Affinage

TMEM131

Transmembrane protein 131 · UniProt Q92545

Length
1883 aa
Mass
205.1 kDa
Annotated
2026-06-10
35 papers in source corpus 4 papers cited in narrative 4 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 3/4 claims corpus-supported (75%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TMEM131 is an endoplasmic reticulum-localized transmembrane protein that couples the recruitment of secretory cargo to its export from the ER, functioning in collagen and broader extracellular matrix biogenesis (PMID:32095531, PMID:39521045). Its amino-terminal bacterial PapD chaperone-like domains recruit premature collagen monomers for proper assembly, while its carboxy terminus binds TRAPPC8 of the TRAPP tethering complex to drive collagen trafficking from the ER to the Golgi; these activities are evolutionarily conserved across C. elegans, Drosophila, and human cells (PMID:32095531). TMEM131 cooperates with TMEM39A to support formation of the large COPII vesicles required for bulk secretion of ECM proteins, with its knockdown reducing both large-vesicle formation and collagen secretion (PMID:39521045). Beyond ECM cargo, ER-resident TMEM131 binds TRAIL and mediates its ER-to-Golgi transport via the COPII component Sec23A, with disruption diverting TRAIL toward ER-associated degradation through ubiquitylation (PMID:41293955).

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2020 High

    Establishing how nascent collagen is matched to ER export machinery, this work defined TMEM131 as a bifunctional protein whose N-terminal PapD-like domains recruit collagen monomers and whose C-terminus links cargo to the TRAPP tethering complex via TRAPPC8.

    Evidence RNAi screen, domain analysis, Co-IP/pulldown with TRAPPC8, ER stress reporters and collagen secretion assays across C. elegans, Drosophila and human cells

    PMID:32095531

    Open questions at the time
    • Structural basis of PapD-like domain binding to collagen monomers not resolved
    • Whether TMEM131 acts catalytically or as a passive scaffold during cargo loading is unclear
    • Stoichiometry and regulation of the TMEM131–TRAPPC8 interaction not defined
  2. 2024 Medium

    Addressing how bulk ECM cargo is packaged into oversized carriers, this study placed TMEM131 in a complex with TMEM39A that is required for large COPII vesicle formation and collagen secretion.

    Evidence TMEM39A-FLAG immunoprecipitation with proteomics, TMEM131 knockdown, collagen secretion assays and co-localization imaging in C. elegans and human sarcoma cells

    PMID:39521045

    Open questions at the time
    • Direct versus indirect nature of the TMEM131–TMEM39A interaction not established
    • Mechanism by which the pair enlarges COPII vesicles is unknown
    • Reciprocal validation in additional cell types is limited
  3. 2025 Medium

    Extending TMEM131 cargo beyond ECM, this work showed it binds TRAIL and routes it from ER to Golgi via Sec23A, with loss of transport shunting TRAIL into ubiquitin-dependent ER-associated degradation.

    Evidence IP-MS of the TMEM131–TRAIL interaction, AECII-specific TRAIL knockout mouse, quantitative proteomics and single-cell RNA sequencing

    PMID:41293955

    Open questions at the time
    • Whether TRAIL trafficking uses the same domains/partners as collagen export is untested
    • Direct binding versus complex-mediated interaction not distinguished
    • Physiological breadth of TMEM131-dependent TRAIL secretion beyond the studied lung epithelial context unknown
  4. 2025 Low

    A transcriptomic study associated TMEM131 with CCL22+ dendritic cell generation through TNF signaling in colorectal tumorigenesis, hinting at a role beyond secretory trafficking.

    Evidence Single-cell RNA sequencing, multiplex immunohistochemistry, flow cytometry and DC injection in colorectal models

    PMID:40698132

    Open questions at the time
    • Primarily correlative transcriptomics with limited direct mechanistic validation of TMEM131
    • Molecular link between TMEM131 secretory function and TNF/CCL22 axis not defined
    • Not independently replicated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TMEM131 selects among diverse cargoes (collagen, ECM proteins, TRAIL) and whether a single mechanism governs cargo recruitment and COPII-dependent export remains open.
  • No unifying model linking cargo recognition to vesicle formation
  • No structural model of TMEM131 in any cargo-export complex
  • Regulation of TMEM131 activity across tissues unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1474244 Extracellular matrix organization 2
Partners
SEC23ATMEM39ATNFSF10TRAPPC8

