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PR00777

Identifier
HIRUDIN  [View Relations]  [View Alignment]  
Accession
PR00777
No. of Motifs
4
Creation Date
01-SEP-1997  (UPDATE 10-JUN-1999)
Title
Hirudin signature
Database References

PFAM; PF00713 Hirudin
INTERPRO; IPR000429
PDB; 2HIR
SCOP; 2HIR
CATH; 2HIR
Literature References
1. HARVEY, R.P., DEGRYSE, E., STEFANI, L., SCHAMBER, F., CAZENAVE, J.P.,
COURTNEY, M., TOLSTOSHEV, P. AND LECOCQ, J.P.
Cloning and expression of a cdna coding for the anticoagulant hirudin from
the bloodsucking leech, Hirudo medicinalis.
PROC.NATL.ACAD.SCI.U.S.A. 83(4) 1084-1088 (1986).
 
2. FOLKERS, P.J., CLORE, G.M., DRISCOLL, P.C., DODT, J., KOHLER, S.
AND GRONENBORN, A.M. 
Solution structure of recombinant hirudin and the Lys-47-Glu mutant: 
a nuclear magnetic resonance and hybrid distance geometry-dynamical
simulated annealing study. 
BIOCHEMISTRY 28(6) 2601-2617 (1989).
 
3. RYDEL, T.J., RAVICHANDRAN, K.G., TULINSKY, A., BODE, W., HUBER, R.,
ROITSCH, C. AND FENTON, J.W.
The structure of a complex of recombinant hirudin and human alpha-thrombin. 
SCIENCE 249 277-280 (1990).

Documentation
Hirudin is a potent thrombin inhibitor secreted by the salivary glands of
the medicinal leech, Hirudo medicinalis [1]. It forms a stable non-covalent
complex with alpha-thrombin, thereby abolishing its ability to cleave
fibrinogen. The protein belongs to the hirudin family.
 
The structure of hirudin has been solved by NMR [2], and the structure 
of a recombinant hirudin-thrombin complex has been determined by X-ray
crystallography to 2.3A [3]. Hirudin consists of an N-terminal globular
domain and an extended C-terminal domain. Residues 1-3 form a parallel beta-
strand with residues 214-217 of thrombin, the nitrogen atom of residue 1
making a hydrogen bond with the Ser195 O gamma atom of the catalytic site.
The C-terminal domain makes numerous electrostatic interactions with an
anion-binding exosite of thrombin, while the last five residues are in
a helical loop that forms many hydrophobic contacts [3].
 
HIRUDIN is a 4-element fingerprint that provides a signature for hirudins.
The fingerprint was derived from an initial alignment of 16 sequences: the
motifs were drawn from conserved regions spanning the full alignment
length - motif 1 encodes 2 beta-turns; motif 2 spans 4 turns and the
first short beta-strand; and motif 3 spans the second strand and a gamma-
turn. Two iterations on OWL29.4 were required to reach convergence, at
which point a true set comprising 19 sequences was identified. Two
partial matches were found, both of which are family members that fail
to make significant matches with one or more motifs. 
 
