LipidDB ID

LipidDB-11108-01241

Entry Name

UniProt Accession

P27958; O36579; O36608; O36609; O36610;

Theoretical PI

8.71

Molecular Weight

327145.97

Genbank Protein ID

AAA45534.1; AAB66324.1; AAB67036.1; AAB67037.1; AAB67038.1;

Genbank Nucleotide ID

M67463; AF009606; AF011751; AF011752; AF011753;

Protein Name

RNA-directed RNA polymerase

Protein Synonyms/Alias

Capsid protein C; p21; gp32; gp35; NS1; gp68; gp70; p23; 3.4.22.-; 3.4.21.98; 3.6.1.15; 3.6.4.13; Hepacivirin; NS3P; p70; NS4A; p8; NS4B; p27; NS5A; p56; 2.7.7.48; NS5B; p68;

Gene Name

Gene Synonyms/Alias

Created Date

01-AUG-1992

Organism

Hepatitis C virus genotype 1a (isolate H) (HCV)

NCBI Taxa ID

11108

Reference

[1] Majeau N, Fromentin R, Savard C, Duval M, Tremblay MJ, Leclerc D.Palmitoylation of hepatitis C virus core protein is important for virionproduction. J Biol Chem. 2009 Dec 4;284(49):33915-25. doi:10.1074/jbc.M109.018549. Epub 2009 Sep 16.[PMID:19783655]
[2] Yu GY, Lee KJ, Gao L, Lai MM. Palmitoylation and polymerization of hepatitis Cvirus NS4B protein. J Virol. 2006 Jun;80(12):6013-23.[PMID:16731940]

Functional Description

Core protein 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. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also 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. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. 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. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity).

