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APP Gene

protein-coding GIFtS: 74

GC21M026174

amyloid beta (A4) precursor protein
(Previous name: Alzheimer disease )
Symbol approved by the HUGO Gene Nomenclature Committee (HGNC) database
(Previous symbol: AD1)

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc , and/or ⁷Ensembl, ⁸miRBase, and/or ⁹Nature:405,311-319 and CroW21)
About This Section

Aliases
A4 ^³
AAA ^², ⁵
ABETA ^²
ABPP ^², ³
AD1 ^², ³, ⁵
APPI ^², ³
CTFgamma ^²
CVAP ^², ³, ⁵
PN-II ^³
PN2 ^²
PreA4 ^³

Descriptions
Alzheimer disease ^¹
Alzheimer disease amyloid protein ^³
Cerebral vascular amyloid peptide ^², ³
Protease nexin-II ^², ³
amyloid beta (A4) precursor protein ^²
amyloid beta A4 protein ^²
amyloid beta precursor protein ^¹
beta-amyloid peptide ^²
human mRNA for amyloid A4 precursor of Alzheimer's disease ⁹
peptidase nexin-II ^²

External Ids
HGNC: 620¹
Entrez Gene: 351²
UniProtKB: P05067³
Ensembl: ENSG00000142192⁷

Search outside databases for aliases for APP gene

Previous GC identifer: GC21M023831

(According to Entrez Gene, Wikipedia's Gene Wiki,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

EntrezGene summary for APP:

This gene encodes a cell surface receptor and transmembrane precursor protein that is cleaved by

secretases to form a number of peptides. Some of these peptides are secreted and can bind to the

acetyltransferase complex APBB1/TIP60 to promote transcriptional activation, while others form the

protein basis of the amyloid plaques found in the brains of patients with Alzheimer disease.

Mutations in this gene have been implicated in autosomal dominant Alzheimer disease and

cerebroarterial amyloidosis (cerebral amyloid angiopathy). Multiple transcript variants encoding

several different isoforms have been found for this gene. [provided by RefSeq]

UniProtKB/Swiss-Prot: A4_HUMAN, P05067

Function: The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent

enhancers of neuronal apoptosis

Gene Wiki entry for APP (Amyloid_precursor_protein)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 36),
and/or miRBase,
Genomic Views according to UCSC and Ensembl, Transcription factor binding sites according to SABiosciences, Whole Chromsome Sequence According to Nature (Cited Here with Permission):405,311-319 and CroW21)
About This Section

Genomic View:

UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 21q21.2|21q21.3 Ensembl cytogenetic band: 21q21.3 HGNC cytogenetic band: 21q21.2
Nature(405: 311-319) cytogenetic band: 21q21.3

APP Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)

GeneLoc gene densities for chromosome 21 GeneLoc Exon Structure

(about GC identifiers)

GC21M026174:	GeneLoc	Nature:405,311-319
Start:	26,174,732 bp from pter	12,830,594 bp from centromere
End:	26,465,003 bp from pter	13,120,880 bp from centromere
Size:	290,272 bases	290,287 bases
Orientation:	minus strand	minus strand

RefSeq DNA sequence:

NC_000021.7 NT_011512.10

Whole chromosome sequencing:
cDNA sequence:	Y00264
genomic clones:	pT364 to Q22F1

(According to ¹UniProtKB, and/or Ensembl, Phosphorylation sites according to ²Phosphosite, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from Invitrogen, Millipore, Sigma-Aldrich, R&D Systems, Enzo Life Sciences, Abnova, OriGene and/or, Abcam,
Biochemical Assays by Invitrogen, Millipore, R&D Systems, Cell Signaling Technology, and/or Enzo Life Sciences, Ontologies according to Gene Ontology Consortium 01 Apr 2009 and Entrez Gene, Antibodies by Invitrogen, Millipore, Sigma-Aldrich, R&D Systems, Cell Signaling Technology, Abcam, Abnova, and/or Novus Biologicals)
About This Section

UniProtKB/Swiss-Prot: A4_HUMAN, P05067 (See protein sequence)

Recommended Name: Amyloid beta A4 protein precursor

Size: 770 amino acids; 86943 Da

Subunit: Binds, via its C-terminus, to the PID domain of several cytoplasmic proteins, including

APBB family members, the APBA family, MAPK8IP1, SHC1 and, Numb and Dab1 (By similarity). Binding

to Dab1 inhibits its serine phosphorylation (By similarity). Also interacts with GPCR-like protein

BPP, FPRL1, APPBP1, IB1, KNS2 (via its TPR domains) (By similarity), APPBP2 (via BaSS) and DDB1.

In vitro, it binds MAPT via the MT-binding domains (By similarity). Associates with microtubules

in the presence of ATP and in a kinesin-dependent manner (By similarity). Interacts, through a

C-terminal domain, with GNAO1. Amyloid beta-42 binds CHRNA7 in hippocampal neurons. Beta-amyloid

associates with HADH2. Soluble APP binds, via its N-terminal head, to FBLN1. Interacts with CPEB1

(By similarity). Interacts with ANKS1B

Subcellular location: Membrane; Single-pass type I membrane protein. Membrane, clathrin-coated pit.

