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PR00289

Identifier
DISINTEGRIN  [View Relations]  [View Alignment]  
Accession
PR00289
No. of Motifs
2
Creation Date
27-JAN-1994  (UPDATE 27-JUN-1999)
Title
Disintegrin signature
Database References

PROSITE; PS00427 DISINTEGRINS
BLOCKS; BL00427
PFAM; PF00200 disintegrin
INTERPRO; IPR001762
PDB; 2ECH
SCOP; 2ECH
CATH; 2ECH
Literature References
1. HUANG, T.F., SHEU, J.R. AND TENG, C.M.
A potent anti-platelet peptide, triflavin, from Trimeresurus flavoviridis
snake venom.
BIOCHEM.J. 277 351-357 (1991).
 
2. AU, L.C., HUANG, Y.B., HUANG, T.F., TEH, G.W., LIN, H.H. AND CHOO, K.B.
A common precursor for a putative hemorrhagic protein and rhodostomin, a
platelet aggregation inhibitor of the venom of Calloselasma rhodostoma - 
Molecular cloning and sequence analysis.
BIOCHEM.BIOPHYS.RES.COMMUN. 181(2) 585-593 (1991).
 
3. PAINE, M.J.I., DESMOND, H.P., THEAKSTON, R.D.G. AND CRAMPTON, J.M.
Purification, cloning, and molecular characterization of a high molecular
weight hemorrhagic metalloprotease, jararhagin, from Bothrops-J raraca
venom - Insights into the disintegrin gene family.
J.BIOL.CHEM. 267(32) 22869-22876 (1992).

Documentation
The adhesion of platelets to the extracellular matrix, and platelet-platelet
interactions, are essential in thrombosis and haemostasis [1]. Platelets
adhere to damaged blood vessels, release biologically active chemicals, and
aggregate, a function that is inhibited in normal blood [1]. The binding
of fibrinogen to the glycoprotein IIb/IIIa complex of activated platelets
is essential to platelet aggregation and is induced by many agonists, 
including ADP, collagen, thrombin, epinephrine and prostaglandin 
endoperoxide analogue. 
 
Snake venoms affect blood coagulation and platelet function in a complex 
manner [2]: some induce aggregation and release reactions, and some inhibit
them [1]. Disintegrin, a component of some snake venoms, rather than
inhibiting the release reactions, operates by inhibiting platelet
aggregation, blocking the binding of fibrinogen to the receptor-glyco-
protein complex of activated platelets [2]. The role of disintegrin in
preventing blood coagulation renders it of medical interest, particularly
with regard to its use as an anti-coagulant [3].
 
DISINTEGRIN is a 2-element fingerprint that provides a signature for the 
disintegrins. The fingerprint was derived from an initial alignment of 8
sequences: motif 1 includes the region encoded by PROSITE pattern
DISINTEGRINS (PS00427), which includes 5 conserved Cys residues involved
in disulphide bond formation (the motifs do not include the cell-attachment
tripeptide Arg-Gly-Asp as the surrounding residues are not sufficiently
well conserved). Two iterations on OWL22.1 were required to reach
convergence, at which point a true set comprising 39 sequences was
identified.
 
