Affinage

FEZ1

Fasciculation and elongation protein zeta-1 · UniProt Q99689

Length
392 aa
Mass
45.1 kDa
Annotated
2026-06-09
61 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FEZ1 (fasciculation and elongation protein zeta-1, ortholog of C. elegans UNC-76) is a kinesin-1 adaptor that drives anterograde microtubule-based transport in neurons and controls axonal outgrowth, fasciculation, and neuronal polarity (PMID:9096408, PMID:12925768, PMID:17173861). It is a natively unfolded, elongated dimer whose self-association requires its N-terminus and an intermolecular Cys-133 disulfide bond, configuring it as a bivalent transport adaptor (PMID:18615714, PMID:20812761). Through its C-terminal coiled-coil region FEZ1 binds the kinesin heavy chain tail and tubulin and recruits cargoes—mitochondria and presynaptic components—for delivery into developing neurites, so that its loss stalls anterograde mitochondrial movement and synaptic protein transport (PMID:12925768, PMID:17669366, PMID:25818806, PMID:33395696). Transport activity is set by phosphorylation: MARK/PAR-1 kinases phosphorylate FEZ1 at Ser58 to license cargo movement, and loss of this control causes FEZ1, kinesin-1, and presynaptic cargoes to co-aggregate in cell bodies and axons, a state also seen in Alzheimer's disease model brains (PMID:27247180). FEZ1 is also a PKCzeta substrate that, together with active PKCzeta and E4B-mediated Lys27 polyubiquitylation, promotes neuronal differentiation and neurite extension (PMID:9971736, PMID:15466860), and it acts within DISC1, CRMP1, and Netrin-1/DCC-Syntaxin-1 signaling modules to support dendritic and axonal development and guidance-cue responses (PMID:22099459, PMID:33771901). Independently, the FEZ1/LZTS1 product functions in mitosis, where it associates with microtubules and Cdk1 and stabilizes Cdc25C to sustain Cdk1 activity; its loss accelerates mitosis, causes chromosome missegregation, and predisposes to tumors (PMID:11504921, PMID:17349584). FEZ1 additionally serves as a constitutive, neuron-enriched host factor for HIV-1: it binds the central pore of capsid hexamers through acidic poly-glutamate stretches and links the incoming capsid to kinesin-1 for inward trafficking toward the nucleus (PMID:19667186, PMID:25818806, PMID:31422020).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1997 High

    Established FEZ1's ancestral function by showing its C. elegans ortholog UNC-76 is required for axon bundling and elongation, with human FEZ1 able to rescue the defect—defining a conserved role in axonal outgrowth.

    Evidence Genetic loss-of-function and cross-species complementation in C. elegans

    PMID:9096408

    Open questions at the time
    • Molecular partners and biochemical activity unresolved
    • No mechanism for how the protein supports outgrowth
  2. 1999 High

    Identified FEZ1 as a PKCzeta substrate and effector, linking it to a kinase signal that triggers cytoplasmic translocation and drives neuronal differentiation.

    Evidence Yeast two-hybrid, co-IP, phosphorylation assay, and PC12 differentiation assay

    PMID:9971736

    Open questions at the time
    • Phosphorylation sites not mapped
    • Downstream effect of phosphorylation on cargo binding not defined
  3. 2001 High

    Connected FEZ1/LZTS1 to the cell cycle, showing PKA-dependent hyperphosphorylation, association with microtubules and p34cdc2, and tumor-suppressor activity with G2/M accumulation.

    Evidence Co-IP, phosphorylation assay, nude mouse tumor suppression and FACS cell-cycle analysis

    PMID:11504921

    Open questions at the time
    • Direct molecular target in the cell cycle not yet identified
    • Relationship between neuronal and mitotic roles unclear
  4. 2003 High

    Placed FEZ1/UNC-76 directly in the kinesin-1 axonal transport pathway by demonstrating direct binding to the kinesin heavy chain tail plus dosage-sensitive genetic interactions.

    Evidence Yeast two-hybrid, copurification, and genetic epistasis with Khc/Klc in Drosophila

    PMID:12925768

    Open questions at the time
    • Specific cargoes transported not identified
    • Regulation of the FEZ1–kinesin interaction unknown
  5. 2004 High

    Showed E4B ubiquitin ligase polyubiquitylates FEZ1 on Lys27 of ubiquitin in a non-degradative manner required for neuritogenesis, defining a PKCzeta-enhanced regulatory modification.

    Evidence In vitro ubiquitylation, co-IP, and dominant-negative E4B neurite outgrowth assay in PC12 cells

    PMID:15466860

    Open questions at the time
    • Functional consequence of K27 linkage on FEZ1 activity not defined
    • Whether this regulates transport vs differentiation unclear
  6. 2005 High

    Established that FEZ1's microtubule association underlies neurite extension and is targeted by JC virus agnoprotein, which dissociates FEZ1 from microtubules.

