Affinage

JTB

Protein JTB · UniProt O76095

Length
146 aa
Mass
16.4 kDa
Annotated
2026-06-10
100 papers in source corpus 2 papers cited in narrative 2 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

JTB (Jumping Translocation Breakpoint) encodes a transmembrane protein originally identified at chromosome 1q21, where jumping translocations fuse the gene to telomeric repeats and yield a truncated product lacking the transmembrane domain (PMID:10321732). The mature protein undergoes N-terminal processing and localizes predominantly to mitochondria rather than the plasma membrane originally predicted (PMID:17369841). Upon overexpression, JTB drives mitochondrial clustering around the nuclear periphery, mitochondrial swelling, and a marked reduction in mitochondrial membrane potential, all dependent on N-terminal cleavage since a cleavage-resistant mutant abolishes these effects (PMID:17369841). Functionally, JTB retards cell growth and confers resistance to TGF-β1-induced apoptosis (PMID:17369841). Beyond these findings, no further mechanistic detail — molecular partners, the protease responsible for processing, or the basis of apoptosis resistance — has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 1999 Medium

    Established JTB as a gene whose disruption is structurally linked to cancer-associated chromosomal rearrangements, defining the truncation event at 1q21.

    Evidence Molecular cloning and chromosomal breakpoint mapping of a jumping translocation junction with sequence analysis

    PMID:10321732

    Open questions at the time
    • Functional consequence of the truncation not tested
    • Subcellular localization and biochemical activity of the protein unresolved at this stage
    • Single-lab breakpoint characterization
  2. 2007 Medium

    Revised the predicted plasma-membrane localization to a mitochondrial one and tied JTB's processing to functional control of mitochondrial integrity, growth, and apoptosis resistance.

    Evidence Subcellular fractionation, JC-1 membrane-potential imaging, wild-type versus cleavage-resistant mutant overexpression, and growth/apoptosis assays in a single lab

    PMID:17369841

    Open questions at the time
    • Protease responsible for N-terminal processing not identified
    • Molecular partners or mechanism connecting JTB to membrane potential loss unknown
    • Mechanism of TGF-β1-induced apoptosis resistance not defined
    • Effects shown under overexpression; endogenous role not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How JTB processing mechanistically perturbs mitochondrial physiology and links to apoptosis resistance and growth control remains unresolved.
  • No identified direct binding partners or substrates
  • No structural model
  • No loss-of-function (endogenous) phenotype characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005739 mitochondrion 1

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 JTB (Jumping Translocation Breakpoint) was identified as a novel gene at chromosome 1q21 encoding a transmembrane protein. In a jumping translocation, JTB fused with telomeric repeats of acceptor telomeres, resulting in a truncated hJTB product devoid of the transmembrane domain. Molecular cloning, chromosomal breakpoint mapping, sequence analysis Oncogene Medium 10321732
2007 JTB protein is processed at its N-terminus and localizes predominantly to mitochondria (not to the plasma membrane as originally predicted). When overexpressed, JTB induces clustering of mitochondria around the nuclear periphery, swelling of mitochondria, and significant reduction of mitochondrial membrane potential (assessed by JC-1 probe). These mitochondrial changes are dependent on N-terminal processing, as a cleavage-resistant mutant fails to produce these effects. JTB expression retards cell growth and confers resistance to TGF-β1-induced apoptosis. Subcellular fractionation, fluorescence microscopy (JC-1 membrane potential probe), overexpression of wild-type vs. cleavage-resistant mutant, cell growth assays, apoptosis assays Oncogene Medium 17369841

