Protein: E3 ubiquitin-protein ligase ipaH9.8 (EC 2.3.2.27) (Invasion plasmid antigen 9.8) (Q8VSC3)
Organism: Shigella flexneri
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.
Subcellular location: Secreted {ECO:0000269|PubMed:11115111}. Host cytoplasm {ECO:0000269|PubMed:11418613, ECO:0000269|PubMed:29144452}. Host nucleus {ECO:0000269|PubMed:11418613}. Note=Secreted via Mxi-Spa type III secretion system (T3SS), and delivered into the host cytoplasm (PubMed:11115111, PubMed:11418613). Transported into the host nucleus (PubMed:11418613). This transport is independent of cytosolic factors, but dependent on temperature and partly on ATP/GTP (PubMed:11418613). {ECO:0000269|PubMed:11115111, ECO:0000269|PubMed:11418613}.
Sequence: MLPINNNFSLPQNSFYNTISGTYADYFSAWDKWEKQALPGEERDEAVSRLKECLINNSDELRLDRLNLSSLPDNLPAQITLLNVSYNQLTNLPELPVTLKKLYSASNKLSELPVLPPALESLQVQHNELENLPALPDSLLTMNISYNEIVSLPSLPQALKNLRATRNFLTELPAFSEGNNPVVREYFFDRNQISHIPESILNLRNECSIHISDNPLSSHALPALQRLTSSPDYHGPRIYFSMSDGQQNTLHRPLADAVTAWFPENKQSDVSQIWHAFEHEEHANTFSAFLDRLSDTVSARNTSGFREQVAAWLEKLSASAELRQQSFAVAADATESCEDRVALTWNNLRKTLLVHQASEGLFDNDTGALLSLGREMFRLEILEDIARDKVRTLHFVDEIEVYLAFQTMLAEKLQLSTAVKEMRFYGVSGVTANDLRTAEAMVRSREENEFTDWFSLWGPWHAVLKRTEADRWAQAEEQKYEMLENEYPQRVADRLKASGLSGDADAEREAGAQVMRETEQQIYRQLTDEVLALRLPENGSQLHHS
InterPro domains: - IPR032674: LRR-containing bacterial E3 ligase, N-terminal (domain) [4-48]
- IPR032675: Leucine-rich repeat domain superfamily (homologous_superfamily) [22-244]
- IPR051071: Leucine-rich repeat-containing bacterial E3 ubiquitin ligases (family) [188-483]
- IPR029487: Novel E3 ligase domain (domain) [253-545]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016740 (transferase activity), GO:0140096 (catalytic activity, acting on a protein), GO:0019787 (ubiquitin-like protein transferase activity), GO:0004842 (ubiquitin-protein transferase activity), GO:0061659 (ubiquitin-like protein ligase activity), GO:0061630 (ubiquitin protein ligase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0048519 (negative regulation of biological process), GO:0009605 (response to external stimulus), GO:0044068 (modulation by symbiont of host cellular process), GO:0009607 (response to biotic stimulus), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0035821 (modulation of process of another organism), GO:0044403 (biological process involved in symbiotic interaction), GO:0048585 (negative regulation of response to stimulus), GO:0051707 (response to other organism), GO:0048522 (positive regulation of cellular process), GO:0051701 (biological process involved in interaction with host), GO:0031341 (regulation of cell killing), GO:0010942 (positive regulation of cell death), GO:0052040 (modulation by symbiont of host programmed cell death), GO:0052173 (response to defenses of other organism), GO:0043207 (response to external biotic stimulus), GO:0010941 (regulation of cell death), GO:0080134 (regulation of response to stress), GO:0044003 (modulation by symbiont of host process), GO:0031343 (positive regulation of cell killing), GO:0075136 (response to host), GO:0051709 (regulation of killing of cells of another organism), GO:0051712 (positive regulation of killing of cells of another organism), GO:0031348 (negative regulation of defense response), GO:0044414 (suppression of host defenses by symbiont), GO:0031347 (regulation of defense response), GO:0052200 (response to host defenses), GO:0043067 (regulation of programmed cell death), GO:0043068 (positive regulation of programmed cell death), GO:0140418 (effector-mediated modulation of host process by symbiont), GO:0052031 (modulation by symbiont of host defense response), GO:0001907 (killing by symbiont of host cells), GO:0052170 (suppression by symbiont of host innate immune response), GO:0052572 (response to host immune response), GO:0030682 (mitigation of host defenses by symbiont), GO:0052553 (modulation by symbiont of host immune response), GO:0052167 (modulation by symbiont of host innate immune response), GO:0052562 (suppression by symbiont of host immune response)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005576 (extracellular region)