VM3CX_DABSI
ID VM3CX_DABSI Reviewed; 619 AA.
AC Q7LZ61; B4UT23;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Coagulation factor X-activating enzyme heavy chain;
DE EC=3.4.24.58;
DE AltName: Full=Coagulation factor X-activating enzyme chain alpha;
DE AltName: Full=RVV-X heavy chain;
DE AltName: Full=Russellysin;
DE AltName: Full=Snake venom metalloproteinase;
DE Short=SVMP;
DE Flags: Precursor;
OS Daboia siamensis (Eastern Russel's viper) (Daboia russelii siamensis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Viperinae; Daboia.
OX NCBI_TaxID=343250;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CARBOHYDRATE COMPOSITION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=18616470; DOI=10.1111/j.1742-4658.2008.06540.x;
RA Chen H.S., Chen J.M., Lin C.W., Khoo K.H., Tsai I.H.;
RT "New insights into the functions and N-glycan structures of factor X
RT activator from Russell's viper venom.";
RL FEBS J. 275:3944-3958(2008).
RN [2]
RP PROTEIN SEQUENCE OF 189-429, ENZYME ACTIVITY, AND GLYCOSYLATION.
RC TISSUE=Venom;
RX PubMed=1629211; DOI=10.1016/s0021-9258(19)49685-3;
RA Takeya H., Nishida S., Miyata T., Kawada S., Saisaka Y., Morita T.,
RA Iwanaga S.;
RT "Coagulation factor X activating enzyme from Russell's viper venom (RVV-X).
RT A novel metalloproteinase with disintegrin (platelet aggregation
RT inhibitor)-like and C-type lectin-like domains.";
RL J. Biol. Chem. 267:14109-14117(1992).
RN [3]
RP PROTEIN SEQUENCE OF 189-207, ENZYME ACTIVITY, SUBUNIT, AND GLYCOSYLATION AT
RP ASN-216; ASN-257; ASN-351 AND ASN-371.
RC TISSUE=Venom;
RX PubMed=8144654; DOI=10.1016/s0021-9258(17)34108-x;
RA Gowda D.C., Jackson C.M., Hensley P., Davidson E.A.;
RT "Factor X-activating glycoprotein of Russell's viper venom. Polypeptide
RT composition and characterization of the carbohydrate moieties.";
RL J. Biol. Chem. 269:10644-10650(1994).
RN [4]
RP ROLE OF GLYCOSYLATION.
RX PubMed=8639544; DOI=10.1021/bi953043e;
RA Gowda D.C., Jackson C.M., Kurzban G.P., McPhie P., Davidson E.A.;
RT "Core sugar residues of the N-linked oligosaccharides of Russell's viper
RT venom factor X-activator maintain functionally active polypeptide
RT structure.";
RL Biochemistry 35:5833-5837(1996).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.91 ANGSTROMS) OF 189-615 IN COMPLEX WITH LC1 AND
RP LC2, METAL-BINDING SITES, GLYCOSYLATION AT ASN-257 AND ASN-371, SUBUNIT,
RP AND DISULFIDE BONDS.
RX PubMed=18060879; DOI=10.1016/j.febslet.2007.11.062;
RA Takeda S., Igarashi T., Mori H.;
RT "Crystal structure of RVV-X: an example of evolutionary gain of specificity
RT by ADAM proteinases.";
RL FEBS Lett. 581:5859-5864(2007).
RN [6]
RP REVIEW.
RX PubMed=11910189; DOI=10.1159/000048067;
RA Tans G., Rosing J.;
RT "Snake venom activators of factor X: an overview.";
RL Haemostasis 31:225-233(2001).
CC -!- FUNCTION: Catalytic subunit of blood coagulation factor X-activating
CC enzyme. Activates coagulation factor X (F10) by cleaving the Arg-Ile
CC bond and is also able to activate coagulation factor IX (F9) and
CC protein S (PROS1) by specific cleavage of Arg-Ile and Arg-Val bonds.
CC {ECO:0000269|PubMed:18616470}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Specifically activates several components of the blood
CC clotting system, including coagulation factor X, coagulation factor
CC IX and protein C by cleavage of Arg-|-Xaa bonds. Has no action on
CC insulin B chain.; EC=3.4.24.58; Evidence={ECO:0000269|PubMed:1629211,
CC ECO:0000269|PubMed:8144654};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- SUBUNIT: Heterotrimer; disulfide-linked. The heterotrimer consists of 1
CC heavy chain and 2 light chains (lectins): LC1 and LC2.
