Details for: SUOX

Gene ID: 6821

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: SUOX

Ensembl ID: ENSG00000139531

Description: sulfite oxidase

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • chondrocyte CL0000138
    CSI 9.07
    rCSI 14.42%
    PRS 93.64
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 8.86
    rCSI 10.74%
    PRS 80.98
  • regulatory T cell CL0000815
    CSI 8.84
    rCSI 10.24%
    PRS 90.37
  • melanocyte of skin CL1000458
    CSI 8.52
    rCSI 11.61%
    PRS 74.54
  • secretory cell CL0000151
    CSI 8.4
    rCSI 8.76%
    PRS 95.59
  • pericyte CL0000669
    CSI 6.56
    rCSI 17.47%
    PRS 78.1
  • conventional dendritic cell CL0000990
    CSI 6.52
    rCSI 5.44%
    PRS 90.7
  • suprabasal keratinocyte CL4033013
    CSI 5.52
    rCSI 9.01%
    PRS 74.65
  • innate lymphoid cell CL0001065
    CSI 5.36
    rCSI 11.07%
    PRS 90.83
  • colon epithelial cell CL0011108
    CSI 5.21
    rCSI 5.46%
    PRS 94.76
  • helper T cell CL0000912
    CSI 4.22
    rCSI 5.97%
    PRS 91.58
  • pancreatic A cell CL0000171
    CSI 3.61
    rCSI 3.79%
    PRS 96.71
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.76
    rCSI 2.49%
    PRS 95.81
  • placental villous trophoblast CL2000060
    CSI 2.71
    rCSI 4.18%
    PRS 95.05
  • basal cell of epidermis CL0002187
    CSI 2.7
    rCSI 4.78%
    PRS 74.09
  • cytotoxic T cell CL0000910
    CSI 2.51
    rCSI 14.38%
    PRS 93.43
  • multi-ciliated epithelial cell CL0005012
    CSI 2.18
    rCSI 2.18%
    PRS 92.6
  • glial cell CL0000125
    CSI 1.44
    rCSI 5.47%
    PRS 92.07

