1 / 17

PRINTS Overview

PRINTS Overview. PRINTS - a database of protein family “ fingerprints ” Fingerprints - groups of motifs excised from alignments used to provide diagnostic signatures for protein families Used in gene family analysis, genome annotation , etc . PRINTS forms basis of derived resources

cosmo
Télécharger la présentation

PRINTS Overview

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. PRINTS Overview • PRINTS - a database of protein family “fingerprints” • Fingerprints - groups of motifs excised from alignments • used to providediagnostic signaturesfor protein families • Used in gene family analysis, genome annotation, etc. • PRINTS forms basis of derived resources • e.g., blocks, emotif,InterPro

  2. Advantages of PRINTS • Several other similar resources - PROSITE, Pfam, SMART… • multiple motif matching allows increased sensitivity • PRINTS approach allows diagnosis of protein subfamilies • PROSITE & PRINTS unique in providing substantial amounts of annotation, aiming to • document the constituent families • rationalise conserved regions instructural & functionalterms

  3. Limitations • The annotation process is entirely manual • hence the rate-limiting step in the growth of the database • PROSITE & PRINTS therefore small by comparison with their automatically-derived counterparts

  4. Fingerprint Production

  5. gc; gx; gn; ga; gt; gp; bb; gr; bb; gd; bb; si; SUMMARY INFORMATION si; ------------------- sd; 37 codes involving 8 elements sd; 0 codes involving 7 elements sd; 0 codes involving 6 elements sd; 0 codes involving 5 elements sd; 0 codes involving 4 elements sd; 1 codes involving 3 elements sd; 0 codes involving 2 elements bb; ci; COMPOSITE FINGERPRINT INDEX ci; --------------------------- cr; cd; 8| 37 37 37 37 37 37 37 37 cd; 7| 0 0 0 0 0 0 0 0 cd; 6| 0 0 0 0 0 0 0 0 cd; 5| 0 0 0 0 0 0 0 0 cd; 4| 0 0 0 0 0 0 0 0 cd; 3| 1 0 0 0 1 1 0 0 cd; 2| 0 0 0 0 0 0 0 0 cd; --+----------------------------------------- cd; | 1 2 3 4 5 6 7 8 bb; tp; PRIO_COLGU PRIO_MACFA PRIO_CEREL PRIO_ODOHE KA; P40251 M1 P40254 M1 P79142 M1 P47852 M1 tp; PRIO_GORGO PRIO_PANTR PRIO_HUMAN O46648 KA; P40252 M1 P40253 M1 P04156 M1 O46648 M1 tp; PRIO_SHEEP PRIO_CALJA PRIO_BOVIN PRP2_BOVIN KA; P23907 M1 P40247 M1 P10279 M1 Q01880 M1 bb; tt; PRIO_COLGU MAJOR PRION PROTEIN PRECURSOR (PRP) (PRP27-30) (PRP33-35C) - COLOBUS GUEREZA. tt; PRIO_MACFA MAJOR PRION PROTEIN PRECURSOR (PRP) (PRP27-30) (PRP33-35C) - MACACA FASCICULARIS (CRAB EATING MACAQUE) tt; PRIO_CEREL MAJOR PRION PROTEIN PRECURSOR (PRP) - CERVUS ELAPHUS (RED DEER). tt; PRIO_ODOHE MAJOR PRION PROTEIN PRECURSOR (PRP) - ODOCOILEUS HEMIONUS (MULE DEER) (BLACK-TAILED DEER). tt; PRIO_GORGO MAJOR PRION PROTEIN PRECURSOR (PRP) (PRP27-30) (PRP33-35C) - GORILLA GORILLA GORILLA (LOWLAND GORILLA) tt; PRIO_PANTR MAJOR PRION PROTEIN PRECURSOR (PRP) (PRP27-30) (PRP33-35C) - PAN TROGLODYTES (CHIMPANZEE) tt; PRIO_HUMAN MAJOR PRION PROTEIN PRECURSOR (PRP) (PRP27-30) (PRP33-35C) (ASCR) - HOMO SAPIENS (HUMAN). ‘Naked’ fingerprint

  6. Fingerprint Annotation • Structured fields : • identifier, accession number, title, creation date, etc • literature references • database cross-links • Free text : • function and structure of the protein family • associated diseases • family relationships • Technical information : • fingerprint details • motif locations, etc