    Evidence In vitro binding, microtubule cosedimentation, and neurite/viral assays

    PMID:15843383

    Open questions at the time
    • Microtubule-binding interface not mapped
    • Relationship to kinesin-1 binding not resolved
  7. 2006 Medium

    Defined FEZ1 as a retroviral restriction factor acting after reverse transcription but before nuclear entry, the first link to viral nuclear trafficking.

    Evidence Expression profiling, retroviral infection with viral DNA quantification, and RNAi knockdown

    PMID:15879557

    Open questions at the time
    • Molecular mechanism of the block undefined
    • Direct viral binding partner not identified
  8. 2006 Medium

    Mapped FEZ1's C-terminal coiled-coil as the hub for homodimerization, FEZ2 heterodimerization, and binding to transcriptional regulators, broadening its interactome.

    Evidence Yeast two-hybrid screen with in vitro pulldown confirmation and deletion mapping

    PMID:16484223

    Open questions at the time
    • Functional significance of transcriptional-regulator interactions untested
    • Cellular relevance of FEZ1/FEZ2 heterodimers unknown
  9. 2006 Medium

    Linked FEZ1 directly to mitochondrial transport and neuronal polarity, showing knockdown represses axon formation and slows anterograde mitochondrial movement.

    Evidence RNAi and live mitochondrial imaging in rat hippocampal neurons

    PMID:17173861

    Open questions at the time
    • Adaptor that couples FEZ1 to mitochondria not identified here
    • Single-lab finding
  10. 2006 High

    Identified the conserved UNC-69/UNC-76 complex regulating axon extension, fasciculation, and presynaptic organization, extending FEZ1 function into synaptic assembly.

    Evidence Yeast two-hybrid, in vivo colocalization, and double-mutant genetics in C. elegans

    PMID:16725058

    Open questions at the time
    • Biochemical role of the complex in transport not defined
    • Human SCOCO equivalence not established here
  11. 2007 High

    Resolved the molecular adaptor link by showing FEZ1 associates with KIF5/kinesin-1 and tubulin and is required for anterograde mitochondrial motility in neurites.

    Evidence Co-IP, pulldown, RNAi, and live imaging in NGF-treated PC12 cells

    PMID:17669366

    Open questions at the time
    • Direct mitochondrial receptor unidentified
    • How phosphorylation gates the KIF5 interaction not addressed
  12. 2007 High

    Established the mitotic mechanism of LZTS1/FEZ1: knockout MEFs degrade Cdc25C, lower Cdk1 activity, missegregate chromosomes, and mice develop cancers, defining a Cdk1/Cdc25C regulatory role.

    Evidence Knockout mouse, MEF analysis, Cdk1 activity assays, and tumor incidence

    PMID:17349584

    Open questions at the time
    • Direct biochemical mechanism of Cdc25C stabilization undefined
    • Integration with neuronal transport role unresolved
  13. 2009 High

    Characterized FEZ1 biophysically as an elongated, natively unfolded dimer and showed PKC phosphorylates its C-terminus to inhibit CLASP2 binding, linking conformation-independent phosphoregulation to partner selection.

    Evidence CD, fluorescence, limited proteolysis, SAXS, and in vitro PKC phosphorylation

    PMID:18615714

    Open questions at the time
    • Functional consequence of CLASP2 inhibition in cells not tested
    • Precise phosphosites not mapped here
  14. 2009 Medium

    Defined neuron-specific FEZ1 expression as the basis for constitutive, IFN-independent resistance to HIV-1 nuclear entry, demonstrated bidirectionally.

    Evidence siRNA in primary neurons and FEZ1 overexpression in microglia with HIV-1 infection assays

    PMID:19667186

    Open questions at the time
    • Molecular target on the virus not yet identified
    • Reconciliation with pro-trafficking role came only later
  15. 2010 Medium

    Identified the Cys-133 intermolecular disulfide as essential for FEZ1 dimerization, providing a structural basis for bivalent adaptor function.

    Evidence In vitro and endogenous pulldowns with mass spectrometry disulfide mapping

    PMID:20812761

    Open questions at the time
    • Redox regulation of dimerization in vivo untested
    • Relationship to N-terminal dimerization interface unclear
  16. 2011 High

    Placed FEZ1 in a DISC1-dependent pathway controlling dendritic growth of adult-born neurons and linked the interaction to schizophrenia risk in human cohorts.

    Evidence Co-IP, in vivo hippocampal knockdown, and genetic epistasis in two patient cohorts

    PMID:22099459

    Open questions at the time
    • Mechanism by which DISC1 modulates FEZ1 transport activity undefined
    • Causal variant not identified
  17. 2013 High

    Provided structural definition of the FEZ1 coiled-coil, showing antiparallel homodimerization and a heterotetrameric FEZ1/SCOCO complex, the human counterpart of UNC-76/UNC-69.

    Evidence NMR, crosslinking-MS, SAXS, and modelling (with companion SCOCO crystal structure and mutagenesis)

    PMID:24098481 PMID:24116125

    Open questions at the time
    • Functional role of the FEZ1/SCOCO tetramer in transport not assayed
    • Stoichiometry in cells not confirmed
  18. 2014 Medium

    Showed Cdc20/APC ubiquitin ligase targets FEZ1 for degradation to limit dendrite growth, with BubR1/HDAC11 controlling APC activity—defining proteolytic control of FEZ1 levels in neurons.

