73,553 results match your criteria cytoplasmic domain

TANGO1 marshals the early secretory pathway for cargo export.

Biochim Biophys Acta Biomembr 2021 Jul 19:183700. Epub 2021 Jul 19.

Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona 08003, Spain; Universitat Pompeu Fabra (UPF), Barcelona 08002, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain. Electronic address:

TANGO1 protein facilitates the endoplasmic reticulum (ER) export of large cargoes that cannot be accommodated in 60 nm transport vesicles. It assembles into a ring in the plane of the ER membrane to create a distinct domain. Its lumenal portion collects and sorts folded cargoes while its cytoplasmic domains collar COPII coats, recruit retrograde COPI-coated membranes that fuse within the TANGO1 ring, thus opening a tunnel for cargo transfer from the ER into a growing export conduit. Read More

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Orf virus ORF120 protein positively regulates the NF-κB pathway by interacting with G3BP1.

J Virol 2021 Jul 21:JVI0015321. Epub 2021 Jul 21.

Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China.

Orf virus (ORFV) is a highly epitheliotropic parapoxvirus with zoonotic significance that induces proliferative lesions in the skin of sheep, goats and humans. Several viral proteins encoded by ORFV, including NF-κB inhibitors, play important roles in hijacking host-associated proteins for viral evasion of the host innate immune response. However, the roles of proteins with unknown functions in viral replication and latent infection remain to be explored. Read More

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A double bilayer to study the nonequilibrium environmental response of GIRK2 in complex states.

Phys Chem Chem Phys 2021 Jul 20. Epub 2021 Jul 20.

State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.

G protein-gated inwardly rectifying potassium (GIRK) channels play essential roles in electrical signaling in neurons and muscle cells. Nonequilibrium environments provide crucial driving forces behind many cellular events. Here, we apply the antiparallel alignment double bilayer model to study GIRK2 in response to the time-dependent membrane potential. Read More

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YPIBP: A repository for phosphoinositide-binding proteins in yeast.

Comput Struct Biotechnol J 2021 24;19:3692-3707. Epub 2021 Jun 24.

Department of Electrical Engineering, College of Electrical Engineering and Computer Science, National Cheng Kung University, Tainan 701, Taiwan.

Phosphoinositides (PIs) are a family of eight lipids consisting of phosphatidylinositol (PtdIns) and its seven phosphorylated forms. PIs have important regulatory functions in the cell including lipid signaling, protein transport, and membrane trafficking. Yeast has been recognized as a eukaryotic model system to study lipid-protein interactions. Read More

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COVID-19: Myths and Reality.

Biochemistry (Mosc) 2021 Jul;86(7):800-817

FORT LLC, R&D Department, Moscow, 119435, Russia.

COVID-19, a new human respiratory disease that has killed nearly 3 million people in a year since the start of the pandemic, is a global public health challenge. Its infectious agent, SARS-CoV-2, differs from other coronaviruses in a number of structural features that make this virus more pathogenic and transmissible. In this review, we discuss some important characteristics of the main SARS-CoV-2 surface antigen, the spike (S) protein, such as (i) ability of the receptor-binding domain (RBD) to switch between the "standing-up" position (open pre-fusion conformation) for receptor binding and the "lying-down" position (closed pre-fusion conformation) for immune system evasion; (ii) advantage of a high binding affinity of the RBD open conformation to the human angiotensin-converting enzyme 2 (ACE2) receptor for efficient cell entry; and (iii) S protein preliminary activation by the intracellular furin-like proteases for facilitation of the virus spreading across different cell types. Read More

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Grass carp (Ctenopharyngodon idella) interferon regulatory factor 8 down-regulates interferon1 expression via interaction with interferon regulatory factor 2 in vitro.

Mol Immunol 2021 Jul 16;137:202-211. Epub 2021 Jul 16.