An update on SPTR37_9f identified a true set of 43 sequences.
Summary Information
43 codes involving  2 elements
Composite Feature Index
24343
12
True Positives
DISA_TRIGA    DISB_TRIGA    DISC_TRIFL    DISF_TRIFL    
DISG_TRIGA DISI_AGKHA DISI_AGKPI DISI_AGKRH
DISI_BITAR DISI_BOTAT DISI_BOTCO DISI_BOTJA
DISI_CROAT DISI_CROBA DISI_CROCC DISI_CROMM
DISI_CROVE DISI_CROVL DISI_CROVV DISI_ECHCA
DISI_ERIMA DISI_LACMU DISI_SISBA DISI_SISTE
DISI_TRIEL DISI_TRIFL DISR_AGKRH DIST_TRIFL
HR1B_TRIFL HRTE_CROAT O35227 O42138
O57413 O93523 P70505 Q28475
Q63180 Q90220 Q90282 Q90495
Q90499 Q91505 Q98995
Sequence Titles
DISA_TRIGA  PUTATIVE VENOM METALLOPROTEINASE PRECURSOR (EC 3.4.24.-) [CONTAINS: DISINTEGRIN TRIGRAMIN ALPHA (PLATELET AGGREGATION ACTIVATION INHIBITOR)] - TRIMERESURUS GRAMINEUS (INDIAN GREEN TREE VIPER) (GREEN HABU SNAKE). 
DISB_TRIGA DISINTEGRIN TRIGRAMIN BETA (PLATELET AGGREGATION ACTIVATION INHIBITOR) - TRIMERESURUS GRAMINEUS (INDIAN GREEN TREE VIPER) (GREEN HABU SNAKE).
DISC_TRIFL DISINTEGRIN (CYTOTOXIC FACTORS CTF-I AND CTF-II) - TRIMERESURUS FLAVOVIRIDIS (HABU).
DISF_TRIFL DISINTEGRIN FLAVORIDIN (RGD-CONTAINING PEPTIDE) (PLATELET AGGREGATION ACTIVATION INHIBITOR) - TRIMERESURUS FLAVOVIRIDIS (HABU).
DISG_TRIGA DISINTEGRIN TRIGRAMIN GAMMA (ALBOLABRIN) (PLATELET AGGREGATION ACTIVATION INHIBITOR) - TRIMERESURUS GRAMINEUS (INDIAN GREEN TREE VIPER) (GREEN HABU SNAKE), AND TRIMERESURUS ALBOLABRIS (WHITE-LIPPED PIT VIPER).
DISI_AGKHA DISINTEGRIN HALYSIN (PLATELET AGGREGATION ACTIVATION INHIBITOR) - AGKISTRODON HALYS BLOMHOFFI (MAMUSHI) (GLOYDIUS BLOMHOFFII).
DISI_AGKPI DISINTEGRIN APPLAGIN (PLATELET AGGREGATION ACTIVATION INHIBITOR) - AGKISTRODON PISCIVORUS PISCIVORUS (EASTERN COTTONMOUTH).
DISI_AGKRH DISINTEGRIN KISTRIN (PLATELET AGGREGATION ACTIVATION INHIBITOR) - AGKISTRODON RHODOSTOMA (MALAYAN PIT VIPER) (CALLOSELASMA RHODOSTOMA).
DISI_BITAR DISINTEGRIN BITAN (PLATELET AGGREGATION ACTIVATION INHIBITOR) (BITISTATIN) (VENOM PROTEIN CM-2) (ARIETIN) - BITIS ARIETANS (AFRICAN PUFF ADDER).
DISI_BOTAT DISINTEGRIN BATROXOSTATIN (PLATELET AGGREGATION ACTIVATION INHIBITOR) - BOTHROPS ATROX (BARBA AMARILLA) (FER-DE-LANCE).
DISI_BOTCO DISINTEGRIN COTIARIN (PLATELET AGGREGATION ACTIVATION INHIBITOR) - BOTHROPS COTIARA (COTIARA).
DISI_BOTJA DISINTEGRIN JARARACIN (PLATELET AGGREGATION ACTIVATION INHIBITOR) - BOTHROPS JARARACA (JARARACA).
DISI_CROAT DISINTEGRIN CROTATROXIN/DURISSIN (PLATELET AGGREGATION ACTIVATION INHIBITOR) - CROTALUS ATROX (WESTERN DIAMONDBACK RATTLESNAKE), AND CROTALUS DURISSUS DURISSUS (CENTRAL AMERICAN RATTLESNAKE).
DISI_CROBA DISINTEGRIN BASILICIN (PLATELET AGGREGATION ACTIVATION INHIBITOR) - CROTALUS BASILISCUS (MEXICAN WEST-COAST RATTLESNAKE).
DISI_CROCC DISINTEGRIN CERASTIN (PLATELET AGGREGATION ACTIVATION INHIBITOR) - CROTALUS CERASTES CERASTES (MOJAVE DESERT SIDEWINDER).
DISI_CROMM DISINTEGRIN MOLOSSIN (PLATELET AGGREGATION ACTIVATION INHIBITOR) - CROTALUS MOLOSSUS MOLOSSUS (NORTHERN BLACK-TAILED RATTLESNAKE).
DISI_CROVE DISINTEGRIN CEREBERIN (PLATELET AGGREGATION ACTIVATION INHIBITOR) - CROTALUS VIRIDIS CERBERUS (ARIZONA BLACK RATTLESNAKE).