Note=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

Mass spectrometry: Mass=6461.6; Method=MALDI; Range=712-767; Source=PubMed:12214090;

Mass spectrometry: Mass=6451.6; Method=MALDI; Range=714-770; Source=PubMed:12214090;

Mass spectrometry: Mass=6436.8; Method=MALDI; Range=715-769; Source=PubMed:12214090;

Mass spectrometry: Mass=5752.5; Method=MALDI; Range=719-767; Source=PubMed:12214090;

Miscellaneous: Chelation of metal ions, notably copper, iron and zinc, can induce

histidine-bridging between beta-amyloid molecules resulting in beta-amyloid-metal aggregates. The

affinity for copper is much higher than for other transient metals and is increased under acidic

conditions. Extracellular zinc-binding increases binding of heparin to APP and inhibits

collagen-binding

Sequence caution: Sequence=AAA58727.1; Type=Miscellaneous discrepancy; Note=Contamination by an Alu

repeat;

PDB structures from and Proteopedia :

1AAP (3D)

1AMB (3D)

1AMC (3D)

1AML (3D)

1BA4 (3D)

1BA6 (3D)

1BJB (3D)

1BJC (3D)

1BRC (3D)

1CA0 (3D)

1HZ3 (3D)

1IYT (3D)

1MWP (3D)

1OWT (3D)

1QCM (3D)

1QWP (3D)

1QXC (3D)

1QYT (3D)

1RW6 (3D)

1TAW (3D)

1TKN (3D)

1UO7 (3D)

1UO8 (3D)

1UOA (3D)

1UOI (3D)

1X11 (3D)

1Z0Q (3D)

1ZE7 (3D)

1ZE9 (3D)

1ZJD (3D)

2BEG (3D)

2BOM (3D)

2BP4 (3D)

2FJZ (3D)

2FK1 (3D)

2FK2 (3D)

2FK3 (3D)

2FKL (3D)

2FMA (3D)

2G47 (3D)

2IPU (3D)

2OTK (3D)

2R0W (3D)

3DXC (3D)

3DXD (3D)

3DXE (3D)

3GCI (3D)

Secondary accessions: P09000 P78438 Q13764 Q13778 Q13793 Q16011 Q16014 Q16019 Q16020 Q6GSC0 Q8WZ99

Q9BT38 Q9UC33 Q9UCA9 Q9UCB6 Q9UCC8 Q9UCD1 Q9UQ58

Alternative splicing: 10 isoforms: P05067-1 P05067-2 P05067-3 P05067-4 P05067-5 P05067-6 P05067-7 P05067-8

P05067-9 P05067-10 (Additional isoforms seem to exist. Experimental confirmation may be lacking for some isoforms)

Post-translational modifications:

Proteolytically processed under normal cellular conditions. Cleavage by alpha-secretase or

alternatively by beta-secretase leads to generation and extracellular release of soluble APP

peptides, S-APP-alpha and S-APP-beta, respectively, and the retention of corresponding

membrane-anchored C-terminal fragments, C83 and C99. Subsequent processing of C83 by

gamma-secretase yields P3 peptides. This is the major secretory pathway and is non-amyloidogenic.

Alternatively, presenilin/nicastrin-mediated gamma-secretase processing of C99 releases the

amyloid beta proteins, amyloid-beta 40 (Abeta40) and amyloid-beta 42 (Abeta42), major components

of amyloid plaques, and the cytotoxic C-terminal fragments, gamma-CTF(50), gamma-CTF(57) and

gamma-CTF(59)¹

Proteolytically cleaved by caspases during neuronal apoptosis. Cleavage at Asp-739 by either

caspase-6, -8 or -9 results in the production of the neurotoxic C31 peptide and the increased

production of beta-amyloid peptides¹

N- and O-glycosylated. O-linkage of chondroitin sulfate to the L-APP isoforms produces the APP

proteoglycan core proteins, the appicans. The chondroitin sulfate chain of appicans contains

4-O-sulfated galactose in the linkage region and chondroitin sulfate E in the repeated

disaccharide region (By similarity)¹

Phosphorylation in the C-terminal on tyrosine, threonine and serine residues is neuron-specific.

Phosphorylation can affect APP processing, neuronal differentiation and interaction with other

proteins. Phosphorylated on Thr-743 in neuronal cells by Cdc5 kinase and Mapk10, in dividing cells

by Cdc2 kinase in a cell-cycle dependent manner with maximal levels at the G2/M phase and, in

vitro, by GSK-3-beta. The Thr-743 phosphorylated form causes a conformational change which reduces

binding of Fe65 family members. Phosphorylation on Tyr-757 is required for SHC binding.

