SSPH1_SALT1
ID SSPH1_SALT1 Reviewed; 700 AA.
AC D0ZVG2; Q9XDN9;
DT 02-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 19-JAN-2010, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=E3 ubiquitin-protein ligase SspH1;
DE EC=2.3.2.27 {ECO:0000269|PubMed:24248594};
DE AltName: Full=RING-type E3 ubiquitin transferase SspH1 {ECO:0000305};
DE AltName: Full=Salmonella secreted protein H1;
DE AltName: Full=Secreted effector protein SspH1;
GN Name=sspH1; OrderedLocusNames=STM14_1483;
OS Salmonella typhimurium (strain 14028s / SGSC 2262).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=588858;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION,
RP SECRETION VIA TYPE III SECRETION SYSTEM, AND INDUCTION.
RX PubMed=10564523; DOI=10.1046/j.1365-2958.1999.01651.x;
RA Miao E.A., Scherer C.A., Tsolis R.M., Kingsley R.A., Adams L.G.,
RA Baumler A.J., Miller S.I.;
RT "Salmonella typhimurium leucine-rich repeat proteins are targeted to the
RT SPI1 and SPI2 type III secretion systems.";
RL Mol. Microbiol. 34:850-864(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=14028s / SGSC 2262;
RX PubMed=19897643; DOI=10.1128/jb.01233-09;
RA Jarvik T., Smillie C., Groisman E.A., Ochman H.;
RT "Short-term signatures of evolutionary change in the Salmonella enterica
RT serovar typhimurium 14028 genome.";
RL J. Bacteriol. 192:560-567(2010).
RN [3]
RP SUBCELLULAR LOCATION, AND SECRETION VIA TYPE III SECRETION SYSTEM.
RX PubMed=10861017; DOI=10.1073/pnas.97.13.7539;
RA Miao E.A., Miller S.I.;
RT "A conserved amino acid sequence directing intracellular type III secretion
RT by Salmonella typhimurium.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:7539-7544(2000).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12819095; DOI=10.1128/iai.71.7.4052-4058.2003;
RA Haraga A., Miller S.I.;
RT "A Salmonella enterica serovar typhimurium translocated leucine-rich repeat
RT effector protein inhibits NF-kappa B-dependent gene expression.";
RL Infect. Immun. 71:4052-4058(2003).
RN [5]
RP FUNCTION, SUBUNIT, INTERACTION WITH HOST PKN1, AND DOMAIN.
RX PubMed=16611232; DOI=10.1111/j.1462-5822.2005.00670.x;
RA Haraga A., Miller S.I.;
RT "A Salmonella type III secretion effector interacts with the mammalian
RT serine/threonine protein kinase PKN1.";
RL Cell. Microbiol. 8:837-846(2006).
RN [6]
RP FUNCTION AS AN UBIQUITIN LIGASE.
RC STRAIN=ATCC 14028 / SGSC 2980 / CDC 6516-60 / NCTC 12023;
RX PubMed=18005683; DOI=10.1016/j.chom.2007.02.002;
RA Rohde J.R., Breitkreutz A., Chenal A., Sansonetti P.J., Parsot C.;
RT "Type III secretion effectors of the IpaH family are E3 ubiquitin
RT ligases.";
RL Cell Host Microbe 1:77-83(2007).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 161-398 IN COMPLEX WITH HUMAN
RP PKN1, INTERACTION WITH HOST PKN1, FUNCTION, SUBUNIT, DOMAIN, MUTAGENESIS OF
RP TYR-325; ASP-343; TYR-366; ASP-368 AND CYS-492, ACTIVE SITE, AND ACTIVITY
RP REGULATION.
RX PubMed=24248594; DOI=10.1128/mcb.01360-13;
RA Keszei A.F., Tang X., McCormick C., Zeqiraj E., Rohde J.R., Tyers M.,
RA Sicheri F.;
RT "Structure of an SspH1-PKN1 complex reveals the basis for host substrate
RT recognition and mechanism of activation for a bacterial E3 ubiquitin
RT ligase.";
RL Mol. Cell. Biol. 34:362-373(2014).