An update on SPTR37_9f identified a true set of 15 sequences, and 1
partial match.
Summary Information
  15 codes involving  4 elements
1 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
415151515
31110
20000
1234
True Positives
ITH1_HIRME    ITH2_HIRME    ITH6_HIRMA    ITHC_HIRME    
ITHD_HIRME ITHE_HIRME ITHF_HIRME ITHG_HIRME
ITHH_HIRME ITHI_HIRME ITHJ_HIRME ITHK_HIRME
ITHV_HIRMA Q07557 Q07558
True Positive Partials
Codes involving 3 elements
ITHP_HIRMA
Sequence Titles
ITH1_HIRME  HIRUDIN VARIANT-1 (LEPIRUDIN) - HIRUDO MEDICINALIS (MEDICINAL LEECH). 
ITH2_HIRME HIRUDIN PA - HIRUDO MEDICINALIS (MEDICINAL LEECH).
ITH6_HIRMA HIRUDIN P6 - HIRUDINARIA MANILLENSIS (BUFFALO LEECH).
ITHC_HIRME HIRUDIN IIA - HIRUDO MEDICINALIS (MEDICINAL LEECH).
ITHD_HIRME HIRUDIN II - HIRUDO MEDICINALIS (MEDICINAL LEECH).
ITHE_HIRME HIRUDIN II' - HIRUDO MEDICINALIS (MEDICINAL LEECH).
ITHF_HIRME HIRUDIN IIB - HIRUDO MEDICINALIS (MEDICINAL LEECH).
ITHG_HIRME HIRUDIN IIIA - HIRUDO MEDICINALIS (MEDICINAL LEECH).
ITHH_HIRME HIRUDIN IIIA' - HIRUDO MEDICINALIS (MEDICINAL LEECH).
ITHI_HIRME HIRUDIN III - HIRUDO MEDICINALIS (MEDICINAL LEECH).
ITHJ_HIRME HIRUDIN IIIB - HIRUDO MEDICINALIS (MEDICINAL LEECH).
ITHK_HIRME HIRUDIN IIIB' - HIRUDO MEDICINALIS (MEDICINAL LEECH).
ITHV_HIRMA HIRUDIN HV1 (BUFRUDIN) - HIRUDINARIA MANILLENSIS (BUFFALO LEECH).
Q07557 HIRUDIN HM2 PRECURSOR (BUFRUDIN) - HIRUDINARIA MANILLENSIS (BUFFALO LEECH).
Q07558 HIRUDIN HM1 PRECURSOR - HIRUDINARIA MANILLENSIS (BUFFALO LEECH).

ITHP_HIRMA HIRULLIN P18 (THROMBIN INHIBITOR HIRULLIN P18) (HIRUDIN P18) - HIRUDINARIA MANILLENSIS (BUFFALO LEECH).
Scan History
OWL29_4    2  50   NSINGLE    
SPTR37_9f 2 24 NSINGLE
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
VYTDCTESGQNLCLC ITH1_HIRME 2 2 -
TYTDCTESGQNLCLC ITHF_HIRME 2 2 -
TYTDCTESGQNLCLC ITHC_HIRME 2 2 -
VYTDCTESGQNLCLC ITHK_HIRME 2 2 -
VYTDCTESGQNLCLC ITHI_HIRME 2 2 -
SYTDCTESGQNYCLC S33329 22 22 -
SYTDCTESGQNYCLC S33328 22 22 -
SYTDCTESGQNYCLC A53883 2 2 -
TYTDCTESGQNLCLC ITH3_HIRME 9 9 -
RYTACTESGQNQCIC ITH6_HIRMA 2 2 -
TYTDCTESGQNLCLC ITH2_HIRME 2 2 -
VYTDCTESGEDLCLC ITHH_HIRME 2 2 -
TYTDCTESGQDLCLC ITHE_HIRME 2 2 -
VYTDCTESGQNLCLC ITHJ_HIRME 2 2 -
TYTDCTESGQDLCLC ITHD_HIRME 2 2 -
VYTDCTESGQNLCLC ITHG_HIRME 2 2 -

Motif 2 width=13
Element Seqn Id St Int Rpt
CEDSNVCGQGNKC ITHI_HIRME 16 -1 -
CEGSNVCGKGNKC ITH3_HIRME 23 -1 -
CVGSNVCGEGKNC A53883 16 -1 -
CVGSNVCGEGKNC S33329 36 -1 -
CVGGNLCGGGKHC S33328 36 -1 -
CEGSNVCGQGNKC ITH1_HIRME 16 -1 -
CEGSNVCGKGNKC ITHF_HIRME 16 -1 -
CEGSNVCGNGNKC ITHC_HIRME 16 -1 -
CQGSNVCGQGNKC ITHK_HIRME 16 -1 -
CEDSNVCGEGNKC ITHG_HIRME 16 -1 -
CEGSNVCGKGNKC ITHD_HIRME 16 -1 -
CQDSNVCGQGNKC ITHJ_HIRME 16 -1 -
CEGSDVCGKGNKC ITHE_HIRME 16 -1 -
CEGSNVCGEGNKC ITHH_HIRME 16 -1 -
CEGSNVCGKGNKC ITH2_HIRME 16 -1 -
CEGNDVCGQGRNC ITH6_HIRMA 16 -1 -

