Affinage

NDC1

Nucleoporin NDC1 · UniProt Q9BTX1

Length
674 aa
Mass
76.3 kDa
Annotated
2026-06-10
26 papers in source corpus 19 papers cited in narrative 19 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NDC1 (TMEM48/NET3) is a conserved integral membrane nucleoporin that anchors nuclear pore complexes (NPCs) in the nuclear envelope by linking the NE membrane to the soluble NPC scaffold (PMID:16600873, PMID:16702233). The protein adopts a conserved topology of six transmembrane segments in its N-terminal half and a large cytoplasmically exposed C-terminal domain that mediates its protein interactions (PMID:16779818). During NPC biogenesis, NDC1-containing membrane vesicles are recruited downstream of the chromatin-bound ELYS/Nup107-160 complex (PMID:18596237), and NDC1 directly binds the soluble nucleoporin Nup53; because the Ndc1-binding site on Nup53 overlaps a membrane-bending region, this interaction modulates Nup53's membrane-deforming activity during pore formation and is essential for vertebrate NPC assembly (PMID:16600873, PMID:24363447). In yeast, Ndc1 partitions among distinct assemblies—a transmembrane complex with Pom152 and Pom34 and alternative complexes with the soluble nucleoporins Nup53/Nup59—and disrupting both interaction groups mislocalizes Ndc1 and dilates pores (PMID:19414609). NDC1 sets NPC density by stabilizing outer-scaffold nucleoporins at the NE, acting partially redundantly with Nup53 in nuclear envelope formation; membrane biogenesis can be decoupled from Ndc1-dependent NPC assembly (PMID:35852146). NDC1 also recruits the nucleoporin ALADIN to the NPC through direct interaction, and the two depend on each other for NPC localization (PMID:19782045, PMID:19703420). In yeast the same protein is required for insertion of the duplicating spindle pole body into the nuclear envelope, a function competed for with NPC biogenesis and governed by interactions with the membrane-shaping proteins Rtn1/Yop1 and the SUN-domain protein Mps3 (PMID:8349727, PMID:22798490, PMID:24515347). Loss-of-function disrupts gametogenesis: mouse Tmem48 mutation causes pachytene meiotic arrest from defective chromosome synapsis (PMID:24045954), and NDC1 forms a germ-cell complex with SEPTIN12 required for normal spermiogenesis (PMID:27854341). In humans, biallelic NDC1 variants that impair ALADIN binding reduce ALADIN recruitment and post-mitotic NPC insertion, causing a triple A-like polyneuropathy syndrome (PMID:39003500).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1993 High

    Established the founding function of Ndc1 by showing it is required for insertion of the duplicating spindle pole body into the nuclear envelope, defining an NE-resident factor acting in G1.

    Evidence EM, immunofluorescence, and genetic order-of-function analysis of temperature-sensitive ndc1 mutants in yeast

    PMID:8349727

    Open questions at the time
    • Did not identify molecular partners mediating SPB insertion
    • Did not connect Ndc1 to NPC assembly
  2. 1999 Medium

    Showed that NDC1 dosage is tightly constrained—both haploinsufficiency and overexpression disrupt SPB duplication—indicating it is a stoichiometry-sensitive component.

    Evidence Yeast genetic dosage experiments with flow cytometry and spindle morphology readouts

    PMID:10468586

    Open questions at the time
    • Mechanism linking dosage to SPB defects not resolved
    • Did not address NPC role
  3. 2004 Medium

    Extended Ndc1 function beyond the SPB to NPC assembly, placing it in the NPC assembly pathway via nucleoporin incorporation and genetic interaction.

    Evidence Temperature-sensitive allele analysis, genetic epistasis with nic96-1, and nucleoporin incorporation assays in yeast

    PMID:15075274

    Open questions at the time
    • Did not define direct binding partners
    • Mechanism of nucleoporin incorporation unresolved
  4. 2006 High

    Defined vertebrate NDC1 as a transmembrane nucleoporin required for NPC/NE assembly that links the NE membrane to soluble nucleoporins through a direct Nup53 interaction, and established conserved six-TM topology with a cytoplasmic C-terminus.

