IPA14_SHIFL
ID IPA14_SHIFL Reviewed; 575 AA.
AC A0A0H2USG1;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 16-SEP-2015, sequence version 1.
DT 03-AUG-2022, entry version 32.
DE RecName: Full=E3 ubiquitin-protein ligase IpaH1.4 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:27572974};
GN Name=ipaH1.4 {ECO:0000303|PubMed:1690703};
GN ORFNames=SF_p0265 {ECO:0000312|EMBL:AAL72349.2};
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, AND INTERACTION WITH HUMAN RBCK1 AND RNF31.
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).
RN [4]
RP FUNCTION.
RX PubMed=28481331; DOI=10.1038/nmicrobiol.2017.63;
RA Noad J., von der Malsburg A., Pathe C., Michel M.A., Komander D.,
RA Randow F.;
RT "LUBAC-synthesized linear ubiquitin chains restrict cytosol-invading
RT bacteria by activating autophagy and NF-kappaB.";
RL Nat. Microbiol. 2:17063-17063(2017).
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, PubMed:28481331). By promoting
CC degradation of host RNF31/HOIP, IpaH1.4 prevents formation of the
CC bacterial ubiquitin coat and activation of host cell innate immunity
CC (PubMed:27572974, PubMed:28481331). {ECO:0000269|PubMed:27572974,
CC ECO:0000269|PubMed:28481331}.
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; AAL72349.2; -; Genomic_DNA.
DR RefSeq; NP_858398.2; NC_004851.1.
DR RefSeq; WP_000597731.1; NZ_WACK01000004.1.
DR IntAct; A0A0H2USG1; 1.
DR STRING; 198214.CP0265; -.
DR EnsemblBacteria; AAL72349; AAL72349; SF_p0265.
DR GeneID; 1238052; -.
DR KEGG; sfl:CP0265; -.
DR PATRIC; fig|198214.7.peg.5527; -.
DR HOGENOM; CLU_018533_2_0_6; -.
DR OMA; TPFPLPM; -.
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..575
FT /note="E3 ubiquitin-protein ligase IpaH1.4"
FT /id="PRO_0000454196"
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..575
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:0000250|UniProtKB:Q8VSC3"
SQ SEQUENCE 575 AA; 64859 MW; C34DFFECFA9ECCA7 CRC64;
MIKSTNIQAI GSGIMHQINN VYSLTPLSLP MELTPSCNEF YLKTWSEWEK 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 VLALRLSENG SNHIA
