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Protein Page:
APP (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
APP a cell surface receptor that influences neurite growth, neuronal adhesion and axonogenesis. Cleaved by secretases to form a number of peptides, some of which bind to the acetyltransferase complex Fe65/TIP60 to promote transcriptional activation. The Abeta peptide is released from the cell, its extracellular deposition and accumulation form the main components of amyloid plaques in Alzheimer's disease. Mutations in this gene have been implicated in autosomal dominant Alzheimer disease and cerebroarterial amyloidosis. Can promote transcription activation through binding to Fe65-Tip60 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. 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. Induces a RAGE-dependent pathway that activates p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1. Binds, via its C-terminus, to the PID domain of several cytoplasmic proteins, including APBB family members, the APBA family, JIP1, SHC1 and, NUMB and DAB1. Binding to DAB1 inhibits its serine phosphorylation. Associates with microtubules in the presence of ATP and in a kinesin-dependent manner. Amyloid beta-42 binds nAChRA7 in hippocampal neurons. Beta-amyloid associates with HADH2. Soluble APP binds, via its N-terminal head, to FBLN1. 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. 10 isoforms of the human protein are produced by alternative splicing. 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. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Belongs to the APP family. Note: This description may include information from UniProtKB.
Protein type: Membrane protein, integral; Cell surface; Apoptosis; Receptor, misc.; Transcription factor
Chromosomal Location of Human Ortholog: 21q21.3
Cellular Component: Golgi apparatus; extracellular space; cell surface; intracellular membrane-bound organelle; integral to plasma membrane; extracellular region; integral to membrane; dendritic spine; coated pit; cytosol; lipid raft; ciliary rootlet; nuclear envelope lumen; apical part of cell; perinuclear region of cytoplasm; axon; cytoplasm; plasma membrane; synapse; spindle midzone; dendritic shaft; neuromuscular junction; receptor complex
Molecular Function: serine-type endopeptidase inhibitor activity; heparin binding; identical protein binding; protein binding; protease activator activity; enzyme binding; DNA binding; transition metal ion binding; PTB domain binding; acetylcholine receptor binding; receptor binding
Biological Process: extracellular matrix organization and biogenesis; adult locomotory behavior; mRNA polyadenylation; locomotory behavior; positive regulation of mitotic cell cycle; protein amino acid phosphorylation; regulation of translation; platelet degranulation; synaptic growth at neuromuscular junction; forebrain development; dendrite development; collateral sprouting in the absence of injury; visual learning; cell adhesion; neuromuscular process controlling balance; neurite development; platelet activation; cholesterol metabolic process; Notch signaling pathway; cellular copper ion homeostasis; regulation of epidermal growth factor receptor activity; mating behavior; axon cargo transport; regulation of multicellular organism growth; endocytosis; axon midline choice point recognition; G2 phase of mitotic cell cycle; smooth endoplasmic reticulum calcium ion homeostasis; negative regulation of neuron differentiation; neuron apoptosis; axonogenesis; suckling behavior; ionotropic glutamate receptor signaling pathway; regulation of protein binding; regulation of synapse structure and activity; innate immune response; positive regulation of transcription from RNA polymerase II promoter; response to oxidative stress; blood coagulation; neuron remodeling
Reference #:  P05067 (UniProtKB)
Alt. Names/Synonyms: A4; AAA; ABETA; ABPP; AD1; AICD-50; AICD-57; AICD-59; AID(50); AID(57); AID(59); Alzheimer disease amyloid protein; amyloid beta (A4) precursor protein; Amyloid beta A4 protein; Amyloid intracellular domain 50; Amyloid intracellular domain 57; Amyloid intracellular domain 59; APP; APPI; beta-amyloid peptide; Beta-amyloid protein 40; Beta-amyloid protein 42; Beta-APP40; Beta-APP42; C31; C80; C83; C99; Cerebral vascular amyloid peptide; CTFgamma; CVAP; Gamma-CTF(50); Gamma-CTF(57); Gamma-CTF(59); Gamma-secretase C-terminal fragment 50; Gamma-secretase C-terminal fragment 57; Gamma-secretase C-terminal fragment 59; N-APP; P3(40); P3(42); peptidase nexin-II; PN-II; PN2; PreA4; Protease nexin-II; S-APP-alpha; S-APP-beta; Soluble APP-alpha; Soluble APP-beta
Gene Symbols: APP
Molecular weight: 86,943 Da
Basal Isoelectric point: 4.73  Predict pI for various phosphorylation states
CST Pathways:  Alzheimer's Disease  |  Apoptosis Regulation
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

APP

Protein Structure Not Found.


