Affinage

Showing MARVELD2 — TRIC is a alias.

MARVELD2

MARVEL domain-containing protein 2 · UniProt Q8N4S9

Length
558 aa
Mass
64.2 kDa
Annotated
2026-06-10
100 papers in source corpus 1 papers cited in narrative 1 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 2/2 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MARVELD2 encodes tricellulin, a protein that localizes to tricellular tight junctions where it serves a non-redundant role in epithelial barrier organization across multiple organ systems (PMID:25666562). A homozygous loss-of-function variant (p.Arg497*) in mice produces defects in the inner ear, heart, mandibular salivary gland, thyroid gland, and olfactory epithelium, demonstrating that tricellulin function at tricellular tight junctions cannot be compensated by other junctional proteins in these tissues (PMID:25666562). Beyond this phenotypic characterization in (PMID:25666562), no direct biochemical mechanism of tricellulin action has been established in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 1 step
  1. 2015 Low

    Established that tricellulin is required non-redundantly at tricellular tight junctions not only in the inner ear but across diverse epithelial tissues, broadening its role beyond hearing.

    Evidence Mouse knockout/knock-in model carrying a loss-of-function variant (p.Arg497*) with histological and phenotypic analysis across multiple tissues

    PMID:25666562

    Open questions at the time
    • Single study describing phenotype without direct biochemical mechanism elucidated
    • No molecular partners or recruitment mechanism at tricellular junctions identified
    • No structural or biophysical basis for tricellulin's barrier function established

Open questions

Synthesis pass · forward-looking unresolved questions
  • The detailed molecular mechanism by which tricellulin organizes or seals tricellular tight junctions remains unresolved.
  • No interacting proteins or assembly mechanism defined in the corpus
  • No biochemical activity assigned to tricellulin
  • Tissue-specific consequences of barrier disruption not mechanistically linked to a molecular function

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005886 plasma membrane 1
Complex memberships
tricellular tight junction

Evidence

Reading pass · 1 per-paper finding extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 MARVELD2 encodes tricellulin, a tricellular tight junction protein; homozygous loss-of-function variants in mice (p.Arg497*) produce defects not only in the inner ear but also in heart, mandibular salivary gland, thyroid gland, and olfactory epithelium, indicating a non-redundant role for tricellulin at tricellular tight junctions in multiple organ systems. Mouse knockout/knock-in model with histological and phenotypic analysis across multiple tissues Human genetics Low 25666562

