Reviewed, UniProtKB/Swiss-Prot Q81258 (POLG_HCVNZ)

Names and origin

Protein names	Recommended name:     Genome polyprotein Cleaved into the following 11 chains:     1- Recommended name:             Core protein p21         Alternative name(s):             Capsid protein C             p21     2- Recommended name:             Core protein p19     3- Recommended name:             Envelope glycoprotein E1         Alternative name(s):             gp32             gp35     4- Recommended name:             Envelope glycoprotein E2         Alternative name(s):             NS1             gp68             gp70     5- Recommended name:             p7     6- Recommended name:             Protease NS2-3                 Short name=p23               EC=3.4.22.-     7- Recommended name:             Serine protease/NTPase/helicase NS3               EC=3.4.21.98               EC=3.6.1.15               EC=3.6.1.-         Alternative name(s):             Hepacivirin             NS3P             p70     8- Recommended name:             Non-structural protein 4A                 Short name=NS4A         Alternative name(s):             p8     9- Recommended name:             Non-structural protein 4B                 Short name=NS4B         Alternative name(s):             p27     10- Recommended name:             Non-structural protein 5A                 Short name=NS5A         Alternative name(s):             p56     11- Recommended name:             RNA-directed RNA polymerase               EC=2.7.7.48         Alternative name(s):             NS5B             p68
Organism	Hepatitis C virus genotype 3a (isolate NZL1) (HCV) [Complete proteome]
Taxonomic identifier	356415 [NCBI]
Taxonomic lineage	Viruses › ssRNA positive-strand viruses, no DNA stage › Flaviviridae › Hepacivirus
Virus host	Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	3021 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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 By similarity. 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). 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. 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. Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation 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. 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. 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. NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication By similarity.
Catalytic activity	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). NTP + H2O = NDP + phosphate.
Cofactor	Binds 1 zinc ion per NS3 protease domain By similarity. Binds 1 zinc ion per NS5A N-terminal domain By similarity.
Enzyme regulation	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.
Subunit structure	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.
Subcellular location	Core protein p21: Host endoplasmic reticulum membrane; Single-pass membrane protein. Host mitochondrion membrane; Single-pass type I membrane protein. Host lipid droplet. Note: The C-terminal transmembrane domain of core protein p21 contains an ER signal leading the nascent polyprotein to the ER membrane. Only a minor proportion of core protein is present in the nucleus and an unknown proportion is secreted. Ref.2 Ref.4 Core protein p19: Virion By similarity. Host cytoplasm By similarity. Host nucleus By similarity. Secreted By similarity. Envelope glycoprotein E1: Virion membrane; Single-pass type I membrane protein Potential. Host endoplasmic reticulum membrane; 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; Single-pass type I membrane protein Potential. Host endoplasmic reticulum membrane; 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: Host endoplasmic reticulum membrane; Multi-pass membrane protein By similarity. Host cell membrane By similarity. Note: The C-terminus of p7 membrane domain acts as a signal sequence. After cleavage by host signal peptidase, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor. Only a fraction localizes to the plasma membrane. Protease NS2-3: Host endoplasmic reticulum membrane; Multi-pass membrane protein Potential. Serine protease/NTPase/helicase NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein By similarity. Note: NS3 is associated to the ER membrane through its binding to NS4A. Non-structural protein 4A: Host endoplasmic reticulum membrane; Single-pass type I membrane protein Potential. Note: Host membrane insertion occurs after processing by the NS3 protease. Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein By similarity. Non-structural protein 5A: Host endoplasmic reticulum membrane; Peripheral membrane protein By similarity. Host cytoplasm › host perinuclear region By similarity. Host mitochondrion By similarity. Note: Host membrane insertion occurs after processing by the NS3 protease. RNA-directed RNA polymerase: Host endoplasmic reticulum membrane; Single-pass type I membrane protein Potential. Note: Host membrane insertion occurs after processing by the NS3 protease.
Domain	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 a highly variable region called hypervariable region 1 (HVR1). E2 also contains two segments involved in CD81-binding. HVR1 is implicated in the SCARB1-mediated cell entry. CD81-binding regions may be involved in sensitivity and/or resistance to IFN-alpha therapy 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 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.
Post-translational modification	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. Envelope E1 and E2 glycoproteins are highly N-glycosylated By similarity. Core protein is phosphorylated by host PKC and PKA By similarity. NS5A is phosphorylated in a basal form termed p56. p58 is an 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. NS4B is palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions 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. Core protein is ubiquitinated; mediated by UBE3A and leading to core protein subsequent proteasomal degradation By similarity.
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. HCV genotype 3a induces increased amount of triglyceride accumulation (steatosis) over other genotypes. This could be due to a stronger FAS promoter up-regulation by the core protein from genotype 3a.
Sequence similarities	Belongs to the hepaciviruses polyprotein family. Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain. Contains 1 peptidase C18 domain. Contains 1 peptidase S29 domain. Contains 1 RdRp catalytic domain.
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.

