LUBEL_DROME
ID LUBEL_DROME Reviewed; 2892 AA.
AC Q8IPJ3; M9PB55; M9PCD7; M9PCS0; Q9VM88;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2013, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=E3 ubiquitin-protein ligase lubel {ECO:0000305};
DE EC=2.3.2.31 {ECO:0000269|PubMed:27702987, ECO:0000269|PubMed:30026495};
DE AltName: Full=Linear Ubiquitin E3 ligase {ECO:0000303|PubMed:27702987};
GN Name=LUBEL {ECO:0000303|PubMed:27702987, ECO:0000312|FlyBase:FBgn0031857};
GN ORFNames=CG11321 {ECO:0000312|FlyBase:FBgn0031857};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000312|EMBL:AEW43899.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C).
RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.;
RL Submitted (DEC-2011) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, DEVELOPMENTAL STAGE, DOMAIN, DISRUPTION
RP PHENOTYPE, ACTIVE SITE, AND MUTAGENESIS OF CYS-2690; CYS-2693; CYS-2704;
RP 2719-CYS--GLY-2892; ARG-2754 AND ASP-2755.
RX PubMed=27702987; DOI=10.15252/embr.201642378;
RA Asaoka T., Almagro J., Ehrhardt C., Tsai I., Schleiffer A., Deszcz L.,
RA Junttila S., Ringrose L., Mechtler K., Kavirayani A., Gyenesei A.,
RA Hofmann K., Duchek P., Rittinger K., Ikeda F.;
RT "Linear ubiquitination by LUBEL has a role in Drosophila heat stress
RT response.";
RL EMBO Rep. 17:1624-1640(2016).
RN [5] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF CYS-2704.
RX PubMed=30026495; DOI=10.1038/s41418-018-0164-x;
RA Aalto A.L., Mohan A.K., Schwintzer L., Kupka S., Kietz C., Walczak H.,
RA Broemer M., Meinander A.;
RT "M1-linked ubiquitination by LUBEL is required for inflammatory responses
RT to oral infection in Drosophila.";
RL Cell Death Differ. 26:860-876(2019).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which conjugates linear 'Met-
CC 1'- and 'Lys-63'-linked polyubiquitin chains to substrates and plays a
CC crucial role in the NF-kappa-B intestinal inflammatory response to oral
CC infection and in the heat stress response (PubMed:27702987,
CC PubMed:30026495). Preferentially interacts with 'Lys-63'-linked, and to
CC a lesser extent 'Lys-48'-linked, polyubiquitin chains
CC (PubMed:27702987). Upon oral infection with a Gram-negative bacterium
CC E.carotovora subsp. carotovora 15, functions with the E2 ubiquitin-
CC conjugating enzyme Ubc10 to mediate the conjugation of 'Lys-63'- and
CC linear 'Met-1'-linked polyubiquitin chains to the substrate key which
CC is essential for activation of the NF-kappa-B signaling cascade in the
CC adult intestinal epithelium (PubMed:27702987, PubMed:30026495). It is
CC not required for systemic immune response to septic infection with
CC either E.carotovora subsp. carotovora 15 or Gram-positive M.luteus
CC bacteria (PubMed:30026495). Function in controlling linear
CC ubiquitination is also essential for regulating the heat stress
CC response in adults. This function may require the E2 ubiquitin-
CC conjugating enzymes Ubc10 or eff (PubMed:27702987).
CC {ECO:0000269|PubMed:27702987, ECO:0000269|PubMed:30026495}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + [acceptor protein]-N(6)-ubiquitinyl-L-lysine.;
CC EC=2.3.2.31; Evidence={ECO:0000269|PubMed:27702987,
CC ECO:0000269|PubMed:30026495};
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=E {ECO:0000312|FlyBase:FBgn0031857};
CC IsoId=Q8IPJ3-1; Sequence=Displayed;
CC Name=C {ECO:0000312|FlyBase:FBgn0031857}; Synonyms=F
CC {ECO:0000312|FlyBase:FBgn0031857};
CC IsoId=Q8IPJ3-2; Sequence=VSP_060445;
CC Name=G {ECO:0000312|FlyBase:FBgn0031857};
CC IsoId=Q8IPJ3-3; Sequence=VSP_060442;
CC Name=I {ECO:0000312|FlyBase:FBgn0031857};
CC IsoId=Q8IPJ3-4; Sequence=VSP_060442, VSP_060445;
CC Name=J {ECO:0000312|FlyBase:FBgn0031857};
CC IsoId=Q8IPJ3-5; Sequence=VSP_060442, VSP_060443, VSP_060444;
CC -!- DEVELOPMENTAL STAGE: Strong expression in 10 to 14 hour embryos.
