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Protamine

Protamine P1
Identifiers
Symbol Protamine_P1
Pfam PF00260
InterPro IPR000221
PROSITE PDOC00047
protamine 1
Identifiers
Symbol PRM1
Entrez 5619
HUGO 9447
OMIM 182880
RefSeq NM_002761
UniProt P04553
Other data
Locus Chr. 16 p13.13
protamine 2
Identifiers
Symbol PRM2
Entrez 5620
HUGO 9448
OMIM 182890
RefSeq NM_002762
UniProt P04554
Other data
Locus Chr. 16 p13.13

Protamines are small, arginine-rich, nuclear proteins that replace histones late in the haploid phase of spermatogenesis and are believed essential for sperm head condensation and DNA stabilization. They may allow for denser packaging of DNA in the spermatozoon than histones, but they must be decompressed before the genetic data can be used for protein synthesis. However, in humans and maybe other primates, 10-15% of the sperm's genome is packaged by histones thought to bind genes that are essential for early embryonic development.

During the formation of sperm, protamine binds to the phosphate backbone of DNA using the arginine-rich domain as an anchor. DNA is then folded into a toroid, an O-shaped structure, although the mechanism is not known. A sperm cell can contain up to 50,000 toroid-shaped structures in its nucleus with each toroid containing about 50 kilobases. Before the toroid is formed, histones are removed from the DNA by transition nuclear proteins, so that protamine can condense it. The effects of this change are 1) an increase in sperm hydrodynamics for better flow through liquids by reducing the head size 2) decrease in the occurrence of DNA damage 3) removal of the epigenetic markers that occur with histone modifications.

The structure of the sperm head is also related to protamine levels. The ratio of protamine 2 to protamine 1 and transition nuclear proteins has been found to change the sperm head shape in various species of Mus, the genus of mice, by altering the expression of protamine 2 via mutations in its promoter region. A decrease in the ratio has been found to increase the competitive ability of sperm in Mus species. However, further testing is required to determine how this ratio influences the shape of the head and whether monogamy influences this selection. In humans, studies show that men who have unbalanced Prm1/Prm2 are subfertile or infertile.

When mixed with insulin, protamines slow down the onset and increase the duration of insulin action (see NPH insulin).

Protamine is used in cardiac surgery, vascular surgery, and interventional radiology procedures to neutralize the anti-clotting effects of heparin. Adverse effects include increased pulmonary artery pressure and decrease peripheral blood pressure, myocardial oxygen consumption, cardiac output, and heart rate.


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