K9IWR0

UniProt ID: K9IWR0
Organism: Desmodus rotundus
Review Status: INITIALIZED
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Gene Description

TODO: Add description for K9IWR0

Existing Annotations Review

GO Term Evidence Action Reason
GO:0007165 signal transduction
IEA
GO_REF:0000108 		MARK AS OVER ANNOTATED
Summary: Signal transduction is a broad inference without direct evidence for this DESRO cytokine.
Reason: Annotation is generic and not directly supported in DESRO; core function is cytokine activity.
GO:0043123 positive regulation of canonical NF-kappaB signal transduction
IEA
GO_REF:0000118 		MARK AS OVER ANNOTATED
Summary: Positive regulation of canonical NF-kappaB signaling is a downstream effect inferred from orthology.
Reason: Specific pathway regulation is not directly evidenced for this DESRO protein.
GO:2001238 positive regulation of extrinsic apoptotic signaling pathway
IEA
GO_REF:0000118 		MARK AS OVER ANNOTATED
Summary: Positive regulation of extrinsic apoptotic signaling pathway is a downstream inference without direct evidence in DESRO.
Reason: Specific apoptotic pathway regulation is not directly evidenced for this protein.
GO:0005125 cytokine activity
IEA
GO_REF:0000120 		ACCEPT
Summary: UniProt describes this protein as a cytokine that binds TNF receptors.
Reason: UniProt functional description supports cytokine activity.
Supporting Evidence:
file:DESRO/K9IWR0/K9IWR0-uniprot.txt
"Cytokine that in its homotrimeric form binds to TNFRSF1A/TNFR1"
GO:0005164 tumor necrosis factor receptor binding
IEA
GO_REF:0000120 		ACCEPT
Summary: UniProt functional description indicates TNF receptor binding.
Reason: Functional description notes binding to TNF receptors.
Supporting Evidence:
file:DESRO/K9IWR0/K9IWR0-uniprot.txt
"Cytokine that in its homotrimeric form binds to TNFRSF1A/TNFR1"
GO:0005576 extracellular region
IEA
GO_REF:0000044 		MODIFY
Summary: Extracellular region is a broad parent term; extracellular space is more specific for a secreted cytokine.
Reason: UniProt indicates secretion; use extracellular space for specificity.
Proposed replacements: extracellular space
Supporting Evidence:
file:DESRO/K9IWR0/K9IWR0-uniprot.txt
"SUBCELLULAR LOCATION: Secreted"
GO:0005615 extracellular space
IEA
GO_REF:0000120 		ACCEPT
Summary: UniProt annotates this protein as secreted.
Reason: Secreted localization is supported in UniProt.
Supporting Evidence:
file:DESRO/K9IWR0/K9IWR0-uniprot.txt
"SUBCELLULAR LOCATION: Secreted"
GO:0006955 immune response
IEA
GO_REF:0000002 		MARK AS OVER ANNOTATED
Summary: Immune response is a broad inference without direct evidence in DESRO.
Reason: General immune response annotation is inferred and not directly supported.
GO:0006959 humoral immune response
IEA
GO_REF:0000104 		MARK AS OVER ANNOTATED
Summary: Humoral immune response is a specific process inferred from orthology without direct DESRO evidence.
Reason: Specific humoral response evidence is lacking for this DESRO protein.
GO:0016020 membrane
IEA
GO_REF:0000120 		ACCEPT
Summary: UniProt indicates membrane localization in addition to secretion.
Reason: Subcellular location includes membrane.
Supporting Evidence:
file:DESRO/K9IWR0/K9IWR0-uniprot.txt
"Membrane"

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000104
Electronic Gene Ontology annotations created by transferring manual GO annotations between related proteins based on shared sequence features
GO_REF:0000108
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
GO_REF:0000118
TreeGrafter-generated GO annotations
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods

Deep Research

Falcon

(K9IWR0-deep-research-falcon.md)
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 27 citations 2026-01-21T11:39:07.018320

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Plan (current status)
- Objective 1 (verify identity): Completed. K9IWR0 is a UniProt accession for lymphotoxin-alpha (LT-α; TNF-β; TNFSF1) from Desmodus rotundus with TNF superfamily domains. No conflicting usage was found. We proceed by inferring function from conserved mammalian LT biology (see Verification below).
- Objectives 2–6 (evidence gathering and synthesis): Completed via targeted literature review prioritizing 2023–2024 sources; quantitative disease associations were extracted where available.
- Objective 7: Submit final answer (this document).

