SULT1C2 Human
Description
Definition and Functional Overview of SULT1C2 Human
SULT1C2 (Sulfotransferase 1C2) is a cytosolic enzyme encoded by the SULT1C2 gene in humans, belonging to the sulfotransferase family responsible for sulfating phenolic compounds, hormones, and xenobiotics using 3'-phosphoadenosine-5'-phosphosulfate (PAPS) as a cofactor . It is a phase II detoxification enzyme critical for metabolizing drugs and endogenous molecules, with a molecular mass of ~37 kDa and a His-tagged recombinant form available for experimental use .
Tissue Expression and Localization
| Tissue | Expression Level | Subcellular Localization |
|---|---|---|
| Stomach | High | Cytoplasmic |
| Duodenum, Jejunum, Ileum, Colon, Rectum | Moderate to High | Cytoplasmic |
| Liver | Moderate | Cytoplasmic |
| Kidney (renal tubules) | Moderate | Cytoplasmic |
| Thyroid gland | Low | Cytoplasmic |
| Lung | Absent | — |
Data derived from the Human Protein Atlas and functional studies .
Hepatocellular Carcinoma (HCC)
SULT1C2 overexpression promotes HCC progression by enhancing:
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Cell proliferation and survival
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Migration and invasion (observed in HepG2 and Huh7 cell lines)
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Glycolysis and fatty acid metabolism (metabolomic profiling)
Knockdown experiments reversed these effects, suggesting SULT1C2 as a potential diagnostic marker and therapeutic target for HCC .
Lung Adenocarcinoma (LUAD)
Epigenetic activation via hypomethylation of the SULT1C2 promoter (cg13968390 site) correlates with elevated expression in LUAD tumors. This modification enhances xenobiotic metabolism but may contribute to carcinogenesis .
Mitochondrial Function
SULT1C2 modulates mitochondrial respiration by:
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Increasing cholesterol sulfate levels, thereby enhancing membrane potential and maximal respiratory capacity .
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Conferring resistance to ischemia/reperfusion injury in kidney models .
Regulation and Transcriptional Control
The SULT1C2 promoter is regulated by DNA methylation, with hypomethylation linked to elevated expression in LUAD . Transcription factors such as NF-κB and AP-1 have been implicated in its activation, though specific mechanisms remain under investigation .
Therapeutic and Diagnostic Potential
Product Specs
Recombinant human SULT1C2, expressed in E. coli, is a single, non-glycosylated polypeptide chain. It consists of 316 amino acids (1-296a.a.) and has a molecular mass of 37.0 kDa. A 20 amino acid His-tag is fused to the N-terminus of SULT1C2. Purification is achieved using proprietary chromatographic techniques.
The SULT1C2 solution (1 mg/ml) is formulated in 20 mM Tris-HCl buffer (pH 8.0), 20% glycerol, 0.1 M NaCl, and 1 mM DTT.
For short-term storage (2-4 weeks), keep at 4°C. For extended periods, store frozen at -20°C. The addition of a carrier protein (0.1% HSA or BSA) is recommended for long-term storage. Avoid repeated freeze-thaw cycles.
MGSSHHHHHH SSGLVPRGSH MALTSDLGKQ IKLKEVEGTL LQPATVDNWS QIQSFEAKPD DLLICTYPKA GTTWIQEIVD MIEQNGDVEK CQRAIIQHRH PFIEWARPPQ PSGVEKAKAM PSPRILKTHL STQLLPPSFW ENNCKFLYVA RNAKDCMVSY YHFQRMNHML PDPGTWEEYF ETFINGKVVW GSWFDHVKGW WEMKDRHQIL FLFYEDIKRD PKHEIRKVMQ FMGKKVDETV LDKIVQETSF EKMKENPMTN RSTVSKSILD QSISSFMRKG TVGDWKNHFT VAQNERFDEI YRRKMEGTSI NFCMEL.
Q&A
What is human SULT1C2 and what is its primary function?
