INLC_LISMG
ID INLC_LISMG Reviewed; 297 AA.
AC P71451; Q48787; Q799Z7;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 25-MAY-2022, entry version 133.
DE RecName: Full=Internalin C {ECO:0000303|PubMed:8878044};
DE Short=InlC {ECO:0000303|PubMed:8878044};
DE AltName: Full=Internalin-related protein A {ECO:0000303|PubMed:8975898};
DE Flags: Precursor;
GN Name=inlC {ECO:0000303|PubMed:8878044};
GN Synonyms=irpA {ECO:0000303|PubMed:8975898};
OS Listeria monocytogenes serotype 1/2a (strain EGD / Mackaness).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Listeriaceae; Listeria.
OX NCBI_TaxID=1334565;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 64-93; 111-113;
RP 121-132; 208-224 AND 274-296, INDUCTION, SUBCELLULAR LOCATION, AND
RP DISRUPTION PHENOTYPE.
RC STRAIN=EGD / Mackaness;
RX PubMed=8878044; DOI=10.1046/j.1365-2958.1996.541414.x;
RA Engelbrecht F., Chun S., Ochs C., Hess J., Lottspeich F., Goebel W.,
RA Sokolovic Z.;
RT "A new PrfA-regulated gene of Listeria monocytogenes encoding a small,
RT secreted protein which belongs to the family of internalins.";
RL Mol. Microbiol. 21:823-837(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 35-47, SUBCELLULAR
RP LOCATION, INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=EGD / Mackaness;
RX PubMed=8975898; DOI=10.1128/iai.65.1.101-109.1997;
RA Domann E., Zechel S., Hain T., Lingnau A., Nichterlein T., Wehland J.,
RA Chakraborty T.;
RT "Identification of a novel PrfA-regulated gene in Listeria monocytogenes
RT that is highly homologous to the leucine-rich repeat containing internalin
RT proteins.";
RL Infect. Immun. 65:101-109(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=EGD / Mackaness;
RX PubMed=9491077; DOI=10.1007/s004380050638;
RA Engelbrecht F., Dickneite C., Lampidis R., Goetz M., Dasgupta U.,
RA Goebel W.;
RT "Sequence comparison of the chromosomal regions encompassing the internalin
RT C genes (inlC) of Listeria monocytogenes and L. ivanovii.";
RL Mol. Gen. Genet. 257:186-197(1998).
RN [4]
RP PROTEIN SEQUENCE OF 35-66; 73-96; 145-154; 208-217; 226-236 AND 274-296,
RP SUBCELLULAR LOCATION, INDUCTION, AND MASS SPECTROMETRY.
RC STRAIN=EGD / Mackaness;
RX PubMed=8641748; DOI=10.1128/iai.64.3.1002-1006.1996;
RA Lingnau A., Chakraborty T., Niebuhr K., Domann E., Wehland J.;
RT "Identification and purification of novel internalin-related proteins in
RT Listeria monocytogenes and Listeria ivanovii.";
RL Infect. Immun. 64:1002-1006(1996).
RN [5]
RP ANTIGENICITY.
RX PubMed=9284184; DOI=10.1128/iai.65.9.3976-3980.1997;
RA Grenningloh R., Darji A., Wehland J., Chakraborty T., Weiss S.;
RT "Listeriolysin and IrpA are major protein targets of the human humoral
RT response against Listeria monocytogenes.";
RL Infect. Immun. 65:3976-3980(1997).
RN [6]
RP INTERACTION WITH HUMAN MUC2, AND SUBUNIT.
RX PubMed=18327567; DOI=10.1007/s00203-008-0358-6;
RA Linden S.K., Bierne H., Sabet C., Png C.W., Florin T.H., McGuckin M.A.,
RA Cossart P.;
RT "Listeria monocytogenes internalins bind to the human intestinal mucin
RT MUC2.";
RL Arch. Microbiol. 190:101-104(2008).
RN [7]
RP FUNCTION, INTERACTION WITH HUMAN DNMBP, INDUCTION, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF LYS-173.
RC STRAIN=EGD / Mackaness;
RX PubMed=19767742; DOI=10.1038/ncb1964;
RA Rajabian T., Gavicherla B., Heisig M., Mueller-Altrock S., Goebel W.,
RA Gray-Owen S.D., Ireton K.;
RT "The bacterial virulence factor InlC perturbs apical cell junctions and
RT promotes cell-to-cell spread of Listeria.";
RL Nat. Cell Biol. 11:1212-1218(2009).