Phosphorylated in the extracellular domain by casein kinases on both soluble and membrane-bound

APP. This phosphorylation is inhibited by heparin¹

Extracellular binding and reduction of copper, results in a corresponding oxidation of Cys-144 and

Cys-158, and the formation of a disulfide bond. In vitro, the APP-Cu(+) complex in the presence of

hydrogen peroxide results in an increased production of beta-amyloid-containing peptides¹

View phosphorylation sites using PhosphoSite²

REFSEQ proteins (5 alternative transcripts):

NP_000475.1 NP_001129601.1 NP_001129602.1 NP_958816.1 NP_958817.1

ENSEMBL proteins:

ENSP00000347366 ENSP00000284981 ENSP00000351796 ENSP00000350578 ENSP00000352760 ENSP00000345463

ENSP00000346129

Human Recombinant Proteins

	Browse Drug Discovery Central at Invitrogen for human recombinant proteins
	Millipore Purified and/or Recombinant APP Protein
	Sigma-Aldrich Proteins for APP
	R&D Systems Recombinant & Natural Proteins for APP
	Browse recombinant and purified proteins available from Enzo Life Sciences
	Recombinant Proteins from Abcam (beta Amyloid 37-42, beta Amyloid 17-42, Amyloid Precursor Protein, Amyloid precursor protein, caspase-cleaved, Secretory Amyloid Precursor Protein , beta Amyloid, Amyloid Precursor Protein Frameshift Mutant , Amyloid beta precursor protein, beta amyloid 1-28, beta Amyloid 1-40, beta Amyloid 1-42, beta amyloid 1-43)
	Human Recombinant Proteins from Abnova (APP)

Browse Origene for full length recombinant human proteins expressed in human HEK293 cells

5/8 Gene Ontology (GO) cellular component terms (links to tree view) (see all 8 ):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005576	extracellular region	TAS	10806211
GO:0005737	cytoplasm	IDA	18029348
GO:0005794	Golgi apparatus	IDA	18029348
GO:0005886	plasma membrane	IDA	18029348
GO:0005887	integral to plasma membrane	TAS	10806211

About this table

Antibodies for APP:

	Invitrogen Antibodies for APP
	Millipore Mono- and Polyclonal Antibodies for the study of APP
	Sigma-Aldrich Antibody Arrays and Antibodies for APP
	R&D Systems Antibodies for APP
	Cell Signaling Technology (CST) Antibodies for APP
	Antibodies from Abcam (beta Amyloid 37-42, beta Amyloid 17-42, Amyloid Precursor Protein, Amyloid precursor protein, caspase-cleaved, Secretory Amyloid Precursor Protein , beta Amyloid, Amyloid Precursor Protein Frameshift Mutant , Amyloid beta precursor protein, beta amyloid 1-28, beta Amyloid 1-40, beta Amyloid 1-42, beta amyloid 1-43), each with their Abpromise^SM
	Monoclonal and Polyclonal Antibodies from Abnova (APP)
	Novus Biologicals Antibodies for APP

Assays for APP:

	Invitrogen Assays for APP
	Millipore Kits and Assays for the Analysis of APP
	R&D Systems ELISAs for APP (see all)
	Browse biochemical assays available from Enzo Life Sciences

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

Graphical View of Domain Structure for InterPro Entry P05067

ProtoNet protein and cluster: P05067

2 Blocks protein families:

IPB002223 Pancreatic trypsin inhibitor (Kunitz)

IPB008155 Amyloidogenic glycoprotein (Amyloid A4)

UniProtKB/Swiss-Prot: A4_HUMAN, P05067

Domain: The basolateral sorting signal (BaSS) is required for sorting of membrane proteins to the

basolateral surface of epithelial cells

Domain: The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the

specific binding of the PID domain. However, additional amino acids either N- or C-terminal to the

NPXY motif are often required for complete interaction. The PID domain-containing proteins which

bind APP require the YENPTY motif for full interaction. These interactions are independent of

phosphorylation on the terminal tyrosine residue. The NPXY site is also involved in

clathrin-mediated endocytosis

Similarity: Belongs to the APP family

Similarity: Contains 1 BPTI/Kunitz inhibitor domain

(According to MGI Jun 06 2009, UniProtKB, IUBMB,and/or Genatlas,
shRNA from OriGene, Sigma-Aldrich, RNAi from Sigma-Aldrich,
RNAi Products, Clones, and Q-PCR Products from Invitrogen, Millipore, OriGene, and/or Abnova, siRNAs from Applied Biosystems, SYBR primers from OriGene, Cell-based Assays from Millipore, Ontologies according to Gene Ontology Consortium 01 Apr 2009 via Entrez Gene.)
About This Section

Inhib. RNA:		Invitrogen RNAi Products for gene knock-down (APP)
		Browse for Gene Knock-down Tools from Millipore
		Abnova Chimera RNAi Products for Gene knock-down (APP)

OriGene 29mer shRNA kit in GFP-retroviral vectors (see all 7): NM_001136016

Applied Biosystems Silencer® siRNAs for APP

Sigma-Aldrich siRNA and siRNA Panels for APP

Sigma-Aldrich shRNA Panels and shRNA for APP

Explore Sigma-Aldrich super-pooled esiRNAs

Clones:		Invitrogen Clones for APP
		Browse Clones for the Expression of Recombinant Proteins Available from Millipore

OriGene GFP tagged cDNA clones in CMV expression vector (see all 7): NM_000484
Myc/DDK tagged cDNA clones in CMV expression vector (see all 7): NM_000484
untagged cDNA clones in CMV expression vector (see all 7): NM_000484

Primers:

Browse Quantitative PCR Central at Invitrogen for Q-PCR LUX™ Primers

OriGene genome-wide validated SYBR primer pairs: NM_000484

UniProtKB/Swiss-Prot: A4_HUMAN, P05067

Function: Functions as a cell surface receptor and performs physiological functions on the surface

of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell

mobility and transcription regulation through protein-protein interactions. Can promote

transcription activation through binding to APBB1-HTATIP and inhibits Notch signaling through

interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and

JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor,

mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper

homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces

neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein

oxidation. Can regulate neurite outgrowth through binding to components of the extracellular

matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain

possess protease inhibitor activity

Function: Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind

transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+)

and Fe(2+), respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40.

Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL

particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate

mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau

aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to

oxidative stress and neurotoxicity

Function: Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate

neurite outgrowth in the brain (By similarity)

Function: The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent

enhancers of neuronal apoptosis

Induction: Increased levels during neuronal differentiation

Genatlas biochemistry entry for APP:

amyloid beta (A4) precursor protein (APP 695) undergoing proteolytic cleavages by either alpha,beta

or gamma secretases in or near the transmembrane domain,to yield several secreted

derivatives,including soluble APP,4kDa,beta peptide (A beta) and a related,3 kDa,protein,expressed

ubiquitously by neuronal and non neuronal cells and sorted to axons in neurons and the basolateral

surface in epithelial cells (see PN2)

11 MGI mutant phenotypes (inferred from 12 alleles) (MGI details for App):

behavior/neurological	cellular	growth/size	hearing/vestibular/ear	lethality-postnatal
life span-post-weaning/aging	nervous system	normal	other	reproductive system
skin/coat/nails

5/8 Gene Ontology (GO) molecular function terms (links to tree view) (see all 8 ):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004867	serine-type endopeptidase inhibitor activity	NAS	11279603
GO:0005506	iron ion binding	IEA	--
GO:0005507	copper ion binding	IEA	--
GO:0008201	heparin binding	IEA	--
GO:0008270	zinc ion binding	IEA	--

About this table

(Pathways according to Invitrogen (maps by GeneGo), Millipore, Cell Signaling Technology, Sigma-Aldrich, KEGG and/or UniProtKB,
Sets of similar genes according to GeneDecks, Proteins Network according to SABiosciences, Interactions according to ¹UniProtKB, ²MINT, and/or ³STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2009 via Entrez Gene.)
About This Section

4 Sigma-Aldrich "Your Favorite Gene" Pathways for APP (Your Favorite Gene powered by Ingenuity)

Reelin Signaling in Neurons
Docosahexaenoic Acid (DHA) Signaling
Amyloid Processing
Mitochondrial Dysfunction

GeneDecks APP for the pathways selected above

About GeneDecksing

Gene Network Central^TM Interacting Genes and Proteins Network for APP

5/131 Interacting proteins for APP (ENSP00000284981³ P05067^{1, 2}) via UniProtKB, MINT, and/or STRING (see all 131 )

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
APBA1	Q02410¹	STRING (score=.999) EBI-77613, EBI-368690
APBB1	O00213¹	STRING (score=.999) EBI-77613, EBI-81694
APBB2	Q92870¹	STRING (score=.994) EBI-77613, EBI-79277
APLP1	P51693¹	STRING (score=.744) EBI-302641, EBI-74648
APLP2	Q06481¹	STRING (score=.792) EBI-302641, EBI-79306

About this table

5/7 Gene Ontology (GO) biological process terms (links to tree view) (see all 7 ):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006878	cellular copper ion homeostasis	TAS	15910549
GO:0006897	endocytosis	IEA	--
GO:0006915	apoptosis	IEA	--
GO:0007155	cell adhesion	IEA	--
GO:0007219	Notch signaling pathway	IEA	--

About this table

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, Sigma-Aldrich, Tocris Bioscience, and/or Novoseek and Drugs according to Enzo Life Sciences and/or PharmGKB)
About This Section

Browse drugs & compounds from Enzo Life Sciences

Sigma-Aldrich Small Molecules for APP:

Antagonist

Compounds for APP available from Tocris Bioscience

Compound	Action	CAS number
Amyloid beta-peptide (1-40) (rat)	Amyloid beta-protein fragment	[144409-98-3]
Amyloid beta-peptide (1-42) (rat)	Predominant amyloid beta-protein fragment	[166090-74-0]
Amyloid beta-Peptide (1-42) (human)	Predominant amyloid beta-protein fragment	[107761-42-2]
Amyloid beta-Peptide (1-40) (human)	Amyloid beta-protein fragment	[131438-79-4]
DAPT	gamma-secretase inhibitor	[208255-80-5]

About this table

10/21 Novoseek chemical compound relationships for APP gene (see all 21 )

Compound	Score	Articles	PubMed IDs for Articles with Shared Sentences (# sentences)
thioflavin t	81.39	14	10686395 (1), 15615711 (1), 18202749 (1), 19399778 (1) (see all 14)
happ	77.42	22	7499323 (2), 16027115 (1), 19369541 (1), 7882025 (1) (see all 14)
aspartate(1-)	69.31	1	17352478 (1)
tv-3279	67.67	6	12206996 (2), 12853332 (2), 17197368 (1), 16935943 (1)
thioflavine s	67.20	5	8780408 (1), 10446806 (1), 1373017 (1), 7964904 (1)
phenserine	67.18	13	16690718 (3), 11273593 (2), 17003227 (2), 15974893 (1) (see all 8)
thioflavin	66.73	3	8292358 (1), 7845465 (1)
ladostigil	63.42	13	17197368 (4), 12206996 (2), 12853332 (2), 16935943 (2)
24s-hydroxy-cholesterol	60.88	8	17717740 (2), 15717023 (1), 17532301 (1), 15148325 (1) (see all 5)
apstatin	53.12	5	10395480 (2), 18084312 (1), 16144980 (1), 11106490 (1)