Human SULT1C2 is a cytosolic enzyme belonging to the Sulfotransferase 1 family that catalyzes the sulfate conjugation of various compounds including drugs, xenobiotic compounds, hormones, and neurotransmitters. The enzyme transfers a sulfo group from the universal sulfate donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to acceptor substrates. This sulfation process typically increases the water solubility of these compounds, facilitating their elimination from the body, though in some cases it may also activate certain compounds .
What is the molecular structure of recombinant human SULT1C2?
Recombinant human SULT1C2 consists of amino acids Ala2-Leu296, often with an N-terminal 6-His tag when produced in expression systems such as E. coli. The recombinant protein maintains the catalytic activity of the native enzyme and can be used for various biological assays . The functional protein contains the catalytic domain necessary for the transfer of sulfate groups from PAPS to various acceptor molecules.
What are the known substrates of human SULT1C2?
SULT1C2 shows confirmed activity towards p-nitrophenol and N-hydroxy-2-acetylamino-fluorene (N-OH-2AAF) . Recent research has also identified cholesterol as a substrate, with SULT1C2 converting it to cholesterol sulfate in mitochondrial membranes . The complete spectrum of physiological substrates remains under investigation, as the role of SULT1C2 in various biological processes continues to be elucidated.
How is SULT1C2 distributed across human tissues?
Human SULT1C2 is primarily expressed in the adult stomach, kidney, and thyroid gland. It is also found in fetal kidney and liver tissues . More specifically, SULT1C2 is mainly expressed throughout the gastrointestinal tract (including the stomach, duodenum, jejunum, ileum, colon, caecum, and rectum), liver, and kidneys, but is notably absent in the lungs . This tissue-specific expression pattern suggests specialized roles in these organs.
How does SULT1C2 expression differ between fetal and adult tissues?
SULT1C2 shows differential expression between fetal and adult tissues. While it is expressed in both fetal kidney and liver, its expression in adult tissues is more prominent in the stomach, kidney, and thyroid gland . This developmental-stage-specific expression suggests potential roles in organ development and maturation. In contrast, the related enzyme SULT1C4 is expressed at higher levels in fetal lung and kidney and at lower levels in fetal heart .
How is SULT1C2 expression regulated in normal versus disease states?
Research has shown that SULT1C2 is overexpressed in hepatocellular carcinoma (HCC) tissues compared to adjacent normal tissues . This differential regulation suggests that SULT1C2 expression may be influenced by oncogenic processes. The mechanisms controlling this upregulation remain under investigation but may involve alterations in transcription factors, epigenetic modifications, or signaling pathways that become dysregulated during carcinogenesis.
What is the evidence linking SULT1C2 to hepatocellular carcinoma (HCC)?
Multiple studies have demonstrated that SULT1C2 is overexpressed in HCC cancerous tissues compared to adjacent normal tissues. Higher SULT1C2 expression has been associated with lower survival rates in HCC patients . Experimental evidence shows that SULT1C2 overexpression promotes the growth, survival, migration, and invasiveness of HCC cells, while knockdown of SULT1C2 significantly inhibits these processes . These findings collectively suggest that SULT1C2 plays a pro-oncogenic role in HCC progression.
What metabolic pathways does SULT1C2 influence in cancer cells?
Transcriptome and metabolome analyses of HCC cell lines before and after SULT1C2 knockdown have revealed that SULT1C2 significantly influences glycolysis and fatty acid metabolism . SULT1C2 knockdown suppresses these metabolic pathways, which are critical for cancer cell proliferation and survival. Rescue experiments demonstrated that the inhibitory effects of SULT1C2 knockdown could be reversed by SULT1C2 overexpression, confirming the direct relationship between SULT1C2 and these metabolic alterations .
How might SULT1C2 serve as a diagnostic marker for HCC?
