P08592 (A4_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 148.
History...
Clusters with 
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Amyloid beta A4 protein Alternative name(s): ABPP Short name=APP Alzheimer disease amyloid A4 protein homolog Amyloidogenic glycoprotein Short name=AG Cleaved into the following 14 chains:
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| Gene names |
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| Organism | Rattus norvegicus (Rat) | ||
| Taxonomic identifier | 10116 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus |
Protein attributes
| Sequence length | 770 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| 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 By similarity. Can promote transcription activation through binding to APBB1-KAT5 and inhibit Notch signaling through interaction with Numb By similarity. 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 By similarity. May be involved in copper homeostasis/oxidative stress through copper ion reduction. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV By similarity. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons By similarity. Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. Rat and mouse beta-amyloid peptides bind only weakly transient metals and have little reducing activity due to substitutions of transient metal chelating residues. Beta-APP42 may activate mononuclear phagocytes in the brain and elicits inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation By similarity. Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain. The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis By similarity. N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6) By similarity. |
| Subunit structure | 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), APPBP2 (via BaSS) By similarity 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 By similarity. Beta-amyloid associates with HADH2 By similarity. Interacts with CPEB1, ANKS1B, TNFRSF21 and AGER By similarity. Interacts with ITM2B. Interacts with ITM2C. Interacts with IDE. Can form homodimers; this is promoted by heparin binding By similarity. Ref.10 Ref.11 |
| 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) By similarity. Beta-APP42 associates with FPRL1 at the cell surface and the complex is then rapidly internalized By similarity. APP sorts to the basolateral surface in epithelial cells By similarity. During neuronal differentiation, the Thr-743 phosphorylated form is located mainly in growth cones, moderately in neurites and sparingly in the cell body. Ref.19 |
| Tissue specificity | In the brain, non-L-APP isoforms are expressed in neurons, isoform APP695 being the predominant form. In astrocytes and microglial cells, almost 50% is L-appican). Ref.8 Ref.9 |
| Developmental stage | From 6 days to 7 months, levels of KPI-containing isoforms increase in the brain cortex and hippocampus. Levels of L-APP increase in all brain regions during the same period, but levels are low compared to non-L-APP isoforms. |
| Induction | Phosphorylation of mature, glycosylated APP occurs 48-72 hours after treatment of neuronal cells with nerve growth factor which correlates with the timing of neurite outgrowth. Ref.19 |
| Domain | The basolateral sorting signal (BaSS) is required for sorting of membrane proteins to the basolateral surface of epithelial cells. 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. |
