CYTL_IXOSC
ID CYTL_IXOSC Reviewed; 133 AA.
AC Q8MVB6;
DT 13-APR-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 25-MAY-2022, entry version 68.
DE RecName: Full=Salivary cystatin-L {ECO:0000305};
DE AltName: Full=Sialostatin-L {ECO:0000303|PubMed:16772304, ECO:0000303|PubMed:20545851, ECO:0000303|PubMed:26078269};
DE Short=SialoL {ECO:0000303|PubMed:19494265};
DE Flags: Precursor;
OS Ixodes scapularis (Black-legged tick) (Deer tick).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Acari;
OC Parasitiformes; Ixodida; Ixodoidea; Ixodidae; Ixodinae; Ixodes.
OX NCBI_TaxID=6945 {ECO:0000312|EMBL:AAM93646.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Rhode Island {ECO:0000312|EMBL:AAM93646.1};
RC TISSUE=Salivary gland {ECO:0000312|EMBL:AAM93646.1};
RX PubMed=12177149; DOI=10.1242/jeb.205.18.2843;
RA Valenzuela J.G., Francischetti I.M., Pham V.M., Garfield M.K., Mather T.N.,
RA Ribeiro J.M.;
RT "Exploring the sialome of the tick Ixodes scapularis.";
RL J. Exp. Biol. 205:2843-2864(2002).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16772304; DOI=10.1074/jbc.m513010200;
RA Kotsyfakis M., Sa-Nunes A., Francischetti I.M., Mather T.N., Andersen J.F.,
RA Ribeiro J.M.;
RT "Antiinflammatory and immunosuppressive activity of sialostatin L, a
RT salivary cystatin from the tick Ixodes scapularis.";
RL J. Biol. Chem. 281:26298-26307(2006).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=17698852; DOI=10.1074/jbc.m703143200;
RA Kotsyfakis M., Karim S., Andersen J.F., Mather T.N., Ribeiro J.M.;
RT "Selective cysteine protease inhibition contributes to blood-feeding
RT success of the tick Ixodes scapularis.";
RL J. Biol. Chem. 282:29256-29263(2007).
RN [4]
RP FUNCTION.
RX PubMed=19494265; DOI=10.4049/jimmunol.0900075;
RA Sa-Nunes A., Bafica A., Antonelli L.R., Choi E.Y., Francischetti I.M.,
RA Andersen J.F., Shi G.P., Chavakis T., Ribeiro J.M., Kotsyfakis M.;
RT "The immunomodulatory action of sialostatin L on dendritic cells reveals
RT its potential to interfere with autoimmunity.";
RL J. Immunol. 182:7422-7429(2009).
RN [5]
RP FUNCTION.
RX PubMed=26078269; DOI=10.4049/jimmunol.1401823;
RA Klein M., Bruehl T.J., Staudt V., Reuter S., Grebe N., Gerlitzki B.,
RA Hoffmann M., Bohn T., Ulges A., Stergiou N., de Graaf J., Loewer M.,
RA Taube C., Becker M., Hain T., Dietzen S., Stassen M., Huber M., Lohoff M.,
RA Campos Chagas A., Andersen J., Kotal J., Langhansova H., Kopecky J.,
RA Schild H., Kotsyfakis M., Schmitt E., Bopp T.;
RT "Tick salivary sialostatin L represses the initiation of immune responses
RT by targeting IRF4-dependent transcription in murine mast cells.";
RL J. Immunol. 195:621-631(2015).
RN [6]
RP FUNCTION.
RX PubMed=25975355; DOI=10.1186/s13071-015-0887-1;
RA Lieskovska J., Palenikova J., Langhansova H., Campos Chagas A., Calvo E.,
RA Kotsyfakis M., Kopecky J.;
RT "Tick sialostatins L and L2 differentially influence dendritic cell
RT responses to Borrelia spirochetes.";
RL Parasit. Vectors 8:275-275(2015).
RN [7] {ECO:0007744|PDB:4ZM8}
RP X-RAY CRYSTALLOGRAPHY (2.67 ANGSTROMS) OF 20-133, FUNCTION, SUBUNIT, AND
RP DISULFIDE BONDS.
RX PubMed=20545851; DOI=10.1111/j.1365-2958.2010.07220.x;
RA Kotsyfakis M., Horka H., Salat J., Andersen J.F.;
RT "The crystal structures of two salivary cystatins from the tick Ixodes
RT scapularis and the effect of these inhibitors on the establishment of
RT Borrelia burgdorferi infection in a murine model.";
RL Mol. Microbiol. 77:456-470(2010).
CC -!- FUNCTION: Inhibitor of cysteine proteinases. Inhibits host immune
CC responses via its inhibition of host cathepsins (PubMed:19494265).
