Human APP - Revision history

Michal Harel at 14:53, 13 January 2012

2012-01-13T14:53:31Z

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	{{STRUCTURE_1mwp\| PDB=1mwp \| SIZE=400\| SCENE= \|right\| CAPTION=Human amyloid precursor protein ~~core~~ domain, [[~~1rw6~~]] }}		{{STRUCTURE_1mwp\| PDB=1mwp \| SIZE=400\| SCENE= \|right\| CAPTION=Human amyloid precursor protein heparin-binding domain, [[1mwp]] }}

Michal Harel at 14:52, 13 January 2012

2012-01-13T14:52:49Z

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	{{~~STRUCTURE_3ktm~~\| PDB=~~3ktm~~ \| SIZE=400\| SCENE= \|right\| CAPTION=Human amyloid precursor protein core domain, [[1rw6]] }}		{{STRUCTURE_1mwp\| PDB=1mwp \| SIZE=400\| SCENE= \|right\| CAPTION=Human amyloid precursor protein core domain, [[1rw6]] }}

Michal Harel at 14:50, 13 January 2012

2012-01-13T14:50:05Z

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	{{~~STRUCTURE_1rw6~~\| PDB=~~1rw6~~ \| SIZE=400\| SCENE= \|right\| CAPTION=Human amyloid precursor protein core domain, [[1rw6]] }}		{{STRUCTURE_3ktm\| PDB=3ktm \| SIZE=400\| SCENE= \|right\| CAPTION=Human amyloid precursor protein core domain, [[1rw6]] }}

Michal Harel at 14:45, 13 January 2012

2012-01-13T14:45:15Z

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	{{STRUCTURE_1rw6\| PDB=1rw6 \| SIZE=~~300~~\| SCENE= \|right\| CAPTION=Human amyloid precursor protein core domain, [[1rw6]] }}		{{STRUCTURE_1rw6\| PDB=1rw6 \| SIZE=400\| SCENE= \|right\| CAPTION=Human amyloid precursor protein core domain, [[1rw6]] }}

Michal Harel at 09:42, 3 July 2011

2011-07-03T09:42:58Z

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	== APP and Alzheimer's disease ==		== APP and Alzheimer's disease ==
	Aβ peptides are generated in neuronal secretory vesicles by proteolytic cleavage of the amyloid precursor protein (APP) by proteases, called β-secretase and γ-secretase that cleave at the N-terminus and variant C-termini of Aβ within APP, respectively, resulting in Aβ of 40 or 42 amino acids (Aβ40 and Aβ42, respectively) (Figure 1). Because the N-termini of Aβ40 and Aβ42 are identical, development of inhibitors that reduce cleavage of APP at the β-secretase site are likely to be effective for reducing Aβ peptide forms with alleviation of neurodegeneration and memory deficit. The APP in the vast majority of AD patients possesses the wild-type β-secretase site sequence. <ref>14</ref>		Aβ peptides are generated in neuronal secretory vesicles by proteolytic cleavage of the amyloid precursor protein (APP) by proteases, called β-secretase and γ-secretase that cleave at the N-terminus and variant C-termini of Aβ within APP, respectively, resulting in Aβ of 40 or 42 amino acids (Aβ40 and Aβ42, respectively) (Figure 1). Because the N-termini of Aβ40 and Aβ42 are identical, development of inhibitors that reduce cleavage of APP at the β-secretase site are likely to be effective for reducing Aβ peptide forms with alleviation of neurodegeneration and memory deficit. The APP in the vast majority of AD patients possesses the wild-type β-secretase site sequence. <ref>14</ref>

			==3D structures of human APP==

			[[Amyloid precursor protein]]

	==Additional Resources==		==Additional Resources==

Michal Harel at 09:27, 3 July 2011

2011-07-03T09:27:01Z

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	{{~~STRUCTURE_3cin~~ \| PDB=~~3cin~~ \| SCENE= }}		{{STRUCTURE_1rw6\| PDB=1rw6 \| SIZE=300\| SCENE= \|right\| CAPTION=Human amyloid precursor protein core domain, [[1rw6]] }}


	== Functions of human APP and Fe65 protein ==		== Functions of human APP and Fe65 protein ==

