Affinage

NDC1

Nucleoporin NDC1 · UniProt Q9BTX1

Length
674 aa
Mass
76.3 kDa
Annotated
2026-04-29
28 papers in source corpus 19 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NDC1 is a conserved multi-pass transmembrane nucleoporin that anchors nuclear pore complexes (NPCs) in the nuclear envelope by bridging the lipid bilayer to soluble scaffold nucleoporins. Its six N-terminal transmembrane segments embed it in the nuclear envelope membrane, where it directly binds Nup53 — an interaction essential for vertebrate NPC assembly that modulates Nup53's membrane-deforming activity — and forms additional complexes with transmembrane pore proteins Pom152/Pom34 and soluble Nup53/Nup59-Nup170 modules in yeast (PMID:16600873, PMID:19414609, PMID:24363447). NDC1 determines NPC density independently of membrane biogenesis and recruits ALADIN to pores; in yeast it additionally mediates spindle pole body insertion into the nuclear envelope, with its partitioning between SPBs and NPCs controlled by interaction with the SUN-domain protein Mps3 (PMID:8349727, PMID:35852146, PMID:19782045, PMID:24515347). Biallelic NDC1 variants that disrupt ALADIN binding cause decreased NPC insertion and ALADIN mislocalization in patient fibroblasts, establishing NDC1 as the causal gene for a triple A-like neuropathy syndrome (PMID:39003500).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1993 High

    The identification of Ndc1p as an integral nuclear envelope membrane protein required for spindle pole body insertion established that a transmembrane component was needed for organelle insertion into the NE.

    Evidence EM, immunofluorescence, and genetic analysis of temperature-sensitive ndc1-1 mutants in S. cerevisiae

    PMID:8349727

    Open questions at the time
    • No connection to NPC assembly yet known
    • Topology and number of transmembrane domains uncertain
    • Mechanism of SPB insertion not defined
  2. 1999 High

    Demonstrating that both haploinsufficiency and overexpression of NDC1 cause monopolar spindles revealed that precise Ndc1 dosage is critical for SPB duplication, suggesting a stoichiometric role rather than simple catalytic activity.

    Evidence Genetic dosage analysis, flow cytometry, and microscopy in S. cerevisiae

    PMID:10468586

    Open questions at the time
    • Whether dosage sensitivity reflects competition for Ndc1 between organelles was unknown
    • No NPC role established for yeast Ndc1
  3. 2004 High

    Discovery that ndc1-39 blocks incorporation of Nup49 into NPCs revealed a dual function for Ndc1 in both SPB and NPC biogenesis, answering whether Ndc1 acts beyond SPB duplication.

    Evidence Temperature-sensitive allele analysis, genetic epistasis with nic96-1, nucleoporin incorporation assay in S. cerevisiae

    PMID:15075274

    Open questions at the time
    • Mechanism of Ndc1 action in NPC assembly unknown
    • Conservation in metazoans undemonstrated
  4. 2006 High

    RNAi of vertebrate NDC1 in HeLa cells and C. elegans demonstrated conserved requirement for NPC/NE assembly, and direct binding to Nup53 identified NDC1 as a membrane anchor linking the NE bilayer to soluble nucleoporins.

    Evidence RNAi, in vitro NPC assembly, in vitro binding to Nup53 in human cells and C. elegans; topology mapping by limited proteolysis in yeast

    PMID:16600873 PMID:16702233 PMID:16779818

    Open questions at the time
    • Whether NDC1-Nup53 interaction is essential for pore assembly was untested
    • Hierarchy of NDC1 recruitment relative to other assembly factors unknown
  5. 2008 High

    Placing NDC1-containing membrane vesicle recruitment downstream of chromatin-bound ELYS and the Nup107-160 complex defined NDC1's position in the NPC assembly hierarchy.

    Evidence Sequential immunodepletion and vesicle fractionation in Xenopus egg extract nuclear assembly system

    PMID:18596237

    Open questions at the time
    • Signal that recruits NDC1 vesicles to the forming pore not identified
    • Whether NDC1 acts before or after POM121 at the membrane not resolved
  6. 2009 High

    Mapping distinct Ndc1 complexes — with transmembrane Pom152/Pom34 and with soluble Nup53/Nup59-Nup170 — and showing that loss of both causes pore dilation and blocks new NPC assembly revealed the structural logic of Ndc1 as a bifunctional membrane anchor; concurrently, NDC1 was shown to recruit ALADIN to NPCs and be required for selective nuclear import.

