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Q8VSC3 (IPA9_SHIFL) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 67. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase ipaH9.8

EC=6.3.2.-
Alternative name(s):
Invasion plasmid antigen ipaH9.8
Gene names
Name:ipaH9.8
Ordered Locus Names:CP0226
ORF Names:pWR501_0234, SFLP090
Encoded onPlasmid pCP301 Ref.6
Plasmid pWR100 Ref.1 Ref.2 Ref.3 Ref.11
Plasmid pINV_F6_M1382 Ref.4
Plasmid pSF5 Ref.5
OrganismShigella flexneri [Complete proteome] [HAMAP]
Taxonomic identifier623 [NCBI]
Taxonomic lineageBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeShigella

Protein attributes

Sequence length545 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein is an E3 ubiquitin ligase that interferes with host's ubiquitination pathway and modulates the acute inflammatory responses, thus facilitating bacterial colonization within the host cell. Interacts with IKBKG (NEMO) and TNIP1 (ABIN-1), a ubiquitin-binding adapter protein, which results in TNIP1-dependent 'Lys-27'-linked polyubiquitination of IKBKG. Consequently, polyubiquitinated IKBKG undergoes proteasome-dependent degradation, which perturbs NF-kappa-B activation during bacterial infection. Uses UBE2D2 (UBCH5B) as an E2 ubiquitin-conjugating enzyme. Mediates polyubiquitination of host U2AF1, leading to its proteasomal degradation. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12

Enzyme regulation

Exists in an autoinhibited state in the absence of substrate protein, probably due to interactions of the leucine-rich repeat domain with the catalytic domain. Is activated upon binding to a substrate protein. Ref.12

Subunit structure

Interacts with human IKBKG (NEMO) and TNIP1 (ABIN-1). Interacts also with human and murine U2AF1 (U2AF35). Ref.8 Ref.10 Ref.12

Subcellular location

Secreted. Host cytoplasm. Host nucleus. Note: Secreted via Mxi-Spa type III secretion system (TTSS), and delivered into the host cytoplasm. Transported into the host nucleus. This transport is independent of cytosolic factors, but dependent on temperature and partly on ATP/GTP. Ref.2 Ref.7

Induction

Induced upon entry into host epithelial cells. Ref.1 Ref.12

Domain

The LRR (leucine-rich repeat) domain forms a slightly curved solenoid and may mediate interaction with target proteins By similarity.

Post-translational modification

Autoubiquitinated (in vitro). Ubiquitinated in the presence of host E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating enzyme and ubiquitin. Ref.12

Disruption phenotype

In murine lung infection model, mutants cause severe inflammatory responses, with increased pro-inflammatory cytokine production levels. Colonization is greatly reduced. Ref.8

Sequence similarities

Belongs to the LRR-containing bacterial E3 ligase family.

Contains 8 LRR (leucine-rich) repeats.

Sequence caution

The sequence AAK18544.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence AAW64849.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself3EBI-6125799,EBI-6125799
IKBKGQ9Y6K98EBI-6125799,EBI-81279From a different organism.
TNIP1Q150254EBI-6125799,EBI-357849From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 545545E3 ubiquitin-protein ligase ipaH9.8
PRO_0000395755

Regions

Repeat57 – 7721LRR 1
Repeat78 – 9922LRR 2
Repeat100 – 11718LRR 3
Repeat118 – 13922LRR 4
Repeat140 – 15718LRR 5
Repeat158 – 17922LRR 6
Repeat182 – 20322LRR 7
Repeat205 – 22824LRR 8
Region1 – 242242Interaction with target proteins By similarity
Region243 – 2508Linker By similarity
Region251 – 545295E3 ubiquitin-protein ligase catalytic domain By similarity

Sites

Active site3371Glycyl thioester intermediate Ref.11

Natural variations

Natural variant2221P → Q in plasmid pWR100, plasmid pSF5 and plasmid pINV_F6_M1382.
Natural variant4741Q → L in plasmid pINV_F6_M1382.
Natural variant5361P → F in plasmid pWR100.
Natural variant5361P → S in plasmid pSF5.