About this table

(GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 219 Homo sapiens; Jun 2 2009) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView,
non coding RNAs according to RNAdb,
ESTs according to GeneTide,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from Invitrogen, Millipore, and/or Abnova,
siRNAs from Applied Biosystems, Sigma-Aldrich,
shRNA from Sigma-Aldrich, OriGene,
Tagged/untagged cDNA clones from OriGene,
Expression Assays from Applied Biosystems)
About This Section

Inhib. RNA:		Invitrogen RNAi Products for gene knock-down (APP)
		Browse for Gene Knock-down Tools from Millipore
		Abnova Chimera RNAi Products for Gene knock-down (APP)

OriGene 29mer shRNA kit in GFP-retroviral vectors (see all 7): NM_001136016

Sigma-Aldrich siRNA and siRNA Panels for APP

Sigma-Aldrich shRNA Panels and shRNA for APP

Explore Sigma-Aldrich super-pooled esiRNAs

Applied Biosystems Silencer® siRNAs:

NM_000484 NM_001136016 NM_001136129 NM_001136130 NM_001136131 NM_201413 NM_201414

REFSEQ mRNAs for APP gene (5 alternative transcripts):

NM_000484.3 NM_001136129.2 NM_001136130.2 NM_201413.2 NM_201414.2

Applied Biosystems TaqMan ® Gene Expression Assays:

NM_000484 NM_001136129 NM_001136130 NM_201413 NM_201414

               OriGene GFP tagged cDNA clones in CMV expression vector (see all 7): NM_000484
                                 Myc/DDK tagged cDNA clones in CMV expression vector (see all 7): NM_000484
                                 untagged cDNA clones in CMV expression vector (see all 7): NM_000484

Additional cDNA sequence:

AB066441.2 AF282245.1 AK294534.1 AK295373.1 AK295621.1 AK296229.1 AK297229.1 AK297412.1

AK298861.1 AK311717.1 AK312326.1 BC004369.1 BC065523.1 BC065529.1 BC110059.1 CR618347.1

CR618842.1 M15533.1 M16765.1 M18734.1 M28373.1 M35675.1 S41243.1 S60721.1

S61380.1 S61383.1 X06981.1 X06982.1 X06989.1 Y00264.1

24/44 DOTS entries (see all 44 ):

DT.95298153 DT.100894758 DT.92047441 DT.97861505 DT.456045 DT.95135651 DT.100680290 DT.100680285

DT.100043645 DT.100680298 DT.100680291 DT.95246943 DT.100680273 DT.98132128 DT.100894757 DT.85105138

DT.99974598 DT.91775407 DT.91775451 DT.97867296 DT.100894759 DT.121133292 DT.121133321 DT.121133336

24/1024 AceView cDNA sequences (see all 1024 ):

CR618842 BQ931658 CD514570 BF222217 AW020412 BI857339 BM971950 AW630017

BM510519 BM694400 AA100382 BQ440126 BG319612 CA440532 AV708880 BM765811

F04912 BM847070 BG030179 BQ421279 CA411568 BM829181 AI219108 M15532

highest scoring ESTs for APP:

AL518480 AL532648 AL537562 AL543516 AL550425 AL550975 AL557346 AU128077 AU137092 BC004369

Unigene Cluster for APP:

Amyloid beta (A4) precursor protein

Hs.434980 [show with all ESTs]

Unigene Representative Sequence: NM_000484

GeneLoc Exon Structure

7 Ensembl transcripts including schematic representations:

ENST00000355226 ENST00000346798 ENST00000358918 ENST00000357903 ENST00000359726 ENST00000348990

ENST00000354192

(Experimental results according to ¹GeneNote and GNF BioGPS,
probe sets-to-genes annotations according to ²GeneAnnot , ³GeneTide , Sets of similar genes according to GeneDecks, Electronic Northern calculations according to data from UniGene (Build 219 Homo sapiens), SAGE tags according to CGAP, plus additional links to SOURCE, and/or GNF BioGPS, and/or EXPOLDB, and/or UniProtKB,
Expression Assays from Applied Biosystems )
About This Section

APP expression in normal and diseased human tissues

Applied Biosystems TaqMan ® Gene Expression Assays for APP

¹ / ² / ³

8 probe-sets matching APP gene

Affymetrix probe-set	Array	# genes	Sensitivity	Specificity	Correlation	Length	Gb_Accession	Consensus	Uniqueness	Score	Rank
Affymetrix probe-set	Array	GeneAnnot data			GeneNote data		GeneTide data
41136_s_at²^{, 3}	U95-A	1	1.00	1.00	0.98	0.87	X13466	0.20	1.00	0.72	1
64309_f_at²^{, 3}	U95-C	1	0.88	1.00	0.93	1.13	AI625555	0.60	1.00	0.82	1
200602_at²^{, 3}	U133-A	1	1.00	1.00	--	--	NM_000484	0.60	1.00	0.82	1
214953_s_at²^{, 3}	U133-A	1	1.00	1.00	--	--	X06989	0.80	0.88	0.84	1
211277_x_at²^{, 3}	U133-A	13	1.00	0.85	--	--	BC004369	0.80	1.00	0.91	1
200602_at²	U133Plus2	1	1.00	1.00	--	--	--	--	--	--	--
214953_s_at²	U133Plus2	1	1.00	1.00	--	--	--	--	--	--	--
211277_x_at²	U133Plus2	13	1.00	0.85	--	--	--	--	--	--	--

