PRSN_PIERA
ID PRSN_PIERA Reviewed; 850 AA.
AC Q9U8Q4;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=Pierisin {ECO:0000303|PubMed:10485873};
DE EC=2.4.2.- {ECO:0000269|PubMed:11592983};
DE AltName: Full=NAD--DNA ADP-ribosyltransferase;
DE AltName: Full=Pierisin-1 {ECO:0000303|PubMed:10485873};
OS Pieris rapae (Small white butterfly) (Artogeia rapae).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Lepidoptera; Glossata; Ditrysia; Papilionoidea;
OC Pieridae; Pierinae; Pieris.
OX NCBI_TaxID=64459 {ECO:0000312|EMBL:BAA84491.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 106-114; 263-275; 338-352;
RP 403-407; 469-484; 502-513; 607-613; 617-636; 699-707; 709-712 AND 762-769,
RP FUNCTION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF GLU-165.
RC TISSUE=Fifth instar larvae;
RX PubMed=10485873; DOI=10.1073/pnas.96.19.10608;
RA Watanabe M., Kono T., Matsushima-Hibiya Y., Kanazawa T., Nishisaka N.,
RA Kishimoto T., Koyama K., Sugimura T., Wakabayashi K.;
RT "Molecular cloning of an apoptosis-inducing protein, pierisin, from cabbage
RT butterfly: possible involvement of ADP-ribosylation in its activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:10608-10613(1999).
RN [2] {ECO:0000305}
RP FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Pupae;
RX PubMed=11592983; DOI=10.1073/pnas.221444598;
RA Takamura-Enya T., Watanabe M., Totsuka Y., Kanazawa T.,
RA Matsushima-Hibiya Y., Koyama K., Sugimura T., Wakabayashi K.;
RT "Mono(ADP-ribosyl)ation of 2'-deoxyguanosine residue in DNA by an
RT apoptosis-inducing protein, pierisin-1, from cabbage butterfly.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:12414-12419(2001).
RN [3]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Fat body;
RX PubMed=15528160; DOI=10.1016/j.cbpb.2004.07.010;
RA Watanabe M., Nakano T., Shiotani B., Matsushima-Hibiya Y., Kiuchi M.,
RA Yukuhiro F., Kanazawa T., Koyama K., Sugimura T., Wakabayashi K.;
RT "Developmental stage-specific expression and tissue distribution of
RT pierisin-1, a guanine-specific ADP-ribosylating toxin, in Pieris rapae.";
RL Comp. Biochem. Physiol. 139:125-131(2004).
RN [4]
RP FUNCTION.
RX PubMed=23637752; DOI=10.1371/journal.pone.0060539;
RA Takahashi-Nakaguchi A., Matsumoto Y., Yamamoto M., Iwabuchi K., Totsuka Y.,
RA Sugimura T., Wakabayashi K.;
RT "Demonstration of cytotoxicity against wasps by pierisin-1: a possible
RT defense factor in the cabbage white butterfly.";
RL PLoS ONE 8:e60539-e60539(2013).
RN [5] {ECO:0007744|PDB:5H6J, ECO:0007744|PDB:5H6K, ECO:0007744|PDB:5H6L, ECO:0007744|PDB:5H6M, ECO:0007744|PDB:5H6N}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 1-233 WITH AND WITHOUT NAD(+),
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 1-267, DOMAIN, DNA-BINDING, AND
RP MUTAGENESIS OF ARG-120; 122-LYS--LYS-124; LYS-122; LYS-123; LYS-124;
RP TRP-127; 181-ARG--ARG-187; ARG-181 AND ARG-187.
RX PubMed=28765284; DOI=10.1074/jbc.m117.776641;
RA Oda T., Hirabayashi H., Shikauchi G., Takamura R., Hiraga K., Minami H.,
RA Hashimoto H., Yamamoto M., Wakabayashi K., Shimizu T., Sato M.;
RT "Structural basis of autoinhibition and activation of the DNA-targeting
RT ADP-ribosyltransferase pierisin-1.";
RL J. Biol. Chem. 292:15445-15455(2017).
