PPAF1_HOLDI
ID PPAF1_HOLDI Reviewed; 365 AA.
AC O97366;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Phenoloxidase-activating factor 1 {ECO:0000305};
DE EC=3.4.21.- {ECO:0000269|PubMed:12185078, ECO:0000269|PubMed:16362048, ECO:0000269|PubMed:17287215, ECO:0000269|PubMed:9652393, ECO:0000305|PubMed:9839951};
DE AltName: Full=Prophenoloxidase-activating factor I {ECO:0000303|PubMed:9652393};
DE AltName: Full=Serine protease PPAF-1 {ECO:0000305};
DE Contains:
DE RecName: Full=Phenoloxidase-activating factor 1 light chain {ECO:0000305};
DE Contains:
DE RecName: Full=Phenoloxidase-activating factor 1 heavy chain {ECO:0000305};
DE Flags: Precursor;
GN Name=PPAF1 {ECO:0000305|PubMed:9839951};
GN Synonyms=PPAF-I {ECO:0000303|PubMed:9839951};
OS Holotrichia diomphalia (Korean black chafer).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Coleoptera; Polyphaga; Scarabaeiformia;
OC Scarabaeidae; Melolonthinae; Holotrichia.
OX NCBI_TaxID=33394 {ECO:0000312|EMBL:BAA34642.1};
RN [1] {ECO:0000312|EMBL:BAA34642.1}
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 110-129; 171-190; 274-283
RP AND 287-300, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR
RP LOCATION, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=9839951; DOI=10.1046/j.1432-1327.1998.2570615.x;
RA Lee S.Y., Cho M.Y., Hyun J.H., Lee K.M., Homma K.I., Natori S.,
RA Kawabata S.I., Iwanaga S., Lee B.L.;
RT "Molecular cloning of cDNA for pro-phenol-oxidase-activating factor I, a
RT serine protease is induced by lipopolysaccharide or 1,3-beta-glucan in
RT coleopteran insect, Holotrichia diomphalia larvae.";
RL Eur. J. Biochem. 257:615-621(1998).
RN [2] {ECO:0000305}
RP PROTEIN SEQUENCE OF 88-91, FUNCTION, CATALYTIC ACTIVITY, PROTEOLYTIC
RP CLEAVAGE, AND DOMAIN.
RX PubMed=16362048; DOI=10.1038/sj.emboj.7600891;
RA Piao S., Song Y.L., Kim J.H., Park S.Y., Park J.W., Lee B.L., Oh B.H.,
RA Ha N.C.;
RT "Crystal structure of a clip-domain serine protease and functional roles of
RT the clip domains.";
RL EMBO J. 24:4404-4414(2005).
RN [3] {ECO:0000305}
RP PROTEIN SEQUENCE OF 110-128, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, SUBCELLULAR LOCATION, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=9652393; DOI=10.1046/j.1432-1327.1998.2540050.x;
RA Lee S.Y., Kwon T.H., Hyun J.H., Choi J.S., Kawabata S.I., Iwanaga S.,
RA Lee B.L.;
RT "In vitro activation of pro-phenol-oxidase by two kinds of pro-phenol-
RT oxidase-activating factors isolated from hemolymph of coleopteran,
RT Holotrichia diomphalia larvae.";
RL Eur. J. Biochem. 254:50-57(1998).
RN [4] {ECO:0000305}
RP PROTEIN SEQUENCE OF 110-117, ACTIVITY REGULATION, DEVELOPMENTAL STAGE, AND
RP PROTEOLYTIC CLEAVAGE.
RX PubMed=11012672; DOI=10.1046/j.1432-1327.2000.01695.x;
RA Kwon T.H., Kim M.S., Choi H.W., Joo C.H., Cho M.Y., Lee B.L.;
RT "A masquerade-like serine proteinase homologue is necessary for
RT phenoloxidase activity in the coleopteran insect, Holotrichia diomphalia
RT larvae.";
RL Eur. J. Biochem. 267:6188-6196(2000).
RN [5] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12185078; DOI=10.1074/jbc.m205508200;
RA Kim M.S., Baek M.J., Lee M.H., Park J.W., Lee S.Y., Soderhall K., Lee B.L.;
RT "A new easter-type serine protease cleaves a masquerade-like protein during
RT prophenoloxidase activation in Holotrichia diomphalia larvae.";
RL J. Biol. Chem. 277:39999-40004(2002).
RN [6] {ECO:0007744|PDB:2OLG}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 88-365 IN COMPLEX WITH CALCIUM,
RP FUNCTION, CATALYTIC ACTIVITY, PROTEOLYTIC CLEAVAGE, GLYCOSYLATION AT
RP ASN-131, AND DISULFIDE BONDS.