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 On PAR with PARP: cellular stress signaling through poly(ADP-ribose) and PARP-1. Genes & development 621 22391446
2007 The PAR proteins: fundamental players in animal cell polarization. Developmental cell 605 17981131
2006 The PAR-aPKC system: lessons in polarity. Journal of cell science 575 16525119
1997 Interactions of mast cell tryptase with thrombin receptors and PAR-2. The Journal of biological chemistry 511 9020112
2003 The Par complex directs asymmetric cell division by phosphorylating the cytoskeletal protein Lgl. Nature 453 12629552
2003 Drosophila PAR-1 and 14-3-3 inhibit Bazooka/PAR-3 to establish complementary cortical domains in polarized cells. Cell 345 14675534
2005 PAR-6-PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiam1. Nature cell biology 313 15723051
1999 PAR-6 is a conserved PDZ domain-containing protein that colocalizes with PAR-3 in Caenorhabditis elegans embryos. Development (Cambridge, England) 252 9834192
2010 Rho-kinase directs Bazooka/Par-3 planar polarity during Drosophila axis elongation. Developmental cell 214 20833361
2001 PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling. Nature cell biology 205 11433294
2011 Identification of RNA-protein interaction networks using PAR-CLIP. Wiley interdisciplinary reviews. RNA 175 22213601
2017 Characterizing Expression and Processing of Precursor and Mature Human tRNAs by Hydro-tRNAseq and PAR-CLIP. Cell reports 173 28793268
2009 Basement membrane proteoglycans: modulators Par Excellence of cancer growth and angiogenesis. Molecules and cells 173 19466598
2011 About PAR: the distinct evolutionary dynamics of the pseudoautosomal region. Trends in genetics : TIG 151 21962971
2019 The Enigmatic Function of PARP1: From PARylation Activity to PAR Readers. Cells 140 31842403
2009 Interaction between PAR-3 and the aPKC-PAR-6 complex is indispensable for apical domain development of epithelial cells. Journal of cell science 135 19401335
2008 Rho-kinase phosphorylates PAR-3 and disrupts PAR complex formation. Developmental cell 130 18267089
2011 Elaborating polarity: PAR proteins and the cytoskeleton. Development (Cambridge, England) 128 21303844
2017 aPKC Cycles between Functionally Distinct PAR Protein Assemblies to Drive Cell Polarity. Developmental cell 127 28781174
2006 Stabilization of cell polarity by the C. elegans RING protein PAR-2. Developmental cell 122 16459299
2006 The Scribble and Par complexes in polarity and migration: friends or foes? Trends in cell biology 121 17067797
2002 E4BP4/NFIL3, a PAR-related bZIP factor with many roles. BioEssays : news and reviews in molecular, cellular and developmental biology 121 12386933
2008 The PAR-6 polarity protein regulates dendritic spine morphogenesis through p190 RhoGAP and the Rho GTPase. Developmental cell 119 18267090
2017 A Single-Cell Biochemistry Approach Reveals PAR Complex Dynamics during Cell Polarization. Developmental cell 117 28829947
2005 Binding and phosphorylation of par-4 by akt is essential for cancer cell survival. Molecular cell 113 16209943
2017 The PAR proteins: from molecular circuits to dynamic self-stabilizing cell polarity. Development (Cambridge, England) 112 28974638
2008 Prothrombin/thrombin and the thrombin receptors PAR-1 and PAR-4 in the brain: localization, expression and participation in neurodegenerative diseases. Thrombosis and haemostasis 112 18841278
2004 Requirement for Par-6 and Bazooka in Drosophila border cell migration. Development (Cambridge, England) 109 15456726
2005 Par-4 links dopamine signaling and depression. Cell 106 16051151
2003 Role and regulation of the thrombin receptor (PAR-1) in human melanoma. Oncogene 105 12789289
2003 Apoptosis by Par-4 in cancer and neurodegenerative diseases. Experimental cell research 101 12565819
2015 Colon Cancer Growth and Dissemination Relies upon Thrombin, Stromal PAR-1, and Fibrinogen. Cancer research 98 26238780
2010 ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development. Developmental cell 97 20619750
2007 Cooperative roles of Par-3 and afadin in the formation of adherens and tight junctions. Journal of cell science 89 17606991