CC {ECO:0000269|PubMed:27702987}.
CC -!- DOMAIN: UBA-like 2 (UBA2), but not UBA-like 1 (UBA1), domain interacts
CC with tetra or longer polyubiquitin chains, and di-ubiquitin chains
CC linked via 'lys-63', and to a lesser extent 'lys-48'. However, neither
CC of the UBA1 or UBA2 domains interact with linear 'Met-1'-linked
CC polyubiquitin chains. {ECO:0000269|PubMed:27702987}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in reduced heat
CC tolerance with adults displaying decreased survival upon heat shock.
CC RNAi-mediated knockdown in the muscles results in only a slight
CC decrease in survival upon heat shock, compared to whole-body knockdown.
CC {ECO:0000269|PubMed:27702987}.
CC -!- SIMILARITY: Belongs to the RBR family. {ECO:0000305}.
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DR EMBL; AE014134; AAF52435.3; -; Genomic_DNA.
DR EMBL; AE014134; AAN10598.2; -; Genomic_DNA.
DR EMBL; AE014134; AGB92692.1; -; Genomic_DNA.
DR EMBL; AE014134; AGB92693.1; -; Genomic_DNA.
DR EMBL; AE014134; AGB92695.1; -; Genomic_DNA.
DR EMBL; AE014134; AGB92696.1; -; Genomic_DNA.
DR EMBL; BT132959; AEW43899.1; -; mRNA.
DR RefSeq; NP_001260156.1; NM_001273227.1. [Q8IPJ3-5]
DR RefSeq; NP_001260157.1; NM_001273228.2. [Q8IPJ3-2]
DR RefSeq; NP_001260159.1; NM_001273230.2. [Q8IPJ3-3]
DR RefSeq; NP_001260160.1; NM_001273231.2. [Q8IPJ3-4]
DR RefSeq; NP_609072.2; NM_135228.4. [Q8IPJ3-5]
DR RefSeq; NP_723214.2; NM_164709.4. [Q8IPJ3-1]
DR SMR; Q8IPJ3; -.
DR STRING; 7227.FBpp0303658; -.
DR PaxDb; Q8IPJ3; -.
DR PRIDE; Q8IPJ3; -.
DR DNASU; 33950; -.
DR EnsemblMetazoa; FBtr0290295; FBpp0288734; FBgn0031857. [Q8IPJ3-5]
DR EnsemblMetazoa; FBtr0331216; FBpp0303658; FBgn0031857. [Q8IPJ3-1]
DR EnsemblMetazoa; FBtr0331217; FBpp0303659; FBgn0031857. [Q8IPJ3-5]
DR EnsemblMetazoa; FBtr0331218; FBpp0303660; FBgn0031857. [Q8IPJ3-2]
DR EnsemblMetazoa; FBtr0331220; FBpp0303662; FBgn0031857. [Q8IPJ3-3]
DR EnsemblMetazoa; FBtr0331221; FBpp0303663; FBgn0031857. [Q8IPJ3-4]
DR GeneID; 33950; -.
DR KEGG; dme:Dmel_CG11321; -.
DR UCSC; CG11321-RB; d. melanogaster. [Q8IPJ3-1]
DR UCSC; CG11321-RC; d. melanogaster.
DR CTD; 33950; -.
DR FlyBase; FBgn0031857; LUBEL.
DR VEuPathDB; VectorBase:FBgn0031857; -.
DR eggNOG; KOG1812; Eukaryota.
DR GeneTree; ENSGT00530000064112; -.
DR HOGENOM; CLU_000929_0_0_1; -.
DR InParanoid; Q8IPJ3; -.
DR OMA; QWLRDNW; -.
DR OrthoDB; 6989at2759; -.
DR SignaLink; Q8IPJ3; -.
DR BioGRID-ORCS; 33950; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 33950; -.
DR PRO; PR:Q8IPJ3; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0031857; Expressed in mouthpart and 12 other tissues.
DR ExpressionAtlas; Q8IPJ3; baseline and differential.
DR Genevisible; Q8IPJ3; DM.
