VCO3_CROAD
ID VCO3_CROAD Reviewed; 1652 AA.
AC J3S836;
DT 18-SEP-2013, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2012, sequence version 1.
DT 03-AUG-2022, entry version 28.
DE RecName: Full=Venom factor;
DE Short=VF;
DE AltName: Full=CVF-like;
DE AltName: Full=Complement C3 homolog;
DE Contains:
DE RecName: Full=VF alpha chain;
DE Contains:
DE RecName: Full=VF gamma chain;
DE Contains:
DE RecName: Full=VF beta chain;
DE Flags: Precursor;
OS Crotalus adamanteus (Eastern diamondback rattlesnake).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Crotalus.
OX NCBI_TaxID=8729;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=23025625; DOI=10.1186/1471-2164-13-312;
RA Rokyta D.R., Lemmon A.R., Margres M.J., Aronow K.;
RT "The venom-gland transcriptome of the eastern diamondback rattlesnake
RT (Crotalus adamanteus).";
RL BMC Genomics 13:312-312(2012).
CC -!- FUNCTION: Complement-activating protein in venom. It is a structural
CC and functional analog of complement component C3b, the activated form
CC of C3. It binds factor B (CFB), which is subsequently cleaved by factor
CC D (CFD) to form the bimolecular complex VF/Bb. VF/Bb is a C3/C5
CC convertase that cleaves both complement components C3 and C5.
CC Structurally, it resembles the C3b degradation product C3c, which is
CC not able to form a C3/C5 convertase. Unlike C3b/Bb, VF/Bb is a stable
CC complex and completely resistant to the actions of complement
CC regulatory factors H (CFH) and I (CFI). Therefore, VF continuously
CC activates complement resulting in the depletion of complement activity
CC (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Heterotrimer of alpha, beta and gamma chains; disulfide-
CC linked. Is active with factor B in the presence of factor D (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- PTM: First processed by the removal of 4 Arg residues by furin-type
CC protease, forming two chains, alpha and gamma/beta precursor, linked by
CC a disulfide bond. Probably, a cobrin-like protease cleaves the C3a-like
CC domain and then the C3d-like domain, generating the mature venom factor
CC (VF) (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the venom complement C3 homolog family.
CC {ECO:0000305}.
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DR EMBL; JU173742; AFJ49268.1; -; mRNA.
DR AlphaFoldDB; J3S836; -.
DR SMR; J3S836; -.
DR PRIDE; J3S836; -.
DR GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0006956; P:complement activation; IEA:InterPro.
DR GO; GO:0006954; P:inflammatory response; IEA:InterPro.
DR CDD; cd00017; ANATO; 1.
DR CDD; cd03583; NTR_complement_C3; 1.
DR Gene3D; 2.40.50.120; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR Gene3D; 2.60.40.690; -; 1.
DR InterPro; IPR009048; A-macroglobulin_rcpt-bd.
DR InterPro; IPR036595; A-macroglobulin_rcpt-bd_sf.
DR InterPro; IPR011625; A2M_N_BRD.
DR InterPro; IPR011626; Alpha-macroglobulin_TED.
DR InterPro; IPR000020; Anaphylatoxin/fibulin.
DR InterPro; IPR018081; Anaphylatoxin_comp_syst.
DR InterPro; IPR001840; Anaphylatoxn_comp_syst_dom.
DR InterPro; IPR041425; C3/4/5_MG1.
DR InterPro; IPR035711; Complement_C3-like.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR001599; Macroglobln_a2.
DR InterPro; IPR019742; MacrogloblnA2_CS.
DR InterPro; IPR002890; MG2.
DR InterPro; IPR041555; MG3.
DR InterPro; IPR040839; MG4.
DR InterPro; IPR001134; Netrin_domain.
DR InterPro; IPR018933; Netrin_module_non-TIMP.
DR InterPro; IPR035815; NTR_complement_C3.
DR InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase.
DR InterPro; IPR008993; TIMP-like_OB-fold.
DR PANTHER; PTHR11412:SF81; PTHR11412:SF81; 1.
