EVA4_RHISA
ID EVA4_RHISA Reviewed; 127 AA.
AC P0C8E9;
DT 25-NOV-2008, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 1.
DT 03-AUG-2022, entry version 24.
DE RecName: Full=Evasin-4 {ECO:0000303|PubMed:18678732, ECO:0000303|PubMed:23910450, ECO:0000303|PubMed:25266725};
DE Short=EVA4 {ECO:0000250|UniProtKB:P0C8E8, ECO:0000305};
DE Flags: Precursor;
OS Rhipicephalus sanguineus (Brown dog tick) (Ixodes sanguineus).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Acari;
OC Parasitiformes; Ixodida; Ixodoidea; Ixodidae; Rhipicephalinae;
OC Rhipicephalus; Rhipicephalus.
OX NCBI_TaxID=34632;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT, AND FUNCTION.
RC TISSUE=Salivary gland;
RX PubMed=18678732; DOI=10.1084/jem.20072689;
RA Deruaz M., Frauenschuh A., Alessandri A.L., Dias J.M., Coelho F.M.,
RA Russo R.C., Ferreira B.R., Graham G.J., Shaw J.P., Wells T.N.C.,
RA Teixeira M.M., Power C.A., Proudfoot A.E.I.;
RT "Ticks produce highly selective chemokine binding proteins with
RT antiinflammatory activity.";
RL J. Exp. Med. 205:2019-2031(2008).
RN [2]
RP FUNCTION.
RX PubMed=23910450; DOI=10.1111/febs.12463;
RA Deruaz M., Bonvin P., Severin I.C., Johnson Z., Krohn S., Power C.A.,
RA Proudfoot A.E.;
RT "Evasin-4, a tick-derived chemokine-binding protein with broad selectivity
RT can be modified for use in preclinical disease models.";
RL FEBS J. 280:4876-4887(2013).
RN [3]
RP FUNCTION.
RX PubMed=23925450; DOI=10.1160/th13-04-0297;
RA Braunersreuther V., Montecucco F., Pelli G., Galan K., Proudfoot A.E.,
RA Belin A., Vuilleumier N., Burger F., Lenglet S., Caffa I., Soncini D.,
RA Nencioni A., Vallee J.P., Mach F.;
RT "Treatment with the CC chemokine-binding protein Evasin-4 improves post-
RT infarction myocardial injury and survival in mice.";
RL Thromb. Haemost. 110:807-825(2013).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF GLU-39; ASP-40; TYR-42; THR-43; THR-49;
RP TYR-51; PHE-52; ASN-54; ASN-70; THR-74; PHE-76; GLN-95; GLN-100 AND
RP TRP-127.
RX PubMed=25266725; DOI=10.1074/jbc.m114.599233;
RA Bonvin P., Dunn S.M., Rousseau F., Dyer D.P., Shaw J., Power C.A.,
RA Handel T.M., Proudfoot A.E.;
RT "Identification of the pharmacophore of the CC chemokine-binding proteins
RT Evasin-1 and -4 using phage display.";
RL J. Biol. Chem. 289:31846-31855(2014).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.29 ANGSTROMS) OF 24-127, DISULFIDE BONDS, SUBUNIT,
RP NMR SPECTROSCOPY, AND RECOMBINANT EXPRESSION.
RX PubMed=32817341; DOI=10.1074/jbc.ra120.013891;
RA Denisov S.S., Ramirez-Escudero M., Heinzmann A.C.A., Ippel J.H.,
RA Dawson P.E., Koenen R.R., Hackeng T.M., Janssen B.J.C., Dijkgraaf I.;
RT "Structural characterization of anti-CCL5 activity of the tick salivary
RT protein evasin-4.";
RL J. Biol. Chem. 295:14367-14378(2020).
CC -!- FUNCTION: Salivary chemokine-binding protein which has chemokine-
CC neutralizing activity and binds to host chemokines CCL1, CCL3, CCL5,
CC CCL7, CCL8, CCL11, CCL14, CCL15, CCL16, CCL17, CCL18, CCL19, CCL21,
CC CCL22, CCL23, CCL24, CCL25 and CCL26 with nanomolar affinity
CC (PubMed:18678732, PubMed:23910450, PubMed:25266725). Binds to CCL3 and
CC CCL5 with 1:1 stoichiometry (PubMed:23910450). Although binding to
CC CCL25 is observed, does not inhibit CCL25-induced chemotaxis
CC (PubMed:25266725).Has been shown to reduce cardiac injury and
CC inflammation in mice through its anti-CCL5 activity (PubMed:23925450).
CC {ECO:0000269|PubMed:18678732, ECO:0000269|PubMed:23910450,
CC ECO:0000269|PubMed:23925450, ECO:0000269|PubMed:25266725}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:18678732,
CC ECO:0000269|PubMed:32817341}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- DOMAIN: N-terminus residues are involved in complex formation with
CC CCL5. A N-terminal derivative peptide composed of residues 37-54
CC inhibits CCL5 activity in monocyte migration assays, suggesting that
CC Evasin-4 derivatives could be used as a starting point for the
CC development of anti-inflammatory drugs. {ECO:0000305|PubMed:32817341}.
CC -!- SIMILARITY: Belongs to the evasin C8 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Hidden powers - Issue 99 of
CC November 2008;
CC URL="https://web.expasy.org/spotlight/back_issues/099";
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DR PDB; 6ST4; X-ray; 1.29 A; A=24-127.
