CFC_TACTR
ID CFC_TACTR Reviewed; 1019 AA.
AC P28175;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Clotting factor C;
DE Short=FC;
DE EC=3.4.21.84 {ECO:0000269|PubMed:3512266, ECO:0000269|PubMed:7822280, ECO:0000269|PubMed:8276848, ECO:0000269|PubMed:8798603};
DE AltName: Full=Limulus factor C {ECO:0000303|PubMed:2007602};
DE Contains:
DE RecName: Full=Clotting factor C heavy chain {ECO:0000303|PubMed:3512266};
DE Contains:
DE RecName: Full=Clotting factor C light chain {ECO:0000303|PubMed:3512266};
DE Contains:
DE RecName: Full=Clotting factor C chain A {ECO:0000303|PubMed:3308457};
DE Contains:
DE RecName: Full=Clotting factor C chain B {ECO:0000303|PubMed:3308457};
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] (ISOFORMS LONG AND SHORT), PARTIAL PROTEIN
RP SEQUENCE, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=2007602; DOI=10.1016/s0021-9258(18)38153-5;
RA Muta T., Miyata T., Misumi Y., Tokunaga F., Nakamura T., Toh Y.,
RA Ikehara Y., Iwanaga S.;
RT "Limulus factor C. An endotoxin-sensitive serine protease zymogen with a
RT mosaic structure of complement-like, epidermal growth factor-like, and
RT lectin-like domains.";
RL J. Biol. Chem. 266:6554-6561(1991).
RN [2]
RP PARTIAL PROTEIN SEQUENCE (ISOFORM LONG), SUBUNIT, PROTEOLYTIC CLEAVAGE, AND
RP GLYCOSYLATION AT ASN-767.
RX PubMed=3308457; DOI=10.1111/j.1432-1033.1987.tb13352.x;
RA Tokunaga F., Miyata T., Nakamura T., Morita T., Kuma K., Miyata T.,
RA Iwanaga S.;
RT "Lipopolysaccharide-sensitive serine-protease zymogen (factor C) of
RT horseshoe crab hemocytes. Identification and alignment of proteolytic
RT fragments produced during the activation show that it is a novel type of
RT serine protease.";
RL Eur. J. Biochem. 167:405-416(1987).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBUNIT, TISSUE
RP SPECIFICITY, GLYCOSYLATION, PROTEOLYTIC CLEAVAGE, AND DISULFIDE BOND.
RX PubMed=3512266; DOI=10.1111/j.1432-1033.1986.tb09427.x;
RA Nakamura T., Morita T., Iwanaga S.;
RT "Lipopolysaccharide-sensitive serine-protease zymogen (factor C) found in
RT Limulus hemocytes. Isolation and characterization.";
RL Eur. J. Biochem. 154:511-521(1986).
RN [4]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=8276848; DOI=10.1016/s0021-9258(17)42383-0;
RA Miura Y., Kawabata S., Iwanaga S.;
RT "A Limulus intracellular coagulation inhibitor with characteristics of the
RT serpin superfamily. Purification, characterization, and cDNA cloning.";
RL J. Biol. Chem. 269:542-547(1994).
RN [5]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND SUBUNIT.
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 [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 which may play important roles in both
CC hemostasis and host defense mechanisms (PubMed:3512266). Its active
CC form catalyzes the activation of clotting factor B (PubMed:3512266).
CC {ECO:0000269|PubMed:3512266}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Selective cleavage of 103-Arg-|-Ser-104 and 124-Ile-|-Ile-125
CC bonds in Limulus clotting factor B to form activated factor B.
CC Cleavage of -Pro-Arg-|-Xaa- bonds in synthetic substrates.;
CC EC=3.4.21.84; Evidence={ECO:0000269|PubMed:3512266,
CC ECO:0000269|PubMed:7822280, ECO:0000269|PubMed:8276848,
CC ECO:0000269|PubMed:8798603};
CC -!- ACTIVITY REGULATION: Activated by Gram-negative bacterial
CC lipopolysaccharides (PubMed:3512266). Inhibited by intracellular
CC coagulation inhibitor 1/LICI-1 and to a lesser extent by intracellular
CC coagulation inhibitors 2/LICI-2 and 3/LICI-3 (PubMed:8276848,
CC PubMed:7822280, PubMed:8798603). Inhibited by the small molecule
CC diisopropyl fluorophosphate (DFP) (PubMed:3512266).
CC {ECO:0000269|PubMed:3512266, ECO:0000269|PubMed:7822280,
CC ECO:0000269|PubMed:8276848, ECO:0000269|PubMed:8798603}.
CC -!- SUBUNIT: Heterodimer of a light chain and a heavy chain linked by a
CC disulfide bond (PubMed:3308457, PubMed:3512266). Forms a covalent
CC heterodimer with intracellular coagulation inhibitor 1/LICI-1
CC (PubMed:8276848). Forms a covalent heterodimer with intracellular
CC coagulation inhibitor 2/LICI-2 (PubMed:7822280).
CC {ECO:0000269|PubMed:3308457, ECO:0000269|PubMed:3512266,
CC ECO:0000269|PubMed:7822280, ECO:0000269|PubMed:8276848}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. Note=Secreted in
CC hemolymph (PubMed:2007602). Localizes in large granules of hemocytes
CC (PubMed:2007602). {ECO:0000269|PubMed:2007602}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long {ECO:0000303|PubMed:2007602};
CC IsoId=P28175-1; Sequence=Displayed;
CC Name=Short {ECO:0000303|PubMed:2007602};
CC IsoId=P28175-2; Sequence=VSP_005413, VSP_005414;
CC -!- TISSUE SPECIFICITY: Expressed in hemocytes (at protein level).
CC {ECO:0000269|PubMed:2007602, ECO:0000269|PubMed:3512266}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:3512266}.
CC -!- PTM: Lipopolysaccharide (LPS) activates clotting factor C by inducing
CC the proteolytic cleavage of the clotting factor C light chain into
CC clotting factor C chains A and B (PubMed:3308457, PubMed:3512266).
CC Clotting factor C chains heavy, A and B remain associated via
CC interchain disulfide bonds (PubMed:3512266).
CC {ECO:0000269|PubMed:3308457, ECO:0000269|PubMed:3512266}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; D90271; BAA14315.1; -; mRNA.
DR EMBL; D90272; BAA14316.1; -; mRNA.
DR PIR; A38738; A38738.
DR AlphaFoldDB; P28175; -.
DR SMR; P28175; -.
DR MEROPS; S01.219; -.
DR iPTMnet; P28175; -.
DR KEGG; ag:BAA14315; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0042381; P:hemolymph coagulation; IDA:UniProtKB.
DR GO; GO:0016485; P:protein processing; IDA:UniProtKB.
DR CDD; cd00033; CCP; 5.
DR CDD; cd00055; EGF_Lam; 1.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.170.130.20; -; 1.
DR Gene3D; 2.40.10.10; -; 1.
DR Gene3D; 3.10.100.10; -; 1.
DR InterPro; IPR001304; C-type_lectin-like.
DR InterPro; IPR016186; C-type_lectin-like/link_sf.
DR InterPro; IPR016187; CTDL_fold.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR004043; LCCL.
DR InterPro; IPR036609; LCCL_sf.
DR InterPro; IPR002049; LE_dom.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR Pfam; PF03815; LCCL; 1.
DR Pfam; PF00059; Lectin_C; 1.
DR Pfam; PF00084; Sushi; 5.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00032; CCP; 5.
DR SMART; SM00034; CLECT; 1.
DR SMART; SM00603; LCCL; 1.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF56436; SSF56436; 1.
DR SUPFAM; SSF57535; SSF57535; 5.
DR SUPFAM; SSF69848; SSF69848; 1.
DR PROSITE; PS50041; C_TYPE_LECTIN_2; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS50820; LCCL; 1.
DR PROSITE; PS50923; SUSHI; 5.
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 Alternative splicing; Cell adhesion; Direct protein sequencing;
KW Disulfide bond; EGF-like domain; Glycoprotein; Hemolymph clotting;
KW Hydrolase; Lectin; Protease; Repeat; Secreted; Serine protease; Signal;
KW Sushi.
FT SIGNAL 1..25
FT CHAIN 26..1019
FT /note="Clotting factor C"
FT /id="PRO_0000028435"
FT CHAIN 26..690
FT /note="Clotting factor C heavy chain"
FT /id="PRO_0000028436"
FT CHAIN 691..1019
FT /note="Clotting factor C light chain"
FT /id="PRO_0000028437"
FT CHAIN 691..762
FT /note="Clotting factor C chain A"
FT /evidence="ECO:0000269|PubMed:3308457"
FT /id="PRO_0000028438"
FT CHAIN 763..1019
FT /note="Clotting factor C chain B"
FT /evidence="ECO:0000269|PubMed:3308457"
FT /id="PRO_0000028439"
FT DOMAIN 102..137
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 140..197
FT /note="Sushi 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 198..256
FT /note="Sushi 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 258..323
FT /note="Sushi 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 325..421
FT /note="LCCL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00123"
FT DOMAIN 436..568
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DOMAIN 574..636
FT /note="Sushi 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 689..750
FT /note="Sushi 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 763..1019
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 809
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 865
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 966
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT BINDING 960
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT CARBOHYD 523
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 534
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 624
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 740
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 767
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:3308457"
FT CARBOHYD 912
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 110..118
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 112..125
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 127..136
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 142..182
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 168..195
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 199..241
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 227..254
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 260..308
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 294..321
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 331..350
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00123"
FT DISULFID 354..374
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00123"
FT DISULFID 464..564
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 538..556
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 576..621
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 607..634
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 720..748
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 794..810
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 932..951
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 962..996
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT VAR_SEQ 492..498
FT /note="LTTTWIG -> TDNVTAT (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:2007602"
FT /id="VSP_005413"
FT VAR_SEQ 499..1019
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:2007602"
FT /id="VSP_005414"
SQ SEQUENCE 1019 AA; 112346 MW; 5BC2864C6715289B CRC64;
MVLASFLVSG LVLGILAQQM RPVQSRGVDL GLCDETRFEC KCGDPGYVFN VPMKQCTYFY
RWRPYCKPCD DLEAKDICPK YKRCQECKAG LDSCVTCPPN KYGTWCSGEC QCKNGGICDQ
RTGACTCRDR YEGAHCEILK GCPLLPSDSQ VQEVRNPPDN PQTIDYSCSP GFKLKGVARI
SCLPNGQWSS FPPKCIRECA KVSSPEHGKV NAPSGNMIEG ATLRFSCDSP YYLIGQETLT
CQGNGQWSGQ IPQCKKLVFC PDLDPVNHAE HQVKIGVEQK YGQFPQGTEV TYTCSGNYFL
MGFNTLKCNP DGSWSGSQPS CVKVADREVD CDSKAVDFLD DVGEPVRIHC PAGCSLTAGT
VWGTAIYHEL SSVCRAAIHA GKLPNSGGAV HVVNNGPYSD FLGSDLNGIK SEELKSLARS
FRFDYVSSST AGRSGCPDGW FEVEENCVYV TSKQRAWERA QGVCTNMAAR LAVLDKDLIP
SSLTETLRGK GLTTTWIGLH RLDAEKPFVW ELMDRSNVVL NDNLTFWASG EPGNETNCVY
LDIRDQLQPV WKTKSCFQPS SFACMMDLSD RNKAKCDDPG PLENGHATLH GQSIDGFYAG
SSIRYSCEVL HYLSGTETVT CTTNGTWSAP KPRCIKVITC QNPPVPSYGS VEIKPPSRTN
SISRVGSPFL RLPRLPLPLA RAAKPPPKPR SSQPSTVDLA SKVKLPEGHY RVGSRAIYTC
ESRYYELLGS QGRRCDSNGN WSGRPASCIP VCGRSDSPRS PFIWNGNSTE IGQWPWQAGI
SRWLADHNMW FLQCGGSLLN EKWIVTAAHC VTYSATAEII DPSQFKIYLG KYYRDDSRDD
DYVQVREALE IHVNPNYDPG NLNFDIALIQ LKTPVTLTTR VQPICLPTDI TTREHLKEGT
LAVVTGWGLN ENNTYSEMIQ QAVLPVVAAS TCEEGYKEAD LPLTVTENMF CAGYKKGRYD
ACSGDSGGPL VFADDSRTER RWVLEGIVSW GSPSGCGKAN QYGGFTKVNV FLSWIRQFI