DR GO; GO:0071797; C:LUBAC complex; IEA:InterPro.
DR GO; GO:0036435; F:K48-linked polyubiquitin modification-dependent protein binding; IDA:FlyBase.
DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; IDA:FlyBase.
DR GO; GO:1990450; F:linear polyubiquitin binding; IDA:FlyBase.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:FlyBase.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:FlyBase.
DR GO; GO:0008270; F:zinc ion binding; ISM:FlyBase.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:FlyBase.
DR GO; GO:0010286; P:heat acclimation; IMP:FlyBase.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR GO; GO:0061059; P:positive regulation of peptidoglycan recognition protein signaling pathway; IDA:FlyBase.
DR GO; GO:0097039; P:protein linear polyubiquitination; IDA:FlyBase.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:FlyBase.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR002867; IBR_dom.
DR InterPro; IPR026254; RNF31-like.
DR InterPro; IPR032065; RNF31-UBA.
DR InterPro; IPR041031; RNF31_C.
DR InterPro; IPR044066; TRIAD_supradom.
DR InterPro; IPR001876; Znf_RanBP2.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR16004; PTHR16004; 2.
DR Pfam; PF18091; E3_UbLigase_RBR; 1.
DR Pfam; PF16678; HOIP-UBA; 1.
DR Pfam; PF01485; IBR; 1.
DR SMART; SM00647; IBR; 2.
DR SMART; SM00184; RING; 2.
DR SMART; SM00547; ZnF_RBZ; 1.
DR PROSITE; PS51873; TRIAD; 1.
DR PROSITE; PS01358; ZF_RANBP2_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Immunity; Metal-binding; Reference proteome; Repeat;
KW Stress response; Transferase; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..2892
FT /note="E3 ubiquitin-protein ligase lubel"
FT /id="PRO_0000448740"
FT DOMAIN 1042..1187
FT /note="UBA-like 1"
FT /evidence="ECO:0000269|PubMed:27702987"
FT DOMAIN 2457..2513
FT /note="UBA-like 2"
FT /evidence="ECO:0000269|PubMed:27702987"
FT ZN_FING 2514..2564
FT /note="RING-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ZN_FING 2601..2660
FT /note="IBR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ZN_FING 2690..2720
FT /note="RING-type 2; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT REGION 23..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 125..252
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 395..423
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 483..631
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 644..672
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 685..737
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 757..865
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 949..975
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1214..1252
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1477..1520
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1557..1653
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1717..2019
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2032..2082
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2191..2316
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2411..2431
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2510..2748
FT /note="TRIAD supradomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT REGION 2514..2892
FT /note="Necessary for linear polyubiquitination and
FT sufficent for inducing DptA in the intestine"
FT /evidence="ECO:0000269|PubMed:30026495"
FT COMPBIAS 143..157
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 204..218
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 227..244
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 535..570
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 610..627
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 646..669
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 784..865
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1220..1252
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1569..1594
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1595..1610
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1611..1625
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1629..1653
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1756..1784
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1792..1838
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1852..1890
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1931..1967
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1975..1996
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2038..2078
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2262..2313
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 2704
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:27702987, ECO:0000269|PubMed:30026495"
FT BINDING 2514
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 2517
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 2537
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 2540
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 2618
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 2621
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 2636
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 2639
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 2644
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 2647
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 2655
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 2660
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 2690
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 2693
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 2709
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 2712
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT VAR_SEQ 286..338
FT /note="Missing (in isoform G, isoform I and isoform J)"
FT /evidence="ECO:0000305"
FT /id="VSP_060442"
FT VAR_SEQ 873..887
FT /note="ESVENIWNTLDESIQ -> GRIQKRISFFEGTKT (in isoform J)"
FT /evidence="ECO:0000305"
FT /id="VSP_060443"
FT VAR_SEQ 888..2892
FT /note="Missing (in isoform J)"
FT /evidence="ECO:0000305"
FT /id="VSP_060444"
FT VAR_SEQ 1160..1200
FT /note="Missing (in isoform C and isoform I)"
FT /evidence="ECO:0000305"
FT /id="VSP_060445"
FT MUTAGEN 2690
FT /note="C->S: Loss of catalytic activity. Abolishes
FT formation of linear polyubiquitin chains, slight reduction
FT in longevity and upon heat shock, adults display reduced
FT induction of Hsp70 and thus a reduction in heat stress
FT tolerance. No obvious effect on adult phenotype and no
FT reduction in immunity to E.coli infection; when associated
FT with S-2693."