CC -!- FUNCTION: Effector proteins function to alter host cell physiology and
CC promote bacterial survival in host tissues (PubMed:10564523,
CC PubMed:18005683, PubMed:16611232, PubMed:24248594). This protein is an
CC E3 ubiquitin-protein ligase that interferes with the host's
CC ubiquitination pathway and targets host proteins for proteasomal
CC degradation (PubMed:10564523, PubMed:18005683, PubMed:16611232,
CC PubMed:24248594). Can ubiquitinate ubiquitin, giving rise to
CC polyubiquitin chains (in vitro) (PubMed:18005683). Polyubiquitinates
CC host PKN1, leading to its proteasomal degradation (PubMed:16611232,
CC PubMed:24248594). Down-modulates production of host pro-inflammatory
CC cytokines by inhibiting NF-kappa-B-dependent gene expression; this
CC depends only partially on its E3 ubiquitin-protein ligase activity
CC (PubMed:12819095). {ECO:0000269|PubMed:10564523,
CC ECO:0000269|PubMed:12819095, ECO:0000269|PubMed:16611232,
CC ECO:0000269|PubMed:18005683, ECO:0000269|PubMed:24248594}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:18005683};
CC -!- ACTIVITY REGULATION: Exists in an autoinhibited state in the absence of
CC substrate protein, due to interactions of the leucine-rich repeat
CC domain with the catalytic domain. Is activated upon binding to a
CC substrate protein. {ECO:0000269|PubMed:24248594}.
CC -!- SUBUNIT: Interacts (via leucine-rich repeat region) with host PKN1 (via
CC the second REM repeat). {ECO:0000269|PubMed:16611232,
CC ECO:0000269|PubMed:24248594}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10564523,
CC ECO:0000269|PubMed:10861017}. Host cytoplasm
CC {ECO:0000269|PubMed:10564523, ECO:0000269|PubMed:10861017}. Host
CC nucleus {ECO:0000269|PubMed:16611232}. Note=Secreted via type III
CC secretion systems 1 and 2 (SPI-1 and SPI-2 TTSS), and delivered into
CC the host cytoplasm. Localizes predominantly to the host nucleus.
CC {ECO:0000269|PubMed:10564523, ECO:0000269|PubMed:10861017}.
CC -!- INDUCTION: Transcription is maximal in the late logarithmic phase of
CC growth. Expression levels are similar in the intracellular and
CC extracellular environments. {ECO:0000269|PubMed:10564523}.
CC -!- DOMAIN: The LRR (leucine-rich repeat) domain mediates interaction with
CC host PKN1 and inhibition of NF-kappa-B-dependent gene expression.
CC {ECO:0000269|PubMed:16611232, ECO:0000269|PubMed:24248594}.
CC -!- PTM: Ubiquitinated in the presence of host E1 ubiquitin-activating
CC enzyme, E2 ubiquitin-conjugating enzyme and ubiquitin.
CC {ECO:0000250|UniProtKB:D0ZPH9}.
CC -!- SIMILARITY: Belongs to the LRR-containing bacterial E3 ligase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF013776; AAD40326.1; -; Genomic_DNA.
DR EMBL; CP001363; ACY87967.1; -; Genomic_DNA.
DR RefSeq; WP_000481981.1; NZ_CP043402.1.
DR PDB; 4NKG; X-ray; 2.90 A; A/C=161-405.
DR PDB; 4NKH; X-ray; 2.75 A; A/B/C/D/E/F=161-398.
DR PDBsum; 4NKG; -.
DR PDBsum; 4NKH; -.
DR AlphaFoldDB; D0ZVG2; -.
DR SMR; D0ZVG2; -.
DR IntAct; D0ZVG2; 12.
DR MINT; D0ZVG2; -.
DR PRIDE; D0ZVG2; -.
DR EnsemblBacteria; ACY87967; ACY87967; STM14_1483.
DR KEGG; seo:STM14_1483; -.
DR PATRIC; fig|588858.6.peg.1452; -.
DR HOGENOM; CLU_018533_1_0_6; -.
DR OMA; PPCNELE; -.
DR BioCyc; SENT588858:STM14_RS07010-MON; -.
DR PHI-base; PHI:3748; -.
DR Proteomes; UP000002695; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0030254; P:protein secretion by the type III secretion system; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR029487; NEL_dom.
DR Pfam; PF14496; NEL; 1.
DR PROSITE; PS51450; LRR; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Host cytoplasm; Host nucleus; Leucine-rich repeat; Repeat;
KW Secreted; Transferase; Ubl conjugation; Ubl conjugation pathway; Virulence.