    Evidence Gain/loss-of-function of APC components, degradation assays, and dendrite morphology

    PMID:24726361

    Open questions at the time
    • Degron on FEZ1 not mapped
    • Interplay with non-degradative E4B ubiquitylation unresolved
  19. 2015 High

    Reversed the antiviral picture by demonstrating FEZ1 promotes early HIV-1 infection as a kinesin-1 adaptor, with depletion causing bidirectional but non-productive viral movement.

    Evidence RNAi, single-particle tracking, and rescue with kinesin-1-binding mutants

    PMID:25818806

    Open questions at the time
    • Direct viral binding site not yet defined here
    • Determinants of net directionality with dynein unresolved
  20. 2016 High

    Identified Ser58 as the MARK/PAR-1 phosphosite that licenses FEZ1's kinesin-1 adaptor function for presynaptic cargo, with loss causing pathological co-aggregation also seen in Alzheimer's models.

    Evidence Mass spectrometry phosphosite mapping, MARK/PAR-1 loss-of-function, imaging, and AD mouse brain analysis

    PMID:27247180

    Open questions at the time
    • How Ser58 phosphorylation alters cargo affinity mechanistically undefined
    • Causal role in disease aggregation not established
  21. 2018 Medium

    Demonstrated FEZ1/UNC-76 limits neuronal mitochondrial density by balancing anterograde and retrograde transport, refining its role beyond simple anterograde delivery.

    Evidence C. elegans genetics, quantitative live transport imaging, and dynein epistasis

    PMID:29895958

    Open questions at the time
    • Mechanism by which FEZ1 affects motor levels unknown
    • Direct coupling to dynein not established
  22. 2019 High

    Resolved the molecular basis of FEZ1-HIV-1 capsid engagement: acidic poly-glutamate stretches bind the positively charged CA hexamer central pore, competing with IP6/nucleotides, and are required for nuclear trafficking.

    Evidence Direct binding, MD simulation, IP6 competition, mutagenesis, and single-particle trafficking

    PMID:31422020

    Open questions at the time
    • Whether capsid binding alters normal cellular cargo handling unknown
    • Structural complex not determined experimentally
  23. 2021 Medium

    Embedded FEZ1 in growth-cone guidance machinery, showing it complexes with CRMP1 and with DCC/Syntaxin-1 and is required for Netrin-1 and Sema3A responses.

    Evidence Co-IP, colocalization, and loss-of-function guidance assays in rat hippocampal neurons

    PMID:33771901

    Open questions at the time
    • Whether transport vs scaffolding underlies guidance defects unclear
    • Single-lab finding
  24. 2021 Medium

    Showed FEZ1 deletion impairs axon/dendrite development and delays synaptic protein transport across model systems, with pharmacological UNC-51/ATG1 activation rescuing defects—pointing to a druggable kinase upstream.

    Evidence FEZ1 deletion in human ES-derived and rat neurons, Drosophila genetics, and rapamycin/metformin rescue

