Affinage

SLC35E1

Solute carrier family 35 member E1 · UniProt Q96K37

Round 2 corrected
Length
410 aa
Mass
44.8 kDa
Annotated
2026-04-28
35 papers in source corpus 1 papers cited in narrative 1 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC35E1 is an orphan member of the SLC35 solute carrier family whose endogenous transport substrate remains unidentified. It physically interacts with the HSV-1 nuclear egress complex (UL34–UL31), and CRISPR/Cas9 knockout of SLC35E1 impairs HSV-1 replication by causing aberrant accumulation of perinuclear enveloped virions and NEC mislocalization, consistent with a role in the de-envelopment step of herpesvirus nuclear egress (PMID:35475666).

Mechanistic history

Synthesis pass · year-by-year structured walk · 1 step
  1. 2022 Medium

    Identification of SLC35E1 as a host factor required for HSV-1 nuclear egress resolved how the viral nuclear egress complex (NEC) engages cellular machinery for de-envelopment at the nuclear membrane.

    Evidence Tandem affinity purification–mass spectrometry of the NEC interactome followed by CRISPR/Cas9 KO with electron microscopy and fluorescence imaging of viral morphogenesis in human cells

    PMID:35475666

    Open questions at the time
    • Single-lab study; independent replication of the KO phenotype has not been reported
    • Endogenous transport substrate of SLC35E1 is unknown, so the mechanistic basis of its contribution to de-envelopment is unclear
    • Whether SLC35E1 has a physiological role in nuclear envelope dynamics or membrane remodeling independent of viral infection has not been tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The native cellular function and transport substrate of SLC35E1 remain uncharacterized, leaving open whether its role in HSV-1 egress reflects a hijacked homeostatic membrane or lipid transport activity.
  • No substrate has been identified for SLC35E1 in any in vitro or in vivo transport assay
  • No structural or biochemical reconstitution data exist
  • Role in non-viral cellular processes is entirely unexplored in the primary literature

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 1
Localization
GO:0005635 nuclear envelope 1
Partners
UL31UL34

Evidence

Reading pass · 1 per-paper finding extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2022 SLC35E1, an orphan transporter, was identified as a cellular protein required for efficient HSV-1 de-envelopment during nuclear egress. SLC35E1 physically interacted with the HSV-1 nuclear egress complex (NEC) composed of UL34 and UL31, as identified by tandem affinity purification coupled with mass spectrometry. CRISPR/Cas9 knockout of SLC35E1 reduced HSV-1 replication, caused aberrant accumulation of perinuclear enveloped virions (PEVs) in the perinuclear space, induced membranous invaginations adjacent to the nuclear membrane containing PEVs, and caused mislocalization of the NEC—phenotypes consistent with a defect in the de-envelopment step of HSV-1 nuclear egress. Tandem affinity purification coupled with mass spectrometry (interactome screening), followed by CRISPR/Cas9 knockout with fluorescence microscopy readout of emerin mislocalization and electron microscopy of viral morphogenesis Journal of virology Medium 35475666

Source papers

Stage 0 corpus · 35 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2012 Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins. Nature 319 22810586
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
2019 A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape. Nature immunology 159 30833792
2017 RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination. BMC biology 135 29117863
2008 Microarray-based prediction of tumor response to neoadjuvant radiochemotherapy of patients with locally advanced rectal cancer. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 99 18166477
2017 The interactome of metabolic enzyme carbonic anhydrase IX reveals novel roles in tumor cell migration and invadopodia/MMP14-mediated invasion. Oncogene 96 28692057
2020 Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases. Molecular cell 88 32707033
2017 The STUbL RNF4 regulates protein group SUMOylation by targeting the SUMO conjugation machinery. Nature communications 86 29180619
2016 Substrate-Trapped Interactors of PHD3 and FIH Cluster in Distinct Signaling Pathways. Cell reports 77 26972000
2018 Interrogating the protein interactomes of RAS isoforms identifies PIP5K1A as a KRAS-specific vulnerability. Nature communications 73 30194290
2020 RIG-I regulates myeloid differentiation by promoting TRIM25-mediated ISGylation. Proceedings of the National Academy of Sciences of the United States of America 47 32513696
2019 LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling. Science (New York, N.Y.) 47 31073040
2022 NUDT21 limits CD19 levels through alternative mRNA polyadenylation in B cell acute lymphoblastic leukemia. Nature immunology 46 36138187
2005 Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries. DNA research : an international journal for rapid publication of reports on genes and genomes 43 16303743
2019 PLEKHA4/kramer Attenuates Dishevelled Ubiquitination to Modulate Wnt and Planar Cell Polarity Signaling. Cell reports 42 31091453
2013 The HECT type ubiquitin ligase NEDL2 is degraded by anaphase-promoting complex/cyclosome (APC/C)-Cdh1, and its tight regulation maintains the metaphase to anaphase transition. The Journal of biological chemistry 40 24163370
2023 Evolutionarily conserved regulators of tau identify targets for new therapies. Neuron 39 36610398
2021 The proximal proteome of 17 SARS-CoV-2 proteins links to disrupted antiviral signaling and host translation. PLoS pathogens 37 34597346
2020 BPA modulates the WDR5/TET2 complex to regulate ERβ expression in eutopic endometrium and drives the development of endometriosis. Environmental pollution (Barking, Essex : 1987) 37 33022573
2021 An antibody-based proximity labeling map reveals mechanisms of SARS-CoV-2 inhibition of antiviral immunity. Cell chemical biology 35 34672954
2017 NEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin. Scientific reports 33 28710492
2019 Exome-Wide Rare Variant Analysis From the DiscovEHR Study Identifies Novel Candidate Predisposition Genes for Endometrial Cancer. Frontiers in oncology 18 31338326
2024 Recognizing SARS-CoV-2 infection of nasopharyngeal tissue at the single-cell level by machine learning method. Molecular immunology 12 39700903
2022 Role of the Orphan Transporter SLC35E1 in the Nuclear Egress of Herpes Simplex Virus 1. Journal of virology 5 35475666
2021 Identification of a Signature Comprising 5 Soluble Carrier Family Genes to Predict the Recurrence of Papillary Thyroid Carcinoma. Technology in cancer research & treatment 5 34590520