ID   IPA25_SHIFL             Reviewed;         563 AA.
AC   A0A0H2USC0;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   16-SEP-2015, sequence version 1.
DT   03-AUG-2022, entry version 27.
DE   RecName: Full=E3 ubiquitin-protein ligase IpaH2.5 {ECO:0000305};
DE            EC=2.3.2.27 {ECO:0000269|PubMed:27572974};
GN   Name=ipaH2.5 {ECO:0000303|PubMed:1690703};
GN   ORFNames=SF_p0054 {ECO:0000312|EMBL:AAL72348.1};
OS   Shigella flexneri.
OG   Plasmid pCP301.
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC   Enterobacteriaceae; Shigella.
OX   NCBI_TaxID=623;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=301 / Serotype 2a; PLASMID=pCP301;
RX   PubMed=12384590; DOI=10.1093/nar/gkf566;
RA   Jin Q., Yuan Z., Xu J., Wang Y., Shen Y., Lu W., Wang J., Liu H., Yang J.,
RA   Yang F., Zhang X., Zhang J., Yang G., Wu H., Qu D., Dong J., Sun L.,
RA   Xue Y., Zhao A., Gao Y., Zhu J., Kan B., Ding K., Chen S., Cheng H.,
RA   Yao Z., He B., Chen R., Ma D., Qiang B., Wen Y., Hou Y., Yu J.;
RT   "Genome sequence of Shigella flexneri 2a: insights into pathogenicity
RT   through comparison with genomes of Escherichia coli K12 and O157.";
RL   Nucleic Acids Res. 30:4432-4441(2002).
RN   [2]
RP   IDENTIFICATION.
RC   STRAIN=M90T / Serotype 5a;
RX   PubMed=1690703; DOI=10.1128/jb.172.4.1905-1915.1990;
RA   Hartman A.B., Venkatesan M.M., Oaks E.V., Buysse J.M.;
RT   "Sequence and molecular characterization of a multicopy invasion plasmid
RT   antigen gene, ipaH, of Shigella flexneri.";
RL   J. Bacteriol. 172:1905-1915(1990).
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH HUMAN RBCK1 AND RNF31,
RP   ACTIVE SITE, AND MUTAGENESIS OF CYS-368.
RX   PubMed=27572974; DOI=10.1038/nmicrobiol.2016.84;
RA   de Jong M.F., Liu Z., Chen D., Alto N.M.;
RT   "Shigella flexneri suppresses NF-kappaB activation by inhibiting linear
RT   ubiquitin chain ligation.";
RL   Nat. Microbiol. 1:16084-16084(2016).
CC   -!- FUNCTION: E3 ubiquitin-protein ligase effector that inhibits host cell
CC       innate immunity during bacterial infection by catalyzing 'Lys-48'-
CC       linked polyubiquitination and subsequent degradation of host RNF31/HOIP
CC       (PubMed:27572974). Host RNF31/HOIP is the catalytic component of the
CC       LUBAC complex, which conjugates linear ('Met-1'-linked) polyubiquitin
CC       chains at the surface of bacteria invading the host cytosol to form the
CC       ubiquitin coat surrounding bacteria (PubMed:27572974). The bacterial
CC       ubiquitin coat acts as an 'eat-me' signal for xenophagy and promotes
CC       NF-kappa-B activation (PubMed:27572974). {ECO:0000269|PubMed:27572974}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC         [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC         cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC         EC=2.3.2.27; Evidence={ECO:0000269|PubMed:27572974};
CC   -!- ACTIVITY REGULATION: Exists in an autoinhibited state in the absence of
CC       substrate protein, probably due to interactions of the leucine-rich
CC       repeat domain with the catalytic domain. Is activated upon binding to a
CC       substrate protein. {ECO:0000250|UniProtKB:Q8VSC3}.
CC   -!- SUBUNIT: Interacts with human RBCK1/HOIL-1 and RNF31/HOIP components of
CC       the LUBAC complex. {ECO:0000269|PubMed:27572974}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q8VSC3}. Host
CC       cytoplasm {ECO:0000250|UniProtKB:Q8VSC3}. Note=Secreted via Mxi-Spa
CC       type III secretion system (TTSS), and delivered into the host
CC       cytoplasm. {ECO:0000250|UniProtKB:Q8VSC3}.
CC   -!- DOMAIN: The LRR (leucine-rich repeat) domain forms a slightly curved
CC       solenoid and may mediate interaction with target proteins.
CC       {ECO:0000250|UniProtKB:P0CE12}.
CC   -!- SIMILARITY: Belongs to the LRR-containing bacterial E3 ligase family.
CC       {ECO:0000305}.
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DR   EMBL; AF386526; AAL72348.1; -; Genomic_DNA.
