{ "bcoid": "GLY_000468", "title": "HCV1a Protein Function (UniProtKB)", "description": "The Hepatitis C virus (genotype 1a, isolate H) Protein Function (UniProtKB) dataset contains biological ...", "filename": "hcv1a_protein_function_uniprotkb.csv", "filetype": "csv", "categories": { "species": "Hepatitis C virus (genotype 1a, isolate H)", "molecule": "Protein", "tags": "Protein Function", "file_type": "csv", "status": "Reviewed", "scope": "internal" }, "minitable": { "content": [ [ "P27958-1...", "protein_xref..." ], [ "P27958-1...", "protein_xref..." ] ], "headers": [ "uniprotkb_ca...", "xref_key..." ], "colwidth": [ "40%", "20%" ] }, "sampledata": { "type": "table", "data": [ [ { "type": "string", "label": "uniprotkb_canonical_ac" }, { "type": "string", "label": "xref_key" }, { "type": "string", "label": "xref_id" }, { "type": "string", "label": "evidence" }, { "type": "string", "label": "annotation" } ], [ "P27958-1", "protein_xref_uniprotkb_fun", "P27958", "23868571", "Induces a specific membrane alteration that serves as a scaffold for the virus replication complex. This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex. NS4B polymerization or in protein-protein interactions activity may contribute to its function in membranous web formation (PubMed:23868571). Plays also a role in the inhibition of host innate response by inhibiting host TLR3-mediated interferon signaling. Mechanistically, promotes host TRIF protein degradation in a caspase8-dependent manner (PubMed:29782532)." ], [ "P27958-1", "protein_xref_uniprotkb_fun", "P27958", "29782532", "Induces a specific membrane alteration that serves as a scaffold for the virus replication complex. This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex. NS4B polymerization or in protein-protein interactions activity may contribute to its function in membranous web formation (PubMed:23868571). Plays also a role in the inhibition of host innate response by inhibiting host TLR3-mediated interferon signaling. Mechanistically, promotes host TRIF protein degradation in a caspase8-dependent manner (PubMed:29782532)." ], [ "P27958-1", "protein_xref_uniprotkb_fun", "P27958", "", "Cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation." ], [ "P27958-1", "protein_xref_uniprotkb_fun", "P27958", "11086025", "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation (PubMed:23799612). Interacts with, and activates STAT3 leading to cellular transformation. Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation (PubMed:11086025). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (PubMed:14602201)." ], [ "P27958-1", "protein_xref_uniprotkb_fun", "P27958", "14602201", "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation (PubMed:23799612). Interacts with, and activates STAT3 leading to cellular transformation. Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation (PubMed:11086025). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (PubMed:14602201)." ], [ "P27958-1", "protein_xref_uniprotkb_fun", "P27958", "23799612", "Packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation (PubMed:23799612). Interacts with, and activates STAT3 leading to cellular transformation. Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation (PubMed:11086025). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (PubMed:14602201)." ], [ "P27958-1", "protein_xref_uniprotkb_fun", "P27958", "12615904", "Forms a heterodimer with envelope glycoprotein E2 that mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to host LDLR, CD81 and SCARB1/SR-BI receptors (PubMed:12615904). However, additional liver specific cofactors may be required for entry. The fusion function is carried by E1 (PubMed:14990718, PubMed:15371595, PubMed:16894197, PubMed:16533059)." ], [ "P27958-1", "protein_xref_uniprotkb_fun", "P27958", "14990718", "Forms a heterodimer with envelope glycoprotein E2 that mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to host LDLR, CD81 and SCARB1/SR-BI receptors (PubMed:12615904). However, additional liver specific cofactors may be required for entry. The fusion function is carried by E1 (PubMed:14990718, PubMed:15371595, PubMed:16894197, PubMed:16533059)." ], [ "P27958-1", "protein_xref_uniprotkb_fun", "P27958", "15371595", "Forms a heterodimer with envelope glycoprotein E2 that mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to host LDLR, CD81 and SCARB1/SR-BI receptors (PubMed:12615904). However, additional liver specific cofactors may be required for entry. The fusion function is carried by E1 (PubMed:14990718, PubMed:15371595, PubMed:16894197, PubMed:16533059)." ], [ "P27958-1", "protein_xref_uniprotkb_fun", "P27958", "16533059", "Forms a heterodimer with envelope glycoprotein E2 that mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to host LDLR, CD81 and SCARB1/SR-BI receptors (PubMed:12615904). However, additional liver specific cofactors may be required for entry. The fusion function is carried by E1 (PubMed:14990718, PubMed:15371595, PubMed:16894197, PubMed:16533059)." ], [ "P27958-1", "protein_xref_uniprotkb_fun", "P27958", "16894197", "Forms a heterodimer with envelope glycoprotein E2 that mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to host LDLR, CD81 and SCARB1/SR-BI receptors (PubMed:12615904). However, additional liver specific cofactors may be required