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Additional Table 3 the 3 GO Terms with the Highest Changes In

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Additional Table 3 The 3 GO terms with the highest changes in enrichment scores at each SCI sub-group Sub-groupsDEGs CategoryGO terms P Fold EnrichmentGenes 0.5 h Upregulated Genes GO_BP positive regulation of TRAIL-activated apoptotic signaling pathway 0.0012 49.0027 ATF3, TIMP3, PTEN cellular response to cycloheximide 0.0012 49.0027 KLF2, MYC, KLF4 positive regulation of cell aging 0.0403 49.0027 TRP53, LMNA GO_CC neuronal cell body membrane 0.0023 8.8052 ATP2B1, KCNA2, KCNB1, HPCA, CX3CR1 microtubule associated complex 0.0153 7.5659 NDEL1, MAP1B, PAFAH1B1, RANBP2 nuclear euchromatin 0.0203 6.8094 JUN, MYC, KLF4, SMARCA4 GO_MF C-4 methylsterol oxidase activity 0.0424 46.5227 MSMO1, CH25H CCR2 chemokine receptor binding 0.0027 34.8920 CCL12, CCL2, CCL7 MRF binding 0.0065 23.2613 TSC22D3, CREBBP, BHLHE40 Downregulated GenesGO_BP intramembranous ossification 0.0005 86.9327 COL1A1, AXIN2, MMP2 endothelium development 0.0282 69.5462 SLC40A1, KDR peripheral nervous system axon regeneration 0.0282 69.5462 TNC, MMP2 GO_CC cytoplasmic microtubule 0.0360 9.9504 BIRC5, MID1, AXIN2 nuclear envelope 0.0096 5.9828 TRPC2, AGPAT5, CHIL3, RRM2, TFDP2 extracellular matrix 0.0009 5.1444 LPL, LUM, TNC, CILP, COL2A1, COL1A1, MFAP4, ... GO_MF tRNA (guanine-N2-)-methyltransferase activity 0.0171 115.1551 TRMT1L, TRMT11 glycine binding 0.0033 34.5465 GLRA1, GRIN2B, SRR integrin binding 0.0198 6.9093 FAP, IGF1, ACTN1, KDR 4 h Upregulated Genes GO_BP antigen processing and presentation of exogenous peptide antigen via MHC class I 0.0001 13.8031 H2-K1, IFI30, FCER1G, FCGR1, FCGR3 antigen processing and presentation of peptide antigen 0.0014 13.8031 SLC11A1, H2-AA, H2-AB1, CTSS toll-like receptor 7 signaling pathway 0.0014 13.8031 HAVCR2, UNC93B1, PIK3AP1, TLR7 GO_CC NLRP3 inflammasome complex 0.0032 11.3000 CASP4, GSDMD, PYCARD, CASP1 AIM2 inflammasome complex 0.0273 10.5938 CASP4, PYCARD, CASP1 CD95 death-inducing signaling complex 0.0273 10.5938 CFLAR, CASP8, FAS GO_MF IgG receptor activity 0.0153 13.6510 FCGRT, FCGR1, FCGR3 peptidase activator activity involved in apoptotic process 0.0153 13.6510 PYCARD, CTSC, CTSH Fc-gamma receptor I complex binding 0.0153 13.6510 LGALS3, FGR, FLNA Downregulated GenesGO_BP regulation of synaptic transmission, dopaminergic 0.0059 23.2616 CNTNAP4, PNKD, CHRNA7 positive regulation of long term synaptic depression 0.0097 18.6093 KCNB1, STAU2, IQSEC2 regulation of cAMP-mediated signaling 0.0097 18.6093 PDE4A, PEX5L, RASD2 GO_CC cone cell pedicle 0.0058 23.5944 SLC32A1, RAPGEF4, PCLO synaptic cleft 0.0016 15.7296 CDH8, DNM3, GRIN2B, GRIN1 spectrin-associated cytoskeleton 0.0139 15.7296 ANK1, ANK3, SPTB GO_MF voltage-gated cation channel activity 0.0099 18.3642 GRIK1, GRIN2D, GRIN1 NMDA glutamate receptor activity 0.0017 15.3035 GRIN2B, GRIN2C, GRIN2D, GRIN1 oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor0.0146 15.3035 TM7SF2, DHCR7, DHCR24 24 h Upregulated Genes GO_BP positive regulation of platelet activation 0.0000 20.5477 PTPRJ, SELP, PLEK, PDPN, TLR4 wound healing involved in inflammatory response 0.0069 20.5477 CD44, HMOX1, CCR2 positive regulation of monocyte aggregation 0.0069 20.5477 CD44, HAS2, NR4A3 GO_CC CHOP-C/EBP complex 0.0062 21.5356 CEBPA, CEBPB, DDIT3 I-kappaB/NF-kappaB complex 0.0009 17.2285 RELA, RELB, NFKB1, NFKB2 lamin filament 0.0196 12.9214 EIF6, LMNB1, LMNA GO_MF CCR2 chemokine receptor binding 0.0141 14.9537 CCL12, CCL2, CCL7 C-C chemokine binding 0.0022 13.2922 ZFP36, CCR5, CCR1, ACKR1 interleukin-1 receptor activity 0.0022 13.2922 IL1R2, IL1R1, IL18RAP, IL1RAP Downregulated GenesGO_BP intramembranous ossification 0.0005 22.8308 CTSK, COL1A1, AXIN2, MMP2 regulation of endothelial cell proliferation 0.0005 22.8308 BMP4, ALDH1A2, TEK, KDR urinary bladder development 0.0080 20.5477 WNT5A, RBP4, TRP63 GO_CC synaptic cleft 0.0195 13.4059 CDH8, GRIN2B, C1QL1 AP-2 adaptor complex 0.0246 11.9164 EPS15, TBC1D5, SGIP1 microfibril 0.0362 9.7498 LTBP1, FBN2, MFAP4 GO_MF GPI-linked ephrin receptor activity 0.0156 14.9537 EPHA5, EPHA7, EPHA3 platelet-derived growth factor binding 0.0003 14.5383 COL3A1, COL1A2, PDGFRB, COL2A1, COL1A1 G-protein coupled purinergic nucleotide receptor activity 0.0054 10.7360 P2RY12, P2RY13, GPR34, P2RY14 3 d Upregulated Genes GO_BP antigen processing and presentation of exogenous peptide antigen via MHC class I 0.0002 12.7159 H2-K1, IFI30, FCER1G, FCGR1, FCGR3 antigen processing and presentation of peptide antigen 0.0018 12.7159 SLC11A1, H2-AA, H2-AB1, CTSS positive regulation of neutrophil apoptotic process 0.0175 12.7159 CD44, ANXA1, HCAR2 GO_CC CHOP-C/EBP complex 0.0162 13.2493 CEBPA, CEBPB, DDIT3 interleukin-6 receptor complex 0.0162 13.2493 IL6, IL6ST, IL6RA collagen type V trimer 0.0162 13.2493 COL5A3, COL5A2, COL5A1 GO_MF Fc-gamma receptor I complex binding 0.0178 12.6146 LGALS3, FGR, FLNA peptidase activator activity involved in apoptotic process 0.0178 12.6146 PYCARD, CTSC, CTSH CCR5 chemokine receptor binding 0.0001 10.8125 NES, CNIH4, STAT1, CCL5, CCL4, STAT3 Downregulated GenesGO_BP spontaneous neurotransmitter secretion 0.0111 16.0729 RIMS2, RIMS1, STX1B development of primary male sexual characteristics 0.0111 16.0729 WNT5A, SFRP1, SFRP2 positive regulation of protein kinase C activity 0.0213 12.0547 WNT5A, AGT, CEMIP GO_CC GABA receptor complex 0.0112 16.0114 GABRG2, GABRA1, GABRB2 synaptic cleft 0.0000 12.0086 CDH8, GRIN2B, GRIN1, C1QL1, GRIA3, ADGRB3 kainate selective glutamate receptor complex 0.0343 9.6068 GRIK1, GRIK5, GRIA4 GO_MF microsatellite binding 0.0112 16.0202 HEY1, HEY2, HEYL neurotransmitter binding 0.0000 12.4602 GRIN2B, SLC6A11, GRIN2D, SLC6A13, GRIN1, ... NMDA glutamate receptor activity 0.0000 12.0152 GRIN2B, GRIN2C, GRIN2D, GRIN1, GRIN3B, ... 