Verification (mandatory steps)
- Identity match: K9IWR0 corresponds to LT-α/TNF-β in Desmodus rotundus per the provided UniProt entry, which places it in the TNF ligand superfamily with canonical TNF domains. No alternative gene/protein with the same accession was identified.
- Organism: Desmodus rotundus (common vampire bat) per the supplied UniProt record.
- Protein family and domains: Tumor necrosis factor (TNF) family domains, consistent with TNFSF1 (LTA) annotations; this aligns with literature describing LT-α/TNF-β biology in mammals (citations below). If bat-specific functional studies are missing, inference is grounded in conserved TNF superfamily features.

Key concepts and definitions (current understanding)
- Ligand identity and forms: Lymphotoxin-alpha (LT-α; TNF-β) is a TNF-superfamily cytokine that exists as a soluble homotrimer (LTα3) and as a membrane-anchored heterotrimer when complexed with LT-β (LTα1β2). LTα3 binds TNFR1 and TNFR2; the membrane LTα1β2 complex signals via LTβR (TNFRSF3) and drives non-canonical NF-κB (alternative) signaling via NIK/IKKα-mediated processing of p100 to p52/RelB (human/mechanistic literature) (Aug 2024, Diabetologia; URL: https://doi.org/10.1007/s00125-024-06241-1) (haukka2024wholeexomeandwholegenome pages 9-10). Non-canonical NF-κB induction and p100→p52 processing in the context of LT pathways are also highlighted in recent mechanistic work (May 2024, Frontiers in Immunology; URL: https://doi.org/10.3389/fimmu.2024.1388496) and an in vitro H. pylori study reporting non-canonical activation (2025; details below) (chen2024ltβrrelbsignalingin pages 16-17, chen2024ltβrrelbsignalingin pages 17-17, gil2025theroleof pages 49-52).
- Receptors and signaling: LTα3→TNFR1/2 predominantly activates canonical NF-κB; LTα1β2→LTβR predominantly activates non-canonical NF-κB through NIK/IKKα and p100 processing to p52/RelB. LTβR-dependent RelB activity is functionally protective in intestinal epithelial repair (May 2024, Frontiers in Immunology; URL: https://doi.org/10.3389/fimmu.2024.1388496) (chen2024ltβrrelbsignalingin pages 16-17, chen2024ltβrrelbsignalingin pages 17-17).
- Cellular sources: LT can be produced by activated T helper (Th1/Th17) cells and certain B-cell subsets; functional roles (e.g., autoimmune models and B-reg cell mechanisms) have been linked to LTα expression in human-focused reviews (Mar 2024, Frontiers in Immunology; URL: https://doi.org/10.3389/fimmu.2024.1289492) (wang2024functionalsignificanceof pages 13-14). In the intestine, T cells can provide the cognate ligand LIGHT (TNFSF14) that signals via LTβR in epithelial cells in damage settings, underscoring the broader TNF-family crosstalk in LTβR signaling (May 2024, Frontiers in Immunology; URL: https://doi.org/10.3389/fimmu.2024.1388496) (chen2024ltβrrelbsignalingin pages 16-17).
- Biological roles: LTβR signaling is essential for secondary lymphoid organogenesis and adult maintenance/homeostasis of lymphoid tissues; it also shapes mucosal immunity, including epithelial programs and goblet-cell differentiation via LT–LTβR pathways (May 2024, Frontiers in Immunology; URL: https://doi.org/10.3389/fimmu.2024.1388496) (chen2024ltβrrelbsignalingin pages 17-17).

Recent developments and latest research (prioritized 2023–2024)
- Epithelial protection and mucosal repair via LTβR–RelB: Intestinal epithelial cell-intrinsic LTβR–RelB signaling limited mucosal damage after methotrexate, with LTβR deficiency causing severe pathology. LIGHT (not LTαβ) was upregulated early and required T cells; IL‑22 and epithelial proliferation were reduced in LTβR-deficient settings, indicating coordinated LTβR/IL‑22 axes for repair (May 2024, Frontiers in Immunology; URL: https://doi.org/10.3389/fimmu.2024.1388496) (chen2024ltβrrelbsignalingin pages 16-17).
- Lymphoid organ development and mucosal immunity: Compiled evidence in 2024 emphasizes that membrane LTαβ–LTβR interactions are essential for secondary lymphoid tissue development/maintenance and regulate mucosal immune programs (goblet cell pathways; ILC3 interactions), reinforcing LT’s role beyond inflammation toward tissue organization (May 2024, Frontiers in Immunology; URL: https://doi.org/10.3389/fimmu.2024.1388496) (chen2024ltβrrelbsignalingin pages 17-17).
- Non-canonical NF-κB activation in infection/inflammation contexts: An in vitro H. pylori study observed p100→p52 processing consistent with non-canonical NF-κB activation, supporting relevance of LTβR-like signaling axes in gastric inflammation and potential carcinogenesis; the authors propose non-canonical NF-κB as a therapeutic target (2025 preclinical; journal unspecified) (gil2025theroleof pages 49-52).
- TNF superfamily in tissue remodeling and fibrosis: 2023 review catalogs translation of TNF-family targeting agents, including LTβR-directed modalities (e.g., baminercept/LTβR‑Ig), in fibrotic/inflammatory pathologies and summarizes clinical evaluation language (Jul 2023, Frontiers in Immunology; URL: https://doi.org/10.3389/fimmu.2023.1219907) (steele2023tnfsuperfamilycontrol pages 14-14).

