PCE_TACTR
ID PCE_TACTR Reviewed; 375 AA.
AC P21902;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Proclotting enzyme;
DE EC=3.4.21.86 {ECO:0000269|PubMed:2266134, ECO:0000269|PubMed:977558, ECO:0000305|PubMed:7822280, ECO:0000305|PubMed:7822328, ECO:0000305|PubMed:8798603};
DE Contains:
DE RecName: Full=Proclotting enzyme light chain {ECO:0000303|PubMed:2266134};
DE Contains:
DE RecName: Full=Proclotting enzyme heavy chain {ECO:0000303|PubMed:2266134};
DE Flags: Precursor;
OS Tachypleus tridentatus (Japanese horseshoe crab).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Merostomata;
OC Xiphosura; Limulidae; Tachypleus.
OX NCBI_TaxID=6853;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC
RP ACTIVITY, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DOMAIN,
RP PROTEOLYTIC CLEAVAGE, DISULFIDE BONDS, GLYCOSYLATION AT ASN-122; ASN-235
RP AND ASN-304, AND PYROGLUTAMATE FORMATION AT GLN-30.
RC TISSUE=Hemocyte;
RX PubMed=2266134; DOI=10.1016/s0021-9258(18)45722-5;
RA Muta T., Hashimoto R., Miyata T., Nishimura H., Toh Y., Iwanaga S.;
RT "Proclotting enzyme from horseshoe crab hemocytes. cDNA cloning, disulfide
RT locations, and subcellular localization.";
RL J. Biol. Chem. 265:22426-22433(1990).
RN [2]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=977558; DOI=10.1093/oxfordjournals.jbchem.a131323;
RA Nakamura S., Takagi T., Iwanaga S., Niwa M., Takahashi K.;
RT "A clottable protein (coagulogen) of horseshoe crab hemocytes. Structural
RT change of its polypeptide chain during gel formation.";
RL J. Biochem. 80:649-652(1976).
RN [3]
RP CATALYTIC ACTIVITY, SUBUNIT, PROTEOLYTIC CLEAVAGE, DISULFIDE BOND, AND
RP GLYCOSYLATION.
RX PubMed=4030738; DOI=10.1093/oxfordjournals.jbchem.a135213;
RA Nakamura T., Morita T., Iwanaga S.;
RT "Intracellular proclotting enzyme in limulus (Tachypleus tridentatus)
RT hemocytes: its purification and properties.";
RL J. Biochem. 97:1561-1574(1985).
RN [4]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=7822280; DOI=10.1074/jbc.270.2.558;
RA Miura Y., Kawabata S., Wakamiya Y., Nakamura T., Iwanaga S.;
RT "A limulus intracellular coagulation inhibitor type 2. Purification,
RT characterization, cDNA cloning, and tissue localization.";
RL J. Biol. Chem. 270:558-565(1995).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=7822328; DOI=10.1074/jbc.270.2.892;
RA Muta T., Seki N., Takaki Y., Hashimoto R., Oda T., Iwanaga A., Tokunaga F.,
RA Iwanaga S.;
RT "Purified horseshoe crab factor G. Reconstitution and characterization of
RT the (1-->3)-beta-D-glucan-sensitive serine protease cascade.";
RL J. Biol. Chem. 270:892-897(1995).
RN [6]
RP CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=8798603; DOI=10.1074/jbc.271.39.23768;
RA Agarwala K.L., Kawabata S., Miura Y., Kuroki Y., Iwanaga S.;
RT "Limulus intracellular coagulation inhibitor type 3. Purification,
RT characterization, cDNA cloning, and tissue localization.";
RL J. Biol. Chem. 271:23768-23774(1996).
CC -!- FUNCTION: This enzyme is closely associated with an endotoxin-sensitive
CC hemolymph coagulation system in limulus (PubMed:2266134). Its active
CC form catalyzes the conversion of coagulogen to insoluble coagulin gel
CC (PubMed:977558, PubMed:7822328). {ECO:0000269|PubMed:2266134,
CC ECO:0000269|PubMed:7822328, ECO:0000269|PubMed:977558}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Selective cleavage of 18-Arg-|- and 47-Arg-|- bonds in
CC coagulogen to form coagulin and fragments.; EC=3.4.21.86;
CC Evidence={ECO:0000269|PubMed:977558, ECO:0000305|PubMed:4030738,
CC ECO:0000305|PubMed:7822280, ECO:0000305|PubMed:7822328,
CC ECO:0000305|PubMed:8798603};
CC -!- ACTIVITY REGULATION: Inhibited by intracellular coagulation inhibitor
CC 2/LICI-2 and to a lesser extent by intracellular coagulation inhibitor
CC 3/LICI-3. {ECO:0000269|PubMed:7822280, ECO:0000269|PubMed:8798603}.