7 d Upregulated Genes GO_BP glycosaminoglycan metabolic process 0.0001 8.2679 GNS, NDST1, HEXA, HEXB, FOXC1, CLN6 positive regulation of platelet activation 0.0010 8.2679 PTPRJ, SELP, PLEK, PDPN, TLR4 toll-like receptor 7 signaling pathway 0.0064 8.2679 HAVCR2, UNC93B1, PIK3AP1, TLR7 GO_CC death-inducing signaling complex 0.0001 8.4970 CFLAR, CASP3, RIPK1, CASP8, FADD, FAS ripoptosome 0.0001 8.4970 CFLAR, RIPK1, TICAM1, CASP8, RIPK3, FADD condensin complex 0.0009 8.4970 NCAPH, NCAPG, SMC2, SMC4, NCAPD2 GO_MF cysteine-type endopeptidase activity involved in execution phase of apoptosis 0.0398 8.3235 CFLAR, CASP3, CASP7 Fc-gamma receptor I complex binding 0.0398 8.3235 LGALS3, FGR, FLNA nicotinate-nucleotide diphosphorylase (carboxylating) activity 0.0398 8.3235 NAMPT, QPRT, NAPRT Downregulated GenesGO_BP positive regulation of long term synaptic depression 0.0002 11.6884 PPP1R9A, MAPT, KCNB1, STAU2, IQSEC2 regulation of cAMP-mediated signaling 0.0002 11.6884 GNAI1, PDE4A, PDE10A, PEX5L, RASD2 regulation of synaptic transmission, dopaminergic 0.0023 11.6884 CNTNAP4, PNKD, CHRNB2, CHRNA7 GO_CC GABA receptor complex 0.0212 11.5455 GABRG2, GABRA1, GABRB2 juxtaparanode region of axon 0.0000 9.2364 EPB41L3, KCNAB2, KCNAB1, KCNA2, KCNA1, ... synaptic cleft 0.0002 8.6591 CDH8, DNM3, GRIN2B, GRIN1, GRIA3, ADGRB3 GO_MF netrin receptor activity 0.0023 11.6774 DCC, UNC5B, UNC5A, UNC5C AMPA glutamate receptor activity 0.0023 11.6774 GRIA2, GRIA1, GRIA3, GRIA4 voltage-gated calcium channel activity involved in AV node cell action potential 0.0207 11.6774 CACNA1G, CACNB2, CACNA1C 28 d Upregulated Genes GO_BP response to interferon-beta 0.0000 11.6059 PLSCR1, IKBKE, IFNAR2, BST2, IFITM1, IFITM2, ... positive regulation of apoptotic cell clearance 0.0024 11.6059 CCL2, C3, MFGE8, C2 positive regulation of neutrophil apoptotic process 0.0210 11.6059 CD44, ANXA1, HCAR2 GO_CC CHOP-C/EBP complex 0.0200 11.9019 CEBPA, CEBPB, DDIT3 ripoptosome 0.0006 9.9183 CFLAR, RIPK1, TICAM1, CASP8, RIPK3 NLRP3 inflammasome complex 0.0052 9.5215 CASP4, GSDMD, PYCARD, CASP1 GO_MF IgG receptor activity 0.0212 11.5231 FCGRT, FCGR1, FCGR3 epidermal growth factor binding 0.0212 11.5231 EGFR, SEC61B, SHC1 peptidase activator activity involved in apoptotic process 0.0212 11.5231 PYCARD, CTSC, CTSH Downregulated GenesGO_BP positive regulation of long term synaptic depression 0.0006 19.9801 PPP1R9A, KCNB1, STAU2, IQSEC2 JUN phosphorylation 0.0091 18.7314 MAPK8, MAPK10, MAPK8IP1 regulation of synaptic transmission, dopaminergic 0.0091 18.7314 CNTNAP4, PNKD, CHRNA7 GO_CC cone cell pedicle 0.0089 18.9058 SLC32A1, RAPGEF4, PCLO potassium channel complex 0.0000 13.7497 KCNH1, KCNAB2, KCNAB1, KCNA2, KCNA6, ... NMDA selective glutamate receptor complex 0.0001 12.6038 DLGAP3, GRIN2B, GRIN2C, GRIN2D, GRIN1, ... GO_MF netrin receptor activity 0.0091 18.7457 DCC, UNC5B, UNC5C NMDA glutamate receptor activity 0.0002 15.6214 GRIN2B, GRIN2C, GRIN2D, GRIN1, GRIN3A voltage-gated cation channel activity 0.0147 14.9966 GRIK1, GRIN2D, GRIN1.
