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SLC45A2

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

Background

Solute carrier family 45 member 2 (SLC45A2) - also known as membrane associated transporter protein (MATP), melanoma antigen AIM1, and MATP gene-is an integral membrane glycoprotein with twelve transmembrane domains that is primarily localized in the internal membranes of melanosomes where it maintains a pH conducive to melanin synthesis. This protein contains a canonical conserved sugar recognition sequence (RxGRR) in its cytosolic loop, which is a hallmark of proton-coupled sugar symporters and has been proven to operate as an acid-dependent importer for sucrose, glucose, fructose and mannose when heterologously expressed in yeast. The physiological significance of SLC45A2 has been indicated by association with the gene for oculocutaneous albinism (OCA4), which is an autosomal recessive disease caused by a defect in melanin biosynthesis from melanocytes affecting skin, hair and eyes. New therapies targeting the genetic mechanisms of OCA4 remain in early developmental phases, largely owing to its inherent low prevalence as an orphan disease; estimated global population frequency is around 1:100.000 but significantly differs between ethnic groups (3%–4% of all OCA cases reported from Dutch variant populations corresponding with only 27% registered during comprehensive evaluations performed within Japan where the p.D157N( c.469G>A) founder mutation predominates). In addition to its relevance in albinism, SLC45A2 is becoming an important player in determining normal human pigmentation variation because the common p.F374L (rs16891982) polymorphism has displayed hallmark of positive selection signals within European populations and accounts for much of skin color diversity between continental groups.

Fig.1. Multistage processes of melanosome formation via SLC45A2. (OA Literature)Fig.1 Schematic representation of the multistage processes of melanosome formation and proteins participating in pH regulation and melanin synthesis.1

SLC45A2 Protein Function: A Hub of Cellular Regulation

From the functional spectrum of SLC45A2 across diverse aspects of melanocyte biology, pigmentation physiology and cancer pathogenesis:

  • Melanosomal pH Regulation and Tyrosinase Activation: The most well-established role of SLC45A2 is in the neutralization of melanosomal pH, which allows for proper functioning of tyrosinase. Tyrosinase, the principal enzyme of melanogenesis, remains nearly inactive at pH < 6.0; yet vATPase constantly loads protons into melanosome lumen to generate an acidic environment that would otherwise inactivate all melanin production.
  • Tyrosinase Trafficking and Melanosome Maturation: SLC45A2 promotes efficient trafficking of tyrosinase from trans-Golgi network (TGN) via a limited number of lysosomal compartments on its way to mature melanosomes. Research in murine melanocytes deficient for the underwhite (uw) locus, a mouse homologue of SLC45A2, demonstrates that tyrosinase processing and folding occur normally but traffics poorly into melanosomes before being redirected to secretion.
  • Therapeutic Biomarker & Drug Target: The dramatic downregulation of SLC45A2 in primary and metastatic melanoma versus benign nevi makes it an important diagnostic discriminator and prognostic marker. Pharmacologic strategies to restore SLC45A2 function via demethylating agents, transcriptional activation or gene delivery vectors also are progressing in pre-clinical evaluation with novel anti-metastatic potential.

SLC45A2 Membrane Protein Product

We engineer a collection of SLC45A2 membrane protein constructs designed to address key challenges associated with major facilitator superfamily transporter research. Since proper organization of the twelve transmembrane α-helices and preservation of structural features relevant to transporter function are important for studying proton-coupled transport and melanosome pH regulation, our platform supports the development of protein constructs tailored to specific experimental requirements. These preparations can be used for structural, biochemical, transporter, and pigmentation-related research, including studies of substrate interactions and SLC45A2-associated transport mechanisms. Protein format, production conditions, and applicable structural or functional characterization strategies are selected according to individual project requirements. Specific quality-control methods and performance data are provided based on the corresponding construct or project documentation.

SLC45A2 Protein Product

Not finding the membrane protein product you need? Contact us to start your one-stop custom service!