Current applications and implementations
- LTβR pathway modulators: Clinical/translational literature collated in 2023 highlights LTβR-directed biologics, notably the LTβR-Ig fusion protein baminercept, as agents evaluated for immune/inflammatory conditions and tissue remodeling contexts. The review’s therapeutic summary indicates repurposing and safety/bioavailability assessments for TNF-superfamily targeting in fibrotic disease settings (Jul 2023, Frontiers in Immunology; URL: https://doi.org/10.3389/fimmu.2023.1219907) (steele2023tnfsuperfamilycontrol pages 14-14).
- Intestinal injury repair implications: The 2024 epithelial LTβR–RelB work suggests that enhancing LTβR signaling, or upstream T-cell-derived LIGHT, may support mucosal repair after chemotherapy—a plausible translational avenue to mitigate mucositis or accelerate recovery (May 2024, Frontiers in Immunology; URL: https://doi.org/10.3389/fimmu.2024.1388496) (chen2024ltβrrelbsignalingin pages 16-17).

Expert opinions and mechanistic analysis from authoritative sources
- Mechanistic consensus: Recent immunology sources converge on a model where membrane LTα1β2–LTβR drives non-canonical NF‑κB via NIK/IKKα/p100→p52/RelB, thereby organizing lymphoid structures and regulating epithelial and stromal programs; LTα3–TNFR1/2 activates canonical NF‑κB, eliciting inflammatory gene expression. The protective epithelial roles of LTβR–RelB (2024) provide causal evidence in vivo for tissue repair programs after cytotoxic injury (May 2024, Frontiers in Immunology; URL: https://doi.org/10.3389/fimmu.2024.1388496) (chen2024ltβrrelbsignalingin pages 16-17).
- Disease mechanism framing: Reviews and targeted studies link LT signaling to lymphoid neogenesis and autoimmune pathophysiology, including contributions from Th1/Th17-derived LTα and B-cell LT-dependent mechanisms, underscoring a dual face of LT in protective organization vs chronic inflammatory pathology (Mar 2024, Frontiers in Immunology; URL: https://doi.org/10.3389/fimmu.2024.1289492) (wang2024functionalsignificanceof pages 13-14).

Statistics and data from recent studies (2023–2024)
- Smoking, epigenetics, and IBD at the LTA/TNF locus: A Jan 2024 Nature Communications study integrating cohort, Mendelian randomization, and methylation analyses reported smoking-related methylation at cg03599224 (LTA/TNF locus) associated with Crohn’s disease risk (P = 1.91 × 10−6); current and previous smoking habits were associated with increased CD (P = 7.09 × 10−10) and UC risk (P < 2 × 10−16), respectively (Jan 2024, Nature Communications; URL: https://doi.org/10.1038/s41467-024-44841-y) (zhang2024altereddnamethylation pages 1-2, zhang2024altereddnamethylation pages 12-13).
- Diabetic kidney disease (DKD) genetics implicating LTA: In 1,064 individuals with type 1 diabetes, LTA variant rs2229092 associated with DKD (OR 0.39, p = 1.47 × 10−4) and replicated in FinnGen (p = 0.0044); the protective C allele associated with lower serum TNFR1/2/3 levels, suggesting attenuated TNF-family signaling (Aug 2024, Diabetologia; URL: https://doi.org/10.1007/s00125-024-06241-1) (haukka2024wholeexomeandwholegenome pages 9-10).
- Ophthalmic inflammation biomarker: Tear LT‑α levels were significantly lower in active vs inactive pterygium (P < 0.001) in a cohort of 172 patients (2021–2023); an optimal diagnostic threshold ≤ 0.49 dg/ml was proposed in a nomogram model (Jan 2024, Scientific Reports; URL: https://doi.org/10.1038/s41598-024-52382-z) (lan2024evaluationoflymphotoxinalpha pages 1-2).
- Hepatocellular carcinoma risk variant: LTA rs1041981 (p.Thr60Asn) associated with HCC in Egyptians (AA vs CC OR 2.9 [1.49–5.49], p = 0.002; dominant model OR 1.8 [1.15–2.97], p = 0.01; recessive model OR 2.3 [1.29–4.23], p = 0.007; A allele vs C allele OR 3.2 [2.22–4.65], p < 0.001) (Mar 2023, Molecular Biology Reports; URL: https://doi.org/10.1007/s11033-023-08281-z) (alhelf2023prognosticsignificanceof pages 6-7, alhelf2023prognosticsignificanceof pages 7-8).

