GIP1 Antibody

Shipped with Ice Packs

In Stock

Cat. No.

BT1240262

Synonyms

GIP1 antibody; At3g13222 antibody; GBF-interacting protein 1 antibody

Quick Inquiry

Description

Mechanisms of Action

GIP1 Antibodies operate through two primary mechanisms:

GIP Receptor (GIPR) Antagonism

Antibodies targeting GIPR block GIP’s interaction with its receptor, inhibiting downstream signaling pathways. Key examples include:

Gipg013: A phage-derived antibody with high affinity for GIPR ( $K_i = 7\ \text{nM}$ in humans). It competitively neutralizes GIP-induced insulin secretion in vitro and in vivo .
AMG 133: A bispecific antibody conjugating a GIPR antagonist to a GLP-1 analogue, enhancing metabolic efficacy through dual receptor modulation .

Mechanistic Pathways:

Target	Action	Key Pathways
GIPR	Blocks GIP binding, reducing cAMP/PKA	Insulin secretion, fat storage, bone remodeling
GLP-1R (in bispecifics)	Agonism via GLP-1 analogues	Insulin secretion, appetite regulation

GIP Neutralization

Antibodies directly binding GIP (e.g., MAB8864 ) prevent its interaction with GIPR, though this approach is less explored in therapeutic contexts.

GIPR Antagonist Antibodies

Antibody	Key Features	Species Specificity	Efficacy Highlights
Gipg013	$K_i = 7\ \text{nM}$ (human GIPR)	Mouse, Rat, Dog, Human	Inhibits GIP-induced insulin secretion in vivo
AMG 133	$IC_{50} = 42.4\ \text{nM}$ (human GIPR)	Human, Cynomolgus, Mouse	Synergistic weight loss in DIO mice vs. monotherapies

Bispecific Molecules (GIPR-Ab/GLP-1):

Parameter	Effect in DIO Mice/Monkeys
Body Weight Reduction	15–20% greater than GIPR-Ab alone
Respiratory Exchange Ratio	Reduced, indicating fat oxidation
GLP-1R Agonism	$EC_{50} = 24.4\ \text{pM}$ (human)

In Vitro Studies:

Antibody	GIPR Antagonism (IC₅₀)	GLP-1R Agonism (EC₅₀)	Species Tested
AMG 133	42.4 nM (human)	24.4 pM (human)	Human, Cynomolgus, Mouse
Murine Surrogate	4.1 nM (mouse GIPR)	90.6 pM (mouse GLP-1R)	Mouse

GIP-Specific Antibodies

MAB8864 (Human GIP Antibody):

Target: GIP (1-39), a truncated, proatherogenic isoform .
Applications: Immunohistochemistry (IHC) in human tissue studies.
Findings: Detected in plasma peptidomics, linked to vascular inflammation .

Obesity and Metabolic Disorders

AMG 133 demonstrates promise in phase 1 trials with:

Safety: Acceptable tolerability profile at tested doses .
Efficacy: Dose-dependent weight loss, improved metabolic parameters.

Comparative Efficacy of Bispecifics:

Therapy	Body Weight Loss (DIO Mice)	Metabolic Impact
GIPR-Ab/GLP-1	15–20% reduction	Enhanced fat oxidation, improved glucose homeostasis
GIPR-Ab alone	Moderate reduction	Limited to GIPR-mediated effects

Bone and Cardiovascular Health

While not directly tested in clinical trials, preclinical studies suggest GIPR antagonism may:

Bone: Reduce bone resorption (GIP promotes bone formation) .
Cardiovascular: Mitigate proatherogenic effects of GIP (1-39) .

Challenges and Future Directions

Species-Specific Efficacy: GIPR antagonists show variable potency across species (e.g., AMG 133 has low potency in mice) .
Combination Therapies: Bispecific molecules (GIPR-Ab/GLP-1) require optimization for receptor internalization and cAMP signaling .
Safety Monitoring: Long-term effects of GIPR antagonism on pancreatic β-cell survival and bone health remain under investigation .

Product Specs

Buffer

Preservative: 0.03% Proclin 300
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4

Form

Liquid

Lead Time

Made-to-order (14-16 weeks)

Synonyms

GIP1 antibody; At3g13222 antibody; GBF-interacting protein 1 antibody

Target Names

GIP1

Uniprot No.

Q8VZS6

Target Background

Function

GIP1, a plant-specific protein, enhances G-box-binding factor (GBF) DNA binding activity. It may act as a nuclear chaperone or lever, regulating the multimeric state of GBFs. This protein may contribute to bZIP-mediated gene regulation. Notably, GIP1 is able to refold denatured rhodanese in vitro. Under non-reducing conditions, it reduces the DNA-binding activity of BZIP16, BZIP68, and GBF1 through direct physical interaction. GIP1 serves as a negative co-regulator in red and blue light-mediated hypocotyl elongation. During the early stages of seedling development, it promotes hypocotyl elongation by regulating the repression effect of BZIP16 and the activation effect of BZIP68 and GBF1 on LHCB2.4 expression. Additionally, GIP1 enhances the transcriptional activity of LBD18 in the EXP14 promoter, suggesting a role as a transcriptional coactivator of LBD18.