2005 Phosphorylation of Par-4 by protein kinase A is critical for apoptosis. Molecular and cellular biology 89 15657440
2020 Par complex cluster formation mediated by phase separation. Nature communications 88 32385244
2007 Acto-myosin reorganization and PAR polarity in C. elegans. Development (Cambridge, England) 88 17287245
2005 PAR proteins and the cytoskeleton: a marriage of equals. Current opinion in cell biology 88 16364625
2004 An overview of the KIN1/PAR-1/MARK kinase family. Biology of the cell 86 15182702
2006 par genes and the pathology of chromosome loss in Vibrio cholerae. Proceedings of the National Academy of Sciences of the United States of America 81 17197419
2015 Establishment of Par-Polarized Cortical Domains via Phosphoregulated Membrane Motifs. Developmental cell 76 26481050
2005 PAR proteins and the establishment of cell polarity during C. elegans development. BioEssays : news and reviews in molecular, cellular and developmental biology 76 15666355
2013 Principles of PAR polarity in Caenorhabditis elegans embryos. Nature reviews. Molecular cell biology 75 23594951
2009 Protease-activated receptor-4 (PAR 4): a role as inhibitor of visceral pain and hypersensitivity. Neurogastroenterology and motility 75 19413681
2001 Bazooka and PAR-6 are required with PAR-1 for the maintenance of oocyte fate in Drosophila. Current biology : CB 75 11516655
2008 EphrinB1 controls cell-cell junctions through the Par polarity complex. Nature cell biology 73 18604196
2019 Thrombin Signaling Promotes Pancreatic Adenocarcinoma through PAR-1-Dependent Immune Evasion. Cancer research 71 31048498
2011 PAR-1 and thrombin: the ties that bind the microenvironment to melanoma metastasis. Cancer research 71 22009534
2013 The PAR network: redundancy and robustness in a symmetry-breaking system. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 70 24062581
2017 Plant-derived phosphocholine facilitates cellular uptake of anti-pulmonary fibrotic HJT-sRNA-m7. Science China. Life sciences 69 28378154
2003 PAR-dependent and geometry-dependent mechanisms of spindle positioning. The Journal of cell biology 69 12642612
2008 MEX-5 asymmetry in one-cell C. elegans embryos requires PAR-4- and PAR-1-dependent phosphorylation. Development (Cambridge, England) 67 18842813
2004 Proteinase-activated receptor 1 (PAR-1) and cell apoptosis. Apoptosis : an international journal on programmed cell death 60 15505415
2007 The Par-1/MARK family of protein kinases: from polarity to metabolism. Cell cycle (Georgetown, Tex.) 58 17721078
2004 Baz, Par-6 and aPKC are not required for axon or dendrite specification in Drosophila. Nature neuroscience 58 15543144
2012 PAR-2 inhibition reverses experimental pulmonary hypertension. Circulation research 57 22461388
2007 Similar requirements for CDC-42 and the PAR-3/PAR-6/PKC-3 complex in diverse cell types. Developmental biology 55 17383625
2008 Par-4 inhibits Akt and suppresses Ras-induced lung tumorigenesis. The EMBO journal 54 18650932
2013 Protease-activated receptor (PAR) 1 and PAR4 differentially regulate factor V expression from human platelets. Molecular pharmacology 52 23307185
2008 PAR-1 kinase regulates epithelial detachment and directional protrusion of migrating border cells. Current biology : CB 52 18976916
2012 Mechanisms of apoptosis by the tumor suppressor Par-4. Journal of cellular physiology 49 22552839
2014 Phosphorylation of LKB1/Par-4 establishes Schwann cell polarity to initiate and control myelin extent. Nature communications 48 25255972
1999 Par-4: an emerging pivotal player in neuronal apoptosis and neurodegenerative disorders. Journal of molecular neuroscience : MN 48 10691289
2010 Expression of proteinase-activated receptor 1-4 (PAR 1-4) in human cancer. Journal of molecular histology 46 20563836
2014 PAR polarity: from complexity to design principles. Experimental cell research 44 25128809
1999 JTB: a novel membrane protein gene at 1q21 rearranged in a jumping translocation. Oncogene 43 10321732
2016 Regulation of Cell Polarity by PAR-1/MARK Kinase. Current topics in developmental biology 41 28236972
2012 PaR-PaR laboratory automation platform. ACS synthetic biology 41 23654257
2017 PAR-TERRA directs homologous sex chromosome pairing. Nature structural & molecular biology 40 28692038