School of Life Science, Nanchang University, Nanchang, 330031, China. Electronic address:

Interferon regulatory factor 8 (IRF8), also known as interferon consensus sequence-binding protein (ICSBP), is a negative regulatory factor of interferon (IFN) and plays an important role in cell differentiation and innate immunity in mammals. In recent years, some irf8 homologous genes have been cloned and confirmed to take part in innate immune response in fish, but the mechanism still remains unclear. In this paper, a grass carp (Ctenopharyngodon idella) irf8 gene (Ciirf8) was cloned and characterized. Read More

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FGGY Carbohydrate Kinase Domain Containing is Expressed and Alternatively Spiced in Skeletal Muscle and Attenuates MAP Kinase and Akt Signaling.

Gene 2021 Jul 16:145836. Epub 2021 Jul 16.

University of North Florida, Department of Biology, 1 UNF Drive, Jacksonville, Florida, 32224. Electronic address:

Skeletal muscle atrophy can result from a range of physiological conditions, including denervation, immobilization, hindlimb unweighting, and aging. To better characterize the molecular genetic events of atrophy, a microarray analysis revealed that FGGY carbohydrate kinase domain containing (Fggy) is expressed in skeletal muscle and is induced in response to denervation. Bioinformatic analysis of the Fggy gene locus revealed two validated isoforms with alternative transcription initiation sites that we have designated Fggy-L-552 and Fggy-S-387. Read More

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A novel CgIFNLP receptor involved in regulating ISG expression in oyster Crassostrea gigas.

Dev Comp Immunol 2021 Jul 15;124:104206. Epub 2021 Jul 15.

Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, 116023, China; Southern Laboratory of Ocean Science and Engineering (Guangdong, Zhuhai), Zhuhai, 519000, China; Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, 116023, China; Dalian Key Laboratory of Aquatic Animal Disease Prevention and Control, Dalian Ocean University, Dalian, 116023, China.

Interferons (IFNs) are the key coordinators of antiviral immunity by binding to their receptors to orchestrate a complex transcriptional network in vertebrates. Recently, the existence of molluscan IFN-like system has been certified by the identification of important components in IFN system, such as IFN-like protein (CgIFNLP) from oyster Crassostrea gigas. In the present study, a novel CgIFNLP receptor (designed CgIFNLPR-1) was identified from C. Read More

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Transient Tertiary Structures of Disordered Dynein Intermediate Chain Regulate its Interactions with Multiple Partners.

J Mol Biol 2021 Jul 14:167152. Epub 2021 Jul 14.

Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331, United States. Electronic address:

The N-terminal domain of dynein intermediate chain (N-IC) is central to the cytoplasmic dynein 'cargo attachment subcomplex' and regulation of motor activity. It is a prototypical intrinsically disordered protein (IDP), serving as a primarily disordered polybivalent molecular scaffold for numerous binding partners, including three dimeric dynein light chains and coiled coil domains of dynein partners dynactin p150 and NudE. At the very N-terminus, a 40 amino acid single alpha helix (SAH) forms the major binding site for both p150 and NudE, while a shorter nascent helix (H2) separated from SAH by a disordered linker, is necessary for tight binding to dynactin p150 but not to NudE. Read More

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The molecular basis of regulation of bacterial capsule assembly by Wzc.

Nat Commun 2021 07 16;12(1):4349. Epub 2021 Jul 16.

Rosalind Franklin Institute, Harwell Campus, Harwell, UK.

Bacterial extracellular polysaccharides (EPSs) play critical roles in virulence. Many bacteria assemble EPSs via a multi-protein "Wzx-Wzy" system, involving glycan polymerization at the outer face of the cytoplasmic/inner membrane. Gram-negative species couple polymerization with translocation across the periplasm and outer membrane and the master regulator of the system is the tyrosine autokinase, Wzc. Read More

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Sorting of cadherin-catenin-associated proteins into individual clusters.

Proc Natl Acad Sci U S A 2021 Jul;118(29)

Department of Dermatology, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611;

The cytoplasmic tails of classical cadherins form a multiprotein cadherin-catenin complex (CCC) that constitutes the major structural unit of adherens junctions (AJs). The CCC in AJs forms junctional clusters, "E clusters," driven by and interactions in the cadherin ectodomain and stabilized by α-catenin-actin interactions. Additional proteins are known to bind to the cytoplasmic region of the CCC. Read More

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Structural basis for potassium transport in prokaryotes by KdpFABC.