RX PubMed=17287215; DOI=10.1074/jbc.m611556200;
RA Piao S., Kim S., Kim J.H., Park J.W., Lee B.L., Ha N.C.;
RT "Crystal structure of the serine protease domain of prophenoloxidase
RT activating factor-I.";
RL J. Biol. Chem. 282:10783-10791(2007).
CC -!- FUNCTION: Serine endopeptidase which, by cleaving prophenoloxidase PPO1
CC and PPO2, is required for the activation of the prophenoloxidase
CC cascade probably following the recognition of pathogen-derived
CC products. {ECO:0000269|PubMed:12185078, ECO:0000269|PubMed:16362048,
CC ECO:0000269|PubMed:17287215, ECO:0000269|PubMed:9652393,
CC ECO:0000269|PubMed:9839951}.
CC -!- ACTIVITY REGULATION: Protein stability and endopeptidase activity are
CC calcium dependent (PubMed:17287215). First cleavage on prophenoloxidase
CC PPO1 and PPO2 is not dependent on calcium; however, cleavage of PPO1
CC and PPO2 to their active forms is dependent on calcium and on the
CC presence of PPAF2 and PPAF3 (PubMed:12185078). Cleavage of PPAF2 is
CC inhibited by calcium (PubMed:11012672, PubMed:12185078). Inhibited by
CC ethylenediaminetetraacetic acid (EDTA), p-nitrophenyl-p'-guanido-
CC benzoate, diisopropylphosphorofluoridate (iPr2PF) and p-
CC (Amidinophenyl)methanesulfonyl fluoride (p-APMSF) (PubMed:9652393,
CC PubMed:17287215). {ECO:0000269|PubMed:11012672,
CC ECO:0000269|PubMed:12185078, ECO:0000269|PubMed:17287215,
CC ECO:0000269|PubMed:9652393}.
CC -!- SUBUNIT: In the active form, heterodimer of a light chain and a heavy
CC chain; disulfide-linked (Probable). {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12185078,
CC ECO:0000269|PubMed:9652393, ECO:0000269|PubMed:9839951}. Note=Secreted
CC in the hemolymph. {ECO:0000269|PubMed:12185078,
CC ECO:0000269|PubMed:9652393, ECO:0000269|PubMed:9839951}.
CC -!- DEVELOPMENTAL STAGE: Expressed in larva (at protein level).
CC {ECO:0000269|PubMed:11012672}.
CC -!- DOMAIN: The clip domain consists of 35-55 residues which are 'knitted'
CC together usually by 3 conserved disulfide bonds forming a clip-like
CC compact structure (By similarity). The clip domain is necessary for
CC regulating the zymogen activation (PubMed:16362048).
CC {ECO:0000255|PROSITE-ProRule:PRU01236, ECO:0000269|PubMed:16362048}.
CC -!- PTM: Cleaved following the recognition of pathogen-derived products,
CC probably by a lysyl endopeptidase. {ECO:0000269|PubMed:11012672,
CC ECO:0000269|PubMed:16362048, ECO:0000269|PubMed:17287215,
CC ECO:0000269|PubMed:9652393, ECO:0000269|PubMed:9839951}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. CLIP subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU01236}.
CC -!- CAUTION: It is not clear if the light chain is degraded after cleavage.
CC {ECO:0000305}.
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DR EMBL; AB013088; BAA34642.1; -; mRNA.
DR PDB; 2OLG; X-ray; 1.70 A; A=88-365.
DR PDBsum; 2OLG; -.
DR AlphaFoldDB; O97366; -.
DR SMR; O97366; -.
DR MEROPS; S01.204; -.
DR iPTMnet; O97366; -.
DR EvolutionaryTrace; O97366; -.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 3.30.1640.30; -; 1.
DR InterPro; IPR022700; CLIP.