Ontologies

Keywords
Biological process	Apoptosis Fusion protein Host-virus interaction Interferon antiviral system evasion RNA replication Transcription Transcription regulation
Cellular component	Capsid protein Envelope protein Host cell membrane Host cytoplasm Host endoplasmic reticulum Host lipid droplet Host membrane Host mitochondrion Host nucleus Membrane Secreted Virion
Disease	Oncogene
Domain	SH3-binding Transmembrane
Ligand	ATP-binding Metal-binding Nucleotide-binding RNA-binding Viral nucleoprotein Zinc
Molecular function	Helicase Hydrolase Nucleotidyltransferase Protease RNA-directed RNA polymerase Ribonucleoprotein Serine protease Thiol protease Transferase
PTM	Acetylation Disulfide bond Glycoprotein Lipoprotein Palmitate Phosphoprotein Ubl conjugation
Technical term	Complete proteome Multifunctional enzyme
Gene Ontology (GO)
Biological process	apoptosis Inferred from electronic annotation. Source: UniProtKB-KW evasion by virus of host immune response Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: InterPro regulation of transcription Inferred from electronic annotation. Source: UniProtKB-KW transcription, RNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transformation of host cell by virus Inferred from electronic annotation. Source: InterPro viral genome replication Inferred from electronic annotation. Source: InterPro
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: InterPro extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell host cell mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell host cell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell host cell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell lipid particle Inferred from electronic annotation. Source: UniProtKB-KW mitochondrion Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW ribonucleoprotein complex Inferred from electronic annotation. Source: UniProtKB-KW viral capsid Inferred from electronic annotation. Source: UniProtKB-KW viral envelope Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW RNA binding Inferred from electronic annotation. Source: UniProtKB-KW RNA-directed RNA polymerase activity Inferred from electronic annotation. Source: UniProtKB-KW SH3 domain binding Inferred from electronic annotation. Source: UniProtKB-KW cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro helicase activity Inferred from electronic annotation. Source: UniProtKB-KW serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro structural molecule activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed; by host By similarity
	Chain	2 – 191	190	Core protein p21 Potential		PRO_0000045652
	Chain	2 – 177	176	Core protein p19 By similarity		PRO_0000045653
	Propeptide	178 – 191	14	ER anchor for the core protein, removed in mature form by host signal peptidase By similarity		PRO_0000045654