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Sites Implicated In
cell cycle regulation: T743‑p
cell growth, altered: T743‑p
intracellular localization: T743‑p
molecular association, regulation: T743‑p, Y757‑p
protein stabilization: T743‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

► Hide Isoforms
 
0 1 T107-ga RGRKQCKtHPHFVIP
0 1 Y115-p HPHFVIPyRCLVGEF
1 1 S198 EESDNVDSADAEEDD
1 1 S206 ADAEEDDSDVWWGGA
0 1 T352-ga MSQSLLKttQEPLAR
0 1 T353-ga SQSLLKttQEPLARD
0 1 T366-ga RDPVKLPttAAstPD
0 1 T367 DPVKLPtTAAstPDA
0 1 T367 DPVKLPtTAAstPDA
0 1 T367-ga DPVKLPttAAstPDA
0 1 S370 KLPttAAStPDAVDK
0 1 S370-ga KLPttAAstPDAVDK
0 1 T371-ga LPttAAstPDAVDKY
0 1 Y378 tPDAVDKYLEtPGDE
0 1 T381-p AVDKYLEtPGDENEH
0 1 T381-ga AVDKYLEtPGDENEH
0 4 S441-p HFQEKVEsLEQEAAN
0 1 T600-ga LMPSLTEtKTTVELL
0 1 T651-ga PAADRGLttRPGsGL
0 1 T652-ga AADRGLttRPGsGLt
0 1 S656-ga GLttRPGsGLtNIKt
0 1 T659-ga tRPGsGLtNIKtEEI
1 0 K662 GsGLtNIKtEEIsEV
0 1 T663-ga sGLtNIKtEEIsEVk
0 1 S667-ga NIKtEEIsEVkMDAE
2 0 K670-sm tEEIsEVkMDAEFRH
3 0 S679-p DAEFRHDsGYEVHHQ
1 0 K687-ne GYEVHHQkLVFFAED
1 0 K699-ne AEDVGSNkGAIIGLM
0 1 K724-ac VITLVMLkkkQytsI
1 0 K724-ne VITLVMLkkkQytsI
0 2 K725-ac ITLVMLkkkQytsIH
1 0 K725-ne ITLVMLkkkQytsIH
0 1 K726 TLVMLkkKQytsIHH
1 0 K726-ne TLVMLkkkQytsIHH
1 1 Y728-p VMLkkkQytsIHHGV
4 0 T729-p MLkkkQytsIHHGVV
5 0 S730-p LkkkQytsIHHGVVE
32 7 T743-p VEVDAAVtPEERHLS
0 42 K751-ub PEERHLSkMQQNGyE
1 0 K751-ne PEERHLSkMQQNGyE
10 855 Y757-p SkMQQNGyENPtykF
0 2 T761-p QNGyENPtykFFEQM
4 238 Y762-p NGyENPtykFFEQMQ
0 4 K763-ub GyENPtykFFEQMQN
1 0 K763-ne GyENPtykFFEQMQN
3823 : Phospho-APP (Thr668) Antibody
6986 : Phospho-APP (Thr668) (D90B8) Rabbit mAb
  APP iso4  
T107 RGRKQCKTHPHFVIP
Y115 HPHFVIPYRCLVGEF
S198-p EESDNVDsADAEEDD
S206-p ADAEEDDsDVWWGGA
- gap
- gap
T291 EEVVRVPTtAAsTPD
T292-p EVVRVPTtAAsTPDA
T292 EVVRVPTTAAsTPDA
T292 EVVRVPTTAAsTPDA
S295-p RVPTtAAsTPDAVDK
