Amyloid-beta precursor protein (APP) is an
integral membrane protein
An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All ''transmembrane proteins'' are IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a signi ...
expressed in many
tissues and concentrated in the
synapse
In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell.
Synapses are essential to the transmission of nervous impulses from ...
s of
neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s. It functions as a
cell surface receptor
Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integral m ...
and has been implicated as a regulator of synapse formation,
neural plasticity
Neuroplasticity, also known as neural plasticity, or brain plasticity, is the ability of neural networks in the brain to change through growth and reorganization. It is when the brain is rewired to function in some way that differs from how it p ...
,
antimicrobial activity,
and
iron export
Human iron metabolism is the set of chemical reactions that maintain human homeostasis of iron at the systemic and cellular level. Iron is both necessary to the body and potentially toxic. Controlling iron levels in the body is a critically imp ...
.
It is coded for by the gene ''APP'' and regulated by
substrate presentation. APP is best known as the precursor molecule whose
proteolysis
Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called protease ...
generates
amyloid beta
Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid precursor protein (APP), which is ...
(Aβ), a polypeptide containing 37 to 49
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
residues, whose
amyloid fibril
Amyloids are aggregates of proteins characterised by a fibrillar morphology of 7–13 nm in diameter, a beta sheet (β-sheet) secondary structure (known as cross-β) and ability to be stained by particular dyes, such as Congo red. In the h ...
lar form is the primary component of
amyloid plaque
Amyloid plaques (also known as neuritic plaques, amyloid beta plaques or senile plaques) are extracellular deposits of the amyloid beta (Aβ) protein mainly in the grey matter of the brain. Degenerative neuronal elements and an abundance of mi ...
s found in the brains of
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
patients.
Genetics
Amyloid-beta precursor protein is an ancient and highly
conserved protein.
In
human
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
s, the
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
''APP'' is located on
chromosome 21
Chromosome 21 is one of the 23 pairs of chromosomes in humans. Chromosome 21 is both the smallest human autosome and chromosome, with 48 million base pairs (the building material of DNA) representing about 1.5 percent of the total DNA in cells. M ...
and contains 18
exon
An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...
s spanning 290
kilobase
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
s.
Several
alternative splicing
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be ...
isoforms of APP have been observed in humans, ranging in length from 639 to 770 amino acids, with certain isoforms preferentially expressed in neurons; changes in the neuronal ratio of these isoforms have been associated with Alzheimer's disease.
Homologous proteins have been identified in other organisms such as ''
Drosophila
''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...
'' (fruit flies), ''
C. elegans
''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...
'' (roundworms), and all
mammal
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
s.
The amyloid beta region of the protein, located in the membrane-spanning domain, is not well conserved across species and has no obvious connection with APP's
native-state biological functions.
Mutations in critical regions of amyloid precursor protein, including the region that generates amyloid beta (Aβ), cause familial susceptibility to Alzheimer's disease.
For example, several mutations outside the Aβ region associated with familial Alzheimer's have been found to dramatically increase production of Aβ.
A mutation (A673T) in the APP gene protects against Alzheimer's disease. This substitution is adjacent to the beta secretase cleavage site and results in a 40% reduction in the formation of amyloid beta in vitro.
Structure
A number of different structural
domains that fold mostly on their own have been found in the APP sequence. The extracellular region, much larger than the intracellular region, is divided into the E1 and E2 domains, linked by an acidic domain (AcD); E1 contains two subdomains including a
growth factor-like domain
A growth factor-like domain (GFLD) is a protein domain structurally related to epidermal growth factor, which has a high binding affinity for the epidermal growth factor receptor. As structural domains within larger proteins, GFLD regions commonly ...
(GFLD) and a
copper
Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkis ...
-binding domain (CuBD) interacting tightly together.
[; see also PDB ID ] A serine protease inhibitor domain, absent from the isoform differentially expressed in the brain, is found between acidic region and E2 domain.
The complete crystal structure of APP has not yet been solved; however, individual domains have been successfully crystallized, the
growth factor-like domain
A growth factor-like domain (GFLD) is a protein domain structurally related to epidermal growth factor, which has a high binding affinity for the epidermal growth factor receptor. As structural domains within larger proteins, GFLD regions commonly ...
,
[; see also PDB ID ] the
copper
Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkis ...
-binding domain,
[; See also 2007 PDB IDs , , .] the complete E1 domain
and the E2 domain.
Post-translational processing
APP undergoes extensive
post-translational modification
Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribosome ...
including
glycosylation
Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not al ...