| Post-translational modification | Proteolytically processed under normal cellular conditions. Cleavage either by alpha-secretase, beta-secretase or theta-secretase leads to generation and extracellular release of soluble APP peptides, S-APP-alpha and S-APP-beta, and the retention of corresponding membrane-anchored C-terminal fragments, C80, C83 and C99. Subsequent processing of C80 and 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) By similarity. Proteolytically cleaved by caspases during neuronal apoptosis By similarity. Cleavage at Asp-739 by either caspase-3, -8 or -9 results in the production of the neurotoxic C31 peptide and the increased production of beta-amyloid peptides By similarity. N-glycosylated. Ref.21 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. Ref.21 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. 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 heparin. Ref.17 Ref.18 Ref.19 Ref.20 Extracellular binding and reduction of copper, results in a corresponding oxidation of Cys-144 and Cys-158, and the formation of a disulfide bond By similarity. Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta which is further cleaved to release an N-terminal fragment of APP (N-APP) By similarity. Beta-amyloid peptides are degraded by IDE By similarity. |
| Miscellaneous | Chelation of metal ions, notably copper, iron and zinc, can induce histidine-bridging between beta-amyloid molecules resulting in beta-amyloid-metal aggregates. Rat and mouse beta-amyloid peptides have an arginine residue substituted for the bridging histidine residue and are thus less capable of forming amyloid aggegates. Extracellular zinc-binding increases binding of heparin to APP and inhibits collagen-binding By similarity. |
| Sequence similarities | Belongs to the APP family. Contains 1 BPTI/Kunitz inhibitor domain. |
| Mass spectrometry | Molecular mass is 5911.3 Da from positions 721 - 770. Determined by MALDI. Ref.6 Molecular mass is 6024.4 Da from positions 720 - 770. Determined by MALDI. Ref.6 |
Ontologies
Alternative products
| This entry describes 8 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform APP770 (identifier: P08592-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform APP695 (identifier: P08592-2) The sequence of this isoform differs from the canonical sequence as follows: 289-289: E → V 290-364: Missing. | ||||||
| Isoform L-APP677 (identifier: P08592-3) The sequence of this isoform is not available. | ||||||
| Note: L-isoforms are referred to as appicans. | ||||||
| Isoform L-APP696 (identifier: P08592-4) The sequence of this isoform is not available. | ||||||
| Note: L-isoforms are referred to as appicans. | ||||||
| Isoform APP714 (identifier: P08592-5) The sequence of this isoform is not available. | ||||||
| Isoform L-APP733 (identifier: P08592-6) The sequence of this isoform is not available. | ||||||
| Note: L-isoforms are referred to as appicans. | ||||||
| Isoform APP751 (identifier: P08592-7) The sequence of this isoform is not available. | ||||||
| Isoform L-APP752 (identifier: P08592-8) The sequence of this isoform is not available. | ||||||
| Note: L-isoforms are referred to as appicans. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||||||
Molecule processing | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 17 | 17 | By similarity | |||||||||
| Chain | 18 – 770 | 753 | Amyloid beta A4 protein | PRO_0000000159 | ||||||||
| Chain | 18 – 687 | 670 | Soluble APP-alpha By similarity | PRO_0000000160 | ||||||||
| Chain | 18 – 671 | 654 | Soluble APP-beta Potential | PRO_0000000161 | ||||||||
| Chain | 18 – 286 | 269 | N-APP By similarity | PRO_0000381971 | ||||||||
| Chain | 672 – 770 | 99 | C99 Potential | PRO_0000000162 | ||||||||
| Chain | 672 – 713 | 42 | Beta-amyloid protein 42 By similarity | PRO_0000000163 | ||||||||
| Chain | 672 – 711 | 40 | Beta-amyloid protein 40 By similarity | PRO_0000000164 | ||||||||
| Chain | 688 – 770 | 83 | C83 By similarity | PRO_0000000165 | ||||||||
| Peptide | 688 – 713 | 26 | P3(42) By similarity | PRO_0000000166 | ||||||||
| Peptide | 688 – 711 | 24 | P3(40) By similarity | PRO_0000000167 | ||||||||
| Chain | 691 – 770 | 80 | C80 | PRO_0000384579 | ||||||||
| Chain | 712 – 770 | 59 | Gamma-secretase C-terminal fragment 59 | PRO_0000000168 | ||||||||
