Recombinant Human Glycosylphosphatidylinositol anchor attachment 1 protein (GPAA1)

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Description

Functional Roles in Biological Processes

GPAA1 is a core component of the GPI transamidase complex, working alongside PIGT and PIGK to mediate GPI anchor transfer to nascent proteins . Key roles include:

GPI Anchor Biosynthesis

  • Mechanism: Facilitates the substitution of GPI anchors for C-terminal signal peptides in target proteins .

  • Subcellular Localization: Primarily active in the ER, with interactions dependent on its transmembrane domains .

Cancer Progression

GPAA1 upregulation is linked to aggressive phenotypes in hepatocellular carcinoma (HCC) and other cancers:

Cancer TypeObserved EffectMolecular ImpactSource
HCCIncreased proliferation, migration, invasionDownregulates MMP2/MMP9; binds SF3B4
Gastric CancerPromotes ERBB signaling, tumor growthRegulates GPI-anchored proteins

Silencing GPAA1 in HCC cells reduces colony formation (Fig. 2D in ) and invasive capabilities (Fig. 2F-G in ).

GPI Anchoring Deficiencies

Biallelic GPAA1 variants cause congenital disorders characterized by:

FeatureDescriptionSource
Developmental DelaySevere motor and cognitive impairments
Neurological SymptomsHypotonia, seizures, cerebellar atrophy, dysarthria, ataxia
Skeletal AbnormalitiesOsteopenia, dysmetria

A novel homozygous variant (c.1726C>T, p.Gln576*) was identified in a 4-year-old male with these phenotypes .

Associated Conditions

DiseaseDescriptionSource
GPIBD15Glycosylphosphatidylinositol biosynthesis defect, type 15
Metabolic DisordersAltered alkaline phosphatase levels (low in ~15% of cases)

Research Applications

Recombinant GPAA1 is utilized in:

  1. Biochemical Assays:

    • ELISA: Detects anti-GPAA1 antibodies in serum .

    • Western Blot: Validates protein expression in cell lysates .

  2. Cancer Studies:

    • siRNA Knockdown: Demonstrates GPAA1’s role in HCC cell proliferation (Fig. 2C in ).

    • Protein Interaction: Confirms binding to splicing factor SF3B4 in HCC .

  3. Genetic Studies:

    • Variant Analysis: LOVD database lists 24 GPAA1 variants, including 10 novel mutations linked to GPIBD15 .

Production and Quality Control

ParameterSpecificationSource
Expression SystemWheat germ (in vitro)
Purity>95% (Coomassie-stained SDS-PAGE)
Storage-80°C in 50 mM Tris-HCl buffer (pH 8.0) with reduced glutathione
StabilityAliquot to avoid freeze-thaw cycles; usable within 3 months post-delivery