CC -!- SUBUNIT: In the active form, heterodimer of a light chain and a heavy
CC chain; disulfide-linked (PubMed:2266134, PubMed:7822280). Forms a
CC covalent heterodimer with intracellular coagulation inhibitor 2/LICI-2
CC (PubMed:7822280). {ECO:0000269|PubMed:2266134,
CC ECO:0000269|PubMed:7822280}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000269|PubMed:2266134}. Secreted {ECO:0000269|PubMed:2266134}.
CC Note=Secreted in hemolymph probably upon bacterial lipopolysaccharide
CC (LPS) stimulation. {ECO:0000303|PubMed:2266134}.
CC -!- TISSUE SPECIFICITY: Expressed in hemocytes (at protein level).
CC {ECO:0000269|PubMed:2266134, ECO:0000269|PubMed:7822280}.
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. {ECO:0000255|PROSITE-ProRule:PRU01236,
CC ECO:0000269|PubMed:2266134}.
CC -!- PTM: Proteolytically cleaved into its mature active form by serine
CC protease factor B (PubMed:2266134, PubMed:4030738). Cleavage produces a
CC 25 kDa light chain containing the CLIP domain and a catalytic 31 kDa
CC heavy chain which remain covalently associated through an interchain
CC disulfide bond (PubMed:2266134, PubMed:4030738). Proteolytically
CC cleaved by clotting factor G subunit beta (PubMed:7822328).
CC {ECO:0000269|PubMed:2266134, ECO:0000269|PubMed:4030738,
CC ECO:0000269|PubMed:7822328}.
CC -!- PTM: Contains six O-linked carbohydrate chains in the N-terminal light
CC chain. {ECO:0000269|PubMed:2266134, ECO:0000269|PubMed:4030738}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. CLIP subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU01236}.
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DR EMBL; M58366; AAA30094.1; -; mRNA.
DR PIR; A23689; A23689.
DR AlphaFoldDB; P21902; -.
DR SMR; P21902; -.
DR MEROPS; S01.221; -.
DR iPTMnet; P21902; -.
DR KEGG; ag:AAA30094; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008236; F:serine-type peptidase activity; IDA:UniProtKB.
DR GO; GO:0042381; P:hemolymph coagulation; IDA:UniProtKB.
DR GO; GO:0016485; P:protein processing; IDA:UniProtKB.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 1.
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; 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 Calcium; Cleavage on pair of basic residues; Cytoplasmic vesicle;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hemolymph clotting; Hydrolase; Metal-binding; Protease;
KW Pyrrolidone carboxylic acid; Secreted; Serine protease; Signal; Zymogen.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..27
FT /evidence="ECO:0000305|PubMed:2266134"
FT /id="PRO_0000028427"
FT CHAIN 30..127
FT /note="Proclotting enzyme light chain"
FT /evidence="ECO:0000305|PubMed:2266134"
FT /id="PRO_0000028428"
FT CHAIN 128..375
FT /note="Proclotting enzyme heavy chain"
FT /evidence="ECO:0000305|PubMed:2266134"
FT /id="PRO_0000028429"
FT DOMAIN 39..84
FT /note="Clip"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DOMAIN 128..375
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 90..113
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 172
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 228
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 326
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT BINDING 194
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O97366"
FT BINDING 196
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O97366"
FT BINDING 199
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O97366"
FT BINDING 202
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O97366"
FT SITE 127..128
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:2266134"
FT MOD_RES 30
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:2266134"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:2266134"
FT CARBOHYD 235
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:2266134"
FT CARBOHYD 304
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:2266134"
FT DISULFID 40..83
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236,
FT ECO:0000269|PubMed:2266134"
FT DISULFID 50..73
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236,
FT ECO:0000269|PubMed:2266134"
FT DISULFID 56..84
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236,
FT ECO:0000269|PubMed:2266134"
FT DISULFID 118..248
FT /note="Interchain (between light and heavy chains)"
FT /evidence="ECO:0000269|PubMed:2266134,
FT ECO:0000269|PubMed:4030738"
FT DISULFID 157..173
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000269|PubMed:2266134"
FT DISULFID 295..311
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000269|PubMed:2266134"
FT DISULFID 322..351
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000269|PubMed:2266134"
SQ SEQUENCE 375 AA; 41592 MW; 94209E514DFCF8FB CRC64;
MLVNNVFSLL CFPLLMSVVR CSTLSRQRRQ FVFPDEEELC SNRFTEEGTC KNVLDCRILL
QKNDYNLLKE SICGFEGITP KVCCPKSSHV ISSTQAPPET TTTERPPKQI PPNLPEVCGI
HNTTTTRIIG GREAPIGAWP WMTAVYIKQG GIRSVQCGGA LVTNRHVITA SHCVVNSAGT
DVMPADVFSV RLGEHNLYST DDDSNPIDFA VTSVKHHEHF VLATYLNDIA ILTLNDTVTF
TDRIRPICLP YRKLRYDDLA MRKPFITGWG TTAFNGPSSA VLREVQLPIW EHEACRQAYE
KDLNITNVYM CAGFADGGKD ACQGDSGGPM MLPVKTGEFY LIGIVSFGKK CALPGFPGVY
TKVTEFLDWI AEHMV
