ID   BV8_BOMVA               Reviewed;          96 AA.
AC   Q9PW66;
DT   26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   25-MAY-2022, entry version 67.
DE   RecName: Full=Prokineticin Bv8 {ECO:0000303|PubMed:10422759};
DE   Flags: Precursor;
OS   Bombina variegata (Yellow-bellied toad).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Bombinatoridae; Bombina.
OX   NCBI_TaxID=8348;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 20-96, FUNCTION, MASS
RP   SPECTROMETRY, AND SUBCELLULAR LOCATION.
RC   TISSUE=Skin secretion;
RX   PubMed=10422759; DOI=10.1016/s0014-2999(99)00229-0;
RA   Mollay C., Wechselberger C., Mignogna G., Negri L., Melchiorri P.,
RA   Barra D., Kreil G.;
RT   "Bv8, a small protein from frog skin and its homologue from snake venom
RT   induce hyperalgesia in rats.";
RL   Eur. J. Pharmacol. 374:189-196(1999).
RN   [2]
RP   FUNCTION.
RC   TISSUE=Skin secretion;
RX   PubMed=12466223; DOI=10.1038/sj.bjp.0704995;
RA   Negri L., Lattanzi R., Giannini E., Metere A., Colucci M., Barra D.,
RA   Kreil G., Melchiorri P.;
RT   "Nociceptive sensitization by the secretory protein Bv8.";
RL   Br. J. Pharmacol. 137:1147-1154(2002).
RN   [3]
RP   FUNCTION.
RC   TISSUE=Skin secretion;
RX   PubMed=16299550; DOI=10.1038/sj.bjp.0706467;
RA   Martucci C., Franchi S., Giannini E., Tian H., Melchiorri P., Negri L.,
RA   Sacerdote P.;
RT   "Bv8, the amphibian homologue of the mammalian prokineticins, induces a
RT   proinflammatory phenotype of mouse macrophages.";
RL   Br. J. Pharmacol. 147:225-234(2006).
RN   [4]
RP   FUNCTION.
RC   TISSUE=Skin secretion;
RX   PubMed=16687502; DOI=10.1523/jneurosci.3870-05.2006;
RA   Vellani V., Colucci M., Lattanzi R., Giannini E., Negri L., Melchiorri P.,
RA   McNaughton P.A.;
RT   "Sensitization of transient receptor potential vanilloid 1 by the
RT   prokineticin receptor agonist Bv8.";
RL   J. Neurosci. 26:5109-5116(2006).
RN   [5]
RP   STRUCTURE BY NMR OF 20-96, SYNTHESIS OF 20-96, FUNCTION, DISULFIDE BOND,
RP   ACTIVITY PROFILE, AND MUTAGENESIS OF 20-ALA--GLY-24.
RX   PubMed=20677202; DOI=10.1002/cbic.201000330;
RA   Morales R.A., Daly N.L., Vetter I., Mobli M., Napier I.A., Craik D.J.,
RA   Lewis R.J., Christie M.J., King G.F., Alewood P.F., Durek T.;
RT   "Chemical synthesis and structure of the prokineticin Bv8.";
RL   ChemBioChem 11:1882-1888(2010).
CC   -!- FUNCTION: Potent agonist for both PKR1/PROKR1 and PKR2/PROKR2, and
CC       inducer of a potent and long-lasting hyperalgesia (PubMed:16299550,
CC       PubMed:20677202). Shows an EC(50) of 0.264 nM, when tested on
CC       neuroblastoma cells (SH-SY5Y) which endogenously express mainly
CC       PKR2/PROKR2 (PubMed:20677202). Also potentiates capsaicin-induced TRPV1
CC       current, when tested on DRG neurons (PubMed:16687502, PubMed:20677202).