Future Directions

  1. Therapeutic Targeting: Inhibiting GPAA1 in HCC may suppress tumor spread .

  2. Diagnostic Biomarker: Elevated GPAA1 levels correlate with poor HCC prognosis .

  3. Gene Therapy: Correcting GPAA1 mutations in GPIBD15 patients remains an area of exploration .

Product Specs

Form
Lyophilized powder
Note: While we prioritize shipping the format currently in stock, we can accommodate specific format requests. Please indicate your desired format in the order notes, and we will fulfill your requirement.
Lead Time
Delivery time may vary based on the purchase method and location. Please consult your local distributors for specific delivery information.
Note: All proteins are shipped with standard blue ice packs unless otherwise specified. If dry ice shipment is required, please contact us in advance for an additional fee.
Notes
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Reconstitution
We recommend briefly centrifuging the vial before opening to ensure the contents are at the bottom. Reconstitute the protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL. We recommend adding 5-50% glycerol (final concentration) and aliquoting for long-term storage at -20°C/-80°C. Our default final glycerol concentration is 50%. Customers can use this as a reference.
Shelf Life
Shelf life is influenced by various factors such as storage conditions, buffer components, temperature, and the protein's intrinsic stability.
Generally, the shelf life for liquid form is 6 months at -20°C/-80°C. For lyophilized form, the shelf life is 12 months at -20°C/-80°C.
Storage Condition
Store at -20°C/-80°C upon receipt. Aliquoting is necessary for multiple uses. Avoid repeated freeze-thaw cycles.
Tag Info
Tag type will be determined during the manufacturing process.
The tag type will be determined during production. If you have a specific tag type in mind, please inform us, and we will prioritize developing the specified tag.
Synonyms
GPAA1; GAA1; Glycosylphosphatidylinositol anchor attachment 1 protein; GPI anchor attachment protein 1; GAA1 protein homolog; hGAA1
Buffer Before Lyophilization
Tris/PBS-based buffer, 6% Trehalose.
Datasheet
Please contact us to get it.
Expression Region
2-621
Protein Length
Full Length of Mature Protein
Species
Homo sapiens (Human)
Target Names
Target Protein Sequence
GLLSDPVRRRALARLVLRLNAPLCVLSYVAGIAWFLALVFPPLTQRTYMSENAMGSTMVE EQFAGGDRARAFARDFAAHRKKSGALPVAWLERTMRSVGLEVYTQSFSRKLPFPDETHER YMVSGTNVYGILRAPRAASTESLVLTVPCGSDSTNSQAVGLLLALAAHFRGQIYWAKDIV FLVTEHDLLGTEAWLEAYHDVNVTGMQSSPLQGRAGAIQAAVALELSSDVVTSLDVAVEG LNGQLPNLDLLNLFQTFCQKGGLLCTLQGKLQPEDWTSLDGPLQGLQTLLLMVLRQASGR PHGSHGLFLRYRVEALTLRGINSFRQYKYDLVAVGKALEGMFRKLNHLLERLHQSFFLYL LPGLSRFVSIGLYMPAVGFLLLVLGLKALELWMQLHEAGMGLEEPGGAPGPSVPLPPSQG VGLASLVAPLLISQAMGLALYVLPVLGQHVATQHFPVAEAEAVVLTLLAIYAAGLALPHN THRVVSTQAPDRGWMALKLVALIYLALQLGCIALTNFSLGFLLATTMVPTAALAKPHGPR TLYAALLVLTSPAATLLGSLFLWRELQEAPLSLAEGWQLFLAALAQGVLEHHTYGALLFP LLSLGLYPCWLLFWNVLFWK
Uniprot No.

Target Background

Function
GPAA1 is essential for the GPI-anchoring of precursor proteins but is not involved in GPI synthesis. It acts before or during the formation of the carbonyl intermediate.
Gene References Into Functions
  1. A splicing mutation was found to decrease GPAA1 mRNA. PMID: 29100095
  2. The lumenal domain of GAA1/GPAA1 has a 3D structure similar to that of an M28-type aminopeptidase. GAA1/GPAA1 is a candidate for the enzyme that catalyzes the peptide bond formation between the omega-site and a phosphoethanolamine group of GPI lipid anchor. PMID: 24743167
  3. A conserved proline in the last transmembrane segment of Gaa1 is required for glycosylphosphatidylinositol recognition by GPI transamidase PMID: 14660601
  4. Gaa1 is passively retained in the ER by a signalless mechanism PMID: 15713669
  5. Increased expression of glycosyl-phosphatidylinositol anchor attachment protein 1 is associated with gene amplification in hepatocellular carcinoma PMID: 16642471
  6. Results show an increased expression level and elevated copy number for GAA1 in head and neck squamous carcinoma, suggesting a role for this GPI anchor subunit in HNSCC. PMID: 18028549

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Database Links

HGNC: 4446

OMIM: 603048

KEGG: hsa:8733

STRING: 9606.ENSP00000347206

UniGene: Hs.627962

Subcellular Location
Endoplasmic reticulum membrane; Multi-pass membrane protein.
Tissue Specificity
Ubiquitously expressed in fetal and adult tissues. Expressed at higher levels in fetal tissues than adult tissues.

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