David Canner at 08:49, 18 October 2010

2010-10-18T08:49:52Z

← Older revision		Revision as of 08:49, 18 October 2010
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	Fe65 is an adaptor protein localized in the nucleus. It interacts with the Alzheimer's disease amyloid precursor protein (APP), transcription factor CP2/LSF/LBP1 and the low-density lipoprotein receptor-related protein. APP functions as a cytosolic anchoring site that can prevent the gene product's nuclear translocation. This encoded protein could play an important role in the pathogenesis of Alzheimer's disease. It is thought to regulate transcription. Also it is observed to block cell cycle progression by downregulating thymidylate synthase expression. Multiple alternatively spliced transcript variants have been described for this gene but some of their full length sequence is not known.[provided by RefSeq].<ref>10</ref>		Fe65 is an adaptor protein localized in the nucleus. It interacts with the Alzheimer's disease amyloid precursor protein (APP), transcription factor CP2/LSF/LBP1 and the low-density lipoprotein receptor-related protein. APP functions as a cytosolic anchoring site that can prevent the gene product's nuclear translocation. This encoded protein could play an important role in the pathogenesis of Alzheimer's disease. It is thought to regulate transcription. Also it is observed to block cell cycle progression by downregulating thymidylate synthase expression. Multiple alternatively spliced transcript variants have been described for this gene but some of their full length sequence is not known.[provided by RefSeq].<ref>10</ref>

	Fe65 plays a central role in the response to DNA damage by translocating to the nucleus and inducing apoptosis. May act by specifically recognizing and binding histone H2AX phosphorylated on 'Tyr-142' (H2AXY142ph) at double-strand breaks (DSBs), recruiting other pro-apoptosis factors such as MAPK8/JNK1.Required for histone H4 acetylation at double-strand breaks (DSBs).Its ability to specifically bind modified histones and chromatin modifying enzymes such as KAT5/TIP60, probably explains its trancription activation activity. <ref>11</ref>		Fe65 plays a central role in the response to [[DNA]] damage by translocating to the nucleus and inducing apoptosis. May act by specifically recognizing and binding histone H2AX phosphorylated on 'Tyr-142' (H2AXY142ph) at double-strand breaks (DSBs), recruiting other pro-apoptosis factors such as MAPK8/JNK1.Required for histone H4 acetylation at double-strand breaks (DSBs).Its ability to specifically bind modified histones and chromatin modifying enzymes such as KAT5/TIP60, probably explains its trancription activation activity. <ref>11</ref>

	== Location ==		== Location ==
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	Cell surface protein that rapidly becomes internalized via clathrin-coated pits. During maturation, the immature APP (N-glycosylated in the endoplasmic reticulum) moves to the Golgi complex where complete maturation occurs (O-glycosylated and sulfated). After alpha-secretase cleavage, soluble APP is released into the extracellular space and the C-terminal is internalized to endosomes and lysosomes. Some APP accumulates in secretory transport vesicles leaving the late Golgi compartment and returns to the cell surface. Gamma-CTF(59) peptide is located to both the cytoplasm and nuclei of neurons. It can be translocated to the nucleus through association with APBB1 (Fe65). Beta-APP42 associates with FRPL1 at the cell surface and the complex is then rapidly internalized. APP sorts to the basolateral surface in epithelial cells. During neuronal differentiation, the Thr-743 phosphorylated form is located mainly in growth cones, moderately in neurites and sparingly in the cell body. Casein kinase phosphorylation can occur either at the cell surface or within a post-Golgi compartment <ref>13</ref>		Cell surface protein that rapidly becomes internalized via clathrin-coated pits. During maturation, the immature APP (N-glycosylated in the endoplasmic reticulum) moves to the Golgi complex where complete maturation occurs (O-glycosylated and sulfated). After alpha-secretase cleavage, soluble APP is released into the extracellular space and the C-terminal is internalized to endosomes and lysosomes. Some APP accumulates in secretory transport vesicles leaving the late Golgi compartment and returns to the cell surface. Gamma-CTF(59) peptide is located to both the cytoplasm and nuclei of neurons. It can be translocated to the nucleus through association with APBB1 (Fe65). Beta-APP42 associates with FRPL1 at the cell surface and the complex is then rapidly internalized. APP sorts to the basolateral surface in epithelial cells. During neuronal differentiation, the Thr-743 phosphorylated form is located mainly in growth cones, moderately in neurites and sparingly in the cell body. Casein kinase phosphorylation can occur either at the cell surface or within a post-Golgi compartment <ref>13</ref>

	== APP and Alzheimer disease ==		== APP and Alzheimer's disease ==
	Aβ peptides are generated in neuronal secretory vesicles by proteolytic cleavage of the amyloid precursor protein (APP) by proteases, called β-secretase and γ-secretase that cleave at the N-terminus and variant C-termini of Aβ within APP, respectively, resulting in Aβ of 40 or 42 amino acids (Aβ40 and Aβ42, respectively) (Figure 1). Because the N-termini of Aβ40 and Aβ42 are identical, development of inhibitors that reduce cleavage of APP at the β-secretase site are likely to be effective for reducing Aβ peptide forms with alleviation of neurodegeneration and memory deficit. The APP in the vast majority of AD patients possesses the wild-type β-secretase site sequence. <ref>14</ref>		Aβ peptides are generated in neuronal secretory vesicles by proteolytic cleavage of the amyloid precursor protein (APP) by proteases, called β-secretase and γ-secretase that cleave at the N-terminus and variant C-termini of Aβ within APP, respectively, resulting in Aβ of 40 or 42 amino acids (Aβ40 and Aβ42, respectively) (Figure 1). Because the N-termini of Aβ40 and Aβ42 are identical, development of inhibitors that reduce cleavage of APP at the β-secretase site are likely to be effective for reducing Aβ peptide forms with alleviation of neurodegeneration and memory deficit. The APP in the vast majority of AD patients possesses the wild-type β-secretase site sequence. <ref>14</ref>

