Rabbit Presenilin 1 Polyclonal Antibody | anti-Presenilin1 antibody

Phospho-Presenilin 1 (Ser353) Antibody

Cat. Num. AAA9614305

• Gene Names: PSEN1; AD3; FAD; PS1; PS-1; S182
• Reactivity: Human, Mouse, Rat; Predicted Reactivity: Horse (89%), Rabbit (90%)
• Applications: Western Blot, Immunohistochemistry, Immunofluorescence, Immunocytochemistry, ELISA
• Purity: The antibody is from purified rabbit serum by affinity purification via sequential chromatography on phospho-peptide and non-phospho-peptide affinity columns.
• Synonyms: Presenilin 1; Polyclonal Antibody; Phospho-Presenilin 1 (Ser353) Antibody; AD3; Ad3h; FAD; Homo Sapiens Clone CC44 Senilin 1; Presenilin-1 CTF12; Protein S182; PS 1; PS-1; PS1-CTF12; PSEN1; PSN1_HUMAN; PSNL1; S182; anti-Presenilin1 antibody

• Host: Rabbit
• Reactivity: Human, Mouse, Rat; Predicted Reactivity: Horse (89%), Rabbit (90%)
• Clonality: Polyclonal
• Isotype: Rabbit IgG
• Specificity: Phospho-Presenilin 1 (Ser353) Antibody detects endogenous levels of Presenilin 1 only when phosphorylated at Ser353.; Tissue Specificity: Detected in azurophile granules in neutrophils and in platelet cytoplasmic granules (at protein level). Expressed in a wide range of tissues including various regions of the brain, liver, spleen and lympHnodes.
• Purity/Purification: The antibody is from purified rabbit serum by affinity purification via sequential chromatography on phospho-peptide and non-phospho-peptide affinity columns.
• Form/Format: Liquid. Rabbit IgG in phosphate buffered saline, pH7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
• Concentration: 1mg/ml (varies by lot)

• Applicable Applications for anti-Presenilin1 antibody: Western Blot (WB), Immunohistochemistry (IHC), Immunofluorescence (IF), Immunocytochemistry (ICC), Peptide ELISA (EIA)
• Application Notes: WB: 1:1000-3000; IF/ICC: 1:100-1:500; IHC: 1:50-1:200; Peptide ELISA: 1:20,000-1:40,000
• Immunogen: A synthesized peptide derived from human Presenilin 1 around the phosphorylation site of Ser353.
• Conjugation: Unconjugated
• Fragment: Fab fragment
• Post Translational Modifications: Heterogeneous proteolytic processing generates N-terminal (NTF) and C-terminal (CTF) fragments of approximately 35 and 20kDa, respectively. During apoptosis, the C-terminal fragment (CTF) is further cleaved by caspase-3 to produce the fragment, PS1-CTF12. After endoproteolysis, the C-terminal fragment (CTF) is phosphorylated on serine residues by PKA and/or PKC. Phosphorylation on Ser-346 inhibits endoproteolysis.
• Subunit Structure: Homodimer. The functional gamma-secretase complex is composed of at least four polypeptides: a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such minimal complex is sufficient for secretase activity. Other components which are associated with the complex include SLC25A64, SLC5A7, PHB and PSEN1 isoform 3. Predominantly heterodimer of a N-terminal (NTF) and a C-terminal (CTF) endoproteolytical fragment. Associates with proteolytic processed C-terminal fragments C83 and C99 of the amyloid precursor protein (APP) (via transmembrane domain). Associates with NOTCH1 (via transmembrane domain). Associates with cadherin/catenin adhesion complexes through direct binding to CDH1 or CDH2. Interaction with CDH1 stabilizes the complex and stimulates cell-cell aggregation. Interaction with CDH2 is essential for trafficking of CDH2 from the endoplasmic reticulum to the plasma membrane. Interacts with CTNND2, CTNNB1, CTNND1, JUP, HERPUD1, FLNA, FLNB, MTCH1, PKP4 and PARL. Interacts through its N-terminus with isoform 3 of GFAP. Interacts with DOCK3 (By similarity). Interacts with isoform 1 and isoform 3 of UBQLN1.
• Similarity: The PAL motif is required for normal active site conformation. Substrates, such as NOTCH1 and APP peptides, are bound between PSEN1 transmembrane domains and via the first lumenal loop and the cytoplasmic loop between the sixth and seventh transmembrane domains. Substrate binding causes a conformation change and formation of an intermolecular antiparallel beta-sheet between PSEN1 and its substrates.Belongs to the peptidase A22A family.
• Subcellular Location: Endoplasmic reticulum. Endoplasmic reticulum membrane>Multi-pass membrane protein. Golgi apparatus membrane>Multi-pass membrane protein. Cytoplasmic granule. Cell membrane>Multi-pass membrane protein. Cell projection>Growth cone. Early endosome. Early endosome membrane>Multi-pass membrane protein. Cell projection>Neuron projection. Cell projection>Axon. Cell junction>Synapse.; Note: Translocates with bound NOTCH1 from the endoplasmic reticulum and/or Golgi to the cell surface (PubMed:10593990). Colocalizes with CDH1/2 at sites of cell-cell contact. Colocalizes with CTNNB1 in the endoplasmic reticulum and the proximity of the plasma membrane (PubMed:9738936). Also present in azurophil granules of neutrophils (PubMed:11987239). Colocalizes with UBQLN1 in the cell membrane and in cytoplasmic juxtanuclear structures called aggresomes (PubMed:21143716).
• Preparation and Storage: Store at -20 degree C. Stable for 12 months from date of receipt.