Experimental info

Mutagenesis1631R → A: Abolishes proteasomal degradation of host proteins; when associated with A-187 and A-210. Ref.11
Mutagenesis1871F → A: Abolishes proteasomal degradation of host proteins; when associated with A-163 and A-210. Ref.11
Mutagenesis2101H → A: Abolishes proteasomal degradation of host proteins; when associated with A-163 and A-187. Ref.11
Mutagenesis3371C → A: Abolishes proteasomal degradation of host proteins. Ref.9 Ref.10 Ref.11
Mutagenesis3371C → A: Loss of activity. Ref.9 Ref.10 Ref.11
Sequence conflict71Missing AA sequence Ref.2

Secondary structure

.............................. 545
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q8VSC3 [UniParc].

Last modified January 4, 2005. Version 2.
Checksum: 5E70042D797B5099

FASTA54561,979
        10         20         30         40         50         60 
MLPINNNFSL PQNSFYNTIS GTYADYFSAW DKWEKQALPG EERDEAVSRL KECLINNSDE 

        70         80         90        100        110        120 
LRLDRLNLSS LPDNLPAQIT LLNVSYNQLT NLPELPVTLK KLYSASNKLS ELPVLPPALE 

       130        140        150        160        170        180 
SLQVQHNELE NLPALPDSLL TMNISYNEIV SLPSLPQALK NLRATRNFLT ELPAFSEGNN 

       190        200        210        220        230        240 
PVVREYFFDR NQISHIPESI LNLRNECSIH ISDNPLSSHA LPALQRLTSS PDYHGPRIYF 

       250        260        270        280        290        300 
SMSDGQQNTL HRPLADAVTA WFPENKQSDV SQIWHAFEHE EHANTFSAFL DRLSDTVSAR 

       310        320        330        340        350        360 
NTSGFREQVA AWLEKLSASA ELRQQSFAVA ADATESCEDR VALTWNNLRK TLLVHQASEG 

       370        380        390        400        410        420 
LFDNDTGALL SLGREMFRLE ILEDIARDKV RTLHFVDEIE VYLAFQTMLA EKLQLSTAVK 

       430        440        450        460        470        480 
EMRFYGVSGV TANDLRTAEA MVRSREENEF TDWFSLWGPW HAVLKRTEAD RWAQAEEQKY 

       490        500        510        520        530        540 
EMLENEYPQR VADRLKASGL SGDADAEREA GAQVMRETEQ QIYRQLTDEV LALRLPENGS 