Sequence Annotation

Topological domain: 2 168 Cytoplasmic.
Transmembrane: 169 189 Helical.
Topological domain: 190 358 Lumenal.
Transmembrane: 359 379 Helical.
Topological domain: 380 725 Lumenal.
Transmembrane: 726 746 Helical.
Topological domain: 747 757 Lumenal.
Transmembrane: 758 778 Helical.
Topological domain: 779 782 Cytoplasmic.
Transmembrane: 783 803 Helical.
Topological domain: 804 813 Lumenal.
Transmembrane: 814 834 Helical.
Topological domain: 835 881 Cytoplasmic.
Transmembrane: 882 902 Helical.
Topological domain: 903 928 Lumenal.
Transmembrane: 929 949 Helical.
Topological domain: 950 1657 Cytoplasmic.
Transmembrane: 1658 1678 Helical.
Topological domain: 1679 1805 Cytoplasmic.
Transmembrane: 1806 1826 Helical.
Topological domain: 1827 1828 Lumenal.
Transmembrane: 1829 1849 Helical.
Topological domain: 1850 1850 Cytoplasmic.
Transmembrane: 1851 1871 Helical.
Topological domain: 1872 1881 Lumenal.
Transmembrane: 1882 1902 Helical.
Topological domain: 1903 1972 Cytoplasmic.
Topological domain: 2003 2990 Cytoplasmic.
Transmembrane: 2991 3011 Helical.
Domain: 899 1026 Peptidase C18.
Domain: 1217 1369 Helicase ATP-binding.
Domain: 2634 2752 RdRp catalytic.
Nucleotide-binding: 1230 1237 ATP.
Region: 2 59 Interaction with DDX3X.
Region: 2 23 Interaction with STAT1.
Region: 122 173 Interaction with APOA2.
Region: 150 159 Mitochondrial targeting signal.
Region: 164 167 Important for lipid dropletslocalization.
Region: 265 296 Fusion peptide.
Region: 385 411 HVR1.
Region: 475 481 HVR2.
Region: 482 494 CD81-binding 1.
Region: 522 553 CD81-binding 2.
Region: 660 671 PKR/eIF2-alpha phosphorylation homologydomain (PePHD).
Region: 1679 1690 NS3-binding (by NS4A).
Region: 2120 2332 Transcriptional activation.
Region: 2120 2208 FKBP8-binding.
Region: 2200 2250 Basal phosphorylation.
Region: 2210 2275 PKR-binding.
Region: 2249 2306 NS4B-binding.
Region: 2351 2420 Basal phosphorylation.
Region: 2354 2377 V3.
Motif: 5 13 Nuclear localization signal.
Motif: 38 43 Nuclear localization signal.
Motif: 58 64 Nuclear localization signal.
Motif: 66 71 Nuclear localization signal.
Motif: 1316 1319 DECH box.
Motif: 2322 2325 SH3-binding.
Motif: 2327 2335 Nuclear localization signal.
Active site: 952 952 For protease NS2-3 activity; shared withdimeric partner.
Active site: 972 972 For protease NS2-3 activity; shared withdimeric partner.
Active site: 993 993 For protease NS2-3 activity; shared withdimeric partner.
Active site: 1083 1083 Charge relay system; for serine proteaseNS3 activity.
Active site: 1107 1107 Charge relay system; for serine proteaseNS3 activity.
Active site: 1165 1165 Charge relay system; for serine proteaseNS3 activity.
Metal binding site: 1123 1123 Zinc.
Metal binding site: 1125 1125 Zinc.
Metal binding site: 1171 1171 Zinc.
Metal binding site: 1175 1175 Zinc.
Metal binding site: 2011 2011 Zinc.
Metal binding site: 2029 2029 Zinc.
Metal binding site: 2031 2031 Zinc.
Metal binding site: 2052 2052 Zinc.
Functional site: 177 178 Cleavage; by host signal peptidase.
Functional site: 191 192 Cleavage; by host signal peptidase.
Functional site: 383 384 Cleavage; by host signal peptidase.
Functional site: 746 747 Cleavage; by host signal peptidase.
Functional site: 809 810 Cleavage; by host signal peptidase.
Functional site: 1026 1027 Cleavage; by protease NS2-3.
Functional site: 1657 1658 Cleavage; by serine protease NS3.
Functional site: 1711 1712 Cleavage; by serine protease NS3.
Functional site: 1972 1973 Cleavage; by serine protease NS3.
Functional site: 2420 2421 Cleavage; by serine protease NS3.
Modified residue: 2 2 N-acetylserine; by host.
Modified residue: 53 53 Phosphoserine; by host.
Modified residue: 99 99 Phosphoserine; by host.
Modified residue: 116 116 Phosphoserine; by host PKA.
Modified residue: 2194 2194 Phosphoserine; by host; in p56.
Modified residue: 2197 2197 Phosphoserine; by host; in p58.
Modified residue: 2201 2201 Phosphoserine; by host; in p58.
Modified residue: 2204 2204 Phosphoserine; by host; in p58.
Modified residue: 2321 2321 Phosphoserine; by host.

Protein Length

3011 AA.

Protein Sequence
(Canonical)

FASTA
(Canonical)