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 TMEM131 amino termini contain bacterial PapD chaperone-like domains that recruit premature collagen monomers for proper assembly and secretion from the ER. Carboxy termini of TMEM131 interact with TRAPPC8, a component of the TRAPP tethering complex, to drive collagen cargo trafficking from ER to the Golgi. These roles were identified via RNAi screen in C. elegans and validated as evolutionarily conserved in C. elegans, Drosophila, and humans. RNA interference screen, domain analysis, Co-IP/pulldown with TRAPPC8, ER stress reporter assays, collagen secretion assays in C. elegans, Drosophila, and human cells Science advances High 32095531
2024 TMEM131 cooperates with TMEM39A to facilitate the formation of large COPII vesicles required for bulk secretion of extracellular matrix (ECM) proteins, including collagen. Knockdown of TMEM131 reduces TMEM39A-associated large vesicle (TMEM39A-LV) formation and collagen secretion in both C. elegans and human sarcoma cells. TMEM131 was identified as a TMEM39A-interacting protein by immunoprecipitation and proteomics. Immunoprecipitation with TMEM39A-FLAG followed by proteomics, RNAi/knockdown of TMEM131, collagen secretion assays, co-localization imaging in C. elegans and human sarcoma cells Journal of genetics and genomics = Yi chuan xue bao Medium 39521045
2025 ER-localized TMEM131 interacts with TRAIL and mediates its transportation from the ER to the Golgi through Sec23 homolog A of the COPII complex. Disruption of this transportation process leads to ER-associated degradation of TRAIL proteins via ubiquitylation. Immunoprecipitation mass spectrometry (IP-MS) to identify TMEM131-TRAIL interaction, AECII-specific TRAIL knockout mouse model, quantitative proteomics, single-cell RNA sequencing Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 41293955
2025 TMEM131 derived CCL22+ dendritic cell generation via the TNF signaling pathway, as identified by single-cell RNA sequencing analysis and functional validation in colorectal tumorigenesis models. Single-cell RNA sequencing, multiplex immunohistochemistry, flow cytometry, bulk RNA sequencing, intraperitoneal injection of DCs Acta pharmaceutica Sinica. B Low 40698132