Western Blot (WB)

(Western blot analysis of PSEN1 (Phospho-Ser353) using TNF-α treated HeLa whole cell lysates.-/+ means absence or presence of N peptide（non-phospho peptide) and P peptide(phospho peptide).)

Immunohistochemistry (IHC)

(Staining Mouse testis tissue by IHC-P. The sample was formaldehyde fixed and a heat mediated antigen retrieval step in citrate buffer was performed. The sample was then blocked and incubated with the primary antibody at 4 degree C overnight. An HRP conjugated anti-Rabbit antibody was used as the secondary antibody.)

Immunohistochemistry (IHC)

(At 1/100 staining Mouse brain tissue by IHC-P. The sample was formaldehyde fixed and a heat mediated antigen retrieval step in citrate buffer was performed. The sample was then blocked and incubated with the primary antibody at 4 degree C overnight. An HRP conjugated anti-Rabbit antibody was used as the secondary antibody.)

Testing Data

(At 25 degree C. The primary antibody was diluted at 1/200 and incubated with the sample for 1 hour at 37 degree C. An Alexa Fluor 594 conjugated goat anti-rabbit IgG (H+L) Ab, diluted at 1/600, was used as the secondary antibody.)

Related Product Information for anti-Presenilin1 antibody

Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein). Requires the presence of the other members of the gamma-secretase complex for protease activity. Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels. Stimulates cell-cell adhesion via its interaction with CDH1; this stabilizes the complexes between CDH1 (E-cadherin) and its interaction partners CTNNB1 (beta-catenin), CTNND1 and JUP (gamma-catenin). Under conditions of apoptosis or calcium influx, cleaves CDH1. This promotes the disassembly of the complexes between CDH1 and CTNND1, JUP and CTNNB1, increases the pool of cytoplasmic CTNNB1, and thereby negatively regulates Wnt signaling. Required for normal embryonic brain and skeleton development, and for normal angiogenesis (By similarity). Mediates the proteolytic cleavage of EphB2/CTF1 into EphB2/CTF2. The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is therefore involved in calcium homeostasis. Involved in the regulation of neurite outgrowth. Is a regulator of presynaptic facilitation, spike transmission and synaptic vesicles replenishment in a process that depends on gamma-secretase activity. It acts through the control of SYT7 presynaptic expression (By similarity).