RN [8]
RP FUNCTION, INTERACTION WITH HUMAN IKKA (CHUK), SUBCELLULAR LOCATION,
RP INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=EGD / Mackaness;
RX PubMed=20855622; DOI=10.1073/pnas.1007765107;
RA Gouin E., Adib-Conquy M., Balestrino D., Nahori M.A., Villiers V.,
RA Colland F., Dramsi S., Dussurget O., Cossart P.;
RT "The Listeria monocytogenes InlC protein interferes with innate immune
RT responses by targeting the I{kappa}B kinase subunit IKK{alpha}.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:17333-17338(2010).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF LYS-173.
RC STRAIN=EGD / Mackaness;
RX PubMed=23403554; DOI=10.1128/iai.01377-12;
RA Leung N., Gianfelice A., Gray-Owen S.D., Ireton K.;
RT "Impact of the Listeria monocytogenes protein InlC on infection in mice.";
RL Infect. Immun. 81:1334-1340(2013).
RN [10] {ECO:0007744|PDB:1XEU}
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 35-297, AND DOMAIN.
RX PubMed=17057330; DOI=10.1107/s0907444906026746;
RA Ooi A., Hussain S., Seyedarabi A., Pickersgill R.W.;
RT "Structure of internalin C from Listeria monocytogenes.";
RL Acta Crystallogr. D 62:1287-1293(2006).
RN [11] {ECO:0007744|PDB:4CC4}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 35-297 IN COMPLEX WITH HUMAN
RP DNMBP (TUBA), FUNCTION, SUBUNIT, DOMAIN, AND MUTAGENESIS OF PHE-146;
RP LYS-173 AND 246-TYR-TYR-247.
RC STRAIN=EGD / Mackaness;
RX PubMed=24332715; DOI=10.1016/j.str.2013.10.017;
RA Polle L., Rigano L.A., Julian R., Ireton K., Schubert W.D.;
RT "Structural details of human tuba recruitment by InlC of Listeria
RT monocytogenes elucidate bacterial cell-cell spreading.";
RL Structure 22:304-314(2014).
CC -!- FUNCTION: A virulence enhancer that has at least 2 dissociable
CC functions in infection; it impairs translocation of host transcription
CC factor NF-kappa-B to the nucleus and antagonizes the function of the
CC Tuba dynamin-binding protein, promoting bacterial spreading
CC (PubMed:20855622, PubMed:19767742, PubMed:24332715). Perturbs the
CC morphology of host cell junctions by impairing host DNMBP (Tuba) and
CC WASL interaction, altering cortical tension at the cell junctions and
CC allowing bacteria to more efficiently form bacteria-filled cell
CC protrusions which promote bacterial spreading within infected host
CC tissue (PubMed:19767742, PubMed:24332715). Down-regulates the host
CC inflammation response usually induced by Listeria infection. Interacts
CC with host I-kappa-B kinase alpha (IKKA, CHUK), which prevents IKKA from
CC phosphorylating NF-kappa-B inhibitor alpha (IKBA, NFKBIA) and thus
CC delays degradation of phospho-IKBA. Translocation of host transcription
CC factor p65 (a subunit of NF-kappa-B, RELA) into the nucleus is
CC impaired, which prevents activation of NF-KB-regulated genes
CC (PubMed:20855622). Recognized by serum from healthy humans exposed to
CC L.monocytogenes as well from patients who have recovered from
CC listeriosis (PubMed:9284184). {ECO:0000269|PubMed:19767742,
CC ECO:0000269|PubMed:20855622, ECO:0000269|PubMed:24332715,
CC ECO:0000269|PubMed:9284184}.
CC -!- SUBUNIT: Interacts in vitro with human intestinal mucin-2 (MUC2) but
CC not with mucin-1; binding is slightly better at pH 5.5, (the pH of the
CC intestine) than at pH 7.4 (PubMed:18327567). Interacts with the SH3 6
CC domain of human DNMBP (Tuba) (PubMed:19767742, PubMed:24332715).
CC Interacts with I-kappa-B kinase alpha (IKKA, CHUK) (PubMed:20855622).
CC {ECO:0000269|PubMed:18327567, ECO:0000269|PubMed:19767742,
CC ECO:0000269|PubMed:20855622, ECO:0000269|PubMed:24332715}.
CC -!- INTERACTION:
CC P71451; O15111: CHUK; Xeno; NbExp=3; IntAct=EBI-21019720, EBI-81249;
CC P71451; Q6XZF7-1: DNMBP; Xeno; NbExp=6; IntAct=EBI-21019720, EBI-16085546;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8641748,
CC ECO:0000269|PubMed:8878044, ECO:0000269|PubMed:8975898}. Host cytoplasm
CC {ECO:0000269|PubMed:20855622}.
CC -!- INDUCTION: Expression induced by PrfA; expressed in bacterial growth
CC medium at very low levels in the absence of extra copies of prfA (at
CC protein level) (PubMed:8878044, PubMed:8641748, PubMed:8975898).