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [SUOX](/details-gene/6821) encodes sulfite oxidase, a homodimeric enzyme located in the mitochondrial intermembrane space that is essential for the final step in the degradation of sulfur-containing amino acids. It catalyzes the oxidation of sulfite to sulfate, a critical detoxification process. Clinically, mutations in [SUOX](/details-gene/6821) lead to isolated sulfite oxidase deficiency ([OMIM 272300](https://omim.org/entry/272300)), a severe autosomal recessive disorder characterized by neurological damage due to the accumulation of toxic sulfite. Expression data indicates that [SUOX](/details-gene/6821) is a significant gene across a wide range of functionally diverse cell types, with particularly high significance in [chondrocyte](/details-cell/CL0000138)s, various T cell subsets including [regulatory T cell](/details-cell/CL0000815)s, and [melanocyte of skin](/details-cell/CL1000458)s, suggesting a fundamental role in cellular metabolism and homeostasis. ## Cellular Roles and Expression Landscape The expression profile of [SUOX](/details-gene/6821) highlights its importance as a fundamental metabolic enzyme across numerous distinct lineages. **Overall**, its highest significance is observed in cells with high metabolic or biosynthetic demands, though these cells belong to disparate functional categories. The most significant expression is found in [chondrocyte](/details-cell/CL0000138)s (CSI: 9.07), which are responsible for producing and maintaining the sulfur-rich extracellular matrix of cartilage. This suggests a critical role for [SUOX](/details-gene/6821) in supplying sulfate for the synthesis of sulfated proteoglycans like chondroitin sulfate. [SUOX](/details-gene/6821) is also highly significant across multiple adaptive immune cell populations, including [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) (CSI: 8.86) and [regulatory T cell](/details-cell/CL0000815)s (CSI: 8.84). This pattern suggests that efficient sulfur metabolism and sulfite detoxification are crucial for T cell maintenance, memory formation, and regulatory function. Its high expression in [conventional dendritic cell](/details-cell/CL0000990)s (CSI: 6.52) further implicates this metabolic pathway in antigen presentation and immune activation. Furthermore, [SUOX](/details-gene/6821) shows high significance in various epithelial and secretory lineages, such as [melanocyte of skin](/details-cell/CL1000458)s (CSI: 8.52), [secretory cell](/details-cell/CL0000151)s (CSI: 8.40), and [suprabasal keratinocyte](/details-cell/CL4033013)s (CSI: 5.52). This broad pattern underscores a housekeeping yet vital function in protecting diverse cell types from sulfite toxicity, a byproduct of cysteine and methionine metabolism. ## Pathways and Molecular Function The function of [SUOX](/details-gene/6821) is centered on sulfur compound metabolism, as annotated by Gene Ontology and Reactome pathways. The protein product is localized to the [mitochondrion](/details-go/GO:0005739), specifically the [mitochondrial intermembrane space](/details-go/GO:0005758). Its core molecular function is [Sulfite oxidase activity](/details-go/GO:0008482), which requires binding to molybdenum ion ([GO:0030151](https://www.ebi.ac.uk/QuickGO/term/GO:0030151)) via a [molybdopterin cofactor](/details-go/GO:0043546), as well as [heme binding](/details-go/GO:0020037). This enzymatic activity is the terminal step in several key metabolic pathways. It is a central component of [Sulfur amino acid metabolism](/details-pathway/R-HSA-1614635) ([R-HSA-1614635](https://reactome.org/content/detail/R-HSA-1614635)), specifically in the [Degradation of cysteine and homocysteine](/details-pathway/R-HSA-1614558) ([R-HSA-1614558](https://reactome.org/content/detail/R-HSA-1614558)). The specific reaction it catalyzes is detailed in the Reactome pathway [Sulfide oxidation to sulfate](/details-pathway/R-HSA-1614517) ([R-HSA-1614517](https://reactome.org/content/detail/R-HSA-1614517)). The critical nature of this function is highlighted by the severe pathology of its deficiency, which has been extensively documented ([Link](https://doi.org/10.1002/humu.9038), [Link](https://doi.org/10.1016/s0092-8674(00)80488-2)). ## Research Directions The widespread and high significance of [SUOX](/details-gene/6821) in diverse cell types points to a fundamental metabolic role, but also raises questions about cell-specific dependencies on this pathway. ### Proposed Hypotheses 1. **Hypothesis 1:** The exceptionally high significance of [SUOX](/details-gene/6821) in [chondrocyte](/details-cell/CL0000138)s indicates that local sulfate production via sulfite oxidation is a rate-limiting step for the synthesis of sulfated glycosaminoglycans (GAGs) essential for cartilage matrix integrity. A reduction in [SUOX](/details-gene/6821) activity, even if not systemic, could predispose cartilage to degradation and pathologies like osteoarthritis. 2. **Hypothesis 2:** High [SUOX](/details-gene/6821) expression in long-lived lymphocyte populations, such as [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203)s, is a protective mechanism required to mitigate cumulative oxidative stress from sulfite over the cell's lifespan. Impaired [SUOX](/details-gene/6821) function may compromise the survival and recall capacity of memory T cells. ### Key Experiments To test Hypothesis 1, a targeted experimental approach could be employed: * **Experiment:** Generate a conditional knockout mouse model with *Suox* deleted specifically in chondrocytes (e.g., using an *Acan-CreERT2* driver). Following tamoxifen-induced deletion in adult mice, assess cartilage health over time using histological staining (e.g., Safranin O for GAGs) and micro-CT imaging. Analyze chondrocyte apoptosis, markers of cellular stress, and the sulfation status of GAGs extracted from the cartilage matrix using mass spectrometry. This would directly test whether chondrocyte-intrinsic [SUOX](/details-gene/6821) activity is essential for maintaining adult cartilage homeostasis. ### Therapeutic Potential The therapeutic context for [SUOX](/details-gene/6821) is focused on correction rather than inhibition. Since its deficiency causes a severe metabolic disease, strategies would aim to restore its function. * **Therapeutic Strategy:** The primary approach would be **activation** or **replacement**. For patients with isolated sulfite oxidase deficiency ([OMIM 272300](https://omim.org/entry/272300)), gene therapy to deliver a functional copy of the [SUOX](/details-gene/6821) gene to key affected tissues (e.g., liver and central nervous system) represents a potential long-term cure. Alternatively, enzyme replacement therapy (ERT), while challenging due to the mitochondrial localization of the protein and the need to cross the blood-brain barrier, could be explored. Inhibition of [SUOX](/details-gene/6821) would be therapeutically detrimental, as it would mimic the disease state by causing toxic sulfite accumulation.

