RUN1_VITRO
ID RUN1_VITRO Reviewed; 1331 AA.
AC V9M398;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 19-MAR-2014, sequence version 1.
DT 03-AUG-2022, entry version 32.
DE RecName: Full=Disease resistance protein RUN1 {ECO:0000305};
DE AltName: Full=NAD(+) hydrolase RUN1;
DE EC=3.2.2.6 {ECO:0000269|PubMed:31439792};
DE AltName: Full=NADP(+) hydrolase RUN1 {ECO:0000305};
DE EC=3.2.2.- {ECO:0000269|PubMed:31439792};
DE AltName: Full=Resistance to Uncinula necator protein {ECO:0000303|PubMed:24033846};
DE Short=MrRUN1 {ECO:0000303|PubMed:24033846};
GN Name=RUN1 {ECO:0000303|PubMed:24033846};
OS Vitis rotundifolia (Muscadine grape).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; Vitales; Vitaceae; Viteae; Vitis.
OX NCBI_TaxID=103349;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF 1288-LYS-ARG-1289.
RX PubMed=24033846; DOI=10.1111/tpj.12327;
RA Feechan A., Anderson C., Torregrosa L., Jermakow A., Mestre P.,
RA Wiedemann-Merdinoglu S., Merdinoglu D., Walker A.R., Cadle-Davidson L.,
RA Reisch B., Aubourg S., Bentahar N., Shrestha B., Bouquet A.,
RA Adam-Blondon A.F., Thomas M.R., Dry I.B.;
RT "Genetic dissection of a TIR-NB-LRR locus from the wild North American
RT grapevine species Muscadinia rotundifolia identifies paralogous genes
RT conferring resistance to major fungal and oomycete pathogens in cultivated
RT grapevine.";
RL Plant J. 76:661-674(2013).
RN [2] {ECO:0007744|PDB:6O0W}
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 23-198 IN COMPLEX WITH NADP,
RP ACTIVE SITE, AND MUTAGENESIS OF ARG-34; 64-ARG-ARG-65; SER-94; TRP-96 AND
RP GLU-100.
RX PubMed=31439792; DOI=10.1126/science.aax1911;
RA Horsefield S., Burdett H., Zhang X., Manik M.K., Shi Y., Chen J., Qi T.,
RA Gilley J., Lai J.S., Rank M.X., Casey L.W., Gu W., Ericsson D.J., Foley G.,
RA Hughes R.O., Bosanac T., von Itzstein M., Rathjen J.P., Nanson J.D.,
RA Boden M., Dry I.B., Williams S.J., Staskawicz B.J., Coleman M.P., Ve T.,
RA Dodds P.N., Kobe B.;
RT "NAD+ cleavage activity by animal and plant TIR domains in cell death
RT pathways.";
RL Science 365:793-799(2019).
CC -!- FUNCTION: Disease resistance (R) protein that confers resistance to
CC multiple powdery and downy mildew by promoting cell death
CC (PubMed:24033846, PubMed:31439792). Acts as a NAD(+) hydrolase
CC (NADase): in response to activation, catalyzes cleavage of NAD(+) into
CC ADP-D-ribose (ADPR) and nicotinamide; NAD(+) cleavage triggering a
CC defense system that promotes cell death (PubMed:31439792). Also able to
CC hydrolyze NADP(+), but not other NAD(+)-related molecules
CC (PubMed:31439792). {ECO:0000269|PubMed:24033846,
CC ECO:0000269|PubMed:31439792}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NAD(+) = ADP-D-ribose + H(+) + nicotinamide;
CC Xref=Rhea:RHEA:16301, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:57967; EC=3.2.2.6;
CC Evidence={ECO:0000269|PubMed:31439792};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16302;
CC Evidence={ECO:0000269|PubMed:31439792};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NADP(+) = ADP-D-ribose 2'-phosphate + H(+) +
CC nicotinamide; Xref=Rhea:RHEA:19849, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17154, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:58673; Evidence={ECO:0000269|PubMed:31439792};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19850;
CC Evidence={ECO:0000269|PubMed:31439792};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24033846}. Cytoplasm
CC {ECO:0000269|PubMed:24033846}. Note=Localizes predominantly to the
CC nucleus. {ECO:0000269|PubMed:24033846}.
CC -!- DOMAIN: The TIR domain mediates NAD(+) hydrolase (NADase) activity.
CC Self-association of TIR domains is required for NADase activity.
CC {ECO:0000255|PROSITE-ProRule:PRU00204}.
CC -!- SIMILARITY: Belongs to the disease resistance TIR-NB-LRR family.
CC {ECO:0000305}.
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DR EMBL; JQ904636; AGC24030.1; -; Genomic_DNA.
DR PDB; 6O0W; X-ray; 1.75 A; A=23-198.
DR PDB; 7RTS; X-ray; 1.74 A; A=23-198.
DR PDB; 7RX1; X-ray; 1.89 A; A/B=23-198.
DR PDB; 7S2Z; X-ray; 2.35 A; A/B/C/D=23-198.
DR PDBsum; 6O0W; -.
