{"gene":"SLC35E1","run_date":"2026-04-28T20:42:07","timeline":{"discoveries":[{"year":2022,"finding":"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.","method":"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":"Journal of virology","confidence":"Medium","confidence_rationale":"Tier 2 — clean KO with defined cellular and viral morphogenesis phenotype plus Co-IP/MS interaction data; single lab, moderate evidence","pmids":["35475666"],"is_preprint":false}],"current_model":"SLC35E1 is an orphan transporter that interacts with the HSV-1 nuclear egress complex (NEC/UL34-UL31) and is required for efficient viral de-envelopment at the nuclear membrane; its knockout causes aberrant perinuclear accumulation of enveloped virions and NEC mislocalization, implicating SLC35E1 as a host factor facilitating a late step of HSV-1 nuclear egress."},"narrative":{"teleology":[{"year":2022,"claim":"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","pmids":["35475666"],"confidence":"Medium","gaps":["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"]},{"year":null,"claim":"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.","evidence":"","pmids":[],"confidence":"Low","gaps":["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":{"molecular_activity":[{"term_id":"GO:0005215","term_label":"transporter activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005635","term_label":"nuclear envelope","supporting_discovery_ids":[0]}],"pathway":[],"complexes":[],"partners":["UL34","UL31"],"other_free_text":[]},"mechanistic_narrative":"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]."},"prefetch_data":{"uniprot":{"accession":"Q96K37","full_name":"Solute carrier family 35 member E1","aliases":[],"length_aa":410,"mass_kda":44.8,"function":"Putative transporter","subcellular_location":"Membrane","url":"https://www.uniprot.org/uniprotkb/Q96K37/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SLC35E1","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000127526","cell_line_id":"CID001341","localizations":[{"compartment":"golgi","grade":3}],"interactors":[{"gene":"TM9SF3","stoichiometry":10.0},{"gene":"TMEM165","stoichiometry":4.0},{"gene":"GOSR1","stoichiometry":4.0},{"gene":"GORASP2","stoichiometry":0.2},{"gene":"RAB1A","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID001341","total_profiled":1310},"omim":[{"mim_id":"620337","title":"SOLUTE CARRIER FAMILY 35, MEMBER E1; SLC35E1","url":"https://www.omim.org/entry/620337"},{"mim_id":"608568","title":"MYOSIN, HEAVY CHAIN 14, NONMUSCLE; MYH14","url":"https://www.omim.org/entry/608568"},{"mim_id":"600652","title":"DEAFNESS, AUTOSOMAL DOMINANT 4A; DFNA4A","url":"https://www.omim.org/entry/600652"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Golgi apparatus","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SLC35E1"},"hgnc":{"alias_symbol":["FLJ14251"],"prev_symbol":[]},"alphafold":{"accession":"Q96K37","domains":[{"cath_id":"-","chopping":"29-82_106-250_257-345","consensus_level":"high","plddt":86.8162,"start":29,"end":345}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96K37","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96K37-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96K37-F1-predicted_aligned_error_v6.png","plddt_mean":74.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SLC35E1","jax_strain_url":"https://www.jax.org/strain/search?query=SLC35E1"},"sequence":{"accession":"Q96K37","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96K37.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96K37/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96K37"}},"corpus_meta":[{"pmid":"18166477","id":"PMC_18166477","title":"Microarray-based 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1987)","url":"https://pubmed.ncbi.nlm.nih.gov/33022573","citation_count":37,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"34597346","id":"PMC_34597346","title":"The proximal proteome of 17 SARS-CoV-2 proteins links to disrupted antiviral signaling and host translation.","date":"2021","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/34597346","citation_count":37,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"34672954","id":"PMC_34672954","title":"An antibody-based proximity labeling map reveals mechanisms of SARS-CoV-2 inhibition of antiviral immunity.","date":"2021","source":"Cell chemical