Disease relevance of HABP2

• Among these genes, overexpression of Lc19, hyaluronan binding protein 2 (HABP2) and crystalline-mu appeared more specific to adenocarcinoma, whereas ceruloplasmin, integrin alpha-11 and collagen type XI alpha 1 were overexpressed at high frequency among both adenocarcinoma and squamous cell carcinoma [1].
• Marburg I polymorphism of factor VII-activating protease and risk of venous thromboembolism [2].
• The factor VII-activating protease (FSAP) variant Marburg I is known to attenuate the profibrinolytic system in vitro and was recently shown to be a significant predictor for the evolution and progression of carotid stenosis [3].
• The Marburg I polymorphism of factor VII-activating protease is not associated with venous thrombosis [4].
• A previous study had shown a strong relationship between a variant in factor VII activating protease (FSAP G511E) and advanced carotid atheroma [5].

Psychiatry related information on HABP2

• Significant differences were observed in the various evaluation scales FSAP (general ability to solve problems), FSSW (general self-esteem), SGKB (state of health), and SKEF (physical fitness) [6].

High impact information on HABP2

• The G534E polymorphism (Marburg I [MI]) of factor VII-activating protease (FSAP) is associated with carotid stenosis and cardiovascular disease [7].
• We have previously demonstrated that FSAP is present in atherosclerotic plaques and it is a potent inhibitor of vascular smooth muscle proliferation and migration in vitro [7].
• These include the ability of a peptide that specifically binds HA (HABR) to reduce locomotion, the ability of HA (0.001-0.1 micrograms/ml), added at 10-30 h after induction to stimulate locomotion back to the original, acute rate, and the ability of an mAb specific to a 56-kD fibroblast HABP to block locomotion [8].
• Hyaluronan (HA) and one of its cell binding sites, fibroblast hyaluronan binding protein (HABP), is shown to contribute to the regulation of 10T1/2 cell locomotion that contain an EJ-ras-metallothionein (MT-1) hybrid gene [8].
• Further, both HA and HABP products are regulated by induction of the ras gene [8].

Biological context of HABP2

• The PHBP gene (HABP2) was located on chromosome 10q25-q26 [9].
• Hyaluronic acid binding protein (HABP) has been purified to homogeneity from normal adult rat kidney by hyaluronate Sepharose affinity chromatography, and its apparent molecular mass was found to be 68 kDa [10].
• The physiological role of FSAP is still speculative, but recent studies suggest a contribution to hemostasis [11].
• Both subunits had novel N-terminal amino acid sequences, indicating that PHBP was a novel hyaluronan-binding protein in human plasma [12].
• Analysis of the respective genomic DNAs revealed one particular single nucleotide polymorphism of FSAP resulting in an identical amino acid exchange (G511E), which correlates with the reduced activities [13].

Anatomical context of HABP2

• Detection of 34 kDa HABP in the serum-free supernatant culture medium of fibroblasts was further evident by immunoblot analysis, thus confirming the secretory nature of HABP and its occurrence in the extracellular matrix [10].
• Thrombelastographies of wild-type and mutant plasmas were performed, facilitating the auto-activation of the intrinsic FSAP pro-enzymes by addition of dextran sulfate (DXS) and accelerated clot lysis by addition of scuPA [13].
• PHBP is a novel human plasma hyaluronan-binding protein that shows significant homology in amino acid sequence to hepatocyte growth factor activator [9].
• The results of Northern blot analysis indicated that liver, kidney, and pancreas expressed PHBP mRNA [12].
• The conditioned medium derived from various cell types such as smooth muscle cells, endothelial cells, osteosarcoma cells or CHO (Chinese-hamster ovary) cells contained an acidic factor that initiated (auto-)activation of FSAP [14].

Associations of HABP2 with chemical compounds

• With the help of enzyme-linked immunosorbent assay (ELISA) and iodinated [125I]HABP, it has been shown that kidney HABP binds specifically to hyaluronic acid (HA) amongst all the glycosaminoglycans (GAGs), however, HABP can interact with other matrix proteins, e.g., laminin, fibronectin, and collagen type IV [10].
• A serine protease isolated from plasma sharing structural characteristics with a hepatocyte growth factor activator-like protease has been demonstrated recently to activate FVII [15].
• The (auto-)activation of FSAP is facilitated by polyanionic glycosaminoglycans, such as heparin or dextran sulphate, whereas calcium ions stabilize the active form of FSAP [14].
• In a purified system, natural RNA augmented the FSAP-dependent Factor VII activation several-fold (as shown by subsequent Factor Xa generation), as well as the FSAP-mediated generation of urokinase [14].
• The distribution of a hyaluronate-binding (HABP) and rhodamine B-isothiocyanate (RITC)-labeled hyaluronate (HA) were studied on both actively motile and stationary chick heart fibroblasts to assess the relationship of these molecules to each other, to other extracellular matrix molecules, to membrane protrusions and to adhesion sites [16].

Regulatory relationships of HABP2

• PHBP did not cleave (activate) prothrombin and plasminogen, but it converted the inactive single chain urinary plasminogen activator to the active two chain form [17].

Other interactions of HABP2

• The results showed that fibrinogen and fibronectin were the major substrates of PHBP [17].
• Later on FSAP was identified as a potent activator of single chain plasminogen activators, in particular of prourokinase, as well [11].
• Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of HABP under reducing as well as nonreducing conditions revealed a single protein band of 34 kDa, thus indicating that kidney HABP is a homodimer and lacks interchain disulfide bond [10].
• RNase A, but not other hydrolytic enzymes (proteases, glycanases and DNase), abolished the FSAP cofactor activity, which was subsequently isolated by anion-exchange chromatography and unequivocally identified as RNA [14].

Analytical, diagnostic and therapeutic context of HABP2

• The objective of this case-control study was to assess FSAP Marburg I's role in the occurrence of venous thromboembolism (VTE) [3].
• Polyclonal antibodies were raised against it, and the monospecificity of the antibodies towards HABP was confirmed by Western blot analysis of tissue extracts [10].
• The specific binding of FSAP to RNA (but not to DNA) was shown by mobility-shift assays and UV crosslinking, thereby identifying FSAP as a new extracellular RNA-binding protein, the K(D) estimated to be 170-350 nM [14].
• We further characterized the expression of WF-HABP in vivo and found that its expression colocalized with CD31-positive cells and was prominently expressed in microvessels in the human aorta and in atherectomy samples [18].
• RITC-HA and HABP, detected by indirect immunofluorescence, were concentrated in the perinuclear region, the leading lamella and retraction processes of actively motile cells, although RITC-HA also occurred diffusely over the rest of the cell body [16].

References