SIFA_SALTY
ID SIFA_SALTY Reviewed; 336 AA.
AC Q56061;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Secreted effector protein SifA;
GN Name=sifA; OrderedLocusNames=STM1224;
OS Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=99287;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DISRUPTION PHENOTYPE.
RC STRAIN=SL1344;
RX PubMed=8861213; DOI=10.1111/j.1365-2958.1996.tb02497.x;
RA Stein M.A., Leung K.Y., Zwick M., Garcia-Del Portillo F., Finlay B.B.;
RT "Identification of a Salmonella virulence gene required for formation of
RT filamentous structures containing lysosomal membrane glycoproteins within
RT epithelial cells.";
RL Mol. Microbiol. 20:151-164(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=11677609; DOI=10.1038/35101614;
RA McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P.,
RA Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D.,
RA Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E.,
RA Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R.,
RA Wilson R.K.;
RT "Complete genome sequence of Salmonella enterica serovar Typhimurium LT2.";
RL Nature 413:852-856(2001).
RN [3]
RP SECRETION VIA TYPE III SECRETION SYSTEM.
RC STRAIN=ATCC 14028s / SGSG 2262;
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, SUBCELLULAR LOCATION, AND SECRETION VIA TYPE III SECRETION
RP SYSTEM.
RX PubMed=12010459; DOI=10.1034/j.1600-0854.2002.30604.x;
RA Brumell J.H., Goosney D.L., Finlay B.B.;
RT "SifA, a type III secreted effector of Salmonella typhimurium, directs
RT Salmonella-induced filament (Sif) formation along microtubules.";
RL Traffic 3:407-415(2002).
RN [5]
RP FUNCTION, AND INTERACTION WITH HOST PLEKHM2.
RX PubMed=15905402; DOI=10.1126/science.1110225;
RA Boucrot E., Henry T., Borg J.-P., Gorvel J.-P., Meresse S.;
RT "The intracellular fate of Salmonella depends on the recruitment of
RT kinesin.";
RL Science 308:1174-1178(2005).
RN [6]
RP DOMAIN.
RC STRAIN=SL1344;
RX PubMed=16849798; DOI=10.1099/mic.0.28995-0;
RA Brown N.F., Szeto J., Jiang X., Coombes B.K., Finlay B.B., Brumell J.H.;
RT "Mutational analysis of Salmonella translocated effector members SifA and
RT SopD2 reveals domains implicated in translocation, subcellular localization
RT and function.";
RL Microbiology 152:2323-2343(2006).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH HOST PLEKHM2,
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LEU-130; MET-131;
RP TRP-197 AND GLU-201.
RX PubMed=18996344; DOI=10.1016/j.chom.2008.08.012;
RA Ohlson M.B., Huang Z., Alto N.M., Blanc M.-P., Dixon J.E., Chai J.,
RA Miller S.I.;
RT "Structure and function of Salmonella SifA indicate that its interactions
RT with SKIP, SseJ, and RhoA family GTPases induce endosomal tubulation.";
RL Cell Host Microbe 4:434-446(2008).
CC -!- FUNCTION: Effector proteins function to alter host cell physiology and
CC promote bacterial survival in host tissues. This protein is required
CC for endosomal tubulation and formation of Salmonella-induced filaments
CC (Sifs), which are filamentous structures containing lysosomal membrane
CC glycoproteins within epithelial cells. Sif formation is concomitant
CC with intracellular bacterial replication. {ECO:0000269|PubMed:12010459,
CC ECO:0000269|PubMed:15905402, ECO:0000269|PubMed:18996344}.
CC -!- SUBUNIT: Interacts with host PLEKHM2. Interacts with SseJ; the
CC interaction is indirect. {ECO:0000269|PubMed:15905402,
CC ECO:0000269|PubMed:18996344}.
CC -!- INTERACTION:
CC Q56061; Q8IWE5: PLEKHM2; Xeno; NbExp=3; IntAct=EBI-10765408, EBI-726484;
CC -!- SUBCELLULAR LOCATION: Secreted. Host cytoplasm. Host cell membrane.
CC Note=Secreted via type III secretion system 2 (SPI-2 TTSS), and
CC delivered into the host cytoplasm. It associates with membranes and
CC colocalizes with microtubules along the length of Sifs in infected
CC cells.
CC -!- DOMAIN: Domains throughout the protein, and not only the N-terminus,
CC are required for secretion and translocation. Both N- and C-terminal
CC domains are also required for formation of tubules.
CC {ECO:0000269|PubMed:16849798}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene do not produce Sifs in
CC epithelial cells and show attenuated virulence in mice.
CC {ECO:0000269|PubMed:8861213}.
CC -!- SIMILARITY: Belongs to the Sif family. {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; U51867; AAA97467.1; -; Genomic_DNA.
DR EMBL; AE006468; AAL20153.1; -; Genomic_DNA.
DR PIR; S71033; S71033.
DR RefSeq; NP_460194.1; NC_003197.2.
DR RefSeq; WP_001520468.1; NC_003197.2.
DR PDB; 3CXB; X-ray; 2.60 A; A=1-336.
DR PDB; 3HW2; X-ray; 3.30 A; A=1-336.
DR PDBsum; 3CXB; -.
DR PDBsum; 3HW2; -.
DR AlphaFoldDB; Q56061; -.
DR SMR; Q56061; -.
DR DIP; DIP-46411N; -.