| Chain | 714 – 770 | 57 | Gamma-secretase C-terminal fragment 57 | PRO_0000000169 | ||||||||
| Chain | 721 – 770 | 50 | Gamma-secretase C-terminal fragment 50 | PRO_0000000170 | ||||||||
| Chain | 740 – 770 | 31 | C31 By similarity | PRO_0000000171 | ||||||||
Regions | ||||||||||||
| Topological domain | 18 – 699 | 682 | Extracellular Potential | |||||||||
| Transmembrane | 700 – 723 | 24 | Helical; Potential | |||||||||
| Topological domain | 724 – 770 | 47 | Cytoplasmic By similarity | |||||||||
| Domain | 291 – 341 | 51 | BPTI/Kunitz inhibitor | |||||||||
| Region | 96 – 110 | 15 | Heparin-binding By similarity | |||||||||
| Region | 135 – 155 | 21 | Copper-binding By similarity | |||||||||
| Region | 181 – 188 | 8 | Zinc-binding By similarity | |||||||||
| Region | 391 – 423 | 33 | Heparin-binding By similarity | |||||||||
| Region | 491 – 522 | 32 | Heparin-binding By similarity | |||||||||
| Region | 523 – 540 | 18 | Collagen-binding By similarity | |||||||||
| Region | 732 – 751 | 20 | Interaction with G(o)-alpha | |||||||||
| Motif | 724 – 734 | 11 | Basolateral sorting signal By similarity | |||||||||
| Motif | 759 – 762 | 4 | NPXY motif; contains endocytosis signal | |||||||||
| Compositional bias | 230 – 260 | 31 | Asp/Glu-rich (acidic) | |||||||||
| Compositional bias | 274 – 280 | 7 | Poly-Thr | |||||||||
Sites | ||||||||||||
| Metal binding | 147 | 1 | Copper 1 By similarity | |||||||||
| Metal binding | 151 | 1 | Copper 1 By similarity | |||||||||
| Metal binding | 168 | 1 | Copper 1 By similarity | |||||||||
| Metal binding | 677 | 1 | Copper or zinc 2 By similarity | |||||||||
| Metal binding | 685 | 1 | Copper or zinc 2 By similarity | |||||||||
| Site | 144 | 1 | Required for Cu(2+) reduction By similarity | |||||||||
| Site | 301 – 302 | 2 | Reactive bond By similarity | |||||||||
| Site | 671 – 672 | 2 | Cleavage; by beta-secretase By similarity | |||||||||
| Site | 672 – 673 | 2 | Cleavage; by caspase-6 | |||||||||
| Site | 687 – 688 | 2 | Cleavage; by alpha-secretase By similarity | |||||||||
| Site | 690 – 691 | 2 | Cleavage; by theta-secretase By similarity | |||||||||
| Site | 711 – 712 | 2 | Cleavage; by gamma-secretase; site 1 By similarity | |||||||||
| Site | 713 – 714 | 2 | Cleavage; by gamma-secretase; site 2 By similarity | |||||||||
| Site | 720 – 721 | 2 | Cleavage; by gamma-secretase; site 3 By similarity | |||||||||
| Site | 739 – 740 | 2 | Cleavage; by caspase-6, caspase-8 or caspase-9 By similarity | |||||||||
Amino acid modifications | ||||||||||||
| Modified residue | 198 | 1 | Phosphoserine; by CK2 By similarity | |||||||||
| Modified residue | 206 | 1 | Phosphoserine; by CK1 By similarity | |||||||||
| Modified residue | 729 | 1 | Phosphothreonine | |||||||||
| Modified residue | 730 | 1 | Phosphoserine; by APP-kinase I Ref.18 | |||||||||
| Modified residue | 743 | 1 | Phosphothreonine; by CDK5 and MAPK10 Ref.20 | |||||||||
| Modified residue | 757 | 1 | Phosphotyrosine; by ABL1 By similarity | |||||||||
| Modified residue | 762 | 1 | Phosphotyrosine By similarity | |||||||||
| Glycosylation | 542 | 1 | N-linked (GlcNAc...) Potential | |||||||||
| Glycosylation | 571 | 1 | N-linked (GlcNAc...) Potential | |||||||||
| Glycosylation | 656 | 1 | O-linked (Xyl...) (chondroitin sulfate); in L-APP isoforms | |||||||||
| Disulfide bond | 38 ↔ 62 | By similarity | ||||||||||
| Disulfide bond | 73 ↔ 117 | By similarity | ||||||||||
| Disulfide bond | 98 ↔ 105 | By similarity | ||||||||||
| Disulfide bond | 133 ↔ 187 | By similarity | ||||||||||
| Disulfide bond | 144 ↔ 174 | By similarity | ||||||||||
| Disulfide bond | 158 ↔ 186 | By similarity | ||||||||||
| Disulfide bond | 291 ↔ 341 | By similarity | ||||||||||
| Disulfide bond | 300 ↔ 324 | By similarity | ||||||||||
| Disulfide bond | 316 ↔ 337 | By similarity | ||||||||||
Natural variations | ||||||||||||
