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Protein

Zinc metalloproteinase/disintegrin

Gene
N/A
Organism
Macrovipera lebetina (Levantine viper) (Vipera lebetina)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Snake venom metalloproteinase lebetase: fibrinolytic and fibrinogenolytic metalloproteinase that hydrolyzes the Aalpha-chain and more slowly the Bbeta-chain of fibrin and fibrinogen. Its fibrinolytic activity is direct, without any plasminogen activation. Also hydrolyzes casein and B-chain of oxidized insulin. Inhibits ADP-induced and collagen-induced platelet aggregation. Shows low hemorrhagic activity. Cleaves the plasma proteinase inhibitors alpha(2)-macroglobulin (A2M) and pregnancy zone protein (PZP), and is inhibited by them.6 Publications
Disintegrin VLE5A: poor inhibitor of platelet aggregation. The disintegrin inhibits the adhesion of the alpha-4/beta-1 (ITGA4/ITGB1) integrin to VCAM-1. Inhibition on alpha-2b/beta-3 (ITGA2B/ITGB3) is low (By similarity).By similarity

Catalytic activityi

The metalloprotease has no strict P1-P1' specificity requirement. Hydrolysis at sites with a Pro residue at P1 is observed with bradykinin, substance P, PZP and alpha chain fibrinogen (FGA).1 Publication

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Enzyme regulationi

Fibrinolytic and caseinolytic activities are inhibited by Cd2+, Cu2+ and Co2+ ions. Not inhibited by Mg2+, Ca2+ and Ba2+. Also inhibited by EDTA, EGTA and 1,10-phenanthroline.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi204 – 2041CalciumBy similarity
Metal bindingi288 – 2881CalciumBy similarity
Metal bindingi337 – 3371Zinc; catalyticBy similarity
Active sitei338 – 3381PROSITE-ProRule annotation
Metal bindingi341 – 3411Zinc; catalyticBy similarity
Metal bindingi347 – 3471Zinc; catalyticBy similarity
Metal bindingi392 – 3921Calcium; via carbonyl oxygenBy similarity
Metal bindingi395 – 3951CalciumBy similarity

GO - Molecular functioni

Complete GO annotation...

Keywords - Molecular functioni

Cell adhesion impairing toxin, Fibrinogenolytic toxin, Fibrinolytic toxin, Hemostasis impairing toxin, Hydrolase, Metalloprotease, Platelet aggregation inhibiting toxin, Protease, Toxin

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Protein family/group databases

MEROPSiM12.164.

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc metalloproteinase/disintegrin
Cleaved into the following 2 chains:
Alternative name(s):
Fibrinolytic protease
Le-3
Short name:
Le3
Lebetase II
Lebetase-2
OrganismiMacrovipera lebetina (Levantine viper) (Vipera lebetina)
Taxonomic identifieri8709 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiLepidosauriaSquamataBifurcataUnidentataEpisquamataToxicoferaSerpentesColubroideaViperidaeViperinaeMacrovipera

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020Sequence analysisAdd
BLAST
Propeptidei21 – 194174PRO_0000318582Add
BLAST
Chaini195 – 397203Snake venom metalloproteinase lebetasePRO_5000146862Add
BLAST
Propeptidei398 – 41316By similarityPRO_0000318583Add
BLAST
Chaini414 – 47865Disintegrin VLE5APRO_5000146863Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei195 – 1951Pyrrolidone carboxylic acidBy similarity
Disulfide bondi312 ↔ 392By similarity
Disulfide bondi352 ↔ 376By similarity
Disulfide bondi354 ↔ 359By similarity
Disulfide bondi426 ↔ 440By similarity
Disulfide bondi434 ↔ 464By similarity
Disulfide bondi439 ↔ 443By similarity
Disulfide bondi452 ↔ 471By similarity

Keywords - PTMi

Disulfide bond, Pyrrolidone carboxylic acid, Zymogen

Expressioni

Tissue specificityi

Expressed by the venom gland.