Gene References Into Functions

MGO3 and GIP1 contribute to the regulation of centromeric cohesion in Arabidopsis. (PMID: 28033038)
GIP1 promotes hypocotyl elongation during the early stages of Arabidopsis seedling development. (PMID: 25387999)
GIP1 plays a central role in the proper recruitment and/or stabilization of centromeric proteins, crucial for specifying centromere identity and maintaining centromeric cohesion in somatic cells. (PMID: 26124146)
GIP1 enhances GBF DNA binding activity by acting as a potent nuclear chaperone or crowbar, potentially regulating the multimeric state of GBFs, thereby contributing to bZIP-mediated gene regulation. (PMID: 16117846)
The possible role of this protein during the nucleation process is discussed. (PMID: 18178112)

Hide All

Database Links

KEGG: ath:AT3G13222

STRING: 3702.AT3G13222.1

UniGene: At.27156

Protein Families

GIP1 family

Subcellular Location

Nucleus.

Tissue Specificity

Expressed in roots, leaves, stems and flowers.

Q&A

FAQs for GIP1 Antibody in Academic Research

Advanced Research Questions

What structural features of GIP1 enable its interaction with Gβγ subunits?

Mechanistic insights:
- GIP1’s hydrophobic cavity (composed of six α-helices) binds the lipid-modified C-terminus of Gβγ, sequestering G proteins in the cytosol .
- Mutagenesis studies show that disrupting the hydrogen-bond network at the cavity entrance reduces binding affinity by >70% .

Structural Domain	Functional Role	Experimental Evidence
Hydrophobic cavity	Binds Gβγ	Cryo-EM of GIP1-Gβγ complex
N-terminal region	Regulates shuttling	Deletion mutants show impaired chemotaxis

How to resolve contradictions in GIP1 localization studies?

Approach:
- Dynamic imaging: Use FRET-based sensors to capture real-time GIP1-Gβγ interactions during chemotaxis .
- Context-dependent analysis: Account for cell type-specific variations (e.g., Dictyostelium vs. mammalian cells) .
- Quantitative Western blotting: Normalize cytosolic/membrane fractions using markers like Na+/K+ ATPase .

What protocols optimize co-IP of GIP1 with trimeric G proteins?

Optimization steps:
- Buffer composition: Use 20 mM HEPES, 150 mM NaCl, 1% digitonin, and GTPγS to stabilize Gα-Gβγ complexes .
- Crosslinking: Apply DSS (disuccinimidyl suberate) to preserve transient interactions .
- Controls: Include Gγ-deficient cells to confirm Gβγ dependency .

How to design assays for GIP1’s role in GPCR signaling dynamics?

Strategies:
- cAMP accumulation assays: Use HEK293T cells transfected with GIPR and measure cAMP via HTRF (e.g., Cisbio kits) .
- Receptor internalization: Tag GLP-1R or GIPR with pH-sensitive fluorophores to track GIP1-mediated endocytosis .

What methods detect GIP1 in post-translational modification studies?

Advanced techniques:
- Phosphoproteomics: Enrich phosphorylated GIP1 via TiO2 columns and analyze via LC-MS/MS.
- Ubiquitination assays: Co-express HA-tagged ubiquitin with GIP1 and perform pull-downs under proteasome inhibition .

Data Analysis & Interpretation

How to interpret conflicting results in GIP1 antibody-based ELISA?

Critical factors:
- Antibody pairing: Use monoclonal 72A1 (C-terminal capture) with polyclonal 6A1A (N-terminal detection) to avoid cross-reactivity with GIP(1–42) .
- Sample handling: Add DPP-4 inhibitors to prevent GIP degradation in plasma .

Pitfall	Solution
Cross-reactivity with GLP-1	Pre-absorb serum with GLP-1 peptides
Low sensitivity	Optimize streptavidin coating density

How to validate GIP1 antibody performance in functional blockade experiments?

Functional validation:
- Receptor binding assays: Compete I125-GIP with purified IgG from immunized animals (IC50 ≤ 10 µg/mL) .
- In vivo sequestration: Administer radiolabeled GIP and measure antibody-bound fraction via gamma counting .

Quick Inquiry

Personal Email Detected

Please use an institutional or corporate email address for inquiries. Personal email accounts ( such as Gmail, Yahoo, and Outlook) are not accepted. *

Name*

Email*

Phone

Country

Source

Quantity&Size*

Product Name

Message

GIP1 Antibody

Description

Mechanisms of Action

GIP Receptor (GIPR) Antagonism

Mechanistic Pathways:

GIP Neutralization

GIPR Antagonist Antibodies

Bispecific Molecules (GIPR-Ab/GLP-1):

In Vitro Studies:

GIP-Specific Antibodies

Obesity and Metabolic Disorders

Comparative Efficacy of Bispecifics:

Bone and Cardiovascular Health

Challenges and Future Directions

Product Specs

Target Background

Q&A

FAQs for GIP1 Antibody in Academic Research

Advanced Research Questions

What structural features of GIP1 enable its interaction with Gβγ subunits?

How to resolve contradictions in GIP1 localization studies?

What protocols optimize co-IP of GIP1 with trimeric G proteins?

How to design assays for GIP1’s role in GPCR signaling dynamics?

What methods detect GIP1 in post-translational modification studies?

Data Analysis & Interpretation

How to interpret conflicting results in GIP1 antibody-based ELISA?

How to validate GIP1 antibody performance in functional blockade experiments?

Quick Inquiry

Category

Service