VCO3_OPHHA
ID VCO3_OPHHA Reviewed; 1641 AA.
AC I2C090;
DT 18-SEP-2013, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2012, sequence version 1.
DT 03-AUG-2022, entry version 33.
DE RecName: Full=Ophiophagus venom factor;
DE Short=OVF;
DE AltName: Full=CVF-like;
DE AltName: Full=Complement C3 homolog;
DE Contains:
DE RecName: Full=OVF alpha chain;
DE Contains:
DE RecName: Full=OVF gamma chain;
DE Contains:
DE RecName: Full=OVF beta chain;
DE Flags: Precursor;
OS Ophiophagus hannah (King cobra) (Naja hannah).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Elapinae; Ophiophagus.
OX NCBI_TaxID=8665;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 23-33; 729-733 AND
RP 1260-1268, FUNCTION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Venom, and Venom gland;
RX PubMed=22561424; DOI=10.1016/j.toxicon.2012.04.344;
RA Zeng L., Sun Q.Y., Jin Y., Zhang Y., Lee W.H., Zhang Y.;
RT "Molecular cloning and characterization of a complement-depleting factor
RT from king cobra, Ophiophagus hannah.";
RL Toxicon 60:290-301(2012).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=24297900; DOI=10.1073/pnas.1314702110;
RA Vonk F.J., Casewell N.R., Henkel C.V., Heimberg A.M., Jansen H.J.,
RA McCleary R.J., Kerkkamp H.M., Vos R.A., Guerreiro I., Calvete J.J.,
RA Wuster W., Woods A.E., Logan J.M., Harrison R.A., Castoe T.A.,
RA de Koning A.P., Pollock D.D., Yandell M., Calderon D., Renjifo C.,
RA Currier R.B., Salgado D., Pla D., Sanz L., Hyder A.S., Ribeiro J.M.,
RA Arntzen J.W., van den Thillart G.E., Boetzer M., Pirovano W., Dirks R.P.,
RA Spaink H.P., Duboule D., McGlinn E., Kini R.M., Richardson M.K.;
RT "The king cobra genome reveals dynamic gene evolution and adaptation in the
RT snake venom system.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:20651-20656(2013).
CC -!- FUNCTION: Complement-activating protein in cobra venom. It is a
CC structural and functional analog of complement component C3b, the
CC activated form of C3. It binds factor B (CFB), which is subsequently
CC cleaved by factor D (CFD) to form the bimolecular complex OVF/Bb.
CC OVF/Bb is a C3/C5 convertase that cleaves both complement components C3
CC and C5. Structurally, it resembles the C3b degradation product C3c,
CC which is not able to form a C3/C5 convertase. Unlike C3b/Bb, OVF/Bb is
CC a stable complex and completely resistant to the actions of complement
CC regulatory factors H (CFH) and I (CFI). Therefore, OVF continuously
CC activates complement (By similarity). As a result, OVF exhibits
CC complement-depleting activity. {ECO:0000250,
CC ECO:0000269|PubMed:22561424}.
CC -!- SUBUNIT: Heterotrimer of alpha, beta and gamma chains; disulfide-
CC linked. May be active with factor B in the presence of factor D.
CC -!- SUBCELLULAR LOCATION: Secreted.
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 (OVF) (By similarity). {ECO:0000250}.
CC -!- PTM: The beta chain is not glycosylated. {ECO:0000269|PubMed:22561424}.
CC -!- SIMILARITY: Belongs to the venom complement C3 homolog family.
CC {ECO:0000305}.
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DR EMBL; JQ418342; AFJ59923.1; -; mRNA.
DR AlphaFoldDB; I2C090; -.
DR SMR; I2C090; -.
DR MEROPS; I39.950; -.
DR PRIDE; I2C090; -.
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; 1.
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; PS01178; ANAPHYLATOXIN_2; 1.
DR PROSITE; PS50189; NTR; 1.
