Details for: FEZ1

Gene ID: 9638

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: FEZ1

Ensembl ID: ENSG00000149557

Description: fasciculation and elongation protein zeta 1

Cell Significance Landscape

Associated with

Significant Cells

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

  • progenitor cell CL0011026
    CSI 22.06
    rCSI 46.92%
    PRS 57.11
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 18.22
    rCSI 23.38%
    PRS 54.37
  • amacrine cell CL0000561
    CSI 17.26
    rCSI 50.02%
    PRS 46.98
  • peripheral nervous system neuron CL2000032
    CSI 16.18
    rCSI 22.05%
    PRS 49.05
  • forebrain radial glial cell CL0013000
    CSI 14.81
    rCSI 47.53%
    PRS 62.64
  • mature astrocyte CL0002627
    CSI 12.32
    rCSI 52.34%
    PRS 51.4
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 9.98
    rCSI 29.45%
    PRS 60.19
  • basal cell CL0000646
    CSI 9.84
    rCSI 13.15%
    PRS 57.49
  • glioblast CL0000030
    CSI 8.5
    rCSI 13.55%
    PRS 49.77
  • cerebellar granule cell CL0001031
    CSI 7.94
    rCSI 11.67%
    PRS 50.97
  • alveolar adventitial fibroblast CL4028006
    CSI 7.85
    rCSI 12.39%
    PRS 58.66
  • interneuron CL0000099
    CSI 7.54
    rCSI 15.14%
    PRS 46.13
  • melanocyte CL0000148
    CSI 7.19
    rCSI 5.33%
    PRS 49.6
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 6.42
    rCSI 10.78%
    PRS 39.21
  • retina horizontal cell CL0000745
    CSI 6.39
    rCSI 9.74%
    PRS 53.24
  • vascular associated smooth muscle cell CL0000359
    CSI 6.25
    rCSI 20.27%
    PRS 57.97
  • mesenchymal cell CL0008019
    CSI 6.16
    rCSI 15.64%
    PRS 51.44
  • erythrocyte CL0000232
    CSI 6.15
    rCSI 13.95%
    PRS 61.39
  • activated type II NK T cell CL0000931
    CSI 6.05
    rCSI 6.81%
    PRS 73.39
  • radial glial cell CL0000681
    CSI 5.83
    rCSI 8.1%
    PRS 55.82
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 5.24
    rCSI 6.05%
    PRS 50.35
  • Schwann cell CL0002573
    CSI 5.18
    rCSI 14.72%
    PRS 55.14
  • Cajal-Retzius cell CL0000695
    CSI 5.15
    rCSI 40.38%
    PRS 69.96
  • Mueller cell CL0000636
    CSI 5.11
    rCSI 11.66%
    PRS 48.98
  • neural crest cell CL0011012
    CSI 4.85
    rCSI 3.83%
    PRS 43.84
  • sncg GABAergic cortical interneuron CL4023015
    CSI 4.61
    rCSI 7.41%
    PRS 41.43
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 4.5
    rCSI 17.01%
    PRS 40.09
  • cerebral cortex endothelial cell CL1001602
    CSI 4.21
    rCSI 7.28%
    PRS 47.04
  • neural cell CL0002319
    CSI 4.2
    rCSI 15.86%
    PRS 44.58
  • fibroblast of lung CL0002553
    CSI 4.04
    rCSI 3.76%
    PRS 56.83
  • glutamatergic neuron CL0000679
    CSI 3.99
    rCSI 8.21%
    PRS 48.21
  • bronchus fibroblast of lung CL2000093
    CSI 3.9
    rCSI 3.17%
    PRS 57.36
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.8
    rCSI 4.73%
    PRS 37.42
  • tracheobronchial smooth muscle cell CL0019019
    CSI 3.55
    rCSI 6.26%
    PRS 65.41
  • ependymal cell CL0000065
    CSI 3.54
    rCSI 7.18%
    PRS 36.99
  • Bergmann glial cell CL0000644
    CSI 3.23
    rCSI 4.42%
    PRS 51.11
  • mesodermal cell CL0000222
    CSI 3.21
    rCSI 3.85%
    PRS 54.98
  • inhibitory interneuron CL0000498
    CSI 3.2
    rCSI 7.38%
    PRS 46.6
  • alveolar type 1 fibroblast cell CL4028004
    CSI 3.18
    rCSI 3.48%
    PRS 60.77
  • GABAergic amacrine cell CL4030027
    CSI 3
    rCSI 10.28%
    PRS 46.31