    Evidence RNAi in HeLa, Xenopus in vitro NE assembly, in vitro Nup53 binding, EM across multiple organisms, and limited proteolysis topology mapping

    PMID:16600873 PMID:16702233 PMID:16779818

    Open questions at the time
    • Did not establish how Nup53 binding affects membrane shape
    • C. elegans data showed it is not absolutely essential, leaving redundancy unexplained
  5. 2008 Medium

    Ordered NDC1 vesicle recruitment within the assembly pathway, showing it depends on chromatin-bound ELYS/Nup107-160.

    Evidence Xenopus in vitro nuclear assembly with antibody inhibition and DNA-binding competition assays

    PMID:18596237

    Open questions at the time
    • Did not identify the receptor coupling vesicles to the ELYS complex
    • Co-recruited POM121 vs NDC1 roles not separated
  6. 2009 High

    Mapped Ndc1 into discrete interaction modules—transmembrane (Pom152/Pom34) and soluble nucleoporin (Nup53/Nup59)—required for targeting and pore integrity, and identified ALADIN as an NDC1-dependent NPC partner.

    Evidence Reciprocal co-IP, genetic double/triple mutants, photoconvertible NPC-assembly imaging and EM in yeast; siRNA, FRET and co-IP for NDC1-ALADIN in human cells

    PMID:19414609 PMID:19703420 PMID:19782045

    Open questions at the time
    • Structural basis of module partitioning not resolved
    • How ALADIN recruitment relates to NPC scaffold assembly unclear
  7. 2012 Medium

    Identified Ndc1 as a limiting factor shared between NPC and SPB biogenesis through interaction with membrane-shaping Rtn1/Yop1.

    Evidence Co-IP, genetic rescue by NDC1 overexpression, EM, and spindle orientation assays in yeast

    PMID:22798490

    Open questions at the time
    • Did not quantify the competitive partitioning mechanism
    • Specificity of Rtn1/Yop1 effects on each pathway unresolved
  8. 2013 High

    Established the molecular logic of NDC1-Nup53 coupling—Ndc1 binds a Nup53 membrane-bending region and modulates its membrane-deforming activity—and showed Tmem48 mutation causes gametogenesis and skeletal defects in mouse with rescue confirming causality.

    Evidence In vitro binding with Nup53 mutagenesis and Xenopus NE assembly; mouse positional cloning/exome sequencing with transgenic rescue and histology

    PMID:24045954 PMID:24363447

    Open questions at the time
    • Structural details of curvature modulation not resolved
    • Mechanism linking NPC defects to synapsis failure not defined
  9. 2014 Medium

    Showed an Ndc1-Mps3 (SUN-domain) interaction at the NE governs distribution of Ndc1 between NPC and SPB, with Pom152 deletion suppressing the binding-deficient allele.

    Evidence Fluorescence cross-correlation spectroscopy in live yeast, allele analysis, and suppressor genetics

    PMID:24515347

    Open questions at the time
    • Did not resolve how partitioning is regulated through the cell cycle
    • Direct Mps3-binding interface not mapped structurally
  10. 2016 Medium

    Identified an NDC1-SEPTIN12 germ-cell complex controlling SEPT12 localization and required for normal spermiogenesis, extending NDC1's roles into sperm morphogenesis.

    Evidence Co-IP, yeast two-hybrid, immunofluorescence, overexpression in germ cell lines, and mouse knockout/knock-in models

    PMID:27854341

    Open questions at the time
    • Whether SEPT12 interaction is NPC-related or independent unresolved
    • Direct binding interface not mapped
  11. 2022 High

    Defined NDC1 as a determinant of NPC density that stabilizes outer-scaffold nucleoporins and acts partially redundantly with Nup53, and decoupled membrane biogenesis from Ndc1-mediated NPC assembly.