Proc Natl Acad Sci U S A 2021 Jul;118(29)

Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University Grossman School of Medicine, New York, NY 10016;

KdpFABC is an oligomeric K transport complex in prokaryotes that maintains ionic homeostasis under stress conditions. The complex comprises a channel-like subunit (KdpA) from the superfamily of K transporters and a pump-like subunit (KdpB) from the superfamily of P-type ATPases. Recent structural work has defined the architecture and generated contradictory hypotheses for the transport mechanism. Read More

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Missense Variant in Insulin Receptor (Y1355H) Segregates in Family with Fatty Liver Disease.

Mol Metab 2021 Jul 13:101299. Epub 2021 Jul 13.

The Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA. Electronic address:

A missense variant in the cytoplasmic domain of the insulin receptor (INSR) was identified by exome sequencing in affected members of a four-generation family with fatty liver disease (FLD). The variant (rs766457461, c.4063T>C, p. Read More

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LACTB2 renders radioresistance by activating PINK1/Parkin-dependent mitophagy in nasopharyngeal carcinoma.

Cancer Lett 2021 Jul 13;518:127-139. Epub 2021 Jul 13.

Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai, 200032, China. Electronic address:

Radiotherapy is a standard and conventional treatment strategy for nasopharyngeal carcinoma (NPC); however, radioresistance remains refractory to clinical outcomes. Understanding the molecular mechanism of radioresistance is crucial for advancing the efficacy of radiotherapy and improving the prognosis of NPC. In this study, β-lactamase-like-protein 2 (LACTB2) was identified as a potential biomarker for radioresistance using tandem mass tag proteomic analysis of NPC cells, gene chip analysis of NPC tissues, and differential gene analysis between NPC and normal nasopharyngeal tissues from the Gene Expression Omnibus database GSE68799. Read More

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Biology of AMPA receptor interacting proteins - From biogenesis to synaptic plasticity.

Neuropharmacology 2021 Jul 13:108709. Epub 2021 Jul 13.

Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, UK. Electronic address:

AMPA-type glutamate receptors mediate the majority of excitatory synaptic transmission in the central nervous system. Their signaling properties and abundance at synapses are both crucial determinants of synapse efficacy and plasticity, and are therefore under sophisticated control. Unique to this ionotropic glutamate receptor (iGluR) is the abundance of interacting proteins that contribute to its complex regulation. Read More

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ROBO1 Promotes Homing, Dissemination, and Survival of Multiple Myeloma within the Bone Marrow Microenvironment.

Blood Cancer Discov 2021 Jul;2(4):338-353

Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA.

The bone marrow (BM) microenvironment actively promotes multiple myeloma (MM) pathogenesis and therapies targeting both cancer cells and the niche are highly effective. We were interested in identifying novel signaling pathways supporting MM-BM crosstalk. Mutations in the transmembrane receptor Roundabout 1 (ROBO1) were recently identified in MM patients, however their functional consequences are uncertain. Read More

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Carboxypeptidase E regulates Activity-dependent TrkB Neuronal surface Insertion and Hippocampal memory.

J Neurosci 2021 Jul 15. Epub 2021 Jul 15.

Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China

Activity-dependent insertion of the tropomyosin-related kinase B (TrkB) receptor into the plasma membrane can explain, in part, the preferential effect of brain-derived neurotrophic factor (BDNF) on active neurons and synapses; however, the underlying molecular mechanisms remain obscure. Here, we report a novel function for carboxypeptidase E (CPE) in controlling chemical long-term potentiation (cLTP) stimuli-induced TrkB surface delivery in hippocampal neurons. Total internal reflection fluorescence (TIRF) assays and line plot assays showed that CPE facilitates TrkB transport from dendritic shafts to the plasma membrane. Read More

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Structures of rhodopsin in complex with G-protein-coupled receptor kinase 1.

Nature 2021 Jul 14;595(7868):600-605. Epub 2021 Jul 14.

Department of Biological Sciences, Purdue University, West Lafayette, IN, USA.