CC -!- FUNCTION: ADP-ribosylates double-stranded DNA by targeting the N2 amino
CC group of dG residues; 10-fold less active on tRNA. Induces apoptosis in
CC a range of human cell lines (PubMed:10485873, PubMed:11592983). May
CC play a role in removing unnecessary or harmful cells during pupation
CC (PubMed:15528160) (Probable). May play a role in defense against
CC parasitic wasps; its habitual predator Cotesia glomerata is only
CC susceptible after removal of its eggshell or the surface of the larval
CC caudal vesicle, while other wasps are damaged by this protein
CC (PubMed:23637752) (Probable). The wild-type catalytic domain (residues
CC 1-233) cannot be expressed in E.coli as it is unstable probably due to
CC its toxicity. A catalytic domain fragment (Glu-165 mutated to Gln)
CC binds dsDNA but not ssDNA; the presence of the linker inhibits DNA-
CC binding (PubMed:28765284). {ECO:0000269|PubMed:10485873,
CC ECO:0000269|PubMed:11592983, ECO:0000269|PubMed:28765284,
CC ECO:0000305|PubMed:15528160, ECO:0000305|PubMed:23637752}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyguanosine in DNA + NAD(+) = an N(2)-(ADP-L-ribosyl)-
CC 2'-deoxyguanosine in DNA + H(+) + nicotinamide; Xref=Rhea:RHEA:71807,
CC Rhea:RHEA-COMP:11367, Rhea:RHEA-COMP:18062, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:85445,
CC ChEBI:CHEBI:142722; Evidence={ECO:0000269|PubMed:11592983};
CC -!- TISSUE SPECIFICITY: Within late stage larvae and pupal stages most
CC protein is found in fat bodies. {ECO:0000269|PubMed:15528160}.
CC -!- DEVELOPMENTAL STAGE: Highest expression is found in fifth instar
CC larvae, decreasing through prepupae, early-phase pupae (1 day after
CC pupation) and late-phase pupae (at protein level). Much lower levels
CC present in adult. {ECO:0000269|PubMed:10485873,
CC ECO:0000269|PubMed:15528160}.
CC -!- DOMAIN: The N-terminus (residues 1-233) has the ADP-ribosylation
CC catalytic domain. NAD(+)-binding or the presence of the linker do not
CC alter the structure of the catalytic domain, however in vitro the
CC presence of the linker masks the DNA- and NAD(+)-binding regions and
CC thus prevents dsDNA-binding by the catalytic domain.
CC {ECO:0000269|PubMed:28765284}.
CC -!- SIMILARITY: Belongs to the pierisin ADP-ribosyltransferase family.
CC {ECO:0000305}.
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DR EMBL; AB030305; BAA84491.1; -; mRNA.
DR PDB; 5H6J; X-ray; 1.90 A; A/B=1-233.
DR PDB; 5H6K; X-ray; 1.80 A; A/B=1-233.
DR PDB; 5H6L; X-ray; 2.10 A; A/B=1-233.
DR PDB; 5H6M; X-ray; 1.90 A; A/B=1-233.
DR PDB; 5H6N; X-ray; 1.80 A; A/B/C/D=1-267.
DR PDBsum; 5H6J; -.
DR PDBsum; 5H6K; -.
DR PDBsum; 5H6L; -.
DR PDBsum; 5H6M; -.
DR PDBsum; 5H6N; -.
DR AlphaFoldDB; Q9U8Q4; -.
DR SMR; Q9U8Q4; -.
DR GO; GO:0030591; F:2'-deoxyguanosine DNA ADP-ribosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IDA:UniProtKB.
DR GO; GO:0030592; P:DNA ADP-ribosylation; IDA:UniProtKB.
DR CDD; cd00161; RICIN; 3.
DR InterPro; IPR035992; Ricin_B-like_lectins.
DR InterPro; IPR000772; Ricin_B_lectin.
DR Pfam; PF14200; RicinB_lectin_2; 3.