	Chain	192 – 383	192	Envelope glycoprotein E1 Potential		PRO_0000045655
	Chain	384 – 752	369	Envelope glycoprotein E2 Potential		PRO_0000045656
	Chain	753 – 815	63	p7 By similarity		PRO_0000045657
	Chain	816 – 1032	217	Protease NS2-3 Potential		PRO_0000045658
	Chain	1033 – 1663	631	Serine protease/NTPase/helicase NS3 Potential		PRO_0000045659
	Chain	1664 – 1717	54	Non-structural protein 4A Potential		PRO_0000045660
	Chain	1718 – 1978	261	Non-structural protein 4B Potential		PRO_0000045661
	Chain	1979 – 2430	452	Non-structural protein 5A Potential		PRO_0000045662
	Chain	2431 – 3021	591	RNA-directed RNA polymerase Potential		PRO_0000045663
Regions
	Topological domain	2 – 168	167	Cytoplasmic Potential
	Transmembrane	169 – 189	21	Potential
	Topological domain	190 – 358	169	Lumenal Potential
	Transmembrane	359 – 379	21	Potential
	Topological domain	380 – 731	352	Lumenal Potential
	Transmembrane	732 – 752	21	Potential
	Topological domain	753 – 763	11	Lumenal Potential
	Transmembrane	764 – 784	21	Potential
	Topological domain	785 – 788	4	Cytoplasmic Potential
	Transmembrane	789 – 809	21	Potential
	Topological domain	810 – 819	10	Lumenal Potential
	Transmembrane	820 – 840	21	Potential
	Topological domain	841 – 887	47	Cytoplasmic Potential
	Transmembrane	888 – 908	21	Potential
	Topological domain	909 – 934	26	Lumenal Potential
	Transmembrane	935 – 955	21	Potential
	Topological domain	956 – 1663	708	Cytoplasmic Potential
	Transmembrane	1664 – 1684	21	Potential
	Topological domain	1685 – 1811	127	Cytoplasmic Potential
	Transmembrane	1812 – 1832	21	Potential
	Topological domain	1833 – 1834	2	Lumenal Potential
	Transmembrane	1835 – 1855	21	Potential
	Topological domain	1856	1	Cytoplasmic Potential
	Transmembrane	1857 – 1877	21	Potential
	Topological domain	1878 – 1887	10	Lumenal Potential
	Transmembrane	1888 – 1908	21	Potential
	Topological domain	1909 – 1978	70	Cytoplasmic Potential
	Topological domain	1979 – 2008	30	In membrane By similarity
	Topological domain	2009 – 3000	992	Cytoplasmic Potential
	Transmembrane	3001 – 3021	21	By similarity
	Domain	1223 – 1375	153	Helicase ATP-binding
	Domain	1382 – 1544	163	Helicase C-terminal
	Domain	2644 – 2762	119	RdRp catalytic
	Nucleotide binding	1236 – 1243	8	ATP Potential
	Region	2 – 59	58	Interaction with DDX3X By similarity
	Region	2 – 23	22	Interaction with STAT1 By similarity
	Region	122 – 173	52	Interaction with APOA2 By similarity
	Region	150 – 159	10	Mitochondrial targeting signal By similarity
	Region	164 – 167	4	Important for lipid droplet localization
	Region	265 – 296	32	Fusion peptide Potential
	Region	385 – 411	27	HVR1 By similarity
	Region	483 – 495	13	CD81-binding 1 Potential
	Region	523 – 554	32	CD81-binding 2 Potential
	Region	666 – 677	12	PKR/eIF2-alpha phosphorylation homology domain (PePHD) By similarity
	Region	1685 – 1696	12	NS3-binding (by NS4A) Potential
	Region	2126 – 2338	213	Transcriptional activation Potential