Functional annotation for K9IWR0 (Desmodus rotundus LT-α/TNF-β)
- Primary function: As a TNF-family ligand, LT-α functions either as a soluble homotrimer (LTα3) that activates TNFR1/TNFR2 to induce canonical NF‑κB–dependent inflammatory programs, or as part of membrane LTα1β2 complexes that signal through LTβR to induce non-canonical NF‑κB via NIK/IKKα/p100→p52/RelB, with key roles in lymphoid tissue organization, epithelial protection and repair, and mucosal immune regulation (Aug 2024, Diabetologia; May 2024, Frontiers in Immunology) (haukka2024wholeexomeandwholegenome pages 9-10, chen2024ltβrrelbsignalingin pages 16-17, chen2024ltβrrelbsignalingin pages 17-17).
- Localization and processing: LT‑α is synthesized with a signal peptide for secretion as LTα3; when co-expressed with LT‑β, the complex is retained at the plasma membrane (LTα1β2) for LTβR engagement (human literature confirms these forms and receptor specificities; Aug 2024, Diabetologia) (haukka2024wholeexomeandwholegenome pages 9-10).
- Pathways: LTα3→TNFR1/2 (canonical NF‑κB); LTα1β2→LTβR (non-canonical NF‑κB through NIK–IKKα–p100 processing) (May 2024, Frontiers in Immunology; 2025 H. pylori in vitro shows p100→p52 activation consistent with alternative NF‑κB) (chen2024ltβrrelbsignalingin pages 16-17, chen2024ltβrrelbsignalingin pages 17-17, gil2025theroleof pages 49-52).
- Biological processes: Required for secondary lymphoid organogenesis/maintenance and mucosal immune programs (goblet cell differentiation, epithelial IL‑23/IL‑22 axes), and contributes to lymphoid neogenesis in chronic inflammation; dysregulation is linked to inflammatory and autoimmune disease mechanisms (Mar 2024, Frontiers in Immunology; May 2024, Frontiers in Immunology) (wang2024functionalsignificanceof pages 13-14, chen2024ltβrrelbsignalingin pages 17-17, chen2024ltβrrelbsignalingin pages 16-17).

Clinical and translational implications
- LTβR-Ig (baminercept) and related modalities represent tangible translational strategies targeting LT pathways; 2023 review coverage notes clinical evaluation and repurposing within TNF-superfamily therapeutics, including fibrotic disease angles (Jul 2023, Frontiers in Immunology; URL: https://doi.org/10.3389/fimmu.2023.1219907) (steele2023tnfsuperfamilycontrol pages 14-14).
- Epithelial repair signaling suggests therapeutic opportunities to modulate LTβR–RelB or its upstream ligands (e.g., LIGHT) to protect against chemotherapy-induced mucositis (May 2024, Frontiers in Immunology; URL: https://doi.org/10.3389/fimmu.2024.1388496) (chen2024ltβrrelbsignalingin pages 16-17).

Bat-specific notes and limitations
- Gene symbol ambiguity: “K9IWR0” is a UniProt accession, not a conventional gene symbol. Species-specific literature directly characterizing Desmodus rotundus LTA was not identified in the 2023–2024 window above. Therefore, functional annotation for K9IWR0 is inferred from conserved TNF-superfamily domain architecture and extensive mammalian LTα/LTβR biology. This is appropriate because LT-ligand and receptor domain constraints, signaling logic (TNFR1/2 vs LTβR), and downstream NF‑κB modules are highly conserved across mammals (evidence cited above for mechanism and function in human/mouse contexts) (haukka2024wholeexomeandwholegenome pages 9-10, chen2024ltβrrelbsignalingin pages 16-17, chen2024ltβrrelbsignalingin pages 17-17).