| Alternative sequence | 289 | 1 | E → V in isoform APP695. | VSP_000015 | ||||||||
| Alternative sequence | 290 – 364 | 75 | Missing in isoform APP695. | VSP_000016 | ||||||||
Experimental info | ||||||||||||
| Mutagenesis | 656 | 1 | S → A: No chondroitin sulfate linkage to isoform L-APP733. Ref.11 Ref.13 | |||||||||
| Mutagenesis | 704 | 1 | G → V: Little oxidized neuronal proteins. Scarce beta-APP42 peptide aggregation. No neurotoxicity. Ref.11 Ref.16 | |||||||||
| Mutagenesis | 732 – 733 | 2 | HH → GL or GP: Almost complete loss of binding to GNAO1. No inhibition of GTPase activity. Ref.11 | |||||||||
| Mutagenesis | 743 | 1 | T → A: No effect on neurite growth and maturation. Ref.11 Ref.19 | |||||||||
| Mutagenesis | 743 | 1 | T → E: Inhibits neurite growth and maturation. Ref.11 Ref.19 | |||||||||
| Mutagenesis | 757 | 1 | Y → G: No DBB1 binding. Ref.10 Ref.11 | |||||||||
| Mutagenesis | 759 | 1 | N → A: Some DBB1 binding. Ref.10 Ref.11 | |||||||||
| Mutagenesis | 762 | 1 | Y → A: Some DBB1 binding. Ref.10 Ref.11 | |||||||||
Secondary structure | ||||||||||||
Helix Strand Turn | ||||||||||||
| Turn | 679 – 686 | 8 | ||||||||||
| Helix | 687 – 695 | 9 | ||||||||||
Sequences
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References
| [1] | "Alzheimer's disease amyloidogenic glycoprotein: expression pattern in rat brain suggests a role in cell contact." Shivers B.D., Hilbich C., Multhaup G., Salbaum J.M., Beyreuther K., Seeburg P.H. EMBO J. 7:1365-1370(1988) [PubMed: 2900758] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP695). Tissue: Brain. |
| [2] | "A new beta amyloid precursor protein cDNA found in Rat6 embryo fibroblasts." Feng J., Song S., Zheng J. Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP770). |
| [3] | "Amyloid beta protein precursor is possibly a heparan sulfate proteoglycan core protein." Schubert D., Schroeder R., LaCorbiere M., Saitoh T., Cole G. Science 241:223-226(1988) [PubMed: 2968652] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-44. |
| [4] | "Purification and tissue level of the beta-amyloid peptide precursor of rat brain." Potempska A., Styles J., Mehta P., Kim K.S., Miller D.L. J. Biol. Chem. 266:8464-8469(1991) [PubMed: 1673681] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-32. |
| [5] | "The sequence of the two extra exons in rat preA4." Kang J., Mueller-Hill B. Nucleic Acids Res. 17:2130-2130(1989) [PubMed: 2648331] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 289-364. Tissue: Liver. |
| [6] | "Distinct intramembrane cleavage of the beta-amyloid precursor protein family resembling gamma-secretase-like cleavage of Notch." Gu Y., Misonou H., Sato T., Dohmae N., Takio K., Ihara Y. J. Biol. Chem. 276:35235-35238(2001) [PubMed: 11483588] [Abstract] Cited for: PROTEIN SEQUENCE OF 720-730, MASS SPECTROMETRY. |
| [7] | "APP gene family. Alternative splicing generates functionally related isoforms." Sandbrink R., Masters C.L., Beyreuther K. Ann. N. Y. Acad. Sci. 777:281-287(1996) [PubMed: 8624099] [Abstract] Cited for: ALTERNATIVE SPLICING. |
| [8] | "The Alzheimer amyloid precursor proteoglycan (appican) is present in brain and is produced by astrocytes but not by neurons in primary neural cultures." Shioi J., Pangalos M.N., Ripellino J.A., Vassilacopoulou D., Mytilineou C., Margolis R.U., Robakis N.K. J. Biol. Chem. 270:11839-11844(1995) [PubMed: 7744833] [Abstract] Cited for: TISSUE SPECIFICITY OF APPICAN. |
| [9] | "Expression of the APP gene family in brain cells, brain development and aging." Sandbrink R., Monning U., Masters C.L., Beyreuther K. Gerontology 43:119-131(1997) [PubMed: 8996834] [Abstract] Cited for: TISSUE SPECIFICITY OF ISOFORMS. |
| [10] | "A 127-kDa protein (UV-DDB) binds to the cytoplasmic domain of the Alzheimer's amyloid precursor protein." Watanabe T., Sukegawa J., Tomita S., Iijima K., Oguchi S., Suzuki T., Nairn A.C., Greengard P. J. Neurochem. 72:549-556(1999) [PubMed: 9930726] [Abstract] Cited for: INTERACTION WITH DDB1, MUTAGENESIS OF TYR-757; ASN-759 AND TYR-762. |