	Region	2126 – 2214	89	FKBP8-binding Potential
	Region	2206 – 2256	51	Basal phosphorylation By similarity
	Region	2216 – 2281	66	PKR-binding Potential
	Region	2255 – 2312	58	NS4B-binding Potential
	Region	2357 – 2430	74	Basal phosphorylation By similarity
	Motif	5 – 13	9	Nuclear localization signal Potential
	Motif	38 – 43	6	Nuclear localization signal Potential
	Motif	58 – 64	7	Nuclear localization signal Potential
	Motif	66 – 71	6	Nuclear localization signal Potential
	Motif	1322 – 1325	4	DECH box By similarity
	Motif	2328 – 2331	4	SH3-binding Potential
	Motif	2333 – 2341	9	Nuclear localization signal Potential
	Compositional bias	2284 – 2333	50	Pro-rich
	Compositional bias	2357 – 2476	120	Ser-rich
	Compositional bias	3002 – 3009	8	Poly-Leu
Sites
	Active site	958	1	For protease NS2-3 activity; shared with dimeric partner By similarity
	Active site	978	1	For protease NS2-3 activity; shared with dimeric partner By similarity
	Active site	999	1	For protease NS2-3 activity; shared with dimeric partner By similarity
	Active site	1089	1	Charge relay system; for serine protease NS3 activity By similarity
	Active site	1113	1	Charge relay system; for serine protease NS3 activity By similarity
	Active site	1171	1	Charge relay system; for serine protease NS3 activity By similarity
	Metal binding	1129	1	Zinc By similarity
	Metal binding	1131	1	Zinc By similarity
	Metal binding	1177	1	Zinc By similarity
	Metal binding	1181	1	Zinc By similarity
	Metal binding	2017	1	Zinc By similarity
	Metal binding	2035	1	Zinc By similarity
	Metal binding	2037	1	Zinc By similarity
	Metal binding	2058	1	Zinc By similarity
	Site	164	1	Responsible for increased FAS up-regulation
	Site	177 – 178	2	Cleavage; by host signal peptidase By similarity
	Site	?191 – ?192	2	Cleavage; by host signal peptidase Potential
	Site	383 – 384	2	Cleavage; by host signal peptidase Potential
	Site	752 – 753	2	Cleavage; by host signal peptidase By similarity
	Site	815 – 816	2	Cleavage; by host signal peptidase By similarity
	Site	1032 – 1033	2	Cleavage; by protease NS2-3 Potential
	Site	1663 – 1664	2	Cleavage; by serine protease NS3 Potential
	Site	1717 – 1718	2	Cleavage; by serine protease NS3 Potential
	Site	1978 – 1979	2	Cleavage; by serine protease NS3 Potential
	Site	2430 – 2431	2	Cleavage; by serine protease NS3 Potential
Amino acid modifications
	Modified residue	2	1	N-acetylserine; by host By similarity
	Modified residue	53	1	Phosphoserine; by host By similarity
	Modified residue	99	1	Phosphoserine; by host By similarity
	Modified residue	116	1	Phosphoserine; by host PKA By similarity
	Modified residue	2200	1	Phosphoserine; by host; in p56 By similarity
	Modified residue	2203	1	Phosphoserine; by host; in p58 By similarity
	Modified residue	2207	1	Phosphoserine; by host; in p58 By similarity
	Modified residue	2210	1	Phosphoserine; by host; in p58 By similarity