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 Function in protein folding of TRiC, a cytosolic ring complex containing TCP-1 and structurally related subunits. The EMBO journal 374 1361170
2006 The chaperonin TRiC controls polyglutamine aggregation and toxicity through subunit-specific interactions. Nature cell biology 253 16980959
2006 Chaperonin TRiC promotes the assembly of polyQ expansion proteins into nontoxic oligomers. Molecular cell 226 16973440
2009 The chaperonin TRiC blocks a huntingtin sequence element that promotes the conformational switch to aggregation. Nature structural & molecular biology 205 19915590
1999 Formation of the VHL-elongin BC tumor suppressor complex is mediated by the chaperonin TRiC. Molecular cell 193 10635329
1999 Group II chaperonins: new TRiC(k)s and turns of a protein folding machine. Journal of molecular biology 158 10550210
2016 TRIC: an automated alignment strategy for reproducible protein quantification in targeted proteomics. Nature methods 144 27479329
2007 TRIC channels are essential for Ca2+ handling in intracellular stores. Nature 144 17611541
2014 A direct regulatory interaction between chaperonin TRiC and stress-responsive transcription factor HSF1. Cell reports 126 25437552
2014 Proteostatic control of telomerase function through TRiC-mediated folding of TCAB1. Cell 125 25467444
2003 The Hsp70 and TRiC/CCT chaperone systems cooperate in vivo to assemble the von Hippel-Lindau tumor suppressor complex. Molecular and cellular biology 121 12697815
2001 Review: cellular substrates of the eukaryotic chaperonin TRiC/CCT. Journal of structural biology 119 11580267
2019 The Chaperonin TRiC/CCT Associates with Prefoldin through a Conserved Electrostatic Interface Essential for Cellular Proteostasis. Cell 111 30955883
2000 Protein folding: versatility of the cytosolic chaperonin TRiC/CCT. Current biology : CB 106 10753735
2020 The Molecular Chaperone CCT/TRiC: An Essential Component of Proteostasis and a Potential Modulator of Protein Aggregation. Frontiers in genetics 96 32265978
2019 Nascent Polypeptide Domain Topology and Elongation Rate Direct the Cotranslational Hierarchy of Hsp70 and TRiC/CCT. Molecular cell 96 31400849
2011 The chaperonin containing TCP1 complex (CCT/TRiC) is involved in mediating sperm-oocyte interaction. The Journal of biological chemistry 94 21880732
2015 Two members of the TRiC chaperonin complex, CCT2 and TCP1 are essential for survival of breast cancer cells and are linked to driving oncogenes. Experimental cell research 86 25704758
2014 Modulation of STAT3 folding and function by TRiC/CCT chaperonin. PLoS biology 86 24756126
2003 TRiC/CCT cooperates with different upstream chaperones in the folding of distinct protein classes. The EMBO journal 81 14517260
2016 TRiC subunits enhance BDNF axonal transport and rescue striatal atrophy in Huntington's disease. Proceedings of the National Academy of Sciences of the United States of America 79 27601642
2003 The group II chaperonin TRiC protects proteolytic intermediates from degradation in the MHC class I antigen processing pathway. Molecular cell 76 14527404
2018 Pathway of Actin Folding Directed by the Eukaryotic Chaperonin TRiC. Cell 74 30100183
2019 The ATP-powered gymnastics of TRiC/CCT: an asymmetric protein folding machine with a symmetric origin story. Current opinion in structural biology 73 30978594
2015 Contribution of the Type II Chaperonin, TRiC/CCT, to Oncogenesis. International journal of molecular sciences 73 26561808
2011 Symmetry-free cryo-EM structures of the chaperonin TRiC along its ATPase-driven conformational cycle. The EMBO journal 73 22045336
2013 TRiC's tricks inhibit huntingtin aggregation. eLife 72 23853712
2008 Mechanism of lid closure in the eukaryotic chaperonin TRiC/CCT. Nature structural & molecular biology 72 18536725
2011 TRIC-A channels in vascular smooth muscle contribute to blood pressure maintenance. Cell metabolism 67 21803293
2009 Essential role of the TRIC-B channel in Ca2+ handling of alveolar epithelial cells and in perinatal lung maturation. Development (Cambridge, England) 63 19515693
1995 The thermosome of Thermoplasma acidophilum and its relationship to the eukaryotic chaperonin TRiC. European journal of biochemistry 62 7867646
2010 Chaperonin TRiC/CCT participates in replication of hepatitis C virus genome via interaction with the viral NS5B protein. Virology 61 21093005
2013 The cytosolic chaperonin CCT/TRiC and cancer cell proliferation. PloS one 60 23613750
2022 Structural visualization of the tubulin folding pathway directed by human chaperonin TRiC/CCT. Cell 58 36493755
2016 Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta. PLoS genetics 57 27441836
2012 Folding of large multidomain proteins by partial encapsulation in the chaperonin TRiC/CCT. Proceedings of the National Academy of Sciences of the United States of America 56 23197838