Source papers

Stage 0 corpus · 35 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 Metabolism of dibenzo-p-dioxin by Sphingomonas sp. strain RW1. Applied and environmental microbiology 202 1575472
1998 Genetic analysis of dioxin dioxygenase of Sphingomonas sp. Strain RW1: catabolic genes dispersed on the genome. Journal of bacteriology 132 9683494
1993 Dibenzofuran 4,4a-dioxygenase from Sphingomonas sp. strain RW1: angular dioxygenation by a three-component enzyme system. Journal of bacteriology 102 8407823
1993 Characterization of 2,2',3-trihydroxybiphenyl dioxygenase, an extradiol dioxygenase from the dibenzofuran- and dibenzo-p-dioxin-degrading bacterium Sphingomonas sp. strain RW1. Journal of bacteriology 68 8226678
1999 A functional 4-hydroxysalicylate/hydroxyquinol degradative pathway gene cluster is linked to the initial dibenzo-p-dioxin pathway genes in Sphingomonas sp. strain RW1. Journal of bacteriology 58 10348858
2020 Broadly conserved roles of TMEM131 family proteins in intracellular collagen assembly and secretory cargo trafficking. Science advances 49 32095531
1997 Molecular characterization of Fdx1, a putidaredoxin-type [2Fe-2S] ferredoxin able to transfer electrons to the dioxin dioxygenase of Sphingomonas sp. RW1. European journal of biochemistry 47 9288905
2010 The serine palmitoyltransferase from Sphingomonas wittichii RW1: An interesting link to an unusual acyl carrier protein. Biopolymers 35 20578000
2014 Genome-wide analysis of Sphingomonas wittichii RW1 behaviour during inoculation and growth in contaminated sand. The ISME journal 31 24936762
2012 Genome-Wide Analysis of Salicylate and Dibenzofuran Metabolism in Sphingomonas Wittichii RW1. Frontiers in microbiology 31 22936930
1998 The reductase RedA2 of the multi-component dioxin dioxygenase system of Sphingomonas sp. RW1 is related to class-I cytochrome P450-type reductases. European journal of biochemistry 31 9654094
2013 Shotgun proteomics suggests involvement of additional enzymes in dioxin degradation by Sphingomonas wittichii RW1. Environmental microbiology 30 24118890
2000 A second [2Fe-2S] ferredoxin from Sphingomonas sp. Strain RW1 can function as an electron donor for the dioxin dioxygenase. Journal of bacteriology 29 10735867
2007 Characterization of a C-C bond hydrolase from Sphingomonas wittichii RW1 with novel specificities towards polychlorinated biphenyl metabolites. Journal of bacteriology 28 17416660
2013 Genome-wide transposon insertion scanning of environmental survival functions in the polycyclic aromatic hydrocarbon degrading bacterium Sphingomonas wittichii RW1. Environmental microbiology 26 23601288
1993 Purification of two isofunctional hydrolases (EC 3.7.1.8) in the degradative pathway for dibenzofuran in Sphingomonas sp. strain RW1. Biodegradation 26 7764304
2012 Proteomic profiling of the dioxin-degrading bacterium Sphingomonas wittichii RW1. Journal of biomedicine & biotechnology 24 23091346
2005 Identification and phenotypic characterization of Sphingomonas wittichii strain RW1 by peptide mass fingerprinting using matrix-assisted laser desorption ionization-time of flight mass spectrometry. Applied and environmental microbiology 22 15870332
2014 Characterization of denitrifying activity by the alphaproteobacterium, Sphingomonas wittichii RW1. Frontiers in microbiology 16 25147547
2021 The probiotic potential of Lactobacillus plantarum strain RW1 isolated from canine faeces. Journal of applied microbiology 10 34709709
2015 Sphingomonas wittichii RW1 gene reporters interrogating the dibenzofuran metabolic network highlight conditions for early successful development in contaminated microcosms. Environmental microbiology reports 10 25683238
2014 Cloning, overexpression, and characterization of a high enantioselective nitrilase from Sphingomonas wittichii RW1 for asymmetric synthesis of (R)-phenylglycine. Applied biochemistry and biotechnology 10 24664232
1995 Evidence of histidine coordination to the catalytic ferrous ion in the ring-cleaving 2,2',3-trihydroxybiphenyl dioxygenase from the dibenzofuran-degrading bacterium Sphingomonas sp. strain RW1. Biochemical and biophysical research communications 10 7488052
2025 Single-cell RNA sequencing reveals Shen-Bai-Jie-Du decoction retards colorectal tumorigenesis by regulating the TMEM131-TNF signaling pathway-mediated differentiation of immunosuppressive dendritic cells. Acta pharmaceutica Sinica. B 8 40698132
2018 A novel β-propeller phytase from the dioxin-degrading bacterium Sphingomonas wittichii RW-1. Applied microbiology and biotechnology 8 30054699
2024 TMEM39A and TMEM131 facilitate bulk transport of ECM proteins through large COPII vesicle formation. Journal of genetics and genomics = Yi chuan xue bao 6 39521045
2021 Separate Upper Pathway Ring Cleavage Dioxygenases Are Required for Growth of Sphingomonas wittichii Strain RW1 on Dibenzofuran and Dibenzo-p-Dioxin. Applied and environmental microbiology 5 33741618
2014 Identification of genes potentially involved in solute stress response in Sphingomonas wittichii RW1 by transposon mutant recovery. Frontiers in microbiology 4 25408691
2024 Immunomodulatory Effects of Lactiplantibacillus plantarum Strain RW1 During Salmonella Infection in Murine Intestinal Epithelial Cells and Dextran Sulfate Sodium-Induced Murine Colitis. Probiotics and antimicrobial proteins 3 39625595
2021 Differential Roles of Three Different Upper Pathway meta Ring Cleavage Product Hydrolases in the Degradation of Dibenzo-p-Dioxin and Dibenzofuran by Sphingomonas wittichii Strain RW1. Applied and environmental microbiology 2 34469199
2017 Swit_4259, an acetoacetate decarboxylase-like enzyme from Sphingomonas wittichii RW1. Acta crystallographica. Section F, Structural biology communications 2 29199988
1996 Use of monoclonal antibodies against dibenzo-p-dioxin degrading Sphingomonas sp. strain RW1. Letters in applied microbiology 2 8936374
2025 TMEM131-Mediated Soluble TRAIL Triggered Type II Alveolar Epithelial Cell Senescence in Radiation-Induced Lung Injury. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 41293955
2022 Physiological role of isocitrate lyase in dibenzo-p-dioxin and dibenzofuran metabolism by Sphingomonas wittichii RW1. Journal, genetic engineering & biotechnology 1 35353212
2025 Analysis of Benzoate 1,2-Dioxygenase Identifies Shared Electron Transfer Components With DxnA1A2 in Rhizorhabdus wittichii RW1. Journal of basic microbiology 0 40405529

Missed literature

Know a paper Affinage missed for TMEM131? Flag it for the maintainers and the community.

No submissions yet.