CC {ECO:0000269|PubMed:18060879, ECO:0000269|PubMed:8144654}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- PTM: N-glycosylated; probably required for conformation. Removal of
CC easily accessible sugars does not change its functional capacity, but
CC removal of the core sugars with N-glycanase causes a virtually complete
CC loss of enzyme activity, apparently as a result of major conformational
CC changes in the molecule. Not O-glycosylated.
CC {ECO:0000269|PubMed:1629211, ECO:0000269|PubMed:18060879,
CC ECO:0000269|PubMed:18616470, ECO:0000269|PubMed:8144654}.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-III
CC subfamily. P-IIId sub-subfamily. {ECO:0000305}.
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DR EMBL; DQ137799; AAZ39881.1; -; mRNA.
DR PIR; A42972; A42972.
DR PDB; 2E3X; X-ray; 2.91 A; A=189-615.
DR PDBsum; 2E3X; -.
DR AlphaFoldDB; Q7LZ61; -.
DR SMR; Q7LZ61; -.
DR MEROPS; M12.158; -.
DR iPTMnet; Q7LZ61; -.
DR KEGG; ag:AAZ39881; -.
DR BRENDA; 3.4.24.58; 6667.
DR EvolutionaryTrace; Q7LZ61; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd04269; ZnMc_adamalysin_II_like; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR Gene3D; 4.10.70.10; -; 1.
DR InterPro; IPR006586; ADAM_Cys-rich.
DR InterPro; IPR018358; Disintegrin_CS.
DR InterPro; IPR001762; Disintegrin_dom.
DR InterPro; IPR036436; Disintegrin_dom_sf.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001590; Peptidase_M12B.
DR InterPro; IPR002870; Peptidase_M12B_N.
DR InterPro; IPR034027; Reprolysin_adamalysin.
DR Pfam; PF08516; ADAM_CR; 1.
DR Pfam; PF00200; Disintegrin; 1.
DR Pfam; PF01562; Pep_M12B_propep; 1.
DR Pfam; PF01421; Reprolysin; 1.
DR PRINTS; PR00289; DISINTEGRIN.
DR SMART; SM00608; ACR; 1.
DR SMART; SM00050; DISIN; 1.
DR SUPFAM; SSF57552; SSF57552; 1.
DR PROSITE; PS50215; ADAM_MEPRO; 1.
DR PROSITE; PS00427; DISINTEGRIN_1; 1.
DR PROSITE; PS50214; DISINTEGRIN_2; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Blood coagulation cascade activating toxin; Calcium;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hemostasis impairing toxin; Hydrolase; Metal-binding; Metalloprotease;
KW Protease; Secreted; Signal; Toxin; Zinc.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..188
FT /evidence="ECO:0000269|PubMed:1629211,
FT ECO:0000269|PubMed:8144654"
FT /id="PRO_0000355226"
FT CHAIN 189..619
FT /note="Coagulation factor X-activating enzyme heavy chain"
FT /id="PRO_0000078204"
FT DOMAIN 199..393
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 401..487
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 465..467
FT /note="D/ECD-tripeptide"
FT ACT_SITE 334
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 333
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 337
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 343
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 403
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 406
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 408
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 410
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 413
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 416
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 467
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 468
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 470
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 482
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 483
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT CARBOHYD 216
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:8144654"
FT CARBOHYD 257
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:18060879,
FT ECO:0000269|PubMed:8144654"
FT CARBOHYD 351
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:8144654"
FT CARBOHYD 371
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:18060879,