    PMID:33395696

    Open questions at the time
    • How UNC-51/ATG1 activates FEZ1 mechanistically undefined
    • Site of ATG1 regulation on FEZ1 not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FEZ1's distinct roles—neuronal kinesin-1 transport, mitotic Cdc25C/Cdk1 regulation, transcriptional partnerships, and viral capsid binding—are coordinated within a single protein, and how its multiple phosphorylation and ubiquitylation events are integrated, remains unresolved.
  • No unified model linking transport and cell-cycle functions
  • Phospho-/ubiquitin code controlling cargo selection not deciphered
  • No high-resolution structure of FEZ1 bound to kinesin-1 or cargo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 1
Localization
GO:0005856 cytoskeleton 3 GO:0005829 cytosol 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-9609507 Protein localization 4 R-HSA-1643685 Disease 3 R-HSA-1640170 Cell Cycle 2
Partners
CLASP2CRMP1DCCDISC1KIF5PRKCZRARASCOC
Complex memberships
FEZ1-kinesin-1 (KIF5) transport complexFEZ1/SCOCO (UNC-76/UNC-69) complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 UNC-76 (FEZ1 ortholog) is required for normal axonal bundling and elongation within axon bundles in C. elegans; the protein is found in cell bodies and processes of all neurons throughout development. At least one human FEZ1 homolog can functionally complement unc-76 in C. elegans, demonstrating conserved function in axonal outgrowth. Genetic loss-of-function in C. elegans, neuronal localization by expression analysis, cross-species functional complementation Proceedings of the National Academy of Sciences of the United States of America High 9096408
1999 FEZ1 (fasciculation and elongation protein zeta-1) is a substrate of PKCzeta: it was identified as a PKCzeta-interacting protein via yeast two-hybrid, interacts with the NH2-terminal V1 domain of PKCzeta, and is phosphorylated by PKCzeta in COS-7 cells. Constitutively active PKCzeta causes cytoplasmic translocation of FEZ1, and staurosporin treatment causes FEZ1 translocation from cytoplasm to plasma membrane. Co-expression of FEZ1 and constitutively active PKCzeta stimulates neuronal differentiation of PC12 cells. Yeast two-hybrid screening, co-immunoprecipitation, phosphorylation assay in COS-7 cells, PKC inhibitor treatment, PC12 differentiation assay The Journal of cell biology High 9971736
2001 FEZ1/LZTS1 protein is hyperphosphorylated by cAMP-dependent kinase (PKA) during cell-cycle progression, associates with microtubule components, and interacts with p34(cdc2) at late S-G2/M stage in vivo. Restoration of FEZ1 in Fez1-negative cancer cells suppresses tumorigenicity and causes G2/M accumulation. Immunoprecipitation of Fez1 with microtubule components and p34(cdc2), phosphorylation assay, tumor suppression assay in nude mice, cell cycle analysis by FACS Proceedings of the National Academy of Sciences of the United States of America High 11504921
2003 Drosophila UNC-76 (FEZ1 ortholog) binds directly to the tail domain of kinesin heavy chain (KHC), forming a stable complex in vivo, as demonstrated by yeast two-hybrid and copurification assays. Loss of Unc-76 function causes locomotion and axonal transport defects similar to kinesin mutants, and Unc-76 shows dosage-sensitive genetic interactions with Khc and kinesin light chain mutations, placing UNC-76 in the kinesin-I axonal transport pathway. Yeast two-hybrid, copurification, genetic epistasis (dosage-sensitive interactions with Khc and Klc mutants), loss-of-function locomotion and axonal transport assay Molecular biology of the cell High 12925768
2004 FEZ1 is polyubiquitylated by the U-box-type ubiquitin ligase E4B on Lys27 of ubiquitin, but this modification does not lead to its proteolytic degradation. The E4B–FEZ1 interaction is enhanced by constitutively active PKCzeta. Expression of dominant-negative E4B inhibits neurite extension induced by NGF or by FEZ1/active-PKCzeta co-expression in PC12 cells, indicating that E4B-mediated ubiquitylation of FEZ1 is required for neuritogenesis. Yeast two-hybrid, co-immunoprecipitation, in vitro polyubiquitylation assay, dominant-negative E4B overexpression in PC12 cells, neurite outgrowth assay The Journal of biological chemistry High 15466860
2005 FEZ1 protein associates with microtubules and directly interacts with JC virus agnoprotein in vitro. Agnoprotein induces the dissociation of FEZ1 from microtubules (microtubule cosedimentation assay), agnoprotein inhibits FEZ1-promoted neurite outgrowth, and FEZ1 overexpression suppresses JCV protein expression and intracellular trafficking, indicating FEZ1 promotes neurite extension via its microtubule association. Yeast two-hybrid, in vitro binding assay, microtubule cosedimentation assay, neurite outgrowth assay in PC12 cells, viral infection/expression assay The Journal of biological chemistry High 15843383
2005 FEZ1 overexpression confers post-entry resistance to retroviruses: infected cells show normal viral DNA synthesis but reduced circular DNA formation, indicating a block after reverse transcription but before nuclear entry. FEZ1 knockdown in resistant cells partially restores infectivity. Affymetrix gene chip expression profiling, retroviral infection assay, viral DNA quantification (Southern/PCR), RNAi knockdown Genes & development Medium 15879557
2006 FEZ1 dimerizes through its C-terminal coiled-coil region, and this same region mediates heterodimerization with FEZ2 and interaction with at least 10 interacting proteins identified by yeast two-hybrid, including transcription regulatory proteins SAP30L, DRAP1, and BAF60a (confirmed by in vitro pulldown with recombinant proteins). Yeast two-hybrid screen of human fetal brain cDNA library, in vitro pulldown with recombinant fusion proteins, deletion mapping The Journal of biological chemistry Medium 16484223