Genular Protein ID: 3982877297

Symbol: SUOX_HUMAN

Name: N/A

UniProtKB Accession Codes:

P51687

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 20 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EC 1 EMBL 3 Ensembl 6 EvolutionaryTrace 1 ExpressionAtlas 1 GO 8 Gene3D 3 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 9 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 PRINTS 2 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 5 Rhea 2 SABIO-RK 1 SMART 1 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 2 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 7599189

Title: Molecular cloning of human liver sulfite oxidase.

PubMed ID: 7599189

DOI: 10.1016/0167-4781(95)00068-r

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 12832761

Title: The 1.2 A structure of the human sulfite oxidase cytochrome b(5) domain.

PubMed ID: 12832761

DOI: 10.1107/s0907444903009934

PubMed ID: 9428520

Title: Molecular basis of sulfite oxidase deficiency from the structure of sulfite oxidase.

PubMed ID: 9428520

DOI: 10.1016/s0092-8674(00)80488-2

PubMed ID: 9600976

Title: Human sulfite oxidase R160Q: identification of the mutation in a sulfite oxidase-deficient patient and expression and characterization of the mutant enzyme.

PubMed ID: 9600976

DOI: 10.1073/pnas.95.11.6394

PubMed ID: 10519592

Title: Isolated sulfite oxidase deficiency: review of two cases in one family.

PubMed ID: 10519592

DOI: 10.1016/s0161-6420(99)90408-6

PubMed ID: 12112661

Title: Isolated sulfite oxidase deficiency: identification of 12 novel SUOX mutations in 10 patients.

PubMed ID: 12112661

DOI: 10.1002/humu.9038

PubMed ID: 12368985

Title: A novel mutation in neonatal isolated sulphite oxidase deficiency.

PubMed ID: 12368985

DOI: 10.1055/s-2002-34491

Sequence Information:

  • Length: 545
  • Mass: 60283
  • Checksum: 39B842C55D39E11F
  • Sequence:
    • MLLLHRAVVL RLQQACRLKS IPSRICIQAC STNDSFQPQR PSLTFSGDNS STQGWRVMGT 
LLGLGAVLAY QDHRCRAAQE STHIYTKEEV SSHTSPETGI WVTLGSEVFD VTEFVDLHPG 
GPSKLMLAAG GPLEPFWALY AVHNQSHVRE LLAQYKIGEL NPEDKVAPTV ETSDPYADDP 
VRHPALKVNS QRPFNAEPPP ELLTENYITP NPIFFTRNHL PVPNLDPDTY RLHVVGAPGG 
QSLSLSLDDL HNFPRYEITV TLQCAGNRRS EMTQVKEVKG LEWRTGAIST ARWAGARLCD 
VLAQAGHQLC ETEAHVCFEG LDSDPTGTAY GASIPLARAM DPEAEVLLAY EMNGQPLPRD 
HGFPVRVVVP GVVGARHVKW LGRVSVQPEE SYSHWQRRDY KGFSPSVDWE TVDFDSAPSI 
QELPVQSAIT EPRDGETVES GEVTIKGYAW SGGGRAVIRV DVSLDGGLTW QVAKLDGEEQ 
RPRKAWAWRL WQLKAPVPAG QKELNIVCKA VDDGYNVQPD TVAPIWNLRG VLSNAWHRVH 
VYVSP