by deamidation of its C-terminal glutamine to
CC glutamate by the deamidase Dop, a prerequisite to the subsequent
CC pupylation process. {ECO:0000269|PubMed:19448618}.
CC -!- MISCELLANEOUS: The glutamate must be located at the C-terminal position
CC to be coupled to the lysine substrate.
CC -!- MISCELLANEOUS: Fusion of Pup to a nonproteasome substrate targets it
CC for proteasomal degradation in an Mpa- and proteasome-dependent manner.
CC -!- SIMILARITY: Belongs to the prokaryotic ubiquitin-like protein family.
CC {ECO:0000305}.
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DR EMBL; EU914921; ACI25441.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP44886.1; -; Genomic_DNA.
DR PIR; B70512; B70512.
DR RefSeq; NP_216627.1; NC_000962.3.
DR RefSeq; WP_003411026.1; NZ_NVQJ01000058.1.
DR PDB; 3M91; X-ray; 1.80 A; B/D=21-63.
DR PDB; 3M9D; X-ray; 4.50 A; G/H/I/P/Q/R=1-64.
DR PDB; 7PXC; EM; 3.84 A; G=1-64.
DR PDBsum; 3M91; -.
DR PDBsum; 3M9D; -.
DR PDBsum; 7PXC; -.
DR AlphaFoldDB; P9WHN5; -.
DR SMR; P9WHN5; -.
DR IntAct; P9WHN5; 1.
DR MINT; P9WHN5; -.
DR STRING; 83332.Rv2111c; -.
DR PaxDb; P9WHN5; -.
DR DNASU; 888788; -.
DR GeneID; 45426086; -.
DR GeneID; 888788; -.
DR KEGG; mtu:Rv2111c; -.
DR TubercuList; Rv2111c; -.
DR eggNOG; ENOG50333JS; Bacteria.
DR OMA; AGQERME; -.
DR BioCyc; MetaCyc:G185E-6317-MON; -.
DR UniPathway; UPA00997; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0070628; F:proteasome binding; IDA:UniProtKB.
DR GO; GO:0031386; F:protein tag; IDA:UniProtKB.
DR GO; GO:0019941; P:modification-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0010498; P:proteasomal protein catabolic process; IDA:UniProtKB.
DR GO; GO:0070490; P:protein pupylation; IDA:UniProtKB.
DR DisProt; DP00877; -.
DR HAMAP; MF_02106; Pup; 1.
DR InterPro; IPR008515; Ubiquitin-like_Pup.
DR Pfam; PF05639; Pup; 1.
DR TIGRFAMs; TIGR03687; pupylate_cterm; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Coiled coil; Isopeptide bond; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1..64
FT /note="Prokaryotic ubiquitin-like protein Pup"
FT /id="PRO_0000383476"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 21..58
FT /note="Mpa/ARC ATPase binding"
FT COILED 23..52
FT /evidence="ECO:0000255"
FT COMPBIAS 21..36
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 64
FT /note="Deamidated glutamine; alternate"
FT /evidence="ECO:0000269|PubMed:19448618"
FT CROSSLNK 64
FT /note="Isoglutamyl lysine isopeptide (Gln-Lys) (interchain
FT with K-? in acceptor proteins); alternate"
FT HELIX 23..49
FT /evidence="ECO:0007829|PDB:3M91"
SQ SEQUENCE 64 AA; 6944 MW; 7D958B770D8766E3 CRC64;
MAQEQTKRGG GGGDDDDIAG STAAGQERRE KLTEETDDLL DEIDDVLEEN AEDFVRAYVQ
KGGQ
