CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-002683
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Amyloid beta A4 protein 
Protein Synonyms/Alias
 ABPP; APP; Alzheimer disease amyloid A4 protein homolog; Amyloidogenic glycoprotein; AG; N-APP; Soluble APP-alpha; S-APP-alpha; Soluble APP-beta; S-APP-beta; C99; Beta-amyloid protein 42; Beta-APP42; Beta-amyloid protein 40; Beta-APP40; C83; P3(42); P3(40); C80; Gamma-secretase C-terminal fragment 59; Gamma-CTF(59); Gamma-secretase C-terminal fragment 57; Gamma-CTF(57); Gamma-secretase C-terminal fragment 50; Gamma-CTF(50); C31 
Gene Name
 App 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Rattus norvegicus (Rat) 
NCBI Taxa ID
 10116 
Lysine Modification
Position
Peptide
Type
References
395HAHFQKAKERLEAKHacetylation[1]
751PEERHLSKMQQNGYEubiquitination[2]
Reference
 [1] Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns.
 Lundby A, Lage K, Weinert BT, Bekker-Jensen DB, Secher A, Skovgaard T, Kelstrup CD, Dmytriyev A, Choudhary C, Lundby C, Olsen JV.
 Cell Rep. 2012 Aug 30;2(2):419-31. [PMID: 22902405]
 [2] Synaptic protein ubiquitination in rat brain revealed by antibody-based ubiquitome analysis.
 Na CH, Jones DR, Yang Y, Wang X, Xu Y, Peng J.
 J Proteome Res. 2012 Sep 7;11(9):4722-32. [PMID: 22871113] 
Functional Description
 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 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 (By similarity). 
Sequence Annotation
 DOMAIN 291 341 BPTI/Kunitz inhibitor.
 REGION 96 110 Heparin-binding (By similarity).
 REGION 135 155 Copper-binding (By similarity).
 REGION 181 188 Zinc-binding (By similarity).
 REGION 391 423 Heparin-binding (By similarity).
 REGION 491 522 Heparin-binding (By similarity).
 REGION 523 540 Collagen-binding (By similarity).
 REGION 732 751 Interaction with G(o)-alpha.
 MOTIF 724 734 Basolateral sorting signal (By
 MOTIF 759 762 NPXY motif; contains endocytosis signal.
 METAL 147 147 Copper 1 (By similarity).
 METAL 151 151 Copper 1 (By similarity).
 METAL 168 168 Copper 1 (By similarity).
 METAL 677 677 Copper or zinc 2 (By similarity).
 METAL 685 685 Copper or zinc 2 (By similarity).
 MOD_RES 198 198 Phosphoserine; by CK2 (By similarity).
 MOD_RES 206 206 Phosphoserine; by CK1 (By similarity).
 MOD_RES 729 729 Phosphothreonine.
 MOD_RES 730 730 Phosphoserine; by APP-kinase I.
 MOD_RES 743 743 Phosphothreonine; by CDK5 and MAPK10.
 MOD_RES 757 757 Phosphotyrosine; by ABL1 (By similarity).
 CARBOHYD 542 542 N-linked (GlcNAc...) (Potential).
 CARBOHYD 571 571 N-linked (GlcNAc...) (Potential).
 CARBOHYD 656 656 O-linked (Xyl...) (chondroitin sulfate);
 DISULFID 38 62 By similarity.
 DISULFID 73 117 By similarity.
 DISULFID 98 105 By similarity.
 DISULFID 133 187 By similarity.
 DISULFID 144 174 By similarity.
 DISULFID 158 186 By similarity.
 DISULFID 291 341 By similarity.
 DISULFID 300 324 By similarity.
 DISULFID 316 337 By similarity.  
Keyword
 3D-structure; Alternative splicing; Amyloid; Apoptosis; Cell adhesion; Coated pit; Complete proteome; Copper; Direct protein sequencing; Disulfide bond; Endocytosis; Glycoprotein; Heparin-binding; Iron; Membrane; Metal-binding; Notch signaling pathway; Phosphoprotein; Protease inhibitor; Proteoglycan; Reference proteome; Serine protease inhibitor; Signal; Transmembrane; Transmembrane helix; Zinc. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 770 AA 
Protein Sequence
MLPSLALLLL AAWTVRALEV PTDGNAGLLA EPQIAMFCGK LNMHMNVQNG KWESDPSGTK 60
TCIGTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHTH IVIPYRCLVG 120
EFVSDALLVP DKCKFLHQER MDVCETHLHW HTVAKETCSE KSTNLHDYGM LLPCGIDKFR 180
GVEFVCCPLA EESDSIDSAD AEEDDSDVWW GGADTDYADG GEDKVVEVAE EEEVADVEEE 240
EAEDDEDVED GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVREV CSEQAETGPC 300
RAMISRWYFD VTEGKCAPFF YGGCGGNRNN FDTEEYCMAV CGSVSSQSLL KTTSEPLPQD 360
PVKLPTTAAS TPDAVDKYLE TPGDENEHAH FQKAKERLEA KHRERMSQVM REWEEAERQA 420
KNLPKADKKA VIQHFQEKVE SLEQEAANER QQLVETHMAR VEAMLNDRRR LALENYITAL 480
QAVPPRPHHV FNMLKKYVRA EQKDRQHTLK HFEHVRMVDP KKAAQIRSQV MTHLRVIYER 540
MNQSLSLLYN VPAVAEEIQD EVDELLQKEQ NYSDDVLANM ISEPRISYGN DALMPSLTET 600
KTTVELLPVN GEFSLDDLQP WHPFGVDSVP ANTENEVEPV DARPAADRGL TTRPGSGLTN 660
IKTEEISEVK MDAEFGHDSG FEVRHQKLVF FAEDVGSNKG AIIGLMVGGV VIATVIVITL 720
VMLKKKQYTS IHHGVVEVDA AVTPEERHLS KMQQNGYENP TYKFFEQMQN 770 
Gene Ontology
 GO:0045177; C:apical part of cell; IEA:Compara.
