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Protein

Genome polyprotein

Gene
N/A
Organism
Hepatitis C virus genotype 1b (strain HC-J4) (HCV)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity
E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. 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 (By similarity).By similarity
P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine. Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity (By similarity).By similarity
Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity).By similarity
NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human 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 (By similarity).By similarity
NS4B 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 (By similarity).By similarity
NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human 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. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity).By similarity
NS5B is an RNA-dependent RNA polymerase that plays an essential role in the virus replication.By similarity

Catalytic activityi

Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.
Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).PROSITE-ProRule annotation
NTP + H2O = NDP + phosphate.
ATP + H2O = ADP + phosphate.

Cofactori

Protein has several cofactor binding sites:
  • Zn2+By similarityNote: Binds 1 zinc ion per NS3 protease domain.By similarity
  • Zn2+By similarityNote: Binds 1 zinc ion per NS5A N-terminal domain.By similarity

Enzyme regulationi

Activity of auto-protease NS2-3 is dependent on zinc ions and completely inhibited by EDTA. Serine protease NS3 is also activated by zinc ions (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei952For protease NS2-3 activity; shared with dimeric partnerPROSITE-ProRule annotation1
Active sitei972For protease NS2-3 activity; shared with dimeric partnerPROSITE-ProRule annotation1
Active sitei993For protease NS2-3 activity; shared with dimeric partnerPROSITE-ProRule annotation1
Active sitei1083Charge relay system; for serine protease NS3 activityBy similarity1
Active sitei1107Charge relay system; for serine protease NS3 activityBy similarity1
Metal bindingi1123ZincBy similarity1
Metal bindingi1125ZincBy similarity1
Active sitei1165Charge relay system; for serine protease NS3 activityBy similarity1
Metal bindingi1171ZincBy similarity1
Metal bindingi1175ZincBy similarity1
Metal bindingi2011ZincBy similarity1
Metal bindingi2029ZincBy similarity1
Metal bindingi2031ZincBy similarity1
Metal bindingi2052ZincBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi1230 – 1237ATPPROSITE-ProRule annotation8

GO - Molecular functioni

  • 14-3-3 protein binding Source: AgBase
  • ATP binding Source: UniProtKB-KW
  • ATP-dependent helicase activity Source: InterPro
  • cysteine-type endopeptidase activity Source: InterPro
  • ion channel activity Source: UniProtKB-KW
  • protein kinase binding Source: AgBase
  • protein kinase C binding Source: AgBase
  • RNA binding Source: UniProtKB-KW
  • RNA-directed RNA polymerase activity Source: UniProtKB-KW
  • serine-type endopeptidase activity Source: InterPro
  • SMAD binding Source: AgBase
  • structural molecule activity Source: InterPro
  • zinc ion binding Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Helicase, Hydrolase, Ion channel, Nucleotidyltransferase, Protease, Ribonucleoprotein, RNA-directed RNA polymerase, Serine protease, Thiol protease, Transferase, Viral ion channel

Keywords - Biological processi

Activation of host autophagy by virus, Apoptosis, Clathrin-mediated endocytosis of virus by host, Fusion of virus membrane with host endosomal membrane, Fusion of virus membrane with host membrane, G1/S host cell cycle checkpoint dysregulation by virus, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Inhibition of host MAVS by virus, Inhibition of host RLR pathway by virus, Inhibition of host STAT1 by virus, Inhibition of host TRAFs by virus, Interferon antiviral system evasion, Ion transport, Modulation of host cell cycle by virus, Transcription, Transcription regulation, Transport, Viral attachment to host cell, Viral immunoevasion, Viral penetration into host cytoplasm, Viral RNA replication, Virus endocytosis by host, Virus entry into host cell

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, RNA-binding, Viral nucleoprotein, Zinc

Enzyme and pathway databases

BRENDAi2.7.7.48. 2642.
3.4.21.98. 2642.

Names & Taxonomyi

Protein namesi
Recommended name:
Genome polyprotein
Cleaved into the following 11 chains:
Alternative name(s):
Capsid protein C
p21
Alternative name(s):
gp32
gp35
Alternative name(s):
NS1
gp68
gp70
Protease NS2-3 (EC:3.4.22.-)
Short name:
p23
Alternative name(s):
Hepacivirin
NS3P
p70
Alternative name(s):
p8
Alternative name(s):
p27
Alternative name(s):
p56
Alternative name(s):
NS5B
p68
OrganismiHepatitis C virus genotype 1b (strain HC-J4) (HCV)
Taxonomic identifieri420174 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA positive-strand viruses, no DNA stageFlaviviridaeHepacivirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000008094 Componenti: Genome

Subcellular locationi

Core protein p21 :
Core protein p19 :
Envelope glycoprotein E1 :
  • Virion membrane Curated; Single-pass type I membrane protein Curated
  • Host endoplasmic reticulum membrane By similarity; Single-pass type I membrane protein By similarity

  • Note: The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase. After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor. A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain. These events explain the final topology of the protein. ER retention of E1 is leaky and, in overexpression conditions, only a small fraction reaches the plasma membrane.
Envelope glycoprotein E2 :
  • Virion membrane Curated; Single-pass type I membrane protein Curated
  • Host endoplasmic reticulum membrane By similarity; Single-pass type I membrane protein By similarity