DR PDBsum; 7RTS; -.
DR PDBsum; 7RX1; -.
DR PDBsum; 7S2Z; -.
DR AlphaFoldDB; V9M398; -.
DR SMR; V9M398; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0043531; F:ADP binding; IEA:InterPro.
DR GO; GO:0050135; F:NAD(P)+ nucleosidase activity; IDA:UniProtKB.
DR GO; GO:0003953; F:NAD+ nucleosidase activity; IDA:UniProtKB.
DR GO; GO:0061809; F:NAD+ nucleotidase, cyclic ADP-ribose generating; IEA:UniProtKB-EC.
DR GO; GO:0050832; P:defense response to fungus; IMP:UniProtKB.
DR GO; GO:0019677; P:NAD catabolic process; IDA:UniProtKB.
DR GO; GO:0043068; P:positive regulation of programmed cell death; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR Gene3D; 1.10.8.430; -; 1.
DR Gene3D; 3.40.50.10140; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.80.10.10; -; 3.
DR InterPro; IPR042197; Apaf_helical.
DR InterPro; IPR045344; C-JID.
DR InterPro; IPR044974; Disease_R_plants.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR025875; Leu-rich_rpt_4.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR002182; NB-ARC.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR11017; PTHR11017; 5.
DR Pfam; PF20160; C-JID; 1.
DR Pfam; PF12799; LRR_4; 1.
DR Pfam; PF13855; LRR_8; 1.
DR Pfam; PF00931; NB-ARC; 1.
DR Pfam; PF01582; TIR; 1.
DR SMART; SM00369; LRR_TYP; 6.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF52200; SSF52200; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Hydrolase; Leucine-rich repeat; NAD; Nucleus;
KW Plant defense; Repeat.
FT CHAIN 1..1331
FT /note="Disease resistance protein RUN1"
FT /id="PRO_0000448791"
FT DOMAIN 25..190
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT DOMAIN 206..434
FT /note="NB-ARC"
FT /evidence="ECO:0000255"
FT REPEAT 429..452
FT /note="LRR 1"
FT /evidence="ECO:0000255"
FT REPEAT 480..509
FT /note="LRR 2"
FT /evidence="ECO:0000255"
FT REPEAT 540..565
FT /note="LRR 3"
FT /evidence="ECO:0000255"
FT REPEAT 616..638
FT /note="LRR 4"
FT /evidence="ECO:0000255"
FT REPEAT 648..673
FT /note="LRR 5"
FT /evidence="ECO:0000255"
FT REPEAT 684..708
FT /note="LRR 6"
FT /evidence="ECO:0000255"
FT REPEAT 709..732
FT /note="LRR 7"
FT /evidence="ECO:0000255"
FT REPEAT 734..756
FT /note="LRR 8"
FT /evidence="ECO:0000255"
FT REPEAT 757..779
FT /note="LRR 9"
FT /evidence="ECO:0000255"
FT REPEAT 781..803
FT /note="LRR 10"
FT /evidence="ECO:0000255"
FT REPEAT 804..826
FT /note="LRR 11"
FT /evidence="ECO:0000255"
FT REPEAT 828..850
FT /note="LRR 12"
FT /evidence="ECO:0000255"
FT REPEAT 851..873
FT /note="LRR 13"
FT /evidence="ECO:0000255"
FT REPEAT 875..897
FT /note="LRR 14"
FT /evidence="ECO:0000255"
FT REPEAT 898..920
FT /note="LRR 15"
FT /evidence="ECO:0000255"
FT REPEAT 922..944
FT /note="LRR 16"
FT /evidence="ECO:0000255"
FT REPEAT 945..967
FT /note="LRR 17"
FT /evidence="ECO:0000255"
FT REPEAT 969..991
FT /note="LRR 18"
FT /evidence="ECO:0000255"
FT REPEAT 992..1014
FT /note="LRR 19"
FT /evidence="ECO:0000255"
FT REPEAT 1017..1040
FT /note="LRR 20"
FT /evidence="ECO:0000255"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1287..1291
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:24033846"
FT ACT_SITE 100
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204,
FT ECO:0000269|PubMed:31439792"
FT BINDING 34..39
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:31439792,
FT ECO:0007744|PDB:6O0W"
FT BINDING 66
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:31439792,
FT ECO:0007744|PDB:6O0W"
FT MUTAGEN 34
FT /note="R->A: Reduced NAD(+) hydrolase activity."
FT /evidence="ECO:0000269|PubMed:31439792"
FT MUTAGEN 64..65
FT /note="RR->AA: Increased NAD(+) hydrolase activity."
FT /evidence="ECO:0000269|PubMed:31439792"
FT MUTAGEN 94
FT /note="S->A: Reduced NAD(+) hydrolase activity."
FT /evidence="ECO:0000269|PubMed:31439792"
FT MUTAGEN 96
FT /note="W->A: Reduced NAD(+) hydrolase activity."
FT /evidence="ECO:0000269|PubMed:31439792"
FT MUTAGEN 100
FT /note="E->A: Abolished NAD(+) hydrolase activity."
