ID   SP153_IXORI             Reviewed;         124 AA.
AC   A8CZZ8;
DT   12-OCT-2022, integrated into UniProtKB/Swiss-Prot.
DT   13-NOV-2007, sequence version 1.
DT   27-NOV-2024, entry version 15.
DE   RecName: Full=Salivary protein 15 Iric-3 {ECO:0000303|PubMed:17896872};
DE            Short=Salp15 Iric-3 {ECO:0000303|PubMed:17896872};
DE   AltName: Full=Salp15-like {ECO:0000305};
DE   Flags: Precursor;
OS   Ixodes ricinus (Common tick) (Acarus ricinus).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Acari;
OC   Parasitiformes; Ixodida; Ixodoidea; Ixodidae; Ixodinae; Ixodes.
OX   NCBI_TaxID=34613;
RN   [1] {ECO:0000312|EMBL:ABU93615.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], INDUCTION, AND TISSUE SPECIFICITY.
RC   TISSUE=Salivary gland;
RX   PubMed=17896872; DOI=10.1089/vbz.2006.0624;
RA   Hovius J.W., Ramamoorthi N., Veer C.V., De Groot K.A., Nijhof A.M.,
RA   Jongejan F., Van Dam A.P., Fikrig E.;
RT   "Identification of Salp15 homologues in Ixodes ricinus ticks.";
RL   Vector Borne Zoonotic Dis. 7:296-303(2007).
RN   [2]
RP   FUNCTION, INTERACTION WITH BORRELIA OUTER SURFACE PROTEIN C, AND
RP   RECOMBINANT EXPRESSION.
RX   PubMed=33401196; DOI=10.1016/j.ttbdis.2020.101630;
RA   Bierwagen P., Sliwiak J., Jaskolski M., Urbanowicz A.;
RT   "Strong interactions between Salp15 homologues from the tick I. ricinus and
RT   distinct types of the outer surface OspC protein from Borrelia.";
RL   Ticks Tick Borne Dis. 12:101630-101630(2021).
CC   -!- FUNCTION: Salivary tick protein that downregulates host immune system
CC       by binding to both dendritic cells, and CD4(+) T cells. Specifically
CC       binds to the CD4 coreceptor on T cells. This interaction prevents the
CC       activation of the Src kinase, Lck, and its downstream substrate Zap-70,
CC       and results in deficient activation of PLCgamma1, the repression of
CC       calcium fluxes triggered by T-cell antigen receptor (TCR) ligation, and
CC       a subsequent reduction in interleukin-2 production. This salivary
CC       protein also binds to DC-SIGN (CD209) on dendritic cells (DC) and
CC       activates the Raf-1 kinase/MEK signaling pathway that results in down-
CC       regulating expression of pro-inflammatory cytokines. Furthermore, it
CC       inhibits T cell proliferation induced by DCs (By similarity). In
CC       addition, it inhibits in vitro keratinocyte inflammation induced by
CC       Borrelia burgdorferi or by the major outer surface protein (OspC) of
CC       Borrelia (By similarity). In addition, it downregulates chemokines and
CC       monocyte chemoattractant protein 1, as well as several antimicrobial
CC       peptides such as defensins, cathelicidin, psoriasin, and RNase 7 (By
CC       similarity). Apart from its immunomodulatory activities, it is also
CC       associated with protection of Borrelia spirochetes from antibody-
CC       mediated killing through its binding to OspC (By similarity)
CC       (PubMed:33401196). In vivo, tests on different immune disease animal
CC       models show promising therapeutic results, e.g., in inhibiting HIV
CC       infection, experimental autoimmune encephalomyelitis, transplantation
CC       rejection, and asthma (By similarity). {ECO:0000250|UniProtKB:A8CZZ0,
CC       ECO:0000250|UniProtKB:Q95WZ4, ECO:0000269|PubMed:33401196}.
CC   -!- SUBUNIT: Interacts with host CD4 (By similarity). Interacts with host
CC       DC-SIGN (CD209) (By similarity). Interacts with Borrelia outer surface
CC       protein C (OspC) (PubMed:33401196). {ECO:0000250|UniProtKB:Q95WZ4,
CC       ECO:0000269|PubMed:33401196}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:17896872}.
CC   -!- TISSUE SPECIFICITY: Expressed in salivary glands (PubMed:17896872).
CC       Detected in fed adult female (PubMed:17896872).
CC       {ECO:0000269|PubMed:17896872}.
CC   -!- INDUCTION: By feeding (Probable). By the presence of Borrelia
CC       burgdorferi (By similarity). {ECO:0000250|UniProtKB:Q95WZ4,
CC       ECO:0000305|PubMed:17896872}.
CC   -!- SIMILARITY: Belongs to the salp15 family. {ECO:0000305}.
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DR   EMBL; EU128528; ABU93615.1; -; mRNA.
DR   AlphaFoldDB; A8CZZ8; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   InterPro; IPR021971; Salp15.
DR   Pfam; PF12115; Salp15; 1.
PE   1: Evidence at protein level;
KW   Glycoprotein; Secreted; Signal.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   CHAIN           23..124
FT                   /note="Salivary protein 15 Iric-3"
FT                   /id="PRO_5002718531"
FT   REGION          105..124
FT                   /note="CD4-binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q95WZ4"
FT   CARBOHYD        82
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        93
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   124 AA;  13846 MW;  F127F263420FD369 CRC64;
     MESFVAMKVV CIILLFVIAA EAESINEKSD VEPSKGKNNS GLQFKFPPYV PNHKAFALRL
     LSLCEQGIYG TKINDLKVDF KNCTFLCIRK YENLTLPLPE DTPCGPNNQT CHKKDECVGY
     IPGC
//