  • Note: The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase. After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor. A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain. These events explain the final topology of the protein. ER retention of E2 is leaky and, in overexpression conditions, only a small fraction reaches the plasma membrane.
p7 :
Serine protease NS3 :
Non-structural protein 4A :
Non-structural protein 5A :
RNA-directed RNA polymerase :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini2 – 168CytoplasmicSequence analysisAdd BLAST167
Transmembranei169 – 189HelicalSequence analysisAdd BLAST21
Topological domaini190 – 358LumenalSequence analysisAdd BLAST169
Transmembranei359 – 379HelicalSequence analysisAdd BLAST21
Topological domaini380 – 725LumenalSequence analysisAdd BLAST346
Transmembranei726 – 746HelicalSequence analysisAdd BLAST21
Topological domaini747 – 757LumenalSequence analysisAdd BLAST11
Transmembranei758 – 778HelicalSequence analysisAdd BLAST21
Topological domaini779 – 782CytoplasmicSequence analysis4
Transmembranei783 – 803HelicalSequence analysisAdd BLAST21
Topological domaini804 – 813LumenalSequence analysis10
Transmembranei814 – 834HelicalSequence analysisAdd BLAST21
Topological domaini835 – 881CytoplasmicSequence analysisAdd BLAST47
Transmembranei882 – 902HelicalSequence analysisAdd BLAST21
Topological domaini903 – 928LumenalSequence analysisAdd BLAST26
Transmembranei929 – 949HelicalSequence analysisAdd BLAST21
Topological domaini950 – 1657CytoplasmicSequence analysisAdd BLAST708
Transmembranei1658 – 1678HelicalSequence analysisAdd BLAST21
Topological domaini1679 – 1805CytoplasmicSequence analysisAdd BLAST127
Transmembranei1806 – 1826HelicalSequence analysisAdd BLAST21
Topological domaini1827 – 1828LumenalSequence analysis2
Transmembranei1829 – 1849HelicalSequence analysisAdd BLAST21
Topological domaini1850CytoplasmicSequence analysis1
Transmembranei1851 – 1871HelicalSequence analysisAdd BLAST21
Topological domaini1872 – 1881LumenalSequence analysis10
Transmembranei1882 – 1902HelicalSequence analysisAdd BLAST21
Topological domaini1903 – 1972CytoplasmicSequence analysisAdd BLAST70
Intramembranei1973 – 2002By similarityAdd BLAST30
Topological domaini2003 – 2989CytoplasmicSequence analysisAdd BLAST987
Transmembranei2990 – 3010HelicalBy similarityAdd BLAST21

GO - Cellular componenti

  • extracellular region Source: UniProtKB-SubCell
  • host cell cytoplasm Source: AgBase
  • host cell cytosol Source: AgBase
  • host cell endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • host cell lipid particle Source: UniProtKB-SubCell
  • host cell membrane Source: AgBase
  • host cell mitochondrial membrane Source: UniProtKB-SubCell
  • host cell nucleus Source: AgBase
  • host cell perinuclear region of cytoplasm Source: AgBase
  • host cell plasma membrane Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
  • integral to membrane of host cell Source: UniProtKB-KW
  • viral envelope Source: UniProtKB-KW
  • viral nucleocapsid Source: UniProtKB-KW
  • virion membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Capsid protein, Host cell membrane, Host cytoplasm, Host endoplasmic reticulum, Host lipid droplet, Host membrane, Host mitochondrion, Host nucleus, Membrane, Secreted, Viral envelope protein, Virion

Pathology & Biotechi

Keywords - Diseasei

Oncogene

Chemistry databases

ChEMBLiCHEMBL3638332.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved; by hostBy similarity
ChainiPRO_00002787422 – 191Core protein p21Sequence analysisAdd BLAST190
ChainiPRO_00002787432 – 177Core protein p19By similarityAdd BLAST176
PropeptideiPRO_0000278744178 – 191ER anchor for the core protein, removed in mature form by host signal peptidaseBy similarityAdd BLAST14
ChainiPRO_0000278745192 – 383Envelope glycoprotein E1Sequence analysisAdd BLAST192
ChainiPRO_0000278746384 – 746Envelope glycoprotein E2Sequence analysisAdd BLAST363
ChainiPRO_0000278747747 – 809p7By similarityAdd BLAST63
ChainiPRO_0000278748810 – 1026Protease NS2-3PROSITE-ProRule annotationAdd BLAST217
ChainiPRO_00002787491027 – 1657Serine protease NS3Sequence analysisAdd BLAST631
ChainiPRO_00002787501658 – 1711Non-structural protein 4ASequence analysisAdd BLAST54
ChainiPRO_00002787511712 – 1972Non-structural protein 4BSequence analysisAdd BLAST261
ChainiPRO_00002787521973 – 2419Non-structural protein 5ASequence analysisAdd BLAST447
ChainiPRO_00002787532420 – 3010RNA-directed RNA polymeraseSequence analysisAdd BLAST591

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserine; by hostBy similarity1
Modified residuei53Phosphoserine; by hostBy similarity1
Modified residuei99Phosphoserine; by hostBy similarity1
Modified residuei116Phosphoserine; by host PKABy similarity1
Glycosylationi196N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi209N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi234N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi250N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi305N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi417N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi423N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi430N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi448N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi478N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi532N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi540N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi556N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi576N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi623N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi645N-linked (GlcNAc...); by hostSequence analysis1
Lipidationi1968S-palmitoyl cysteine; by hostBy similarity1
Lipidationi1972S-palmitoyl cysteine; by hostBy similarity1
Modified residuei2194Phosphoserine; by host; in p56Curated1
Modified residuei2197Phosphoserine; by host; in p58By similarity1
Modified residuei2201Phosphoserine; by host; in p58By similarity1
Modified residuei2204Phosphoserine; by host; in p58By similarity1