Gene Ontology

GO:0044165; C:host cell endoplasmic reticulum; IEA:UniProtKB-KW
GO:0044186; C:host cell lipid particle; IEA:UniProtKB-KW
GO:0033650; C:host cell mitochondrion; IEA:UniProtKB-KW
GO:0042025; C:host cell nucleus; IEA:UniProtKB-KW
GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-KW
GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW
GO:0044385; C:integral to membrane of host cell; IEA:UniProtKB-KW
GO:0030529; C:ribonucleoprotein complex; IEA:UniProtKB-KW
GO:0019031; C:viral envelope; IEA:UniProtKB-KW
GO:0019013; C:viral nucleocapsid; IEA:UniProtKB-KW
GO:0005524; F:ATP binding; IEA:UniProtKB-KW
GO:0008026; F:ATP-dependent helicase activity; IEA:InterPro
GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro
GO:0017151; F:DEAD/H-box RNA helicase binding; IPI:AgBase
GO:0042802; F:identical protein binding; IPI:IntAct
GO:0005216; F:ion channel activity; IEA:UniProtKB-KW
GO:0003723; F:RNA binding; IEA:UniProtKB-KW
GO:0003968; F:RNA-directed RNA polymerase activity; IEA:UniProtKB-KW
GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro
GO:0070008; F:serine-type exopeptidase activity; IEA:InterPro
GO:0005198; F:structural molecule activity; IEA:InterPro
GO:0008270; F:zinc ion binding; IEA:InterPro
GO:0006915; P:apoptotic process; IEA:UniProtKB-KW
GO:0075512; P:clathrin-mediated endocytosis of virus by host cell; IEA:UniProtKB-KW
GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW
GO:0039520; P:induction by virus of host autophagy; IEA:UniProtKB-KW
GO:0039645; P:modulation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW
GO:0050689; P:negative regulation of defense response to virus by host; TAS:AgBase
GO:0032715; P:negative regulation of interleukin-6 production; IDA:AgBase
GO:0034136; P:negative regulation of toll-like receptor 2 signaling pathway; IDA:AgBase
GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; IDA:AgBase
GO:0034156; P:negative regulation of toll-like receptor 7 signaling pathway; IDA:AgBase
GO:0034164; P:negative regulation of toll-like receptor 9 signaling pathway; IDA:AgBase
GO:0039707; P:pore formation by virus in membrane of host cell; IEA:UniProtKB-KW
GO:0051259; P:protein oligomerization; IEA:UniProtKB-KW
GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProtKB-KW
GO:0039545; P:suppression by virus of host MAVS activity; IEA:UniProtKB-KW
GO:0039546; P:suppression by virus of host MAVS activity by MAVS proteolysis; TAS:AgBase
GO:0039563; P:suppression by virus of host STAT1 activity; IEA:UniProtKB-KW
GO:0039547; P:suppression by virus of host TRAF activity; IEA:UniProtKB-KW
GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW
GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW
GO:0019087; P:transformation of host cell by virus; IEA:InterPro
GO:0019082; P:viral protein processing; TAS:AgBase
GO:0039694; P:viral RNA genome replication; IEA:InterPro
GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW

Interpro

InterPro; IPR011492; DEAD_Flavivir
InterPro; IPR002521; HCV_core_C
InterPro; IPR002522; HCV_core_N
InterPro; IPR002519; HCV_env
InterPro; IPR002531; HCV_NS1
InterPro; IPR002518; HCV_NS2
InterPro; IPR000745; HCV_NS4a
InterPro; IPR001490; HCV_NS4b
InterPro; IPR002868; HCV_NS5a
InterPro; IPR013193; HCV_NS5a_1B_dom
InterPro; IPR024350; HCV_NS5a_C
InterPro; IPR014001; Helicase_ATP-bd
InterPro; IPR001650; Helicase_C
InterPro; IPR013192; NS5A_1a
InterPro; IPR027417; P-loop_NTPase
InterPro; IPR004109; Peptidase_S29
InterPro; IPR007094; RNA-dir_pol_PSvirus
InterPro; IPR002166; RNA_pol_HCV
InterPro; IPR009003; Trypsin-like_Pept_dom

Pfam

Pfam; PF07652; Flavi_DEAD;
Pfam; PF01543; HCV_capsid;
Pfam; PF01542; HCV_core;
Pfam; PF01539; HCV_env;
Pfam; PF01560; HCV_NS1;
Pfam; PF01538; HCV_NS2;
Pfam; PF01006; HCV_NS4a;
Pfam; PF01001; HCV_NS4b;
Pfam; PF01506; HCV_NS5a;
Pfam; PF08300; HCV_NS5a_1a;
Pfam; PF08301; HCV_NS5a_1b;
Pfam; PF12941; HCV_NS5a_C;
Pfam; PF02907; Peptidase_S29;
Pfam; PF00998; RdRP_3;

SMART

SMART; SM00487; DEXDc;

PROSITE

PROSITE; PS51693; HCV_NS2_PRO;
PROSITE; PS51192; HELICASE_ATP_BIND_1;
PROSITE; PS50507; RDRP_SSRNA_POS;

PRINTS