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  • Ion Channels

    Ion Channels

    UC Davis UC Davis Previously Published Works Title THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels. Permalink https://escholarship.org/uc/item/1442g5hg Journal British journal of pharmacology, 176 Suppl 1(S1) ISSN 0007-1188 Authors Alexander, Stephen PH Mathie, Alistair Peters, John A et al. Publication Date 2019-12-01 DOI 10.1111/bph.14749 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Ion channels. British Journal of Pharmacology (2019) 176, S142–S228 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels Stephen PH Alexander1 , Alistair Mathie2 ,JohnAPeters3 , Emma L Veale2 , Jörg Striessnig4 , Eamonn Kelly5, Jane F Armstrong6 , Elena Faccenda6 ,SimonDHarding6 ,AdamJPawson6 , Joanna L Sharman6 , Christopher Southan6 , Jamie A Davies6 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK 2Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK 3Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK 4Pharmacology and Toxicology, Institute of Pharmacy, University of Innsbruck, A-6020 Innsbruck, Austria 5School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK 6Centre for Discovery Brain Science, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties.
  • Multi-Functionality of Proteins Involved in GPCR and G Protein Signaling: Making Sense of Structure–Function Continuum with In

    Multi-Functionality of Proteins Involved in GPCR and G Protein Signaling: Making Sense of Structure–Function Continuum with In

    Cellular and Molecular Life Sciences (2019) 76:4461–4492 https://doi.org/10.1007/s00018-019-03276-1 Cellular andMolecular Life Sciences REVIEW Multi‑functionality of proteins involved in GPCR and G protein signaling: making sense of structure–function continuum with intrinsic disorder‑based proteoforms Alexander V. Fonin1 · April L. Darling2 · Irina M. Kuznetsova1 · Konstantin K. Turoverov1,3 · Vladimir N. Uversky2,4 Received: 5 August 2019 / Revised: 5 August 2019 / Accepted: 12 August 2019 / Published online: 19 August 2019 © Springer Nature Switzerland AG 2019 Abstract GPCR–G protein signaling system recognizes a multitude of extracellular ligands and triggers a variety of intracellular signal- ing cascades in response. In humans, this system includes more than 800 various GPCRs and a large set of heterotrimeric G proteins. Complexity of this system goes far beyond a multitude of pair-wise ligand–GPCR and GPCR–G protein interactions. In fact, one GPCR can recognize more than one extracellular signal and interact with more than one G protein. Furthermore, one ligand can activate more than one GPCR, and multiple GPCRs can couple to the same G protein. This defnes an intricate multifunctionality of this important signaling system. Here, we show that the multifunctionality of GPCR–G protein system represents an illustrative example of the protein structure–function continuum, where structures of the involved proteins represent a complex mosaic of diferently folded regions (foldons, non-foldons, unfoldons, semi-foldons, and inducible foldons). The functionality of resulting highly dynamic conformational ensembles is fne-tuned by various post-translational modifcations and alternative splicing, and such ensembles can undergo dramatic changes at interaction with their specifc partners.