Post-translational modificationi

Specific enzymatic cleavages in vivo yield mature proteins. The structural proteins, core, E1, E2 and p7 are produced by proteolytic processing by host signal peptidases. The core protein is synthesized as a 21 kDa precursor which is retained in the ER membrane through the hydrophobic signal peptide. Cleavage by the signal peptidase releases the 19 kDa mature core protein. The other proteins (p7, NS2-3, NS3, NS4A, NS4B, NS5A and NS5B) are cleaved by the viral proteases (By similarity).By similarity
Envelope E1 and E2 glycoproteins are highly N-glycosylated.By similarity
Core protein is phosphorylated by host PKC and PKA.By similarity
Core protein is ubiquitinated; mediated by UBE3A and leading to core protein subsequent proteasomal degradation.By similarity
NS5A is phosphorylated in a basal form termed p56. p58 is a hyperphosphorylated form of p56. p56 and p58 coexist in the cell in roughly equivalent amounts. Hyperphosphorylation is dependent on the presence of NS4A. Human AKT1, RPS6KB1/p70S6K, MAP2K1/MEK1, MAP2K6/MKK6 and CSNK1A1/CKI-alpha kinases may be responsible for NS5A phosphorylation (By similarity).By similarity
NS4B is palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions (By similarity).By similarity
The N-terminus of a fraction of NS4B molecules seems to be relocated post-translationally from the cytoplasm to the ER lumen, with a 5th transmembrane segment. The C-terminus of NS2 may be lumenal with a fourth transmembrane segment (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei177 – 178Cleavage; by host signal peptidaseBy similarity2
Sitei191 – 192Cleavage; by host signal peptidaseSequence analysis2
Sitei383 – 384Cleavage; by host signal peptidaseSequence analysis2
Sitei746 – 747Cleavage; by host signal peptidaseBy similarity2
Sitei809 – 810Cleavage; by host signal peptidaseBy similarity2
Sitei1026 – 1027Cleavage; by protease NS2-3PROSITE-ProRule annotation2
Sitei1657 – 1658Cleavage; by serine protease NS3Sequence analysis2
Sitei1711 – 1712Cleavage; by serine protease NS3Sequence analysis2
Sitei1972 – 1973Cleavage; by serine protease NS3Sequence analysis2
Sitei2419 – 2420Cleavage; by serine protease NS3Sequence analysis2

Keywords - PTMi

Acetylation, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Interactioni

Subunit structurei

Core protein is a homomultimer that binds the C-terminal part of E1 and interacts with numerous cellular proteins. Interaction with human STAT1 SH2 domain seems to result in decreased STAT1 phosphorylation, leading to decreased IFN-stimulated gene transcription. In addition to blocking the formation of phosphorylated STAT1, the core protein also promotes ubiquitin-mediated proteasome-dependent degradation of STAT1. Interacts with, and constitutively activates human STAT3. Associates with human LTBR and TNFRSF1A receptors and possibly induces apoptosis. Binds to human SP110 isoform 3/Sp110b, HNRPK, C1QR1, YWHAE, UBE3A/E6AP, DDX3X, APOA2 and RXRA proteins. Interacts with human CREB3 nuclear transcription protein, triggering cell transformation. May interact with human p53. Also binds human cytokeratins KRT8, KRT18, KRT19 and VIM (vimentin). E1 and E2 glycoproteins form a heterodimer that binds to human LDLR, CLDN1, CD81 and SCARB1 receptors. E2 binds and inhibits human EIF2AK2/PKR. Also binds human CD209/DC-SIGN and CLEC4M/DC-SIGNR. p7 forms a homoheptamer in vitro. NS2 forms a homodimer containing a pair of composite active sites at the dimerization interface. NS2 seems to interact with all other non-structural (NS) proteins. NS4A interacts with NS3 serine protease and stabilizes its folding. NS3-NS4A complex is essential for the activation of the latter and allows membrane anchorage of NS3. NS3 interacts with human TANK-binding kinase TBK1 and MAVS. NS4B and NS5A form homodimers and seem to interact with all other non-structural (NS) proteins. NS5A also interacts with human EIF2AK2/PKR, FKBP8, GRB2, BIN1, PIK3R1, SRCAP, VAPB and with most Src-family kinases. NS5B is a homooligomer and interacts with human VAPB, HNRNPA1 and SEPT6 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
EIF2AK2P195252EBI-6918883,EBI-640775From a different organism.
FYNP062412EBI-710506,EBI-515315From a different organism.
GRB2P629932EBI-710506,EBI-401755From a different organism.
HCKP086312EBI-710506,EBI-346340From a different organism.
LckP062402EBI-710506,EBI-1401From a different organism.
LYNP079482EBI-710506,EBI-79452From a different organism.
PKN2Q165137EBI-10006231,EBI-2511350From a different organism.
SMAD3P840226EBI-9213553,EBI-347161From a different organism.
YWHAEP622585EBI-9213553,EBI-356498From a different organism.

GO - Molecular functioni

  • 14-3-3 protein binding Source: AgBase
  • protein kinase binding Source: AgBase
  • protein kinase C binding Source: AgBase
  • SMAD binding Source: AgBase

Protein-protein interaction databases

IntActiO92972. 12 interactors.

Chemistry databases

BindingDBiO92972.

