VM3M1_NAJMO
ID VM3M1_NAJMO Reviewed; 609 AA.
AC Q10749; Q8JGN1;
DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 3.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Snake venom metalloproteinase-disintegrin-like mocarhagin;
DE Short=MOC;
DE Short=Mocarhagin-1;
DE Short=SVMP;
DE EC=3.4.24.-;
DE AltName: Full=Zinc metalloproteinase mocarhagin;
DE Flags: Precursor;
OS Naja mossambica (Mozambique spitting cobra).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Elapinae; Naja.
OX NCBI_TaxID=8644;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RA Sako D., Shaw G.D.;
RT "Molecular characterization of mocarhagins: a multi-gene family of
RT metalloproteinases expressed in cobra venom.";
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000305}
RP PROTEIN SEQUENCE OF 192-215, AND FUNCTION.
RC TISSUE=Venom {ECO:0000269|PubMed:8664285};
RX PubMed=8664285; DOI=10.1021/bi952456c;
RA Ward C.M., Andrews R.K., Smith I., Berndt M.C.;
RT "Mocarhagin, a novel cobra venom metalloproteinase, cleaves the platelet
RT von Willebrand factor receptor glycoprotein Ibalpha. Identification of the
RT sulfated tyrosine/anionic sequence Tyr-276-Glu-282 of glycoprotein Ibalpha
RT as a binding site for von Willebrand factor and alpha-thrombin.";
RL Biochemistry 35:4929-4938(1996).
RN [3]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=7592904; DOI=10.1074/jbc.270.45.26734;
RA De Luca M., Dunlop L.C., Andrews R.K., Flannery J.V. Jr., Ettling R.,
RA Cumming D.A., Veldman G.M., Berndt M.C.;
RT "A novel cobra venom metalloproteinase, mocarhagin, cleaves a 10-amino acid
RT peptide from the mature N terminus of P-selectin glycoprotein ligand
RT receptor, PSGL-1, and abolishes P-selectin binding.";
RL J. Biol. Chem. 270:26734-26737(1995).
RN [4]
RP FUNCTION.
RX PubMed=8931262; DOI=10.1016/0041-0101(96)00115-8;
RA Ward C.M., Vinogradov D.V., Andrews R.K., Berndt M.C.;
RT "Characterization of mocarhagin, a cobra venom metalloproteinase from Naja
RT mocambique mocambique, and related proteins from other Elapidae venoms.";
RL Toxicon 34:1203-1206(1996).
RN [5]
RP FUNCTION.
RX PubMed=12598411; DOI=10.1038/sj.bjp.0705095;
RA Jarvis G.E., Atkinson B.T., Frampton J., Watson S.P.;
RT "Thrombin-induced conversion of fibrinogen to fibrin results in rapid
RT platelet trapping which is not dependent on platelet activation or GPIb.";
RL Br. J. Pharmacol. 138:574-583(2003).
RN [6]
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: Snake venom zinc metalloproteinase that inhibits platelet
CC aggregation by cleaving platelet glycoprotein Ib alpha (GP1BA) at Glu-
CC 298/Asp-299, and abolishes binding of von Willebrand factor (VWF) to
CC GPIBA. Cleaves P-selectin glycoprotein ligand-1 (PSGL-1/SELPLG) at Tyr-
CC 51/Asp-52, and completely abolishes the binding of PSGL-1 to P-
CC selectin. Anionic amino acid sequences containing sulfated tyrosines
CC are needed for cleavages. Inhibits the thrombin-induced platelet
CC aggregation, and the thrombin-induced release of ATP and ADP. Has
CC lectin activity (inhibited by heparin). {ECO:0000269|PubMed:12598411,
CC ECO:0000269|PubMed:7592904, ECO:0000269|PubMed:8664285,
CC ECO:0000269|PubMed:8931262}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by EDTA and diisopropyl fluorophosphate
CC (DFP). Also inhibited by an excess of zinc or calcium ions.
CC {ECO:0000269|PubMed:7592904}.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8664285}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000269|PubMed:8664285}.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-III
CC subfamily. P-IIIa sub-subfamily. {ECO:0000305}.