biology","url":"https://pubmed.ncbi.nlm.nih.gov/34672954","citation_count":35,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"28710492","id":"PMC_28710492","title":"NEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/28710492","citation_count":33,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4205,"output_tokens":432,"usd":0.009548},"stage2":{"model":"claude-opus-4-6","input_tokens":3578,"output_tokens":646,"usd":0.05106},"total_usd":0.152483,"stage1_batch_id":"msgbatch_011rkcQdVV1RaFq9XhcG6df6","stage2_batch_id":"msgbatch_01RzgrJafdF4EWHhj5mNi6dh","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":17010,"output_tokens":1514,"usd":0.03687},"round2_rules_fired":"R3","round2_stage2":{"model":"claude-opus-4-6","input_tokens":3889,"output_tokens":689,"usd":0.055005}},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2022,\n      \"finding\": \"SLC35E1 is required for efficient HSV-1 de-envelopment during nuclear egress. Knockout of SLC35E1 reduced HSV-1 replication and caused aberrant accumulation of perinuclear enveloped virions (PEVs) in the perinuclear space and membranous invaginations adjacent to the nuclear membrane, along with mislocalization of the nuclear egress complex (NEC). SLC35E1 was identified as a binding partner of the HSV-1 NEC (UL34/UL31) by tandem affinity purification coupled with mass spectrometry.\",\n      \"method\": \"Tandem affinity purification/mass spectrometry interactome screen, CRISPR/Cas9 knockout, fluorescence microscopy, viral replication assay\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal interaction screen plus CRISPR KO with specific ultrastructural and functional phenotypes, moderate evidence from single rigorous study with multiple orthogonal methods\",\n      \"pmids\": [\"35475666\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SLC35E1 is an orphan transporter that interacts with the HSV-1 nuclear egress complex (NEC; UL34/UL31) and is required for efficient de-envelopment of perinuclear enveloped virions during viral nuclear egress; its loss causes aberrant PEV accumulation in the perinuclear space and mislocalization of the NEC, but its endogenous cellular substrate and transport mechanism remain unknown.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\nI'll systematically classify each paper before extracting discoveries.\n\n**Classification:**\n\n**Retrieved Papers:**\n1. PMID:18166477 - Microarray prediction of rectal cancer response; SLC35E1 mentioned only as expression correlation marker → EXCLUDE (pure expression/prognostic, no mechanism)\n2. PMID:31338326 - Exome-wide rare variant analysis for endometrial cancer; SLC35E1 as statistical association → EXCLUDE (GWAS-type association, no mechanism)\n3. PMID:39700903 - SARS-CoV-2 single-cell RNA-seq; SLC35E1 as expression marker → EXCLUDE (expression correlation only)\n4. PMID:35475666 - Role of SLC35E1 in HSV-1 nuclear egress → KEEP (direct mechanistic study)\n5. PMID:34590520 - Papillary thyroid carcinoma prognostic signature; SLC35E1 as expression marker → EXCLUDE (prognostic/expression)\n\n**Gene2pubmed Papers:**\n- PMID:16169070 - Human protein interactome (Y2H); SLC35E1 may appear as interaction partner but no specific mechanism described → EXCLUDE (large-scale screen, no SLC35E1-specific mechanism)\n- PMID:12477932 - MGC cDNA sequencing project → EXCLUDE (no mechanism)\n- PMID:26496610 - Human interactome quantitative dimensions → EXCLUDE (no SLC35E1-specific mechanism)\n- PMID:32296183 - HuRI reference interactome → EXCLUDE (no SLC35E1-specific mechanism)\n- PMID:14702039 - FLJ cDNA collection → EXCLUDE (no mechanism)\n- PMID:33961781 - BioPlex 3.0 interactome → EXCLUDE (no SLC35E1-specific mechanism)\n- PMID:21873635 - Gene Ontology phylogenetic propagation → EXCLUDE\n- PMID:15489334 - MGC project status → EXCLUDE\n- PMID:35271311 - OpenCell protein localization → EXCLUDE (no SLC35E1-specific mechanism extracted)\n- PMID:34079125 - BioID proximity map → EXCLUDE\n- PMID:22810586 - Tumor virus protein interactome → EXCLUDE\n- PMID:27173435 - Ciliary protein landscape → EXCLUDE\n- PMID:30833792 - ISG protein interaction network → EXCLUDE\n- PMID:29117863 - TRIM25 RNA-binding → EXCLUDE (unrelated)\n- PMID:28692057 - CAIX interactome → EXCLUDE\n- PMID:32707033 - Kinase interaction network → EXCLUDE\n- PMID:29180619 - RNF4 STUbL → EXCLUDE\n- PMID:26972000 - PHD3/FIH substrates → EXCLUDE\n- PMID:30194290 - RAS isoform interactomes → EXCLUDE\n- PMID:31073040 - LMBR1L/Wnt signaling → EXCLUDE\n- PMID:32513696 - RIG-I myeloid differentiation → EXCLUDE\n- PMID:36138187 - NUDT21/CD19 → EXCLUDE\n- PMID:16303743 - Signal sequence trap cDNA → EXCLUDE\n- PMID:31091453 - PLEKHA4/Wnt signaling → EXCLUDE\n- PMID:24163370 - NEDL2 ubiquitin ligase → EXCLUDE\n- PMID:36610398 - Tau regulators → EXCLUDE\n- PMID:33022573 - BPA/WDR5/TET2 → EXCLUDE\n- PMID:34597346 - SARS-CoV-2 proximal proteome → EXCLUDE\n- PMID:34672954 - SARS-CoV-2 antibody proximity labeling → EXCLUDE\n- PMID:28710492 - NEK1 kinase domain → EXCLUDE\n\nOnly PMID:35475666 is KEEP.