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PR00334

Identifier
KININOGEN  [View Relations]  [View Alignment]  
Accession
PR00334
No. of Motifs
3
Creation Date
27-JUL-1992  (UPDATE 10-JUN-1999)
Title
HMW kininogen signature
Database References

INTERPRO; IPR002395
Literature References
1. COLMAN, R.W. AND MULLER-ESTERL, W. 
Nomenclature of kininogens.
THROMB.HAEMOSTASIS 60 340-341 (1988).
 
2. SUGO, T., IKARA, N., KATO, H., IWANAGA, S. AND FUJII, S.
Functional sites of bovine high molecular weight kininogen as a cofactor in
kaolin-mediated activation of factor XII (Hageman Factor).
BIOCHEMISTRY 19 3215-3220 (1980).
 
3. DE LA CADENA, R. AND COLMAN, R.W.
The sequence HGLGHGHEQQHGLGHGH in the light chain of high molecular weight
kininogen serves as a primary structural feature for zinc-dependent binding
to an anionic surface.
PROTEIN SCI. 1 151-160 (1992).

Documentation
High molecular weight kininogen (HK) [1] is synthesised as a single poly-
peptide chain in the liver and secreted into the plasma, where it complexes
with prekallikrein and factor XI. On cleavage by human plasma kallikrein,
or factor XIIa, HK liberates bradykinin, which mimics inflammatory 
phenomena such as pain induction, vasodilation and increased vascular
permeability. The mature HK protein comprises 626 residues. Kallikrein-
cleavage yields the nonapeptide bradykinin, together with a cleaved product
containing an N-terminal heavy chain, bound to a C-terminal light chain by
a single interchain disulphide bridge.
 
Cleavage of HK is required for expression of its procoagulant activity,
which is contained in the light chain. This activity depends on a number of
factors, including the binding of cleaved HK to anionic surfaces [2], which
function is thought to be mediated through a His-Gly-rich region. Recent 
evidence has suggested that critical amino acid sequences within the 
His-Gly-rich region of HK serve as a primary structural feature for binding
to a negatively charged surface [3].
 
KININOGEN is a 3-element fingerprint that provides a signature for the
HK family. The fingerprint was derived from an initial alignment of 4 
sequences, the motifs encoding 3 of the His-Gly-rich regions: motif 2
contains part of the putative structural feature identified by De La Cadena
and Colman as responsible for interaction with negatively charged surfaces.
Two iterations on OWL17.1 were required to reach convergence, at which
point a true set comprising 7 sequences was identified.
 
An update on SPTR37_9f identified a true set of 5 sequences.
Summary Information
5 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3555
2000
123
True Positives
KNH1_BOVIN    KNH2_BOVIN    KNH_HUMAN     KNH_RAT       
O08677
Sequence Titles
KNH1_BOVIN  KININOGEN, HMW I PRECURSOR (THIOL PROTEINASE INHIBITOR) [CONTAINS: BRADYKININ] - BOS TAURUS (BOVINE). 
KNH2_BOVIN KININOGEN, HMW II PRECURSOR (THIOL PROTEINASE INHIBITOR) [CONTAINS: BRADYKININ] - BOS TAURUS (BOVINE).
KNH_HUMAN KININOGEN, HMW PRECURSOR (ALPHA-2-THIOL PROTEINASE INHIBITOR) [CONTAINS: BRADYKININ] - HOMO SAPIENS (HUMAN).
KNH_RAT KININOGEN, HMW PRECURSOR [CONTAINS: BRADYKININ] - RATTUS NORVEGICUS (RAT).
O08677 KININOGEN PRECURSOR (HMW PREKININOGEN) - MUS MUSCULUS (MOUSE).
Scan History
OWL17_0    2  50   NSINGLE    
OWL18_0 1 50 NSINGLE
OWL19_1 1 50 NSINGLE
OWL26_0 1 50 NSINGLE
SPTR37_9f 2 10 NSINGLE
Initial Motifs
Motif 1  width=22
Element Seqn Id St Int Rpt
RDSGKEQGPTHGHGWDHGKQIK KNH1_BOVIN 415 415 -
RDSGKEQGHTRRHDWGHEKQRK KNH_HUMAN 416 416 -
RDSGKEQGHTRRHDWGHEKQRK A27899 39 39 -
RDSGKEQGPTHGHGWDHGKQIK KNH2_BOVIN 413 413 -

Motif 2 width=24
Element Seqn Id St Int Rpt
GLGHKHKHDQGHGHHRSHGLGHGH KNH2_BOVIN 439 4 -
GHGHKHERDQGHGHQRGHGLGHGH A27899 64 3 -
GLGHKHKHDQGHGHHGSHGLGHGH KNH1_BOVIN 441 4 -
GHGHKHERDQGHGHQRGHGLGHGH KNH_HUMAN 441 3 -

Motif 3 width=23
Element Seqn Id St Int Rpt
GHKHKHGHGHGKHKNKGKKNGKH KNH_HUMAN 493 28 -
GHGHKHGHGHGKHKNKGKNNGKH KNH2_BOVIN 469 6 -
GHKHKHGHGHGKHKNKGKKNGKH A27899 116 28 -
GHGHKHGHGHGKHKNKGKNNGKH KNH1_BOVIN 471 6 -
Final Motifs
Motif 1  width=22
Element Seqn Id St Int Rpt
RDSGKEQGPTHGHGWDHGKQIK KNH2_BOVIN 413 413 -
RDSGKEQGPTHGHGWDHGKQIK KNH1_BOVIN 415 415 -
RDPGNEQGPIHGHGWLHAKQIK KNH_RAT 414 414 -
RDSGKEQGHTRRHDWGHEKQRK KNH_HUMAN 416 416 -
RDAETEQGPTHGHGWLHEKQIK O08677 413 413 -

Motif 2 width=24
Element Seqn Id St Int Rpt
GLGHKHKHDQGHGHHRSHGLGHGH KNH2_BOVIN 439 4 -
GLGHKHKHDQGHGHHGSHGLGHGH KNH1_BOVIN 441 4 -
HQGHKHGHGIGHGHQKPHGLGHGH KNH_RAT 439 3 -
GHGHKHERDQGHGHQRGHGLGHGH KNH_HUMAN 441 3 -
HRGHKHGHDHGHWSPRRHGLGHGH O08677 439 4 -

Motif 3 width=23
Element Seqn Id St Int Rpt
GHGHKHGHGHGKHKNKGKNNGKH KNH2_BOVIN 469 6 -
GHGHKHGHGHGKHKNKGKNNGKH KNH1_BOVIN 471 6 -
GHGHGHGHGRDKHTNKDKNNVKH KNH_RAT 492 29 -
GHKHKHGHGHGKHKNKGKKNGKH KNH_HUMAN 493 28 -
GHGHGHGHGHGKHTNKDKNSVKQ O08677 514 51 -