DR SMART; SM00458; RICIN; 4.
DR SUPFAM; SSF50370; SSF50370; 4.
DR PROSITE; PS50231; RICIN_B_LECTIN; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Direct protein sequencing; DNA-binding;
KW Glycosyltransferase; NAD; Nucleotidyltransferase; Repeat; Transferase.
FT CHAIN 1..850
FT /note="Pierisin"
FT /id="PRO_0000097052"
FT DOMAIN 267..409
FT /note="Ricin B-type lectin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
FT DOMAIN 413..560
FT /note="Ricin B-type lectin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
FT DOMAIN 564..707
FT /note="Ricin B-type lectin 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
FT REGION 1..233
FT /note="ADP-ribosylation domain"
FT /evidence="ECO:0000305|PubMed:28765284"
FT REGION 234..267
FT /note="Linker"
FT /evidence="ECO:0000305|PubMed:28765284"
FT MOTIF 117..135
FT /note="PN (phosphate-nicotinamide) loop"
FT /evidence="ECO:0000305|PubMed:28765284"
FT BINDING 70..72
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:28765284,
FT ECO:0007744|PDB:5H6J"
FT BINDING 85
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:28765284,
FT ECO:0007744|PDB:5H6J"
FT BINDING 107
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:28765284,
FT ECO:0007744|PDB:5H6J"
FT BINDING 114..116
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:28765284,
FT ECO:0007744|PDB:5H6J"
FT BINDING 127
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:28765284,
FT ECO:0007744|PDB:5H6J"
FT BINDING 163..165
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:28765284,
FT ECO:0007744|PDB:5H6J"
FT MUTAGEN 120
FT /note="R->S: Slight reduction in DNA-binding by catalytic
FT domain."
FT /evidence="ECO:0000269|PubMed:28765284"
FT MUTAGEN 122..124
FT /note="KKK->AAA: Loss of DNA-binding by catalytic domain."
FT /evidence="ECO:0000269|PubMed:28765284"
FT MUTAGEN 122
FT /note="K->A: Considerably reduced DNA-binding by catalytic
FT domain."
FT /evidence="ECO:0000269|PubMed:28765284"
FT MUTAGEN 123
FT /note="K->A: No change in DNA-binding by catalytic domain."
FT /evidence="ECO:0000269|PubMed:28765284"
FT MUTAGEN 124
FT /note="K->A: Considerably reduced DNA-binding by catalytic
FT domain."
FT /evidence="ECO:0000269|PubMed:28765284"
FT MUTAGEN 127
FT /note="W->A: Slight reduction in DNA-binding by catalytic
FT domain."
FT /evidence="ECO:0000269|PubMed:28765284"
FT MUTAGEN 165
FT /note="E->D: Reduced cytotoxic activity."
FT /evidence="ECO:0000269|PubMed:10485873"
FT MUTAGEN 165
FT /note="E->Q: Complete loss of cytotoxic activity."
FT /evidence="ECO:0000269|PubMed:10485873"
FT MUTAGEN 181..187
FT /note="RELHNGR->AELHNGA: Loss of DNA-binding by catalytic
FT domain."
FT /evidence="ECO:0000269|PubMed:28765284"
FT MUTAGEN 181
FT /note="R->A: Considerably reduced DNA-binding by catalytic
FT domain."
FT /evidence="ECO:0000269|PubMed:28765284"
FT MUTAGEN 187
FT /note="R->A: Slight reduction in DNA-binding by catalytic
FT domain."