FT CHAIN 1..700
FT /note="E3 ubiquitin-protein ligase SspH1"
FT /id="PRO_0000391757"
FT REPEAT 217..238
FT /note="LRR 1"
FT REPEAT 239..257
FT /note="LRR 2"
FT REPEAT 258..279
FT /note="LRR 3"
FT REPEAT 280..297
FT /note="LRR 4"
FT REPEAT 298..319
FT /note="LRR 5"
FT REPEAT 320..337
FT /note="LRR 6"
FT REPEAT 338..360
FT /note="LRR 7"
FT REPEAT 361..381
FT /note="LRR 8"
FT REGION 1..395
FT /note="Interaction with target proteins"
FT REGION 396..403
FT /note="Linker"
FT /evidence="ECO:0000250"
FT REGION 404..700
FT /note="E3 ubiquitin-protein ligase catalytic domain"
FT ACT_SITE 492
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000269|PubMed:24248594"
FT MUTAGEN 325
FT /note="Y->A: Abolishes interaction with host PKN1 and PKN1-
FT mediated release from the autoinhibited state."
FT /evidence="ECO:0000269|PubMed:24248594"
FT MUTAGEN 343
FT /note="D->A: Abolishes interaction with host PKN1 and PKN1-
FT mediated release from the autoinhibited state."
FT /evidence="ECO:0000269|PubMed:24248594"
FT MUTAGEN 366
FT /note="Y->A: Abolishes interaction with host PKN1 and PKN1-
FT mediated release from the autoinhibited state."
FT /evidence="ECO:0000269|PubMed:24248594"
FT MUTAGEN 368
FT /note="D->A: Decreases interaction with host PKN1."
FT /evidence="ECO:0000269|PubMed:24248594"
FT MUTAGEN 492
FT /note="C->A: Abolishes ubiquitination and subsequent
FT proteasomal degradation of host PKN1."
FT /evidence="ECO:0000269|PubMed:24248594"
FT HELIX 163..172
FT /evidence="ECO:0007829|PDB:4NKH"
FT HELIX 179..195
FT /evidence="ECO:0007829|PDB:4NKH"
FT STRAND 199..201
FT /evidence="ECO:0007829|PDB:4NKH"
FT STRAND 219..223
FT /evidence="ECO:0007829|PDB:4NKH"
FT STRAND 240..243
FT /evidence="ECO:0007829|PDB:4NKH"
FT STRAND 261..263
FT /evidence="ECO:0007829|PDB:4NKH"
FT STRAND 281..283
FT /evidence="ECO:0007829|PDB:4NKH"
FT STRAND 301..303
FT /evidence="ECO:0007829|PDB:4NKH"
FT STRAND 321..323
FT /evidence="ECO:0007829|PDB:4NKH"
FT STRAND 341..343
FT /evidence="ECO:0007829|PDB:4NKH"
FT HELIX 354..358
FT /evidence="ECO:0007829|PDB:4NKH"
FT STRAND 364..366
FT /evidence="ECO:0007829|PDB:4NKH"
FT HELIX 374..387
FT /evidence="ECO:0007829|PDB:4NKH"
FT STRAND 390..392
FT /evidence="ECO:0007829|PDB:4NKH"
SQ SEQUENCE 700 AA; 77119 MW; 141612145C01D582 CRC64;
MFNIRNTQPS VSMQAIAGAA APEASPEEIV WEKIQVFFPQ ENYEEAQQCL AELCHPARGM
LPDHISSQFA RLKALTFPAW EENIQCNRDG INQFCILDAG SKEILSITLD DAGNYTVNCQ
GYSEAHDFIM DTEPGEECTE FAEGASGTSL RPATTVSQKA AEYDAVWSKW ERDAPAGESP
GRAAVVQEMR DCLNNGNPVL NVGASGLTTL PDRLPPHITT LVIPDNNLTS LPELPEGLRE
LEVSGNLQLT SLPSLPQGLQ KLWAYNNWLA SLPTLPPGLG DLAVSNNQLT SLPEMPPALR
ELRVSGNNLT SLPALPSGLQ KLWAYNNRLT SLPEMSPGLQ ELDVSHNQLT RLPQSLTGLS
SAARVYLDGN PLSVRTLQAL RDIIGHSGIR IHFDMAGPSV PREARALHLA VADWLTSARE
GEAAQADRWQ AFGLEDNAAA FSLVLDRLRE TENFKKDAGF KAQISSWLTQ LAEDAALRAK
TFAMATEATS TCEDRVTHAL HQMNNVQLVH NAEKGEYDNN LQGLVSTGRE MFRLATLEQI
AREKAGTLAL VDDVEVYLAF QNKLKESLEL TSVTSEMRFF DVSGVTVSDL QAAELQVKTA
ENSGFSKWIL QWGPLHSVLE RKVPERFNAL REKQISDYED TYRKLYDEVL KSSGLVDDTD
AERTIGVSAM DSAKKEFLDG LRALVDEVLG SYLTARWRLN