CC       Induces a biphasic hyperalgesia to tactile and thermal stimuli after
CC       systemic injection of this protein into rat (PubMed:10422759,
CC       PubMed:12466223). The initial phase of hyperalgesia is caused by a
CC       local action on nociceptors, because intraplantar injection of this
CC       protein causes a strong and localized hyperalgesia with a similar time
CC       course to that of the initial phase of hyperalgesia seen with systemic
CC       injection. The secondary phase of hyperalgesia is not seen with local
CC       intraplantar injection and is therefore probably attributable to a
CC       central action of this protein (PubMed:16687502). At subnanomolar
CC       concentrations, this protein both induces potent chemotaxis of
CC       macrophages and stimulates LPS-induced production of the pro-
CC       inflammatory cytokines IL-1 and IL-12 (PubMed:16299550). In vivo, this
CC       protein potently stimulates the contraction of the guinea-pig
CC       gastrointestinal (GI) smooth muscle (at nanomolar concentration)
CC       (PubMed:10422759). {ECO:0000269|PubMed:10422759,
CC       ECO:0000269|PubMed:12466223, ECO:0000269|PubMed:16299550,
CC       ECO:0000269|PubMed:20677202, ECO:0000305|PubMed:16687502}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10422759}.
CC   -!- TISSUE SPECIFICITY: Expressed by the skin glands.
CC       {ECO:0000305|PubMed:10422759}.
CC   -!- MASS SPECTROMETRY: Mass=8020; Method=Unknown;
CC       Evidence={ECO:0000269|PubMed:10422759};
CC   -!- SIMILARITY: Belongs to the AVIT (prokineticin) 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; AF168790; AAD45816.1; -; mRNA.
DR   PDB; 2KRA; NMR; -; A=20-96.
DR   PDBsum; 2KRA; -.
DR   AlphaFoldDB; Q9PW66; -.
DR   BMRB; Q9PW66; -.
DR   SMR; Q9PW66; -.
DR   EvolutionaryTrace; Q9PW66; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR009523; Prokineticin.
DR   InterPro; IPR023569; Prokineticin_domain.
DR   PANTHER; PTHR18821; PTHR18821; 1.
DR   Pfam; PF06607; Prokineticin; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Disulfide bond;
KW   G-protein coupled receptor impairing toxin; Secreted; Signal; Toxin.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000269|PubMed:10422759"
FT   CHAIN           20..96
FT                   /note="Prokineticin Bv8"
FT                   /evidence="ECO:0000303|PubMed:10422759"
FT                   /id="PRO_0000025812"
FT   REGION          20..24
FT                   /note="May be important for binding to prokineticin
FT                   receptor 2"
FT                   /evidence="ECO:0000305|PubMed:20677202"
FT   DISULFID        26..38
FT                   /evidence="ECO:0000269|PubMed:20677202"
FT   DISULFID        32..50
FT                   /evidence="ECO:0000269|PubMed:20677202"
FT   DISULFID        37..78
FT                   /evidence="ECO:0000269|PubMed:20677202"
FT   DISULFID        60..86
FT                   /evidence="ECO:0000269|PubMed:20677202"
FT   DISULFID        80..95
FT                   /evidence="ECO:0000269|PubMed:20677202"
FT   MUTAGEN         20..24
FT                   /note="Missing: Does not activate prokineticin receptor 2."
FT                   /evidence="ECO:0000269|PubMed:20677202"
FT   HELIX           29..31
FT                   /evidence="ECO:0007829|PDB:2KRA"
FT   STRAND          49..52
FT                   /evidence="ECO:0007829|PDB:2KRA"
FT   STRAND          66..68
FT                   /evidence="ECO:0007829|PDB:2KRA"
FT   STRAND          86..88
FT                   /evidence="ECO:0007829|PDB:2KRA"
FT   STRAND          90..95
FT                   /evidence="ECO:0007829|PDB:2KRA"
SQ   SEQUENCE   96 AA;  10102 MW;  A12490A7437609B4 CRC64;
     MKCFAQIVVL LLVIAFSHGA VITGACDKDV QCGSGTCCAA SAWSRNIRFC IPLGNSGEDC
     HPASHKVPYD GKRLSSLCPC KSGLTCSKSG EKFKCS