FT ECO:0000269|PubMed:8144654"
FT DISULFID 215..251
FT /evidence="ECO:0000269|PubMed:18060879"
FT DISULFID 308..388
FT /evidence="ECO:0000269|PubMed:18060879"
FT DISULFID 348..372
FT /evidence="ECO:0000269|PubMed:18060879"
FT DISULFID 350..355
FT /evidence="ECO:0000269|PubMed:18060879"
FT DISULFID 404..433
FT /evidence="ECO:0000269|PubMed:18060879"
FT DISULFID 415..428
FT /evidence="ECO:0000269|PubMed:18060879"
FT DISULFID 417..423
FT /evidence="ECO:0000269|PubMed:18060879"
FT DISULFID 427..450
FT /evidence="ECO:0000269|PubMed:18060879"
FT DISULFID 441..447
FT /evidence="ECO:0000269|PubMed:18060879"
FT DISULFID 446..472
FT /evidence="ECO:0000269|PubMed:18060879"
FT DISULFID 459..479
FT /evidence="ECO:0000269|PubMed:18060879"
FT DISULFID 466..498
FT /evidence="ECO:0000269|PubMed:18060879"
FT DISULFID 491..503
FT /evidence="ECO:0000269|PubMed:18060879"
FT DISULFID 510..560
FT /evidence="ECO:0000269|PubMed:18060879"
FT DISULFID 525..571
FT /evidence="ECO:0000269|PubMed:18060879"
FT DISULFID 538..548
FT /evidence="ECO:0000269|PubMed:18060879"
FT DISULFID 555..597
FT /evidence="ECO:0000269|PubMed:18060879"
FT DISULFID 577
FT /note="Interchain (with C-158 in coagulation factor X-
FT activating enzyme light chain LC2)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068,
FT ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000269|PubMed:18060879"
FT DISULFID 591..603
FT /evidence="ECO:0000269|PubMed:18060879"
FT CONFLICT 191
FT /note="S -> A (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 199..207
FT /evidence="ECO:0007829|PDB:2E3X"
FT TURN 209..214
FT /evidence="ECO:0007829|PDB:2E3X"
FT HELIX 219..235
FT /evidence="ECO:0007829|PDB:2E3X"
FT HELIX 236..238
FT /evidence="ECO:0007829|PDB:2E3X"
FT STRAND 240..249
FT /evidence="ECO:0007829|PDB:2E3X"
FT HELIX 262..275
FT /evidence="ECO:0007829|PDB:2E3X"
FT HELIX 277..280
FT /evidence="ECO:0007829|PDB:2E3X"
FT STRAND 284..290
FT /evidence="ECO:0007829|PDB:2E3X"
FT HELIX 295..297
FT /evidence="ECO:0007829|PDB:2E3X"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:2E3X"
FT TURN 310..312
FT /evidence="ECO:0007829|PDB:2E3X"
FT STRAND 313..318
FT /evidence="ECO:0007829|PDB:2E3X"
FT HELIX 324..337
FT /evidence="ECO:0007829|PDB:2E3X"
FT TURN 338..340
FT /evidence="ECO:0007829|PDB:2E3X"
FT HELIX 371..384
FT /evidence="ECO:0007829|PDB:2E3X"
FT HELIX 395..397
FT /evidence="ECO:0007829|PDB:2E3X"
FT TURN 430..432
FT /evidence="ECO:0007829|PDB:2E3X"
FT STRAND 442..444
FT /evidence="ECO:0007829|PDB:2E3X"
FT STRAND 458..460
FT /evidence="ECO:0007829|PDB:2E3X"
FT TURN 492..495
FT /evidence="ECO:0007829|PDB:2E3X"
FT HELIX 506..514
FT /evidence="ECO:0007829|PDB:2E3X"
FT HELIX 523..530
FT /evidence="ECO:0007829|PDB:2E3X"
FT STRAND 534..536
FT /evidence="ECO:0007829|PDB:2E3X"
FT HELIX 553..555
FT /evidence="ECO:0007829|PDB:2E3X"
FT STRAND 570..573
FT /evidence="ECO:0007829|PDB:2E3X"
FT STRAND 590..592
FT /evidence="ECO:0007829|PDB:2E3X"
FT STRAND 595..597
FT /evidence="ECO:0007829|PDB:2E3X"
FT STRAND 603..605
FT /evidence="ECO:0007829|PDB:2E3X"
FT HELIX 606..609
FT /evidence="ECO:0007829|PDB:2E3X"
SQ SEQUENCE 619 AA; 69648 MW; 71084A3B46338797 CRC64;
MMQVLLVTIS LAVFPYQGSS IILESGNVND YEVVYPQKVT ALPKGAVQQP EQKYEDTMQY
EFEVNGEPVV LHLEKNKILF SEDYSETHYY PDGREITTNP PVEDHCYYHG RIQNDAHSSA
SISACNGLKG HFKLRGEMYF IEPLKLSNSE AHAVYKYENI EKEDEIPKMC GVTQTNWESD
KPIKKASQLV STSAQFNKIF IELVIIVDHS MAKKCNSTAT NTKIYEIVNS ANEIFNPLNI
HVTLIGVEFW CDRDLINVTS SADETLNSFG EWRASDLMTR KSHDNALLFT DMRFDLNTLG
ITFLAGMCQA YRSVEIVQEQ GNRNFKTAVI MAHELSHNLG MYHDGKNCIC NDSSCVMSPV
LSDQPSKLFS NCSIHDYQRY LTRYKPKCIF NPPLRKDIVS PPVCGNEIWE EGEECDCGSP
ANCQNPCCDA ATCKLKPGAE CGNGLCCYQC KIKTAGTVCR RARDECDVPE HCTGQSAECP
RDQLQQNGKP CQNNRGYCYN GDCPIMRNQC ISLFGSRANV AKDSCFQENL KGSYYGYCRK
ENGRKIPCAP QDVKCGRLFC LNNSPRNKNP CNMHYSCMDQ HKGMVDPGTK CEDGKVCNNK
RQCVDVNTAY QSTTGFSQI