  7. Annotated Fingerprint gc; PRION gx; PR00341 gt; Prion protein signature gp; INTERPRO; IPR000817 gp; PROSITE; PS00291 PRION_1; PS00706 PRION_2 gp; BLOCKS; BL00291 gp; PFAM; PF00377 prion bb; gr; 1. STAHL, N. AND PRUSINER, S.B. gr; Prions and prion proteins. gr; FASEB J. 5 2799-2807 (1991). gr; gr; 2. BRUNORI, M., CHIARA SILVESTRINI, M. AND POCCHIARI, M. gr; The scrapie agent and the prion hypothesis. gr; TRENDS BIOCHEM.SCI. 13 309-313 (1988). gr; gr; 3. PRUSINER, S.B. gr; Scrapie prions. gr; ANNU.REV.MICROBIOL. 43 345-374 (1989). bb; gd; Prion protein (PrP) is a small glycoprotein found in high quantity in the brain of animals infected with gd; certain degenerative neurological diseases, such as sheep scrapie and bovine spongiform encephalopathy (BSE), gd; and the human dementias Creutzfeldt-Jacob disease (CJD) and Gerstmann-Straussler syndrome (GSS). PrP is gd; encoded in the host genome and is expressed both in normal and infected cells. During infection, however, the gd; PrP molecules become altered and polymerise, yielding fibrils of modified PrP protein. gd; gd; PrP molecules have been found on the outer surface of plasma membranes of nerve cells, to which they are gd; anchored through a covalent-linked glycolipid, suggesting a role as a membrane receptor. PrP is also gd; expressed in other tissues, indicating that it may have different functions depending on its location. gd; gd; The primary sequences of PrP's from different sources are highly similar: all bear an N-terminal domain gd; containing multiple tandem repeats of a Pro/Gly rich octapeptide; sites of Asn-linked glycosylation; an gd; essential disulphide bond; and 3 hydrophobic segments. These sequences show some similarity to a chicken gd; glycoprotein, thought to be an acetylcholine receptor-inducing activity (ARIA) molecule. It has been gd; suggested that changes in the octapeptide repeat region may indicate a predisposition to disease, but it is gd; not known for certain whether the repeat can meaningfully be used as a fingerprint to indicate susceptibility. gd; gd; PRION is an 8-element fingerprint that provides a signature for the prion proteins. The fingerprint was gd; derived from an initial alignment of 5 sequences: the motifs were drawn from conserved regions spanning gd; virtually the full alignment length, including the 3 hydrophobic domains and the octapeptide repeats gd; (WGQPHGGG). Two iterations on OWL18.0 were required to reach convergence, at which point a true set comprising gd; 9 sequences was identified. Several partial matches were also found: these include a fragment (PRIO_RAT) gd; lacking part of the sequence bearing the first motif,and the PrP homologue found in chicken - this matches gd; well with only 2 of the 3 hydrophobic motifs (1 and 5) and one of the other conserved regions (6), but has an gd; N-terminal signature based on a sextapeptide repeat (YPHNPG) rather than the characteristic PrP octapeptide.

  8. Fingerprint Types • Family : • eg, 5-HT2A receptors • similar structure/function • Super-family : • eg, GPCRs • common structural framework (7 transmembrane helices) • transduce extracellular signals by coupling to G-proteins • often different physiological functions • Domain family : • eg, sequences containing SH2 domains • different structure, functions etc • (non-receptor protein tyrosine kinases, structural proteins such as tensin; small adaptor molecules such as oncoprotein Crk; etc…)