    Evidence 3D-EM tomography, photoconversion nucleoporin turnover, RNAi, double-mutant analysis and membrane-synthesis manipulation in C. elegans

    PMID:35852146

    Open questions at the time
    • Molecular basis of scaffold stabilization not resolved
    • How redundancy with Nup53 is partitioned mechanistically unclear
  12. 2024 Medium

    Linked NDC1 to human disease by showing biallelic variants impairing ALADIN binding reduce ALADIN recruitment and post-mitotic NPC insertion, causing a triple A-like polyneuropathy.

    Evidence Diagnostic exome/RNA sequencing and patient-derived fibroblast functional assays for ALADIN localization and NPC insertion

    PMID:39003500

    Open questions at the time
    • Tissue-specificity of the neuropathy phenotype not explained
    • Why adrenal insufficiency is absent unlike classical triple A unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NDC1's NE/NPC scaffolding function relates to its reported roles in cancer signaling (BCAP31/PI3K-AKT) and to vesicle-trafficking factors (ARRDC5/SEC22A) in spermatogenesis remains undefined.
  • NDC1-BCAP31 mechanism activating PI3K/AKT not dissected
  • ARRDC5/SEC22A link to NDC1 inferred rather than directly tested
  • No structural model of the full NDC1 interactome

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0060090 molecular adaptor activity 4
Localization
GO:0005635 nuclear envelope 4 GO:0005815 microtubule organizing center 2
Pathway
R-HSA-9609507 Protein localization 2
Partners
ALADINMPS3NUP53POM152POM34RTN1SEPT12
Complex memberships
NDC1-SEPTIN12 complexNPC (nuclear pore complex)Ndc1-Pom152-Pom34 complexspindle pole body (yeast)