References (URLs and publication dates)
- Chen QX et al. LTβR–RelB signaling in intestinal epithelial cells protects from chemotherapy-induced mucosal damage. Frontiers in Immunology. May 2024. URL: https://doi.org/10.3389/fimmu.2024.1388496 (chen2024ltβrrelbsignalingin pages 16-17, chen2024ltβrrelbsignalingin pages 17-17)
- Zhang H et al. Altered DNA methylation within DNMT3A, AHRR, LTA/TNF loci mediates the effect of smoking on inflammatory bowel disease. Nature Communications. Jan 2024. URL: https://doi.org/10.1038/s41467-024-44841-y (zhang2024altereddnamethylation pages 1-2, zhang2024altereddnamethylation pages 12-13)
- Haukka JK et al. Whole-exome and whole-genome sequencing of 1064 individuals with type 1 diabetes reveals novel genes for diabetic kidney disease. Diabetologia. Aug 2024. URL: https://doi.org/10.1007/s00125-024-06241-1 (haukka2024wholeexomeandwholegenome pages 9-10)
- Lan G et al. Evaluation of lymphotoxin‑alpha in pterygium and diagnostic value in active and inactive pterygium states. Scientific Reports. Jan 2024. URL: https://doi.org/10.1038/s41598-024-52382-z (lan2024evaluationoflymphotoxinalpha pages 1-2)
- Alhelf M et al. Prognostic significance of the genetic variant of lymphotoxin alpha (p.Thr60Asn) in Egyptian patients with advanced hepatocellular carcinoma. Molecular Biology Reports. Mar 2023. URL: https://doi.org/10.1007/s11033-023-08281-z (alhelf2023prognosticsignificanceof pages 6-7, alhelf2023prognosticsignificanceof pages 7-8)
- Steele H et al. TNF superfamily control of tissue remodeling and fibrosis. Frontiers in Immunology. Jul 2023. URL: https://doi.org/10.3389/fimmu.2023.1219907 (steele2023tnfsuperfamilycontrol pages 14-14)
- Loew Gil E. The role of lymphotoxin in Helicobacter pylori in vitro infection. 2025 (journal unspecified). Mechanistic observations on alternative NF‑κB activation (p100→p52) in vitro. (gil2025theroleof pages 49-52)

Conclusion
The Desmodus rotundus LTA protein (K9IWR0) is best functionally annotated as a conserved TNF-superfamily ligand functioning in two principal modes: (1) soluble LTα3 signaling via TNFR1/TNFR2 to induce canonical inflammatory programs; and (2) membrane LTα1β2 signaling via LTβR to drive non-canonical NF‑κB (NIK/IKKα/p100→p52/RelB), essential for lymphoid organogenesis/maintenance and for epithelial–mucosal immune crosstalk. Recent 2023–2024 studies strengthen evidence for LTβR–RelB’s protective epithelial role in mucosal repair, implicate the LTA/TNF locus in smoking-mediated IBD risk via DNA methylation, and associate LTA genetic variation with DKD and HCC risk in humans. Translationally, LTβR-Ig (baminercept) and related TNF-family modulators remain active areas for therapeutic exploration in inflammatory and fibrotic contexts. While bat-specific experimental data are limited, these conclusions are well supported by conserved domain architecture and mammalian LT pathway biology (chen2024ltβrrelbsignalingin pages 16-17, chen2024ltβrrelbsignalingin pages 17-17, zhang2024altereddnamethylation pages 1-2, haukka2024wholeexomeandwholegenome pages 9-10, lan2024evaluationoflymphotoxinalpha pages 1-2, alhelf2023prognosticsignificanceof pages 6-7, alhelf2023prognosticsignificanceof pages 7-8, zhang2024altereddnamethylation pages 12-13, steele2023tnfsuperfamilycontrol pages 14-14, gil2025theroleof pages 49-52).

References

  1. (haukka2024wholeexomeandwholegenome pages 9-10): Jani K. Haukka, Anni A. Antikainen, Erkka Valo, Anna Syreeni, Emma H. Dahlström, Bridget M. Lin, Nora Franceschini, Andrzej S. Krolewski, Valma Harjutsalo, Per-Henrik Groop, and Niina Sandholm. Whole-exome and whole-genome sequencing of 1064 individuals with type 1 diabetes reveals novel genes for diabetic kidney disease. Diabetologia, 67:2494-2506, Aug 2024. URL: https://doi.org/10.1007/s00125-024-06241-1, doi:10.1007/s00125-024-06241-1. This article has 7 citations and is from a highest quality peer-reviewed journal.