2006 Role of the chaperonin CCT/TRiC complex in G protein betagamma-dimer assembly. The Journal of biological chemistry 56 16702223
2001 Type D retrovirus Gag polyprotein interacts with the cytosolic chaperonin TRiC. Journal of virology 54 11222675
2017 The chaperonin TRiC forms an oligomeric complex in the malaria parasite cytosol. Cellular microbiology 50 28067475
2018 The TRiC chaperonin controls reovirus replication through outer-capsid folding. Nature microbiology 48 29531365
2004 The HIF prolyl hydroxylase PHD3 is a potential substrate of the TRiC chaperonin. FEBS letters 47 15251459
2019 An ensemble of cryo-EM structures of TRiC reveal its conformational landscape and subunit specificity. Proceedings of the National Academy of Sciences of the United States of America 45 31492816
1976 Factors affecting the sensitivity of replicating McCoy cells in the isolation and growth of chlamydia A (TRIC agents). The Journal of hygiene 43 6592
2019 TRiC/CCT Chaperonin: Structure and Function. Sub-cellular biochemistry 42 31939165
2016 Pore architecture of TRIC channels and insights into their gating mechanism. Nature 42 27698420
2014 Trophoblast retrieval and isolation from the cervix (TRIC) for noninvasive prenatal screening at 5 to 20 weeks of gestation. Fertility and sterility 42 24825422
2007 Splice-site mutations in the TRIC gene underlie autosomal recessive nonsyndromic hearing impairment in Pakistani families. Journal of human genetics 42 18084694
2022 Snapshots of actin and tubulin folding inside the TRiC chaperonin. Nature structural & molecular biology 41 35449234
2010 Ca2+ overload and sarcoplasmic reticulum instability in tric-a null skeletal muscle. The Journal of biological chemistry 41 20858894
2020 Plasmodium chaperonin TRiC/CCT identified as a target of the antihistamine clemastine using parallel chemoproteomic strategy. Proceedings of the National Academy of Sciences of the United States of America 40 32127489
2010 Charade of the SR K+-channel: two ion-channels, TRIC-A and TRIC-B, masquerade as a single K+-channel. Biophysical journal 39 20643059
2018 TRiC controls transcription resumption after UV damage by regulating Cockayne syndrome protein A. Nature communications 38 29531219
2014 The molecular chaperone TRiC/CCT binds to the Trp-Asp 40 (WD40) repeat protein WDR68 and promotes its folding, protein kinase DYRK1A binding, and nuclear accumulation. The Journal of biological chemistry 37 25342745
2022 Ginkgolide B targets and inhibits creatine kinase B to regulate the CCT/TRiC-SK1 axis and exerts pro-angiogenic activity in middle cerebral artery occlusion mice. Pharmacological research 36 35513225
2014 Caenorhabditis elegans chaperonin CCT/TRiC is required for actin and tubulin biogenesis and microvillus formation in intestinal epithelial cells. Molecular biology of the cell 35 25143409
2011 Functional Subunits of Eukaryotic Chaperonin CCT/TRiC in Protein Folding. Journal of amino acids 34 22312474
2019 TRiC/CCT chaperonins are essential for organ growth by interacting with insulin/TOR signaling in Drosophila. Oncogene 33 30792539
2018 In Vivo Function of the Chaperonin TRiC in α-Actin Folding during Sarcomere Assembly. Cell reports 32 29320728
2017 Structure of the human TRiC/CCT Subunit 5 associated with hereditary sensory neuropathy. Scientific reports 32 28623285
2012 Interactions of subunit CCT3 in the yeast chaperonin CCT/TRiC with Q/N-rich proteins revealed by high-throughput microscopy analysis. Proceedings of the National Academy of Sciences of the United States of America 32 23112166
2021 Structural and functional dissection of reovirus capsid folding and assembly by the prefoldin-TRiC/CCT chaperone network. Proceedings of the National Academy of Sciences of the United States of America 31 33836586
2014 The TRiC/CCT chaperone is implicated in Alzheimer's disease based on patient GWAS and an RNAi screen in Aβ-expressing Caenorhabditis elegans. PloS one 31 25080104
2020 The TRiC/CCT Chaperonin and Its Role in Uncontrolled Proliferation. Advances in experimental medicine and biology 28 32297209
2012 TRIC channels supporting efficient Ca(2+) release from intracellular stores. Pflugers Archiv : European journal of physiology 28 23242030
1994 Tcp20, a subunit of the eukaryotic TRiC chaperonin from humans and yeast. The Journal of biological chemistry 28 8034610
2015 Vaccinia-Related Kinase 2 Controls the Stability of the Eukaryotic Chaperonin TRiC/CCT by Inhibiting the Deubiquitinating Enzyme USP25. Molecular and cellular biology 27 25755282
2015 Chaperonin TRiC/CCT Modulates the Folding and Activity of Leukemogenic Fusion Oncoprotein AML1-ETO. The Journal of biological chemistry 26 26706127
1994 TRiC-P5, a novel TCP1-related protein, is localized in the cytoplasm and in the nuclear matrix. Journal of cell science 26 7876352