,
phosphorylation
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
,
sialylation Sialic acids are a class of alpha-keto acid sugars with a nine-carbon backbone.
The term "sialic acid" (from the Greek for saliva, - ''síalon'') was first introduced by Swedish biochemist Gunnar Blix in 1952. The most common member of this g ...
, and
tyrosine sulfation Tyrosine sulfation is a posttranslational modification where a sulfate group is added to a tyrosine residue of a protein molecule. Secreted proteins and extracellular parts of membrane proteins that pass through the Golgi apparatus may be sulfated. ...
, as well as many types of
proteolytic
Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases, ...
processing to generate peptide fragments.
It is commonly cleaved by
protease
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...
s in the
secretase Secretases are enzymes that "snip" pieces off a longer protein that is embedded in the cell membrane. 300px, Processing of the amyloid-beta precursor protein Among other roles in the cell, secretases act on the amyloid-beta precursor protein (APP) ...
family;
alpha secretase
Alpha secretases are a family of proteolytic enzymes that cleave amyloid precursor protein (APP) in its transmembrane region. Specifically, alpha secretases cleave within the fragment that gives rise to the Alzheimer's disease-associated peptide am ...
and
beta secretase
Beta-secretase 1, also known as beta-site amyloid precursor protein cleaving enzyme 1, beta-site APP cleaving enzyme 1 (BACE1), membrane-associated aspartic protease 2, memapsin-2, aspartyl protease 2, and ASP2, is an enzyme that in humans is enco ...
both remove nearly the entire extracellular domain to release membrane-anchored
carboxy-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
fragments that may be associated with
apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
.
Cleavage by
gamma secretase
Gamma secretase is a multi-subunit protease complex, itself an integral membrane protein, that cleaves single-pass transmembrane proteins at residues within the transmembrane domain. Proteases of this type are known as intramembrane proteases. Th ...
within the membrane-spanning domain after beta-secretase cleavage generates the amyloid-beta fragment; gamma secretase is a large multi-subunit complex whose components have not yet been fully characterized, but include
presenilin
Presenilins are a family of related multi-pass transmembrane proteins which constitute the catalytic subunits of the gamma-secretase intramembrane protease protein complex. They were first identified in screens for mutations causing early onset ...
, whose gene has been identified as a major genetic risk factor for Alzheimer's.
The amyloidogenic processing of APP has been linked to its presence in
lipid raft
The plasma membranes of cells contain combinations of glycosphingolipids, cholesterol and protein receptors organised in glycolipoprotein lipid microdomains termed lipid rafts. Their existence in cellular membranes remains somewhat controversial. ...
s. When APP molecules occupy a lipid raft region of membrane, they are more accessible to and differentially cleaved by beta secretase, whereas APP molecules outside a raft are differentially cleaved by the non-amyloidogenic alpha secretase.
Gamma secretase activity has also been associated with lipid rafts.
The role of
cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
in lipid raft maintenance has been cited as a likely explanation for observations that high cholesterol and
apolipoprotein E
Apolipoprotein E (APOE) is a protein involved in the metabolism of fats in the body of mammals. A subtype is implicated in Alzheimer's disease and cardiovascular disease.
APOE belongs to a family of fat-binding proteins called apolipoproteins. ...
genotype
The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...
are major risk factors for Alzheimer's disease.
Biological function
Although the native biological role of APP is of obvious interest to Alzheimer's research, thorough understanding has remained elusive.
Experimental models of Alzheimer's disease
Experimental models of Alzheimer's disease are organism or cellular models used in research to investigate biological questions about Alzheimer's disease as well as develop and test novel therapeutic treatments. Alzheimer's disease is a progressive ...
are commonly used by researchers to gain better understandings about the biological function of APP in disease pathology and progression.
Synaptic formation and repair
The most-substantiated role for APP is in synaptic formation and repair;
its
expression
Expression may refer to:
Linguistics
* Expression (linguistics), a word, phrase, or sentence
* Fixed expression, a form of words with a specific meaning
* Idiom, a type of fixed expression
* Metaphorical expression, a particular word, phrase, o ...
is
upregulated
In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary pro ...
during neuronal
differentiation and after neural injury. Roles in
cell signaling
In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...
,
long-term potentiation
In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons ...
, and
cell adhesion
Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indir ...
have been proposed and supported by as-yet limited research.
In particular, similarities in post-translational processing have invited comparisons to the signaling role of the surface
receptor
Receptor may refer to:
* Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...
protein
Notch.
APP
knockout mice are viable and have relatively minor
phenotypic
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
effects including impaired long-term potentiation and memory loss without general neuron loss.
