ID   CYTLG_IXOSC             Reviewed;         133 AA.
AC   B7PKZ2;
DT   13-APR-2016, integrated into UniProtKB/Swiss-Prot.
DT   10-FEB-2009, sequence version 1.
DT   03-AUG-2022, entry version 54.
DE   RecName: Full=Salivary cystatin-L {ECO:0000250|UniProtKB:Q8MVB6};
DE   AltName: Full=Sialostatin L {ECO:0000250|UniProtKB:Q8MVB6};
DE            Short=SialoL {ECO:0000250|UniProtKB:Q8MVB6};
DE   Flags: Precursor;
GN   ORFNames=IscW_ISCW018603 {ECO:0000312|EMBL:EEC07264.1};
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|Proteomes:UP000001555};
RN   [1]
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.
CC   -!- FUNCTION: Inhibitor of cysteine proteinases. Inhibits host immune
CC       responses via its inhibition of host cathepsins. Contributes to the
CC       suppression of the host's immune response to tick salivary proteins and
CC       is important for successful feeding on hosts. Inhibits differentiation
CC       of host dendritic cells. Inhibits proliferation of host T-cells in
CC       response to antigen stimulus. Down-regulates TLR2-mediated host
CC       responses to infection by B.burgdorferi and the production of the
CC       chemokine CCL3 by host dendritic cells. Down-regulates host responses
CC       to infection by B.burgdorferi and the production of IFNB1 by host
CC       dendritic cells. Down-regulates IL1B production by host mast cells, and
CC       this then leads to impaired activation of IL1R1, resulting in decreased
CC       IL9 production. Inhibits host inflammatory reactions and recruitment of
CC       host neutrophils. Inhibits papain and cathepsin L (CTSL) (in vitro).
CC       Inhibits cathepsin S (CTSS) (in vitro). Inhibits CTSV and CTSC, but to
CC       a lesser degree (in vitro). {ECO:0000250|UniProtKB:Q8MVB6}.
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:0000250|UniProtKB:Q8MVB6}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q8MVB6}.
CC   -!- SIMILARITY: Belongs to the cystatin family. {ECO:0000305}.
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DR   EMBL; DS737013; EEC07264.1; -; Genomic_DNA.
DR   RefSeq; XP_002434440.1; XM_002434395.1.
DR   AlphaFoldDB; B7PKZ2; -.
DR   SMR; B7PKZ2; -.
DR   STRING; 6945.B7PKZ2; -.
DR   MEROPS; I25.049; -.
DR   GeneID; 8053084; -.
DR   KEGG; isc:IscW_ISCW018603; -.
DR   VEuPathDB; VectorBase:ISCI018603; -.
DR   VEuPathDB; VectorBase:ISCW018603; -.
DR   HOGENOM; CLU_1898537_0_0_1; -.
DR   InParanoid; B7PKZ2; -.
DR   OrthoDB; 1565344at2759; -.
DR   PhylomeDB; B7PKZ2; -.
DR   Proteomes; UP000001555; Unassembled WGS sequence.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0031982; C:vesicle; IBA:GO_Central.
DR   GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IDA:UniProtKB.
DR   GO; GO:0044622; P:negative regulation of cell migration in another organism; IMP: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   3: Inferred from homology;
KW   Disulfide bond; Protease inhibitor; Reference proteome; Secreted; Signal;
KW   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_5005396730"
FT   DOMAIN          30..117
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:0000250|UniProtKB:Q8MVB6"
FT   DISULFID        111..130
FT                   /evidence="ECO:0000250|UniProtKB:Q8MVB6"
SQ   SEQUENCE   133 AA;  14213 MW;  53553F8750A28287 CRC64;
     MTSSFALVLL LGGVAVCVAT GVFGGYSERA NHQANPEFLN LAHYATSTWS AQQPGKTHFD
     TVAEVLKVET QVVAGTNYRL TLKVAESTCE LTSTYNKDTC LPKADAAHRT CTTVVFESLQ
     GDKSVSSFEC EAA