Based on its overexpression in HCC tissues and correlation with patient survival rates, SULT1C2 shows potential as a diagnostic marker for HCC . The differential expression between cancerous and normal tissues provides a basis for developing diagnostic assays. Unlike some SULT family members that suppress cancer (such as SULT2B1, which removes oxysterols via sulfation), SULT1C2 appears to promote cancer progression, making it a distinctive marker within the sulfotransferase family . Further validation in larger patient cohorts and development of specific detection methods would be necessary for clinical application.
How does SULT1C2 affect mitochondrial respiration?
SULT1C2, in the presence of 3-phosphoadenosine 5'-phosphosulfate (PAPS), increases mitochondrial respiratory capacity, particularly state-III respiration. This effect is observed when SULT1C2 and PAPS are added to freshly isolated mitochondria, resulting in enhanced maximal respiratory capacity in response to succinate, ADP, and rotenone . The mechanism involves SULT1C2-mediated modification of cholesterol to cholesterol sulfate in mitochondrial membranes, which subsequently increases membrane potential and respiratory capacity.
What is the role of SULT1C2 in protecting against ischemia/reperfusion injury?
In vivo studies using gene delivery of SULT1C2 expression plasmids have demonstrated that SULT1C2 can confer resistance to ischemia/reperfusion injury in kidney tissues . This protective effect is associated with increased mitochondrial membrane potential. Mitochondria isolated from SULT1C2 gene-transduced kidneys exhibit elevated state-III respiration compared to controls, suggesting that SULT1C2's protective role is mediated through enhancement of mitochondrial function .
How does SULT1C2-produced cholesterol sulfate influence mitochondrial function?
SULT1C2 converts cholesterol to cholesterol sulfate in mitochondrial membranes, as demonstrated by lipidomics and thin-layer chromatography of mitochondria treated with SULT1C2 and PAPS . The addition of cholesterol sulfate at nanomolar concentrations to freshly isolated mitochondria increases maximal respiratory capacity, mimicking the effect of SULT1C2. This suggests that cholesterol sulfate is a key mediator of SULT1C2's effects on mitochondrial function, potentially by altering membrane properties or influencing electron transport chain components .
How is the enzymatic activity of SULT1C2 typically measured?
The enzymatic activity of recombinant human SULT1C2 can be determined using a phosphatase-coupled assay. The detailed protocol typically involves:
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Preparing a reaction mixture containing Coupling Phosphatase 3, p-nitrophenol, PAPS, and assay buffer
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Diluting rhSULT1C2 to an appropriate concentration (e.g., 40 μg/mL) in assay buffer
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Preparing a phosphate standard curve for quantification
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Combining the enzyme with the reaction mixture and incubating at 37°C
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Adding Malachite Green Reagents to detect released phosphate
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Measuring absorbance at 620 nm and calculating specific activity using the formula:
| Specific Activity (pmol/min/μg) = | Phosphate released (nmol) × (1000 pmol/nmol) |
|---|---|
| Incubation time (min) × amount of enzyme (μg) |
This method allows for reliable quantification of SULT1C2 activity .
What cell lines are commonly used for SULT1C2 research in cancer studies?
HepG2 and Huh7 cell lines are commonly used in SULT1C2 research related to hepatocellular carcinoma. These human liver cancer cell lines serve as valuable models for investigating the effects of SULT1C2 expression or knockdown on cancer cell behavior . Experiments typically involve analyzing the effects of SULT1C2 manipulation on cell growth, survival, migration, and invasiveness, as well as transcriptomic and metabolomic changes in these cell lines.
What techniques are used to study SULT1C2's effect on mitochondrial lipids?
To study SULT1C2's effect on mitochondrial lipids, researchers employ techniques such as lipidomics and thin-layer chromatography. In thin-layer chromatography, the Rf values of cholesterol (0.94-0.97) and cholesterol sulfate (0.48-0.52) allow for their separation and identification . The table below shows typical Rf values for different samples:
| Sample | Rf Value |
|---|---|
| Cholesterol standard | 0.97 |
| Cholesterol sulfate standard | 0.52 |
| Control mitochondrial cholesterol band | 0.95 |
| Mitochondria + SULT1C2 + PAPS cholesterol band | 0.96 |
| Mitochondria + SULT1C2 + PAPS cholesterol-SO4 band | 0.48 |
| Mitochondria from IPC kidney-cholesterol band | 0.94 |
| Mitochondria from IPC kidney-cholesterol sulfate band | 0.52 |
These techniques help identify and quantify the conversion of cholesterol to cholesterol sulfate mediated by SULT1C2 .