About this table

Data from

(Publications) and GNF BioGPS
About these images
About these images

CGAP SAGE TAG: ATCGCTTTCT

SOURCE GeneReport for Unigene cluster: Hs.434980
Expression variation in blood from EXPOLDB for APP
UniProtKB/Swiss-Prot: A4_HUMAN, P05067
Tissue specificity: Expressed in all fetal tissues examined with highest levels in brain, kidney,
heart and spleen. Weak expression in liver. In adult brain, highest expression found in the
frontal lobe of the cortex and in the anterior perisylvian cortex-opercular gyri. Moderate
expression in the cerebellar cortex, the posterior perisylvian cortex-opercular gyri and the
temporal associated cortex. Weak expression found in the striate, extra-striate and motor
cortices. Expressed in cerebrospinal fluid, and plasma. Isoform APP695 is the predominant form in
neuronal tissue, isoform APP751 and isoform APP770 are widely expressed in non-neuronal cells.
Isoform APP751 is the most abundant form in T-lymphocytes. Appican is expressed in astrocytes

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD and/or ⁵MGI Jun 06 2009, with possible further links to Flybase and/or WormBase, Gene Trees according to Ensembl)
About This Section

Orthologs for APP gene from 5/10 species (see all 10 )

Organism	Gene	Locus	Description	Human Similarity	NCBI accessions
dog (Canis familiaris)	APP¹	--	amyloid beta (A4) precursor protein	87.58(n) 91.8(a)	403407 NM_001006601.1 NP_001006601.1
chimpanzee (Pan troglodytes)	APP¹	--	amyloid beta (A4) precursor protein	95.44(n) 94.53(a)	473931 NM_001013018.1 NP_001013036.1
cow (Bos taurus)	APP¹	--	amyloid beta (A4) precursor protein	91.27(n) 97.7(a)	280722 NM_001076796.1 NP_001070264.1
rat (Rattus norvegicus)	App¹	--	amyloid beta (A4) precursor protein	85.9(n) 92.23(a)	54226 NM_019288.1 NP_062161.1
mouse (Mus musculus)	App^{1, 5}	16 (56.00 cM)⁵	amyloid beta (A4) precursor protein^{1, 5}	89.26(n)¹ 97.41(a)¹	11820¹ NM_007471.2¹ NP_031497.2¹ AF199003⁵ AF199004⁵ (see all 61)

About this table Species with no ortholog for APP

ENSEMBL Gene Tree for APP

(Paralogs according to ¹HomoloGene
and ²Ensembl, Pseudogenes according to ³Pseudogene.org)
About This Section

Paralogs for APP gene

APLP2² APLP1²

(According to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, and UniProtKB, Linkage Disequilibrium by HapMap, Genotyping Reagents from Applied Biosystems)
About This Section

10/2473 NCBI SNPs in APP are shown (see all 2473 )
(Click for Applied Biosystems TaqMan ® Genotyping Assay) (see all 592)

AB	SNP ID	Valid	Chr 21 pos	Sequence	Recs	AA Chg	Type	More	Recs	Pop	Total sample	More
AB	Genomic Data				Transcription Data				Allele Frequencies
				--	--	--		--	--			--
	rs9305282^1,2	A,C,F,H	26434454(+)	`GAGATC/GAACAA`	4	--	int¹ ut5¹		7	EU EA WA NA	552
	rs466448^1,2	A,C,F,H	26465979(+)	`CAGATG/ATATCC`	3	--	ng3¹		12	EA EU WA NA NS	2278
	rs364048^1,2	C,F,H	26465912(+)	`TGGATT/CAAACA`	3	--	ng3¹		18	NS EU EA WA	1122
	rs364051^1,2	A,C,F	26466117(+)	`CTCCCT/CTGCTC`	3	--	ng3¹ trp³		5	NS	140
	rs2019263^1,2	C,F,H	26174474(-)	`CAAAGG/AGAAAA`	3	--	ng5¹		4	EU EA WA	414
	rs466433^1,2	C,F	26465834(+)	`ACCTCA/GAACGC`	3	--	ng3¹		5	NS	186
	rs459543^1,2	C,F	26464920(+)	`ACGCTC/GCTCCG`	5	--	ut5¹ ese³		6	MN NS	318
--	rs363973^1,2	C,H	26466857(+)	`tactcA/Ctgcct`	3	--	ng3¹		3	EA WA	276
	rs1059461^1,2	F	26174915(-)	`GAGAAG/AAGGCA`	7	--	ut3¹ ese³ trp³		1	MN	184
--	rs45455403^1,2	F	26175262(-)	`ACACAC/AGTTTG`	7	--	ut3¹		5	NS	190

About this table

HapMap Linkage Disequilibrium images for APP (up to first 250kb)