CC Transcription induced upon a shift to growth in minimal medium and also
CC in infected mouse cells; expression is low 1 hour post-infection and
CC reaches its maximum 5 hour post-infection (PubMed:8878044). Detected by
CC 5 hours post infection in human Caco-2 cells (at protein level)
CC (PubMed:19767742). In infected HeLa cells expression increases
CC gradually over time (at protein level) (PubMed:20855622).
CC {ECO:0000269|PubMed:19767742, ECO:0000269|PubMed:20855622,
CC ECO:0000269|PubMed:8641748, ECO:0000269|PubMed:8878044,
CC ECO:0000269|PubMed:8975898}.
CC -!- DOMAIN: Consists of the cap domain (residues 35-76) and LRR repeat
CC region (77-213) and an Ig-like region (207-297), where the latter 2
CC overlap slightly (PubMed:17057330). The LRR repear region interacts via
CC its concave face with host DNMBP (Tuba) (PubMed:24332715).
CC {ECO:0000269|PubMed:17057330, ECO:0000269|PubMed:24332715}.
CC -!- MASS SPECTROMETRY: Mass=29.763; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:8641748};
CC -!- DISRUPTION PHENOTYPE: Significant reduction in virulence when injected
CC intravenously into C57BL/6 mice; no effect on intracellular growth of
CC bacteria in infected cell lines (PubMed:8878044, PubMed:20855622,
CC PubMed:23403554). Slightly reduced virulence when injected
CC intravenously into BALB/c mice; no effect on intracellular growth of
CC bacteria in infected cell lines (PubMed:8975898). Decreased bacterial
CC spreading in polarized epithelial cells (human Caco-2 BBE1 cell line),
CC decreased formation of host cell plasma membrane protusions, host cell
CC junctions are not perturbed by bacteria (PubMed:19767742).
CC Significantly increased production of cytokines, significantly
CC increased recruitment of neutrophils to the peritoneum, after
CC intraperitoneal injection into BALB/c mice (PubMed:20855622).
CC {ECO:0000269|PubMed:19767742, ECO:0000269|PubMed:20855622,
CC ECO:0000269|PubMed:23403554, ECO:0000269|PubMed:8878044,
CC ECO:0000269|PubMed:8975898}.
CC -!- MISCELLANEOUS: In infected host cells Listeria surface protein ActA
CC induces formation of F-actin 'comet tails' that propel bacteria. Motile
CC bacteria ultimately encounter the host plasma membrane, deforming it
CC into protrusions. Finally, pathogen-containing protrusions are engulfed
CC by adjacent mammalian cells. {ECO:0000305|PubMed:19767742}.
CC -!- SIMILARITY: Belongs to the internalin family. {ECO:0000305}.
CC -!- CAUTION: Conflicting results are seen for mutagenesis of Lys-173. It is
CC seen to reduce binding to the SH3 6 domain of human DNMBP (Tuba) by
CC surface plasmon resonance (PubMed:19767742). In the crystal structure
CC with Tuba this reside is seen not to be in the protein-protein
CC interface, and pull-down assays show it interacts normally with Tuba
CC (PubMed:24332715). Two studies show this residue is important for
CC virulence in the mouse model (PubMed:19767742, PubMed:23403554).
CC {ECO:0000269|PubMed:19767742, ECO:0000269|PubMed:23403554,
CC ECO:0000269|PubMed:24332715}.
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DR EMBL; X95822; CAA65088.1; -; Genomic_DNA.
DR EMBL; X98458; CAA67098.1; -; Genomic_DNA.
DR EMBL; Y07640; CAA68919.1; -; Genomic_DNA.
DR PDB; 1XEU; X-ray; 2.05 A; A=35-297.
DR PDB; 4CC4; X-ray; 2.60 A; A/C/E=35-297.
DR PDBsum; 1XEU; -.
DR PDBsum; 4CC4; -.
DR AlphaFoldDB; P71451; -.
DR SMR; P71451; -.
DR IntAct; P71451; 3.
DR PATRIC; fig|1234141.3.peg.2214; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR Gene3D; 2.60.40.1220; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR014755; Cu-Rt/internalin_Ig-like.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR024634; Internalin_N.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR025875; Leu-rich_rpt_4.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR012569; LRR-contain_adjacent_dom.
DR InterPro; IPR032675; LRR_dom_sf.
DR Pfam; PF12354; Internalin_N; 1.
DR Pfam; PF12799; LRR_4; 2.
DR Pfam; PF08191; LRR_adjacent; 1.
DR SMART; SM00369; LRR_TYP; 4.
DR SUPFAM; SSF81296; SSF81296; 1.
DR PROSITE; PS51450; LRR; 5.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Host cytoplasm;
KW Leucine-rich repeat; Repeat; Secreted; Signal; Virulence.
