L6_LINUS
ID L6_LINUS Reviewed; 1294 AA.
AC Q40253;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Disease resistance protein L6 {ECO:0000305};
DE AltName: Full=NAD(+) hydrolase L6;
DE EC=3.2.2.6 {ECO:0000269|PubMed:31439792};
DE AltName: Full=NADP(+) hydrolase L6 {ECO:0000305};
DE EC=3.2.2.- {ECO:0000269|PubMed:31439792};
DE Flags: Precursor;
GN Name=L6 {ECO:0000303|PubMed:7549479};
OS Linum usitatissimum (Flax) (Linum humile).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; fabids; Malpighiales; Linaceae; Linum.
OX NCBI_TaxID=4006;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=7549479; DOI=10.2307/3870095;
RA Lawrence G.J., Finnegan E.J., Ayliffe M.A., Ellis J.G.;
RT "The L6 gene for flax rust resistance is related to the Arabidopsis
RT bacterial resistance gene RPS2 and the tobacco viral resistance gene N.";
RL Plant Cell 7:1195-1206(1995).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF GLU-135.
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).
RN [3] {ECO:0007744|PDB:3OZI}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 29-229, SUBUNIT, AND MUTAGENESIS
RP OF ARG-73; LYS-100; GLY-101; ILE-104; SER-129; LYS-130; TRP-131; CYS-132;
RP TYR-156; ASP-159; PRO-160; SER-161; ARG-164; THR-185; ASP-198; LYS-200;
RP GLY-201; TRP-202; ASP-208 AND LYS-216.
RX PubMed=21402359; DOI=10.1016/j.chom.2011.02.009;
RA Bernoux M., Ve T., Williams S., Warren C., Hatters D., Valkov E., Zhang X.,
RA Ellis J.G., Kobe B., Dodds P.N.;
RT "Structural and functional analysis of a plant resistance protein TIR
RT domain reveals interfaces for self-association, signaling, and
RT autoregulation.";
RL Cell Host Microbe 9:200-211(2011).
CC -!- FUNCTION: TIR-NB-LRR receptor-like protein that confers resistance to
CC the flax rust phytopathogenic fungus (M.lini) (PubMed:7549479). Acts as
CC a NAD(+) hydrolase (NADase): in response to activation, catalyzes
CC cleavage of NAD(+) into ADP-D-ribose (ADPR) and nicotinamide; NAD(+)
CC cleavage triggering a defense system that promotes cell death
CC (PubMed:31439792). Also able to hydrolyze NADP(+), but not other
CC NAD(+)-related molecules (PubMed:31439792).
CC {ECO:0000269|PubMed:31439792, ECO:0000269|PubMed:7549479}.
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 -!- SUBUNIT: Homooligomer; homooligomerization is required for activity.
CC {ECO:0000269|PubMed:21402359}.
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; U27081; AAA91022.1; -; Genomic_DNA.
DR PIR; T18546; T18546.
DR PDB; 3OZI; X-ray; 2.30 A; A/B=29-229.
DR PDBsum; 3OZI; -.
DR AlphaFoldDB; Q40253; -.
DR SMR; Q40253; -.
DR KEGG; ag:AAA91022; -.
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:0006952; P:defense response; IEA:UniProtKB-KW.
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; IPR044974; Disease_R_plants.
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 PANTHER; PTHR11017; PTHR11017; 1.
DR Pfam; PF00931; NB-ARC; 1.
DR Pfam; PF01582; TIR; 1.
DR SMART; SM00255; TIR; 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; Hydrolase; Leucine-rich repeat; NAD; Plant defense; Repeat;
KW Signal.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..1294
FT /note="Disease resistance protein L6"
FT /evidence="ECO:0000255"
FT /id="PRO_5004231414"
FT DOMAIN 59..221
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT DOMAIN 241..480
FT /note="NB-ARC"
FT /evidence="ECO:0000255"
FT REPEAT 246..268
FT /note="LRR 1"
FT /evidence="ECO:0000255"
FT REPEAT 468..492
FT /note="LRR 2"
FT /evidence="ECO:0000255"
FT REPEAT 604..625
FT /note="LRR 3"
FT /evidence="ECO:0000255"
FT REPEAT 626..650
FT /note="LRR 4"
FT /evidence="ECO:0000255"
FT REPEAT 904..928
FT /note="LRR 5"
FT /evidence="ECO:0000255"
FT REPEAT 1012..1039
FT /note="LRR 6"
FT /evidence="ECO:0000255"
FT REPEAT 1063..1085
FT /note="LRR 7"
FT /evidence="ECO:0000255"
FT REPEAT 1086..1109
FT /note="LRR 8"
FT /evidence="ECO:0000255"
FT REPEAT 1179..1203
FT /note="LRR 9"
FT /evidence="ECO:0000255"
FT REPEAT 1205..1229
FT /note="LRR 10"
FT /evidence="ECO:0000255"
FT REPEAT 1254..1278
FT /note="LRR 11"
FT /evidence="ECO:0000255"
FT REGION 34..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 135
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204,
FT ECO:0000305|PubMed:31439792"
FT BINDING 68..73
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:V9M398"
FT BINDING 101
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:V9M398"
FT MUTAGEN 73
FT /note="R->A: Abolished ability to promote cell death
FT without affecting homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 100
FT /note="K->A: Slightly reduced ability to promote cell death
FT without affecting homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 101
FT /note="G->C: Abolished ability to promote cell death
FT without affecting homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 104
FT /note="I->A: Abolished ability to promote cell death
FT without affecting homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 129
FT /note="S->A: Abolished ability to promote cell death
FT without affecting homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 130
FT /note="K->A: Reduced ability to promote cell death without
FT affecting homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 131
FT /note="W->A: Abolished ability to promote cell death
FT without affecting homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 132
FT /note="C->S: Abolished ability to promote cell death
FT without affecting homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 135
FT /note="E->A: Loss of NAD(+) hydrolase activity."