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.96
    rCSI 3.81%
    PRS 40.38
  • interstitial cell of Cajal CL0002088
    CSI 2.93
    rCSI 3.73%
    PRS 63.18
  • cardiac muscle cell CL0000746
    CSI 2.85
    rCSI 4.09%
    PRS 47.02
  • choroid plexus epithelial cell CL0000706
    CSI 2.78
    rCSI 4.55%
    PRS 46.56
  • skin fibroblast CL0002620
    CSI 2.76
    rCSI 2.38%
    PRS 63
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 2.71
    rCSI 9.75%
    PRS 37.78
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.58
    rCSI 3.08%
    PRS 39.06
  • retinal ganglion cell CL0000740
    CSI 2.58
    rCSI 5.69%
    PRS 43.47
  • glial cell CL0000125
    CSI 2.57
    rCSI 9.78%
    PRS 48.3
  • cerebral cortex neuron CL0010012
    CSI 2.42
    rCSI 9.88%
    PRS 52.09
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.17
    rCSI 4.87%
    PRS 39.97
  • macrophage CL0000235
    CSI 2.16
    rCSI 3.93%
    PRS 77.42
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 2.13
    rCSI 4.62%
    PRS 45.61
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.13
    rCSI 3.75%
    PRS 38.26
  • retinal bipolar neuron CL0000748
    CSI 2.07
    rCSI 3.88%
    PRS 45.5
  • macroglial cell CL0000126
    CSI 2.06
    rCSI 5.28%
    PRS 57.16
  • vascular leptomeningeal cell CL4023051
    CSI 1.99
    rCSI 3.48%
    PRS 48.99
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 1.96
    rCSI 3.56%
    PRS 49.17
  • GABAergic neuron CL0000617
    CSI 1.93
    rCSI 6.48%
    PRS 42.85
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.82
    rCSI 5.7%
    PRS 40.7
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.75
    rCSI 4.24%
    PRS 37.96
  • OFF-bipolar cell CL0000750
    CSI 1.61
    rCSI 2.2%
    PRS 64.85
  • neuron CL0000540
    CSI 1.54
    rCSI 4.1%
    PRS 46.9
  • pancreatic stellate cell CL0002410
    CSI 1.37
    rCSI 8%
    PRS 66.45
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.37
    rCSI 33.08%
    PRS 39.41
  • midbrain dopaminergic neuron CL2000097
    CSI 1.31
    rCSI 8.41%
    PRS 60.09
  • Purkinje cell CL0000121
    CSI 1.1
    rCSI 14.41%
    PRS 78.95
  • direct pathway medium spiny neuron CL4023026
    CSI 1.07
    rCSI 25.69%
    PRS 38.51
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 1.07
    rCSI 3.34%
    PRS 43.26
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 1.07
    rCSI 3.51%
    PRS 44.3
  • cerebral cortex pyramidal neuron CL4023111
    CSI 1.03
    rCSI 6.32%
    PRS 73.07
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.98
    rCSI 2.82%
    PRS 58.45
  • neural progenitor cell CL0011020
    CSI 0.97
    rCSI 4.29%
    PRS 48.19
  • ON midget ganglion cell CL4033046
    CSI 0.92
    rCSI 18.69%
    PRS 48.16
  • H1 horizontal cell CL0004217
    CSI 0.89
    rCSI 3.52%
    PRS 57.31
  • central nervous system neuron CL2000029
    CSI 0.77
    rCSI 5.63%
    PRS 43.88
  • enteroglial cell CL4040002
    CSI 0.74
    rCSI 3.89%
    PRS 62.71
  • OFF midget ganglion cell CL4033047
    CSI 0.69
    rCSI 14.13%
    PRS 49.48
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.62
    rCSI 3.64%
    PRS 40.59
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 0.49
    rCSI 1.17%
    PRS 44.73
  • ON parasol ganglion cell CL4033052
    CSI 0.49
    rCSI 6.94%
    PRS 48.67
  • medium spiny neuron CL1001474
    CSI 0.33
    rCSI 2.82%
    PRS 44.37
  • pluripotent stem cell CL0002248
    CSI 0.15
    rCSI 4.43%
    PRS 77.57