DISI_CROVL DISINTEGRIN LUTOSIN (PLATELET AGGREGATION ACTIVATION INHIBITOR) - CROTALUS VIRIDIS LUTOSUS (GREAT BASIN RATTLESNAKE).
DISI_CROVV DISINTEGRIN VIRIDIN (PLATELET AGGREGATION ACTIVATION INHIBITOR) - CROTALUS VIRIDIS VIRIDIS (PRAIRIE RATTLESNAKE).
DISI_ECHCA DISINTEGRIN ECHISTATIN (PLATELET AGGREGATION ACTIVATION INHIBITOR) (CARINATIN) - ECHIS CARINATUS (SAW-SCALED VIPER).
DISI_ERIMA DISINTEGRIN ERISTICOPHIN (PLATELET AGGREGATION ACTIVATION INHIBITOR) - ERISTOCOPHIS MACMAHONI (LEAF-NOSED VIPER).
DISI_LACMU DISINTEGRIN LACHESIN (PLATELET AGGREGATION ACTIVATION INHIBITOR) - LACHESIS MUTA MUTA (BUSHMASTER).
DISI_SISBA DISINTEGRIN BARBOURIN (PLATELET AGGREGATION ACTIVATION INHIBITOR) - SISTRURUS BARBOURI (SOUTHEASTERN PIGMY RATTLESNAKE).
DISI_SISTE DISINTEGRIN TERGEMININ (PLATELET AGGREGATION ACTIVATION INHIBITOR) - SISTRURUS TERGEMINUS (RATTLESNAKE).
DISI_TRIEL DISINTEGRIN ELEGANTIN (PLATELET AGGREGATION ACTIVATION INHIBITOR) - TRIMERESURUS ELEGANS (SAKISHIMA HABU).
DISI_TRIFL DISINTEGRIN FLAVOSTATIN (RGD-CONTAINING PEPTIDE) (PLATELET AGGREGATION ACTIVATION INHIBITOR) - TRIMERESURUS FLAVOVIRIDIS (HABU).
DISR_AGKRH HEMORRHAGIC PROTEIN-RHODOSTOMIN PRECURSOR (EC 3.4.24.-) (RHO) [CONTAINS: DISINTEGRIN RHODOSTOMIN] - AGKISTRODON RHODOSTOMA (MALAYAN PIT VIPER) (CALLOSELASMA RHODOSTOMA).
DIST_TRIFL DISINTEGRIN TRIFLAVIN (RGD-CONTAINING PEPTIDE) (PLATELET AGGREGATION ACTIVATION INHIBITOR) - TRIMERESURUS FLAVOVIRIDIS (HABU).
HR1B_TRIFL HEMORRHAGIC METALLOPROTEINASE HR1B (EC 3.4.24.52) (TRIMERELYSIN I) - TRIMERESURUS FLAVOVIRIDIS (HABU).
HRTE_CROAT HEMORRHAGIC METALLOPROTEINASE HT-E PRECURSOR (EC 3.4.24.44) (ATROLYSIN E) (HEMORRHAGIC TOXIN E) - CROTALUS ATROX (WESTERN DIAMONDBACK RATTLESNAKE).
O35227 A DISINTEGRIN AND METALLOPROTEASE DOMAIN (ADAM 7) - MUS MUSCULUS (MOUSE).
O42138 METALLOPROTEINASE-DISINTEGRIN-LIKE PROTEIN (EC 3.4.24.-) - AGKISTRODON CONTORTRIX LATICINCTUS.
O57413 TRIMUTASE PRECURSOR (EC 3.4.24.-) - TRIMERESURUS MUCROSQUAMATUS (TAIWAN HABU).
O93523 BOTHROPASIN (EC 3.4.24.49) - BOTHROPS JARARACA (JARARACA).
P70505 FERTILIN ALPHA - RATTUS NORVEGICUS (RAT).
Q28475 EPIDIDYMAL APICAL PROTEIN I-PRECURSOR - MACACA FASCICULARIS (CRAB EATING MACAQUE) (CYNOMOLGUS MONKEY).
Q63180 EPIDIDYMAL APICAL PROTEIN I-PRECURSOR - RATTUS NORVEGICUS (RAT).
Q90220 HALYSTATIN PRECURSOR (EC 3.4.24.-) - GLOYDIUS HALYS (HALYS VIPER).
Q90282 CATROCOLLASTATIN PRECURSOR (EC 3.4.24.-) - CROTALUS ATROX (WESTERN DIAMONDBACK RATTLESNAKE).
Q90495 ECARIN PRECURSOR - ECHIS CARINATUS (SAW-SCALED VIPER).
Q90499 METALLOPROTEASE (EC 3.4.24.-) - ECHIS PYRAMIDUM (CARPET VIPER).
Q91505 TRIMUCIN PRECURSOR (EC 3.4.24.-) - TRIMERESURUS MUCROSQUAMATUS (TAIWAN HABU).
Q98995 LEBETASE LE3 PRECURSOR (EC 3.4.24.-) - VIPERA LEBETINA (ELEPHANT SNAKE) (LEVENTINE VIPER).
Scan History
OWL22_1    2  100  NSINGLE    
OWL26_0 1 100 NSINGLE
SPTR37_9f 2 50 NSINGLE
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
CGHGDCCEQCKFSKSGTECR DISJ_BOTJA 403 403 -
CADGLCCDQCRFIKKGTVCR DISI_CROAT 28 28 -
CAEGLCCDQCRFKGAGKICR DISI_BOTAT 29 29 -
CADGLCCDQCRFKKKRTICR DIST_TRIFL 27 27 -
CAEGLCCDQCKFMKEGTVCR DISI_AGKPI 29 29 -
CADGLCCDQCRFKKKTGICR DISF_TRIFL 27 27 -
CGEGLCCDQCSFIEEGTVCR DISA_TRIGA 436 436 -
CESGPCCRNCKFLKEGTICK DISI_ECHCA 2 2 -