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 Yeast Ndc1p is required for spindle pole body (SPB) duplication, specifically for insertion of the nascent SPB into the nuclear envelope. The protein encodes 656 amino acids with six or seven putative transmembrane domains and localizes to the nuclear envelope by immunofluorescence. Order-of-function experiments place NDC1 function in G1 after alpha-factor arrest but before cdc34 arrest. Electron microscopy of temperature-sensitive ndc1-1 mutants, immunofluorescence localization, genetic order-of-function experiments, molecular cloning The Journal of cell biology High 8349727
1999 NDC1 is haploinsufficient in diploid yeast; a single chromosomal copy cannot support viability, leading to aneuploidy. Overexpression of NDC1 causes SPB duplication defects, monopolar spindles, and increase-in-ploidy phenotypes, demonstrating that both increased and decreased NDC1 dosage disrupt SPB duplication. Yeast genetic dosage experiments, flow cytometry, microscopy of spindle morphology Proceedings of the National Academy of Sciences of the United States of America Medium 10468586
2004 Yeast Ndc1p is required for NPC assembly in addition to SPB duplication. The ndc1-39 temperature-sensitive allele blocks SPB insertion into the nuclear envelope and fails to incorporate the nucleoporin Nup49p into NPCs. Genetic interaction (enhanced growth defects) between ndc1-39 and nic96-1 NPC assembly mutant places Ndc1p in the NPC assembly pathway. Temperature-sensitive allele analysis, genetic epistasis (double mutant), nucleoporin incorporation assay, nuclear protein import assay Eukaryotic cell Medium 15075274
2006 Vertebrate NDC1 is a transmembrane nucleoporin required for NPC and nuclear envelope assembly. RNAi depletion in HeLa cells interferes with assembly of FG-repeat nucleoporins into NPCs. NDC1 interacts directly with Nup53 in vitro, suggesting it links the NE membrane to soluble nucleoporins to anchor the NPC in the membrane. RNAi knockdown, biochemical depletion in Xenopus in vitro NE assembly, in vitro binding assay (NDC1–Nup53 interaction) Molecular cell High 16600873
2006 Human NDC1 (hNDC1) likely possesses six transmembrane segments and is located at the nuclear pore wall in mammals, frogs, insects, and nematodes. Depletion of hNDC1 from HeLa cells interferes with assembly of FG-repeat nucleoporins into NPCs. Loss of NDC1 function in C. elegans causes severe NPC defects and high larval/embryonic mortality, but homozygous NDC1-deficient worms can be propagated, indicating NDC1 is not absolutely essential. RNAi depletion, immunofluorescence, electron microscopy, C. elegans genetics The Journal of cell biology High 16702233
2006 The overall topology of Ndc1p is conserved from yeast to humans: six transmembrane segments in the N-terminal half, a large soluble C-terminal half (~300 aa) with the N- and C-termini exposed to the cytoplasm. Limited proteolysis of yeast Ndc1p in cellular membranes confirms the cytoplasmic orientation of its C-terminus. The human homologue (NET3/NDC1) contains three FG repeats in the C-terminus characteristic of nucleoporins. Limited proteolysis in cellular membranes, topology prediction, sequence analysis The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology Medium 16779818
2008 Recruitment of vesicles containing the integral membrane nucleoporins POM121 and NDC1 to the forming nucleus depends on chromatin-bound ELYS/Nup107-160 complex, placing NDC1-containing vesicle recruitment downstream of ELYS and the Nup107-160 complex in the nuclear pore assembly pathway. Xenopus in vitro nuclear assembly, antibody inhibition, immunofluorescence, DNA-binding antibiotic competition assays Molecular biology of the cell Medium 18596237
2009 Yeast Ndc1 forms a distinct complex 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 groups of Ndc1 interactions causes defects in Ndc1 targeting and NPC structure with significant pore dilation. Depletion of Pom34 in cells lacking NUP53 and NUP59 blocks new NPC assembly. Co-immunoprecipitation, genetic double/triple mutant analysis, photoconvertible fluorescent protein fusions to track new NPC assembly, electron microscopy The Journal of cell biology High 19414609
2009 NDC1 is required for anchoring ALADIN at the NPC; siRNA depletion of NDC1 (but not GP210 or POM121) causes mislocalization of GFP-ALADIN. Conversely, depletion of ALADIN also leads to loss of NDC1 at the NPC. Direct association between NDC1 and ALADIN was demonstrated by FRET measurements. siRNA knockdown, GFP-ALADIN localization by fluorescence microscopy, FRET measurements Biochemical and biophysical research communications Medium 19782045
2009 NDC1 directly interacts with nucleoporin ALADIN, and this interaction is required for targeting ALADIN to NPCs. NDC1 is also required for selective nuclear import. Co-immunoprecipitation, siRNA knockdown with localization readout, nuclear import assay Biochemical and biophysical research communications Medium 19703420
