Disease relevance of PRM1

• High doses of intravenous protamine cause generalized vascular permeability changes in brain and other organs, and concomitant hypoproteinemia [1].
• Both specific and nonspecific binding of 125I-thrombin to the endothelial cell surface was partially inhibited in the presence of protamine sulfate, after the removal of cell surface heparan sulfate by the treatment of cells with crude Flavobacterium heparinum enzyme or purified heparitinase [2].
• Complexes of enterobacterial common antigen with protamine sulfate, with methylated bovine serum albumin or with a fraction of outer membrane proteins of two different Shigella wild types proved to be highly immunogenic in rabbits upon intravenous immunization, in contrast to the enterobacterial common antigen preparations by themselves [3].
• To elucidate the mechanism of protamine-induced hypotension, we examined the effects of protamine on catecholamine secretion in bovine adrenal medullary cells and on the serum norepinephrine in the rat [4].
• Highly purified Sendai virus contained a protein kinase activity which atatlysed the phosphorylation of endogenous polypeptides or exogenous protamine sulphate [5].

High impact information on PRM1

• Protamine-mediated transport of albumin into brain and other organs of the rat. Binding and endocytosis of protamine-albumin complex by microvascular endothelium [1].
• The transcytosis of protamine through the cerebral microvascular barrier was documented with an internal carotid artery perfusion technique [1].
• Binding of albumin to protamine was demonstrated using equilibrium dialysis, and protamine was shown to selectively augment the uptake of albumin, but not sucrose, in isolated bovine or human brain capillaries [1].
• Platelet factor 4, protamine sulfate and diisopropylphosphoryl thrombin, all antagonists of the antithrombin III cofactor activity of heparin, significantly reduced the capacity of the preparation to inhibit thrombin [6].
• Purified preparations of a distinct autophosphorylation-activated protein kinase from bovine kidney phosphorylated and inactivated purified preparations of protein phosphatase 2A2 (PP2A2) by about 80% with the autophosphorylation-activated protein kinase, protamine kinase, and 32P-labeled myelin basic protein as substrates [7].

Chemical compound and disease context of PRM1

• Neutralization of heparin with its antidote protamine is associated with side effects such as pulmonary hypertension [8].

Biological context of PRM1

• The bovine genome immediately surrounding (approximately equal to 20 kilobase pairs) the protamine gene has been mapped and reveals that the sequence flanking the 5' segment of the gene is unique, while the sequence flanking the 3' segment is repetitive [9].
• We have since utilized the BPK59 clone as a probe, to isolate both alleles of the protamine gene from a bovine genomic library constructed in Charon 28 [9].
• Nucleotide sequence of a bovine protamine cDNA [10].
• We have redetermined the primary sequence for bull protamine using HPLC peptide mapping and automated amino-acid sequencing techniques and report, on the basis of these findings, that the previously published amino-acid sequence for this protein is incorrect [11].
• However, bovine P1 protamine cDNA shared greater sequence homology with mouse P1 [12].

Anatomical context of PRM1

• A bovine P1 protamine cDNA from a bull testis cDNA library was isolated utilizing a series of oligonucleotide probes [12].
• The results indicate that this protamine kinase of kidney cytosol is a novel protein kinase [13].
• Insulin stimulates the activity of a protamine kinase in isolated rat hepatocytes [14].
• Purification and properties of a distinct protamine kinase from the cytosol of bovine kidney cortex [13].
• This kinase, which phosphorylates casein and phosvitin but not histone and protamine using either ATP or GTP, co-fractionates with coated vesicles as assayed by gel filtration, electrophoresis, and sedimentation [15].

Associations of PRM1 with chemical compounds

• Our results show that the number of clustered arginine residues present in the DNA binding domain is the most important factor affecting the condensation and stability of the DNA-protamine complex prior to the formation of inter-protamine disulfide cross-links [16].
• Analyses of total free sulfhydryls show that all seven of the bull protamine cysteines are cross-linked as disulfides in mature sperm [17].
• We have identified the disulfide cross-links in bull protamine by titrating intact bull sperm with dithiothreitol (DTT) and following the modification of each cysteine residue with tritiated iodoacetate [17].
• 0. Intra- and intermolecular disulfides were identified by correlating the reduction of specific disulfides with the dissociation of protamine from DNA in partially reduced sperm and sperm treated with N,N'-ethylenedimaleimide, a bifunctional disulfide cross-linking agent [17].
• In the presence of polylysine or protamine, marked phosphorylation is observed [18].

Physical interactions of PRM1

• To this end, studies revealed that protamine was binding to the particulate substrate in a ratio of protamine/opsin of 0.7:1 [19].

Regulatory relationships of PRM1

• The results show that MBPK-1 and MBPK-2 are protamine kinase-activating kinases and suggest that MBPK-1 and MBPK-2 may be related to mitogen-activated protein kinase [20].
• Together with previous observations, the results indicate that the protamine kinase could contribute to the insulin-stimulated phosphorylation of eIF-4E [21].

Other interactions of PRM1

• A second protamine variant, protamine P2, has to date been isolated only from human and murine spermatozoa where it represents the major fraction of basic nuclear protein [22].
• The profiles of protamine inhibition of triolein-phosphatidyl-N,N-dimethyl ethanolamine (PDME) and triolein-phosphatidyl-N-monomethyl ethanolamine (PMME) emulsions were intermediate between those of PC and PE emulsions [23].
• A second enzyme, a constitutively released PK that phosphorylates casein or phosvitin and not protamine sulfate or mixed histones, was identified and characterized [24].
• The primary structure of mammalian protamine I can be divided into three domains, a central DNA binding domain that is arginine-rich and amino- and carboxyl-terminal domains that are rich in cysteine residues [25].
• The purified protamine kinase exhibited about 5% activity with casein, 8% with histone H2B, and less than 0.1% with histone H1, histone H4, glycogen synthase a from rabbit skeletal muscle, ovalbumin, bovine serum albumin, and phosvitin [13].

Analytical, diagnostic and therapeutic context of PRM1

• This protamine kinase exhibited an apparent Mr = 43,000 as estimated by gel permeation chromatography on Sephacryl S-200 and an apparent Mr = 45,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis [13].
• Using transmission electron microscopy and light scattering, we show that bull protamine forms particles with DNA that are morphologically similar to the subunits of native bull sperm chromatin [25].
• Concomitant intraarticular injection of aBSA with the cationic protein protamine chloride (pI approximately 10) strongly reduced the retention of aBSA [26].
• Unspecific binding of a protamine, namely fluorescein-labelled clupeine Z, to double-stranded calf thymus DNA was studied using fluorescence titration methods and chemical relaxation techniques [27].
• Vertebrate protamine gene evolution I. Sequence alignments and gene structure [28].

References