Motif 2 width=13
Element Seqn Id St Int Rpt
DYCNGKTCDCPRN DISI_ECHCA 30 8 -
EHCTGQSSECPAD DISJ_BOTJA 432 9 -
DTCTGQSADCPRN DISI_CROAT 56 8 -
DRCTGQSADCPRN DISI_BOTAT 57 8 -
DRCTGQSADCPRW DIST_TRIFL 55 8 -
DYCNGISAGCPRN DISI_AGKPI 56 7 -
DRCTGLSNDCPRW DISF_TRIFL 55 8 -
DYCNGRSAGCPRN DISA_TRIGA 464 8 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
CAEGLCCDQCRFIKKGKICR DISI_CROBA 28 28 -
CAEGLCCDQCRFIKKGKICR DISI_LACMU 29 29 -
CAEGLCCDQCRFIKKGKICR DISI_CROVE 29 29 -
CAEGLCCDQCRFKKKRTICR O57413 437 437 -
CAEGLCCDQCRFKKKRTICR Q91505 437 437 -
CADGLCCDQCRFIKKGKICR DISI_CROMM 29 29 -
CADGLCCDQCRFIKKGKICR DISI_CROVV 28 28 -
CAEGLCCDQCRFMKKGTVCR HRTE_CROAT 434 434 -
CADGLCCDQCRFKKKRTICR DISI_TRIEL 29 29 -
CADGLCCDQCRFKKKRTICR DISI_TRIFL 27 27 -
CADGLCCDQCRFMKKGTVCR DISI_CROCC 29 29 -
CADGLCCDQCRFMKKGTVCR DISI_SISTE 29 29 -
CADGLCCDQCRFMKKGTVCR DISI_SISBA 29 29 -
CADGLCCDQCRFIKKGTVCR DISI_CROVL 29 29 -
CADGLCCDQCRFIKKGTVCR DISI_CROAT 28 28 -
CAEGLCCDQCRFKGAGKICR DISI_BOTJA 29 29 -
CAEGLCCDQCRFKGAGKICR DISI_BOTCO 29 29 -
CAEGLCCDQCRFKGAGKICR DISI_BOTAT 29 29 -
CADGLCCDQCRFKKKRTICR DIST_TRIFL 27 27 -
CAEGLCCDQCRFKKKGTICR DISC_TRIFL 32 32 -
CAEGLCCDQCRFMKKGTVCR DISI_AGKHA 29 29 -
CAEGLCCDQCRFMKKGTVCR Q90220 436 436 -
CGEGLCCEQCKFSRAGKICR DISI_AGKRH 27 27 -
CGEGLCCEQCKFSRAGKICR DISR_AGKRH 434 434 -
CGEGLCCDQCSFMKKGTICR DISG_TRIGA 29 29 -
CAEGLCCDQCKFMKEGTVCR DISI_AGKPI 29 29 -
CADGLCCDQCRFKKKTGICR DISF_TRIFL 27 27 -
CGEGPCCDQCSFMKKGTICR DISB_TRIGA 29 29 -
CNYGECCDQCRFKKAGTVCR DISI_BITAR 42 42 -
CGEGLCCDQCSFIEEGTVCR DISA_TRIGA 436 436 -
CADGVCCDQCRFTRAGTECR O42138 443 443 -
CESGECCDQCRFRTAGTECR HR1B_TRIFL 251 251 -
CGNGECCDKCKIRKAGTECR Q90495 445 445 -
CATGPCCRRCKFKRAGKVCR DISI_ERIMA 7 7 -
CADGECCNQCRFRPARTECR Q90499 444 444 -
CGHGDCCEQCKFSKSGTECR Q90282 441 441 -
CGHGDCCEQCKFSKSGTECR O93523 442 442 -
CVSGKCCRNCKFLRAGTVCK Q98995 434 434 -
CESGPCCRNCKFLKEGTICK DISI_ECHCA 2 2 -
CAEGECCESCQIKKAGSICR Q28475 442 442 -
CVEGECCESCQMKKEGVICR Q63180 441 441 -
CVEGECCESCQMKKEGAVCR O35227 441 441 -
CSEGLCCYKCTFKKKGTLCR P70505 479 479 -