(in which this Gene is Involved, According to OMIM, UniProtKB, Novoseek, PharmGKB, Genatlas, GeneTests, Blood group antigen gene mutations by BGMUT, HGMD, GAD, HuGE Navigator, BCGD, and/or TGDB.)
About This Section

OMIM: 104760

UniProtKB/Swiss-Prot: A4_HUMAN, P05067

Defects in APP are the cause of Alzheimer disease type 1 (AD1) [MIM:104300]. AD1 is a

familial early-onset form of Alzheimer disease. It can be associated with cerebral amyloid

angiopathy. Alzheimer disease is a neurodegenerative disorder characterized by progressive

dementia, loss of cognitve abilities, and deposition of fibrillar amyloid proteins as

intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid

deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide

(s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase

processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31

derived from APP, are also implicated in neuronal death

Defects in APP are the cause of amyloidosis cerebroarterial Dutch type (AMYLCAD)

[MIM:605714]; also known as hereditary cerebral hemorrhage with amyloidosis Dutch type (HCHWAD).

AMYLCAD is a hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the

cerebral vessels. Beta-APP40 is the predominant form of cerebrovascular amyloid. Amyloid is not

found outside the nervous system. The principal clinical characteristics are recurrent cerebral

and cerebellar hemorrhages, recurrent strokes, cerebral ischemia, cerebral infarction, and

progressive mental deterioration. Onset of the disease is in middle age (44 to 60 years). Patients

develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid

deposits are rare and largely in the form of pre-amyloid lesions or diffuse plaque-like

structures. They are Congo red negative and lack the dense amyloid cores commonly present in

Alzheimer disease

Defects in APP are the cause of amyloidosis cerebroarterial Italian type (AMYLCAIT)

[MIM:605714]. AMYLCAIT is a hereditary localized amyloidosis due to amyloid-beta A4 peptide(s)

deposition in the cerebral vessels, resulting in cerebral amyloid angiopathy. Amyloid is not found

outside the nervous system. It is a condition very similar to AMYLCAD, but the clinical course is

less severe. Patients manifest mild cognitive decline, recurrent strokes, and epilepsy in some

cases. There are extensive amyloid deposits in leptomeningeal and cortical vessels and, to a

lesser extent, in the neuropil of the cerebral cortex, in the absence of neurofibrillary tangles

Defects in APP are the cause of amyloidosis cerebroarterial Iowa type (AMYLCAIW)

[MIM:605714]. AMYLCAIW is a hereditary amyloidosis due to amyloid-beta A4 peptide(s) deposition.

Patients have progressive aphasic dementia, leukoencephalopathy, and occipital calcifications

10/96 Novoseek disease relationships for APP gene (see all 96 )

Disease	Score	Articles	PubMed IDs for Articles with Shared Sentences (# sentences)
alzheimers disease	97.73	3721	9037522 (6), 15992373 (5), 11033334 (4), 12727689 (4) (see all 99)
senile plaques	96.92	915	1704190 (4), 7671455 (4), 1562053 (3), 1703383 (3) (see all 99)
neurofibrillary tangles	90.26	133	7684484 (3), 16413130 (2), 15575491 (2), 7824200 (1) (see all 99)
cerebral amyloid angiopathy	89.26	82	1303239 (2), 11760381 (2), 9295214 (2), 11021833 (2) (see all 67)
amyloid deposition	87.84	72	8761343 (2), 7639729 (2), 1632967 (1), 10681074 (1) (see all 61)
neurodegeneration	84.40	167	15645264 (2), 14529455 (2), 9865935 (2), 8590049 (2) (see all 99)
neurodegenerative diseases	81.96	81	8294927 (1), 8021287 (1), 15672443 (1), 16027166 (1) (see all 67)
dementia	79.87	158	1723832 (3), 15184603 (3), 9717183 (2), 18300294 (2) (see all 99)
amyloidosis	79.65	116	8267600 (2), 9133629 (2), 9014180 (2), 2113597 (1) (see all 93)
brain diseases	79.59	60	9614075 (2), 7619525 (1), 11059791 (1), 15558879 (1) (see all 51)

About this table

GeneTests: APP

Early-Onset Familial Alzheimer Disease

Human Gene Mutation Database: APP
Genetic Association Database: APP
Human Genome Epidemiology Navigator: APP (64 documents)

(Possibly Related Articles in Doctor's Guide)
About This Section

(in PubMed. Associations of this gene to articles via ¹Novoseek, ²HGNC, ³Entrez Gene, ⁴UniProtKB/Swiss-Prot, ⁵UniProtKB/TrEMBL, ⁶GAD, and/or ⁷PharmGKB)
About This Section

10/2664 PubMed articles for APP gene (see all 2664 ):