DR InterPro; IPR038565; CLIP_sf.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR Pfam; PF12032; CLIP; 1.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00680; CLIP; 1.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR PROSITE; PS51888; CLIP; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Hydrolase; Immunity; Innate immunity; Metal-binding;
KW Protease; Secreted; Serine protease; Signal; Zymogen.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..109
FT /note="Phenoloxidase-activating factor 1 light chain"
FT /evidence="ECO:0000305|PubMed:11012672,
FT ECO:0000305|PubMed:16362048, ECO:0000305|PubMed:17287215,
FT ECO:0000305|PubMed:9652393, ECO:0000305|PubMed:9839951"
FT /id="PRO_5004160790"
FT CHAIN 110..365
FT /note="Phenoloxidase-activating factor 1 heavy chain"
FT /evidence="ECO:0000305|PubMed:11012672,
FT ECO:0000305|PubMed:16362048, ECO:0000305|PubMed:17287215,
FT ECO:0000305|PubMed:9652393, ECO:0000305|PubMed:9839951"
FT /id="PRO_0000443316"
FT DOMAIN 24..74
FT /note="Clip"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DOMAIN 110..364
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 155
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 220
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 315
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT BINDING 175
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:17287215,
FT ECO:0007744|PDB:2OLG"
FT BINDING 177
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:17287215,
FT ECO:0007744|PDB:2OLG"
FT BINDING 180
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:17287215,
FT ECO:0007744|PDB:2OLG"
FT BINDING 183
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:17287215,
FT ECO:0007744|PDB:2OLG"
FT SITE 109..110
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:11012672,
FT ECO:0000269|PubMed:9652393, ECO:0000269|PubMed:9839951"
FT CARBOHYD 131
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17287215,
FT ECO:0007744|PDB:2OLG"
FT DISULFID 25..73
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 35..64
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 41..74
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 101..240
FT /note="Interchain (between light and heavy chains)"
FT /evidence="ECO:0000269|PubMed:17287215,
FT ECO:0007744|PDB:2OLG"
FT DISULFID 140..156
FT /evidence="ECO:0000269|PubMed:17287215,
FT ECO:0007744|PDB:2OLG"
FT DISULFID 184..191
FT /evidence="ECO:0000269|PubMed:17287215,
FT ECO:0007744|PDB:2OLG"
FT DISULFID 284..301
FT /evidence="ECO:0000269|PubMed:17287215,
FT ECO:0007744|PDB:2OLG"
FT DISULFID 311..340
FT /evidence="ECO:0000269|PubMed:17287215,
FT ECO:0007744|PDB:2OLG"
FT HELIX 94..96
FT /evidence="ECO:0007829|PDB:2OLG"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:2OLG"
FT STRAND 124..130
FT /evidence="ECO:0007829|PDB:2OLG"
FT STRAND 136..144
FT /evidence="ECO:0007829|PDB:2OLG"
FT STRAND 146..152
FT /evidence="ECO:0007829|PDB:2OLG"
FT HELIX 154..156
FT /evidence="ECO:0007829|PDB:2OLG"
FT HELIX 160..164
FT /evidence="ECO:0007829|PDB:2OLG"
FT STRAND 167..174
FT /evidence="ECO:0007829|PDB:2OLG"
FT TURN 186..189
FT /evidence="ECO:0007829|PDB:2OLG"
FT STRAND 197..199
FT /evidence="ECO:0007829|PDB:2OLG"
FT STRAND 201..206
FT /evidence="ECO:0007829|PDB:2OLG"
FT STRAND 222..228
FT /evidence="ECO:0007829|PDB:2OLG"
FT STRAND 253..259
FT /evidence="ECO:0007829|PDB:2OLG"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:2OLG"
FT STRAND 272..278
FT /evidence="ECO:0007829|PDB:2OLG"
FT HELIX 281..288
FT /evidence="ECO:0007829|PDB:2OLG"
FT STRAND 299..302
FT /evidence="ECO:0007829|PDB:2OLG"
FT STRAND 318..323
FT /evidence="ECO:0007829|PDB:2OLG"
FT HELIX 324..326
FT /evidence="ECO:0007829|PDB:2OLG"
FT STRAND 327..336
FT /evidence="ECO:0007829|PDB:2OLG"
FT STRAND 347..351
FT /evidence="ECO:0007829|PDB:2OLG"
FT HELIX 352..355
FT /evidence="ECO:0007829|PDB:2OLG"
FT HELIX 356..360
FT /evidence="ECO:0007829|PDB:2OLG"
SQ SEQUENCE 365 AA; 40195 MW; EC69F6093923F4C5 CRC64;
MKQVHFFILW FFVLNLYSIK AQAGCRTPNG ENARCVPINN CKILYDSVLT SDPEVIRFLR
ASQCGYNGQP LVCCGSSASY QPPPTSASIR NRRPELLPND CGYQVEADKI LNGDDTVPEE
FPWTAMIGYK NSSNFEQFAC GGSLINNRYI VTAAHCVAGR VLRVVGALNK VRLGEWNTAT
DPDCYGAVRV CVPDKPIDLG IEETIQHPDY VDGSKDRYHD IALIRLNRQV EFTNYIRPVC
LPQPNEEVQV GQRLTVVGWG RTETGQYSTI KQKLAVPVVH AEQCAKTFGA AGVRVRSSQL
CAGGEKAKDS CGGDSGGPLL AERANQQFFL EGLVSFGATC GTEGWPGIYT KVGKYRDWIE
GNIRP