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 [FEZ1](/details-gene/9638) (fasciculation and elongation protein zeta 1) is a protein-coding gene located on chromosome 11q24.2. It plays a crucial role in nervous system development, particularly in processes such as axon guidance, neuron projection development, and mitochondrial transport within neurons. Its function is substantiated by its high expression significance in various neuronal and progenitor cell populations. The protein is known to be involved in cytoskeletal organization through its interactions with microtubules and protein kinase C, and it participates in protein-protein interactions via its coiled-coil domain [Link](https://doi.org/10.1074/jbc.m513280200). Its ortholog in *C. elegans*, *unc-76*, was identified as a key factor in axonal outgrowth, highlighting a conserved function in establishing neuronal connectivity [Link](https://doi.org/10.1073/pnas.94.7.3414). ## Cellular Roles and Expression Landscape The expression profile of [FEZ1](/details-gene/9638) strongly indicates its specialization in the developing and mature nervous system. **Overall**, the gene shows the highest significance in neuronal precursor populations, including `[progenitor cell](/details-cell/CL0011026)` (CSI: 22.06) and `[neuroblast (sensu Vertebrata)](/details-cell/CL0000031)` (CSI: 18.22), suggesting a foundational role in neurogenesis. Its importance extends to various differentiated neuronal subtypes and supporting cells. It is a significant marker in retinal cells like the `[amacrine cell](/details-cell/CL0000561)` (CSI: 17.26), as well as in `[peripheral nervous system neuron](/details-cell/CL2000032)` (CSI: 16.18) and central nervous system `[interneuron](/details-cell/CL0000099)` (CSI: 7.54). Furthermore, its expression in glial cells, such as `[forebrain radial glial cell](/details-cell/CL0013000)` (CSI: 14.81) and `[mature astrocyte](/details-cell/CL0002627)` (CSI: 12.32), is consistent with its broad involvement in maintaining the architecture and function of the nervous system. Notably, significant expression is also observed in `[glioblast](/details-cell/CL0000030)` (CSI: 8.50), suggesting its functions in neuronal development may be co-opted in neural-origin cancers. ## Pathways and Molecular Function [FEZ1](/details-gene/9638) is annotated to a suite of biological processes centered on neuronal development and function. It is a key participant in `[Nervous system development](/details-cell/GO:0007399)` and more specifically in `[Axon guidance](/details-cell/GO:0007411)` and `[Positive regulation of neuron projection development](/details-cell/GO:0010976)`. This is consistent with early research demonstrating its requirement for proper neuritogenesis [Link](https://doi.org/10.1074/jbc.m402916200). At the molecular level, its function is mediated by `[Protein binding](/details-cell/GO:0005515)`, including specific interactions with `[Protein kinase c binding](/details-cell/GO:0005080)`. Studies have shown that [FEZ1](/details-gene/9638) forms dimers, a process critical for its role in cellular transport [Link](https://doi.org/10.1021/pr100314q). Its localization to the `[Cytoplasm](/details-cell/GO:0005737)`, `[Microtubule](/details-cell/GO:0005874)`, `[Axon](/details-cell/GO:0030424)`, and `[Growth cone](/details-cell/GO:0030426)` underpins its role in cytoskeletal dynamics. Overexpression of [FEZ1](/details-gene/9638) has been shown to affect microtubule-dependent processes, leading to nuclear morphology changes [Link](https://doi.org/10.1016/j.yexcr.2008.02.012). Furthermore, [FEZ1](/details-gene/9638) plays a vital role in neuronal bioenergetics through its involvement in `[Mitochondrion organization](/details-cell/GO:0007005)` and `[Positive regulation of anterograde axonal transport of mitochondrion](/details-cell/GO:0061881)`, ensuring mitochondria are correctly positioned within neurons. ## Research Directions The significant expression of [FEZ1](/details-gene/9638) in `[glioblast](/details-cell/CL0000030)` suggests that its developmental functions in cell migration and cytoskeletal organization may be hijacked to promote tumor progression and invasion. This presents a compelling avenue for future investigation. **Testable Hypotheses:** 1. Given its high significance in `[progenitor cell](/details-cell/CL0011026)` and `[neuroblast (sensu Vertebrata)](/details-cell/CL0000031)`, knockout of [FEZ1](/details-gene/9638) in a developing mouse model will disrupt neuronal migration and lamination in the cerebral cortex, leading to severe neurodevelopmental defects. 2. [FEZ1](/details-gene/9638) facilitates glioblastoma cell invasion by organizing the microtubule network and regulating mitochondrial transport to the leading edge of migrating cells, providing the necessary energy for cellular motility. **Proposed Experiment:** To test the second hypothesis, one could utilize a human glioblastoma cell line (e.g., U87 or LN-229). [FEZ1](/details-gene/9638) expression would be silenced using CRISPR-Cas9 or shRNA. The impact on cell migration and invasion would be quantified using a transwell (Boyden chamber) assay. To probe the underlying mechanism, mitochondrial distribution in control versus knockdown cells would be visualized using MitoTracker dye and live-cell imaging during a wound-healing assay. Changes in microtubule organization and dynamics could be assessed via immunofluorescence staining for alpha-tubulin. A positive result would show reduced migration coupled with disorganized mitochondrial localization and an altered microtubule network in the [FEZ1](/details-gene/9638)-deficient cells. **Therapeutic Potential:** As an intracellular scaffolding protein, [FEZ1](/details-gene/9638) represents a challenging therapeutic target for traditional small molecules. However, if its role in promoting glioblastoma invasion is confirmed, its downstream effectors or upstream regulators may offer more druggable nodes. Inhibition, rather than activation, would be the therapeutic goal. Strategies could involve developing protein-protein interaction inhibitors that disrupt the binding of [FEZ1](/details-gene/9638) to key cargo or motor proteins, thereby selectively crippling the motility of invasive cancer cells that are highly dependent on this pathway.

