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Q8VSC3

- IPA9_SHIFL

UniProt

Q8VSC3 - IPA9_SHIFL

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Protein

E3 ubiquitin-protein ligase ipaH9.8

Gene

ipaH9.8

Organism
Shigella flexneri
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.5 Publications

Enzyme regulationi

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.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei337 – 3371Glycyl thioester intermediate1 Publication

GO - Molecular functioni

  1. identical protein binding Source: IntAct
  2. ligase activity Source: UniProtKB-KW
  3. ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

  1. modulation by symbiont of host I-kappaB kinase/NF-kappaB cascade Source: UniProtKB
  2. pathogenesis Source: UniProtKB
  3. protein K27-linked ubiquitination Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway, Virulence

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase ipaH9.8 (EC:6.3.2.-)
Alternative name(s):
Invasion plasmid antigen ipaH9.8
Gene namesi
Name:ipaH9.8
Ordered Locus Names:CP0226
ORF Names:pWR501_0234, SFLP090
Encoded oniPlasmid pCP3011 Publication
Plasmid pWR1004 Publications
Plasmid pINV_F6_M13821 Publication
Plasmid pSF51 Publication
OrganismiShigella flexneri
Taxonomic identifieri623 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeShigella
ProteomesiUP000001006: Plasmid pCP301

Subcellular locationi

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.

GO - Cellular componenti

  1. extracellular region Source: UniProtKB
  2. host cell cytosol Source: UniProtKB
  3. host cell nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Host nucleus, Secreted

Pathology & Biotechi

Disruption phenotypei

In murine lung infection model, mutants cause severe inflammatory responses, with increased pro-inflammatory cytokine production levels. Colonization is greatly reduced.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi163 – 1631R → A: Abolishes proteasomal degradation of host proteins; when associated with A-187 and A-210. 1 Publication
Mutagenesisi187 – 1871F → A: Abolishes proteasomal degradation of host proteins; when associated with A-163 and A-210. 1 Publication
Mutagenesisi210 – 2101H → A: Abolishes proteasomal degradation of host proteins; when associated with A-163 and A-187. 1 Publication
Mutagenesisi337 – 3371C → A: Abolishes proteasomal degradation of host proteins. 3 Publications
Mutagenesisi337 – 3371C → A: Loss of activity. 3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 545545E3 ubiquitin-protein ligase ipaH9.8PRO_0000395755Add
BLAST

Post-translational modificationi

Autoubiquitinated (in vitro). Ubiquitinated in the presence of host E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating enzyme and ubiquitin.1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

PRIDEiQ8VSC3.

Expressioni

Inductioni

Induced upon entry into host epithelial cells.1 Publication

Interactioni

Subunit structurei

Interacts with human IKBKG (NEMO) and TNIP1 (ABIN-1). Interacts also with human and murine U2AF1 (U2AF35).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-6125799,EBI-6125799
IKBKGQ9Y6K98EBI-6125799,EBI-81279From a different organism.
TNIP1Q150254EBI-6125799,EBI-357849From a different organism.

Protein-protein interaction databases

DIPiDIP-46341N.
IntActiQ8VSC3. 2 interactions.
MINTiMINT-7993760.
STRINGi198214.CP0226.

Structurei

Secondary structure

1
545
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi254 – 2596Combined sources
Helixi264 – 27310Combined sources
Helixi274 – 2763Combined sources
Helixi283 – 29311Combined sources
Helixi305 – 31814Combined sources
Helixi320 – 35940Combined sources
Helixi366 – 38621Combined sources
Turni387 – 3893Combined sources
Helixi400 – 4089Combined sources
Turni409 – 4146Combined sources
Helixi434 – 44815Combined sources
Helixi451 – 4555Combined sources
Helixi458 – 4669Combined sources
Helixi469 – 48416Combined sources
Helixi486 – 49813Combined sources
Helixi504 – 53027Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3L3PX-ray3.20A254-545[»]
ProteinModelPortaliQ8VSC3.
SMRiQ8VSC3. Positions 254-534.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati57 – 7721LRR 1Add
BLAST
Repeati78 – 9922LRR 2Add
BLAST
Repeati100 – 11718LRR 3Add
BLAST
Repeati118 – 13922LRR 4Add
BLAST
Repeati140 – 15718LRR 5Add
BLAST
Repeati158 – 17922LRR 6Add
BLAST
Repeati182 – 20322LRR 7Add
BLAST
Repeati205 – 22824LRR 8Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 242242Interaction with target proteinsBy similarityAdd
BLAST
Regioni243 – 2508LinkerBy similarity
Regioni251 – 545295E3 ubiquitin-protein ligase catalytic domainBy similarityAdd
BLAST

Domaini

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

Sequence similaritiesi

Contains 8 LRR (leucine-rich) repeats.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiNOG148478.
HOGENOMiHOG000264729.
KOiK13791.
OMAiISYNEIV.
OrthoDBiEOG6103XQ.