Interactioni

Subunit structurei

Monomer (metalloproteinase). Heterodimer; disulfide-linked (disintegrin) (By similarity).By similarity

Structurei

3D structure databases

ProteinModelPortaliQ98995.
SMRiQ98995. Positions 196-397, 415-476.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini201 – 397197Peptidase M12BPROSITE-ProRule annotationAdd
BLAST
Domaini405 – 47874DisintegrinPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi456 – 4583Cell attachment site; atypical (VGD)

Sequence similaritiesi

Contains 1 disintegrin domain.PROSITE-ProRule annotation
Contains 1 peptidase M12B domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

HOVERGENiHBG006978.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR018358. Disintegrin_CS.
IPR001762. Disintegrin_dom.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
PfamiPF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
[Graphical view]
PRINTSiPR00289. DISINTEGRIN.
SMARTiSM00050. DISIN. 1 hit.
[Graphical view]
SUPFAMiSSF57552. SSF57552. 1 hit.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS00427. DISINTEGRIN_1. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q98995-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIQVLLVTIC LAVFPYQGSS KTLKSGNVND YEVVNPQAVT GLPKGAVKQP
60 70 80 90 100
EKKYEDTMQY EFEVNGEPVV LHLEKNRGLF SKDYSETHYS PDGREITTNP
110 120 130 140 150
AVEDHCYYHG RIQNDADSTA SISACNGLKG YFTLRGETYL IEPLKLPDSE
160 170 180 190 200
AHAVYKYENI EKEDEAPKMC GVTQTNWASD EPIKKASQLN LTPEQQRFEP
210 220 230 240 250
RYIELVIVAD HAMVTKYNGD LAAITTWVHQ LVNNINGFYR DLNVHITLSA
260 270 280 290 300
VEVWTNGDLI NVQPAASVTL NLFGEWRERD LLNRRMHDHA QLLTGIDLDD
310 320 330 340 350
NIIGLAYDDS MCDPRYSVGI VQDHSAIIRL VAVTMAHELG HNLGMNHDGD
360 370 380 390 400
QCNCGANGCV MSVVLIEQRS YQFSDCSKNK YQTYLTNRNP QCILNQPLRT
410 420 430 440 450
DTVSTPVSGN ELLQNSGNPC CDPVTCQPRR GEHCVSGKCC RNCKFLRAGT
460 470
VCKRAVGDDM DDYCTGISSD CPRNPYKD
Length:478
Mass (Da):53,480
Last modified:February 1, 1997 - v1
Checksum:i781915F7D897BF03
GO

Mass spectrometryi

Molecular mass is 22912±20 Da from positions 195 - 397. Determined by MALDI. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X97894 mRNA. Translation: CAA66471.1.
PIRiJC4880.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X97894 mRNA. Translation: CAA66471.1.
PIRiJC4880.

3D structure databases

ProteinModelPortaliQ98995.
SMRiQ98995. Positions 196-397, 415-476.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

MEROPSiM12.164.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

HOVERGENiHBG006978.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR018358. Disintegrin_CS.
IPR001762. Disintegrin_dom.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
PfamiPF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
[Graphical view]
PRINTSiPR00289. DISINTEGRIN.
SMARTiSM00050. DISIN. 1 hit.
[Graphical view]
SUPFAMiSSF57552. SSF57552. 1 hit.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS00427. DISINTEGRIN_1. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiVM2L2_MACLB
AccessioniPrimary (citable) accession number: Q98995
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: February 1, 1997
Last modified: October 14, 2015
This is version 96 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

2 lebetase isoforms have been isolated designated lebetase I (22.719 Da, pI 5.0) and lebetase II (22.912 Da, pI 5.3).1 Publication
Disintegrin VLE5A does not interact with the collagen-binding alpha-1/beta-1 (ITGA1/ITGB1) and alpha-2/beta-1 (ITGA2/ITGB1) integrins.By similarity
The disintegrin belongs to the dimeric disintegrin subfamily.

Keywords - Technical termi

Direct protein sequencing

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.