2006 FEZ1 promotes axon formation in hippocampal neurons; RNAi-mediated silencing of FEZ1 represses axon formation and retards anterograde mitochondrial movement in neurites, and causes mitochondrial elongation, placing FEZ1 upstream of mitochondrial transport in establishing neuronal polarity. RNAi knockdown in rat embryo hippocampal neurons, live-cell imaging of mitochondrial motility, immunofluorescence Biochemical and biophysical research communications Medium 17173861
2006 C. elegans UNC-69 physically interacts with UNC-76 (FEZ1 ortholog) and they colocalize as puncta in neuronal processes. The UNC-69/UNC-76 complex cooperates to regulate axon extension, fasciculation, and presynaptic organization. Genetic analysis shows overlapping loss-of-function phenotypes (axon outgrowth/guidance defects and synaptic vesicle mislocalization). Yeast two-hybrid, co-localization imaging in C. elegans neurons, genetic loss-of-function double-mutant analysis Journal of biology High 16725058
2007 FEZ1 associates with kinesin superfamily protein 5 (KIF5/kinesin-1) and tubulin by co-immunoprecipitation and pulldown assay in PC12 cells. NGF-stimulated FEZ1 co-localizes with mitochondria in neurites, and FEZ1 siRNA knockdown reduces anterograde mitochondrial motility, suggesting FEZ1/kinesin complex mediates mitochondrial transport along microtubules. Co-immunoprecipitation, pulldown assay, RNAi knockdown, live-cell imaging of mitochondrial motility in NGF-treated PC12 cells Biochemical and biophysical research communications High 17669366
2007 Lzts1 knockout MEFs show increased Cdc25C degradation during M phase, leading to decreased Cdk1 activity. This results in accelerated mitotic progression, resistance to taxol/nocodazole-induced M phase arrest, and improper chromosome segregation. Lzts1-deficient mice show increased incidence of spontaneous and carcinogen-induced cancers, establishing LZTS1 as a regulator of Cdk1/Cdc25C interaction during mitosis. Knockout mouse model, MEF isolation, Western blot for Cdc25C and Cdk1 activity, drug sensitivity assay, chromosome segregation analysis, tumor incidence monitoring Cancer cell High 17349584
2009 Neuronal FEZ1 expression (high in neurons, low in astrocytes/microglia) underlies intrinsic resistance to HIV-1 nuclear entry: siRNA knockdown of endogenous FEZ1 in neurons increases HIV-1 infectivity, while FEZ1 overexpression in microglia (sensitive cells) increases resistance. FEZ1 resistance is not IFN-inducible, defining it as a constitutive neuron-specific antiviral factor acting before nuclear entry. siRNA knockdown in primary neurons, FEZ1 overexpression in microglia, pseudotyped HIV-1 infection assay with quantification of early infection Proceedings of the National Academy of Sciences of the United States of America Medium 19667186
2009 FEZ1 is a natively unfolded protein that dimerizes in solution. Small-angle X-ray scattering reveals an elongated dimeric shape; in vitro pulldown shows dimerization involves the N-terminus. PKC phosphorylates FEZ1 predominantly in its C-terminal region, and this phosphorylation inhibits FEZ1 interaction with the CLASP2-interacting domain in vitro, without major conformational changes. Circular dichroism, fluorescence spectroscopy, limited proteolysis, SAXS, in vitro pulldown, in vitro PKC phosphorylation assay Proteins High 18615714
2010 FEZ1 forms an intermolecular disulfide bond through Cys-133 that is essential for dimerization, demonstrated in the fragment FEZ1(92-194), full-length recombinant FEZ1, and endogenous FEZ1 from HEK293 cells. This disulfide-mediated dimerization may enable FEZ1 to act as a bivalent transport adaptor. In vitro pulldown of recombinant FEZ1 fragments, mass spectrometry analysis, isolation of endogenous FEZ1 from HEK293 cells, disulfide bond identification Journal of proteome research Medium 20812761
2011 FEZ1 interacts with DISC1 to synergistically regulate dendritic growth of newborn neurons in the adult mouse hippocampus. This FEZ1-DISC1 pathway is parallel to and complementary with the DISC1-NDEL1 pathway that regulates cell positioning; epistasis analysis of two independent patient cohorts shows interaction between FEZ1 and DISC1 (but not FEZ1 and NDEL1) for schizophrenia risk. Co-immunoprecipitation, in vivo knockdown in adult mouse hippocampus, morphological analysis of newborn neurons, genetic epistasis analysis in two patient cohorts Neuron High 22099459
2013 FEZ1 forms a stable complex with SCOCO (UNC-69 homolog) through coiled-coil interactions. Structural analysis by NMR, crosslinking-MS, and SAXS shows FEZ1(92-194) homodimerizes in antiparallel topology, and the FEZ1/SCOCO interaction interface is consistent with the UNC-76/UNC-69 interaction. A heterotetrameric complex model is supported by SAXS. NMR, cross-linking coupled with mass spectrometry, SAXS, molecular modelling, in vitro complex formation PloS one High 24116125
2013 SCOCO forms a parallel left-handed coiled-coil dimer and forms a stable homogeneous complex with the coiled-coil domain of FEZ1. SCOCO dimerization and surface residue R117 are important for the SCOCO-FEZ1 interaction, established by crystal structure determination and mutagenesis. X-ray crystallography of SCOCO coiled-coil domain at 2.7 Å, site-directed mutagenesis (E93V/K97L and N125L/N132V double mutants), multi-angle laser light scattering, native mass spectrometry, in vitro complex formation assay PloS one High 24098481