| [11] | "The amyloid precursor protein interacts with Go heterotrimeric protein within a cell compartment specialized in signal transduction." Brouillet E., Trembleau A., Galanaud D., Volovitch M., Bouillot C., Valenza C., Prochiantz A., Allinquant B. J. Neurosci. 19:1717-1727(1999) [PubMed: 10024358] [Abstract] Cited for: INTERACTION WITH GNAO1, MUTAGENESIS OF 732-HIS-HIS-733. |
| [12] | "The beta A4 amyloid precursor protein binding to copper." Hesse L., Beher D., Masters C.L., Multhaup G. FEBS Lett. 349:109-116(1994) [PubMed: 7913895] [Abstract] Cited for: COPPER-BINDING. |
| [13] | "The chondroitin sulfate attachment site of appican is formed by splicing out exon 15 of the amyloid precursor gene." Pangalos M.N., Efthimiopoulos S., Shioi J., Robakis N.K. J. Biol. Chem. 270:10388-10391(1995) [PubMed: 7737970] [Abstract] Cited for: CHARACTERISTICS OF APPICAN, MUTAGENESIS OF SER-656. |
| [14] | "The A beta peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction." Huang X., Atwood C.S., Hartshorn M.A., Multhaup G., Goldstein L.E., Scarpa R.C., Cuajungco M.P., Gray D.N., Lim J., Moir R.D., Tanzi R.E., Bush A.I. Biochemistry 38:7609-7616(1999) [PubMed: 10386999] [Abstract] Cited for: BETA-AMYLOID METAL-BINDING. |
| [15] | "Histidine-13 is a crucial residue in the zinc ion-induced aggregation of the A beta peptide of Alzheimer's disease." Liu S.T., Howlett G., Barrow C.J. Biochemistry 38:9373-9378(1999) [PubMed: 10413512] [Abstract] Cited for: BETA-AMYLOID ZINC-BINDING. |
| [16] | "Role of glycine-33 and methionine-35 in Alzheimer's amyloid beta-peptide 1-42-associated oxidative stress and neurotoxicity." Kanski J., Varadarajan S., Aksenova M., Butterfield D.A. Biochim. Biophys. Acta 1586:190-198(2002) [PubMed: 11959460] [Abstract] Cited for: IMPORTANCE OF GLY-704 IN FREE RADICAL PROPAGATION, MUTAGENESIS OF GLY-704. |
| [17] | "The cytoplasmic domain of Alzheimer's amyloid precursor protein is phosphorylated at Thr654, Ser655, and Thr668 in adult rat brain and cultured cells." Oishi M., Nairn A.C., Czernik A.J., Lim G.S., Isohara T., Gandy S.E., Greengard P., Suzuki T. Mol. Med. 3:111-123(1997) [PubMed: 9085254] [Abstract] Cited for: PHOSPHORYLATION. |
| [18] | "Phosphorylation of the cytoplasmic domain of Alzheimer's beta-amyloid precursor protein at Ser655 by a novel protein kinase." Isohara T., Horiuchi A., Watanabe T., Ando K., Czernik A.J., Uno I., Greengard P., Nairn A.C., Suzuki T. Biochem. Biophys. Res. Commun. 258:300-305(1999) [PubMed: 10329382] [Abstract] Cited for: PHOSPHORYLATION AT SER-730. |
| [19] | "Role of phosphorylation of Alzheimer's amyloid precursor protein during neuronal differentiation." Ando K., Oishi M., Takeda S., Iijima K., Isohara T., Nairn A.C., Kirino Y., Greengard P., Suzuki T. J. Neurosci. 19:4421-4427(1999) [PubMed: 10341243] [Abstract] Cited for: PHOSPHORYLATION, INDUCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF THR-743. |
| [20] | "Neuron-specific phosphorylation of Alzheimer's beta-amyloid precursor protein by cyclin-dependent kinase 5." Iijima K., Ando K., Takeda S., Satoh Y., Seki T., Itohara S., Greengard P., Kirino Y., Nairn A.C., Suzuki T. J. Neurochem. 75:1085-1091(2000) [PubMed: 10936190] [Abstract] Cited for: PHOSPHORYLATION AT THR-743. |
| [21] | "Appican, the proteoglycan form of the amyloid precursor protein, contains chondroitin sulfate E in the repeating disaccharide region and 4-O-sulfated galactose in the linkage region." Tsuchida K., Shioi J., Yamada S., Boghosian G., Wu A., Cai H., Sugahara K., Robakis N.K. J. Biol. Chem. 276:37155-37160(2001) [PubMed: 11479316] [Abstract] Cited for: STRUCTURE OF CARBOHYDRATE IN APPICAN. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | X07648 mRNA. Translation: CAA30488.1. AF513015 mRNA. Translation: AAM90259.1. X14066 mRNA. Translation: CAA32229.1. | ||||||||||||||||||