G-protein-coupled receptor (GPCR) kinases (GRKs) selectively phosphorylate activated GPCRs, thereby priming them for desensitization. Although it is unclear how GRKs recognize these receptors, a conserved region at the GRK N terminus is essential for this process. Here we report a series of cryo-electron microscopy single-particle reconstructions of light-activated rhodopsin (Rho*) bound to rhodopsin kinase (GRK1), wherein the N terminus of GRK1 forms a helix that docks into the open cytoplasmic cleft of Rho*. Read More

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CRIP1 cooperates with BRCA2 to drive the nuclear enrichment of RAD51 and to facilitate homologous repair upon DNA damage induced by chemotherapy.

Oncogene 2021 Jul 14. Epub 2021 Jul 14.

Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, PR China.

Homologous recombination (HR) repair is an important determinant of chemosensitivity. However, the mechanisms underlying HR regulation remain largely unknown. Cysteine-rich intestinal protein 1 (CRIP1) is a member of the LIM/double-zinc finger protein family and is overexpressed and associated with prognosis in several tumor types. Read More

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Pch2 orchestrates the meiotic recombination checkpoint from the cytoplasm.

PLoS Genet 2021 Jul 14;17(7):e1009560. Epub 2021 Jul 14.

Instituto de Biología Funcional y Genómica (IBFG), Consejo Superior de Investigaciones Científicas (CSIC) and University of Salamanca, Salamanca, Spain.

During meiosis, defects in critical events trigger checkpoint activation and restrict cell cycle progression. The budding yeast Pch2 AAA+ ATPase orchestrates the checkpoint response launched by synapsis deficiency; deletion of PCH2 or mutation of the ATPase catalytic sites suppress the meiotic block of the zip1Δ mutant lacking the central region of the synaptonemal complex. Pch2 action enables adequate levels of phosphorylation of the Hop1 axial component at threonine 318, which in turn promotes activation of the Mek1 effector kinase and the ensuing checkpoint response. Read More

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E2F4's cytoplasmic role in multiciliogenesis is mediated via an N-terminal domain that binds two components of the centriole replication machinery, Deup1 and SAS6.

Mol Biol Cell 2021 Jul 14:mbcE21010039. Epub 2021 Jul 14.

David H. Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, MA, USA.

Multiciliated cells play critical roles in the airway, reproductive organs and brain. Generation of multiple cilia requires both activation of a specialized transcriptional program and subsequent massive amplification of centrioles within the cytoplasm. The E2F4 transcription factor is required for both roles, and consequently for multiciliogenesis. Read More

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Human cytomegalovirus UL42 protein inhibits the degradation of glycoprotein B through inhibition of Nedd4 family ubiquitin E3 ligases.

Microbiol Immunol 2021 Jul 14. Epub 2021 Jul 14.

Department of Microbiology and Immunology, Gifu Pharmaceutical University, Gifu, Japan.

Human cytomegalovirus (HCMV) is a globally ubiquitous pathogen and causes congenital infection as well as opportunistic infection in immunocompromised patients. The HCMV UL42 gene encodes a membrane protein that regulates the function of Nedd4 family ubiquitin E3 ligases through its PPxY motif. As HCMV envelope glycoprotein B (gB) also has a PPxY motif at its C-terminal cytoplasmic domain, we examined whether there was any relationship between UL42 protein with gB. Read More

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Excess membrane binding of monomeric alpha-, beta-, and gamma-synuclein is invariably associated with inclusion formation and toxicity.

Hum Mol Genet 2021 Jul 12. Epub 2021 Jul 12.

Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115 USA.

α-synuclein (αS) has been well-documented to play a role in human synucleinopathies such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). First, the lesions found in PD/DLB brains-Lewy bodies and Lewy neurites-are rich in aggregated αS. Second, genetic evidence links missense mutations and increased αS expression to familial forms of PD/DLB. Read More

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Diversity and function of arthropod endosymbiont toxins.

Trends Microbiol 2021 Jul 9. Epub 2021 Jul 9.

