Sandbox GGC6: Difference between revisions

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==Fibrinogen alpha chain==
=='''Neurotrophin-4'''==
<StructureSection load='3VEV' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Sandbox GGC6'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.


== Function ==
<StructureSection load='1b98' size='400' side='right' caption='Neurotrophin-4' scene=''>
protease thrombin cleaves fibrinogen into monomers. The formation of monomers, fibrinogen beta, and fibrinogen alpha is insoluble fibrin matrix. fibrin works as a binding or trapping agent in the coagulation process, which creates blood clot.  
Neurotrophin-4 (NT-4) belongs to a group of nerve growth factors that influence nerve cell proliferation through selective and non-covalent interactions with the nerve growth factor receptor. <ref>PMID: 16411893</ref>


For small wounds, the polymerized fibrin with platelets forms a hemostatic plug over the wounds site. Fibrin is also anti inflammatory which it protects against IFNG- mediated hemorrhage.
Afibrinogenemic pregnant patients will result in spontaneous miscarriage. Fibrinogen supplemental will allow the patients to sustain the pregnancy, therefore, maternal fibrinogen plays a important role for successful pregnancy.<ref>PMID: 16026273</ref>


== '''Function''' ==
NT-4 functions as a growth factor in many biological pathways and processes to induce neuronal proliferation. <ref>PMID: 10631974</ref>
=== Biological Processes ===
Positive regulation of neurotrophin TRK receptor signaling pathway:
NT-4 functions as a ligand when binding to neurotrophin receptor tyrosine kinase NTRK2. Auto-phosphorylated NTRK2 dimers that are formed on tyrosine residues in receptor tail as a result of NT-4 binding.
Adult locomotory behavior <ref>PMID: 10681461</ref>, neuron projection morphogenesis:
generating projection structures of a neuron, <ref>PMID: 21873635</ref>
ganglion mother cell fate determination,<ref>PMID: 10681461</ref> epidermis development, <ref>PMID: 9973328</ref> innervation, long term memory, <ref>PMID: 10869436</ref> chemical synaptic transmission modulation and nerve development, <ref>PMID: 21873635</ref> mechanoreceptor differentiation, negative regulation of neuron apoptotic process, and positive regulation of peptidyl-serine phosphorylation, <ref>PMID: 21873635</ref> nerve growth signaling pathway, <ref>PMID:11520933</ref> and sensory organ boundary specification (taste bud development). <ref>PMID: 10479455</ref>
== Disease ==
== Disease ==
'''Congenital afibrinogenemia (CAFBN)'''
NT-4, along with other growth factors including neurotrophin-3 (NT-3), brain-derived neurotrophic factor (<scene name='78/781192/Bdnf/1'>BDNF</scene>), and nerve growth factor (NGF) have all shown to be essential for survival of neurons. <ref>PMID: 10631974</ref> <ref>PMID: 16411893</ref> These growth factors have been associated with parts of the cerebrum including the frontal lobe and limbic system because of their involvement in neurological processes like behavior, learning, and memory. <ref>PMID: 16411893</ref> Availability and binding affinity are two factors that contribute to development of Alzheimer's disease and Huntington's disease, as well as neurodegenerative and psychiatric disorders. <ref>PMID: 16411893</ref> Both increased and decreased levels of NT-4 are associated with various disease states that effect mental development and decline. Serum concentration levels of NT-4 and BDNF were found to be higher in patients with autism and in patients with mental retardation <ref>Serum neurotrophin concentrations in autism and mental retardation: a pilot study
Miyazaki, Kaoru et al.
Brain and Development, Volume 26, Issue 5, 292 - 295</ref> Defects or mutations in NT-4 has been associated with development of glaucoma.
== Relevance ==
NT-4 is essential for neuron survival and proliferation throughout ones life span so maintaining proper amounts in the body is needed to stay healthy. Neuron growth factors are currently being used as biomarkers to study the relationship between them and various mental disease states including depression, schizophrenia, autism, Alzheimer's and Huntington's disease.  Knowing the cause of variance in these levels is key for prevention of certain neurological disorders.
Depletion and/or unavailable receptor binding sites are also being studied to further understand these mechanisms.
== Structural highlights ==
NT-4 is a homodimer; Its <scene name='78/781192/Protein-ligand/1'>structure</scene> includes 2 Neurotrophin-4 factors bound with a chloride ion. NT-4 is 130 amino acids in length. This chloride ion is a ligand that binds to nerve growth factor receptors.
<scene name='78/781192/N_to_c_rainbow/1'>N to C sequence</scene>
{{Template:ColorKey_N52C3Rainbow}}


This is an inherited blood disorder where the blood does not clot normally. This disease is caused by truncating mutations. Changing in position Arg-35 when Thrombin cleaves the site of Fibrinopeptide leads to alpha- Dysfibrinogenemias. <ref>doi: 10.1160/TH14-07-0629</ref>
Copy and paste the following line where you want the scene link to appear (scroll down if needed) and edit the TextToBeDisplayed:


Nosebleeds, bleeding from the gums and tongue are commons after a minor trauma for people with this disease. bleedings in the brain and internal organs can occur for affected individuals which can lead to be fatal. However, it's rare. Women with this disease can experience an abnormal heavy menstrual bleeding, they could also have a difficult time carrying a pregnancy, and could result in miscarriages. Newborn with this disease can experience bleeding from the umbilical cord stump after birth. The treatment for this disease includes cryoprecipitate, fibrinogen, and plasma (contains clotting factors). <ref>PMID: 19598064</ref>
<scene name='78/781192/Temperature/1'>Temperature Value</scene>
{{Template:ColorKey_TemperatureRelative}}


'''Amyloidosis 8 (AMYL8)'''
[[Image:1b98 entity 1 front image-800x800.png]]


This is hereditary disease which insoluble amyloid proteins deposits in body tissues and organs. This tends to abnormal protein build-up and leads to damaged organs and deaths. The disease is caused by a mutation fibrinogen alpha chain.<ref>PMID: 23227278</ref>


This disease does not show symptoms until it gets advanced. The symptoms could be lack of appetite, weight loss, fatigue, shortness of breath, weakness. Due to abnormal protein build-up in organs and tissues, most of them can be affected including heart, kidney, livers, skin, etc. Amyloidosis can affect those organs and leads to cardiomyopathy, liver damage, and nephrotic syndrome. However, nervous system is not affected. <ref>doi: 10.1038/ng0393-252(/ref>
</StructureSection>
 
nephrotic syndrome
== Relevance ==


== Structural highlights ==
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. <scene name='78/781192/Hydrophobic_and_polar/2'>this shows polar and unpolar structure of 1XKT </scene>
</StructureSection>
== References ==
== References ==
<references/>
<references/>
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