for entry. The fusion function is carried by E1 (PubMed:14990718, PubMed:15371595, PubMed:16894197, PubMed:16533059)." ], [ "P27958-1", "protein_xref_uniprotkb_fun", "P27958", "", "Peptide cofactor which forms a non-covalent complex with the N-terminal of NS3 serine protease." ], [ "P27958-1", "protein_xref_uniprotkb_fun", "P27958", "", "Plays an essential role in the virus replication." ], [ "P27958-1", "protein_xref_uniprotkb_fun", "P27958", "27320856", "Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host reticulum endoplasmic and as a consequence releases Ca2+ in the cytoplasm of infected cell. Targets also host mitochondria and induces mitochondrial depolarization (PubMed:29039530). In turn, high levels of cytoplasmic calcium may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication. In addition of its role as a viroporin, acts as a lipid raft adhesion factor (PubMed:27320856)." ], [ "P27958-1", "protein_xref_uniprotkb_fun", "P27958", "29039530", "Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host reticulum endoplasmic and as a consequence releases Ca2+ in the cytoplasm of infected cell. Targets also host mitochondria and induces mitochondrial depolarization (PubMed:29039530). In turn, high levels of cytoplasmic calcium may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication. In addition of its role as a viroporin, acts as a lipid raft adhesion factor (PubMed:27320856)." ], [ "P27958-1", "protein_xref_uniprotkb_fun", "P27958", "16301520", "Displays three enzymatic activities: a serine protease with a chymotrypsin-like fold, a NTPase and a RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (PubMed:8189513). NS3/NS4A complex also prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand. Cleaves and inhibits the host antiviral protein MAVS (PubMed:16301520)." ], [ "P27958-1", "protein_xref_uniprotkb_fun", "P27958", "8189513", "Displays three enzymatic activities: a serine protease with a chymotrypsin-like fold, a NTPase and a RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (PubMed:8189513). NS3/NS4A complex also prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand. Cleaves and inhibits the host antiviral protein MAVS (PubMed:16301520)." ], [ "P27958-1", "protein_xref_uniprotkb_fun", "P27958", "12615904", "Forms a heterodimer with envelope glycoprotein E1 that mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to host LDLR, CD81 and SCARB1/SR-BI receptors (PubMed:12615904), but additional liver specific cofactors may be required for entry. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection." ], [ "P27958-1", "protein_xref_uniprotkb_fun", "P27958", "", "Component of the replication complex involved in RNA-binding. Its interaction with host VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. The hyperphosphorylated form of NS5A is an inhibitor of viral replication." ] ] }, "readme": "Name\n - HCV1a Protein Function (UniProtKB)\n\nVersion\n - 1.7.13\n\nCreated on\n - 2020-04-09T15:57:45.462784\n\nModified on\n - 2020-04-09T17:58:23.388650\n\nCreated by\n - Jeet Vora [jeetvora@gwu.edu], Rahi Navelkar [rsn13@gwu.edu], Robel Kahsay [rykahsay@gwu.edu]\n\nAuthors\n - Maria Martin [martin@ebi.ac.uk], Preethi Vasudev [pvasudev@ebi.ac.uk]\n\nChecksum\n - \n\nUsability Domain\n - The Hepatitis C virus (genotype 1a, isolate H) Protein Function (UniProtKB) dataset contains biological function annotation for hcv1a [taxid:11108] protein accesions from the UniProtKB database. The dataset is derived from 2019-09 UniProtKB release. If you use this dataset please provide proper attribution to EMBL-EBI-UniProtKB and GlyGen\n\nDescription Domain\n Keywords\n - protein function\n - UniProtKB\n\n Pipeline Steps\n - Step-1: The script loads the UniProtKB function annotations triplestore containing triples from nt file and extracts the data as a csv dataset\n\nExecution Domain\n Scripts - https://github.com/GW-HIVE/glygen-backend-integration/blob/master/pipeline/integrator/make-protein-dataset.py\n\n\n Software Prerequisites\n Name: Python\n Version: 2.7.5\n URI: https://www.python.org/download/releases/2.7.5/\n\nI/O Domain\n Input Subdomain\n Name: uniprot-proteome-hepatitis-c-virus-1a.nt\n URI: https://data.glygen.org/ln2wwwdata/source/uniprot-proteome-hepatitis-c-virus-1a.nt\n Name: hcv1a_protein_masterlist.csv\n URI: https://data.glygen.org/ln2wwwdata/reviewed/hcv1a_protein_masterlist.csv\n Output Subdomain\n Name: hcv1a_protein_function_uniprotkb.csv\n URI: http://data.glygen.org/ln2wwwdata/reviewed/hcv1a_protein_function_uniprotkb.csv\n Name: hcv1a_protein_function_uniprotkb.stat.csv\n URI: http://data.glygen.org/ln2wwwdata/reviewed/hcv1a_protein_function_uniprotkb.stat.csv\n\nFields\n Name: \"uniprotkb_canonical_ac\"\n Description: \"\"\n Unique Values: \"1\"\n Name: \"evidence\"\n Description: \"NCBI PubMed Id (PMID) or DOI (Digital Object Identifier) as evidence for the entry/annotation\"\n Unique Values: \"15\"\n Name: \"annotation\"\n Description: \"Function annotation from UniProtKB|RefSeq database\"\n Unique Values: \"10\"\n Name: \"xref_id\"\n Description: \"ID of the X-ref\"\n Unique Values: \"1\"\n Name: \"xref_key\"\n Description: \"Source key associated to the xref_id\"\n Unique Values: \"1\"", "downloadurl": "/ln2data/releases/data/v-1.7.13/reviewed/hcv1a_protein_function_uniprotkb.csv" }