FT /evidence="ECO:0000269|PubMed:31439792"
FT MUTAGEN 156
FT /note="Y->A: Abolished ability to promote cell death and
FT impaired homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 159
FT /note="D->A: Reduced ability to promote cell death without
FT affecting homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 160
FT /note="P->Y: Abolished ability to promote cell death and
FT impaired homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 161
FT /note="S->A: Reduced ability to promote cell death without
FT affecting homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 164
FT /note="R->A,E: Reduced ability to promote cell death and
FT impaired homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 185
FT /note="T->A: Reduced ability to promote cell death without
FT affecting homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 198
FT /note="D->A: Slightly reduced ability to promote cell death
FT without affecting homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 200
FT /note="K->E: Reduced ability to promote cell death and
FT impaired homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 201
FT /note="G->C: Reduced ability to promote cell death without
FT affecting homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 201
FT /note="G->R: Abolished ability to promote cell death and
FT impaired homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 201
FT /note="G->Y: Reduced ability to promote cell death and
FT impaired homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 202
FT /note="W->A: Reduced ability to promote cell death and
FT impaired homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 208
FT /note="D->A: Reduced ability to promote cell death and
FT impaired homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 216
FT /note="K->A: Slightly reduced ability to promote cell death
FT without affecting homooligomerization."
FT /evidence="ECO:0000269|PubMed:21402359"
FT MUTAGEN 216
FT /note="K->E: Does not affect ability to promote cell death
FT while homooligomerization is abolished."
FT /evidence="ECO:0000269|PubMed:21402359"
SQ SEQUENCE 1294 AA; 146765 MW; 802B62800FCA7AE5 CRC64;
MSYLREVATA VALLLPFILL NKFWRPNSKD SIVNDDDDST SEVDAISDST NPSGSFPSVE
YEVFLSFRGP DTREQFTDFL YQSLRRYKIH TFRDDDELLK GKEIGPNLLR AIDQSKIYVP
IISSGYADSK WCLMELAEIV RRQEEDPRRI ILPIFYMVDP SDVRHQTGCY KKAFRKHANK
FDGQTIQNWK DALKKVGDLK GWHIGKNDKQ GAIADKVSAD IWSHISKENL ILETDELVGI
DDHITAVLEK LSLDSENVTM VGLYGMGGIG KTTTAKAVYN KISSCFDCCC FIDNIRETQE
KDGVVVLQKK LVSEILRIDS GSVGFNNDSG GRKTIKERVS RFKILVVLDD VDEKFKFEDM
LGSPKDFISQ SRFIITSRSM RVLGTLNENQ CKLYEVGSMS KPRSLELFSK HAFKKNTPPS
YYETLANDVV DTTAGLPLTL KVIGSLLFKQ EIAVWEDTLE QLRRTLNLDE VYDRLKISYD
ALNPEAKEIF LDIACFFIGQ NKEEPYYMWT DCNFYPASNI IFLIQRCMIQ VGDDDEFKMH
DQLRDMGREI VRREDVLPWK RSRIWSAEEG IDLLLNKKGS SKVKAISIPW GVKYEFKSEC
FLNLSELRYL HAREAMLTGD FNNLLPNLKW LELPFYKHGE DDPPLTNYTM KNLIIVILEH
SHITADDWGG WRHMMKMAER LKVVRLASNY SLYGRRVRLS DCWRFPKSIE VLSMTAIEMD
EVDIGELKKL KTLVLKFCPI QKISGGTFGM LKGLRELCLE FNWGTNLREV VADIGQLSSL
KVLKTTGAKE VEINEFPLGL KELSTSSRIP NLSQLLDLEV LKVYDCKDGF DMPPASPSED
ESSVWWKVSK LKSLQLEKTR INVNVVDDAS SGGHLPRYLL PTSLTYLKIY QCTEPTWLPG
IENLENLTSL EVNDIFQTLG GDLDGLQGLR SLEILRIRKV NGLARIKGLK DLLCSSTCKL
RKFYITECPD LIELLPCELG GQTVVVPSMA ELTIRDCPRL EVGPMIRSLP KFPMLKKLDL
AVANITKEED LDAIGSLEEL VSLELELDDT SSGIERIVSS SKLQKLTTLV VKVPSLREIE
GLEELKSLQD LYLEGCTSLG RLPLEKLKEL DIGGCPDLTE LVQTVVAVPS LRGLTIRDCP
RLEVGPMIQS LPKFPMLNEL TLSMVNITKE DELEVLGSLE ELDSLELTLD DTCSSIERIS
FLSKLQKLTT LIVEVPSLRE IEGLAELKSL RILYLEGCTS LERLWPDQQQ LGSLKNLNVL
DIQGCKSLSV DHLSALKTTL PPRARITWPD QPYR