| IPI | IPI00212319. IPI00231884. | ||||||||||||||||||
| PIR | S00550. S03607. S23094. | ||||||||||||||||||
| RefSeq | NP_062161.1. NM_019288.1. | ||||||||||||||||||
| UniGene | Rn.2104. | ||||||||||||||||||
3D structure databases | |||||||||||||||||||
| PDBe RCSB PDB PDBj |
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| ProteinModelPortal | P08592. | ||||||||||||||||||
| SMR | P08592. Positions 28-189, 287-342, 374-565, 672-699, 739-770. | ||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||
| DIP | DIP-6114N. DIP-618N. DIP-685N. | ||||||||||||||||||
| IntAct | P08592. 4 interactions. | ||||||||||||||||||
| STRING | P08592. | ||||||||||||||||||
Protein family/group databases | |||||||||||||||||||
| MEROPS | I02.015. | ||||||||||||||||||
| TCDB | 1.C.50.1.1. amyloid beta,-protein peptide (Abeta,PP) family. | ||||||||||||||||||
PTM databases | |||||||||||||||||||
| PhosphoSite | P08592. | ||||||||||||||||||
Protocols and materials databases | |||||||||||||||||||
| StructuralBiologyKnowledgebase | Search... | ||||||||||||||||||
Genome annotation databases | |||||||||||||||||||
| Ensembl | ENSRNOT00000044081; ENSRNOP00000040243; ENSRNOG00000006997. ENSRNOT00000048854; ENSRNOP00000041613; ENSRNOG00000006997. | ||||||||||||||||||
| GeneID | 54226. | ||||||||||||||||||
| KEGG | rno:54226. | ||||||||||||||||||
| UCSC | NM_019288. rat. | ||||||||||||||||||
Organism-specific databases | |||||||||||||||||||
| CTD | 351. | ||||||||||||||||||
| RGD | 2139. App. | ||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||
| eggNOG | roNOG06213. | ||||||||||||||||||
| GeneTree | ENSGT00530000063252. | ||||||||||||||||||
| HOVERGEN | HBG000051. | ||||||||||||||||||
| InParanoid | P08592. | ||||||||||||||||||
| OMA | RKQCKTH. | ||||||||||||||||||
Gene expression databases | |||||||||||||||||||
| ArrayExpress | P08592. | ||||||||||||||||||
| Genevestigator | P08592. | ||||||||||||||||||
| GermOnline | ENSRNOG00000006997. Rattus norvegicus. | ||||||||||||||||||
Family and domain databases | |||||||||||||||||||
| InterPro | IPR008155. Amyloid_glyco. IPR013803. Amyloid_glyco_Abeta. IPR011178. Amyloid_glyco_Cu-bd. IPR024329. Amyloid_glyco_E2_domain. IPR008154. Amyloid_glyco_extra. IPR019744. Amyloid_glyco_extracell_CS. IPR015849. Amyloid_glyco_heparin-bd. IPR019745. Amyloid_glyco_intracell_CS. IPR019543. APP_amyloid_C. IPR002223. Prot_inh_Kunz-m. IPR020901. Prtase_inh_Kunz-CS. [Graphical view] | ||||||||||||||||||
| Gene3D | G3DSA:4.10.230.10. Amyloid_glyco_Abeta. 1 hit. G3DSA:3.30.1490.140. Amyloid_glyco_Cu-bd. 1 hit. G3DSA:3.90.570.10. Amyloid_glyco_heparin-bd. 1 hit. G3DSA:4.10.410.10. Prot_inh_Kunz-m. 1 hit. | ||||||||||||||||||
| KO | K04520. | ||||||||||||||||||
| Pfam | PF10515. APP_amyloid. 1 hit. PF12924. APP_Cu_bd. 1 hit. PF12925. APP_E2. 1 hit. PF02177. APP_N. 1 hit. PF03494. Beta-APP. 1 hit. PF00014. Kunitz_BPTI. 1 hit. [Graphical view] | ||||||||||||||||||
| PRINTS | PR00203. AMYLOIDA4. PR00759. BASICPTASE. PR00204. BETAAMYLOID. | ||||||||||||||||||
| SMART | SM00006. A4_EXTRA. 1 hit. SM00131. KU. 1 hit. [Graphical view] | ||||||||||||||||||
| SUPFAM | SSF56491. A4_extra. 1 hit. SSF89811. Amyloid_glyco_Cu-bd. 1 hit. SSF57362. Prot_inh_Kunz-m. 1 hit. SSF109843. SSF109843. 1 hit. | ||||||||||||||||||
| PROSITE | PS00319. A4_EXTRA. 1 hit. PS00320. A4_INTRA. 1 hit. PS00280. BPTI_KUNITZ_1. 1 hit. PS50279. BPTI_KUNITZ_2. 1 hit. [Graphical view] | ||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||
Other | |||||||||||||||||||
| NextBio | 610648. | ||||||||||||||||||
Entry information
| Entry name | A4_RAT | ||||||||
| Accession | Primary (citable) accession number: P08592 Secondary accession number(s): Q547B7 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
Relevant documents
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |