IPA7_SHIFL
ID IPA7_SHIFL Reviewed; 565 AA.
AC P18014; Q7BCM7; Q7BEH5; Q99Q94;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, sequence version 2.
DT 25-MAY-2022, entry version 139.
DE RecName: Full=Probable E3 ubiquitin-protein ligase ipaH7.8;
DE EC=2.3.2.27 {ECO:0000269|PubMed:30872533};
DE AltName: Full=Probable RING-type E3 ubiquitin transferase ipaH7.8 {ECO:0000305};
GN Name=ipaH7.8 {ECO:0000303|PubMed:30872533}; OrderedLocusNames=CP0078;
GN ORFNames=pWR501_0084, SFLP133;
OS Shigella flexneri.
OG Plasmid pWR100, Plasmid pCP301, and Plasmid pSF5.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Shigella.
OX NCBI_TaxID=623;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-8, AND SUBCELLULAR
RP LOCATION.
RC STRAIN=M90T / Serotype 5a; PLASMID=pWR100;
RX PubMed=11115111; DOI=10.1046/j.1365-2958.2000.02179.x;
RA Buchrieser C., Glaser P., Rusniok C., Nedjari H., d'Hauteville H.,
RA Kunst F., Sansonetti P.J., Parsot C.;
RT "The virulence plasmid pWR100 and the repertoire of proteins secreted by
RT the type III secretion apparatus of Shigella flexneri.";
RL Mol. Microbiol. 38:760-771(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=M90T / Serotype 5a; PLASMID=pWR100;
RX PubMed=11292750; DOI=10.1128/iai.69.5.3271-3285.2001;
RA Venkatesan M.M., Goldberg M.B., Rose D.J., Grotbeck E.J., Burland V.,
RA Blattner F.R.;
RT "Complete DNA sequence and analysis of the large virulence plasmid of
RT Shigella flexneri.";
RL Infect. Immun. 69:3271-3285(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Serotype 5; PLASMID=pSF5;
RX PubMed=16704117; DOI=10.1007/s11427-006-0141-3;
RA Xiong Z., Tang X., Yang F., Zhang X., Yang J., Chen L., Nie H., Yan Y.,
RA Jiang Y., Wang J., Xue Y., Xu X., Zhu Y., Dong J., An L., Wang X., Jin Q.;
RT "Comparison of the virulence plasmid genomes of two strains of Shigella
RT which lost the ability to bind Congo red.";
RL Sci. China, Ser. C, Life Sci. 49:141-148(2006).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 34-565.
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 [6]
RP SUBCELLULAR LOCATION, AND SECRETION VIA TYPE III SECRETION SYSTEM.
RC STRAIN=YSH6000 / Serotype 2a;
RX PubMed=11418613; DOI=10.1074/jbc.m101882200;
RA Toyotome T., Suzuki T., Kuwae A., Nonaka T., Fukuda H., Imajoh-Ohmi S.,
RA Toyofuku T., Hori M., Sasakawa C.;
RT "Shigella protein IpaH(9.8) is secreted from bacteria within mammalian
RT cells and transported to the nucleus.";
RL J. Biol. Chem. 276:32071-32079(2001).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF CYS-357.
RX PubMed=30872533; DOI=10.1126/science.aau1330;
RA Sandstrom A., Mitchell P.S., Goers L., Mu E.W., Lesser C.F., Vance R.E.;
RT "Functional degradation: A mechanism of NLRP1 inflammasome activation by
RT diverse pathogen enzymes.";
RL Science 364:0-0(2019).
CC -!- FUNCTION: E3 ubiquitin ligase effector protein that interferes with
CC host's ubiquitination pathway (PubMed:30872533). Functions to alter
CC host cell physiology and promote bacterial survival in host tissues
CC (PubMed:30872533). Catalyzes ubiquitination of mouse Nlrp1b allele 1
CC protein, releasing the cleaved C-terminal part of Nlrp1b, which
CC polymerizes and forms the Nlrp1b inflammasome followed by host cell
CC pyroptosis (PubMed:30872533). {ECO:0000269|PubMed:30872533}.
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:30872533};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:D0ZVG2}. Host
CC cytoplasm {ECO:0000250|UniProtKB:D0ZVG2}. Note=Secreted via Mxi-Spa
CC type III secretion system (TTSS), and delivered into the host
CC cytoplasm. {ECO:0000250|UniProtKB:D0ZVG2}.
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:D0ZPH9}.
CC -!- PTM: Ubiquitinated in the presence of host E1 ubiquitin-activating
CC enzyme, E2 ubiquitin-conjugating enzyme and ubiquitin.
CC {ECO:0000250|UniProtKB:D0ZPH9}.
CC -!- SIMILARITY: Belongs to the LRR-containing bacterial E3 ligase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA26526.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF386526; AAL72346.1; -; Genomic_DNA.
DR EMBL; AF348706; AAK18394.1; -; Genomic_DNA.
DR EMBL; AY879342; AAW64892.1; -; Genomic_DNA.
DR EMBL; AL391753; CAC05787.1; -; Genomic_DNA.
DR EMBL; M32063; AAA26526.1; ALT_FRAME; Genomic_DNA.
DR PIR; A35149; A35149.
DR RefSeq; NP_085238.1; NC_002698.1.
DR RefSeq; NP_858211.1; NC_004851.1.
DR RefSeq; WP_010921637.1; NZ_CP026800.1.
DR RefSeq; YP_006960361.1; NC_019197.1.
DR RefSeq; YP_009062469.1; NC_024996.1.
DR PDB; 3CKD; X-ray; 2.65 A; A/B/C=274-560.
DR PDBsum; 3CKD; -.
DR AlphaFoldDB; P18014; -.
DR SMR; P18014; -.
DR STRING; 198214.CP0078; -.
DR EnsemblBacteria; AAL72346; AAL72346; SF_p0078.
DR GeneID; 1238049; -.
DR KEGG; sfl:CP0078; -.
DR PATRIC; fig|198214.7.peg.5325; -.
DR HOGENOM; CLU_018533_2_0_6; -.
DR OMA; LTSNEHY; -.
DR PRO; PR:P18014; -.
DR Proteomes; UP000001006; Plasmid pCP301.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0034055; P:effector-mediated induction of programmed cell death in host; IMP:CACAO.
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 3D-structure; Direct protein sequencing; Host cytoplasm;
KW Leucine-rich repeat; Plasmid; Reference proteome; Repeat; Secreted;
KW Transferase; Ubl conjugation; Ubl conjugation pathway; Virulence.
FT CHAIN 1..565
FT /note="Probable E3 ubiquitin-protein ligase ipaH7.8"
FT /id="PRO_0000084218"
FT REPEAT 58..79
FT /note="LRR 1"
FT REPEAT 80..97
FT /note="LRR 2"
FT REPEAT 98..119
FT /note="LRR 3"
FT REPEAT 120..137
FT /note="LRR 4"
FT REPEAT 138..157
FT /note="LRR 5"
FT REPEAT 158..179
FT /note="LRR 6"
FT REPEAT 180..199
FT /note="LRR 7"
FT REPEAT 202..223
FT /note="LRR 8"
FT REPEAT 225..248
FT /note="LRR 9"
FT REGION 1..262
FT /note="Interaction with target proteins"
FT /evidence="ECO:0000250"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 263..270
FT /note="Linker"
FT /evidence="ECO:0000250"
FT REGION 271..565
FT /note="E3 ubiquitin-protein ligase catalytic domain"
FT /evidence="ECO:0000305|PubMed:30872533"
FT ACT_SITE 357
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000250|UniProtKB:D0ZVG2"
FT MUTAGEN 357
FT /note="C->A: Abolished ubiquitin ligase activity and
FT ability to ubiquitinate host Nlrp1b."
FT /evidence="ECO:0000269|PubMed:30872533"
FT CONFLICT 527
FT /note="E -> Q (in Ref. 5; AAA26526)"
FT /evidence="ECO:0000305"
FT HELIX 274..279
FT /evidence="ECO:0007829|PDB:3CKD"
FT TURN 284..286
FT /evidence="ECO:0007829|PDB:3CKD"
FT TURN 288..290
FT /evidence="ECO:0007829|PDB:3CKD"
FT TURN 292..294
FT /evidence="ECO:0007829|PDB:3CKD"
FT HELIX 295..297
FT /evidence="ECO:0007829|PDB:3CKD"
FT HELIX 303..314
FT /evidence="ECO:0007829|PDB:3CKD"
FT HELIX 325..338
FT /evidence="ECO:0007829|PDB:3CKD"
FT HELIX 340..352
FT /evidence="ECO:0007829|PDB:3CKD"
FT STRAND 356..358
FT /evidence="ECO:0007829|PDB:3CKD"
FT HELIX 361..379
FT /evidence="ECO:0007829|PDB:3CKD"
FT TURN 380..384
FT /evidence="ECO:0007829|PDB:3CKD"
FT HELIX 386..410
FT /evidence="ECO:0007829|PDB:3CKD"
FT HELIX 418..428
FT /evidence="ECO:0007829|PDB:3CKD"
FT TURN 429..434
FT /evidence="ECO:0007829|PDB:3CKD"
FT HELIX 452..474
FT /evidence="ECO:0007829|PDB:3CKD"
FT HELIX 478..486
FT /evidence="ECO:0007829|PDB:3CKD"
FT HELIX 489..515
FT /evidence="ECO:0007829|PDB:3CKD"
FT HELIX 524..553
FT /evidence="ECO:0007829|PDB:3CKD"
SQ SEQUENCE 565 AA; 64532 MW; 9294E03F99189520 CRC64;
MFSVNNTHSS VSCSPSINSN STSNEHYLRI LTEWEKNSSP GEERGIAFNR LSQCFQNQEA
VLNLSDLNLT SLPELPKHIS ALIVENNKLT SLPKLPAFLK ELNADNNRLS VIPELPESLT
TLSVRSNQLE NLPVLPNHLT SLFVENNRLY NLPALPEKLK FLHVYYNRLT TLPDLPDKLE
ILCAQRNNLV TFPQFSDRNN IRQKEYYFHF NQITTLPESF SQLDSSYRIN ISGNPLSTRV
LQSLQRLTSS PDYHGPQIYF SMSDGQQNTL HRPLADAVTA WFPENKQSDV SQIWHAFEHE
EHANTFSAFL DRLSDTVSAR NTSGFREQVA AWLEKLSASA ELRQQSFAVA ADATESCEDR
VALTWNNLRK TLLVHQASEG LFDNDTGALL SLGREMFRLE ILEDIARDKV RTLHFVDEIE
VYLAFQTMLA EKLQLSTAVK EMRFYGVSGV TANDLRTAEA MVRSREENEF TDWFSLWGPW
HAVLKRTEAD RWAQAEEQKY EMLENEYSQR VADRLKASGL SGDADAEREA GAQVMRETEQ
QIYRQLTDEV LALRLSENGS RLHHS
