Details for: CACTIN

Gene ID: 58509

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: CACTIN

Ensembl ID: ENSG00000105298

Description: cactin, spliceosome C complex subunit

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.33
    rCSI 4.11%
    PRS 99.83

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.
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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 [CACTIN](/details-gene/58509) is a protein-coding gene located on chromosome 19p13.3 that functions as a subunit of the spliceosome C complex. It plays a dual role in cellular biology, participating fundamentally in mRNA splicing and also acting as a critical negative regulator of the innate immune response. Functional annotations strongly link [CACTIN](/details-gene/58509) to the inhibition of NF-kappaB and Toll-like receptor signaling pathways. While initially identified as the renal carcinoma antigen NY-REN-24, expression data highlights its particular significance in developmental neuronal cells, suggesting a complex and multifaceted role that spans RNA processing, immune modulation, and potentially neurodevelopment. ## Cellular Roles and Expression Landscape The expression profile of [CACTIN](/details-gene/58509) points to a specialized, though perhaps context-dependent, function. - **Overall**, the gene shows its highest level of significance in [caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064) (CSI: 2.33), suggesting a potential role in the development or function of this specific neuronal subtype. - Despite this top neuronal hit, the bulk of functional data for [CACTIN](/details-gene/58509) is derived from its role in the immune system. Its involvement in responding to stimuli like interleukin-1, lipopolysaccharide, and tumor necrosis factor indicates it is a key component in cells of the innate immune system, such as monocytes and macrophages, although they do not appear as the top cell type in this broad, **Overall** context. - The protein is primarily localized within the [nucleus](/details-cell/GO:0005634), specifically in the [nucleoplasm](/details-cell/GO:0005654), [nuclear speck](/details-cell/GO:0016607), and the [spliceosomal complex](/details-cell/GO:0005681), consistent with its role in splicing. It is also found in the [cytoplasm](/details-cell/GO:0005737), which aligns with its function in modulating cytosolic signaling pathways like NF-kappaB. ## Pathways and Molecular Function The functions of [CACTIN](/details-gene/58509) are centered on two major cellular processes: RNA metabolism and the negative regulation of innate immunity. **RNA Processing:** As a core component of the [spliceosomal complex](/details-cell/GO:0005681), [CACTIN](/details-gene/58509) is essential for pre-mRNA splicing. It is involved in the [catalytic step 2 spliceosome](/details-cell/GO:0071013) and participates in the major pathway of [mRNA splicing](/details-pathway/R-HSA-72163) ([R-HSA-72172](https://reactome.org/content/detail/R-HSA-72172)). Research demonstrates that human [CACTIN](/details-gene/58509) interacts with other splicing factors, such as DHX8 and SRRM2, to ensure the efficiency of pre-mRNA splicing and to maintain sister chromatid cohesion, linking RNA processing with cell cycle fidelity ([Link](https://doi.org/10.1242/jcs.194068)). **Innate Immune Regulation:** [CACTIN](/details-gene/58509) acts as a significant brake on inflammatory signaling. It is a well-documented [negative regulator of the innate immune response](/details-go/GO:0045824). Its inhibitory functions are extensive and include: - **NF-kappaB Signaling:** It negatively regulates [canonical NF-kappaB signal transduction](/details-go/GO:0043124) and [NF-kappaB transcription factor activity](/details-go/GO:0032088). This is achieved by targeting the MHC class III protein IkappaB-like (IkappaBL), thereby inhibiting the pathway ([Link](https://doi.org/10.1074/jbc.m110.139113)). The stability of [CACTIN](/details-gene/58509) itself is enhanced by TRIM39, which further suppresses NF-kappaB-mediated signaling ([Link](https://doi.org/10.1007/s00018-015-2040-x)). - **TLR and Cytokine Signaling:** It negatively regulates the [Toll-like receptor signaling pathway](/details-go/GO:0034122) in response to lipopolysaccharide ([GO:0071222](https://www.ebi.ac.uk/QuickGO/term/GO:0071222)). This extends to downstream effects, including the negative regulation of [interferon-beta production](/details-go/GO:0032688) and the [production of inflammatory cytokines](/details-go/GO:0032720) like TNF and IL-8 ([GO:0032717](https://www.ebi.ac.uk/QuickGO/term/GO:0032717)). ## Research Directions The dual functionality of [CACTIN](/details-gene/58509) in both fundamental RNA splicing and specific immune regulation, combined with its notable significance in a developing neuron, presents several compelling avenues for future research. **Testable Hypotheses:** 1. Given its role as a splicing factor and an immune regulator, [CACTIN](/details-gene/58509) may selectively modulate the splicing of key immune-related transcripts (e.g., isoforms of NF-kappaB pathway components or cytokine receptors) upon inflammatory stimulation, thereby fine-tuning the cellular response. 2. The high significance of [CACTIN](/details-gene/58509) in [caudal ganglionic eminence derived cortical interneurons](/details-cell/CL4023064) suggests a role in neurodevelopment. It may be required for the alternative splicing of transcripts essential for interneuron migration, specification, or synaptic integration during cortical development. **Proposed Experiment:** To test the first hypothesis, one could employ a human macrophage cell line (e.g., U937). Cells would be treated with siRNA to knock down [CACTIN](/details-gene/58509) expression, followed by stimulation with lipopolysaccharide (LPS). High-throughput RNA-sequencing would then be performed to identify differential splicing events between control and knockdown cells, both at baseline and after LPS stimulation. Candidate splicing events in key immune genes could be validated by RT-qPCR. This would directly test whether [CACTIN](/details-gene/58509) alters splicing patterns as part of its mechanism for regulating the inflammatory response. **Therapeutic Potential:** The role of [CACTIN](/details-gene/58509) as a negative regulator of inflammation makes it an interesting, albeit complex, therapeutic target. - For inflammatory disorders, strategies aimed at **enhancing** [CACTIN](/details-gene/58509) function or stability could be beneficial. This might involve developing small molecules that stabilize the interaction between [CACTIN](/details-gene/58509) and proteins like TRIM39, thereby potentiating its inhibitory effect on NF-kappaB. - Conversely, in the context of cancer, where it was identified as the NY-REN-24 antigen ([Link](https://doi.org/10.1002/(sici)1097-0215(19991112)83:4<456::aid-ijc4>3.0.co;2-5)), its role is less clear. If its expression suppresses anti-tumor immunity via NF-kappaB inhibition in immune cells, then targeted **inhibition** within the tumor microenvironment could be a strategy. However, as an intracellular protein, it is not easily targetable with antibodies, suggesting that small molecule inhibitors disrupting its protein-protein interactions would be a more plausible approach.