Structurei

Secondary structure

13010
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi750 – 760Combined sources11
Helixi762 – 767Combined sources6
Helixi769 – 777Combined sources9
Helixi786 – 789Combined sources4
Helixi790 – 792Combined sources3
Helixi797 – 802Combined sources6
Beta strandi1224 – 1227Combined sources4
Beta strandi1232 – 1235Combined sources4
Turni1236 – 1238Combined sources3
Helixi1239 – 1245Combined sources7
Turni1246 – 1248Combined sources3
Beta strandi1251 – 1256Combined sources6
Helixi1258 – 1270Combined sources13
Beta strandi1277 – 1279Combined sources3
Beta strandi1292 – 1295Combined sources4
Helixi1296 – 1301Combined sources6
Turni1302 – 1306Combined sources5
Beta strandi1311 – 1315Combined sources5
Helixi1323 – 1335Combined sources13
Helixi1337 – 1339Combined sources3
Beta strandi1342 – 1346Combined sources5
Beta strandi1362 – 1366Combined sources5
Helixi1382 – 1385Combined sources4
Beta strandi1386 – 1393Combined sources8
Helixi1397 – 1408Combined sources12
Turni1409 – 1411Combined sources3
Beta strandi1414 – 1417Combined sources4
Helixi1423 – 1425Combined sources3
Beta strandi1428 – 1436Combined sources9
Beta strandi1448 – 1453Combined sources6
Beta strandi1456 – 1462Combined sources7
Beta strandi1467 – 1469Combined sources3
Beta strandi1471 – 1478Combined sources8
Helixi1483 – 1486Combined sources4
Helixi1488 – 1490Combined sources3
Beta strandi1491 – 1495Combined sources5
Beta strandi1497 – 1503Combined sources7
Helixi1514 – 1525Combined sources12
Helixi1532 – 1543Combined sources12
Helixi1555 – 1563Combined sources9
Helixi1570 – 1577Combined sources8
Turni1578 – 1580Combined sources3
Helixi1584 – 1596Combined sources13
Helixi1615 – 1617Combined sources3
Beta strandi1627 – 1629Combined sources3
Helixi1640 – 1648Combined sources9
Beta strandi2421 – 2425Combined sources5
Helixi2444 – 2449Combined sources6
Helixi2453 – 2455Combined sources3
Beta strandi2456 – 2458Combined sources3
Helixi2461 – 2463Combined sources3
Helixi2464 – 2471Combined sources8
Helixi2481 – 2494Combined sources14
Helixi2504 – 2509Combined sources6
Beta strandi2513 – 2515Combined sources3
Beta strandi2519 – 2521Combined sources3
Helixi2524 – 2528Combined sources5
Helixi2532 – 2547Combined sources16
Beta strandi2549 – 2551Combined sources3
Beta strandi2555 – 2559Combined sources5
Beta strandi2563 – 2565Combined sources3
Turni2568 – 2570Combined sources3
Beta strandi2578 – 2581Combined sources4
Helixi2584 – 2606Combined sources23
Helixi2607 – 2609Combined sources3
Helixi2611 – 2613Combined sources3
Helixi2616 – 2629Combined sources14
Beta strandi2630 – 2638Combined sources9
Helixi2643 – 2646Combined sources4
Helixi2649 – 2659Combined sources11
Helixi2666 – 2678Combined sources13
Turni2679 – 2681Combined sources3
Beta strandi2683 – 2686Combined sources4
Beta strandi2692 – 2696Combined sources5
Beta strandi2701 – 2703Combined sources3
Helixi2706 – 2724Combined sources19
Beta strandi2728 – 2735Combined sources8
Beta strandi2738 – 2744Combined sources7
Helixi2748 – 2764Combined sources17
Beta strandi2769 – 2771Combined sources3
Beta strandi2776 – 2778Combined sources3
Helixi2779 – 2781Combined sources3
Beta strandi2787 – 2793Combined sources7
Beta strandi2799 – 2805Combined sources7
Helixi2808 – 2819Combined sources12
Helixi2826 – 2834Combined sources9
Helixi2838 – 2842Combined sources5
Helixi2844 – 2854Combined sources11
Beta strandi2858 – 2860Combined sources3
Beta strandi2862 – 2866Combined sources5
Beta strandi2869 – 2873Combined sources5
Helixi2875 – 2877Combined sources3
Helixi2878 – 2886Combined sources9
Helixi2888 – 2891Combined sources4
Helixi2898 – 2911Combined sources14
Helixi2916 – 2933Combined sources18
Helixi2935 – 2944Combined sources10
Helixi2946 – 2948Combined sources3
Beta strandi2949 – 2951Combined sources3
Helixi2959 – 2963Combined sources5
Turni2967 – 2970Combined sources4
Turni2975 – 2977Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1NB4X-ray2.00A/B2420-2989[»]
1NB6X-ray2.60A/B2420-2989[»]
1NB7X-ray2.90A/B2420-2989[»]
2F55X-ray3.30A/B/C1216-1650[»]
2MTSNMR-A747-809[»]
2XHUX-ray2.29A/B2420-2989[»]
2XHVX-ray1.90A/B2420-2989[»]
2XHWX-ray2.66A2420-2989[»]
2YOJX-ray1.76A/B2420-2989[»]
3CSOX-ray2.71A/B2420-2989[»]
3GNVX-ray2.75A/B2420-2989[»]
3GNWX-ray2.39A/B2420-2989[»]
3GOLX-ray2.85A/B2420-2989[»]
3HKYX-ray1.90A/B2420-2989[»]
3LKHX-ray2.05A/B2420-2989[»]
3MWVX-ray2.20A/B2420-2989[»]
3MWWX-ray2.80A/B2420-2989[»]
3SKAX-ray1.73A/B2420-2989[»]
3SKEX-ray1.97A/B2420-2989[»]
3SKHX-ray2.50A/B2420-2989[»]
3TYQX-ray1.60A/B2420-2989[»]
3TYVX-ray1.65A/B2420-2989[»]
3U4OX-ray1.77A/B2420-2989[»]
3U4RX-ray2.00A/B2420-2989[»]
3UPHX-ray2.00A/B2420-2989[»]
3UPIX-ray2.00A/B2420-2989[»]
4DRUX-ray2.10A/B2420-2982[»]
4EAWX-ray2.00A/B2420-2981[»]
4GMCX-ray2.70A/B2420-2989[»]
4IZ0X-ray2.22A/B2420-2989[»]
4J02X-ray2.00A/B2420-2989[»]
4J04X-ray2.00A/B2420-2989[»]
4J06X-ray2.00A/B2420-2989[»]
4J08X-ray2.10A/B2420-2989[»]
4J0AX-ray2.40A/B2420-2989[»]
4JJSX-ray2.20A/B2420-2989[»]
4JJUX-ray1.91A/B2420-2989[»]
4JTWX-ray3.00A/B2420-2989[»]
4JTYX-ray2.60A/B2420-2989[»]
4JTZX-ray2.80A/B2420-2989[»]
4JU1X-ray2.90A/B2420-2989[»]
4JU2X-ray2.70A/B2420-2989[»]
4JU3X-ray2.00A/B2420-2989[»]
4JU4X-ray2.40A/B2420-2989[»]
4JU6X-ray2.20A/B2420-2989[»]
4JU7X-ray2.20A/B2420-2989[»]
4JVQX-ray2.40A/B2420-2989[»]
4JY0X-ray2.20A/B2420-2989[»]
4JY1X-ray2.60A/B2420-2989[»]
4MZ4X-ray1.63A/B2420-2989[»]
4OOWX-ray2.57A/B2420-2989[»]
4RY4X-ray2.59A/B2420-2989[»]
4RY5X-ray2.71A/B2420-2989[»]
4RY6X-ray2.52A/B2420-2989[»]
4RY7X-ray3.00A/B2420-2989[»]
5CZBX-ray1.96A/B2420-2981[»]
ProteinModelPortaliO92972.
SMRiO92972.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO92972.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini903 – 1026Peptidase C18PROSITE-ProRule annotationAdd BLAST124
Domaini1217 – 1369Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST153
Domaini2633 – 2751RdRp catalyticPROSITE-ProRule annotationAdd BLAST119