			==Additional Resources==
			For additional information, see: [[Alzheimer's Disease]]

	== References ==		== References ==
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	3. Ando K, Iijima KI, Elliott JI, Kirino Y, Suzuki T. Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of beta-amyloid.J Biol Chem. 2001 Oct 26;276(43):40353-61. Epub 2001 Aug 21. [http://www.ncbi.nlm.nih.gov/pubmed/11517218itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=5 PMID: 11517218]		3. Ando K, Iijima KI, Elliott JI, Kirino Y, Suzuki T. Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of beta-amyloid.J Biol Chem. 2001 Oct 26;276(43):40353-61. Epub 2001 Aug 21. [http://www.ncbi.nlm.nih.gov/pubmed/11517218itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=5 PMID: 11517218]




	4. Sabo SL, Ikin AF, Buxbaum JD, Greengard P. The Alzheimer amyloid precursor protein (APP) and FE65, an APP-binding protein, regulate cell movement. J Cell Biol. 2001;153:1403–1414. [PubMed Sabo SL, Ikin AF, Buxbaum JD, Greengard P. The Alzheimer amyloid precursor protein (APP) and FE65, an APP-binding protein, regulate cell movement. J Cell Biol. 2001;153:1403–1414. [PubMed PMID: 11425871		4. Sabo SL, Ikin AF, Buxbaum JD, Greengard P. The Alzheimer amyloid precursor protein (APP) and FE65, an APP-binding protein, regulate cell movement. J Cell Biol. 2001;153:1403–1414. [PubMed Sabo SL, Ikin AF, Buxbaum JD, Greengard P. The Alzheimer amyloid precursor protein (APP) and FE65, an APP-binding protein, regulate cell movement. J Cell Biol. 2001;153:1403–1414. [PubMed PMID: 11425871

David Canner: Sandbox220 moved to Human APP

2010-10-18T08:47:53Z

Sandbox220 moved to Human APP

← Older revision	Revision as of 08:47, 18 October 2010
(No difference)

David Canner at 08:47, 18 October 2010

2010-10-18T08:47:13Z

← Older revision		Revision as of 08:47, 18 October 2010
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	{{STRUCTURE_3cin \| PDB=3cin \| SCENE= }}		{{STRUCTURE_3cin \| PDB=3cin \| SCENE= }}
	== Functions of human APP and Fe65 protein ==		== Functions of human APP and Fe65 protein ==

Eran Hodis: /* APP and Alzheimer disease */

2009-11-01T12:39:20Z

APP and Alzheimer disease

← Older revision		Revision as of 12:39, 1 November 2009
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	== APP and Alzheimer disease ==		== APP and Alzheimer disease ==
	Aβ peptides are generated in neuronal secretory vesicles by proteolytic cleavage of the amyloid precursor protein (APP) by proteases, called β-secretase and γ-secretase that cleave at the N-terminus and variant C-termini of Aβ within APP, respectively, resulting in Aβ of 40 or 42 amino acids (Aβ40 and Aβ42, respectively) (Figure 1). Because the N-termini of Aβ40 and Aβ42 are identical, development of inhibitors that reduce cleavage of APP at the β-secretase site are likely to be effective for reducing Aβ peptide forms with alleviation of neurodegeneration and memory deficit. The APP in the vast majority of AD patients possesses the wild-type β-secretase site sequence. <ref>14<ref>		Aβ peptides are generated in neuronal secretory vesicles by proteolytic cleavage of the amyloid precursor protein (APP) by proteases, called β-secretase and γ-secretase that cleave at the N-terminus and variant C-termini of Aβ within APP, respectively, resulting in Aβ of 40 or 42 amino acids (Aβ40 and Aβ42, respectively) (Figure 1). Because the N-termini of Aβ40 and Aβ42 are identical, development of inhibitors that reduce cleavage of APP at the β-secretase site are likely to be effective for reducing Aβ peptide forms with alleviation of neurodegeneration and memory deficit. The APP in the vast majority of AD patients possesses the wild-type β-secretase site sequence. <ref>14</ref>

	== References ==		== References ==