Details for: CHURC1 FNTB

Gene ID: 100529261

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: CHURC1 FNTB

Ensembl ID: ENSG00000125954

Description: CHURC1-FNTB readthrough

Cell Significance Landscape

Significant Cells

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

  • cerebellar granule cell CL0001031
    CSI 4.51
    rCSI 6.62%
    PRS 97.64
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 3.03
    rCSI 5.51%
    PRS 97.6
  • chondrocyte CL0000138
    CSI 2.45
    rCSI 3.89%
    PRS 98.13
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.87
    rCSI 4.19%
    PRS 97.35
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.64
    rCSI 4%
    PRS 96.33
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.15
    rCSI 3.59%
    PRS 97.19
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.86
    rCSI 3.26%
    PRS 96.67
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.81
    rCSI 2.91%
    PRS 96.71
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.59
    rCSI 3.49%
    PRS 96.75
  • blood vessel smooth muscle cell CL0019018
    CSI 0.56
    rCSI 4.53%
    PRS 99.15

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 [CHURC1-FNTB](/details-gene/100529261) is a protein-coding gene located on chromosome 14q23.3 which is transcribed as a readthrough between the neighboring *CHURC1* and *FNTB* genes. The resulting protein product is the farnesyltransferase subunit beta (FNTB), a critical component of the heterodimeric farnesyl-protein transferase (FPTase) enzyme. This enzyme catalyzes the post-translational farnesylation of proteins, a lipid modification essential for the membrane localization and function of key signaling molecules, including members of the Ras superfamily. Expression data indicates that **[CHURC1-FNTB](/details-gene/100529261)** is highly significant in the central nervous system, with its most prominent expression observed in [cerebellar granule cells](/details-cell/CL0001031), [differentiation-committed oligodendrocyte precursors](/details-cell/CL4023059), and various cortical neurons. ## Cellular Roles and Expression Landscape The expression profile of **[CHURC1-FNTB](/details-gene/100529261)** suggests a fundamental role in the cellular biology of the central nervous system. **Overall**, the gene shows its highest significance in [cerebellar granule cells](/details-cell/CL0001031) (CSI: 4.51) and [differentiation-committed oligodendrocyte precursors](/details-cell/CL4023059) (CSI: 3.03), indicating it is a crucial component of both neuronal and glial cell machinery. Its importance extends to other neural cell types, including [astrocytes of the cerebral cortex](/details-cell/CL0002605) and multiple glutamatergic cortical neuron populations such as [L2/3-6 intratelencephalic projecting glutamatergic neurons](/details-cell/CL4023040) and [L6b glutamatergic cortical neurons](/details-cell/CL4023038). Outside of the CNS, **[CHURC1-FNTB](/details-gene/100529261)** is also significantly expressed in [chondrocytes](/details-cell/CL0000138) and [blood vessel smooth muscle cells](/details-cell/CL0019018). This pattern suggests that while farnesylation is a ubiquitous and essential cellular process, the FNTB subunit may be particularly active or rate-limiting in cells with complex membrane signaling and structural dynamics. The absence of hematopoietic and immune cells from the top expression list suggests a more specialized, rather than universally high, level of activity across all tissues. ## Pathways and Molecular Function The protein encoded by **[CHURC1-FNTB](/details-gene/100529261)** is the beta subunit of the farnesyl-protein transferase (FPTase), which it forms along with an alpha subunit (FNTA). This enzyme is a key prenyltransferase that catalyzes the covalent attachment of a 15-carbon farnesyl pyrophosphate group to a cysteine residue near the C-terminus of target proteins, typically within a "CaaX box" motif. This post-translational modification, known as farnesylation, is critical for mediating protein-membrane and protein-protein interactions. The most well-known substrates for FPTase are members of the Ras family of small GTPases, which are central regulators of cell proliferation, differentiation, and survival. By facilitating the localization of Ras to the plasma membrane, FPTase is essential for its oncogenic signaling activity. The structure and function of human FPTase have been well-characterized, providing a basis for understanding its substrate selectivity and mechanism of action ([Link](https://doi.org/10.1021/bi00070a028), [Link](https://doi.org/10.1073/pnas.241407898)). ## Research Directions The expression pattern and molecular function of **[CHURC1-FNTB](/details-gene/100529261)** suggest several avenues for future research, particularly concerning its role in neural development and its potential as a therapeutic target. **Testable Hypotheses:** 1. Given its high significance in [differentiation-committed oligodendrocyte precursors](/details-cell/CL4023059), **[CHURC1-FNTB](/details-gene/100529261)**-mediated farnesylation is likely essential for oligodendrocyte maturation and the initiation of myelination. This process may depend on the proper membrane localization of key farnesylated signaling proteins that drive morphological changes and myelin sheath formation. 2. The prominent expression across diverse neuronal subtypes, including [cerebellar granule cells](/details-cell/CL0001031), suggests a critical role for farnesylation in maintaining synaptic integrity and neuronal homeostasis. A reduction in FNTB activity could impair the function of farnesylated proteins involved in synaptic vesicle trafficking or cytoskeletal regulation, potentially contributing to neurodegenerative processes. **Proposed Experiment:** To test the hypothesis regarding the role of **[CHURC1-FNTB](/details-gene/100529261)** in myelination, a conditional knockout mouse model could be employed. Specifically, the *Fntb* gene could be selectively deleted in oligodendrocyte precursor cells (OPCs) using a Cre-Lox system (e.g., Olig2-Cre). The resulting phenotype could be assessed by comparing the extent of myelination in the brains of knockout and wild-type animals via immunohistochemistry for myelin basic protein (MBP) and electron microscopy. Functional deficits could be evaluated through behavioral tests that assess motor coordination. **Therapeutic Potential:** The FPTase enzyme, of which FNTB is a core subunit, is a well-established target for anticancer therapies due to its role in activating oncogenic Ras proteins. Several farnesyltransferase inhibitors (FTIs) have been developed and clinically tested ([Link](https://doi.org/10.1021/jm020587n), [Link](https://doi.org/10.1021/jm010531d)). Therefore, **inhibition** of the protein product of **[CHURC1-FNTB](/details-gene/100529261)** is a validated therapeutic strategy. However, the high expression of this gene in the central nervous system raises a significant concern for potential neurotoxicity and on-target side effects with systemic FTI administration. Future drug development efforts may need to focus on agents with limited blood-brain barrier penetration or on targeted delivery systems to improve the therapeutic window for non-CNS malignancies.