  2. (chen2024ltβrrelbsignalingin pages 16-17): Qiangxing Chen, Amanda R. Muñoz, Anna A. Korchagina, Yajun Shou, Jensine Vallecer, Austin W. Todd, Sergey A. Shein, Alexei V. Tumanov, and Ekaterina Koroleva. Ltβr-relb signaling in intestinal epithelial cells protects from chemotherapy-induced mucosal damage. Frontiers in Immunology, May 2024. URL: https://doi.org/10.3389/fimmu.2024.1388496, doi:10.3389/fimmu.2024.1388496. This article has 2 citations and is from a peer-reviewed journal.

  3. (chen2024ltβrrelbsignalingin pages 17-17): Qiangxing Chen, Amanda R. Muñoz, Anna A. Korchagina, Yajun Shou, Jensine Vallecer, Austin W. Todd, Sergey A. Shein, Alexei V. Tumanov, and Ekaterina Koroleva. Ltβr-relb signaling in intestinal epithelial cells protects from chemotherapy-induced mucosal damage. Frontiers in Immunology, May 2024. URL: https://doi.org/10.3389/fimmu.2024.1388496, doi:10.3389/fimmu.2024.1388496. This article has 2 citations and is from a peer-reviewed journal.

  4. (gil2025theroleof pages 49-52): E Loew Gil. The role of lymphotoxin in helicobacter pylori in vitro infection. Unknown journal, 2025.

  5. (wang2024functionalsignificanceof pages 13-14): Yanqing Wang, Farooq Riaz, Wei Wang, Jincheng Pu, Yuanyuan Liang, Zhenzhen Wu, Shengnan Pan, Jiamin Song, Lufei Yang, Youwei Zhang, Huihong Wu, Fang Han, Jianping Tang, and Xuan Wang. Functional significance of dna methylation: epigenetic insights into sjögren’s syndrome. Frontiers in Immunology, Mar 2024. URL: https://doi.org/10.3389/fimmu.2024.1289492, doi:10.3389/fimmu.2024.1289492. This article has 11 citations and is from a peer-reviewed journal.

  6. (steele2023tnfsuperfamilycontrol pages 14-14): Hope Steele, Jason Cheng, Ashley Willicut, Garrison Dell, Joey Breckenridge, Erica Culberson, Andrew Ghastine, Virginie Tardif, and Rana Herro. Tnf superfamily control of tissue remodeling and fibrosis. Frontiers in Immunology, Jul 2023. URL: https://doi.org/10.3389/fimmu.2023.1219907, doi:10.3389/fimmu.2023.1219907. This article has 71 citations and is from a peer-reviewed journal.

  7. (zhang2024altereddnamethylation pages 1-2): Han Zhang, Rahul Kalla, Jie Chen, Jianhui Zhao, Xuan Zhou, Alex Adams, Alexandra Noble, Nicholas T. Ventham, Judith Wellens, Gwo-Tzer Ho, Malcolm G. Dunlop, Jan Krzysztof Nowak, Yuan Ding, Zhanju Liu, Jack Satsangi, Evropi Theodoratou, and Xue Li. Altered dna methylation within dnmt3a, ahrr, lta/tnf loci mediates the effect of smoking on inflammatory bowel disease. Nature Communications, Jan 2024. URL: https://doi.org/10.1038/s41467-024-44841-y, doi:10.1038/s41467-024-44841-y. This article has 32 citations and is from a highest quality peer-reviewed journal.

  8. (zhang2024altereddnamethylation pages 12-13): Han Zhang, Rahul Kalla, Jie Chen, Jianhui Zhao, Xuan Zhou, Alex Adams, Alexandra Noble, Nicholas T. Ventham, Judith Wellens, Gwo-Tzer Ho, Malcolm G. Dunlop, Jan Krzysztof Nowak, Yuan Ding, Zhanju Liu, Jack Satsangi, Evropi Theodoratou, and Xue Li. Altered dna methylation within dnmt3a, ahrr, lta/tnf loci mediates the effect of smoking on inflammatory bowel disease. Nature Communications, Jan 2024. URL: https://doi.org/10.1038/s41467-024-44841-y, doi:10.1038/s41467-024-44841-y. This article has 32 citations and is from a highest quality peer-reviewed journal.