2014 Cdc20/APC (anaphase-promoting complex) ubiquitin ligase controls dendrite growth in neurons by targeting FEZ1 for degradation. BubR1 modulates Cdc20/APC activity and thereby FEZ1 levels; BubR1 is deacetylated by HDAC11, which disinhibits Cdc20/APC. This pathway operates in hippocampal dentate granule cells and olfactory bulb neurons. Overexpression and knockdown of Cdc20/APC and BubR1 in neurons, ubiquitin-mediated degradation assay, dendrite morphology analysis, acetylation status analysis of BubR1 Cell reports Medium 24726361
2015 HIV-1 associates with the kinesin-1 adaptor FEZ1; RNAi depletion of FEZ1 blocks early HIV-1 infection with virus showing bidirectional but no net movement toward the nucleus. The ability of exogenously expressed FEZ1 to promote HIV-1 infection requires its binding to kinesin-1. Both dynein and kinesin-1 are required for HIV-1 trafficking to the nucleus. RNAi knockdown, live-cell single-particle tracking of HIV-1 particles, exogenous expression of FEZ1 variants (including kinesin-1 binding mutants), early infection assay Nature communications High 25818806
2016 MARK/PAR-1 kinases phosphorylate FEZ1 at serine 58, regulating its function as a kinesin-1 adapter for presynaptic cargo transport. Loss of MARK/PAR-1 causes FEZ1, kinesin-1, and presynaptic cargoes to co-aggregate in cell bodies and axons instead of being transported. Unphosphorylated FEZ1 co-aggregates with kinesin-1 and cargoes are also found in Alzheimer's disease model mouse brains. Phosphorylation assay, mass spectrometry identification of phosphorylation site, MARK/PAR-1 loss-of-function in neurons, immunofluorescence, live-cell imaging, analysis of transgenic AD mouse brain Scientific reports High 27247180
2018 In C. elegans, UNC-76/FEZ1 and UNC-16/JIP3 limit mitochondrial density in neuronal processes by maintaining the balance of anterograde and retrograde mitochondrial transport. unc-76 mutants show increased mitochondrial density, elevated kinesin heavy and light chain levels in neurons, and a net anterograde bias in mitochondrial flux that is partly dependent on dynein. Genetic loss-of-function (unc-76 mutants), live-cell fluorescence imaging of mitochondrial transport, quantification of mitochondrial density and flux, genetic epistasis with dynein mutants Scientific reports Medium 29895958
2019 FEZ1 directly interacts with HIV-1 capsid protein (CA) hexamers, specifically binding through acidic poly-glutamate stretches to the positively charged central pore of CA hexamers. This interaction competes with nucleotides and inositol hexaphosphate (IP6) at the same site. Mutation of FEZ1 capsid-interacting residues significantly reduces HIV-1 trafficking toward the nucleus and early infection. Direct binding assay, all-atom molecular dynamics simulations, competition assay with IP6/nucleotides, site-directed mutagenesis of FEZ1 interacting residues, single-particle HIV-1 trafficking assay, early infection assay Cell reports High 31422020
2021 FEZ1 forms a complex with CRMP1 at neuronal growth cones and is required for axonal development; FEZ1 deficiency causes growth cone collapse and impaired axonal development similar to CRMP1 loss. Separately, FEZ1 forms a complex with DCC and Syntaxin-1 (components of the Netrin-1 signaling pathway), and FEZ1-deficient neurons fail to respond to Netrin-1 or Sema3A guidance cues. Co-immunoprecipitation, co-localization imaging, loss-of-function (FEZ1 deficiency) in rat hippocampal neurons, axon/dendrite morphology analysis, guidance cue response assay (Netrin-1, Sema3A) eNeuro Medium 33771901
2021 FEZ1 deletion in rat motor neurons strongly impairs axon and dendrite development and significantly delays synaptic protein transport into developing neurites. Drosophila unc-76 mutants show severe locomotion impairment and reduced synaptic boutons at neuromuscular junctions. Pharmacological activation of UNC-51/ATG1 (a FEZ1-activating kinase) with rapamycin and metformin ameliorates these defects. FEZ1 deletion in human ES-derived and rat neurons, neurite morphology analysis, synaptic protein transport assay, Drosophila unc-76 genetic analysis, pharmacological rescue with rapamycin/metformin Human molecular genetics Medium 33395696
2017 FEZ1 interacts with the retinoic acid receptor (RAR) through its coiled-coil region (interacting with the ligand-binding domain of RAR). In the presence of retinoic acid, FEZ1 induces hoxb4 gene expression, demonstrating a role in transcriptional regulation. In vitro binding assay, co-immunoprecipitation, interaction interface mapping, 86-gene panel expression assay in cells co-expressing FEZ1 and RAR FEBS open bio Medium 29321952
2009 FEZ1 interacts with NEK1 and CLASP2 through coiled-coil interactions in vitro, and all three proteins co-localize with gamma-tubulin in a perinuclear/centrosomal region in mammalian cells. FEZ1/CLASP2 co-localization is inhibited by PMA treatment, and CLASP2 is phosphorylated by active PKC isoforms, suggesting PKC regulates FEZ1/CLASP2 centrosomal complex. In vitro pulldown (coiled-coil interactions), co-localization imaging, PMA treatment, PKC phosphorylation assay Molecular and cellular biochemistry Low 19924516
2022 SCOC, ULK1, and NBR1 directly bind to FEZ1 protein to form a protein complex, as demonstrated by immunoprecipitation. All four proteins (FEZ1/SCOC/ULK1/NBR1) are targets of miR-129-5p, and their expression is regulated coordinately in neuronal autophagy. Immunoprecipitation, dual-luciferase reporter system (miR-129-5p target validation), overexpression/interference of miR-129-5p in neuronal cells Bioengineered Low 35435132