S295 RVPTtAASTPDAVDK
T296 VPTtAAsTPDAVDKy
Y303-p TPDAVDKyLETPGDE
T306 AVDKyLETPGDENEH
T306 AVDKyLETPGDENEH
S366 HFQEKVESLEQEAAN
T525 LMPSLTETKTTVELL
T576 PAADRGLTTRPGSGL
T577 AADRGLTTRPGSGLT
S581 GLTTRPGSGLTNIkT
T584 TRPGSGLTNIkTEEI
K587-sm GSGLTNIkTEEISEV
T588 SGLTNIkTEEISEVk
S592 NIkTEEISEVkMDAE
K595-sm TEEISEVkMDAEFRH
S604 DAEFRHDSGYEVHHQ
K612 GYEVHHQKLVFFAED
K624 AEDVGSNKGAIIGLM
K649 VITLVMLKKKQYtsI
K649 VITLVMLKKKQYtsI
K650 ITLVMLKKKQYtsIH
K650 ITLVMLKKKQYtsIH
K651 TLVMLKKKQYtsIHH
K651 TLVMLKKKQYtsIHH
Y653 VMLKKKQYtsIHHGV
T654-p MLKKKQYtsIHHGVV
S655-p LKKKQYtsIHHGVVE
T668-p VEVDAAVtPEERHLS
K676 PEERHLSKMQQNGyE
K676 PEERHLSKMQQNGyE
Y682-p SKMQQNGyENPTyKF
T686 QNGyENPTyKFFEQM
Y687-p NGyENPTyKFFEQMQ
K688 GyENPTyKFFEQMQN
K688 GyENPTyKFFEQMQN
3823 : Phospho-APP (Thr668) Antibody
6986 : Phospho-APP (Thr668) (D90B8) Rabbit mAb
  APP iso8  
T107 RGRKQCKTHPHFVIP
Y115 HPHFVIPYRCLVGEF
S198 EESDNVDSADAEEDD
S206 ADAEEDDSDVWWGGA
- gap
- gap
T347 VCGSAIPTTAASTPD
T348 CGSAIPTTAASTPDA
T348 CGSAIPTTAASTPDA
T348 CGSAIPTTAASTPDA
S351 AIPTTAASTPDAVDK
S351 AIPTTAASTPDAVDK
T352 IPTTAASTPDAVDKY
Y359 TPDAVDKYLETPGDE
T362 AVDKYLETPGDENEH
T362 AVDKYLETPGDENEH
S422 HFQEKVESLEQEAAN
T581 LMPSLTETKTTVELL
T632 PAADRGLTTRPGSGL
T633 AADRGLTTRPGSGLT
S637 GLTTRPGSGLTNIKT
T640 TRPGSGLTNIKTEEI
K643 GSGLTNIKTEEISEV
T644 SGLTNIKTEEISEVK
S648 NIKTEEISEVKMDAE
K651 TEEISEVKMDAEFRH
S660 DAEFRHDSGYEVHHQ
K668 GYEVHHQKLVFFAED
K680 AEDVGSNKGAIIGLM
K705 VITLVMLKKKQYtsI
K705 VITLVMLKKKQYtsI
K706 ITLVMLKKKQYtsIH
K706 ITLVMLKKKQYtsIH
K707 TLVMLKKKQYtsIHH
K707 TLVMLKKKQYtsIHH
Y709 VMLKKKQYtsIHHGV
T710-p MLKKKQYtsIHHGVV
S711-p LKKKQYtsIHHGVVE
T724-p VEVDAAVtPEERHLS
K732 PEERHLSKMQQNGyE
K732 PEERHLSKMQQNGyE
Y738-p SKMQQNGyENPTyKF
T742 QNGyENPTyKFFEQM
Y743-p NGyENPTyKFFEQMQ
K744 GyENPTyKFFEQMQN
K744 GyENPTyKFFEQMQN
3823 : Phospho-APP (Thr668) Antibody
6986 : Phospho-APP (Thr668) (D90B8) Rabbit mAb
  mouse