Motif 2 width=13
Element Seqn Id St Int Rpt
DRCTGQSADCPRN DISI_CROBA 56 8 -
DRCTGQSADCPRN DISI_LACMU 57 8 -
DRCTGQSADCPRN DISI_CROVE 57 8 -
DRCTGQSADCPRN O57413 465 8 -
DRCTGQSADCPRN Q91505 465 8 -
DRCTGQSADCPRN DISI_CROMM 57 8 -
DRCTGQSADCPRN DISI_CROVV 56 8 -
DTCTGQSADCPRN HRTE_CROAT 462 8 -
DRCTGQSADCPRN DISI_TRIEL 57 8 -
DRCTGQSADCPRN DISI_TRIFL 55 8 -
DTCTGQSADCPRN DISI_CROCC 57 8 -
DTCTGQSADCPRN DISI_SISTE 57 8 -
DTCTGQSADCPRN DISI_SISBA 57 8 -
DTCTGQSADCPRN DISI_CROVL 57 8 -
DTCTGQSADCPRN DISI_CROAT 56 8 -
DRCTGQSADCPRN DISI_BOTJA 57 8 -
DRCTGQSADCPRN DISI_BOTCO 57 8 -
DRCTGQSADCPRN DISI_BOTAT 57 8 -
DRCTGQSADCPRW DIST_TRIFL 55 8 -
DRCTGLSDDCPRW DISC_TRIFL 60 8 -
DYCNGISAGCPRN DISI_AGKHA 57 8 -
DYCNGISAGCPRN Q90220 464 8 -
DRCTGQSADCPRY DISI_AGKRH 55 8 -
DRCTGQSADCPRY DISR_AGKRH 462 8 -
DYCNGISAGCPRN DISG_TRIGA 57 8 -
DYCNGISAGCPRN DISI_AGKPI 56 7 -
DRCTGLSNDCPRW DISF_TRIFL 55 8 -
DYCNGRSAGCPRN DISB_TRIGA 57 8 -
DYCTGKSSDCPWN DISI_BITAR 70 8 -
DYCNGRSAGCPRN DISA_TRIGA 464 8 -
DLCTGQSAECPTD O42138 472 9 -
ESCTGQSADCPTD HR1B_TRIFL 280 9 -
EHCTGQSAECPRN Q90495 474 9 -
DYCTGKSCDCPRN DISI_ERIMA 35 8 -
EYCTGQSGECPLD Q90499 473 9 -
EHCTGQSSECPAD Q90282 470 9 -
EHCTGQSSECPAD O93523 471 9 -
DYCTGISSDCPRN Q98995 462 8 -
DYCNGKTCDCPRN DISI_ECHCA 30 8 -
EMCTGHSPACPKD Q28475 471 9 -
EVCTGYSPECPKD Q63180 470 9 -
EVCTGYSPECPKD O35227 470 9 -
EYCNGITGECPAN P70505 508 9 -