Genular Protein ID: 1439329911

Symbol: FNTB_HUMAN

Name: Protein farnesyltransferase subunit beta

UniProtKB Accession Codes:

P49356 B2RDX6 B4E1A0

Database IDs:

AGR 2 AlphaFoldDB 1 Antibodypedia 1 BRENDA 2 Bgee 1 BindingDB 1 BioGRID 2 BioGRID-ORCS 2 BioMuta 1 CCDS 1 CDD 1 CORUM 1 CTD 2 ChEBI 11 ChEMBL 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 12 DrugCentral 1 EC 2 EMBL 8 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 7 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 2 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 14 PDBsum 14 PIR 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 3 RefSeq 2 Rhea 3 SFLD 1 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8494894

Title: Characterization of recombinant human farnesyl-protein transferase: cloning, expression, farnesyl diphosphate binding, and functional homology with yeast prenyl-protein transferases.

PubMed ID: 8494894

DOI: 10.1021/bi00070a028

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 12508121

Title: The DNA sequence and analysis of human chromosome 14.

PubMed ID: 12508121

DOI: 10.1038/nature01348

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: 8276393

Title: cDNA cloning of the two subunits of human CAAX farnesyltransferase and chromosomal mapping of FNTA and FNTB loci and related sequences.

PubMed ID: 8276393

DOI: 10.1006/geno.1993.1432

PubMed ID: 17081983

Title: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.

PubMed ID: 17081983

DOI: 10.1016/j.cell.2006.09.026

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 11687658

Title: The crystal structure of human protein farnesyltransferase reveals the basis for inhibition by CaaX tetrapeptides and their mimetics.

PubMed ID: 11687658

DOI: 10.1073/pnas.241407898

PubMed ID: 12036349

Title: 3-aminopyrrolidinone farnesyltransferase inhibitors: design of macrocyclic compounds with improved pharmacokinetics and excellent cell potency.