► Hide Isoforms
 
T107 RGRKQCKTHTHIVIP
Y115 HTHIVIPYRCLVGEF
S198 EESDSVDSADAEEDD
S206 ADAEEDDSDVWWGGA
T352 STQSLLKTTSEPLPQ
T353 TQSLLKTTSEPLPQD
T366 QDPDKLPTTAASTPD
T367 DPDKLPTTAASTPDA
T367 DPDKLPTTAASTPDA
T367 DPDKLPTTAASTPDA
S370 KLPTTAASTPDAVDK
S370 KLPTTAASTPDAVDK
T371 LPTTAASTPDAVDKY
Y378 TPDAVDKYLETPGDE
T381 AVDKYLETPGDENEH
T381 AVDKYLETPGDENEH
S441-p HFQEKVEsLEQEAAN
T600 LMPSLTETKTTVELL
T651 PAADRGLTTRPGSGL
T652 AADRGLTTRPGSGLT
S656 GLTTRPGSGLTNIKT
T659 TRPGSGLTNIKTEEI
K662 GSGLTNIKTEEISEV
T663 SGLTNIKTEEISEVK
S667 NIKTEEISEVKMDAE
K670 TEEISEVKMDAEFGH
S679-p DAEFGHDsGFEVRHQ
K687 GFEVRHQKLVFFAED
K699 AEDVGSNKGAIIGLM
K724 VITLVMLKKkQYTSI
K724 VITLVMLKKkQYTSI
K725 ITLVMLKKkQYTSIH
K725 ITLVMLKKkQYTSIH
K726-ub TLVMLKKkQYTSIHH
K726 TLVMLKKKQYTSIHH
Y728 VMLKKkQYTSIHHGV
T729 MLKKkQYTSIHHGVV
S730 LKKkQYTSIHHGVVE
T743-p VEVDAAVtPEERHLS
K751-ub PEERHLSkMQQNGyE
K751 PEERHLSKMQQNGyE
Y757-p SkMQQNGyENPTykF
T761 QNGyENPTykFFEQM
Y762-p NGyENPTykFFEQMQ
K763-ub GyENPTykFFEQMQN
K763 GyENPTyKFFEQMQN
3823 : Phospho-APP (Thr668) Antibody
6986 : Phospho-APP (Thr668) (D90B8) Rabbit mAb
  APP iso2  
T107 RGRKQCKTHTHIVIP
Y115 HTHIVIPYRCLVGEF
S198 EESDSVDSADAEEDD
S206 ADAEEDDSDVWWGGA
- gap
- gap
T291 EEVVRVPTtAASTPD
T292 EVVRVPTTAASTPDA
T292-gl EVVRVPTtAASTPDA
T292 EVVRVPTTAASTPDA
S295 RVPTtAASTPDAVDK
S295 RVPTtAASTPDAVDK
T296 VPTtAASTPDAVDKY
Y303 TPDAVDKYLETPGDE
T306 AVDKYLETPGDENEH
T306 AVDKYLETPGDENEH
S366-p HFQEKVEsLEQEAAN
T525 LMPSLTETKTTVELL
T576 PAADRGLTTRPGSGL
T577 AADRGLTTRPGSGLT
S581 GLTTRPGSGLTNIKT
T584 TRPGSGLTNIKTEEI
K587 GSGLTNIKTEEISEV
T588 SGLTNIKTEEISEVK
S592 NIKTEEISEVKMDAE
K595 TEEISEVKMDAEFGH
S604 DAEFGHDSGFEVRHQ
K612 GFEVRHQKLVFFAED
K624 AEDVGSNKGAIIGLM
K649 VITLVMLKKKQyTSI
K649 VITLVMLKKKQyTSI
K650 ITLVMLKKKQyTSIH
K650 ITLVMLKKKQyTSIH
K651 TLVMLKKKQyTSIHH
K651 TLVMLKKKQyTSIHH
Y653-p VMLKKKQyTSIHHGV
T654 MLKKKQyTSIHHGVV
S655 LKKKQyTSIHHGVVE
T668-p VEVDAAVtPEERHLS
K676 PEERHLSKMQQNGyE
K676 PEERHLSKMQQNGyE
Y682-p SKMQQNGyENPTyKF
T686 QNGyENPTyKFFEQM
Y687-p NGyENPTyKFFEQMQ
K688 GyENPTyKFFEQMQN
K688 GyENPTyKFFEQMQN
3823 : Phospho-APP (Thr668) Antibody
6986 : Phospho-APP (Thr668) (D90B8) Rabbit mAb
  rat