DR   RefSeq; NP_858187.1; NC_004851.1.
DR   STRING; 198214.CP0054; -.
DR   EnsemblBacteria; AAL72348; AAL72348; SF_p0054.
DR   GeneID; 1238051; -.
DR   KEGG; sfl:CP0054; -.
DR   PATRIC; fig|198214.7.peg.5294; -.
DR   HOGENOM; CLU_018533_2_0_6; -.
DR   Proteomes; UP000001006; Plasmid pCP301.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0090729; F:toxin activity; IDA:UniProtKB.
DR   GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR   Gene3D; 3.80.10.10; -; 1.
DR   InterPro; IPR001611; Leu-rich_rpt.
DR   InterPro; IPR032675; LRR_dom_sf.
DR   InterPro; IPR032674; LRR_E3_ligase_N.
DR   InterPro; IPR029487; NEL_dom.
DR   Pfam; PF14496; NEL; 1.
DR   Pfam; PF12468; TTSSLRR; 1.
DR   PROSITE; PS51450; LRR; 4.
PE   1: Evidence at protein level;
KW   Host cytoplasm; Leucine-rich repeat; Plasmid; Reference proteome; Repeat;
KW   Secreted; Transferase; Ubl conjugation pathway; Virulence.
FT   CHAIN           1..563
FT                   /note="E3 ubiquitin-protein ligase IpaH2.5"
FT                   /id="PRO_0000454197"
FT   REPEAT          69..90
FT                   /note="LRR 1"
FT                   /evidence="ECO:0000255"
FT   REPEAT          91..115
FT                   /note="LRR 2"
FT                   /evidence="ECO:0000255"
FT   REPEAT          117..130
FT                   /note="LRR 3"
FT                   /evidence="ECO:0000255"
FT   REPEAT          131..150
FT                   /note="LRR 4"
FT                   /evidence="ECO:0000255"
FT   REPEAT          151..170
FT                   /note="LRR 5"
FT                   /evidence="ECO:0000255"
FT   REPEAT          171..195
FT                   /note="LRR 6"
FT                   /evidence="ECO:0000255"
FT   REPEAT          197..209
FT                   /note="LRR 7"
FT                   /evidence="ECO:0000255"
FT   REPEAT          210..233
FT                   /note="LRR 8"
FT                   /evidence="ECO:0000255"
FT   REGION          1..270
FT                   /note="Interaction with target proteins"
FT                   /evidence="ECO:0000250|UniProtKB:P0CE12"
FT   REGION          271..281
FT                   /note="Linker"
FT                   /evidence="ECO:0000250|UniProtKB:P0CE12"
FT   REGION          282..563
FT                   /note="E3 ubiquitin-protein ligase catalytic domain"
FT                   /evidence="ECO:0000250|UniProtKB:P0CE12"
FT   ACT_SITE        368
FT                   /note="Glycyl thioester intermediate"
FT                   /evidence="ECO:0000305|PubMed:27572974"
FT   MUTAGEN         368
FT                   /note="C->S: Abolished E3 ubiquitin-protein ligase activity
FT                   and ability to ubiquitinate host RNF31/HOIP."
FT                   /evidence="ECO:0000269|PubMed:27572974"
SQ   SEQUENCE   563 AA;  63587 MW;  035926759C043DB3 CRC64;
     MIKSTNIQVI GSGIMHQINN IHSLTLFSLP VSLSPSCNEY YLKVWSEWER NGTPGEQRNI
     AFNRLKICLQ NQEAELNLSE LDLKTLPDLP PQITTLEIRK NLLTHLPDLP PMLKVIHAQF
     NQLESLPALP ETLEELNAGD NKIKELPFLP ENLTHLRVHN NRLHILPLLP PELKLLVVSG
     NRLDSIPPFP DKLEGLALAN NFIEQLPELP FSMNRAVLMN NNLTTLPESV LRLAQNAFVN
     VAGNPLSGHT MRTLQQITTG PDYSGPQIFF SMGNSATISA PEHSLADAVT AWFPENKQSD
     VSQIWHAFEH EEHANTFSAF LDRLSDTVSA RNTSGFREQV AAWLEKLSAS AELRQQSFAV
     AADATESCED RVALTWNNLR KTLLVHQASE GLFDNDTGAL LSLGREMFRL EILEDIARDK
     VRTLHFVDEI EVYLAFQTML AEKLQLSTAV KEMRFYGVSG VTANDLRTAE AMVRSREENE
     FTDWFSLWGP WHAVLKRTEA DRWAQAEEQK YEMLENEYSQ RVADRLKASG LSGDADAERE
     AGAQVMRETE QQIYRQLTDE VLA