  9. (lan2024evaluationoflymphotoxinalpha pages 1-2): Guoli Lan, Xie Fang, Yanlin Zhong, Shunrong Luo, Xianwen Xiao, Zhiwen Xie, Lianghuan Luo, Yiqiu Zhang, Hanqiao Li, Yuan Lin, and Huping Wu. Evaluation of lymphotoxin-alpha in pterygium and diagnostic value in active and inactive pterygium states. Scientific Reports, Jan 2024. URL: https://doi.org/10.1038/s41598-024-52382-z, doi:10.1038/s41598-024-52382-z. This article has 5 citations and is from a peer-reviewed journal.

  10. (alhelf2023prognosticsignificanceof pages 6-7): Maha Alhelf, Rasha M. S. Shoaib, Afaf Elsaid, Nermeen Bastawy, Nanis S. Elbeltagy, Eman T. Salem, Sherif Refaat, and Eman H. Abuelnadar. Prognostic significance of the genetic variant of lymphotoxin alpha (p.thr60asn) in egyptian patients with advanced hepatocellular carcinoma. Molecular Biology Reports, 50:4317-4327, Mar 2023. URL: https://doi.org/10.1007/s11033-023-08281-z, doi:10.1007/s11033-023-08281-z. This article has 2 citations and is from a peer-reviewed journal.

  11. (alhelf2023prognosticsignificanceof pages 7-8): Maha Alhelf, Rasha M. S. Shoaib, Afaf Elsaid, Nermeen Bastawy, Nanis S. Elbeltagy, Eman T. Salem, Sherif Refaat, and Eman H. Abuelnadar. Prognostic significance of the genetic variant of lymphotoxin alpha (p.thr60asn) in egyptian patients with advanced hepatocellular carcinoma. Molecular Biology Reports, 50:4317-4327, Mar 2023. URL: https://doi.org/10.1007/s11033-023-08281-z, doi:10.1007/s11033-023-08281-z. This article has 2 citations and is from a peer-reviewed journal.

Citations

  1. haukka2024wholeexomeandwholegenome pages 9-10
  2. wang2024functionalsignificanceof pages 13-14
  3. gil2025theroleof pages 49-52
  4. steele2023tnfsuperfamilycontrol pages 14-14
  5. lan2024evaluationoflymphotoxinalpha pages 1-2
  6. zhang2024altereddnamethylation pages 1-2
  7. zhang2024altereddnamethylation pages 12-13
  8. alhelf2023prognosticsignificanceof pages 6-7
  9. alhelf2023prognosticsignificanceof pages 7-8
  10. 1.49–5.49
  11. 1.15–2.97
  12. 1.29–4.23
  13. 2.22–4.65
  14. https://doi.org/10.1007/s00125-024-06241-1
  15. https://doi.org/10.3389/fimmu.2024.1388496
  16. https://doi.org/10.3389/fimmu.2024.1289492
  17. https://doi.org/10.3389/fimmu.2023.1219907
  18. https://doi.org/10.1038/s41467-024-44841-y
  19. https://doi.org/10.1038/s41598-024-52382-z
  20. https://doi.org/10.1007/s11033-023-08281-z
  21. https://doi.org/10.1007/s00125-024-06241-1,
  22. https://doi.org/10.3389/fimmu.2024.1388496,
  23. https://doi.org/10.3389/fimmu.2024.1289492,
  24. https://doi.org/10.3389/fimmu.2023.1219907,
  25. https://doi.org/10.1038/s41467-024-44841-y,
  26. https://doi.org/10.1038/s41598-024-52382-z,
  27. https://doi.org/10.1007/s11033-023-08281-z,

📚 Additional Documentation

Notes

(K9IWR0-notes.md)

K9IWR0 Research Notes

Key findings

  • UniProt names this protein lymphotoxin-alpha [file:DESRO/K9IWR0/K9IWR0-uniprot.txt "RecName: Full=Lymphotoxin-alpha"].
  • UniProt indicates the protein is secreted [file:DESRO/K9IWR0/K9IWR0-uniprot.txt "SUBCELLULAR LOCATION: Secreted"].
  • Deep research confirms the identity as lymphotoxin-alpha [file:DESRO/K9IWR0/K9IWR0-deep-research-falcon.md "K9IWR0 is a UniProt accession for lymphotoxin-alpha"]
  • UniProt places this protein in the tumor necrosis factor family [file:DESRO/K9IWR0/K9IWR0-uniprot.txt "Belongs to the tumor necrosis factor family."].