FT /evidence="ECO:0000269|PubMed:28765284"
FT TURN 11..14
FT /evidence="ECO:0007829|PDB:5H6K"
FT HELIX 18..21
FT /evidence="ECO:0007829|PDB:5H6K"
FT HELIX 25..33
FT /evidence="ECO:0007829|PDB:5H6K"
FT HELIX 38..43
FT /evidence="ECO:0007829|PDB:5H6K"
FT STRAND 50..54
FT /evidence="ECO:0007829|PDB:5H6K"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:5H6K"
FT HELIX 63..65
FT /evidence="ECO:0007829|PDB:5H6K"
FT STRAND 68..74
FT /evidence="ECO:0007829|PDB:5H6K"
FT HELIX 76..82
FT /evidence="ECO:0007829|PDB:5H6K"
FT HELIX 95..98
FT /evidence="ECO:0007829|PDB:5H6K"
FT HELIX 100..106
FT /evidence="ECO:0007829|PDB:5H6K"
FT STRAND 111..117
FT /evidence="ECO:0007829|PDB:5H6K"
FT STRAND 119..129
FT /evidence="ECO:0007829|PDB:5H6N"
FT TURN 130..133
FT /evidence="ECO:0007829|PDB:5H6K"
FT STRAND 134..142
FT /evidence="ECO:0007829|PDB:5H6K"
FT HELIX 150..154
FT /evidence="ECO:0007829|PDB:5H6K"
FT HELIX 155..157
FT /evidence="ECO:0007829|PDB:5H6K"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:5H6K"
FT STRAND 165..169
FT /evidence="ECO:0007829|PDB:5H6K"
FT HELIX 174..176
FT /evidence="ECO:0007829|PDB:5H6K"
FT STRAND 177..184
FT /evidence="ECO:0007829|PDB:5H6K"
FT STRAND 187..193
FT /evidence="ECO:0007829|PDB:5H6K"
FT STRAND 210..212
FT /evidence="ECO:0007829|PDB:5H6N"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:5H6K"
FT TURN 222..225
FT /evidence="ECO:0007829|PDB:5H6K"
FT HELIX 240..242
FT /evidence="ECO:0007829|PDB:5H6N"
FT HELIX 244..246
FT /evidence="ECO:0007829|PDB:5H6N"
FT STRAND 247..252
FT /evidence="ECO:0007829|PDB:5H6N"
SQ SEQUENCE 850 AA; 98082 MW; 2C891698B2C0880E CRC64;
MADRQPYMTN GIQAAVVEWI RALDLEIISL LLSRAWPMAL LATSELRWRP TVLTDTDNVV
RLDRRQRLVR WDRRPPNEIF LDGFVPIVTR ENPDWEETDL YGFAKNNHPS IFVSTTKTQR
NKKKYVWTPR NANRGIVYQY EIYAPGGVDV NDSFSDASPW PNQMEVAFPG GIQNIYIRSA
RELHNGRIQR IWINPNFLDP GDLEPIVSSS RTPQVIWRMN HPDGGHRDQR SERSASSYDD
LMYGGTGNVQ EDTFGDEPNN PKPIAAGEFM IESIKDKNSF LDLSKNVNGG VIHSNLYSGG
DNQIWVFSYD DNKKAYRIQS YQNSYLYLSW DSNASSKEMI LRGYTNSGSN NQYWQIEQTG
KNYRLRNLLN LDMIITAQDK PSAFGGKEVI VNTEISNSNT KISQEWKMIP FDFRPIIDGD
YNIFNVDLSN QVVDFSNQPD LLVHGHIFCD NENQTWHFTY NSTYHAYKIW SGRKSNLLLT
WDSNAASKEM VVRAYTESRS KNQYWRIEQT GSKSYKVRNL ENSSMILGLT RVSTPYGGLN
LMVEDDSDGH SDLHSDWDIK PIFYQDIPDG DYNIFNDNFP NIAIDFTNQE GSLIHGHNFC
SNNNQKWSFV FDGKRKAYRI KSGVRSNLWL SWDSNASSKE MVLRAYTESG SSNQYWRLDE
ANDGSYRIRN LQDYYKLIAL TNKNTPYGGK ELIVSDNKES GNTWYLKKLG EVPLPNRKFR
IATKLNYKKV IDSSTSYNLI ITHDLNFASS IWELVYDSSK KAYNIYSSDI NNLGWIYQNK
NFFVKLGNID GPDHGDLRYF WTIEYSMQTG CYLIRSLHDP ANAVGYTDSE SVITDTSTYS
DNQLFHFILM