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 59Interaction with DDX3XBy similarityAdd BLAST58
Regioni2 – 23Interaction with STAT1By similarityAdd BLAST22
Regioni122 – 173Interaction with APOA2By similarityAdd BLAST52
Regioni150 – 159Mitochondrial targeting signalBy similarity10
Regioni164 – 167Important for lipid droplets localizationBy similarity4
Regioni265 – 296Fusion peptideSequence analysisAdd BLAST32
Regioni385 – 411HVR1By similarityAdd BLAST27
Regioni475 – 481HVR2By similarity7
Regioni482 – 494CD81-binding 1Sequence analysisAdd BLAST13
Regioni522 – 553CD81-binding 2Sequence analysisAdd BLAST32
Regioni660 – 671PKR/eIF2-alpha phosphorylation homology domain (PePHD)By similarityAdd BLAST12
Regioni1679 – 1690NS3-binding (by NS4A)Sequence analysisAdd BLAST12
Regioni2120 – 2332Transcriptional activationSequence analysisAdd BLAST213
Regioni2120 – 2208FKBP8-bindingSequence analysisAdd BLAST89
Regioni2200 – 2250Basal phosphorylationBy similarityAdd BLAST51
Regioni2210 – 2275PKR-bindingSequence analysisAdd BLAST66
Regioni2210 – 2249ISDRBy similarityAdd BLAST40
Regioni2249 – 2306NS4B-bindingSequence analysisAdd BLAST58
Regioni2351 – 2419Basal phosphorylationBy similarityAdd BLAST69
Regioni2354 – 2377V3By similarityAdd BLAST24

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi5 – 13Nuclear localization signalSequence analysis9
Motifi38 – 43Nuclear localization signalSequence analysis6
Motifi58 – 64Nuclear localization signalSequence analysis7
Motifi66 – 71Nuclear localization signalSequence analysis6
Motifi1316 – 1319DECH box4
Motifi2322 – 2325SH3-bindingSequence analysis4
Motifi2327 – 2335Nuclear localization signalSequence analysis9

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi796 – 803Poly-Leu8
Compositional biasi1432 – 1435Poly-Val4
Compositional biasi2282 – 2327Pro-richAdd BLAST46
Compositional biasi2993 – 2998Poly-Leu6

Domaini

The transmembrane regions of envelope E1 and E2 glycoproteins are involved in heterodimer formation, ER localization, and assembly of these proteins. Envelope E2 glycoprotein contain two highly variable regions called hypervariable region 1 and 2 (HVR1 and HVR2). E2 also contain two segments involved in CD81-binding. HVR1 is implicated in the SCARB1-mediated cell entry. HVR2 and CD81-binding regions may be involved in sensitivity and/or resistance to IFN-alpha therapy (By similarity).By similarity
The N-terminus of NS5A acts as membrane anchor. The central part of NS5A seems to be intrinsically disordered and interacts with NS5B and host PKR. The C-terminus of NS5A contains a variable region called variable region 3 (V3) (By similarity).By similarity
The SH3-binding domain of NS5A is involved in the interaction with human Bin1, GRB2 and Src-family kinases.By similarity
The N-terminal one-third of serine protease NS3 contains the protease activity. This region contains a zinc atom that does not belong to the active site, but may play a structural rather than a catalytic role. This region is essential for the activity of protease NS2-3, maybe by contributing to the folding of the latter. The helicase activity is located in the C-terminus of NS3 (By similarity).By similarity

Sequence similaritiesi

Belongs to the hepacivirus polyprotein family.Curated
Contains 1 helicase ATP-binding domain.PROSITE-ProRule annotation
Contains 1 peptidase C18 domain.PROSITE-ProRule annotation
Contains 1 peptidase S29 domain.Curated
Contains 1 RdRp catalytic domain.PROSITE-ProRule annotation