	Lipidation	1978	1	S-palmitoyl cysteine; by host By similarity
	Glycosylation	196	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	209	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	234	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	305	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	417	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	423	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	430	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	448	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	476	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	557	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	581	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	651	1	N-linked (GlcNAc...); by host Potential
	Disulfide bond	2120 ↔ 2168		By similarity
Experimental info
	Mutagenesis	164	1	F → Y: Reduced FAS up-regulation by the core protein. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q81258-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 38712CCBC0C19562	FASTA	3,021	329,578
	10 20 30 40 50 60 MSTLPKPQRK TKRNTIRRPQ DVKFPGGGQI VGGVYVLPRR GPRLGVRATR KTSERSQPRG 70 80 90 100 110 120 RRQPIPKARR SEGRSWAQPG YPWPLYGNEG CGWAGWLLSP RGSRPSWGPN DPRRRSRNLG 130 140 150 160 170 180 KVIDTLTCGF ADLMGYIPLV GAPVGGVARA LAHGVRALED GINFATGNLP GCSFSIFLLA 190 200 210 220 230 240 LFSCLIHPAA SLEWRNTSGL YVLTNDCSNS SIVYEADDVI LHTPGCVPCV QDGNTSTCWT 250 260 270 280 290 300 PVTPTVAVRY VGATTASIRS HVDLLVGAAT MCSALYVGDM CGAVFLVGQA FTFRPRRHQT 310 320 330 340 350 360 VQTCNCSLYP GHLSGHRMAW DMMMNWSPAV GMVVAHVLRL PQTLFDIMAG AHWGILAGLA 370 380 390 400 410 420 YYSMQGNWAK VAIIMVMFSG VDAHTYTTGG TASRHTQAFA GLFDIGPQQK LQLVNTNGSW 430 440 450 460 470 480 HINSTALNCN ESINTGFIAG LFYYHKFNST GCPQRLSSCK PITFFRQGWG PLTDANITGP 490 500 510 520 530 540 SDDRPYCWHY APRPCDIVPA SSVCGPVYCF TPSPVVVGTT DARGVPTYTW GENEKDVFLL 550 560 570 580 590 600 KSQRPPSGRW FGCSWMNSTG FLKTCGAPPC NIYGGEGNPH NESDLFCPTD CFRKHPETTY 610 620 630 640 650 660 SRCGAGPWLT PRCMVDYPYR LWHYPCTVDF RLFKVRMFVG GFEHRFTAAC NWTRGERCDI 670 680 690 700 710 720 EDRDRSEQHP LLHSTTELAI LPCSFTPMPA LSTGLIHLHQ NIVDVQYLYG VGSGMVGWAL 730 740 750 760 770 780 KWEFVILVFL LLADARVCVA LWLMLMISQT EAALENLVTL NAVAAAGTHG IGWYLVAFCA 790 800 810 820 830 840 AWYVRGKLVP LVTYSLTGLW SLALLVLLLP QRAYAWSGED SATLGAGVLV LFGFFTLSPW 850 860 870 880 890 900 YKHWIGRLMW WNQYTICRCE SALHVWVPPL LARGSRDGVI LLTSLLYPSL IFDITKLLMA 910 920 930 940 950 960 VLGPLYLIQA TITTTPYFVR AHVLVRLCML VRSVIGGKYF QMIILSIGRW FNTYLYDHLA 970 980 990 1000 1010 1020 PMQHWAAAGL KDLAVATEPV IFSPMEIKVI TWGADTAACG DILCGLPVSA RLGREVLLGP 1030 1040 1050 1060 1070 1080 ADDYREMGWR LLAPITAYAQ QTRGLLGTIV TSLTGRDKNV VTGEVQVLST ATQTFLGTTV 1090 1100 1110 1120 1130 1140 GGVIWTVYHG AGSRTLAGAK HPALQMYTNV DQDLVGWPAP PGAKSLEPCA CGSSDLYLVT 1150 1160 1170 1180 1190 1200 RDADVIPARR RGDSTASLLS PRPLACLKGS SGGPVMCPSG HVAGIFRAAV CTRGVAKSLQ 1210 1220 1230 1240 1250 1260 