CC Contributes to the suppression of the host's immune response to tick
CC salivary proteins and is important for successful feeding on hosts
CC (PubMed:17698852). Inhibits differentiation of host dendritic cells
CC (PubMed:19494265, PubMed:25975355). Inhibits proliferation of host T-
CC cells in response to antigen stimulus (PubMed:19494265). Down-regulates
CC TLR2-mediated host responses to infection by B.burgdorferi and the
CC production of the chemokine CCL3 by host dendritic cells
CC (PubMed:25975355). Down-regulates host responses to infection by
CC B.burgdorferi and the production of IFNB1 by host dendritic cells
CC (PubMed:25975355). Down-regulates IL1B production by host mast cells,
CC and this then leads to impaired activation of IL1R1, resulting in
CC decreased IL9 production (PubMed:26078269). Inhibits host inflammatory
CC reactions and recruitment of host neutrophils (PubMed:16772304).
CC Inhibits papain and cathepsin-L (CTSL) (in vitro) (PubMed:16772304,
CC PubMed:17698852, PubMed:20545851). Inhibits cathepsin-S (CTSS) (in
CC vitro) (PubMed:17698852, PubMed:20545851). Inhibits CTSV and CTSC, but
CC to a lesser degree (in vitro) (PubMed:16772304, PubMed:17698852).
CC {ECO:0000269|PubMed:16772304, ECO:0000269|PubMed:17698852,
CC ECO:0000269|PubMed:19494265, ECO:0000269|PubMed:20545851,
CC ECO:0000269|PubMed:25975355, ECO:0000269|PubMed:26078269}.
CC -!- SUBUNIT: Monomer. Can form homodimers in vitro, but probably not in
CC vivo. Homodimers are predicted to be inactive; dimerization disrupts
CC the interaction with target proteases. {ECO:0000269|PubMed:20545851}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16772304}.
CC -!- TISSUE SPECIFICITY: Detected in saliva (at protein level)
CC (PubMed:16772304). Detected in salivary gland and midgut
CC (PubMed:17698852). {ECO:0000269|PubMed:16772304,
CC ECO:0000269|PubMed:17698852}.
CC -!- DISRUPTION PHENOTYPE: Combined, RNAi-mediated down-regulation of
CC Salivary cystatin-L and Salivary cystatin-L2 in salivary glands
CC strongly impairs the tick's ability to feed on hosts. About 40% of the
CC ticks cannot feed and die. The remainder show much reduced blood
CC intake, appear unhealthy and display strongly reduced egg laying. RNAi-
CC treated ticks show an impaired ability to suppress the host's immune
CC response to tick salivary proteins. {ECO:0000269|PubMed:17698852}.
CC -!- SIMILARITY: Belongs to the cystatin 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; AF483724; AAM93646.1; -; mRNA.
DR PDB; 4ZM8; X-ray; 2.68 A; A/B/C/D=20-133.
DR PDBsum; 4ZM8; -.
DR AlphaFoldDB; Q8MVB6; -.
DR SMR; Q8MVB6; -.
DR MEROPS; I25.049; -.
DR VEuPathDB; VectorBase:ISCI018603; -.
DR VEuPathDB; VectorBase:ISCW018603; -.
DR HOGENOM; CLU_1898537_0_0_1; -.
DR EvolutionaryTrace; Q8MVB6; -.
DR Proteomes; UP000001555; Unplaced.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR CDD; cd00042; CY; 1.
DR InterPro; IPR000010; Cystatin_dom.
DR InterPro; IPR046350; Cystatin_sf.
DR InterPro; IPR018073; Prot_inh_cystat_CS.
DR Pfam; PF00031; Cystatin; 1.
DR SMART; SM00043; CY; 1.
DR SUPFAM; SSF54403; SSF54403; 1.
DR PROSITE; PS00287; CYSTATIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Protease inhibitor; Reference proteome;
KW Secreted; Signal; Thiol protease inhibitor.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..133
FT /note="Salivary cystatin-L"
FT /evidence="ECO:0000255|RuleBase:RU362130"
FT /id="PRO_5005401154"
FT DOMAIN 30..118
FT /note="Cystatin"
FT /evidence="ECO:0000255"
FT SITE 24
FT /note="Reactive site"
FT /evidence="ECO:0000250|UniProtKB:P01040"
FT DISULFID 89..100
FT /evidence="ECO:0000269|PubMed:20545851,
FT ECO:0007744|PDB:4ZM8"
FT DISULFID 111..130
FT /evidence="ECO:0000269|PubMed:20545851,
FT ECO:0007744|PDB:4ZM8"
FT HELIX 36..51
FT /evidence="ECO:0007829|PDB:4ZM8"
FT STRAND 58..90
FT /evidence="ECO:0007829|PDB:4ZM8"
FT TURN 97..99
FT /evidence="ECO:0007829|PDB:4ZM8"
FT STRAND 109..118
FT /evidence="ECO:0007829|PDB:4ZM8"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:4ZM8"
SQ SEQUENCE 133 AA; 14282 MW; F07CF496B55995B7 CRC64;
MTSTFALVLL LGGMAVCVAT GVFGGYSERA NHQANPEFLN LAHYATSTWS AQQPGKTHFD
TVAEVVKVET QVVAGTNYRL TLKVAESTCE LTSTYNKDTC LPKADAAHRT CTTVVFENLQ
GDKSVSPFEC EAA