    Evidence Reciprocal Co-IP, photoconvertible protein chase, EM in yeast; siRNA, FRET, and nuclear import assays in HeLa cells

    PMID:19414609 PMID:19703420 PMID:19782045

    Open questions at the time
    • Structural basis of NDC1-ALADIN interaction unknown
    • Whether ALADIN anchoring and NPC assembly roles are mechanistically coupled was unclear
  7. 2012 Medium

    Interaction with reticulon proteins Rtn1/Yop1 and the finding that Ndc1 overexpression rescues their deletion phenotype supported a model in which membrane-shaping proteins facilitate Ndc1 partitioning between SPBs and NPCs.

    Evidence Co-IP, overexpression rescue, EM, and genetic analysis in S. cerevisiae

    PMID:22798490

    Open questions at the time
    • Whether reticulons act on Ndc1 directly or indirectly through membrane curvature not distinguished
    • No in vitro reconstitution
  8. 2013 High

    Demonstrating that the NDC1-binding site on Nup53 overlaps with its membrane-bending region established that NDC1 binding modulates Nup53 membrane-deforming activity, providing a mechanistic explanation for NDC1's essential role in NPC assembly; separately, a splice-disrupting Tmem48/Ndc1 mutation in mice caused pachytene arrest and skeletal defects, revealing an essential gametogenesis function.

    Evidence In vitro binding, mutagenesis, membrane deformation assay, Xenopus NPC assembly; mouse mutant characterization with transgenic rescue

    PMID:24045954 PMID:24363447

    Open questions at the time
    • Whether NDC1-Nup53 interface represents a druggable target unknown
    • Whether gametogenesis defect reflects NPC density, ALADIN anchoring, or another function of NDC1
  9. 2014 High

    The ndc1-L562S mutation that abolishes Mps3 binding causes lethal SPB duplication failure, and suppression by POM152 deletion revealed that Mps3 controls Ndc1 distribution between NPCs and SPBs.

    Evidence Fluorescence cross-correlation spectroscopy, genetic allele and suppressor analysis in S. cerevisiae

    PMID:24515347

    Open questions at the time
    • Structural basis of Ndc1-Mps3 interaction not determined
    • Whether a mammalian SUN-domain protein plays an analogous role unknown
  10. 2022 High

    3D-EM and FRAP studies in C. elegans embryos showed that Ndc1 determines NPC density independently of membrane biogenesis and acts in partial redundancy with Nup53, decoupling membrane growth from pore insertion.

    Evidence 3D-EM tomography, FRAP, genetic epistasis, and membrane synthesis manipulation in C. elegans

    PMID:35852146

    Open questions at the time
    • Mechanism by which Ndc1 controls NPC number not molecularly defined
    • Whether Ndc1-Nup53 redundancy operates through the same membrane-bending mechanism as in Xenopus unknown
  11. 2024 High

    Biallelic NDC1 variants disrupting ALADIN binding were shown to cause decreased ALADIN recruitment and reduced post-mitotic NPC insertion in patient fibroblasts, establishing NDC1 as a disease gene for triple A-like neuropathy.

    Evidence Patient fibroblast analysis, immunofluorescence for ALADIN/NDC1, exome/RNA sequencing

    PMID:39003500

    Open questions at the time
    • Whether NPC insertion defect or ALADIN loss is the primary pathogenic mechanism in patient tissue remains unresolved
    • No animal model recapitulating the human disease phenotype reported

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis of NDC1's interactions with Nup53, ALADIN, and Mps3, the mechanism by which NDC1 controls NPC number independently of membrane supply, and whether NDC1's gametogenesis role reflects NPC density, ALADIN anchoring, or an NPC-independent function.
  • No high-resolution structure of NDC1 or its complexes
  • Mechanism coupling NDC1 to NPC number control undefined
  • Relative contributions of NPC and ALADIN defects to disease pathology unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0060090 molecular adaptor activity 3
Localization
GO:0005635 nuclear envelope 8 GO:0005886 plasma membrane 1
Pathway
R-HSA-9609507 Protein localization 6 R-HSA-1852241 Organelle biogenesis and maintenance 4 R-HSA-1640170 Cell Cycle 3
Partners
AAASBCAP31MPS3NUP53NUP59POM152POM34SEPT12
Complex memberships
Ndc1-Nup53/Nup59-Nup170 (yeast soluble NPC anchor)Ndc1-Pom152-Pom34 (yeast transmembrane NPC ring)