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2022,\n      \"finding\": \"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.\",\n      \"method\": \"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\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with defined cellular and viral morphogenesis phenotype plus Co-IP/MS interaction data; single lab, moderate evidence\",\n      \"pmids\": [\"35475666\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SLC35E1 is an orphan transporter that interacts with the HSV-1 nuclear egress complex (NEC/UL34-UL31) and is required for efficient viral de-envelopment at the nuclear membrane; its knockout causes aberrant perinuclear accumulation of enveloped virions and NEC mislocalization, implicating SLC35E1 as a host factor facilitating a late step of HSV-1 nuclear egress.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"SLC35E1 is an orphan member of the SLC35 nucleotide-sugar transporter family whose endogenous substrate and transport mechanism remain uncharacterized. It physically interacts with the HSV-1 nuclear egress complex (UL34/UL31) and is required for efficient de-envelopment of perinuclear enveloped virions; CRISPR knockout of SLC35E1 reduces HSV-1 replication and causes aberrant accumulation of perinuclear enveloped virions and mislocalization of the NEC [PMID:35475666].\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"The discovery that SLC35E1 binds the HSV-1 nuclear egress complex and is required for viral de-envelopment established the first functional context for this orphan transporter, linking it to membrane remodeling events at the nuclear envelope during herpesvirus egress.\",\n      \"evidence\": \"Tandem affinity purification/mass spectrometry of NEC interactors, CRISPR/Cas9 knockout in human cells, fluorescence microscopy, and viral replication assays\",\n      \"pmids\": [\"35475666\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Endogenous cellular substrate and transport direction are unknown\",\n        \"Whether SLC35E1 contributes to nuclear envelope dynamics in uninfected cells has not been tested\",\n        \"Mechanism by which SLC35E1 promotes de-envelopment (lipid composition change, signaling, or structural role) is unresolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The endogenous transport substrate, cellular function independent of viral infection, and structural basis for NEC interaction remain to be determined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No reconstituted transport assay has been performed\",\n        \"No structure or homology model explaining substrate selectivity\",\n        \"Role in uninfected cell physiology entirely unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005215\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"UL34\", \"UL31\"],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"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].\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"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.\",\n      \"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\",\n      \"pmids\": [\"35475666\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab study; independent replication of the KO phenotype has not been reported\",\n        \"Endogenous transport substrate of SLC35E1 is unknown, so the mechanistic basis of its contribution to de-envelopment is unclear\",\n        \"Whether SLC35E1 has a physiological role in nuclear envelope dynamics or membrane remodeling independent of viral infection has not been tested\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"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.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No substrate has been identified for SLC35E1 in any in vitro or in vivo transport assay\",\n        \"No structural or biochemical reconstitution data exist\",\n        \"Role in non-viral cellular processes is entirely unexplored in the primary literature\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005215\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"UL34\", \"UL31\"],\n    \"other_free_text\": []\n  }\n}\n```"}