How does SULT1C2 differ from other members of the sulfotransferase family in its biological functions?
SULT1C2 exhibits distinct tissue expression patterns and substrate specificities compared to other sulfotransferase family members. While SULT1C2 appears to promote cancer progression, other SULTs like SULT2B1 suppress cancer by removing oxysterols through sulfation . SULT1C2 is most closely related to SULT1C4, but they differ in their expression patterns, with SULT1C4 being more highly expressed in fetal lung and kidney and at lower levels in fetal heart . Unlike SULT1E1, which suppresses MCF-7 cell growth when overexpressed, SULT1C2 promotes cancer cell proliferation and invasiveness .
What are the challenges in identifying the physiological substrates of SULT1C2?
The identification of physiological substrates for SULT1C2 presents several challenges:
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Currently identified substrates (p-nitrophenol, N-OH-2AAF) do not fully explain the pro-cancer effects observed with SULT1C2 overexpression .
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The physiological substrates remain largely unknown, necessitating comprehensive screening approaches .
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The cell-specific nature of SULT activity complicates the extrapolation of findings between different tissue types.
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The broad substrate specificity of sulfotransferases requires careful validation of potential substrates in physiologically relevant contexts.
Advanced approaches combining proteomics, metabolomics, and activity-based protein profiling may help overcome these challenges.
What therapeutic strategies could target SULT1C2 in cancer treatment?
Based on current understanding, several therapeutic strategies could potentially target SULT1C2 in cancer treatment:
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Direct inhibition of SULT1C2 enzymatic activity through small molecule inhibitors
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RNA interference or antisense oligonucleotides to reduce SULT1C2 expression
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Targeting the metabolic pathways influenced by SULT1C2, particularly glycolysis and fatty acid metabolism
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Development of antibody-drug conjugates targeting cells with high SULT1C2 expression
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Combination therapies that address both SULT1C2-dependent and independent pathways in cancer progression
The development of these strategies would require further understanding of SULT1C2's precise mechanisms of action in cancer cells and validation in preclinical models before clinical translation .
Product Science Overview
Sulfotransferase Family, Cytosolic 1C, Member 2 (SULT1C2) is a member of the sulfotransferase enzyme family, which plays a crucial role in the sulfate conjugation of various hormones, neurotransmitters, drugs, and xenobiotic compounds. These enzymes are cytosolic and exhibit distinct tissue distributions and substrate specificities .
The SULT1C2 gene is located on chromosome 2q12.3 and encodes a protein that belongs to the SULT1 subfamily . The gene structure, including the number and length of exons, is similar among family members . The SULT1C2 protein consists of 296 amino acids and is responsible for transferring a sulfo moiety from 3’-phospho-5’-adenylyl sulfate (PAPS) to phenol-containing compounds .
SULT1C2 catalyzes the sulfate conjugation of phenolic compounds, which is a critical process for the metabolism and detoxification of various endogenous and exogenous substances . Unlike some other sulfotransferases, SULT1C2 does not sulfonate steroids, dopamine, acetaminophen, or alpha-naphthol . It is particularly noted for catalyzing the sulfonation of the carcinogenic N-Hydroxy-2-acetylaminofluorene, leading to highly reactive intermediates capable of forming DNA adducts, potentially resulting in mutagenesis .
Recombinant SULT1C2 is produced using recombinant DNA technology, which involves cloning the SULT1C2 gene into an expression vector and introducing it into a host cell, such as Escherichia coli (E. coli). The host cells then express the SULT1C2 protein, which can be purified and used for various research and industrial applications .