FIPVETLSTQ ARSPSFSDNS TPPAVPQSYQ VGYLHAPTGS GKSTKVPAAY VAQGYNVLVL 1270 1280 1290 1300 1310 1320 NPSVAATLGF GSFMSRAYGI DPNIRTGNRT VTTGAKLTYS TYGKFLADGG CSGGAYDVII 1330 1340 1350 1360 1370 1380 CDECHAQDAT SILGIGTVLD QAETAGVRLT VLATATPPGS ITVPHSNIEE VALGSEGEIP 1390 1400 1410 1420 1430 1440 FYGKAIPIAL LKGGRHLIFC HSKKKCDEIA SKLRGMGLNA VAYYRGLDVS VIPTTGDVVV 1450 1460 1470 1480 1490 1500 CATDALMTGF TGDFDSVIDC NVAVEQYVDF SLDPTFSIET RTAPQDAVSR SQRRGRTGRG 1510 1520 1530 1540 1550 1560 RLGTYRYVAS GERPSGMFDS VVLCECYDAG CSWYDLQPAE TTVRLRAYLS TPGLPVCQDH 1570 1580 1590 1600 1610 1620 LDFWESVFTG LTHIDAHFLS QTKQQGLNFS YLTAYQATVC ARAQAPPPSW DEMWKCLVRL 1630 1640 1650 1660 1670 1680 KPTLHGPTPL LYRLGPVQNE TCLTHPITKY LMACMSADLE VTTSTWVLLG GVLAALAAYC 1690 1700 1710 1720 1730 1740 LSVGCVVIVG HIELEGKPAL VPDKEVLYQQ YDEMEECSQA APYIEQAQVI AHQFKEKILG 1750 1760 1770 1780 1790 1800 LLQRATQQQA VIEPIVTTNW QKLEAFWHKH MWNFVSGIQY LAGLSTLPGN PAVASLMAFT 1810 1820 1830 1840 1850 1860 ASVTSPLTTN QTMFFNILGG WVATHLAGPQ SSSAFVVSGL AGAAIGGIGL GRVLLDILAG 1870 1880 1890 1900 1910 1920 YGAGVSGALV AFKIMGGECP TAEDMVNLLP AILSPGALVV GVICAAILRR HVGPGEGAVQ 1930 1940 1950 1960 1970 1980 WMNRLIAFAS RGNHVSPTHY VPESDAAARV TALLSSLTVT SLLRRLHQWI NEDYPSPCSD 1990 2000 2010 2020 2030 2040 DWLRTIWDWV CSVLADFKAW LSAKIMPALP GLPFISCQKG YKGVWRGDGV MSTRCPCGAA 2050 2060 2070 2080 2090 2100 ITGHVKNGSM RLAGPRTCAN MWHGTFPINE YTTGPSTPCP SPNYTRALWR VAANSYVEVR 2110 2120 2130 2140 2150 2160 RVGDFHYITG ATEDELKCPC QVPAAEFFTE VDGVRLHRYA PPCKPLLRDD ITFMVGLHSY 2170 2180 2190 2200 2210 2220 TIGSQLPCEP EPDVSVLTSM LRDPSHITAE TAARRLARGS PPSEASSSAS QLSAPSLKAT 2230 2240 2250 2260 2270 2280 CQTHRPHPDA ELVDANLLWR QEMGSNITRV ESETKVVVLD SFEPLRAETD DVEPSVAAEC 2290 2300 2310 2320 2330 2340 FKKPPKYPPA LPIWARPDYN PPLLDRWKAP DYVPPTVHGC ALPPRGAPPV PPPRRKRTIQ 2350 2360 2370 2380 2390 2400 LDGSNVSAAL AALAEKSFPS SKPQEENSSS SGVDTQSSTT SKVPPSPGGE SDSESCSSMP 2410 2420 2430 2440 2450 2460 PLEGEPGDPD LSCDSWSTVS DSEEQSVVCC SMSYSWTGAL ITPCSAEEEK LPISPLSNSL 2470 2480 2490 2500 2510 2520 LRHHNLVYST SSRSASQRQK KVTFDRLQVL DDHYKTALKE VKERASRVKA RMLTIEEACA 2530 2540 2550 2560 2570 2580 LVPPHSARSK FGYSAKDVRS LSSRAINQIR SVWEDLLEDT TTPIPTTIMA KNEVFCVDPA 2590 2600 2610 2620 2630 2640 KGGRKPARLI VYPDLGVRVC EKRALYDVIQ KLSIETMGPA YGFQYSPQQR VERLLKMWTS 2650 2660 2670 2680 2690 2700 KKTPLGFSYD TRCFDSTVTE QDIRVEEEIY QCCNLEPEAR KVISSLTERL YCGGPMFNSK 2710 2720 2730 2740 2750 2760 GAQCGYRRCR ASGVLPTSFG NTITCYIKAT AAAKAANLRN PDFLVCGDDL VVVAESDGVD 2770 2780 2790 2800 2810 2820 EDRAALRAFT EAMTRYSAPP GDAPQATYDL ELITSCSSNV SVARDDKGRR YYYLTRDATT 2830 2840 2850 2860 2870 2880 PLARAAWETA RHTPVNSWLG NIIMYAPTIW VRMVMMTHFF SILQSQEILD RPLDFEMYGA 2890 2900 2910 2920 2930 2940 TYSVTPLDLP AIIERLHGLS AFTLHSYSPV ELNRVAGTLR KLGCPPLRAW RHRARAVRAK 2950 2960 2970 2980 2990 3000 LIAQGGKAKI CGLYLFNWAV RTKTNLTPLP AAGQLDLSSW FTVGVGGNDI YHSVSRARTR 3010 3020 HLLLCLLLLT VGVGIFLLPA R