Department of Biology, Indiana University, Bloomington, IN, USA. Electronic address:

Bacterial endosymbionts induce dramatic phenotypes in their arthropod hosts, including cytoplasmic incompatibility, feminization, parthenogenesis, male killing, parasitoid defense, and pathogen blocking. The molecular mechanisms underlying these effects remain largely unknown but recent evidence suggests that protein toxins secreted by the endosymbionts play a role. Here, we describe the diversity and function of endosymbiont proteins with homology to known bacterial toxins. Read More

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The Orphan GPCR Receptor, GPR88, Interacts with Nuclear Protein Partners in the Cerebral Cortex.

Cereb Cortex 2021 Jul 9. Epub 2021 Jul 9.

Cellular Biology and Molecular Pharmacology of Central Receptors, Institut de Psychiatrie et de Neurosciences de Paris, Inserm U1266, Paris 75014, France.

GPR88 is an orphan G-protein-coupled receptor (GPCR) highly expressed in striatal medium spiny neurons (MSN), also found in cortical neurons at low level. In MSN, GPR88 has a canonical GPCR plasma membrane/cytoplasmic expression, whereas in cortical neurons, we previously reported an atypical intranuclear localization. Molecular size analysis suggests that GPR88, expressed in plasma membrane of MSN or in nuclear compartment of cortical neurons, corresponds to the full-length protein. Read More

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KIR3DL3-HHLA2 is a human immunosuppressive pathway and a therapeutic target.

Sci Immunol 2021 Jul;6(61)

Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

The B7 family ligand HERV-H LTR-associating protein 2 (HHLA2) is an attractive target for cancer immunotherapy because of its coinhibitory function, overexpression in human cancers, and association with poor prognoses. However, the knowledge of the HHLA2 pathway is incomplete. HHLA2 has an established positive receptor transmembrane and immunoglobulin (Ig) domain containing 2 (TMIGD2) but a poorly characterized negative receptor human killer cell Ig-like receptor, three Ig domains, and long cytoplasmic tail (KIR3DL3). Read More

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Autophagic Degradation of Gasdermin D Protects against Nucleus Pulposus Cell Pyroptosis and Retards Intervertebral Disc Degeneration In Vivo.

Oxid Med Cell Longev 2021 17;2021:5584447. Epub 2021 Jun 17.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Intervertebral disc degeneration (IDD) is the primary culprit of low back pain and renders heavy social burden worldwide. Pyroptosis is a newly discovered form of programmed cell death, which is also involved in nucleus pulposus (NP) cells during IDD progression. Moderate autophagy activity is critical for NP cell survival, but its relationship with pyroptosis remains unknown. Read More

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NT157 Inhibits HCC Migration via Downregulating the STAT3/Jab1 Signaling Pathway.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211027916

Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.

Purpose: The high fatality-to-case ratio of hepatocellular carcinoma is directly related to metastasis. The signal transducer and activator of transcription-3 is a key mediator of the cytokine and growth factor signaling pathways and drives the transcription of genes responsible for cancer-associated phenotypes. However, so far, no specific inhibitor for signal transducer and activator of transcription-3 has been used in clinical practice. Read More

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Burkholderia multivorans requires species-specific GltJK for entry of a contact-dependent growth inhibition system protein.

Mol Microbiol 2021 Jul 8. Epub 2021 Jul 8.

Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY, 40536, USA.

Interbacterial antagonism and communication are driving forces behind microbial community development. In many Gram-negative bacteria, contact-dependent growth inhibition (CDI) systems contribute to these microbial interactions. CDI systems deliver the toxic C-terminus of a large surface exposed protein to the cytoplasm of neighboring bacteria upon cell-cell contact. Read More

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Structure/Function Analysis of human ZnT8 (SLC30A8): A Diabetes Risk Factor and Zinc Transporter.

Curr Res Struct Biol 2020 27;2:144-155. Epub 2020 Jun 27.

Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.

The human zinc transporter ZnT8 (SLC30A8) is expressed primarily in pancreatic β-cells and plays a key function in maintaining the concentration of blood glucose through its role in insulin storage, maturation and secretion. ZnT8 is an autoantigen for Type 1 diabetes (T1D) and is associated with Type 2 diabetes (T2D) through its risk allele that encodes a major non-synonymous single nucleotide polymorphism (SNP) at Arg325. Loss of function mutations improve insulin secretion and are protective against diabetes. Read More

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