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Protein

E3 ubiquitin-protein ligase ipaH9.8

Gene

ipaH9.8

Organism
Shigella flexneri
Status
Reviewed-Annotation score: 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

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

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)DescriptionActionsGraphical viewLength
Active sitei337Glycyl thioester intermediate1 Publication1

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

  • modulation by symbiont of host I-kappaB kinase/NF-kappaB cascade Source: UniProtKB
  • pathogenesis Source: UniProtKB
  • protein K27-linked ubiquitination Source: UniProtKB

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway, Virulence

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase ipaH9.8 (EC:2.3.2.27)
Alternative name(s):
Invasion plasmid antigen ipaH9.8
RING-type E3 ubiquitin transferase ipaH9.8Curated
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 lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeShigella
Proteomesi
  • UP000001006 Componenti: 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

  • extracellular region Source: UniProtKB
  • host cell cytosol Source: UniProtKB
  • host cell nucleus Source: UniProtKB

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)DescriptionActionsGraphical viewLength
Mutagenesisi163R → A: Abolishes proteasomal degradation of host proteins; when associated with A-187 and A-210. 1 Publication1
Mutagenesisi187F → A: Abolishes proteasomal degradation of host proteins; when associated with A-163 and A-210. 1 Publication1
Mutagenesisi210H → A: Abolishes proteasomal degradation of host proteins; when associated with A-163 and A-187. 1 Publication1
Mutagenesisi337C → A: Abolishes proteasomal degradation of host proteins. 3 Publications1
Mutagenesisi337C → A: Loss of activity. 3 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003957551 – 545E3 ubiquitin-protein ligase ipaH9.8Add BLAST545

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

PaxDbiQ8VSC3.
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

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

DIPiDIP-46341N.
IntActiQ8VSC3. 2 interactors.
MINTiMINT-7993760.

Structurei

Secondary structure

1545
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi23 – 35Combined sources13
Helixi43 – 55Combined sources13
Beta strandi59 – 62Combined sources4
Beta strandi80 – 83Combined sources4
Beta strandi101 – 103Combined sources3
Beta strandi121 – 123Combined sources3
Beta strandi141 – 143Combined sources3
Beta strandi161 – 163Combined sources3
Beta strandi185 – 187Combined sources3
Helixi198 – 201Combined sources4
Beta strandi208 – 210Combined sources3
Helixi220 – 229Combined sources10
Beta strandi237 – 239Combined sources3
Helixi254 – 259Combined sources6
Helixi264 – 273Combined sources10
Helixi274 – 276Combined sources3
Helixi283 – 293Combined sources11
Helixi305 – 318Combined sources14
Helixi320 – 359Combined sources40
Helixi366 – 386Combined sources21
Turni387 – 389Combined sources3
Helixi400 – 408Combined sources9
Turni409 – 414Combined sources6
Helixi434 – 448Combined sources15
Helixi451 – 455Combined sources5
Helixi458 – 466Combined sources9
Helixi469 – 484Combined sources16
Helixi486 – 498Combined sources13
Helixi504 – 530Combined sources27

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3L3PX-ray3.20A254-545[»]
5B0NX-ray1.80A/B22-244[»]
5B0TX-ray2.00A22-244[»]
ProteinModelPortaliQ8VSC3.
SMRiQ8VSC3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati57 – 77LRR 1Add BLAST21
Repeati78 – 99LRR 2Add BLAST22
Repeati100 – 117LRR 3Add BLAST18
Repeati118 – 139LRR 4Add BLAST22
Repeati140 – 157LRR 5Add BLAST18
Repeati158 – 179LRR 6Add BLAST22
Repeati182 – 203LRR 7Add BLAST22
Repeati205 – 228LRR 8Add BLAST24

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 242Interaction with target proteinsBy similarityAdd BLAST242
Regioni243 – 250LinkerBy similarity8
Regioni251 – 545E3 ubiquitin-protein ligase catalytic domainBy similarityAdd BLAST295

Domaini

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

Sequence similaritiesi

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiENOG4108QHK. Bacteria.
COG4886. LUCA.
HOGENOMiHOG000264729.
KOiK13791.
OMAiRNECSIH.

Family and domain databases

Gene3Di3.80.10.10. 1 hit.
InterProiView protein in InterPro
IPR032675. L_dom-like.
IPR032674. LRR_E3_ligase_N.
IPR029487. NEL_dom.
PfamiView protein in Pfam
PF14496. NEL. 1 hit.
PF12468. TTSSLRR. 1 hit.
SUPFAMiSSF52058. SSF52058. 1 hit.

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti7Missing AA sequence (PubMed:11115111).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti222P → Q in plasmid pWR100, plasmid pSF5 and plasmid pINV_F6_M1382. 1
Natural varianti474Q → L in plasmid pINV_F6_M1382. 1
Natural varianti536P → F in plasmid pWR100. 1
Natural varianti536P → S in plasmid pSF5. 1

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; SF_p0226.
GeneIDi1238048.
13917118.
KEGGisfl:CP0226.
PATRICifig|198214.7.peg.5483.

Similar proteinsi

Entry informationi

Entry nameiIPA9_SHIFL
AccessioniPrimary (citable) accession number: Q8VSC3
Secondary accession number(s): O85159
, Q2TH74, Q6XVV1, Q9AFM5, Q9AJV1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 13, 2010
Last sequence update: January 4, 2005
Last modified: July 5, 2017
This is version 91 of the entry and version 2 of the sequence. See 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