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 Yeast Ndc1p is an integral membrane protein with six or seven transmembrane domains that localizes to the nuclear envelope and is required for insertion of the nascent spindle pole body (SPB) into the nuclear envelope during SPB duplication; temperature-sensitive ndc1-1 mutants fail to insert the nascent SPB into the NE, resulting in a monopolar spindle. Electron microscopy, immunofluorescence, order-of-function experiments, molecular cloning The Journal of cell biology High 8349727
1999 NDC1 dosage is critical for SPB duplication; haploinsufficiency causes aneuploidy and overexpression causes SPB duplication defects indistinguishable from ndc1-1 loss-of-function, leading to monopolar spindles and polyploidy. Genetic dosage analysis, flow cytometry, microscopy in S. cerevisiae Proceedings of the National Academy of Sciences of the United States of America High 10468586
2004 Yeast Ndc1p is required for NPC assembly in addition to SPB duplication; the ndc1-39 temperature-sensitive allele causes failure to incorporate nucleoporin Nup49p into NPCs, and the ndc1-39 nic96-1 double mutant shows enhanced growth defects, placing Ndc1p functionally in the NPC assembly pathway. Temperature-sensitive allele analysis, genetic epistasis, nucleoporin incorporation assay, yeast genetics Eukaryotic cell High 15075274
2006 The topology of Ndc1p places six transmembrane segments in the N-terminal half with the C-terminus exposed to the cytoplasm; limited proteolysis of yeast Ndc1p in cellular membranes confirmed the cytoplasmic orientation of its C-terminus. Human NDC1 contains three FG repeats in the C-terminus, consistent with it being a nuclear pore protein. Limited proteolysis, topology prediction, charge distribution analysis The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology Medium 16779818
2006 Vertebrate NDC1 is a transmembrane nucleoporin required for NPC assembly; RNAi depletion in HeLa cells interferes with assembly of FG-repeat nucleoporins into NPCs. In C. elegans, loss of NDC1 causes severe NPC defects and high larval/embryonic mortality. RNAi, immunofluorescence, cell biology in HeLa cells and C. elegans The Journal of cell biology High 16702233
2006 Vertebrate NDC1 is required for NPC and nuclear envelope assembly; RNAi depletion causes NPC/NE assembly defects in vivo and in vitro. NDC1 interacts with soluble nucleoporin Nup53 in vitro, suggesting NDC1 links the NE membrane to soluble nucleoporins to anchor NPCs in the membrane. RNAi, biochemical depletion, in vitro NPC assembly assay, in vitro binding assay (Nup53) Molecular cell High 16600873
2008 During nuclear pore assembly in higher eukaryotes, membrane vesicles containing NDC1 (and POM121) are recruited to the forming nucleus in a manner dependent on chromatin-bound ELYS/Nup107-160 complex, placing NDC1 recruitment after ELYS and Nup107-160 in the pore assembly hierarchy. Xenopus egg extract nuclear assembly assay, immunodepletion, vesicle fractionation, antibody inhibition Molecular biology of the cell High 18596237
2009 Yeast Ndc1 forms distinct complexes: one with transmembrane proteins Pom152 and Pom34, and two alternative complexes with soluble nucleoporins Nup53 and Nup59 (which in turn bind Nup170 and Nup157). Disruption of both transmembrane and soluble Ndc1 interaction partners causes Ndc1 mistargeting and NPC structural defects with pore dilation, and blocks new NPC assembly. Co-immunoprecipitation, photoconvertible fluorescent protein chase, genetic epistasis, electron microscopy The Journal of cell biology High 19414609
2009 NDC1 anchors ALADIN within the NPC; siRNA depletion of NDC1 (but not GP210 or POM121) causes mislocalization of ALADIN from NPCs. Reciprocally, depletion of ALADIN causes loss of NDC1 from NPCs. FRET measurements demonstrate a direct association between NDC1 and ALADIN at NPCs. siRNA knockdown, GFP-ALADIN localization, FRET, fluorescence microscopy in HeLa cells Biochemical and biophysical research communications High 19782045
2009 NDC1 directly interacts with ALADIN and this interaction is required for targeting ALADIN to NPCs; furthermore, NDC1 is required for selective nuclear protein import. Co-immunoprecipitation, siRNA knockdown, nuclear import assay Biochemical and biophysical research communications Medium 19703420