PE 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Complement system impairing toxin;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Magnesium;
KW Metal-binding; Secreted; Signal; Thioester bond; Toxin.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:22561424"
FT CHAIN 23..1641
FT /note="Ophiophagus venom factor"
FT /id="PRO_0000423454"
FT CHAIN 23..644
FT /note="OVF alpha chain"
FT /id="PRO_0000423455"
FT PROPEP 645..728
FT /evidence="ECO:0000269|PubMed:22561424"
FT /id="PRO_0000423456"
FT CHAIN 729..980
FT /note="OVF gamma chain"
FT /id="PRO_0000423457"
FT PROPEP 981..1259
FT /evidence="ECO:0000269|PubMed:22561424"
FT /id="PRO_0000423458"
FT CHAIN 1260..1641
FT /note="OVF beta chain"
FT /id="PRO_0000423459"
FT DOMAIN 672..707
FT /note="Anaphylatoxin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00022"
FT DOMAIN 1496..1639
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT REGION 649..727
FT /note="C3a-like domain"
FT /evidence="ECO:0000250"
FT REGION 731..742
FT /note="Factor B binding site"
FT /evidence="ECO:0000250"
FT REGION 981..1259
FT /note="C3d-like domain"
FT /evidence="ECO:0000250"
FT REGION 1186..1249
FT /note="Factor H binding site"
FT /evidence="ECO:0000250"
FT BINDING 507
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 530
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 531
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 533
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT CARBOHYD 181
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 209
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 535..796
FT /note="Interchain (between alpha and gamma chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00022,
FT ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 604..639
FT /evidence="ECO:0000250"
FT DISULFID 672..699
FT /evidence="ECO:0000250"
FT DISULFID 673..706
FT /evidence="ECO:0000250"
FT DISULFID 686..707
FT /evidence="ECO:0000250"
FT DISULFID 852..1491
FT /note="Interchain (between gamma and beta chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00022,
FT ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 1336..1467
FT /evidence="ECO:0000250"
FT DISULFID 1367..1436
FT /evidence="ECO:0000250"
FT DISULFID 1484..1489
FT /evidence="ECO:0000250"
FT DISULFID 1496..1568
FT /evidence="ECO:0000250"
FT DISULFID 1515..1639
FT /evidence="ECO:0000250"
FT DISULFID 1615..1624
FT /evidence="ECO:0000250"
FT CROSSLNK 989..992
FT /note="Isoglutamyl cysteine thioester (Cys-Gln)"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1641 AA; 183928 MW; DAAAAB1DF4E084F4 CRC64;
MEGMALYLVA ALLIGFPGSS HGALYTLITP GVLRTDTEEQ ILVEAHGDNT PKQLDIFVHD
FPRKQKILFQ KRVDMNPAGD MLVTPTIKIP AEEVSKDSRQ NQYVVVQVTG PQVRLEKVVL
LSYQSGFVFI QTDKGIYTPG SPVLYRVFSM DHNMRQMDKT VVVEFQTPEG IVVSSNRIDL
NFTRPYNLPE LGSLGTWKIV AKYEHSPENY TAYFDVRKYV LPSFEVHLQP SEKSFYIDGN
ENFHVSITAR YLYGEEVEGV AFVLFGVKID GAKKSIPDSL TRIPILDGDG EATLKRDTLR
SRFPNLNELV GHTLYASVTV ITESGSDMVA TEQSGIHIVT SPYQIYFTKT PKYFKPGMPY
ELTVYVTNPD GSPAAKVPVV SEAIHSEGTT LSDGTAKLIL NTPLDTQSLL ITVRTNHGDL
PRERQATKSM TATAYQTQGG SGNYLHVAIT STEIKPGDNL PVNFNVRGNA NSLNQVKYFT
YLVGRQPKGA GQNLVAMNLR ITPDLIPSFR FVAYYQVGNN EIVADSVWVD VKDTCMGTLV
VKGASLTDNQ IHMPGAAMKI KLEGDPGAQV GLVAVDKAVY VLNDKYKISQ AKIWDTIEKS
DFGCTAGGGQ NNLGVFEDAG LALTTSTNLN TKQRSDTKCP QPANRRRRSS VLLLDSKASK
AAQFQDQDLR KCCEDSMHEN PMGYTCEKRA KYIQEGDACK AAFLECCRYI KGILDENQWE
SGLFLPRNDN EDGFIQDSDI IPRTDFPKSW LWHTVQLTEQ PNSNGISSKT MSIYLKESIT
TWEVLAVSFT PTKGICVAEP YEIKVMKDFF IDLRVPYSVV RKEQVEIRAV LYNYAGRDIY
VRVELLYNPA FCSASTEEQR YRQQFTIKAL SSRAVPFVIV PLQQGLHDIE VRASVQGWES
VSDGVKKKLK VVPEGVQKCI VTIIKLDPRA KGVDGTQREV VKARKLDDKV PDTEIETKIT
IQADPVAQII ENSIDGSKLN HLIITPSGCG EQNMIRMTAP VIATYYLDTT EQWETLGRNH
RNEAVKQIMT GYAQQMVYKK ANHSYAAFTN RASSTWLTAY VVKVFAMATK MVAGISHEII
CGGVRWLILN RQQPDGAFKE NAPVLSGTMQ GGIQGDESEV TVTAFTLVAL LESKTICNDS
VNSLDSSIKK ATDYLLKKYE KLQRPYTTAL TAYALAAADR LNDDRVLMAA STGKNRWEEY
NAHTHNVEGT SYALLALLKM KKFDQTGPIV RWLTDQNFYG GTYGQTQATV MLFQALAEYK
IQMPTHKDLN LDIIIKLPER ELPLHYRLDA TNAILARTAE TKLNQDFTVS ASGDGTATMT
ILTVYNAQLQ EKANVCNKFH LDVSVENIHL NFKHAKGAKG ALMLKICMRY LGEVDSTMTI
IDISMLTGFL PDAEDLTRLS EGVDRYISRY EVDNNMAQKV AVIIYLDKVS HSEDECLQFK
ILKHFEVGFI QPGSVKVYSY YNLDEQCTKF YHPDKGTGLL NKICVGNICR CAAETCSLLS
QQEKIDLPLR IQKACASNVD YVYKTKLLRI EEKDGYDIYV MDVLEVIKPG TDENPQANAR
QYISQRKCQE ALNLNVNDDY LIWGLRSDLW PMKDKFSYLI TKNTWIERWP HEDECQDEEF
QNLCLDFAHL SNILTIFGCP T
