Q8VSC3

EV
Gene name
ipaH9.8
Protein name
E3 ubiquitin-protein ligase ipaH9.8
Names
IR, Invasion plasmid antigen ipaH9.8, RING-type E3 ubiquitin transferase ipaH9.8
Species
Shigella flexneri
KEGG Pathway
sfl:CP0226
EC number
2.3.2.27: Aminoacyltransferases
Protein Class
FAMILY NOT NAMED (PTHR47114)

Descriptions

Shigellar flexneri IpaH9.8 E3 ligase inhibits MAPK kinase dependent signaling by targeting components of this pathway and disrupts both NF-κB-dependent gene expression and the activity of U2AF35 via the ubiquitination. The C-terminal region of IpaH9.8 can exist as a monomer that is able to catalyze the ubiquitination of U2AF35 and as a dimer that does not possess this activity. Under non-reducing conditions, the sole cysteine (Cys 337) of the C-terminal region of IpaH9.8 forms an intermolecular disulfide bridge resulting in the extension of an α-helix and formation of a domain-swapped dimer. Furthermore, the N-terminal domain (leucine-rich repeat) can autoinhibit the activity of full-length IpaH9.8, and substrate (human substrate U2AF35 and yeast substrate Ste7) binding releases this inhibition.

Autoinhibitory domains (AIDs)

22-244 (Leucine-rich repeat domain) EV

Target domain

251-545 (E3 ubiquitin-protein ligase catalytic domain)

Relief mechanism

Partner binding

Assay

Mutagenesis experiment, Structural analysis

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

7 structures for Q8VSC3

Entry ID Method Resolution Chain Position Source
3L3P X-ray 320 A A 254-545 PDB
5B0N X-ray 180 A A/B 22-244 PDB
5B0T X-ray 200 A A 22-244 PDB
6K2D X-ray 360 A B 22-252 PDB
6LOJ X-ray 372 A A 22-244 PDB
6LOL X-ray 275 A A 22-545 PDB
AF-Q8VSC3-F1 Predicted AlphaFoldDB

4 variants for Q8VSC3

Variant ID(s) Position Change Description Diseaes Association Provenance
222 P>Q plasmid pWR100, plasmid pSF5 and plasmid pINV_F6_M1382 [UniProt] No
474 Q>L plasmid pINV_F6_M1382 [UniProt] No
536 P>F plasmid pWR100 [UniProt] No
536 P>S plasmid pSF5 [UniProt] No

No associated diseases with Q8VSC3

2 regional properties for Q8VSC3

Type Name Position InterPro Accession
domain Novel E3 ligase domain 261 - 471 IPR029487
domain LRR-containing bacterial E3 ligase, N-terminal 4 - 48 IPR032674

Functions

Description
EC Number 2.3.2.27 Aminoacyltransferases
Subcellular Localization
  • Secreted
  • Host cytoplasm
  • Host nucleus
  • 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)
PANTHER Family PTHR47114 FAMILY NOT NAMED
PANTHER Subfamily PTHR47114:SF2 OLIGODENDROCYTE-MYELIN GLYCOPROTEIN
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

3 GO annotations of cellular component

Name Definition
extracellular region The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite.
host cell cytosol The part of the host cell cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
host cell nucleus A membrane-bounded organelle as it is found in the host cell in which chromosomes are housed and replicated. The host is defined as the larger of the organisms involved in a symbiotic interaction.

3 GO annotations of molecular function

Name Definition
identical protein binding Binding to an identical protein or proteins.
ubiquitin protein ligase activity Catalysis of the transfer of ubiquitin to a substrate protein via the reaction X-ubiquitin + S -> X + S-ubiquitin, where X is either an E2 or E3 enzyme, the X-ubiquitin linkage is a thioester bond, and the S-ubiquitin linkage is an amide bond: an isopeptide bond between the C-terminal glycine of ubiquitin and the epsilon-amino group of lysine residues in the substrate or, in the linear extension of ubiquitin chains, a peptide bond the between the C-terminal glycine and N-terminal methionine of ubiquitin residues.
ubiquitin-protein transferase activity Catalysis of the transfer of ubiquitin from one protein to another via the reaction X-Ub + Y --> Y-Ub + X, where both X-Ub and Y-Ub are covalent linkages.

5 GO annotations of biological process

Name Definition
proteasome-mediated ubiquitin-dependent protein catabolic process The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome.
protein autoubiquitination The ubiquitination by a protein of one or more of its own amino acid residues, or residues on an identical protein. Ubiquitination occurs on the lysine residue by formation of an isopeptide crosslink.
protein K27-linked ubiquitination A protein ubiquitination process in which a polymer of ubiquitin, formed by linkages between lysine residues at position 27 of the ubiquitin monomers, is added to a protein.
suppression by symbiont of host I-kappaB kinase/NF-kappaB cascade Any process that stops, prevents, or reduces the frequency, rate or extent of host NF-kappaB-mediated signal transduction pathways during the host defense response. The host is defined as the larger of the organisms involved in a symbiotic interaction.
suppression by symbiont of host inflammatory response Any process in which a symbiont stops, prevents, or reduces the frequency, rate or extent of the inflammatory response of the host organism; the inflammatory response is the immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The host is defined as the larger of the organisms involved in a symbiotic interaction.

No homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
No homologous proteins
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