Disease relevance of F11

• Studies of plasmas from individuals with Hageman trait (factor XII deficiency), plasma thromboplastin antecedent (PTA, factor XI) deficiency, Fletcher trait (plasma prekallikrein deficiency) and Fitzgerald trait (high molecular weight-kininogen deficiency) have revealed the importance of these proteins in blood coagulation [1].
• Anti-human FXI antibody significantly reduces thrombus growth in a baboon thrombosis model without bleeding problems (Gruber, A., and Hanson, S. R. (2003) Blood 102, 953-955) [2].
• Plasma thromboplastin antecedent (Factor XI) deficiency in a black family [3].
• Investigation of the WB clotting profile was performed before and after ex vivo addition of rFVIIa 20 nm to WB from 26 patients with hemophilia A, two patients with severe hemophilia B, and individuals with deficiencies of FV, FX, FXI, and FXIII [4].
• A deficiency of FXI is an unusual hemorrhagic diathesis in that the bleeding tendency can be highly variable, ranging from severe deficiencies with no symptoms to mild and moderate deficiencies requiring multiple blood transfusions for hemorrhages [5].

Psychiatry related information on F11

• Patients who achieved independent ambulation were significantly younger (P<.05), had better gait scores on admission (P<.05), and tended to be less severely injured-based on duration of posttraumatic amnesia (PTA; P=.058)-than those who did not ambulate independently [6].
• CONCLUSIONS: These results should influence decision making in the management of claudication and it may be possible to prioritise PTA waiting lists to ensure patients with greatest potential benefit are treated with most urgency [7].
• The earliest stage of recovery from moderate to severe closed head injury is a period of PTA that typically includes memory loss for events preceding and surrounding the injury and memory loss for events occurring since the injury [8].
• In our induction and maintenance therapy group, 32 recipients (65%) underwent a simultaneous pancreas-kidney transplant (SPK), 8 (16%) a pancreas transplant alone (PTA), and 9 (19%) a pancreas after previous kidney transplant (PAK) [9].
• GCS is used for classification by 60%, PTA 48%, retrograde amnesia by 50%, and LOC by 63% of institutions [10].

High impact information on F11

• A neurite outgrowth-promoting activity of F11 characterized by in vitro culture of tectal cells is independent of F11-Ng-CAM and F11-RN binding [11].
• F11 is a glycosyl phosphatidylinositol-anchored axonal surface glycoprotein belonging to a neural subgroup of the immunoglobulin superfamily [11].
• In this report, we demonstrate that the F11 protein displays three distinguishable activities: binding to the cell recognition molecule Ng-CAM, interaction with the extracellular matrix glycoprotein restrictin (RN), and a neurite outgrowth-promoting activity [11].
• The axonal recognition molecule F11 is a multifunctional protein: specific domains mediate interactions with Ng-CAM and restrictin [11].
• By analyzing deletion mutants expressed in transfected COS cells, epitope mapping of monoclonal antibodies, and neurite outgrowth assays, we reveal that these activities can be localized to distinct regions within the F11 protein [11].

Chemical compound and disease context of F11

• Complexes between C1-inhibitor, kallikrein, high molecular weight kininogen, plasma thromboplastin antecedent, and plasmin in normal human plasma and hereditary angioneurotic edema plasmas containing dysmorphic C1-inhibitors: role of cold activation [12].
• We report here the complete cDNA sequence of F11 130 kd polypeptide, a chick neural cell surface-associated glycoprotein implicated in neurite fasciculation and elongation [13].
• The serotypes of P-fimbriae found most frequently among mannose-resistant haemagglutination-positive E. coli from urinary tract infections were the F11, F7 and F8 fimbriae, and among meningitic strains, F11, F8 and F9 fimbriae [14].
• Significant synergistic effects on the toxicity of the six insecticides were found by using PB, TPP, and DEM in F0 parents; on methamidophos, avermectin, and imidacloprid by PB, TPP, and DEM in F11 progeny; on fipronil by PB and DEM in F11 progeny; and on fenvalerate and cypermethrin by PB in F11 progeny [15].
• A conjugative R-plasmid PE004, Inc F11, conferring resistance to ampicillin, tetracycline, streptomycin, kanamycin and trimethoprim was obtained from an E. coli serotype 026 isolate from the stool of a child with acute diarrhoea [16].

Biological context of F11

• However, a synthetic glycoprotein Ibalpha peptide, Asp269-Asp287, containing a thrombin binding site had no effect on the binding of FXI to activated platelets [17].
• Factor XI (FXI), the zymogen of the blood coagulation protease FXIa, and the structurally homologous protein plasma prekallikrein circulate in plasma in noncovalent complexes with H-kininogen (HK) [18].
• Activation of factor XI (FXI) by thrombin on stimulated platelets plays a physiological role in hemostasis, providing additional thrombin generation required in cases of severe hemostatic challenge [19].
• When normal plasma or plasma deficient in HF, PK, HMW-K or PTA was exposed to Sephadex-EA and was separated by centrifugation, each supernatant plasma except that deficient in HF shortened the prolonged partial thromboplastin time (PTT) of HF-deficient plasma [1].
• Dinucleotide repeat polymorphism in the human coagulation factor XI gene, intron B (F11), detected using the polymerase chain reaction [20].