FT /evidence="ECO:0000269|PubMed:27702987"
FT MUTAGEN 2693
FT /note="C->S: Loss of catalytic activity. Abolishes
FT formation of linear polyubiquitin chains, slight reduction
FT in longevity and upon heat shock, adults display reduced
FT induction of Hsp70 and thus a reduction in heat stress
FT tolerance. No obvious effect on adult phenotype and no
FT reduction in immunity to E.coli infection; when associated
FT with S-2690."
FT /evidence="ECO:0000269|PubMed:27702987"
FT MUTAGEN 2704
FT /note="C->A: Reduces formation of linear ubiquitin chains."
FT /evidence="ECO:0000269|PubMed:27702987,
FT ECO:0000269|PubMed:30026495"
FT MUTAGEN 2719..2892
FT /note="Missing: Reduces formation of linear polyubiquitin
FT chains, slight reduction in longevity and upon heat shock
FT adults display reduced induction of Hsp70 and thus a
FT reduction in heat stress tolerance. No obvious effect on
FT adult phenotype and no reduction in immunity to E.coli
FT infection."
FT /evidence="ECO:0000269|PubMed:27702987"
FT MUTAGEN 2754
FT /note="R->A: Reduces formation of linear polyubiquitin
FT chains."
FT /evidence="ECO:0000269|PubMed:27702987"
FT MUTAGEN 2755
FT /note="D->A: Reduces formation of linear polyubiquitin
FT chains."
FT /evidence="ECO:0000269|PubMed:27702987"
SQ SEQUENCE 2892 AA; 320914 MW; B80CDCC97487BC89 CRC64;
MTTHQLLNKN VRTMPSWVME ANDRIGPKPP PTPPNGVAGG LPKAPALPPK AKSTPEPDYE
IIEFSSQQYS NEPMKTTVIR TKTPDNKLKC TLCGSQNPWV TCAECAGQIF CASCDDMFHK
HPKRKQHMRK AVEQGTPPIP PKAQAGGGAP PPVAPPRRSK RGLLTPFLGR KDQMLPPPSP
TPSHKSLGGW RGSLGGGATP PVPPIATSSA NQMNNRPLPD PPRSEGGGSS RSGTPKSVFD
TIQRPPSVQL EKIKSKASAT LDRMAILQQR YRQQKARQDL SANSEQHLSN EAGFEHWSNI
SPSPSHFRSG SMSSGLNSSH FDLSDDSQFH NSLLLQQRQA AGAQRRQMST SVFNLNSNPR
RPLSEAQNGG AWLANQRIQQ AQSLAQLNCA GCQQSQQHPG WAQHPHQALP QHQHPDQWSQ
FGSQQQFNNS NLSLNVGPGY MSQQHHPHYP PPVFMTQRGM MPNVYPGAPG YPMMHPGVMG
MPPSAASRAA SRSRYAASPT PSRKSMSLRR KRNSYVDDEL TDDEDSDQDD RRSLVSNRSG
MTSASRSQHH QNHIQPRQRR LSSASQLIAS DELDGDQVHH KMRNRRGSIA KSVQSEWLPE
RRENEGTLTR NKTATDSART SRIYSDLESE GSGARALVQA KIQQKLQEAD QHKSSKKAEP
KRKPEMKDEN TQAAAVVQKV VVPPAHEESA SEYEEVVEEV TASESEAEAQ TAPDPQEVPD
EIGADDLGPP PSTPDHEWEC EFCTFVNEPN IKICSICCKT PSKPPVQPNK AKKVEEKPQP
PAEKSNNIKA SSKTETKPVQ KPTTKSQQPS QKSVAALSKT THTNSTSSSK ASPAVNSKTT