On the other hand, transgenic mice with upregulated APP expression have also been reported to show impaired long-term potentiation.
The logical inference is that because Aβ accumulates excessively in Alzheimer's disease its precursor, APP, would be elevated as well. However, neuronal cell bodies contain less APP as a function of their proximity to amyloid plaques.
The data indicate that this deficit in APP results from a decline in production rather than an increase in catalysis. Loss of a neuron's APP may affect physiological deficits that contribute to dementia.
Somatic recombination
In neurons of the human
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
,
somatic recombination
Somatic recombination, as opposed to the genetic recombination that occurs in meiosis, is an alteration of the DNA of a somatic cell that is inherited by its daughter cells. The term is usually reserved for large-scale alterations of DNA such as ch ...
occurs frequently in the gene that encodes APP.
Neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s from individuals with sporadic
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
show greater ''APP'' gene diversity due to somatic recombination than neurons from healthy individuals.
Anterograde neuronal transport
Molecules synthesized in the cell bodies of neurons must be conveyed outward to the distal synapses. This is accomplished via
fast anterograde transport. It has been found that APP can mediate interaction between cargo and
kinesin
A kinesin is a protein belonging to a class of motor proteins found in eukaryotic cells.
Kinesins move along microtubule (MT) filaments and are powered by the hydrolysis of adenosine triphosphate (ATP) (thus kinesins are ATPases, a type of enzy ...
and thus facilitate this transport. Specifically, a short peptide 15-amino-acid sequence from the cytoplasmic carboxy-terminus is necessary for interaction with the motor protein.
Additionally, it has been shown that the interaction between APP and kinesin is specific to the peptide sequence of APP. In a recent experiment involving transport of peptide-conjugated colored
beads
A bead is a small, decorative object that is formed in a variety of shapes and sizes of a material such as stone, bone, shell, glass, plastic, wood, or pearl and with a small hole for threading or stringing. Beads range in size from under ...
, controls were conjugated to a single amino acid,
glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...
, such that they display the same terminal carboxylic acid group as APP without the intervening 15-amino-acid sequence mentioned above. The control beads were not motile, which demonstrated that the terminal
COOH moiety of peptides is not sufficient to mediate transport.
Iron export
A different perspective on Alzheimer's is revealed by a mouse study that has found that APP possesses
ferroxidase
Ferroxidase also known as Fe(II):oxygen oxidoreductase is an enzyme that catalyzes the oxidization of iron II to iron III:
: 4 Fe2+ + 4 H+ + O2 ⇔ 4 Fe3+ + 2H2O
Examples
Human genes encoding proteins with ferroxidase activity include:
* C ...
activity similar to
ceruloplasmin
Ceruloplasmin (or caeruloplasmin) is a ferroxidase enzyme that in humans is encoded by the ''CP'' gene.
Ceruloplasmin is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism. It was first described in 194 ...
, facilitating
iron export
Human iron metabolism is the set of chemical reactions that maintain human homeostasis of iron at the systemic and cellular level. Iron is both necessary to the body and potentially toxic. Controlling iron levels in the body is a critically imp ...
through interaction with
ferroportin
Ferroportin-1, also known as solute carrier family 40 member 1 (SLC40A1) or iron-regulated transporter 1 (IREG1), is a protein that in humans is encoded by the ''SLC40A1'' gene, and is part of the Ferroportin (Fpn) FamilyTC# 2.A.100. Ferroportin i ...
; it seems that this activity is blocked by zinc trapped by accumulated Aβ in Alzheimer's.
It has been shown that a
single nucleotide polymorphism
In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...
in the
5'UTR of APP
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
can disrupt its translation.
The hypothesis that APP has ferroxidase activity in its E2 domain and facilitates export of Fe(II) is possibly incorrect since the proposed ferroxidase site of APP located in the E2 domain does not have ferroxidase activity.
As APP does not possess ferroxidase activity within its E2 domain, the mechanism of APP-modulated iron efflux from ferroportin has come under scrutiny. One model suggests that APP acts to stabilize the iron efflux protein ferroportin in the plasma membrane of cells thereby increasing the total number of ferroportin molecules at the membrane. These iron-transporters can then be activated by known mammalian ferroxidases (i.e. ceruloplasmin or
hephaestin
Hephaestin, also known as HEPH, is a protein which in humans is encoded by the ''HEPH'' gene.
Function
Hephaestin is involved in the metabolism and homeostasis of iron and possibly copper. It is a transmembrane copper-dependent ferroxidase resp ...
).