PubMed ID: 12036349

DOI: 10.1021/jm010531d

PubMed ID: 12825937

Title: Dual protein farnesyltransferase-geranylgeranyltransferase-I inhibitors as potential cancer chemotherapeutic agents.

PubMed ID: 12825937

DOI: 10.1021/jm020587n

PubMed ID: 15451670

Title: Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity.

PubMed ID: 15451670

DOI: 10.1016/j.jmb.2004.08.056

PubMed ID: 16893176

Title: Conversion of protein farnesyltransferase to a geranylgeranyltransferase.

PubMed ID: 16893176

DOI: 10.1021/bi060295e

PubMed ID: 19246009

Title: Structural basis for binding and selectivity of antimalarial and anticancer ethylenediamine inhibitors to protein farnesyltransferase.

PubMed ID: 19246009

DOI: 10.1016/j.chembiol.2009.01.014

Sequence Information:

  • Length: 437
  • Mass: 48774
  • Checksum: 8E8E571846146709
  • Sequence:
    • MASPSSFTYY CPPSSSPVWS EPLYSLRPEH ARERLQDDSV ETVTSIEQAK VEEKIQEVFS 
SYKFNHLVPR LVLQREKHFH YLKRGLRQLT DAYECLDASR PWLCYWILHS LELLDEPIPQ 
IVATDVCQFL ELCQSPEGGF GGGPGQYPHL APTYAAVNAL CIIGTEEAYD IINREKLLQY 
LYSLKQPDGS FLMHVGGEVD VRSAYCAASV ASLTNIITPD LFEGTAEWIA RCQNWEGGIG 
GVPGMEAHGG YTFCGLAALV ILKRERSLNL KSLLQWVTSR QMRFEGGFQG RCNKLVDGCY 
SFWQAGLLPL LHRALHAQGD PALSMSHWMF HQQALQEYIL MCCQCPAGGL LDKPGKSRDF 
YHTCYCLSGL SIAQHFGSGA MLHDVVLGVP ENALQPTHPV YNIGPDKVIQ ATTYFLQKPV 
PGFEELKDET SAEPATD

Genular Protein ID: 1800519470

Symbol: B4DL54_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4DL54 H0YHI0

Database IDs:

ARBA 6 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 BioMuta 1 CDD 1 CTD 1 ChEBI 5 ChiTaRS 1 DNASU 1 EMBL 5 Ensembl 2 GO 5 Gene3D 1 GeneCards 1 HGNC 1 HOGENOM 1 InterPro 5 NCBI Taxonomy 1 OMA 1 OrthoDB 1 PANTHER 2 PaxDb 1 Pfam 2 Proteomes 2 RefSeq 1 Rhea 3 RuleBase 1 SFLD 1 STRING 1 SUPFAM 1 UCSC 1 VEuPathDB 1 eggNOG 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 12508121

Title: The DNA sequence and analysis of human chromosome 14.

PubMed ID: 12508121

DOI: 10.1038/nature01348

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

Sequence Information:

  • Length: 471
  • Mass: 52785
  • Checksum: BD7006BBA398CE82
  • Sequence:
    • MCGDCVEKEY PNRGNTCLEN GSFLLNFTGC AVCSKRDFML ITNKSLKEED GEEIVTYDHL 
CKNCHHVIAR HEYTFSIMDE FQAKVEEKIQ EVFSSYKFNH LVPRLVLQRE KHFHYLKRGL 
RQLTDAYECL DASRPWLCYW ILHSLELLDE PIPQIVATDV CQFLELCQSP EGGFGGGPGQ 
YPHLAPTYAA VNALCIIGTE EAYDIINREK LLQYLYSLKQ PDGSFLMHVG GEVDVRSAYC 
AASVASLTNI ITPDLFEGTA EWIARCQNWE GGIGGVPGME AHGGYTFCGL AALVILKRER 
SLNLKSLLQW VTSRQMRFEG GFQGRCNKLV DGCYSFWQAG LLPLLHRALH AQGDPALSMS 
HWMFHQQALQ EYILMCCQCP AGGLLDKPGK SRDFYHTCYC LSGLSIAQHF GSGAMLHDVV 
LGVPENALQP THPVYNIGPD KVIQATTYFL QKPVPGFEEL KDETSAEPAT D