2012 Ndc1 physically interacts with the membrane-shaping proteins Rtn1 and Yop1 in yeast. Overexpression of NDC1 (but not other SPB insertion factors) rescues both SPB and NPC defects in rtn1Δ yop1Δ cells, suggesting Ndc1 is a common essential component competed for between NPC and SPB biogenesis pathways. Co-immunoprecipitation, genetic rescue by overexpression, electron microscopy, spindle orientation assay Genetics Medium 22798490
2013 The interaction between Nup53 and the integral membrane protein Ndc1 is essential for vertebrate NPC assembly. The Ndc1-binding site on Nup53 overlaps with a membrane-bending region, and Ndc1 binding modulates Nup53's membrane-deforming activity. Nup53–Nup155 interaction is also critical for NPC formation as the main determinant of Nup155 recruitment to the assembling pore. In vitro binding assays, mutagenesis of Nup53 interaction domains, Xenopus in vitro NE assembly, depletion/rescue experiments Journal of cell science High 24363447
2013 A mutation in mouse Tmem48 (NDC1) causes gametogenesis defects with meiotic arrest at pachytene stage due to defective chromosome synapsis, and skeletal malformations with fused vertebrae and ribs. TMEM48 is specifically expressed in germ cells. Transgenic rescue with wild-type Tmem48 fully rescues phenotypes, confirming causality. Mouse genetics (positional cloning, whole exome sequencing), transgenic rescue, histology, immunocytochemistry The Journal of biological chemistry High 24045954
2014 Yeast Ndc1 interacts with the SUN domain-containing protein Mps3 at the nuclear envelope, as shown by fluorescence cross-correlation spectroscopy in live cells. The ndc1-L562S allele, unable to associate with Mps3, is lethal due to SPB duplication defects. Deletion of POM152 fully suppresses the growth and Mps3-binding defect of ndc1-L562S, suggesting Ndc1-Mps3 interaction controls distribution of Ndc1 between NPC and SPB. Fluorescence cross-correlation spectroscopy (FCCS) in live cells, genetic allele analysis, suppressor genetics The Journal of cell biology Medium 24515347
2016 NDC1 forms a complex with SEPTIN12 (SEPT12) in male germ cells. NDC1 overexpression restricts SEPT12 localization to the nucleus and represses SEPT12 filament formation. In sperm with mutated SEPT12, NDC1 disperses from the sperm neck to the manchette region and annulus. SEPT12-NDC1 complexes are required for normal spermiogenesis and sperm morphology. Co-immunoprecipitation, yeast 2-hybrid, immunofluorescence co-localization, overexpression experiments in germ cell lines, mouse knockout/knock-in models International journal of molecular sciences Medium 27854341
2022 In C. elegans, Ndc1 determines NPC density at the reforming nuclear envelope. Loss of ndc1 results in faster turnover of the outer scaffold nucleoporin Nup160 at the NE (measured by FRAP-like photoconversion). NE formation fails in the absence of both Ndc1 and Nup53, indicating partially redundant roles. Upregulation of membrane synthesis restores nuclear growth after ndc1 loss but not after nup53 loss, demonstrating that membrane biogenesis can be decoupled from Ndc1-mediated NPC assembly. 3D-EM tomography, photoconvertible fluorescent protein fusions for nucleoporin turnover, RNAi depletion, genetic double-mutant analysis, membrane synthesis manipulation eLife High 35852146
2023 ARRDC5 affects NDC1 localization during spermatogenesis by influencing SEC22A-mediated vesicle trafficking and transport of NDC1 and SUN5 to the head-tail coupling apparatus. In Arrdc5 knockout mice, sperm show bent-head defects and reduced motility due to failure of proper head-tail attachment. Mouse knockout model, mass spectrometry identification of NDC1 as ARRDC5 interactor, co-localization studies, intracytoplasmic sperm injection rescue Development (Cambridge, England) Low 37997706
2024 NDC1 activates PI3K/AKT signaling in hepatocellular carcinoma cells by interacting with BCAP31. Co-immunoprecipitation and mass spectrometry confirmed the NDC1–BCAP31 interaction. Co-immunoprecipitation, mass spectrometry, overexpression and knockdown in HCC cell lines, mouse xenograft Journal of biochemical and molecular toxicology Low 38348718
2024 Biallelic NDC1 in-frame deletions or missense variants 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, resulting in polyneuropathy and a triple A-like syndrome without adrenal insufficiency. Diagnostic exome/RNA sequencing, skin fibroblast functional assays (ALADIN localization, NPC insertion assay), clinical correlation HGG advances Medium 39003500

Source papers

Stage 0 corpus · 26 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 134 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 34 19782045
2009 The transmembrane nucleoporin NDC1 is required for targeting of ALADIN to nuclear pore complexes. Biochemical and biophysical research communications 28 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
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 15 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 Biallelic NDC1 variants that interfere with ALADIN binding are associated with neuropathy and triple A-like syndrome. HGG advances 3 39003500
2024 NUP155 and NDC1 interaction in NSCLC: a promising target for tumor progression. Frontiers in pharmacology 3 39720592
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

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