2009 Proteinase activated receptor (PAR) involvement in mediating arthritis pain and inflammation. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 40 19184346
2022 Mice expressing fluorescent PAR2 reveal that endocytosis mediates colonic inflammation and pain. Proceedings of the National Academy of Sciences of the United States of America 39 35110404
2011 NAD+ depletion or PAR polymer formation: which plays the role of executioner in ischaemic cell death? Acta physiologica (Oxford, England) 38 21091637
2005 Thrombin and PAR-1-AP increase proinflammatory cytokine expression in C6 cells. The Journal of surgical research 38 16143343
2006 Expression of protease activated receptor-2 (PAR-2) in gastric cancer. Journal of surgical oncology 37 16425301
2012 Quantitative mass spectrometry and PAR-CLIP to identify RNA-protein interactions. Nucleic acids research 36 22885304
2019 PARP-1 activity (PAR) determines the sensitivity of cervical cancer to olaparib. Gynecologic oncology 34 31434613
2017 PAR-1 promotes microtubule breakdown during dendrite pruning in Drosophila. The EMBO journal 33 28554895
2015 Regulation of epithelial cell polarity by PAR-3 depends on Girdin transcription and Girdin-Gαi3 signaling. Journal of cell science 33 25977476
2010 Protease-activated receptor-2 (PAR(2)) in human periodontitis. Journal of dental research 33 20530726
2007 Characterization of Jumping translocation breakpoint (JTB) gene product isolated as a TGF-beta1-inducible clone involved in regulation of mitochondrial function, cell growth and cell death. Oncogene 31 17369841
2005 Regulation of cancer cell survival by Par-4. Annals of the New York Academy of Sciences 31 16382046
2015 PAR-4 and anillin regulate myosin to coordinate spindle and furrow position during asymmetric division. The Journal of cell biology 30 26416962
2008 Apoptosis and tumor resistance conferred by Par-4. Cancer biology & therapy 30 18836307
2020 The PAR-1 antagonist vorapaxar ameliorates kidney injury and tubulointerstitial fibrosis. Clinical science (London, England : 1979) 29 33078834
2019 HIV-1 Tat promotes astrocytic release of CCL2 through MMP/PAR-1 signaling. Glia 29 31124192
2015 A Par-1-Par-3-Centrosome Cell Polarity Pathway and Its Tuning for Isotropic Cell Adhesion. Current biology : CB 29 26455305
2014 Canonical and noncanonical roles of Par-1/MARK kinases in cell migration. International review of cell and molecular biology 29 25262242
2022 A particle size threshold governs diffusion and segregation of PAR-3 during cell polarization. Cell reports 28 35417695
2011 Systemic Par-4 inhibits non-autochthonous tumor growth. Cancer biology & therapy 28 21613819
2008 Par-4 binds to topoisomerase 1 and attenuates its DNA relaxation activity. Cancer research 28 18676842
2007 PAR-3 and PAR-1 inhibit LET-99 localization to generate a cortical band important for spindle positioning in Caenorhabditis elegans embryos. Molecular biology of the cell 28 17761536
2021 Studying PAR-Dependent Chromatin Remodeling to Tackle PARPi Resistance. Trends in molecular medicine 27 34030964
2020 A Conserved PDZ-Binding Motif in aPKC Interacts with Par-3 and Mediates Cortical Polarity. Current biology : CB 27 32084408
2015 Protease-activated receptor (PAR)-2 is required for PAR-1 signalling in pulmonary fibrosis. Journal of cellular and molecular medicine 27 25689283
2003 Human corneal epithelial cells express functional PAR-1 and PAR-2. Investigative ophthalmology & visual science 27 12506061
2000 The two-receptor system PAR-1/PAR-4 mediates alpha-thrombin-induced [Ca(2+)](i) mobilization in human astrocytoma cells. Journal of cancer research and clinical oncology 26 10664248
2021 Par-3 family proteins in cell polarity & adhesion. The FEBS journal 25 33565714
2015 Macrophage Migration Inhibitory Factor Mediates PAR-Induced Bladder Pain. PloS one 25 26020638
2007 Protease-activated receptor-2 (PAR-2) in cervical cancer proliferation. Gynecologic oncology 25 17936340
2002 PAR-1- and PAR-3-type thrombin receptor expression in primary cultures of human renal cell carcinoma cells. International journal of oncology 25 11743661

Missed literature

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

No submissions yet.