Keywords - Domaini

SH3-binding, Transmembrane, Transmembrane helix

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR011492. DEAD_Flavivir.
IPR002521. HCV_core_C.
IPR002522. HCV_core_N.
IPR002519. HCV_env.
IPR002531. HCV_NS1.
IPR002518. HCV_NS2.
IPR000745. HCV_NS4a.
IPR001490. HCV_NS4b.
IPR002868. HCV_NS5a.
IPR013193. HCV_NS5a_1B_dom.
IPR024350. HCV_NS5a_C.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR013192. NS5A_1a.
IPR027417. P-loop_NTPase.
IPR009003. Peptidase_S1_PA.
IPR004109. Peptidase_S29.
IPR007094. RNA-dir_pol_PSvirus.
IPR002166. RNA_pol_HCV.
[Graphical view]
PfamiPF07652. Flavi_DEAD. 1 hit.
PF01543. HCV_capsid. 1 hit.
PF01542. HCV_core. 1 hit.
PF01539. HCV_env. 1 hit.
PF01560. HCV_NS1. 1 hit.
PF01538. HCV_NS2. 1 hit.
PF01006. HCV_NS4a. 1 hit.
PF01001. HCV_NS4b. 1 hit.
PF01506. HCV_NS5a. 1 hit.
PF08300. HCV_NS5a_1a. 1 hit.
PF08301. HCV_NS5a_1b. 1 hit.
PF12941. HCV_NS5a_C. 1 hit.
PF02907. Peptidase_S29. 1 hit.
PF00998. RdRP_3. 1 hit.
[Graphical view]
ProDomiPD001388. HCV_env. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00487. DEXDc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEiPS51693. HCV_NS2_PRO. 1 hit.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O92972-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTNPKPQRK TKRNTNRRPQ DVKFPGGGQI VGGVYLLPRR GPRLGVRATR
60 70 80 90 100
KASERSQPRG RRQPIPKARR PEGRAWAQPG YPWPLYGNEG LGWAGWLLSP
110 120 130 140 150
RGSRPSWGPT DPRRRSRNLG KVIDTLTCGF ADLMGYIPLV GAPLGGAARA
160 170 180 190 200
LAHGVRVLED GVNYATGNLP GCSFSIFLLA LLSCLTIPAS AYEVRNVSGI
210 220 230 240 250
YHVTNDCSNS SIVYEAADVI MHTPGCVPCV REGNSSRCWV ALTPTLAARN
260 270 280 290 300
ASVPTTTIRR HVDLLVGTAA FCSAMYVGDL CGSIFLVSQL FTFSPRRHET
310 320 330 340 350
VQDCNCSIYP GHVSGHRMAW DMMMNWSPTT ALVVSQLLRI PQAVVDMVAG
360 370 380 390 400
AHWGVLAGLA YYSMVGNWAK VLIVALLFAG VDGETHTTGR VAGHTTSGFT
410 420 430 440 450
SLFSSGASQK IQLVNTNGSW HINRTALNCN DSLQTGFFAA LFYAHKFNSS
460 470 480 490 500
GCPERMASCR PIDWFAQGWG PITYTKPNSS DQRPYCWHYA PRPCGVVPAS
510 520 530 540 550
QVCGPVYCFT PSPVVVGTTD RSGVPTYSWG ENETDVMLLN NTRPPQGNWF
560 570 580 590 600
GCTWMNSTGF TKTCGGPPCN IGGVGNRTLI CPTDCFRKHP EATYTKCGSG
610 620 630 640 650
PWLTPRCLVD YPYRLWHYPC TLNFSIFKVR MYVGGVEHRL NAACNWTRGE
660 670 680 690 700
RCNLEDRDRS ELSPLLLSTT EWQILPCAFT TLPALSTGLI HLHQNIVDVQ
710 720 730 740 750
YLYGVGSAFV SFAIKWEYIL LLFLLLADAR VCACLWMMLL IAQAEAALEN
760 770 780 790 800
LVVLNAASVA GAHGILSFLV FFCAAWYIKG RLAPGAAYAF YGVWPLLLLL
810 820 830 840 850
LALPPRAYAL DREMAASCGG AVLVGLVFLT LSPYYKVFLT RLIWWLQYFI
860 870 880 890 900
TRAEAHMQVW VPPLNVRGGR DAIILLTCAV HPELIFDITK LLLAILGPLM
910 920 930 940 950
VLQAGITRVP YFVRAQGLIR ACMLVRKVAG GHYVQMAFMK LGALTGTYVY
960 970 980 990 1000
NHLTPLRDWA HAGLRDLAVA VEPVVFSAME TKVITWGADT AACGDIILGL
1010 1020 1030 1040 1050
PVSARRGKEI FLGPADSLEG QGWRLLAPIT AYSQQTRGVL GCIITSLTGR
1060 1070 1080 1090 1100
DKNQVEGEVQ VVSTATQSFL ATCINGVCWT VYHGAGSKTL AGPKGPITQM
1110 1120 1130 1140 1150
YTNVDLDLVG WQAPPGARSM TPCSCGSSDL YLVTRHADVI PVRRRGDSRG
1160 1170 1180 1190 1200
SLLSPRPVSY LKGSSGGPLL CPSGHVVGVF RAAVCTRGVA KAVDFIPVES
1210 1220 1230 1240 1250
METTMRSPVF TDNSSPPAVP QTFQVAHLHA PTGSGKSTKV PAAYAAQGYK
1260 1270 1280 1290 1300
VLVLNPSVAA TLGFGAYMSK AHGIDPNIRT GVRTITTGGS ITYSTYGKFL
1310 1320 1330 1340 1350
ADGGCSGGAY DIIICDECHS TDSTTILGIG TVLDQAETAG ARLVVLATAT
1360 1370 1380 1390 1400
PPGSVTVPHP NIEEIGLSNN GEIPFYGKAI PIEAIKGGRH LIFCHSKKKC
1410 1420 1430 1440 1450
DELAAKLTGL GLNAVAYYRG LDVSVIPPIG DVVVVATDAL MTGFTGDFDS
1460 1470 1480 1490 1500
VIDCNTCVTQ TVDFSLDPTF TIETTTVPQD AVSRSQRRGR TGRGRSGIYR
1510 1520 1530 1540 1550
FVTPGERPSG MFDSSVLCEC YDAGCAWYEL TPAETSVRLR AYLNTPGLPV
1560 1570 1580 1590 1600
CQDHLEFWES VFTGLTHIDA HFLSQTKQAG DNFPYLVAYQ ATVCARAQAP
1610 1620 1630 1640 1650
PPSWDQMWKC LIRLKPTLHG PTPLLYRLGA VQNEVILTHP ITKYIMACMS
1660 1670 1680 1690 1700
ADLEVVTSTW VLVGGVLAAL AAYCLTTGSV VIVGRIILSG KPAVVPDREV
1710 1720 1730 1740 1750
LYQEFDEMEE CASQLPYIEQ GMQLAEQFKQ KALGLLQTAT KQAEAAAPVV
1760 1770 1780 1790 1800
ESKWRALETF WAKHMWNFIS GIQYLAGLST LPGNPAIASL MAFTASITSP
1810 1820 1830 1840 1850
LTTQNTLLFN ILGGWVAAQL APPSAASAFV GAGIAGAAVG SIGLGKVLVD
1860 1870 1880 1890 1900
ILAGYGAGVA GALVAFKVMS GEVPSTEDLV NLLPAILSPG ALVVGVVCAA