Genular Protein ID: 3057607159

Symbol: CATIN_HUMAN

Name: Renal carcinoma antigen NY-REN-24

UniProtKB Accession Codes:

Q8WUQ7 A6NNA9 A9UL12 O75229 Q7LE08 Q9BTA6 Q9Y5A4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 EMBL 7 EMDB 4 Ensembl 4 ExpressionAtlas 1 GO 24 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 4 PDBsum 4 PIR 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 1 RefSeq 2 SMART 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

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: 10508479

Title: Antigens recognized by autologous antibody in patients with renal-cell carcinoma.

PubMed ID: 10508479

DOI: 10.1002/(sici)1097-0215(19991112)83:4&lt;456::aid-ijc4&gt;3.0.co;2-5

PubMed ID: 11991638

Title: Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis.

PubMed ID: 11991638

DOI: 10.1017/s1355838202021088

PubMed ID: 20829348

Title: Cactin targets the MHC class III protein IkappaB-like (IkappaBL) and inhibits NF-kappaB and interferon-regulatory factor signaling pathways.

PubMed ID: 20829348

DOI: 10.1074/jbc.m110.139113

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

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: 26363554

Title: TRIM39 negatively regulates the NFkappaB-mediated signaling pathway through stabilization of Cactin.

PubMed ID: 26363554

DOI: 10.1007/s00018-015-2040-x

PubMed ID: 28062851

Title: Human cactin interacts with DHX8 and SRRM2 to assure efficient pre-mRNA splicing and sister chromatid cohesion.

PubMed ID: 28062851

DOI: 10.1242/jcs.194068

PubMed ID: 28112733

Title: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.

PubMed ID: 28112733

DOI: 10.1038/nsmb.3366

PubMed ID: 34365507

Title: SDE2 is an essential gene required for ribosome biogenesis and the regulation of alternative splicing.

PubMed ID: 34365507

DOI: 10.1093/nar/gkab647

Sequence Information:

  • Length: 758
  • Mass: 88702
  • Checksum: F540F151EB96BEFB
  • Sequence:
    • MGRDTRSRSR SAGRRGRRRQ SQSGSRSRSR SHGRRNRRRR EDEGRRRRRR RSRERRSDSE 
EERWQRSGMR SRSPPRPKWH SRDGSSQSDS GEEQSRGQWA RRRRRARSWS PSSSASSSAS 
PGRSQSPRAA AAALSQQQSL QERLRLREER KQQEELMKAF ETPEEKRARR LAKKEAKERK 
KREKMGWGEE YMGYTNTDNP FGDNNLLGTF IWNKALEKKG ISHLEEKELK ERNKRIQEDN 
RLELQKVKQL RLEREREKAM REQELEMLQR EKEAEHFKTW EEQEDNFHLQ QAKLRSKIRI 
RDGRAKPIDL LAKYISAEDD DLAVEMHEPY TFLNGLTVAD MEDLLEDIQV YMELEQGKNA 
DFWRDMTTIT EDEISKLRKL EASGKGPGER REGVNASVSS DVQSVFKGKT YNQLQVIFQG 
IEGKIRAGGP NLDMGYWESL LQQLRAHMAR ARLRERHQDV LRQKLYKLKQ EQGVESEPLF 
PILKQEPQSP SRSLEPEDAA PTPPGPSSEG GPAEAEVDGA TPTEGDGDGD GEGEGEGEAV 
LMEEDLIQQS LDDYDAGRYS PRLLTAHELP LDAHVLEPDE DLQRLQLSRQ QLQVTGDASE 
SAEDIFFRRA KEGMGQDEAQ FSVEMPLTGK AYLWADKYRP RKPRFFNRVH TGFEWNKYNQ 
THYDFDNPPP KIVQGYKFNI FYPDLIDKRS TPEYFLEACA DNKDFAILRF HAGPPYEDIA 
FKIVNREWEY SHRHGFRCQF ANGIFQLWFH FKRYRYRR