Motif 3 width=16
Element Seqn Id St Int Rpt
NGKGNQCVTGEGTPNP ITH3_HIRME 40 4 -
DGEKNQCVTGEGTPKP ITH1_HIRME 33 4 -
NGEENQCVTGEGTPKP ITHF_HIRME 33 4 -
DGEENQCVTGEGTPKP ITHC_HIRME 33 4 -
NGEKNQCVTGEGTPKP ITHK_HIRME 33 4 -
NGEKNQCVTGEGTPKP ITHI_HIRME 33 4 -
NGEKNQCVTGEGTPKP ITHG_HIRME 33 4 -
NGEENQCVTGEGTPKP ITHD_HIRME 33 4 -
NGEKNQCVTGEGTPKP ITHJ_HIRME 33 4 -
NGEENQCVTGEGTPKP ITHE_HIRME 33 4 -
DGEKNECVTGEGTPKP ITHH_HIRME 33 4 -
QGKDNQCVTGEGTPKP ITH2_HIRME 33 4 -
DSSGKKCVEGEGTRKP ITH6_HIRMA 31 2 -
DGSGNKCVDGEGTPKP S33328 51 2 -
SSSGNQCVHGEGTPKP S33329 51 2 -
SSSGNQCVHGEGTPKP A53883 31 2 -

Motif 4 width=16
Element Seqn Id St Int Rpt
PQSHNDGDFEEIPEEY ITHC_HIRME 48 -1 -
PQSHNDGDFEEIPEEY ITHG_HIRME 48 -1 -
PQSHNDGDFEEIPEEY ITHD_HIRME 48 -1 -
PQSHNDGDFEEIPEEY ITHJ_HIRME 48 -1 -
PQSHNDGDFEEIPEEY ITHE_HIRME 48 -1 -
PQSHNDGDFEEIPEEY ITHH_HIRME 48 -1 -
PQSHNQGDFEPIPEDA ITH2_HIRME 48 -1 -
PQNEGQHDFDPIPEEY ITH6_HIRMA 46 -1 -
PQSHNDGDFEEIPEEY ITHK_HIRME 48 -1 -
PQSHNDGDFEEIPEEY ITHI_HIRME 48 -1 -
PQSHNDGDFEEIPEEY ITHF_HIRME 48 -1 -
PQSHNDGDFEEIPEEY ITH1_HIRME 48 -1 -
PKSQTEGDFEEIPDED S33328 66 -1 -
PKSQTEGDFEEIPDED S33329 66 -1 -
PKSQTEGDFEEIPDEX A53883 46 -1 -
PESHNNGDFEEIPEEY ITH3_HIRME 55 -1 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
VYTDCTESGQNLCLC ITH1_HIRME 2 2 -
TYTDCTESGQNLCLC ITHF_HIRME 2 2 -
TYTDCTESGQNLCLC ITHC_HIRME 2 2 -
VYTDCTESGQNLCLC ITHK_HIRME 2 2 -
VYTDCTESGQNLCLC ITHI_HIRME 2 2 -
VYTDCTESGQNLCLC ITHG_HIRME 2 2 -
TYTDCTESGQDLCLC ITHD_HIRME 2 2 -
VYTDCTESGQNLCLC ITHJ_HIRME 2 2 -
TYTDCTESGQDLCLC ITHE_HIRME 2 2 -
VYTDCTESGEDLCLC ITHH_HIRME 2 2 -
TYTDCTESGQNLCLC ITH2_HIRME 2 2 -
SYTDCTESGQNYCLC Q07557 22 22 -
SYTDCTESGQNYCLC ITHV_HIRMA 2 2 -
SYTDCTESGQNYCLC Q07558 22 22 -
RYTACTESGQNQCIC ITH6_HIRMA 2 2 -