2012 Ndc1 physically interacts with reticulon proteins Rtn1 and Yop1 in yeast; overexpression of NDC1 rescues both SPB and NPC defects in rtn1Δ yop1Δ cells, suggesting that NPC and SPB biogenesis compete for Ndc1 and that Rtn1/Yop1 facilitate this process. Co-immunoprecipitation, overexpression rescue, electron microscopy, genetic analysis Genetics Medium 22798490
2013 The interaction between Nup53 and NDC1 is essential for vertebrate NPC assembly. The NDC1-binding site on Nup53 overlaps with a membrane-bending region, suggesting that NDC1 binding modulates Nup53's membrane-deforming activity during NPC assembly. In vitro binding assay, mutagenesis, membrane deformation assay, Xenopus egg extract NPC assembly Journal of cell science High 24363447
2013 Mouse TMEM48 (NDC1) is specifically expressed in germ cells; a splice-disrupting mutation in Tmem48 causes spermatogenesis arrest at mid-to-late pachytene with defective homologous chromosome synapsis, and skeletal malformations; transgenic rescue with wild-type Tmem48 fully restores the phenotype. Mouse mutant (sks) characterization, linkage analysis, exome sequencing, transgenic rescue, immunocytochemistry The Journal of biological chemistry High 24045954
2014 Ndc1 interacts with the SUN-domain protein Mps3 on the nuclear envelope; a specific ndc1-L562S mutation abolishes Mps3 binding and causes lethality due to SPB duplication failure. Deletion of POM152 suppresses the ndc1-L562S defect, suggesting that Ndc1-Mps3 interaction controls distribution of Ndc1 between the NPC and SPB. Fluorescence cross-correlation spectroscopy, genetic allele analysis, suppressor analysis in S. cerevisiae The Journal of cell biology High 24515347
2016 SEPT12 and NDC1 form a complex in male germ cells; NDC1 is localized at the nuclear membrane of spermatids and at the neck of mature spermatozoa. NDC1 overexpression restricts SEPT12 localization to the nucleus and represses SEPT12 filament formation. In SEPT12-mutant sperm, NDC1 is mislocalized from the sperm neck to the manchette region. Co-immunoprecipitation, colocalization (immunofluorescence), overexpression studies in male germ cell lines, mouse models International journal of molecular sciences Medium 27854341
2022 In C. elegans, Ndc1 determines NPC density at the nuclear envelope independently of membrane biogenesis; loss of ndc1 results in faster turnover of the outer scaffold nucleoporin Nup160 at the NE. NE formation fails when both Ndc1 and Nup53 are absent, indicating partially redundant roles. Upregulation of membrane synthesis rescues the nuclear growth defect from ndc1 loss but not from nup53 loss, decoupling membrane biogenesis from Ndc1-mediated NPC assembly. 3D-EM tomography, FRAP/fluorescence turnover assay, genetic epistasis, membrane synthesis manipulation in C. elegans embryo eLife High 35852146
2023 ARRDC5 affects spermatogenesis by regulating the localization of NDC1 and SUN5; ARRDC5 may influence SEC22A-mediated vesicle transport and localization of NDC1, SUN5 and other head-tail coupling apparatus proteins required for sperm head-tail attachment. Knockout mouse model, mass spectrometry, co-immunoprecipitation, immunofluorescence Development (Cambridge, England) Medium 37997706
2024 NDC1 interacts with BCAP31 (co-immunoprecipitation confirmed by mass spectrometry) and activates the PI3K/AKT signaling pathway; NDC1 overexpression enhances HCC cell proliferation, invasion, and migration, while knockdown has opposite effects. Co-immunoprecipitation, mass spectrometry, gain- and loss-of-function experiments, xenograft mouse model Journal of biochemical and molecular toxicology Medium 38348718
2024 Biallelic NDC1 variants (in-frame deletions or missense mutations) affecting amino acids required for ALADIN binding cause decreased recruitment of ALADIN to the nuclear envelope and decreased post-mitotic NPC insertion in patient-derived skin fibroblasts, establishing a direct pathogenic mechanism for neuropathy and triple A-like syndrome. Patient fibroblast analysis, immunofluorescence for ALADIN/NDC1 localization, exome/RNA sequencing HGG advances High 39003500