SLC45A2 Stable Cell Line Product

Physiologically representative cellular platforms are a prerequisite for decoding SLC45A2-mediated melanosomal transport and accelerating therapeutic development pipelines. We infuse state of the art high-throughput selection platforms with stable SLC45A2 cell lines that retain true-to-life melanosomal membrane localization and native glycosylation, along with weak stressor responsiveness in standard driving media. We have developed loss-of-function models via shRNA-depleted and dominant-negative SLC45A2-expressing cells to permit mechanistic interrogation of SLC45A2-driven tumor suppression, along with corresponding high-throughput screening systems for synthetic lethality. Every cell line is well characterized by genomic integration, somal pH with ratiometric fluorescent indicators, and functional assays of melanin content quantification, as well as melanogenesis-related cellular processes such as tyrosinase trafficking or adhesion. Such expandable values characterize cellular resources critical for investigating pigmentation disorders, screening compounds that ameliorate metastatic features, and preclinical characterization of potential biologics directed against the SLC45A2 axis.

SLC45A2 Stable Cell Line Product

Not finding the stable cell line product you need? Contact us to start your one-stop custom service!

SLC45A2 Recombinant Antibody Product

Advance your SLC45A2 studies with our suite of sequence-defined, high-affinity monoclonal antibodies developed for detection and characterization of this twelve-pass transmembrane transporter. Depending on the individual clone, antibodies may recognize epitopes within different regions of SLC45A2 and support applications for studying its expression, localization, and membrane-associated biology. Validated applications may include Western blotting, ELISA, flow cytometric analysis, immunofluorescence, and confocal microscopy, depending on the characteristics and validation data available for each antibody. These reagents can support SLC45A2 antibody discovery and detection research in relevant cellular models. Conformation or state specificity, species reactivity, cross-reactivity, epitope accessibility, and application suitability should be determined according to the clone-specific datasheet and available experimental evidence.

SLC45A2 Recombinant Antibody Product

Not finding the recombinant antibody product you need? Contact us to start your one-stop custom service!

Product Features

  • High Purity & Activity: High purity and verified integrity for dependable downstream work.
  • Diverse Expression Systems: Choice of expression formats to match routine or specialized projects.
  • Species Reactivity: Products available for human, mouse, pig, and other species.
  • Validated Applications: Application-tested to deliver consistent signals across common lab workflows.
  • Superior Batch-to-Batch Consistency: Stringent quality controls to ensure low variability from batch to batch.
  • Customization Options: Tags/Labels/package Modifications available upon request.

Custom SLC45A2 Membrane Protein and Antibody Discovery Services

On top of our catalog products we have dedicated capabilities in custom services for membrane protein and antibody discovery&development:

  • Production & Validation: Cloning of the synthesized optimized gene into an expression vector, plus small-scale expression trials to help determine the best expression conditions.
  • Custom Antibody Production: Produced via large-scale expression in mammalian/insect/cell culture or bacterial expression systems, purified in detergent or reconstituted into nanodiscs.
  • Engineered Cell Lines: Creation of stable cell lines that physiologically mimic endogenous SLC45A2 expression and activity.
  • Functional Assessment Systems: Designing and executing assays to assess protein function and ligand binding.

Frequently Asked Questions (FAQ)

  1. Are your SLC45A2 products for clinical application?

    All SLC45A2 products and services are for research use only, not for clinical diagnosis.

  2. What types of SLC45A2 products do you offer?

    We provide various products such as recombinant SLC45A2 membrane proteins (L374 and F374 full-length variants & pathogenic mutants), stable cell lines stably expressing wild-type/mutant SLC45A2, high-quality anti-SLC45Ab antibodies, along with all custom services.

  3. Is your recombinant SLC45A2 supplied in a formulation compatible with direct reconstitution into lipid nanodiscs or synthetic melanosome-mimetic vesicles for structural biology and transport mechanism studies?

    Yes, the protein is purified in a mild, non-ionic detergent buffer and buffer-exchanged into a lipid-compatible system. This supports immediate insertion into synthetic membranes for cryo-electron microscopy, stopped-flow fluorimetry, or reconstituted proton-substrate symport assays without additional dialysis or detergent exchange steps.

  4. Are disease-associated SLC45A2 variants linked to oculocutaneous albinism type 4 available for comparative transport kinetics, melanosome targeting, and protein stability studies?

    Yes, we provide recombinant proteins and also the stable cell lines which contain known pathogenic substitutions in transmembrane helices or cytoplasmic loops where proton coupling/coordinate of substrate is disrupted.

Reference
  1. Koirala, Mahesh, et al. "Computational investigation of the pH dependence of stability of melanosome proteins: implication for melanosome formation and disease." International journal of molecular sciences 22.15 (2021): 8273. Under Open Access license CC BY 4.0, without modification. https://doi.org/10.3390/ijms22158273
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