1910 1920 1930 1940 1950
ILRRHVGPGE GAVQWMNRLI AFASRGNHVS PTHYVPESDA AARVTQILSS
1960 1970 1980 1990 2000
LTITQLLKRL HQWINEDCST PCSGSWLRDV WDWICTVLTD FKTWLQSKLL
2010 2020 2030 2040 2050
PRLPGVPFLS CQRGYKGVWR GDGIMQTTCP CGAQIAGHVK NGSMRIVGPR
2060 2070 2080 2090 2100
TCSNTWHGTF PINAYTTGPC TPSPAPNYSR ALWRVAAEEY VEVTRVGDFH
2110 2120 2130 2140 2150
YVTGMTTDNV KCPCQVPAPE FFTEVDGVRL HRYAPACKPL LREDVTFQVG
2160 2170 2180 2190 2200
LNQYLVGSQL PCEPEPDVTV LTSMLTDPSH ITAETAKRRL ARGSPPSLAS
2210 2220 2230 2240 2250
SSASQLSAPS LKATCTTHHD SPDADLIEAN LLWRQEMGGN ITRVESENKV
2260 2270 2280 2290 2300
VILDSFEPLH AEGDEREISV AAEILRKSRK FPSALPIWAR PDYNPPLLES
2310 2320 2330 2340 2350
WKDPDYVPPV VHGCPLPPTK APPIPPPRRK RTVVLTESNV SSALAELATK
2360 2370 2380 2390 2400
TFGSSGSSAV DSGTATALPD LASDDGDKGS DVESYSSMPP LEGEPGDPDL
2410 2420 2430 2440 2450
SDGSWSTVSE EASEDVVCCS MSYTWTGALI TPCAAEESKL PINPLSNSLL
2460 2470 2480 2490 2500
RHHNMVYATT SRSASLRQKK VTFDRLQVLD DHYRDVLKEM KAKASTVKAK
2510 2520 2530 2540 2550
LLSIEEACKL TPPHSAKSKF GYGAKDVRNL SSRAVNHIRS VWEDLLEDTE
2560 2570 2580 2590 2600
TPIDTTIMAK SEVFCVQPEK GGRKPARLIV FPDLGVRVCE KMALYDVVST
2610 2620 2630 2640 2650
LPQAVMGSSY GFQYSPKQRV EFLVNTWKSK KCPMGFSYDT RCFDSTVTES
2660 2670 2680 2690 2700
DIRVEESIYQ CCDLAPEARQ AIRSLTERLY IGGPLTNSKG QNCGYRRCRA
2710 2720 2730 2740 2750
SGVLTTSCGN TLTCYLKATA ACRAAKLQDC TMLVNGDDLV VICESAGTQE
2760 2770 2780 2790 2800
DAAALRAFTE AMTRYSAPPG DPPQPEYDLE LITSCSSNVS VAHDASGKRV
2810 2820 2830 2840 2850
YYLTRDPTTP LARAAWETAR HTPINSWLGN IIMYAPTLWA RMILMTHFFS
2860 2870 2880 2890 2900
ILLAQEQLEK ALDCQIYGAC YSIEPLDLPQ IIERLHGLSA FTLHSYSPGE
2910 2920 2930 2940 2950
INRVASCLRK LGVPPLRTWR HRARSVRAKL LSQGGRAATC GRYLFNWAVR
2960 2970 2980 2990 3000
TKLKLTPIPA ASQLDLSGWF VAGYSGGDIY HSLSRARPRW FPLCLLLLSV
3010
GVGIYLLPNR
Length:3,010
Mass (Da):326,767
Last modified:February 20, 2007 - v2
Checksum:i0480D428ABDE9847
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti52A → T in strain: Isolate pCV-J4L4S and Isolate HC-J4/91. 1
Natural varianti70R → Q in strain: Isolate HC-J4/91. 1
Natural varianti231R → Q in strain: Isolate pCV-J4L2S and Isolate pCV-J4L6S. 1
Natural varianti250N → D in strain: Isolate HC-J4/91 and Isolate pCV-J4L4S. 1
Natural varianti304C → Y in strain: Isolate pCV-J4L2S. 1
Natural varianti384 – 390ETHTTGR → ATYTSGG in strain: Isolate HC-J4/91. 7
Natural varianti394H → R in strain: Isolate HC-J4/91 and Isolate pCV-J4L4S. 1
Natural varianti434Q → H in strain: Isolate HC-J4/91. 1
Natural varianti438F → L in strain: Isolate pCV-J4L4S. 1
Natural varianti444A → T in strain: Isolate pCV-J4L4S and Isolate HC-J4/91. 1
Natural varianti450S → P in strain: Isolate pCV-J4L4S. 1
Natural varianti464W → G in strain: Isolate HC-J4/91. 1
Natural varianti476K → E in strain: Isolate pCV-J4L4S and Isolate HC-J4/91. 1
Natural varianti480S → P in strain: Isolate HC-J4/91. 1
Natural varianti496V → I in strain: Isolate pCV-J4L4S and Isolate HC-J4/91. 1
Natural varianti536V → M in strain: Isolate pCV-J4L2S. 1
Natural varianti934V → I in strain: Isolate pCV-J4L2S. 1
Natural varianti937A → V in strain: Isolate pCV-J4L6S. 1
Natural varianti1043I → V in strain: Isolate pCV-J4L2S and Isolate pCV-J4L4S. 1
Natural varianti1215S → T in strain: Isolate pCV-J4L6S. 1
Natural varianti1223F → S in strain: Isolate pCV-J4L2S. 1
Natural varianti1528Y → H in strain: Isolate pCV-J4L4S. 1
Natural varianti1662L → P in strain: Isolate pCV-J4L2S. 1
Natural varianti1753K → R in strain: Isolate pCV-J4L2S. 1
Natural varianti1805N → H in strain: Isolate pCV-J4L2S. 1
Natural varianti1949S → P in strain: Isolate pCV-J4L4S. 1
Natural varianti2138K → R in strain: Isolate pCV-J4L4S. 1
Natural varianti2385Y → H in strain: Isolate pCV-J4L4S. 1
Natural varianti2785C → R in strain: Isolate pCV-J4L2S. 1
Natural varianti2824I → V in strain: Isolate pCV-J4L2S. 1
Natural varianti2999S → F in strain: Isolate HC-J4/91. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D10750 Genomic RNA. Translation: BAA01583.1.
AF054247 Genomic RNA. Translation: AAC15722.1.
AF054248 Genomic RNA. Translation: AAC15723.1.
AF054249 Genomic RNA. Translation: AAC15724.1.
AF054250 Genomic RNA. Translation: AAC15725.1.
PIRiA61196.
PQ0246.
PQ0804.
PS0329.