  9. Automatic Annotation via PRECIS

  10. Annotation Mapping

  11. CC field mapping

  12. gc; OPSD gx; PR gn; COMPOUND(12) ga; 21-MAR-2002 gt; Rhodopsin signature gp; PRINTS; PR00237 GPCRRHODOPSN; PR00238 OPSIN; PR00579 RHODOPSIN gp; PROSITE; PS00237 G_PROTEIN_RECEP_F1_1; PS50262 G_PROTEIN_RECEP_F1_2 gp; PROSITE; PS00238 OPSIN gp; PFAM; PF00001 7tm_1 gp; INTERPRO; IPR000276; IPR001760 gp; PDB; 1BOJ; 1BOK; 1EDS; 1EDV; 1EDW; 1EDX; 1F88; 1FDF gp; SCOP; 1BOJ; 1BOK; 1EDS; 1EDV; 1EDW; 1EDX; 1F88; 1FDF gp; CATH; 1BOJ; 1BOK; 1EDS; 1EDV; 1EDW; 1EDX; 1F88; 1FDF gp; MIM; 180380; 268000; 163500 bb; gr; 1. HUNT, D.M., FITZGIBBON, J., SLOBODYANYUK, S.J., BOWMAKER, J.K. AND DULAI, K.S. gr; Molecular evolution of the cottoid fish endemic to Lake Baikal deduced from nuclear DNA gr; evidence. gr; MOL.PHYLOGENET.EVOL. 8 415-422 (1997). gr; gr; 2. FYHRQUIST, N., DONNER, K., HARGRAVE, P.A., MCDOWELL, J.H., POPP, M.P. gr; AND SMITH, W.C. gr; Rhodopsins from three frog and toad species: sequences and functional comparisons. gr; EXP.EYE RES. 66 295-305 (1998). gr; gr; 3. SUNG, C.H., DAVENPORT, C.M., HENNESSEY, J.C., MAUMENEE, I.H., JACOBSON, gr; S.G., HECKENLIVELY, J.R., NOWAKOWSKI, R., FISHMAN, G., GOURAS, P. AND NATHANS, J. gr; Rhodopsin mutations in autosomal dominant retinitis pigmentosa. gr; PROC.NATL.ACAD.SCI.USA 88 6481-6485 (1991). gr; gr;4. PALCZEWSKI, K., KUMASAKA, T., HORI, T., BEHNKE, C.A., MOTOSHIMA, H., FOX, B.A., LE, TRONG, gr;I., TELLER, D.C., OKADA, T., STENKAMP, R.E., YAMAMOTO, M. AND MIYANO, M. gr;Crystal structure of rhodopsin: a G protein-coupled receptor. gr; SCIENCE 289 739-745 (2000). gr; gr;5. YEAGLE, P.L., DANIS, C., CHOI, G., ALDERFER, J.L. AND ALBERT, A.D. gr;Three dimensional structure of the seventh transmembrane helical domain of the G-protein gr;receptor, rhodopsin. gr;MOL.VISION 6 125-131 (2000).

  13. gd; Function: gd; Visual pigments are the light-absorbing molecules that mediate vision. They consist of gd; an apoprotein, opsin, covalently linked to cis-retinal. gd; gd; Additional Information: gd; Integral membrane protein. gd; gd; Disease: gd; Defects in rho are one of the causes of autosomal dominant retinitis pigmentosa (adrp). gd; Patients typically have night vision blindness and loss of midperipheral visual field; gd; as their condition progresses, they lose their far peripheral visual field and gd; eventually central vision as well. (OPSD_HUMAN; P08100; Q16414) gd; gd; Defects in rho are one of the causes of autosomal recessive retinitis pigmentosa (arrp). gd; (OPSD_HUMAN; P08100; Q16414) gd; gd; Defects in rho are also one of the causes of congenital stationary night blindness (csnb4). gd; (OPSD_HUMAN; P08100; Q16414) gd; gd; Family and structural information: gd; The structure has been determined, e.g. "Crystal structure of rhodopsin: a G gd; protein-coupled receptor" [4] and "Three dimensional structure of the seventh gd; transmembrane helical domain of the G-protein receptor, rhodopsin” [5]. gd; gd; Belongs to family 1 of g-protein coupled receptors. Opsin subfamily. gd; gd; Keywords: Retinal protein; Transmembrane; G-protein coupled receptor; Phosphorylation; gd; Lipoprotein; Palmitate; Acetylation; Retinitis pigmentosa; Disease mutation; gd; 3D-structure; Glycoprotein; Vision; Photoreceptor. gd; gd; OPSD is a 12-element fingerprint that provides a signature for the rhodopsin proteins. gd; The fingerprint was derived from an initial alignment of 23 sequences: the motifs were gd; drawn from conserved regions spanning virtually the full alignment length. Two iterations gd; on SPTR40_18f were required to reach convergence, at which point a true set comprising 79 gd; sequences was identified.

  14. Limitations • Annotation SWISS-PROT dependent • only well-structured, annotated sequence database available • inherits SWISS-PROTerrors gd; Polymorphism at position 171 may be related to the gd; alleles of scarpie incubation-control (sic) gene in this species. • fails where SWISS-PROT annotationlimited or inconsistent gd; The muscarinic acetylcholine receptor mediates various cellular responses, including gd; inhibition of adenylate cyclase, breakdown of phosphoinositides & modulation of potassium gd; channels through the action of g proteins. Primary transducing effect is inhibition of gd; adenylate cyclase. gd; The muscarinic acetylcholine receptor mediates various cellular responses, including gd; inhibition of adenylate cyclase, breakdown of phosphoinositides & modulation of potassium gd; channels through the action of g proteins. Primary transducing effect is adenylate gd; cyclase inhibition.

  15. BioMinT • Augmentation of core PRECIS annotation • biological literature abstracts • full texts online • PRECIS as 1st pass in iterative annotation process • Concise SWISS-PROT information wrt families • Synonyms, gene names, etc • Exploitable database X-links (eg, OMIM) • Literature abstracts

More Related