CYTL2_IXOSC
ID CYTL2_IXOSC Reviewed; 132 AA.
AC B7PKZ1; Q4PMS6;
DT 13-APR-2016, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Salivary cystatin-L2 {ECO:0000305};
DE AltName: Full=Sialostatin-L2 {ECO:0000303|PubMed:17698852, ECO:0000303|PubMed:20545851, ECO:0000303|PubMed:24686067};
DE Flags: Precursor;
GN ORFNames=IscW_ISCW018602 {ECO:0000312|EMBL:EEC07263.1};
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:EEC07263.1};
RN [1] {ECO:0000312|EMBL:AAY66685.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=ISN-L-110 {ECO:0000312|EMBL:AAY66685.1};
RC TISSUE=Salivary gland {ECO:0000312|EMBL:AAY66685.1};
RA Ribeiro J.M.C.;
RT "An updated catalog of salivary gland transcripts from Ixodes scapularis
RT ticks.";
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Wikel;
RG Ixodes scapularis Genome Project Consortium;
RA Caler E., Hannick L.I., Bidwell S., Joardar V., Thiagarajan M., Amedeo P.,
RA Galinsky K.J., Schobel S., Inman J., Hostetler J., Miller J., Hammond M.,
RA Megy K., Lawson D., Kodira C., Sutton G., Meyer J., Hill C.A., Birren B.,
RA Nene V., Collins F., Alarcon-Chaidez F., Wikel S., Strausberg R.;
RT "Annotation of Ixodes scapularis.";
RL Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, INDUCTION BY FEEDING, AND TISSUE
RP 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=24686067; DOI=10.1128/iai.01679-14;
RA Chen G., Wang X., Severo M.S., Sakhon O.S., Sohail M., Brown L.J.,
RA Sircar M., Snyder G.A., Sundberg E.J., Ulland T.K., Olivier A.K.,
RA Andersen J.F., Zhou Y., Shi G.P., Sutterwala F.S., Kotsyfakis M.,
RA Pedra J.H.;
RT "The tick salivary protein sialostatin L2 inhibits caspase-1-mediated
RT inflammation during Anaplasma phagocytophilum infection.";
RL Infect. Immun. 82:2553-2564(2014).
RN [5]
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 [6] {ECO:0007744|PDB:3LH4}
RP X-RAY CRYSTALLOGRAPHY (1.52 ANGSTROMS) OF 19-132, 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, probably via its inhibition of host cathepsins. Contributes
CC to the suppression of the host's immune response to tick salivary
CC proteins and is important for successful feeding on hosts
CC (PubMed:17698852). Down-regulates TLR2-mediated host responses to
CC infection by B.burgdorferi and the production of chemokines CCL3 and
CC CXCL10 by host dendritic cells (PubMed:25975355). Enhances infection by
CC the tick-transmitted pathogen B.burgdorferi (in vitro)
CC (PubMed:20545851). Inhibits host inflammatory responses to
CC A.phagocytophilum infection (PubMed:24686067). Inhibits papain (in
CC vitro) (PubMed:20545851). Inhibits cathepsin-L (CTSL) (in vitro)
CC (PubMed:17698852, PubMed:20545851). Inhibits cathepsin-L2 (CTSV) (in
CC vitro) (PubMed:17698852). {ECO:0000269|PubMed:17698852,
CC ECO:0000269|PubMed:20545851, ECO:0000269|PubMed:24686067, ECO:0000305}.
CC -!- SUBUNIT: Monomer. {ECO:0000305|PubMed:20545851}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Detected in salivary gland and midgut.
CC {ECO:0000269|PubMed:17698852}.
CC -!- INDUCTION: Strongly up-regulated in salivary gland during feeding.
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}.
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DR EMBL; DQ066048; AAY66685.1; -; mRNA.
DR EMBL; DS737013; EEC07263.1; -; Genomic_DNA.
DR RefSeq; XP_002434439.1; XM_002434394.1.
DR PDB; 3LH4; X-ray; 1.80 A; A=19-132.
DR PDB; 3MWZ; X-ray; 1.52 A; A=19-132.
DR PDBsum; 3LH4; -.
DR PDBsum; 3MWZ; -.
DR AlphaFoldDB; B7PKZ1; -.
DR SMR; B7PKZ1; -.
DR STRING; 6945.B7PKZ1; -.
DR MEROPS; I25.049; -.
DR GeneID; 8053083; -.
DR KEGG; isc:IscW_ISCW018602; -.
DR VEuPathDB; VectorBase:ISCI018602; -.
DR VEuPathDB; VectorBase:ISCW018602; -.
DR HOGENOM; CLU_1898537_0_0_1; -.
DR InParanoid; B7PKZ1; -.
DR OrthoDB; 1565344at2759; -.
DR PhylomeDB; B7PKZ1; -.
DR EvolutionaryTrace; B7PKZ1; -.
DR Proteomes; UP000001555; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0031982; C:vesicle; IBA:GO_Central.
DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:2000117; P:negative regulation of cysteine-type endopeptidase activity; IDA:UniProtKB.
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..18
FT /evidence="ECO:0000255"
FT CHAIN 19..132
FT /note="Salivary cystatin-L2"
FT /evidence="ECO:0000255|RuleBase:RU362130"
FT /id="PRO_5005396719"
FT DOMAIN 28..117
FT /note="Cystatin"
FT /evidence="ECO:0000255"
FT SITE 24
FT /note="Reactive site"
FT /evidence="ECO:0000250|UniProtKB:P01040"
FT DISULFID 88..99
FT /evidence="ECO:0000269|PubMed:20545851,
FT ECO:0007744|PDB:3LH4"
FT DISULFID 110..129
FT /evidence="ECO:0000269|PubMed:20545851,
FT ECO:0007744|PDB:3LH4"
FT CONFLICT 10
FT /note="V -> L (in Ref. 1; AAY66685)"
FT /evidence="ECO:0000305"
FT CONFLICT 125
FT /note="S -> N (in Ref. 1; AAY66685)"
FT /evidence="ECO:0000305"
FT STRAND 27..29
FT /evidence="ECO:0007829|PDB:3MWZ"
FT HELIX 36..50
FT /evidence="ECO:0007829|PDB:3MWZ"
FT STRAND 57..89
FT /evidence="ECO:0007829|PDB:3MWZ"
FT TURN 96..98
FT /evidence="ECO:0007829|PDB:3MWZ"
FT STRAND 107..116
FT /evidence="ECO:0007829|PDB:3MWZ"
FT STRAND 122..129
FT /evidence="ECO:0007829|PDB:3MWZ"
SQ SEQUENCE 132 AA; 14323 MW; 2173096707E6D174 CRC64;
MTSSLALVLV FGGAAVCAEL ALRGGYRERS NQDDPEYLEL AHYATSTWSA QQPGKTHFDT
VVEVLKVETQ TVAGTNYRLT LKVAESTCEL TSTYNKDTCQ ANANAAQRTC TTVIYRNLQG
EKSISSFECA AA