 GO:0030424; C:axon; ISS:UniProtKB.
 GO:0009986; C:cell surface; IEA:Compara.
 GO:0035253; C:ciliary rootlet; IEA:Compara.
 GO:0005905; C:coated pit; IEA:UniProtKB-SubCell.
 GO:0031410; C:cytoplasmic vesicle; IEA:Compara.
 GO:0043198; C:dendritic shaft; IEA:Compara.
 GO:0043197; C:dendritic spine; IEA:Compara.
 GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
 GO:0016021; C:integral to membrane; ISS:UniProtKB.
 GO:0031594; C:neuromuscular junction; IEA:Compara.
 GO:0048471; C:perinuclear region of cytoplasm; IEA:Compara.
 GO:0005886; C:plasma membrane; IEA:Compara.
 GO:0051233; C:spindle midzone; IEA:Compara.
 GO:0003677; F:DNA binding; ISS:UniProtKB.
 GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
 GO:0016504; F:peptidase activator activity; IDA:RGD.
 GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
 GO:0046914; F:transition metal ion binding; IEA:InterPro.
 GO:0008344; P:adult locomotory behavior; ISS:UniProtKB.
 GO:0008088; P:axon cargo transport; ISS:UniProtKB.
 GO:0016199; P:axon midline choice point recognition; ISS:UniProtKB.
 GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
 GO:0006878; P:cellular copper ion homeostasis; ISS:UniProtKB.
 GO:0008203; P:cholesterol metabolic process; IEA:Compara.
 GO:0048669; P:collateral sprouting in absence of injury; ISS:UniProtKB.
 GO:0016358; P:dendrite development; ISS:UniProtKB.
 GO:0006897; P:endocytosis; ISS:UniProtKB.
 GO:0030198; P:extracellular matrix organization; ISS:UniProtKB.
 GO:0030900; P:forebrain development; IEA:Compara.
 GO:0000085; P:G2 phase of mitotic cell cycle; ISS:UniProtKB.
 GO:0006917; P:induction of apoptosis; IDA:RGD.
 GO:0035235; P:ionotropic glutamate receptor signaling pathway; ISS:UniProtKB.
 GO:0007617; P:mating behavior; ISS:UniProtKB.
 GO:0006378; P:mRNA polyadenylation; ISS:UniProtKB.
 GO:0045665; P:negative regulation of neuron differentiation; IEA:Compara.
 GO:0050885; P:neuromuscular process controlling balance; IEA:Compara.
 GO:0051402; P:neuron apoptotic process; IEA:Compara.
 GO:0016322; P:neuron remodeling; ISS:UniProtKB.
 GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
 GO:0045931; P:positive regulation of mitotic cell cycle; ISS:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Compara.
 GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
 GO:0007176; P:regulation of epidermal growth factor-activated receptor activity; ISS:UniProtKB.
 GO:0040014; P:regulation of multicellular organism growth; ISS:UniProtKB.
 GO:0043393; P:regulation of protein binding; IEA:Compara.
 GO:0050803; P:regulation of synapse structure and activity; ISS:UniProtKB.
 GO:0006417; P:regulation of translation; ISS:UniProtKB.
 GO:0006979; P:response to oxidative stress; IEA:Compara.
 GO:0051563; P:smooth endoplasmic reticulum calcium ion homeostasis; IEA:Compara.
 GO:0001967; P:suckling behavior; IEA:Compara.
 GO:0051124; P:synaptic growth at neuromuscular junction; IEA:Compara.
 GO:0008542; P:visual learning; ISS:UniProtKB. 
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. 
Pfam
 PF10515; APP_amyloid
 PF12924; APP_Cu_bd
 PF12925; APP_E2
 PF02177; APP_N
 PF03494; Beta-APP
 PF00014; Kunitz_BPTI 
SMART
 SM00006; A4_EXTRA
 SM00131; KU 
PROSITE
 PS00319; A4_EXTRA
 PS00320; A4_INTRA
 PS00280; BPTI_KUNITZ_1
 PS50279; BPTI_KUNITZ_2 
PRINTS
 PR00203; AMYLOIDA4.
 PR00759; BASICPTASE.
 PR00204; BETAAMYLOID.