DR Pfam; PF00207; A2M; 1.
DR Pfam; PF07703; A2M_BRD; 1.
DR Pfam; PF07677; A2M_recep; 1.
DR Pfam; PF01821; ANATO; 1.
DR Pfam; PF17790; MG1; 1.
DR Pfam; PF01835; MG2; 1.
DR Pfam; PF17791; MG3; 1.
DR Pfam; PF17789; MG4; 1.
DR Pfam; PF01759; NTR; 1.
DR Pfam; PF07678; TED_complement; 2.
DR PRINTS; PR00004; ANAPHYLATOXN.
DR SMART; SM01360; A2M; 1.
DR SMART; SM01359; A2M_N_2; 1.
DR SMART; SM01361; A2M_recep; 1.
DR SMART; SM00104; ANATO; 1.
DR SMART; SM00643; C345C; 1.
DR SUPFAM; SSF47686; SSF47686; 1.
DR SUPFAM; SSF48239; SSF48239; 1.
DR SUPFAM; SSF49410; SSF49410; 1.
DR SUPFAM; SSF50242; SSF50242; 1.
DR PROSITE; PS00477; ALPHA_2_MACROGLOBULIN; 1.
DR PROSITE; PS01177; ANAPHYLATOXIN_1; 1.
DR PROSITE; PS01178; ANAPHYLATOXIN_2; 1.
DR PROSITE; PS50189; NTR; 1.
PE 2: Evidence at transcript level;
KW Cleavage on pair of basic residues; Complement system impairing toxin;
KW Disulfide bond; Magnesium; Metal-binding; Secreted; Signal; Thioester bond;
KW Toxin.
FT SIGNAL 1..22
FT /evidence="ECO:0000250"
FT CHAIN 23..1652
FT /note="Venom factor"
FT /id="PRO_0000423448"
FT CHAIN 23..656
FT /note="VF alpha chain"
FT /id="PRO_0000423449"
FT PROPEP 657..740
FT /evidence="ECO:0000250"
FT /id="PRO_0000423450"
FT CHAIN 741..991
FT /note="VF gamma chain"
FT /id="PRO_0000423451"
FT PROPEP 992..1270
FT /evidence="ECO:0000250"
FT /id="PRO_0000423452"
FT CHAIN 1271..1652
FT /note="VF beta chain"
FT /id="PRO_0000423453"
FT DOMAIN 684..719
FT /note="Anaphylatoxin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00022"
FT DOMAIN 1507..1650
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT REGION 661..739
FT /note="C3a-like domain"
FT /evidence="ECO:0000250"
FT REGION 743..754
FT /note="Factor B binding site"
FT /evidence="ECO:0000250"
FT REGION 992..1270
FT /note="C3d-like domain"
FT /evidence="ECO:0000250"
FT REGION 1197..1260
FT /note="Factor H binding site"
FT /evidence="ECO:0000250"
FT BINDING 519
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 542
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 543
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 545
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT DISULFID 547..808
FT /note="Interchain (between alpha and gamma chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00022,
FT ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 616..651
FT /evidence="ECO:0000250"
FT DISULFID 684..711
FT /evidence="ECO:0000250"
FT DISULFID 685..718
FT /evidence="ECO:0000250"
FT DISULFID 698..719
FT /evidence="ECO:0000250"
FT DISULFID 864..1502
FT /note="Interchain (between gamma and beta chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00022,
FT ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 1347..1478
FT /evidence="ECO:0000250"
FT DISULFID 1378..1447
FT /evidence="ECO:0000250"
FT DISULFID 1495..1500
FT /evidence="ECO:0000250"
FT DISULFID 1507..1579
FT /evidence="ECO:0000250"
FT DISULFID 1526..1650
FT /evidence="ECO:0000250"
FT DISULFID 1626..1635
FT /evidence="ECO:0000250"
FT CROSSLNK 1000..1003
FT /note="Isoglutamyl cysteine thioester (Cys-Gln)"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1652 AA; 184923 MW; D60231FDF0F971A6 CRC64;
MEGMALYLVA ALLIGFPASS FGALYTFITP GVLRTDTEEK ILVEAHGDNA PKQLDISVHD
FPRKQKILYQ TRVDMNPAGG MLVTPTITIP AKDLNKDSRQ NQYVVVQVTA PGLRLEKVVL
LSYQSGFVFI QTDKGIYTPG SPVRYRVFSM DHNMHRMDKT VIVEFQTPQG IVVSSNPVNP
ASSLIRPYNL PELVSFGTWK AVAKYENSPE ESYTALFDVR EYVLPGFEVR VQPSEKFLYI
DGNTDFHVSI TARYLYGKRV EGVAFVLFGV KIDGNKKSIP ESLTRIPIID GDGEATLERH
TLSRRFQRLN DLVGHNLYVS VTVITDSGSD MVVTEQSGIH IVTSPYQISF TKTPKYFKPG
MPYELMVYVT NPDGSPAANV PVVSESIHSK GTTLSDGTAK LILNTPLNIQ SLSITVKTNH
RDLPRERQAM KSMTATAYQT QGGSGNYLHI AITSTEIKPG DNLPVSFNVR GNANSLNQIQ
YFTYLILTKG KIFKVGRQPR GAGQNLVTMT LPITPDLIPS FRFLAYYQVG NSEIVADSVW
VDVKDTCMGT LVVKGASSRD NRIQKPGAAM KIKLEGDPGA RVGLVAVDKA VYVLSDEYKI
SQTKIWDTIE KSDFGCTAGS GQNNLGVFED AGLALATSTS LNTKQRSDAK CPQPENRRRR
RSVVLLDSKA SKAAQFPDQA LRKCCEDGMH ENPMGYSCEK REKYIQEGDA CKAAFLECCR
YIKGIHDENK REDELFLARS DFEDEFFGED NIISRSDFPE SWLWLTENLN AVPNNEGISS
KTVPFYLRDS ITTWEVLAVS ITPTKGICVA EPYEITVMKD FFIDLRLPYS VVKNEQVEVR
AILYNYVDDD IDVRVELLHN PAFCSVATET QRYRTQVTIK ALSSWAVPFV IVPLQQGLHD
IEVRASVRGQ LASDGVKKKL KVVPEGMRKD IVTVIELDPS TKGVGGTQEQ LVKANELDGK
VPDTEIETKI SVQGDRVAQI VENSIDGNKL SHLIITPSGC GEQNMITMTP SVIATYYLDT
TGQWETLGVD RRTEAVQQIK KGYAQQLVYK KADHSYAAFV NRDSSSWLTA YVVKVFAMAT
KVVPDISHEI ICGGVKWLIL NRQQPDGVFK ENAPVIHGEM LGGTKGAEPE VSLTAFILIA
LLESRSICNE HINILESSIN KAADYLLKKY EKLQRPYTTA LTAYALAAAG LLNDDRVLMA
ASTERNRWEE HNAYTYNIEG TSYALLALLK MEKFAEANPV VRWLTDQKYY GGTYGQTQAT
VVGFQGLAEY EIAMPSHKDL NLDIVIKLPE REVPISYRID ATNALRAQTT ETKLNEDFTV
SASGDGKATM TILTVYNAQL REDANVCNQF HLEVSVERID SNLKQAKGAK ETLKLKICTR
YLGEVDSTMT IIDVSMLTGF LPDAEDLTRL SKGVDRYISK FEIDNNMAQK GAVIIYLDKV
SHSEDECLQF RIQKHFEVGF IQPGSVKVYS YYNLDEQCTR FYHPDKGTGL LNKICHGNVC
RCAEETCSLL NQQKKIDLQL RIQKACEPNV DYVYKAKLLR IEEKDASDIY VMDVLEVIKG
GTDRNPQAKP RQYVSQRKCQ EALNLKVNND YLIWGLSSDL WHKKDEISYL ITRNTWIERW
PNEDECQDEE FQNLCNDFTQ LSNTLTIFGC PN