Regulation of amyloid protein precursor (APP) binding to collagen and mapping of the binding sites on APP and collagen type I. (PubMed id 8576160)^{1, 3, 4} Beher D.... Multhaup G. (1996)
Mutagenesis identifies new signals for beta-amyloid precursor protein endocytosis, turnover, and the generation of secreted fragments, including Abeta42. (PubMed id 10383380)^{1, 3, 4} Perez R.G.... Koo E.H. (1999)
Regulation of FE65 nuclear translocation and function by amyloid beta-protein precursor in osmotically stressed cells. (PubMed id 18468999)^{1, 3, 4} Nakaya T....Suzuki T. (2008)
Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of beta-amyloid. (PubMed id 11517218)^{1, 3, 4} Ando K.... Suzuki T. (2001)
A novel mutation in the PSEN2 gene (T430M) associated with variable expression in a family with early-onset Alzheimer disease. (PubMed id 12925374)^{1, 3, 6} Ezquerra M....Oliva R. (2003)
A second cytotoxic proteolytic peptide derived from amyloid beta- protein precursor. (PubMed id 10742146)^{1, 3, 4} Lu D.C.... Bredesen D.E. (2000)
Linkage and mutational analysis of familial Alzheimer disease kindreds for the APP gene region. (PubMed id 1415269)^{1, 3, 4} Kamino K.... Schellenberg G.D. (1992)
Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene. (PubMed id 1944558)^{1, 3, 4} Chartier-Harlin M.-C.... Mullan M. (1991)
Prevalence of pathogenic mutations in an Italian clinical series of patients with familial dementia. (PubMed id 15975068)^{1, 3, 6} Signorini S....Binetti G. (2004)
Mutations in presenilin 1, presenilin 2 and amyloid precursor protein genes in patients with early-onset Alzheimer's disease in Poland. (PubMed id 14769392)^{1, 3, 6} Zekanowski C....Barcikowska M. (2003)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, and/or H-InvDB)
About This Section

Entrez Gene: 351	HGNC: 620	AceView: APP	Ensembl:ENSG00000142192	euGenes: HUgn351
ECgene: APP	H-InvDB: APP

(According to HUGE)
About This Section

(According to ATLAS, HORDE, IMGT, MTDB, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
Alzheimer Research Forum	http://www.alzforum.org/res/com/mut/app/default.asp
AD mutations	http://www.molgen.ua.ac.be/ADmutations/
GeneReviews	http://www.genetests.org/query?gene=APP
NIEHS-SNPs	http://egp.gs.washington.edu/data/app/
Wikipedia	http://en.wikipedia.org/wiki/Amyloid_beta

Licensable Technologies for APP
(Available from WIS Yeda, Salk, Tufts)

About This Section

(Reagents available from Applied Biosystems, Antibodies and assays by Cell Signaling Technology, Abcam, Novus Biologicals,
Sigma-Aldrich, R&D Systems, Millipore, Abnova, and/or Invitrogen, Clones available from OriGene,and/or Invitrogen, Drugs and/or compounds by Sigma-Aldrich,
Enzo Life Sciences, and/or Tocris Bioscience)
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Products for APP:

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Search OriGene for APP

Tocris compounds for APP

Search www.enzolifesicences.com for proteins, assays, substrates, inhibitors & antibodies

Antibodies for APP

GeneCards Homepage - Last full update: 2 Jul 2009 Incremental update: 13 Oct 2009

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Gene Index: 3 5 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

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APP Gene at Home site.
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APP Gene

protein-coding GIFtS: 74

Aliases &
Descriptions
for APP

Summaries
for APP

Genomic Location
for APP

Proteins
for APP

Protein Domains/
Families
for APP

Gene Function
for APP

Pathways & Interactions
for APP

Drugs & Compounds
for APP

Transcripts
for APP

Expression
for APP

Orthologs
for APP

Paralogs
for APP

SNPs/Variants
for APP

Disorders & Mutations
for APP

Medical News
for APP

Publications
for APP

Search for APP

Genome Databases showing APP

Other Databases showing APP

Specialized Databases showing APP

Licensable Technologies
for APP

Services
for APP

Gene Index: 3 5 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

APP (Gene Symbol)
A4
AAA
ABETA
ABPP
AD1
APPI
CTFgamma
CVAP
PN-II
PN2
PreA4
Alzheimer disease
Alzheimer disease amyloid protein
Cerebral vascular amyloid peptide
Protease nexin-II
amyloid beta (A4) precursor protein
amyloid beta A4 protein
amyloid beta precursor protein
beta-amyloid peptide
human mRNA for amyloid A4 precursor of Alzheimer's disease
peptidase nexin-II

APP Gene

protein-coding GIFtS: 74

Aliases & Descriptionsfor APP

Summariesfor APP

Genomic Locationfor APP

Proteinsfor APP

Protein Domains/Familiesfor APP

Gene Functionfor APP

Pathways & Interactionsfor APP

Drugs & Compoundsfor APP

Transcriptsfor APP

Expression for APP

Orthologsfor APP

Paralogsfor APP

SNPs/Variantsfor APP

Disorders & Mutationsfor APP

Medical Newsfor APP

Publicationsfor APP

Search for APP

Genome Databases showing APP

Other Databases showing APP

Specialized Databases showing APP

Licensable Technologiesfor APP

Servicesfor APP

Gene Index: 3 5 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

Aliases &
Descriptions
for APP

Summaries
for APP

Genomic Location
for APP

Proteins
for APP

Protein Domains/
Families
for APP

Gene Function
for APP

Pathways & Interactions
for APP

Drugs & Compounds
for APP

Transcripts
for APP

Expression
for APP

Orthologs
for APP

Paralogs
for APP

SNPs/Variants
for APP

Disorders & Mutations
for APP

Medical News
for APP

Publications
for APP

Licensable Technologies
for APP

Services
for APP