2017 Genetic expansion of chaperonin-containing TCP-1 (CCT/TRiC) complex subunits yields testis-specific isoforms required for spermatogenesis in planarian flatworms. Molecular reproduction and development 24 29095551
2013 Sarcoplasmic reticulum K(+) (TRIC) channel does not carry essential countercurrent during Ca(2+) release. Biophysical journal 24 24010658
2012 Human TRiC complex purified from HeLa cells contains all eight CCT subunits and is active in vitro. Cell stress & chaperones 24 23011926
2008 New molecular components supporting ryanodine receptor-mediated Ca(2+) release: roles of junctophilin and TRIC channel in embryonic cardiomyocytes. Pharmacology & therapeutics 24 19095005
2016 Crystal structures of the TRIC trimeric intracellular cation channel orthologues. Cell research 23 27909292
2023 Pathway and mechanism of tubulin folding mediated by TRiC/CCT along its ATPase cycle revealed using cryo-EM. Communications biology 22 37193829
2019 TRIC-A Channel Maintains Store Calcium Handling by Interacting With Type 2 Ryanodine Receptor in Cardiac Muscle. Circulation research 22 31805819
2013 Vaccinia-related kinase 2 mediates accumulation of polyglutamine aggregates via negative regulation of the chaperonin TRiC. Molecular and cellular biology 22 24298020
1972 Some consequences of the multiple infection of cell cultures by TRIC organisms. The Journal of hygiene 22 4501841
2018 The chaperonin TRiC/CCT is essential for the action of bacterial glycosylating protein toxins like Clostridium difficile toxins A and B. Proceedings of the National Academy of Sciences of the United States of America 21 30181275
2017 TRiC/CCT chaperonins are essential for maintaining myofibril organization, cardiac physiological rhythm, and lifespan. FEBS letters 21 28963798
2011 DFNB49 is an important cause of non-syndromic deafness in Czech Roma patients but not in the general Czech population. Clinical genetics 21 22097895
2004 A new locus for nonsyndromic deafness DFNB49 maps to chromosome 5q12.3-q14.1. Human genetics 21 15538632
2016 Regulation of GPCR expression through an interaction with CCT7, a subunit of the CCT/TRiC complex. Molecular biology of the cell 20 27708139
2011 Chaperonins induce an amyloid-like transformation of ovine prion protein: the fundamental difference in action between eukaryotic TRiC and bacterial GroEL. Biochimica et biophysica acta 20 21856455
2024 Brain malformations and seizures by impaired chaperonin function of TRiC. Science (New York, N.Y.) 19 39480921
2023 Recognition of the CCT5 di-Glu degron by CRL4DCAF12 is dependent on TRiC assembly. The EMBO journal 19 36715408
2015 Noninvasive detection of trophoblast protein signatures linked to early pregnancy loss using trophoblast retrieval and isolation from the cervix (TRIC). Fertility and sterility 19 26051097
2005 Efficient production of native actin upon translation in a bacterial lysate supplemented with the eukaryotic chaperonin TRiC. Biological chemistry 19 16201870
2019 tRic: a user-friendly data portal to explore the expression landscape of tRNAs in human cancers. RNA biology 18 31432762
2015 Molecular genetics of MARVELD2 and clinical phenotype in Pakistani and Slovak families segregating DFNB49 hearing loss. Human genetics 18 25666562
1974 Interactions of TRIC agents with macrophages: effects on lysosomal enzymes of the cell. The Journal of hygiene 18 4522724
2023 Structural basis of plp2-mediated cytoskeletal protein folding by TRiC/CCT. Science advances 17 36921056
2020 TRIC-A shapes oscillatory Ca2+ signals by interaction with STIM1/Orai1 complexes. PLoS biology 17 32330125
2018 Development of a yeast internal-subunit eGFP labeling strategy and its application in subunit identification in eukaryotic group II chaperonin TRiC/CCT. Scientific reports 17 29403048
2007 Conformational rearrangements of tail-less complex polypeptide 1 (TCP-1) ring complex (TRiC)-bound actin. Biochemistry 17 17417821
2024 In situ analysis reveals the TRiC duty cycle and PDCD5 as an open-state cofactor. Nature 16 39663456
2023 A hierarchical assembly pathway directs the unique subunit arrangement of TRiC/CCT. Molecular cell 16 37625406
2023 Absence of TRIC-B from type XIV Osteogenesis Imperfecta osteoblasts alters cell adhesion and mitochondrial function - A multi-omics study. Matrix biology : journal of the International Society for Matrix Biology 15 37348683
2017 Dampened activity of ryanodine receptor channels in mutant skeletal muscle lacking TRIC-A. The Journal of physiology 15 28387457
2015 MARVELD2 (DFNB49) mutations in the hearing impaired Central European Roma population--prevalence, clinical impact and the common origin. PloS one 15 25885414
2008 The CCT/TRiC chaperonin is required for maturation of sphingosine kinase 1. The international journal of biochemistry & cell biology 15 18775504

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