Source papers

Stage 0 corpus · 28 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 The conserved transmembrane nucleoporin NDC1 is required for nuclear pore complex assembly in vertebrate cells. Molecular cell 184 16600873
2006 NDC1: a crucial membrane-integral nucleoporin of metazoan nuclear pore complexes. The Journal of cell biology 139 16702233
2008 Capture of AT-rich chromatin by ELYS recruits POM121 and NDC1 to initiate nuclear pore assembly. Molecular biology of the cell 133 18596237
1993 NDC1: a nuclear periphery component required for yeast spindle pole body duplication. The Journal of cell biology 126 8349727
2009 Role of the Ndc1 interaction network in yeast nuclear pore complex assembly and maintenance. The Journal of cell biology 115 19414609
2013 Interaction of Nup53 with Ndc1 and Nup155 is required for nuclear pore complex assembly. Journal of cell science 64 24363447
2004 A novel allele of Saccharomyces cerevisiae NDC1 reveals a potential role for the spindle pole body component Ndc1p in nuclear pore assembly. Eukaryotic cell 49 15075274
2015 Overexpression and biological function of TMEM48 in non-small cell lung carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 46 26392108
2011 Bulk segregant analysis followed by high-throughput sequencing reveals the Neurospora cell cycle gene, ndc-1, to be allelic with the gene for ornithine decarboxylase, spe-1. Eukaryotic cell 45 21515825
1999 Altered dosage of the Saccharomyces cerevisiae spindle pole body duplication gene, NDC1, leads to aneuploidy and polyploidy. Proceedings of the National Academy of Sciences of the United States of America 44 10468586
2014 The SUN protein Mps3 controls Ndc1 distribution and function on the nuclear membrane. The Journal of cell biology 39 24515347
2009 The nuclear pore complex protein ALADIN is anchored via NDC1 but not via POM121 and GP210 in the nuclear envelope. Biochemical and biophysical research communications 33 19782045
2009 The transmembrane nucleoporin NDC1 is required for targeting of ALADIN to nuclear pore complexes. Biochemical and biophysical research communications 27 19703420
2020 TMEM48 promotes cell proliferation and invasion in cervical cancer via activation of the Wnt/β-catenin pathway. Journal of receptor and signal transduction research 24 32896205
2012 Integrity and function of the Saccharomyces cerevisiae spindle pole body depends on connections between the membrane proteins Ndc1, Rtn1, and Yop1. Genetics 24 22798490
2019 Real-world Experience of Carotid Artery Stenting in Japan: Analysis of 8458 Cases from the JR-NET3 Nationwide Retrospective Multi-center Registries. Neurologia medico-chirurgica 22 30880307
2022 Ndc1 drives nuclear pore complex assembly independent of membrane biogenesis to promote nuclear formation and growth. eLife 21 35852146
2016 SEPT12-NDC1 Complexes Are Required for Mammalian Spermiogenesis. International journal of molecular sciences 21 27854341
2011 An alternatively spliced domain of the NDC1 NAD(P)H dehydrogenase gene strongly influences the expression of the ACTIN2 reference gene in Arabidopsis thaliana. Plant science : an international journal of experimental plant biology 16 22195593
2013 A mutation in the nuclear pore complex gene Tmem48 causes gametogenesis defects in skeletal fusions with sterility (sks) mice. The Journal of biological chemistry 14 24045954
2006 Topology of yeast Ndc1p: predictions for the human NDC1/NET3 homologue. The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology 11 16779818
2023 ARRDC5 deficiency impairs spermatogenesis by affecting SUN5 and NDC1. Development (Cambridge, England) 8 37997706
2024 NDC1 promotes hepatocellular carcinoma tumorigenesis by targeting BCAP31 to activate PI3K/AKT signaling. Journal of biochemical and molecular toxicology 3 38348718
2024 NUP155 and NDC1 interaction in NSCLC: a promising target for tumor progression. Frontiers in pharmacology 3 39720592
2024 Biallelic NDC1 variants that interfere with ALADIN binding are associated with neuropathy and triple A-like syndrome. HGG advances 2 39003500
2023 Characterisation of the trans-membrane nucleoporins GP210 and NDC1 in Arabidopsis thaliana. Plant science : an international journal of experimental plant biology 2 37116717
2025 Electro-oxidative Deoxyfluorination of Arenes with NEt3·3HF. The Journal of organic chemistry 1 39868529
2025 Efficient Cerebral Infarction Segmentation Using U-Net and U-Net3 + Models. Journal of imaging informatics in medicine 0 40588699