QLHHS 

« Hide

References

« Hide 'large scale' references
[1]"Induction of type III secretion in Shigella flexneri is associated with differential control of transcription of genes encoding secreted proteins."
Demers B., Sansonetti P.J., Parsot C.
EMBO J. 17:2894-2903(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-12 AND 480-494, INDUCTION.
Strain: M90T / Serotype 5a.
[2]"The virulence plasmid pWR100 and the repertoire of proteins secreted by the type III secretion apparatus of Shigella flexneri."
Buchrieser C., Glaser P., Rusniok C., Nedjari H., d'Hauteville H., Kunst F., Sansonetti P.J., Parsot C.
Mol. Microbiol. 38:760-771(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-9, SUBCELLULAR LOCATION.
Strain: M90T / Serotype 5a.
[3]"Complete DNA sequence and analysis of the large virulence plasmid of Shigella flexneri."
Venkatesan M.M., Goldberg M.B., Rose D.J., Grotbeck E.J., Burland V., Blattner F.R.
Infect. Immun. 69:3271-3285(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: M90T / Serotype 5a.
[4]"Comparison of two major forms of the Shigella virulence plasmid pINV: positive selection is a major force driving the divergence."
Lan R., Stevenson G., Reeves P.R.
Infect. Immun. 71:6298-6306(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: M1382 / Serotype 6.
[5]"Comparison of the virulence plasmid genomes of two strains of Shigella which lost the ability to bind Congo red."
Xiong Z., Tang X., Yang F., Zhang X., Yang J., Chen L., Nie H., Yan Y., Jiang Y., Wang J., Xue Y., Xu X., Zhu Y., Dong J., An L., Wang X., Jin Q.
Sci. China, Ser. C, Life Sci. 49:141-148(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: Serotype 5.
[6]"Genome sequence of Shigella flexneri 2a: insights into pathogenicity through comparison with genomes of Escherichia coli K12 and O157."
Jin Q., Yuan Z., Xu J., Wang Y., Shen Y., Lu W., Wang J., Liu H., Yang J., Yang F., Zhang X., Zhang J., Yang G., Wu H., Qu D., Dong J., Sun L., Xue Y. expand/collapse author list , Zhao A., Gao Y., Zhu J., Kan B., Ding K., Chen S., Cheng H., Yao Z., He B., Chen R., Ma D., Qiang B., Wen Y., Hou Y., Yu J.
Nucleic Acids Res. 30:4432-4441(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: 301 / Serotype 2a.
[7]"Shigella protein IpaH(9.8) is secreted from bacteria within mammalian cells and transported to the nucleus."
Toyotome T., Suzuki T., Kuwae A., Nonaka T., Fukuda H., Imajoh-Ohmi S., Toyofuku T., Hori M., Sasakawa C.
J. Biol. Chem. 276:32071-32079(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, SECRETION VIA TYPE III SECRETION SYSTEM.
Strain: YSH6000 / Serotype 2a.
[8]"Shigella effector IpaH9.8 binds to a splicing factor U2AF(35) to modulate host immune responses."
Okuda J., Toyotome T., Kataoka N., Ohno M., Abe H., Shimura Y., Seyedarabi A., Pickersgill R., Sasakawa C.
Biochem. Biophys. Res. Commun. 333:531-539(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH MURINE U2AF1.
Strain: YSH6000 / Serotype 2a.
[9]"Type III secretion effectors of the IpaH family are E3 ubiquitin ligases."
Rohde J.R., Breitkreutz A., Chenal A., Sansonetti P.J., Parsot C.
Cell Host Microbe 1:77-83(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS A LIGASE, MUTAGENESIS OF CYS-337.
[10]"A bacterial E3 ubiquitin ligase IpaH9.8 targets NEMO/IKKgamma to dampen the host NF-kappaB-mediated inflammatory response."
Ashida H., Kim M., Schmidt-Supprian M., Ma A., Ogawa M., Sasakawa C.
Nat. Cell Biol. 12:66-73(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HOST IKBKG AND TNIP1, MUTAGENESIS OF CYS-337.
Strain: YSH6000 / Serotype 2a.
[11]"Structure of an SspH1-PKN1 complex reveals the basis for host substrate recognition and mechanism of activation for a bacterial E3 ubiquitin ligase."
Keszei A.F., Tang X., McCormick C., Zeqiraj E., Rohde J.R., Tyers M., Sicheri F.
Mol. Cell. Biol. 34:362-373(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ARG-163; PHE-187; HIS-210 AND CYS-337, ACTIVE SITE, FUNCTION.
Strain: M90T / Serotype 5a.
[12]"A disulfide driven domain swap switches off the activity of Shigella IpaH9.8 E3 ligase."
Seyedarabi A., Sullivan J.A., Sasakawa C., Pickersgill R.W.
FEBS Lett. 584:4163-4168(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 254-545, FUNCTION, INTERACTION WITH HUMAN U2AF1, AUTOUBIQUITINATION, ENZYME REGULATION.
Strain: YSH6000 / Serotype 2a.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF047365 Genomic DNA. Translation: AAC23714.1.
AL391753 Genomic DNA. Translation: CAC05853.1.
AF348706 Genomic DNA. Translation: AAK18544.1. Different initiation.
AY206445 Genomic DNA. Translation: AAP79029.1.
AY879342 Genomic DNA. Translation: AAW64849.1. Different initiation.
AF386526 Genomic DNA. Translation: AAL72345.2.
RefSeqNP_858359.2. NC_004851.1.
YP_006960318.1. NC_019197.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3L3PX-ray3.20A254-545[»]
ProteinModelPortalQ8VSC3.
SMRQ8VSC3. Positions 254-534.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-46341N.
IntActQ8VSC3. 2 interactions.
MINTMINT-7993760.
STRING198214.CP0226.

Proteomic databases

PRIDEQ8VSC3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaAAL72345; AAL72345; CP0226.
GeneID1238048.
13917118.
KEGGsfl:CP0226.
PATRIC18722784. VBIShiFle86970_5483.

Organism-specific databases

CMRSearch...

Phylogenomic databases

eggNOGNOG148478.
HOGENOMHOG000264729.
KOK13791.
OMAISYNEIV.
OrthoDBEOG6103XQ.

Family and domain databases

InterProIPR029487. NEL_dom.
[Graphical view]
PfamPF14496. NEL. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameIPA9_SHIFL
AccessionPrimary (citable) accession number: Q8VSC3
Secondary accession number(s): O85159 expand/collapse secondary AC list , Q2TH74, Q6XVV1, Q9AFM5, Q9AJV1
Entry history
Integrated into UniProtKB/Swiss-Prot: July 13, 2010
Last sequence update: January 4, 2005
Last modified: June 11, 2014
This is version 67 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references