► Hide Isoforms
 
T107 RGRKQCKTHTHIVIP
Y115 HTHIVIPYRCLVGEF
S198 EESDSIDSADAEEDD
S206 ADAEEDDSDVWWGGA
T352 SSQSLLKTTSEPLPQ
T353 SQSLLKTTSEPLPQD
T366 QDPVKLPTTAASTPD
T367 DPVKLPTTAASTPDA
T367 DPVKLPTTAASTPDA
T367 DPVKLPTTAASTPDA
S370 KLPTTAASTPDAVDK
S370 KLPTTAASTPDAVDK
T371 LPTTAASTPDAVDKY
Y378 TPDAVDKYLETPGDE
T381 AVDKYLETPGDENEH
T381 AVDKYLETPGDENEH
S441-p HFQEKVEsLEQEAAN
T600 LMPSLTETKTTVELL
T651 PAADRGLTTRPGSGL
T652 AADRGLTTRPGSGLT
S656 GLTTRPGSGLTNIKT
T659 TRPGSGLTNIKTEEI
K662 GSGLTNIKTEEISEV
T663 SGLTNIKTEEISEVK
S667 NIKTEEISEVKMDAE
K670 TEEISEVKMDAEFGH
S679 DAEFGHDSGFEVRHQ
K687 GFEVRHQKLVFFAED
K699 AEDVGSNKGAIIGLM
K724 VITLVMLKKKQYtsI
K724 VITLVMLKKKQYtsI
K725 ITLVMLKKKQYtsIH
K725 ITLVMLKKKQYtsIH
K726 TLVMLKKKQYtsIHH
K726 TLVMLKKKQYtsIHH
Y728 VMLKKKQYtsIHHGV
T729-p MLKKKQYtsIHHGVV
S730-p LKKKQYtsIHHGVVE
T743-p VEVDAAVtPEERHLS
K751-ub PEERHLSkMQQNGyE
K751 PEERHLSKMQQNGyE
Y757-p SkMQQNGyENPTyKF
T761 QNGyENPTyKFFEQM
Y762-p NGyENPTyKFFEQMQ
K763 GyENPTyKFFEQMQN
K763 GyENPTyKFFEQMQN
3823 : Phospho-APP (Thr668) Antibody
6986 : Phospho-APP (Thr668) (D90B8) Rabbit mAb
  APP iso2  
T107 RGRKQCKTHTHIVIP
Y115 HTHIVIPYRCLVGEF
S198 EESDSIDSADAEEDD
S206 ADAEEDDSDVWWGGA
- gap
- gap
T291 EEVVRVPTTAASTPD
T292 EVVRVPTTAASTPDA
T292 EVVRVPTTAASTPDA
T292 EVVRVPTTAASTPDA
S295 RVPTTAASTPDAVDK
S295 RVPTTAASTPDAVDK
T296 VPTTAASTPDAVDKY
Y303 TPDAVDKYLETPGDE
T306 AVDKYLETPGDENEH
T306 AVDKYLETPGDENEH
S366 HFQEKVESLEQEAAN
T525 LMPSLTETKTTVELL
T576 PAADRGLTTRPGSGL
T577 AADRGLTTRPGSGLT
S581 GLTTRPGSGLTNIKT
T584 TRPGSGLTNIKTEEI
K587 GSGLTNIKTEEISEV
T588 SGLTNIKTEEISEVK
S592 NIKTEEISEVKMDAE
K595 TEEISEVKMDAEFGH
S604 DAEFGHDSGFEVRHQ
K612 GFEVRHQKLVFFAED
K624 AEDVGSNKGAIIGLM
K649 VITLVMLKKKQYTSI
K649 VITLVMLKKKQYTSI
K650 ITLVMLKKKQYTSIH
K650 ITLVMLKKKQYTSIH
K651 TLVMLKKKQYTSIHH
K651 TLVMLKKKQYTSIHH
Y653 VMLKKKQYTSIHHGV
T654 MLKKKQYTSIHHGVV
S655 LKKKQYTSIHHGVVE
T668-p VEVDAAVtPEERHLS
K676-ub PEERHLSkMQQNGYE
K676 PEERHLSKMQQNGYE
Y682 SkMQQNGYENPTYKF
T686 QNGYENPTYKFFEQM
Y687 NGYENPTYKFFEQMQ
K688 GYENPTYKFFEQMQN
K688 GYENPTYKFFEQMQN
3823 : Phospho-APP (Thr668) Antibody
6986 : Phospho-APP (Thr668) (D90B8) Rabbit mAb
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