SSIPIKTPSK STLKTSSENE SDNSLAKSLL HKESVENIWN TLDESIQAQA EQVLKKAQKV
STACGGTPPR EIAAVEMGTS PPPQSISTQT YDALPFNTKQ EEIIPVVPDR FTTPEPNKME
RRPHYRSNSQ LQQESERYRS ANDLRYHDGF GLDPYSAGLV TKRPNFINEL RMLQLQVSSP
FDMPHETFGV KHEPARDPET EMHIILKELE LYKFTVEELE AALKYCSPET HPIQWLRENW
HKLVQTVQSL STKYGQERGE NTIGTVSQNE AREALRNSGG NVWQAVADCI QQRQQKYRKL
AAKGNFLRDD IVNALTAHQG NVEQALVELN RTQLKPFLMR IWGSPNGVEN ESGVAIDTKS
DIHDFLNTHA LDCLQPPLAG QSPSPAQANP FDQPRTDESP VKSTYATPSP YQMEDSTLKN
LEILIGNMEQ NQAKQNQEVL RSIETMLDTF KGKPELEYET DPEIMRILTK SPISTMKPSG
PAEDKSTDDV KNFVWQHIQE IVPNLVQQVE QELMEKPEEV AKIEAEQPKE PEPLLEPQPE
PTPSVDPAVY IMEEVIKPNL REASIREEVQ PSFIYATEIA NFKLEFDRGT ERWHEAEWES
SDLTDAERIV YKCYMAPNEQ PKEDVVDVAV ESSVNSLPTA KAQEESAPEV PIEAQKIENT
EVTQPETVNE ELRQQEKLET PLVITSETIS ETVSQTANES DKQKSIENNL QIKQNVAEVQ
VQSDDQPSTS RDANRRAKRS QQSRKGRSRE QSQKPTNRTK LPNNIDQKVN ESKTAAKETE
AVKDKDLSAA ASNIQSDVTA SDPKTSTPLK ILSEGTNSNT LETMENVTST DINDNVTIEV
ISNRSEEVPA IQDLGKTKDI SEPTANPIEE ITSIQNSTTI SEQSEGPQEP EIPIEVSETT
EALQVPREEA SIEIVSPPNE EQTKSPTSQE VNIQDTSHII SLPITDVTPT PEIINIAPST
SSISKEQKQS PKRLSKIPVR TLSSSSLRSE SRSSNRTPTA NDEIEREETT SQGVPIGETV
SSPKSEQLSD NQEVNLVSQE TQSKKDTNIV EEPATQPLGL ELEEHSPNAT AVAVSPTDSD
EVFEDAPEFS GSDGTRPHDE TASDAELYSL DSDGQRAETK SPEDEVVILL DEESQMESSI
AQSESNASLD SHSSESETSK VVLKEFVPSG DPAKQNLSEL VEDTQRLIKQ MRDEISMDEF
ESTDEDEYSD EYSDEYDEGE EEEWYDSEGE EEGDFDGEEG NTYNEHASYI EEASTGDEGT
EIEDIMEEDE DLADDDEPLQ SQIPLDIEPV ISPALSVTPT NQETDTIAHT EVVSSTGTRL
ETELPNPAME SILPSQSVQE DIKVEAIPIQ SAPPIADSET RPAEQPVELV LEIPSEVEPT
PVEEPTALPI TPAPPIVDSE SRPVEPPVET VLEEPKKVTP SMKGKTANSG TASKGPSTSS
STKTNKSTVS KIPKPTNEPT NKSNSTPLNK KVPLRSKSFS APMGISSVKR IQEVYLQKQS
SSIATSRVPL KSSPVTKKSI NDAISRFNSN QADGPSTSGA AAAAAAALLK PRSQPRIPKK
KYHETCFSDD DYETSATEEE QEEPNLAEPQ KAEQLKRKMS MPVFRAYPSV QEPVIEDPAI
LARKYVDQEL VTNIAEAQIA ATLVSMKFSE DVALWAAREC SDLDQAIAML QQECELCMNS
YPMNQMVSML KCLHKCCKQC AKSYFTVQIT DRSINDCSCP FCKLPELSNE AQHEDEHLEY
FSNLDIFLKS ILDNDVHELF QRKLRDRSLL QDPNFKWCIQ CSSGFFARPK QKRLICPDCG
SVTCAQCRKP WERQHEGSSC EAYLEWKREN DPELQAQGVQ EHLAQNGIDC PKCKFRYSLA
RGGCMHFTCT QCKFEFCYGC ARPFMMGAKC TVSTYCAKLG LHAHHPRNCL FYLRDKIPLQ
LQFLLKEQNV KFDTEPMQIK DESSSSSKAR AQARCPIPLQ KETPQGLVDT VCNTEVPDKH
AGMCRTHYVE YLAGKVAKAG IDPLPIFDLT DCVQELRRRG IALPERGPWD TDEIYKNMCS
EVIKKHIPLK SA