📄 View Raw YAML

 
id: K9IWR0
gene_symbol: K9IWR0
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9430
  label: Desmodus rotundus
description: 'TODO: Add description for K9IWR0'
existing_annotations:
  - term:
      id: GO:0007165
      label: signal transduction
    evidence_type: IEA
    original_reference_id: GO_REF:0000108
    review:
      summary: Signal transduction is a broad inference without direct evidence 
        for this DESRO cytokine.
      action: MARK_AS_OVER_ANNOTATED
      reason: Annotation is generic and not directly supported in DESRO; core 
        function is cytokine activity.
  - term:
      id: GO:0043123
      label: positive regulation of canonical NF-kappaB signal transduction
    evidence_type: IEA
    original_reference_id: GO_REF:0000118
    review:
      summary: Positive regulation of canonical NF-kappaB signaling is a 
        downstream effect inferred from orthology.
      action: MARK_AS_OVER_ANNOTATED
      reason: Specific pathway regulation is not directly evidenced for this 
        DESRO protein.
  - term:
      id: GO:2001238
      label: positive regulation of extrinsic apoptotic signaling pathway
    evidence_type: IEA
    original_reference_id: GO_REF:0000118
    review:
      summary: Positive regulation of extrinsic apoptotic signaling pathway is a
        downstream inference without direct evidence in DESRO.
      action: MARK_AS_OVER_ANNOTATED
      reason: Specific apoptotic pathway regulation is not directly evidenced 
        for this protein.
  - term:
      id: GO:0005125
      label: cytokine activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: UniProt describes this protein as a cytokine that binds TNF 
        receptors.
      action: ACCEPT
      reason: UniProt functional description supports cytokine activity.
      supported_by:
        - &id001
          reference_id: file:DESRO/K9IWR0/K9IWR0-uniprot.txt
          supporting_text: '"Cytokine that in its homotrimeric form binds to TNFRSF1A/TNFR1"'
  - term:
      id: GO:0005164
      label: tumor necrosis factor receptor binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: UniProt functional description indicates TNF receptor binding.
      action: ACCEPT
      reason: Functional description notes binding to TNF receptors.
      supported_by:
        - *id001
  - term:
      id: GO:0005576
      label: extracellular region
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: Extracellular region is a broad parent term; extracellular space 
        is more specific for a secreted cytokine.
      action: MODIFY
      reason: UniProt indicates secretion; use extracellular space for 
        specificity.
      proposed_replacement_terms:
        - id: GO:0005615
          label: extracellular space
      supported_by:
        - &id002
          reference_id: file:DESRO/K9IWR0/K9IWR0-uniprot.txt
          supporting_text: '"SUBCELLULAR LOCATION: Secreted"'
  - term:
      id: GO:0005615
      label: extracellular space
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: UniProt annotates this protein as secreted.
      action: ACCEPT
      reason: Secreted localization is supported in UniProt.
      supported_by:
        - *id002
  - term:
      id: GO:0006955
      label: immune response
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: Immune response is a broad inference without direct evidence in 
        DESRO.
      action: MARK_AS_OVER_ANNOTATED
      reason: General immune response annotation is inferred and not directly 
        supported.
  - term:
      id: GO:0006959
      label: humoral immune response
    evidence_type: IEA
    original_reference_id: GO_REF:0000104
    review:
      summary: Humoral immune response is a specific process inferred from 
        orthology without direct DESRO evidence.
      action: MARK_AS_OVER_ANNOTATED
      reason: Specific humoral response evidence is lacking for this DESRO 
        protein.
  - term:
      id: GO:0016020
      label: membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: UniProt indicates membrane localization in addition to secretion.
      action: ACCEPT
      reason: Subcellular location includes membrane.
      supported_by:
        - reference_id: file:DESRO/K9IWR0/K9IWR0-uniprot.txt
          supporting_text: '"Membrane"'
references:
  - id: GO_REF:0000002
    title: Gene Ontology annotation through association of InterPro records with
      GO terms
    findings: []
  - id: GO_REF:0000044
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular 
      Location vocabulary mapping, accompanied by conservative changes to GO 
      terms applied by UniProt
    findings: []
  - id: GO_REF:0000104
    title: Electronic Gene Ontology annotations created by transferring manual 
      GO annotations between related proteins based on shared sequence features
    findings: []
  - id: GO_REF:0000108
    title: Automatic assignment of GO terms using logical inference, based on on
      inter-ontology links
    findings: []
  - id: GO_REF:0000118
    title: TreeGrafter-generated GO annotations
    findings: []
  - id: GO_REF:0000120
    title: Combined Automated Annotation using Multiple IEA Methods
    findings: []