FT SIGNAL 1..34
FT /evidence="ECO:0000269|PubMed:8641748,
FT ECO:0000269|PubMed:8975898"
FT CHAIN 35..297
FT /note="Internalin C"
FT /evidence="ECO:0000255"
FT /id="PRO_5015096846"
FT REPEAT 74..96
FT /note="LRR 1"
FT /evidence="ECO:0000255"
FT REPEAT 97..120
FT /note="LRR 2"
FT /evidence="ECO:0000255"
FT REPEAT 122..139
FT /note="LRR 3"
FT /evidence="ECO:0000255"
FT REPEAT 140..161
FT /note="LRR 4"
FT /evidence="ECO:0000255"
FT REPEAT 162..184
FT /note="LRR 5"
FT /evidence="ECO:0000255"
FT REPEAT 186..207
FT /note="LRR 6"
FT /evidence="ECO:0000255"
FT MUTAGEN 146
FT /note="F->A: Reduced binding to the SH3 6 domain of human
FT DNMBP (Tuba), decreased bacterial spreading in an infected
FT polarized enterocyte cell line, host cell junctions are no
FT longer perturbed."
FT /evidence="ECO:0000269|PubMed:24332715"
FT MUTAGEN 173
FT /note="K->A: Reduced binding to the SH3 6 domain of human
FT DNMBP (Tuba); conflicting results are also found. Host NF-
FT kappa-B is still not translocated into the nucleus,
FT decreased virulence in C57BL/6 mice, bacteria replicate
FT less well in mouse liver."
FT /evidence="ECO:0000269|PubMed:19767742,
FT ECO:0000269|PubMed:23403554, ECO:0000269|PubMed:24332715"
FT MUTAGEN 246..247
FT /note="YY->AA: Prevents InlC-only crystals."
FT /evidence="ECO:0000269|PubMed:24332715"
FT CONFLICT 56
FT /note="V -> A (in Ref. 2; CAA67098)"
FT /evidence="ECO:0000305"
FT CONFLICT 232..234
FT /note="TNT -> ANA (in Ref. 2; CAA67098)"
FT /evidence="ECO:0000305"
FT HELIX 43..46
FT /evidence="ECO:0007829|PDB:1XEU"
FT HELIX 50..60
FT /evidence="ECO:0007829|PDB:1XEU"
FT STRAND 67..69
FT /evidence="ECO:0007829|PDB:1XEU"
FT HELIX 71..74
FT /evidence="ECO:0007829|PDB:1XEU"
FT STRAND 78..81
FT /evidence="ECO:0007829|PDB:1XEU"
FT HELIX 93..95
FT /evidence="ECO:0007829|PDB:1XEU"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:1XEU"
FT HELIX 113..115
FT /evidence="ECO:0007829|PDB:1XEU"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:1XEU"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:1XEU"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:1XEU"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:1XEU"
FT STRAND 166..168
FT /evidence="ECO:0007829|PDB:1XEU"
FT HELIX 178..182
FT /evidence="ECO:0007829|PDB:1XEU"
FT STRAND 188..190
FT /evidence="ECO:0007829|PDB:1XEU"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:4CC4"
FT STRAND 210..219
FT /evidence="ECO:0007829|PDB:1XEU"
FT STRAND 227..232
FT /evidence="ECO:0007829|PDB:1XEU"
FT STRAND 246..248
FT /evidence="ECO:0007829|PDB:1XEU"
FT HELIX 249..251
FT /evidence="ECO:0007829|PDB:1XEU"
FT STRAND 253..255
FT /evidence="ECO:0007829|PDB:1XEU"
FT STRAND 258..262
FT /evidence="ECO:0007829|PDB:1XEU"
FT STRAND 268..280
FT /evidence="ECO:0007829|PDB:1XEU"
FT STRAND 283..296
FT /evidence="ECO:0007829|PDB:1XEU"
SQ SEQUENCE 297 AA; 33192 MW; 85B35FF31CEBB9F5 CRC64;
MLKKNNWLQN AVIAMLVLIV GLCINMGSGT KVQAESIQRP TPINQVFPDP GLANAVKQNL
GKQSVTDLVS QKELSGVQNF NGDNSNIQSL AGMQFFTNLK ELHLSHNQIS DLSPLKDLTK
LEELSVNRNR LKNLNGIPSA CLSRLFLDNN ELRDTDSLIH LKNLEILSIR NNKLKSIVML
GFLSKLEVLD LHGNEITNTG GLTRLKKVNW IDLTGQKCVN EPVKYQPELY ITNTVKDPDG
RWISPYYISN GGSYVDGCVL WELPVYTDEV SYKFSEYINV GETEAIFDGT VTQPIKN
