DP00588_C002: Core protein p19FASTA viewXML view

General information
DisProt:DP00588_C002
Name:Core protein p19
Synonym(s):POLG_HCVH
Genome polyprotein [cleavage product 2]
First appeared in release:Release 5.0 (02/10/2010)
UniProt:P27958
UniGene: 
SwissProt: POLG_HCVH
TrEMBL:  
NCBI (GI): 130461
Source organism:Hepatitis C virus genotype 1a (isolate H) (HCV)
Sequence length:176
Percent disordered:46%
Homologues: 


Native sequence

        10         20         30         40         50         60
         |          |          |          |          |          |
STNPKPQRKT KRNTNRRPQD VKFPGGGQIV GGVYLLPRRG PRLGVRATRK TSERSQPRGR - 60
RQPIPKARRP EGRTWAQPGY PWPLYGNEGC GWAGWLLSPR GSRPSWGPTD PRRRSRNLGK - 120
VIDTLTCGFA DLMGYIPLVG APLGGAARAL AHGVRVLEDG VNYATGNLPG CSFSIF



Functional narrative    

Hepatitis C virus (HCV) core protein plays an important role in the assembly and packaging of the viral genome. HCV core protein is the first to be synthesized during the early phases of HCV infection. It can influence cellular immunity, cell growth, apoptosis, cell transformation, and eventually tumor development (hepatocellular carcinoma and possibly B lymphoma). 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). (UniProt). Core protein p19 is cleavage product 2 of Genome polyprotein, comprising aa 2-177 of the polyprotein.

Region 2: 1-45 Region 1: 1-81

Map of ordered and disordered regions







Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.


Region 1
Type:Disordered
Name:C82 N-terminal region
Location:1 - 81
Length:81
Region sequence:

STNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGR
RQPIPKARRPEGRTWAQPGYP

Modification type: Engineered
Fragment
PDB:  
Structural/functional type: Relationship to function unknown
Functional classes: Molecular assembly
Chaperones
Functional subclasses: Protein-RNA binding
Protein-protein binding
Detection methods:
  1. Sensitivity to proteolysis (277 K; protein 0.2 mM; trypsin)

  2. Circular dichroism (CD) spectroscopy, far-UV (298 K; pH: 7.2; C82 protein (lyophilised); phosphate 10 mM)

  3. Nuclear magnetic resonance (NMR) (278 K; pH: 6.6; C82 protein 0.4 mM; DSS 0.2 mM; NaCl 50 mM; NaN3 0.1 %; phosphate 25 mM; protease inhibitors (1x))

References:
  1. Duvignaud JB, Savard C, Fromentin R, Majeau N, Leclerc D, Gagné SM. "Structure and dynamics of the N-terminal half of hepatitis C virus core protein: An intrinsically unstructured protein." Biochem Biophys Res Commun. 2008; 378(1): 27-31. PubMed: 18992225

Comments:
The construct C82 used by Duvignaud et al (2009) represents aa 1-81 of the Core protein plus the initiator methionine inserted before aa 1.




Region 2
Type:Disordered
Name:N-terminal region
Location:1 - 45
Length:45
Region sequence:

STNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGV

Modification type: Engineered
Fragment
PDB: 1CWX:A
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. Nuclear magnetic resonance (NMR) (293 K; pH: 5.9; D2-TRIFLUOROETHANOL 40 %; NaCl 0.1 M; SODIUM PHOSPHATE 0.01 M)

References:
  1. Ladaviere, L., Deleage, G., Montserret, R., Dalbon, P., Jolivet, M., Penin, F. "Structural Analysis of the Immunodominant Antigenic Region of the Hepatitis C Virus Capsid Protein by NMR." unpublished. .

Comments:
Primary citation is not in PubMed; citation is from PDB.


Structure shows a helix-loop=helix motif at aa 17-37, with the rest of the construct unstructured.




Comments


Previous entry DP00588 has been split into polyprotein (DP00588) and cleavage products (DP00588_C0XX).



Core protein p21 (cleavage product 1 of Genome polyprotein) is the immature version of the mature Core protein p19 (cleavage product 2 of Genome polyprotein). Reports of disorder are shown on Core protein p19 (DP00588_C002).


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