FT /evidence="ECO:0000269|PubMed:31439792"
FT MUTAGEN 1288..1289
FT /note="KR->TS: Abolished nuclear localization."
FT /evidence="ECO:0000269|PubMed:24033846"
FT STRAND 27..33
FT /evidence="ECO:0007829|PDB:7RTS"
FT HELIX 35..38
FT /evidence="ECO:0007829|PDB:7RTS"
FT TURN 39..41
FT /evidence="ECO:0007829|PDB:7RTS"
FT HELIX 42..52
FT /evidence="ECO:0007829|PDB:7RTS"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:7RTS"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:6O0W"
FT HELIX 71..78
FT /evidence="ECO:0007829|PDB:7RTS"
FT STRAND 80..87
FT /evidence="ECO:0007829|PDB:7RTS"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:7RTS"
FT HELIX 95..110
FT /evidence="ECO:0007829|PDB:7RTS"
FT TURN 112..115
FT /evidence="ECO:0007829|PDB:7S2Z"
FT STRAND 117..125
FT /evidence="ECO:0007829|PDB:7RTS"
FT HELIX 127..133
FT /evidence="ECO:0007829|PDB:7RTS"
FT HELIX 137..140
FT /evidence="ECO:0007829|PDB:7RTS"
FT HELIX 146..148
FT /evidence="ECO:0007829|PDB:6O0W"
FT TURN 149..151
FT /evidence="ECO:0007829|PDB:6O0W"
FT HELIX 152..163
FT /evidence="ECO:0007829|PDB:7RTS"
FT STRAND 168..170
FT /evidence="ECO:0007829|PDB:7RTS"
FT HELIX 175..190
FT /evidence="ECO:0007829|PDB:7RTS"
SQ SEQUENCE 1331 AA; 152353 MW; 7780FA1601930CE8 CRC64;
MASTSSSRAS SSSSSSSTPS IPRTITYDVF LSFRGEDTRF NFTDHLYSAL GRRGIRTFRD
DKLRRGEAIA PELLKAIEES RSSVIVFSEN YARSRWCLDE LVKIMECHKD KKDPGHAVFP
IFYHVDPSHV RKQEGSFGEA FAGYGENLKD KIPRWRTALT EAANLSGWPL QDGYESNQIK
EITDSIFRRL KCKRLDAGAN LVGIDSHVKE MIWRLHMESS DVRMVGMYGV GGIGKTTIAK
VIYNELSREF EYMSFLENIR EKFNTQGVSP LQNQLLDDIL KGEGSQNINS VAHGASMIKD
ILSSKIVFIV LDDVDDQSQL EYLLRHREWL GEGSRVIITT RNKHVLDVQK VDDLYEVKGL
NFEEACELFS LYAFEQNLPK SDYRNLSHRV VGYCQGLPLA LKVLGCLLLK KTIPEWESEL
RKLDREPEAE ILSVLKRSYD GLGRTEKSIF LDVACFFKGE DRDFVSKILD ACDFHAEIGI
KNLNDKCLIT LQYNRIRMHD LIQQMGWEIV REKFPDEPNK WSRLWDTCDF ERALTAYKGI
KRVETISLDL SKLKRVCSNS NAFAKMTRLR LLKVQSSLDI DFEPEYIDAD DKVELYDVVM
KNASKMRLGR GFKFPSYELR YLRWDGYPLD FLPSNFDGGK LVELHLKCSN IKQLRLGNKD
LEMLKVIDLS YSRKLSQMSE FSSMPNLERL FLRGCVSLID IHPSVGNMKK LTTLSLKSCK
KLKNLPDSIG DLESLEILDL AYCSKFEKFP EKGGNMKSLT ELDLQNTAIK DLPDSIGDLE
SLKYLDLSDC SKFEKFPEKG GNMKSLRELD LRNTAIKDLP DSIRDLESLE RLYLSYCSKF
EKFPEKGGNM KSLMELDLQN TAIKDLPDSI GDLESLKYLD LSNCSKFEKF PEKGGNMKSL
TELFLENTAI KDLPDSIGDL ESLVSLNLSD CSKFEKFPEK GGNMKSLNWL YLNNTAIKDL
PDSIGDLESL MRLYLSNSSK FEKLPEKVGN MKSLELLDLR NTAIKDLPDS IGDLEPLEKL
SLSNCPKFEV LPLSLKAIDA HLCTSKEDLS RLLWLCHRNW LKSTTEEFDR WQLSAFIPES
SGIPEWITYQ NLGSEVTEKL PINWCEDPDF PGFVLSCLYR PSDYSSAYNF CHDFKCELNL
HGNGFTFTDE CSHSCWCDCH VNFKDSRDLV CVYWYPKTAI PEEDHHKYTH INASFTHRFE
GHPFFCEDIK KIKCGINVIF LGDQRNHMPM LEHPQNSGDN GSALQDANGN VHGANQDDEH
YHIPTLGLLG NFHDNGSAVL EDTLGNRKRR RDDSLPDVVE EPHYKKIGSH PTPISCFELH
HQYQSEQNHM W