Cross-referencesi

Web resourcesi

euHCVdb

The European HCV database

Virus Pathogen Resource

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D10750 Genomic RNA. Translation: BAA01583.1.
AF054247 Genomic RNA. Translation: AAC15722.1.
AF054248 Genomic RNA. Translation: AAC15723.1.
AF054249 Genomic RNA. Translation: AAC15724.1.
AF054250 Genomic RNA. Translation: AAC15725.1.
PIRiA61196.
PQ0246.
PQ0804.
PS0329.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1NB4X-ray2.00A/B2420-2989[»]
1NB6X-ray2.60A/B2420-2989[»]
1NB7X-ray2.90A/B2420-2989[»]
2F55X-ray3.30A/B/C1216-1650[»]
2MTSNMR-A747-809[»]
2XHUX-ray2.29A/B2420-2989[»]
2XHVX-ray1.90A/B2420-2989[»]
2XHWX-ray2.66A2420-2989[»]
2YOJX-ray1.76A/B2420-2989[»]
3CSOX-ray2.71A/B2420-2989[»]
3GNVX-ray2.75A/B2420-2989[»]
3GNWX-ray2.39A/B2420-2989[»]
3GOLX-ray2.85A/B2420-2989[»]
3HKYX-ray1.90A/B2420-2989[»]
3LKHX-ray2.05A/B2420-2989[»]
3MWVX-ray2.20A/B2420-2989[»]
3MWWX-ray2.80A/B2420-2989[»]
3SKAX-ray1.73A/B2420-2989[»]
3SKEX-ray1.97A/B2420-2989[»]
3SKHX-ray2.50A/B2420-2989[»]
3TYQX-ray1.60A/B2420-2989[»]
3TYVX-ray1.65A/B2420-2989[»]
3U4OX-ray1.77A/B2420-2989[»]
3U4RX-ray2.00A/B2420-2989[»]
3UPHX-ray2.00A/B2420-2989[»]
3UPIX-ray2.00A/B2420-2989[»]
4DRUX-ray2.10A/B2420-2982[»]
4EAWX-ray2.00A/B2420-2981[»]
4GMCX-ray2.70A/B2420-2989[»]
4IZ0X-ray2.22A/B2420-2989[»]
4J02X-ray2.00A/B2420-2989[»]
4J04X-ray2.00A/B2420-2989[»]
4J06X-ray2.00A/B2420-2989[»]
4J08X-ray2.10A/B2420-2989[»]
4J0AX-ray2.40A/B2420-2989[»]
4JJSX-ray2.20A/B2420-2989[»]
4JJUX-ray1.91A/B2420-2989[»]
4JTWX-ray3.00A/B2420-2989[»]
4JTYX-ray2.60A/B2420-2989[»]
4JTZX-ray2.80A/B2420-2989[»]
4JU1X-ray2.90A/B2420-2989[»]
4JU2X-ray2.70A/B2420-2989[»]
4JU3X-ray2.00A/B2420-2989[»]
4JU4X-ray2.40A/B2420-2989[»]
4JU6X-ray2.20A/B2420-2989[»]
4JU7X-ray2.20A/B2420-2989[»]
4JVQX-ray2.40A/B2420-2989[»]
4JY0X-ray2.20A/B2420-2989[»]
4JY1X-ray2.60A/B2420-2989[»]
4MZ4X-ray1.63A/B2420-2989[»]
4OOWX-ray2.57A/B2420-2989[»]
4RY4X-ray2.59A/B2420-2989[»]
4RY5X-ray2.71A/B2420-2989[»]
4RY6X-ray2.52A/B2420-2989[»]
4RY7X-ray3.00A/B2420-2989[»]
5CZBX-ray1.96A/B2420-2981[»]
ProteinModelPortaliO92972.
SMRiO92972.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO92972. 12 interactors.

Chemistry databases

BindingDBiO92972.
ChEMBLiCHEMBL3638332.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

euHCVdbiAF054247.
AF054248.
AF054249.
AF054250.
D10750.

Enzyme and pathway databases

BRENDAi2.7.7.48. 2642.
3.4.21.98. 2642.

Miscellaneous databases

EvolutionaryTraceiO92972.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR011492. DEAD_Flavivir.
IPR002521. HCV_core_C.
IPR002522. HCV_core_N.
IPR002519. HCV_env.
IPR002531. HCV_NS1.
IPR002518. HCV_NS2.
IPR000745. HCV_NS4a.
IPR001490. HCV_NS4b.
IPR002868. HCV_NS5a.
IPR013193. HCV_NS5a_1B_dom.
IPR024350. HCV_NS5a_C.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR013192. NS5A_1a.
IPR027417. P-loop_NTPase.
IPR009003. Peptidase_S1_PA.
IPR004109. Peptidase_S29.
IPR007094. RNA-dir_pol_PSvirus.
IPR002166. RNA_pol_HCV.
[Graphical view]
PfamiPF07652. Flavi_DEAD. 1 hit.
PF01543. HCV_capsid. 1 hit.
PF01542. HCV_core. 1 hit.
PF01539. HCV_env. 1 hit.
PF01560. HCV_NS1. 1 hit.
PF01538. HCV_NS2. 1 hit.
PF01006. HCV_NS4a. 1 hit.
PF01001. HCV_NS4b. 1 hit.
PF01506. HCV_NS5a. 1 hit.
PF08300. HCV_NS5a_1a. 1 hit.
PF08301. HCV_NS5a_1b. 1 hit.
PF12941. HCV_NS5a_C. 1 hit.
PF02907. Peptidase_S29. 1 hit.
PF00998. RdRP_3. 1 hit.
[Graphical view]
ProDomiPD001388. HCV_env. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00487. DEXDc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEiPS51693. HCV_NS2_PRO. 1 hit.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPOLG_HCVJ4
AccessioniPrimary (citable) accession number: O92972
Secondary accession number(s): O92969
, O92970, O92971, Q02828
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: February 20, 2007
Last modified: November 30, 2016
This is version 137 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Miscellaneous

Cell culture adaptation of the virus leads to mutations in NS5A, reducing its inhibitory effect on replication.By similarity
Core protein exerts viral interference on hepatitis B virus when HCV and HBV coinfect the same cell, by suppressing HBV gene expression, RNA encapsidation and budding.By similarity

Caution

The core gene probably also codes for alternative reading frame proteins (ARFPs). Many functions depicted for the core protein might belong to the ARFPs.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Multifunctional enzyme

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.