NCBI and Uniprot Product Information

• NCBI GI #: 4506163
• NCBI GeneID: 5663
• NCBI Accession #: NP_000012.1
• NCBI GenBank Nucleotide #: NM_000021.3
• UniProt Accession #: P49768; O95465; Q14762; Q15719; Q15720; Q96P33; Q9UIF0; B2R6D3
• Molecular Weight: 52,668 Da
• NCBI Official Full Name: presenilin-1 isoform I-467
• NCBI Official Synonym Full Names: presenilin 1
• NCBI Official Symbol: PSEN1
• NCBI Official Synonym Symbols: AD3; FAD; PS1; PS-1; S182
• NCBI Protein Information: presenilin-1
• UniProt Protein Name: Presenilin-1
• UniProt Gene Name: PSEN1
• UniProt Synonym Gene Names: AD3; PS1; PSNL1; PS-1; PS1-CTF12
• UniProt Entry Name: PSN1_HUMAN

NCBI Description

Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1; PSEN2) or in the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor, such that they either directly regulate gamma-secretase activity or themselves are protease enzymes. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene, the full-length nature of only some have been determined. [provided by RefSeq, Aug 2008]

Uniprot Description

PSEN1: probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). Requires the other members of the gamma-secretase complex to have a protease activity. May play a role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. Regulates epithelial- cadherin function. Five alternative splice isoforms have been identified.

Protein type: Membrane protein, integral; EC 3.4.23.-; Cell surface; Mitochondrial; Membrane protein, multi-pass; Protease

Chromosomal Location of Human Ortholog: 14q24.3

Cellular Component: Golgi apparatus; nuclear outer membrane; centrosome; cell surface; smooth endoplasmic reticulum; mitochondrion; integral to plasma membrane; lysosomal membrane; integral to membrane; lipid raft; kinetochore; ciliary rootlet; cell soma; membrane; perinuclear region of cytoplasm; mitochondrial inner membrane; apical plasma membrane; cytoplasmic vesicle; dendritic shaft; neuromuscular junction; endoplasmic reticulum membrane; nuclear membrane; rough endoplasmic reticulum; endoplasmic reticulum; cell cortex; Z disc; Golgi membrane; growth cone; axon

Molecular Function: protein binding; cadherin binding; calcium channel activity; endopeptidase activity; beta-catenin binding; aspartic-type endopeptidase activity; PDZ domain binding

Biological Process: positive regulation of catalytic activity; extracellular matrix organization and biogenesis; activation of MAPKK activity; positive regulation of apoptosis; beta-amyloid formation; regulation of synaptic plasticity; positive regulation of coagulation; Wnt receptor signaling pathway through beta-catenin; choline transport; T cell receptor signaling pathway; mitochondrial transport; post-embryonic development; T cell activation during immune response; extracellular matrix disassembly; positive regulation of MAP kinase activity; epithelial cell proliferation; cell-cell adhesion; negative regulation of axonogenesis; negative regulation of neuron apoptosis; embryonic limb morphogenesis; autophagic vacuole formation; somitogenesis; regulation of phosphorylation; skin morphogenesis; Notch receptor processing; negative regulation of ubiquitin-protein ligase activity; neuron development; Cajal-Retzius cell differentiation; hemopoietic progenitor cell differentiation; response to oxidative stress; negative regulation of apoptosis; regulation of synaptic transmission, glutamatergic; protein maturation; neuron migration; protein amino acid glycosylation; cell fate specification; myeloid dendritic cell differentiation; negative regulation of transcription from RNA polymerase II promoter; protein transport; amyloid precursor protein catabolic process; beta-amyloid metabolic process; regulation of resting membrane potential; brain morphogenesis; heart looping; positive regulation of receptor recycling; dorsoventral neural tube patterning; blood vessel development; Notch signaling pathway; L-glutamate transport; thymus development; membrane protein ectodomain proteolysis; memory; negative regulation of epidermal growth factor receptor activity; smooth endoplasmic reticulum calcium ion homeostasis; neuron apoptosis; endoplasmic reticulum calcium ion homeostasis; cerebral cortex cell migration; skeletal morphogenesis; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; regulation of protein binding; protein processing; synaptic vesicle targeting; response to DNA damage stimulus

Disease: Alzheimer Disease 3; Pick Disease Of Brain; Frontotemporal Dementia; Acne Inversa, Familial, 3; Cardiomyopathy, Dilated, 1u