Hormonal regulation
The amyloid-β precursor protein (AβPP), and all associated secretases, are expressed early in development and play a key role in the
endocrinology of reproduction Hormonal regulation occurs at every stage of development. A milieu of hormones simultaneously affects development of the fetus during embryogenesis and the mother, including human chorionic gonadotropin (hCG) and progesterone (P4).
Embryogenes ...
– with the differential processing of AβPP by secretases regulating
human embryonic stem cell
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...
(hESC)
proliferation as well as their
differentiation into neural precursor cells (NPC). The pregnancy hormone
human chorionic gonadotropin
Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantation ...
(hCG) increases AβPP expression
and hESC proliferation while
progesterone
Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...
directs AβPP processing towards the non-amyloidogenic pathway, which promotes hESC differentiation into NPC.
AβPP and its
cleavage products do not promote the proliferation and differentiation of post-mitotic neurons; rather, the overexpression of either wild-type or mutant AβPP in post-mitotic neurons induces apoptotic death following their re-entry into the
cell cycle
The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...
.
It is postulated that the loss of sex steroids (including progesterone) but the elevation in
luteinizing hormone
Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) ...
, the adult equivalent of hCG, post-
menopause
Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
and during
andropause drives amyloid-β production
and re-entry of post-mitotic neurons into the cell cycle.
Interactions
Amyloid precursor protein has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with:
*
APBA1
Amyloid beta A4 precursor protein-binding family A member 1 is a protein that in humans is encoded by the ''APBA1'' gene.
Function
The protein encoded by this gene is a member of the X11 protein family. It is a neuronal adaptor protein that in ...
,
[
* ]APBA2
Amyloid beta A4 precursor protein-binding family A member 2 is a protein that in humans is encoded by the ''APBA2'' gene.
Structure
This protein has phosphotyrosine-binding domain (PTB domain or PID) in the middle and two PDZ domains at C-termi ...
,
* APBA3
Amyloid beta A4 precursor protein-binding family A member 3 is a protein that in humans is encoded by the ''APBA3'' gene.
Function
The protein encoded by this gene is a member of the X11 protein family. It is an adapter protein that interacts ...
,
* APBB1
Amyloid beta A4 precursor protein-binding family B member 1 is a protein that in humans is encoded by the ''APBB1'' gene.
Function
The protein encoded by this gene is a member of the Fe65 protein family. It is an adaptor protein localized in th ...
,
* APPBP1
NEDD8-activating enzyme E1 regulatory subunit is a protein that in humans is encoded by the ''NAE1'' gene.
Function
The protein encoded by this gene binds to the beta-amyloid precursor protein. Beta-amyloid precursor protein is a cell surface ...
,
* APPBP2,
* BCAP31
B-cell receptor-associated protein 31 is a protein that in humans is encoded by the ''BCAP31'' gene.
Interactions
BCAP31 has been shown to interact with:
* APP,
* BCL2L1,
* BCL2,
* CASP8, and
* VAMP3
Vesicle-associated membrane protein 3 ...
,
* BLMH
Bleomycin hydrolase is an enzyme that in humans is encoded by the ''BLMH'' gene.
Bleomycin hydrolase (BMH) is a cytoplasmic cysteine peptidase that is highly conserved through evolution. Its biological function is hydrolysis of the reactive elect ...
* CLSTN1
Calsyntenin-1 is a protein that in humans is encoded by the ''CLSTN1'' gene.
Clinical relevance
Mutations in this gene have been shown associated to pathogenic mechanisms of Alzheimer's disease.
Interactions
CLSTN1 has been shown to inte ...
,
* CAV1,
* COL25A1,
* FBLN1
FBLN1 is the gene encoding fibulin-1, an extracellular matrix and plasma protein.
Function
Fibulin-1 is a secreted glycoprotein that is found in association with extracellular matrix structures including fibronectin-containing fibers, elastin-co ...
,
* GSN,
* HSD17B10, and
* SHC1
SHC-transforming protein 1 is a protein that in humans is encoded by the ''SHC1'' gene. SHC has been found to be important in the regulation of apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of pro ...
.
APP interacts with reelin
Reelin, encoded by the ''RELN'' gene, is a large secreted extracellular matrix glycoprotein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this import ...
, a protein implicated in a number of brain disorders, including Alzheimer's disease.
References
Further reading
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External links
GeneReviews/NCBI/NIH/UW entry on Early-Onset Familial Alzheimer Disease
*
Entrez Gene: APP amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)
*
{{Amyloidosis
Alzheimer's disease
Single-pass transmembrane proteins
Neurochemistry
Amyloidosis
Precursor proteins