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 The Caenorhabditis elegans gene unc-76 and its human homologs define a new gene family involved in axonal outgrowth and fasciculation. Proceedings of the National Academy of Sciences of the United States of America 153 9096408
1999 The FEZ1 gene at chromosome 8p22 encodes a leucine-zipper protein, and its expression is altered in multiple human tumors. Proceedings of the National Academy of Sciences of the United States of America 138 10097140
2015 HIV-1 capsids bind and exploit the kinesin-1 adaptor FEZ1 for inward movement to the nucleus. Nature communications 114 25818806
2003 Three-dimensional structure of FEZ-1, a monomeric subclass B3 metallo-beta-lactamase from Fluoribacter gormanii, in native form and in complex with D-captopril. Journal of molecular biology 110 12507470
2001 FEZ1/LZTS1 gene at 8p22 suppresses cancer cell growth and regulates mitosis. Proceedings of the National Academy of Sciences of the United States of America 92 11504921
1999 Mammalian homologue of the Caenorhabditis elegans UNC-76 protein involved in axonal outgrowth is a protein kinase C zeta-interacting protein. The Journal of cell biology 86 9971736
2011 Interaction between FEZ1 and DISC1 in regulation of neuronal development and risk for schizophrenia. Neuron 85 22099459
2003 The kinesin-associated protein UNC-76 is required for axonal transport in the Drosophila nervous system. Molecular biology of the cell 78 12925768
2004 Association analysis of FEZ1 variants with schizophrenia in Japanese cohorts. Biological psychiatry 66 15522253
2019 FEZ1 Is Recruited to a Conserved Cofactor Site on Capsid to Promote HIV-1 Trafficking. Cell reports 64 31422020
2005 Identification of FEZ1 as a protein that interacts with JC virus agnoprotein and microtubules: role of agnoprotein-induced dissociation of FEZ1 from microtubules in viral propagation. The Journal of biological chemistry 61 15843383
2007 Fez1/Lzts1 absence impairs Cdk1/Cdc25C interaction during mitosis and predisposes mice to cancer development. Cancer cell 58 17349584
2001 Biochemical characterization of the FEZ-1 metallo-beta-lactamase of Legionella gormanii ATCC 33297T produced in Escherichia coli. Antimicrobial agents and chemotherapy 58 11257043
2007 Axonal guidance protein FEZ1 associates with tubulin and kinesin motor protein to transport mitochondria in neurites of NGF-stimulated PC12 cells. Biochemical and biophysical research communications 57 17669366
2006 Fasciculation and elongation protein zeta-1 (FEZ1) participates in the polarization of hippocampal neuron by controlling the mitochondrial motility. Biochemical and biophysical research communications 55 17173861
2008 Mice lacking the schizophrenia-associated protein FEZ1 manifest hyperactivity and enhanced responsiveness to psychostimulants. Human molecular genetics 53 18647754
2004 Functional regulation of FEZ1 by the U-box-type ubiquitin ligase E4B contributes to neuritogenesis. The Journal of biological chemistry 51 15466860
2001 Fez1/lzts1 alterations in gastric carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 47 11410489
2004 Fez1 is layer-specifically expressed in the adult mouse neocortex. The European journal of neuroscience 45 15579145
2002 FEZ1/LZTS1 is down-regulated in high-grade bladder cancer, and its restoration suppresses tumorigenicity in transitional cell carcinoma cells. The American journal of pathology 44 11943719
2002 NBR1 interacts with fasciculation and elongation protein zeta-1 (FEZ1) and calcium and integrin binding protein (CIB) and shows developmentally restricted expression in the neural tube. European journal of biochemistry 43 11856312
2006 FEZ1 dimerization and interaction with transcription regulatory proteins involves its coiled-coil region. The Journal of biological chemistry 39 16484223
2004 Expression of fasciculation and elongation protein zeta-1 (FEZ1) in the developing rat brain. Brain research. Molecular brain research 38 14992819
2005 Reduced FEZ1/LZTS1 expression and outcome prediction in lung cancer. Cancer research 37 15735004
2014 Dendrite development regulated by the schizophrenia-associated gene FEZ1 involves the ubiquitin proteasome system. Cell reports 34 24726361
2008 Down-regulation of tumor suppressor gene FEZ1/LZTS1 in breast carcinoma involves promoter methylation and associates with metastasis. Breast cancer research and treatment 34 18686028
2006 The short coiled-coil domain-containing protein UNC-69 cooperates with UNC-76 to regulate axonal outgrowth and normal presynaptic organization in Caenorhabditis elegans. Journal of biology 33 16725058
2002 Differential expression of FEZ1/LZTS1 gene in lung cancers and their cell cultures. Clinical cancer research : an official journal of the American Association for Cancer Research 31 12114433
2009 Human FEZ1 has characteristics of a natively unfolded protein and dimerizes in solution. Proteins 30 18615714