Genular Protein ID: 210216464

Symbol: FEZ1_HUMAN

Name: Fasciculation and elongation protein zeta-1

UniProtKB Accession Codes:

Q99689 O00679 O00728 Q6IBI7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CORUM 1 CTD 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 4 ExpressionAtlas 1 GO 22 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 4 SIGNOR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9096408

Title: The Caenorhabditis elegans gene unc-76 and its human homologs define a new gene family involved in axonal outgrowth and fasciculation.

PubMed ID: 9096408

DOI: 10.1073/pnas.94.7.3414

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: 15466860

Title: Functional regulation of FEZ1 by the U-box-type ubiquitin ligase E4B contributes to neuritogenesis.

PubMed ID: 15466860

DOI: 10.1074/jbc.m402916200

PubMed ID: 16484223

Title: FEZ1 dimerization and interaction with transcription regulatory proteins involves its coiled-coil region.

PubMed ID: 16484223

DOI: 10.1074/jbc.m513280200

PubMed ID: 18439996

Title: Over-expression of GFP-FEZ1 causes generation of multi-lobulated nuclei mediated by microtubules in HEK293 cells.

PubMed ID: 18439996

DOI: 10.1016/j.yexcr.2008.02.012

PubMed ID: 20812761

Title: Human FEZ1 protein forms a disulfide bond mediated dimer: implications for cargo transport.

PubMed ID: 20812761

DOI: 10.1021/pr100314q

PubMed ID: 22354037

Title: Genome-wide siRNA screen reveals amino acid starvation-induced autophagy requires SCOC and WAC.

PubMed ID: 22354037

DOI: 10.1038/emboj.2012.36

PubMed ID: 24098481

Title: Crystal structure of the human short coiled coil protein and insights into SCOC-FEZ1 complex formation.

PubMed ID: 24098481

DOI: 10.1371/journal.pone.0076355

Sequence Information:

  • Length: 392
  • Mass: 45119
  • Checksum: 4226ED5EA17706F2
  • Sequence:
    • MEAPLVSLDE EFEDLRPSCS EDPEEKPQCF YGSSPHHLED PSLSELENFS SEIISFKSME 
DLVNEFDEKL NVCFRNYNAK TENLAPVKNQ LQIQEEEETL QDEEVWDALT DNYIPSLSED 
WRDPNIEALN GNCSDTEIHE KEEEEFNEKS ENDSGINEEP LLTADQVIEE IEEMMQNSPD 
PEEEEEVLEE EDGGETSSQA DSVLLQEMQA LTQTFNNNWS YEGLRHMSGS ELTELLDQVE 
GAIRDFSEEL VQQLARRDEL EFEKEVKNSF ITVLIEVQNK QKEQRELMKK RRKEKGLSLQ 
SSRIEKGNQM PLKRFSMEGI SNILQSGIRQ TFGSSGTDKQ YLNTVIPYEK KASPPSVEDL 
QMLTNILFAM KEDNEKVPTL LTDYILKVLC PT