Family and domain databases

InterProiIPR029487. NEL_dom.
[Graphical view]
PfamiPF14496. NEL. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8VSC3-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MLPINNNFSL PQNSFYNTIS GTYADYFSAW DKWEKQALPG EERDEAVSRL
60 70 80 90 100
KECLINNSDE LRLDRLNLSS LPDNLPAQIT LLNVSYNQLT NLPELPVTLK
110 120 130 140 150
KLYSASNKLS ELPVLPPALE SLQVQHNELE NLPALPDSLL TMNISYNEIV
160 170 180 190 200
SLPSLPQALK NLRATRNFLT ELPAFSEGNN PVVREYFFDR NQISHIPESI
210 220 230 240 250
LNLRNECSIH ISDNPLSSHA LPALQRLTSS PDYHGPRIYF SMSDGQQNTL
260 270 280 290 300
HRPLADAVTA WFPENKQSDV SQIWHAFEHE EHANTFSAFL DRLSDTVSAR
310 320 330 340 350
NTSGFREQVA AWLEKLSASA ELRQQSFAVA ADATESCEDR VALTWNNLRK
360 370 380 390 400
TLLVHQASEG LFDNDTGALL SLGREMFRLE ILEDIARDKV RTLHFVDEIE
410 420 430 440 450
VYLAFQTMLA EKLQLSTAVK EMRFYGVSGV TANDLRTAEA MVRSREENEF
460 470 480 490 500
TDWFSLWGPW HAVLKRTEAD RWAQAEEQKY EMLENEYPQR VADRLKASGL
510 520 530 540
SGDADAEREA GAQVMRETEQ QIYRQLTDEV LALRLPENGS QLHHS
Length:545
Mass (Da):61,979
Last modified:January 4, 2005 - v2
Checksum:i5E70042D797B5099
GO

Sequence cautioni

The sequence AAK18544.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAW64849.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti7 – 71Missing AA sequence (PubMed:11115111)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti222 – 2221P → Q in plasmid pWR100, plasmid pSF5 and plasmid pINV_F6_M1382.
Natural varianti474 – 4741Q → L in plasmid pINV_F6_M1382.
Natural varianti536 – 5361P → F in plasmid pWR100.
Natural varianti536 – 5361P → S in plasmid pSF5.

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_858359.2. NC_004851.1.
WP_010921715.1. NC_019197.1.
YP_006960318.1. NC_019197.1.

Genome annotation databases

EnsemblBacteriaiAAL72345; AAL72345; CP0226.
GeneIDi1238048.
13917118.
KEGGisfl:CP0226.
PATRICi18722784. VBIShiFle86970_5483.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
RefSeqi NP_858359.2. NC_004851.1.
WP_010921715.1. NC_019197.1.
YP_006960318.1. NC_019197.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3L3P X-ray 3.20 A 254-545 [» ]
ProteinModelPortali Q8VSC3.
SMRi Q8VSC3. Positions 254-534.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

DIPi DIP-46341N.
IntActi Q8VSC3. 2 interactions.
MINTi MINT-7993760.
STRINGi 198214.CP0226.

Proteomic databases

PRIDEi Q8VSC3.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

EnsemblBacteriai AAL72345 ; AAL72345 ; CP0226 .
GeneIDi 1238048.
13917118.
KEGGi sfl:CP0226.
PATRICi 18722784. VBIShiFle86970_5483.

Phylogenomic databases

eggNOGi NOG148478.
HOGENOMi HOG000264729.
KOi K13791.
OMAi ISYNEIV.
OrthoDBi EOG6103XQ.

Family and domain databases

InterProi IPR029487. NEL_dom.
[Graphical view ]
Pfami PF14496. NEL. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    Plasmid: pWR100
  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.
    Plasmid: pWR100
  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.
    Plasmid: pWR100
  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.
    Plasmid: pINV_F6_M1382
  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.
    Plasmid: pSF5
  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.
    , 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.
    Plasmid: pCP301
  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.
    Plasmid: pWR100
  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.

Entry informationi

Entry nameiIPA9_SHIFL
AccessioniPrimary (citable) accession number: Q8VSC3
Secondary accession number(s): O85159
, Q2TH74, Q6XVV1, Q9AFM5, Q9AJV1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 13, 2010
Last sequence update: January 4, 2005
Last modified: November 26, 2014
This is version 71 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Plasmid

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3