Anatomical context of F11

• Thus, the inhibitor appeared to interfere with these clotting factor assays, possibly by inactivating PTA in the substrate plasmas in the test system [21].
• By immunolocalization techniques, and using specific antibodies directed against the various contact factors, we now demonstrate that plasma prekallikrein (PK), factor XI (FXI), and factor XII (FXII) are present on the exterior face of the human neutrophil [22].
• Single FXI mRNA species were identified by RT-PCR in platelet and bone marrow RNA, but not leukocyte RNA, that are the same size as the message from liver RNA [23].
• Wild-type FXI mRNA was also identified in three leukemia cell lines with megakaryocyte features (MEG-01, HEL 92.1.7, and CHRF-288-11) [23].
• Investigations determined the relative preference of prekallikrein (PK) or factor XI/XIa (FXI/FXIa) binding to endothelial cells (HUVECs) [24].

Associations of F11 with chemical compounds

• Experiments with full-length recombinant FXI mutants show that, in the presence of Zn(2+), glycocalicin binds FXI at a heparin-binding site in A3 (Lys(252) and Lys(253)) and not by amino acids previously shown to be required for platelet binding (Ser(248), Arg(250), Lys(255), Phe(260), and Gln(263)) [25].
• The platelet glycoprotein (GP) Ib-IX-V complex is the receptor for FXI [25].
• Thus, we examined the effect of synthetic peptides of each of the seven leucine-rich repeats on the binding of 125I-FXI to activated platelets [17].
• Using a collection of 53 thrombin mutants, we identified 16 mutants with <50% of the wild-type thrombin FXI-activating activity in the presence of dextran sulfate [19].
• The FXI Apple 3 (A3) domain mediates binding to platelets in the presence of HK and zinc ions (Zn(2+)) or prothrombin and calcium ions [25].

Physical interactions of F11

• We conclude that FXI binds to glycoprotein Ibalpha at sites comprising the leucine-rich repeat sequences within the NH2-terminal globular domain that are separate and distinct from the thrombin-binding site [17].
• Monoclonal antibodies against F2 are superior to F4 or F1 antibodies as inhibitors of HK binding to FXI [18].
• FXI circulates as a complex with the glycoprotein high molecular weight kininogen (HK) [25].
• Nr-CAM can also interact laterally with contactin/F11 within the plasma membrane in the form of a complex that may transmit signals to regulate axonal growth [26].

Regulatory relationships of F11

• All leucine-rich repeat (LRR) peptides derived from glycoprotein Ibalpha were able to inhibit FXI binding to activated platelets in the following order of decreasing potency: LRR7, LRR1, LRR4, LRR5, LRR6, LRR3, and LRR2 [17].
• We have shown previously that F11 promotes neurite extension of chick tectal neurons by interaction with the tectal receptor NrCAM, a member of the L1 subgroup of the Ig superfamily [27].
• Pituitary adenylate cyclase-activating peptide (PACAP) induces differentiation in the neuronal F11 cell line through a PKA-dependent pathway [28].
• These results suggest that the molecular interactions of F11 might be regulated by the presence of tenascin-R and tenascin-C [29].
• Functional interactions of the immunoglobulin superfamily member F11 are differentially regulated by the extracellular matrix proteins tenascin-R and tenascin-C [29].

Other interactions of F11

• In the absence of plasma prekallikrein, maximal activation of plasma thromboplastin antecedent was slightly delayed in plasma, a delay not observed with similarly treated purified Hageman factor [30].
• In addition to a low titer of PTA (less than 0.01 U/ml), plasma assayed at 20-fold dilution also showed low titers of Hageman (factor XII, 0.02 U/ml), Fletcher (plasma prekallikrein, 0.02 U/ml), and Fitzgerald (high molecular weight kininogen, less than 0.01 U/ml) factors [21].
• To determine the contribution of each FXI apple domain to HK-FXI complex formation, we examined binding of recombinant single apple domain-tissue plasminogen activator fusion proteins to HK [18].
• Whale plasma contained inhibitory activities against thrombin, activated Stuart factor, activated PTA, activated Fletcher factor, and plasmin [31].
• Hageman factor (HF, factor XII), adsorbed to negatively charged agents, is transformed to an activated state in which it initiates reactions of the intrinsic pathway of thrombin formation by activating plasma thromboplastin antecedent (PTA, factor XI) [32].

Analytical, diagnostic and therapeutic context of F11

• Using surface plasmon resonance, we determined that FXI binds specifically to glycocalicin, the extracellular domain of GPIbalpha, in a Zn(2+)-dependent fashion (K(d) = approximately 52 nM) [25].
• We mapped the KLK3 gene and the marker KLK3c to the long arm of human chromosome 4 between F11 and D4S426 using a radiation hybrid panel [33].
• A good correlation (correlation coefficient 0.68) existed between the PTA procoagulant assays and radioimmunoassays among 50 normal adults (25 males and 25 females) [34].
• Sequencing of PCR products confirmed that the FXI mRNA species in platelets is identical to the one in liver [23].
• A sensitive ELISA failed to detect FXI antigen in the propositus [35].

References