DR IntAct; Q56061; 2.
DR STRING; 99287.STM1224; -.
DR PaxDb; Q56061; -.
DR PRIDE; Q56061; -.
DR EnsemblBacteria; AAL20153; AAL20153; STM1224.
DR GeneID; 1252742; -.
DR KEGG; stm:STM1224; -.
DR PATRIC; fig|99287.12.peg.1294; -.
DR HOGENOM; CLU_826077_0_0_6; -.
DR OMA; ETMTMCG; -.
DR PhylomeDB; Q56061; -.
DR BioCyc; SENT99287:STM1224-MON; -.
DR EvolutionaryTrace; Q56061; -.
DR Proteomes; UP000001014; 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:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0032880; P:regulation of protein localization; IMP:AgBase.
DR Gene3D; 1.10.1740.30; -; 1.
DR InterPro; IPR010637; Sif.
DR InterPro; IPR044928; SifA_C_sf.
DR Pfam; PF06767; Sif; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Host cell membrane; Host cytoplasm; Host membrane; Membrane;
KW Reference proteome; Secreted; Virulence.
FT CHAIN 1..336
FT /note="Secreted effector protein SifA"
FT /id="PRO_0000097760"
FT REGION 1..330
FT /note="Interaction with host PLEKHM2"
FT MUTAGEN 130
FT /note="L->D: Loss of interaction with host PLEKHM2. Fails
FT to induce host endosomal tubulation; when associated with
FT D-131."
FT /evidence="ECO:0000269|PubMed:18996344"
FT MUTAGEN 131
FT /note="M->D: Alters interaction with host PLEKHM2. Fails to
FT induce host endosomal tubulation; when associated with D-
FT 130."
FT /evidence="ECO:0000269|PubMed:18996344"
FT MUTAGEN 197
FT /note="W->A: Fails to induce host endosomal tubulation;
FT when associated with A-201."
FT /evidence="ECO:0000269|PubMed:18996344"
FT MUTAGEN 201
FT /note="E->A: Fails to induce host endosomal tubulation;
FT when associated with A-197."
FT /evidence="ECO:0000269|PubMed:18996344"
FT HELIX 25..34
FT /evidence="ECO:0007829|PDB:3CXB"
FT HELIX 35..37
FT /evidence="ECO:0007829|PDB:3CXB"
FT HELIX 42..54
FT /evidence="ECO:0007829|PDB:3CXB"
FT STRAND 55..58
FT /evidence="ECO:0007829|PDB:3CXB"
FT HELIX 62..75
FT /evidence="ECO:0007829|PDB:3CXB"
FT HELIX 78..81
FT /evidence="ECO:0007829|PDB:3CXB"
FT STRAND 84..87
FT /evidence="ECO:0007829|PDB:3CXB"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:3CXB"
FT STRAND 96..101
FT /evidence="ECO:0007829|PDB:3CXB"
FT STRAND 107..114
FT /evidence="ECO:0007829|PDB:3CXB"
FT STRAND 116..123
FT /evidence="ECO:0007829|PDB:3CXB"
FT STRAND 126..132
FT /evidence="ECO:0007829|PDB:3CXB"
FT STRAND 145..153
FT /evidence="ECO:0007829|PDB:3CXB"
FT TURN 154..157
FT /evidence="ECO:0007829|PDB:3CXB"
FT STRAND 158..167
FT /evidence="ECO:0007829|PDB:3CXB"
FT STRAND 169..171
FT /evidence="ECO:0007829|PDB:3CXB"
FT STRAND 174..177
FT /evidence="ECO:0007829|PDB:3CXB"
FT HELIX 180..187
FT /evidence="ECO:0007829|PDB:3CXB"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:3CXB"
FT TURN 194..196
FT /evidence="ECO:0007829|PDB:3CXB"
FT HELIX 197..220
FT /evidence="ECO:0007829|PDB:3CXB"
FT TURN 221..223
FT /evidence="ECO:0007829|PDB:3CXB"
FT HELIX 228..241
FT /evidence="ECO:0007829|PDB:3CXB"
FT HELIX 258..267
FT /evidence="ECO:0007829|PDB:3CXB"
FT TURN 270..272
FT /evidence="ECO:0007829|PDB:3HW2"
FT HELIX 273..276
FT /evidence="ECO:0007829|PDB:3HW2"
FT HELIX 283..303
FT /evidence="ECO:0007829|PDB:3CXB"
FT HELIX 307..324
FT /evidence="ECO:0007829|PDB:3CXB"
SQ SEQUENCE 336 AA; 38498 MW; 83C6185148A774B9 CRC64;
MPITIGNGFL KSEILTNSPR NTKEAWWKVL WEKIKDFFFS TGKAKADRCL HEMLFAERAP
TRERLTEIFF ELKELACASQ RDRFQVHNPH ENDATIILRI MDQNEENELL RITQNTDTFS
CEVMGNLYFL MKDRPDILKS HPQMTAMIKR RYSEIVDYPL PSTLCLNPAG APILSVPLDN
IEGYLYTELR KGHLDGWKAQ EKATYLAAKI QSGIEKTTRI LHHANISEST QQNAFLETMA
MCGLKQLEIP PPHTHIPIEK MVKEVLLADK TFQAFLVTDP STSQSMLAEI VEAISDQVFH
AIFRIDPQAI QKMAEEQLTT LHVRSEQQSG CLCCFL