Motif 2 width=13
Element Seqn Id St Int Rpt
CEGSNVCGQGNKC ITH1_HIRME 16 -1 -
CEGSNVCGKGNKC ITHF_HIRME 16 -1 -
CEGSNVCGNGNKC ITHC_HIRME 16 -1 -
CQGSNVCGQGNKC ITHK_HIRME 16 -1 -
CEDSNVCGQGNKC ITHI_HIRME 16 -1 -
CEDSNVCGEGNKC ITHG_HIRME 16 -1 -
CEGSNVCGKGNKC ITHD_HIRME 16 -1 -
CQDSNVCGQGNKC ITHJ_HIRME 16 -1 -
CEGSDVCGKGNKC ITHE_HIRME 16 -1 -
CEGSNVCGEGNKC ITHH_HIRME 16 -1 -
CEGSNVCGKGNKC ITH2_HIRME 16 -1 -
CVGSNVCGEGKNC Q07557 36 -1 -
CVGSNVCGEGKNC ITHV_HIRMA 16 -1 -
CVGGNLCGGGKHC Q07558 36 -1 -
CEGNDVCGQGRNC ITH6_HIRMA 16 -1 -

Motif 3 width=16
Element Seqn Id St Int Rpt
DGEKNQCVTGEGTPKP ITH1_HIRME 33 4 -
NGEENQCVTGEGTPKP ITHF_HIRME 33 4 -
DGEENQCVTGEGTPKP ITHC_HIRME 33 4 -
NGEKNQCVTGEGTPKP ITHK_HIRME 33 4 -
NGEKNQCVTGEGTPKP ITHI_HIRME 33 4 -
NGEKNQCVTGEGTPKP ITHG_HIRME 33 4 -
NGEENQCVTGEGTPKP ITHD_HIRME 33 4 -
NGEKNQCVTGEGTPKP ITHJ_HIRME 33 4 -
NGEENQCVTGEGTPKP ITHE_HIRME 33 4 -
DGEKNECVTGEGTPKP ITHH_HIRME 33 4 -
QGKDNQCVTGEGTPKP ITH2_HIRME 33 4 -
SSSGNQCVHGEGTPKP Q07557 51 2 -
SSSGNQCVHGEGTPKP ITHV_HIRMA 31 2 -
DGSGNKCVDGEGTPKP Q07558 51 2 -
DSSGKKCVEGEGTRKP ITH6_HIRMA 31 2 -

Motif 4 width=16
Element Seqn Id St Int Rpt
PQSHNDGDFEEIPEEY ITH1_HIRME 48 -1 -
PQSHNDGDFEEIPEEY ITHF_HIRME 48 -1 -
PQSHNDGDFEEIPEEY ITHC_HIRME 48 -1 -
PQSHNDGDFEEIPEEY ITHK_HIRME 48 -1 -
PQSHNDGDFEEIPEEY ITHI_HIRME 48 -1 -
PQSHNDGDFEEIPEEY ITHG_HIRME 48 -1 -
PQSHNDGDFEEIPEEY ITHD_HIRME 48 -1 -
PQSHNDGDFEEIPEEY ITHJ_HIRME 48 -1 -
PQSHNDGDFEEIPEEY ITHE_HIRME 48 -1 -
PQSHNDGDFEEIPEEY ITHH_HIRME 48 -1 -
PQSHNQGDFEPIPEDA ITH2_HIRME 48 -1 -
PKSQTEGDFEEIPDED Q07557 66 -1 -
PKSQTEGDFEEIPDEX ITHV_HIRMA 46 -1 -
PKSQTEGDFEEIPDED Q07558 66 -1 -
PQNEGQHDFDPIPEEY ITH6_HIRMA 46 -1 -