CC -!- CAUTION: Asp-351 is present instead of the conserved His which is
CC expected to be zinc-binding residue. There is therefore some
CC uncertainty concerning the enzymatic activity of this protein.
CC {ECO:0000305}.
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DR EMBL; AY101383; AAM51550.1; -; mRNA.
DR AlphaFoldDB; Q10749; -.
DR SMR; Q10749; -.
DR MEROPS; M12.159; -.
DR PRIDE; Q10749; -.
DR TopDownProteomics; Q10749; -.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0030195; P:negative regulation of blood coagulation; IDA:UniProtKB.
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.
PE 1: Evidence at protein level;
KW Calcium; Cell adhesion impairing toxin; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Hemostasis impairing toxin; Hydrolase;
KW Metal-binding; Metalloprotease; Platelet aggregation inhibiting toxin;
KW Protease; Secreted; Signal; Toxin; Zinc; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..191
FT /evidence="ECO:0000269|PubMed:8664285"
FT /id="PRO_0000326257"
FT CHAIN 192..609
FT /note="Snake venom metalloproteinase-disintegrin-like
FT mocarhagin"
FT /id="PRO_0000078194"
FT DOMAIN 205..400
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 408..494
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 472..474
FT /note="D/ECD-tripeptide"
FT BINDING 208
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 292
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 341
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 345
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 395
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 398
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 410
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 413
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 415
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 417
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 420
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 423
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT CARBOHYD 303
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 507
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 316..395
FT /evidence="ECO:0000250"
FT DISULFID 356..379
FT /evidence="ECO:0000250"
FT DISULFID 358..363
FT /evidence="ECO:0000250"
FT DISULFID 411..440
FT /evidence="ECO:0000250"
FT DISULFID 422..435
FT /evidence="ECO:0000250"
FT DISULFID 424..430
FT /evidence="ECO:0000250"
FT DISULFID 434..457
FT /evidence="ECO:0000250"
FT DISULFID 448..454
FT /evidence="ECO:0000250"
FT DISULFID 453..479
FT /evidence="ECO:0000250"
FT DISULFID 466..486
FT /evidence="ECO:0000250"
FT DISULFID 473..505
FT /evidence="ECO:0000250"
FT DISULFID 498..510
FT /evidence="ECO:0000250"
FT DISULFID 517..567
FT /evidence="ECO:0000250"
FT DISULFID 532..575
FT /evidence="ECO:0000250"
FT DISULFID 545..555
FT /evidence="ECO:0000250"
FT DISULFID 562..601
FT /evidence="ECO:0000250"
FT DISULFID 595..606
FT /evidence="ECO:0000250"
FT CONFLICT 194..199
FT /note="TPEQDR -> CPELIP (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 205
FT /note="K -> C (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 609 AA; 68176 MW; FE717DCAE344A40D CRC64;
MIQALLVAIC LAVFPYQGSS IILESGNVND YEVVYPQKVP ALSKGGVQNP QPETKYEDTM
QYEFHVNGEP VVLHLERNKG LFSEDYTETH YAPDGREITT SSPVQDHCYY HGYIQNEADS
SAVISACDGL KGHFKHQGET YFIEPLELSD SEAHAIYKDE NVEEEEEIPK ICGVTQTTWE
SDEPIEKSSQ LTNTPEQDRY LQAKKYIEFY VVVDNVMYRK YTGKLHVITR RVYEMVNALN
TMYRRLNFHI ALIGLEIWSN GNEINVQSDV QATLDLFGEW RENKLLPRKR NDNAQLLTST
EFNGTTTGLG YIGSLCSPKK SVAVVQDHSK STSMVAITMA HQMGHNLGMN DDRASCTCGS
NKCIMSTKYY ESLSEFSSCS VQEHREYLLR DRPQCILNKP SRKAIVTPPV CGNYFVERGE
ECDCGSPEDC QNTCCDAATC KLQHEAQCDS GECCEKCKFK GAGAECRAAK NDCDFPELCT
GRSAKCPKDS FQRNGHPCQN NQGYCYNGTC PTLTNQCATL WGPGAKMSPG LCFMLNWNAR
SCGLCRKENG RKILCAAKDV KCGRLFCKKK NSMICHCPPP SKDPNYGMVA PGTKCGVKKV
CRNRQCVKV