2018 UNC-16/JIP3 and UNC-76/FEZ1 limit the density of mitochondria in C. elegans neurons by maintaining the balance of anterograde and retrograde mitochondrial transport. Scientific reports 29 29895958
2005 Overexpression of fasciculation and elongation protein zeta-1 (FEZ1) induces a post-entry block to retroviruses in cultured cells. Genes & development 28 15879557
2016 Phosphorylation of FEZ1 by Microtubule Affinity Regulating Kinases regulates its function in presynaptic protein trafficking. Scientific reports 27 27247180
2004 Probing the specificity of the subclass B3 FEZ-1 metallo-beta-lactamase by site-directed mutagenesis. The Journal of biological chemistry 26 15159411
2003 Down-regulation of FEZ1/LZTS1 gene with frequent loss of heterozygosity in oral squamous cell carcinomas. International journal of oncology 26 12851677
2009 The brain-specific factor FEZ1 is a determinant of neuronal susceptibility to HIV-1 infection. Proceedings of the National Academy of Sciences of the United States of America 20 19667186
2017 Disruption to schizophrenia-associated gene Fez1 in the hippocampus of HDAC11 knockout mice. Scientific reports 19 28928414
2017 Novel schizophrenia risk factor pathways regulate FEZ1 to advance oligodendroglia development. Translational psychiatry 18 29249816
2007 Fez1/Lzts1 a new mitotic regulator implicated in cancer development. Cell division 18 17718912
2006 The FEZ1 gene shows no association to schizophrenia in Caucasian or African American populations. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 17 16936715
2010 Functions of fasciculation and elongation protein zeta-1 (FEZ1) in the brain. TheScientificWorldJournal 16 20730382
2010 Human FEZ1 protein forms a disulfide bond mediated dimer: implications for cargo transport. Journal of proteome research 16 20812761
2008 Fez1/Lzts1-deficient mice are more susceptible to N-butyl-N-(4-hydroxybutil) nitrosamine (BBN) carcinogenesis. Carcinogenesis 16 18192690
2008 Over-expression of GFP-FEZ1 causes generation of multi-lobulated nuclei mediated by microtubules in HEK293 cells. Experimental cell research 16 18439996
2007 Failure to confirm the association between the FEZ1 gene and schizophrenia in a Japanese population. Neuroscience letters 16 17374448
2009 FEZ1 interacts with CLASP2 and NEK1 through coiled-coil regions and their cellular colocalization suggests centrosomal functions and regulation by PKC. Molecular and cellular biochemistry 15 19924516
2021 FEZ1 Forms Complexes with CRMP1 and DCC to Regulate Axon and Dendrite Development. eNeuro 14 33771901
2011 Four mood stabilizers commonly induce FEZ1 expression in human astrocytes. Bipolar disorders 14 22017218
2011 FEZ2 has acquired additional protein interaction partners relative to FEZ1: functional and evolutionary implications. PloS one 13 21408165
2014 Fasciculation and elongation protein zeta-1 (FEZ1) expression in reactive astrocytes in a rat model of Parkinson's disease. Neuropathology and applied neurobiology 11 23888906
2022 miR-129-5p targets FEZ1/SCOC/ULK1/NBR1 complex to restore neuronal function in mice with post-stroke depression. Bioengineered 10 35435132
2013 Crystal structure of the human short coiled coil protein and insights into SCOC-FEZ1 complex formation. PloS one 10 24098481
2009 Expression of fasciculation and elongation protein zeta-1 (FEZ1) in cultured rat neonatal astrocytes. Molecular and cellular biochemistry 10 19199094
2021 Loss of FEZ1, a gene deleted in Jacobsen syndrome, causes locomotion defects and early mortality by impairing motor neuron development. Human molecular genetics 8 33395696
2018 Methylphenidate and Guanfacine Ameliorate ADHD-Like Phenotypes in Fez1-Deficient Mice. Molecular neuropsychiatry 8 29888233
2019 Is there a new pathway relationship between melatonin and FEZ1 in experimental rat model of Alzheimer's disease? Bratislavske lekarske listy 7 30685996
2023 Single-cell transcriptomics implicates the FEZ1-DKK1 axis in the regulation of corneal epithelial cell proliferation and senescence. Cell proliferation 6 36851859
2023 FEZ1 participates in human embryonic brain development by modulating neuronal progenitor subpopulation specification and migrations. iScience 6 38213789
2017 Fasciculation and elongation zeta-1 protein (FEZ1) interacts with the retinoic acid receptor and participates in transcriptional regulation of the Hoxb4 gene. FEBS open bio 6 29321952
2013 Structural analysis of intermolecular interactions in the kinesin adaptor complex fasciculation and elongation protein zeta 1/ short coiled-coil protein (FEZ1/SCOCO). PloS one 6 24116125
2023 Expression of the schizophrenia associated gene FEZ1 in the early developing fetal human forebrain. Frontiers in neuroscience 3 37746155
2025 Blood transcriptomics identifies FEZ1 as a potential biomarker for inflammatory bowel disease. Computers in biology and medicine 2 39894009

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