DR PDB; 6STC; X-ray; 1.69 A; A=24-127.
DR PDB; 6STE; X-ray; 1.79 A; A/B/C/D=24-127.
DR PDBsum; 6ST4; -.
DR PDBsum; 6STC; -.
DR PDBsum; 6STE; -.
DR AlphaFoldDB; P0C8E9; -.
DR SMR; P0C8E9; -.
DR VEuPathDB; VectorBase:LOC119390864; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0019957; F:C-C chemokine binding; IDA:UniProtKB.
DR GO; GO:1900137; P:negative regulation of chemokine activity; IDA:UniProtKB.
DR InterPro; IPR045797; EVA_Class_A.
DR InterPro; IPR007110; Ig-like_dom.
DR Pfam; PF19429; EVA_Class_A; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Glycoprotein; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..127
FT /note="Evasin-4"
FT /evidence="ECO:0000305|PubMed:18678732"
FT /id="PRO_0000354059"
FT CARBOHYD 54
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 64
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 83
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 106
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 50..69
FT /evidence="ECO:0000269|PubMed:32817341,
FT ECO:0007744|PDB:6ST4, ECO:0007744|PDB:6STC,
FT ECO:0007744|PDB:6STE"
FT DISULFID 65..112
FT /evidence="ECO:0000269|PubMed:32817341,
FT ECO:0007744|PDB:6ST4, ECO:0007744|PDB:6STC,
FT ECO:0007744|PDB:6STE"
FT DISULFID 86..117
FT /evidence="ECO:0000269|PubMed:32817341,
FT ECO:0007744|PDB:6ST4, ECO:0007744|PDB:6STC,
FT ECO:0007744|PDB:6STE"
FT DISULFID 107..126
FT /evidence="ECO:0000269|PubMed:32817341,
FT ECO:0007744|PDB:6ST4, ECO:0007744|PDB:6STC,
FT ECO:0007744|PDB:6STE"
FT MUTAGEN 39
FT /note="E->A: Significantly reduced binding to CCL5 and
FT slight reduction in inhibition of chemokine activity."
FT /evidence="ECO:0000269|PubMed:25266725"
FT MUTAGEN 40
FT /note="D->A: No effect on binding to CCL5."
FT /evidence="ECO:0000269|PubMed:25266725"
FT MUTAGEN 42
FT /note="Y->A: Significantly reduced binding to CCL5 and
FT slight reduction in inhibition of chemokine activity."
FT /evidence="ECO:0000269|PubMed:25266725"
FT MUTAGEN 43
FT /note="T->A: No effect on binding to CCL5."
FT /evidence="ECO:0000269|PubMed:25266725"
FT MUTAGEN 49
FT /note="T->A: No effect on binding to CCL5."
FT /evidence="ECO:0000269|PubMed:25266725"
FT MUTAGEN 51
FT /note="Y->A: No effect on binding to CCL5."
FT /evidence="ECO:0000269|PubMed:25266725"
FT MUTAGEN 52
FT /note="F->A: No effect on binding to CCL5."
FT /evidence="ECO:0000269|PubMed:25266725"
FT MUTAGEN 54
FT /note="N->A: No effect on binding to CCL5."
FT /evidence="ECO:0000269|PubMed:25266725"
FT MUTAGEN 70
FT /note="N->A: No effect on binding to CCL5."
FT /evidence="ECO:0000269|PubMed:25266725"
FT MUTAGEN 74
FT /note="T->A: Slightly reduced binding to CCL5."
FT /evidence="ECO:0000269|PubMed:25266725"
FT MUTAGEN 76
FT /note="F->A: No effect on binding to CCL5."
FT /evidence="ECO:0000269|PubMed:25266725"
FT MUTAGEN 95
FT /note="Q->A: No effect on binding to CCL5."
FT /evidence="ECO:0000269|PubMed:25266725"
FT MUTAGEN 100
FT /note="Q->A: Slightly reduced binding to CCL5."
FT /evidence="ECO:0000269|PubMed:25266725"
FT MUTAGEN 127
FT /note="W->A: No effect on binding to CCL5."
FT /evidence="ECO:0000269|PubMed:25266725"
FT STRAND 46..53
FT /evidence="ECO:0007829|PDB:6STE"
FT STRAND 65..70
FT /evidence="ECO:0007829|PDB:6ST4"
FT STRAND 75..79
FT /evidence="ECO:0007829|PDB:6ST4"
FT STRAND 85..90
FT /evidence="ECO:0007829|PDB:6ST4"
FT HELIX 94..98
FT /evidence="ECO:0007829|PDB:6ST4"
FT TURN 100..102
FT /evidence="ECO:0007829|PDB:6STC"
FT STRAND 105..113
FT /evidence="ECO:0007829|PDB:6ST4"
FT STRAND 116..126
FT /evidence="ECO:0007829|PDB:6ST4"
SQ SEQUENCE 127 AA; 14126 MW; EF315B8BFE23E602 CRC64;
MAFKYWFVFA AVLYARQWLS TKCEVPQMTS SSAPDLEEED DYTAYAPLTC YFTNSTLGLL
APPNCSVLCN STTTWFNETS PNNASCLLTV DFLTQDAILQ ENQPYNCSVG HCDNGTCAGP
PRHAQCW