References

[1]	"Entire nucleotide sequence and characterization of a hepatitis C virus of genotype V/3a." Sakamoto M., Akahane Y., Tsuda F., Tanaka T., Woodfield D.G., Okamoto H. J. Gen. Virol. 75:1761-1768(1994) [PubMed: 8021605] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Up-regulation of fatty acid synthase promoter by hepatitis C virus core protein: genotype-3a core has a stronger effect than genotype-1b core." Jackel-Cram C., Babiuk L.A., Liu Q. J. Hepatol. 46:999-1008(2007) [PubMed: 17188392] [Abstract] Cited for: SUBCELLULAR LOCATION OF CORE PROTEIN, FUNCTION OF CORE PROTEIN, MUTAGENESIS OF PHE-164.
[3]	"Properties of the hepatitis C virus core protein: a structural protein that modulates cellular processes." McLauchlan J. J. Viral Hepat. 7:2-14(2000) [PubMed: 10718937] [Abstract] Cited for: REVIEW.
[4]	"Structural biology of hepatitis C virus." Penin F., Dubuisson J., Rey F.A., Moradpour D., Pawlotsky J.-M. Hepatology 39:5-19(2004) [PubMed: 14752815] [Abstract] Cited for: REVIEW, SUBCELLULAR LOCATION.
[5]	"An RNA-binding protein, hnRNP A1, and a scaffold protein, septin 6, facilitate hepatitis C virus replication." Kim C.S., Seol S.K., Song O.-K., Park J.H., Jang S.K. J. Virol. 81:3852-3865(2007) [PubMed: 17229681] [Abstract] Cited for: INTERACTION WITH HNRNPA1 AND SEPT6.

Web resources

euHCVdb

The European HCV database

HCV database

Cross-references

Sequence databases
EMBLGenBankDDBJ	D17763 Genomic RNA. Translation: BAA04609.1.
PIR	PQ0401. PQ0804.
RefSeq	YP_001469631.1.
3D structure databases
HSSP	HSSP built from PDB template 1CWX based on UniProtKB Q8JYS1.
ModBase	Search...
Organism-specific databases
euHCVdb	D17763.
Family and domain databases
InterPro	IPR014001. DEAD-like_N. IPR001650. DNA/RNA_helicase_C. IPR002522. HCV_capsid. IPR002521. HCV_core. IPR002519. HCV_env. IPR002531. HCV_NS1. IPR000745. HCV_NS4a. IPR001490. HCV_NS4b. IPR002868. HCV_NS5a. IPR013193. HCV_NS5a_1b. IPR014021. Helicase_SF1/SF2_ATP-bd. IPR002518. Pept_C18_HCV_NS2. IPR004109. Peptidase_S29. IPR007094. RNA-dir_pol_PSvirus. IPR002166. RNA_pol_HCV. IPR013192. Znf_HCV_NS5a. [Graphical view]
Pfam	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. PF02907. Peptidase_S29. 1 hit. PF00998. RdRP_3. 1 hit. [Graphical view]
SMART	SM00487. DEXDc. 1 hit. [Graphical view]
PROSITE	PS51192. HELICASE_ATP_BIND_1. 1 hit. PS51194. HELICASE_CTER. 1 hit. PS50507. RDRP_SSRNA_POS. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

POLG_HCVNZ

Accession

Primary (citable) accession number: Q81258

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 10, 2006
Last sequence update:	January 23, 2007
Last modified:	November 3, 2009
This is version 75 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Virus (Virus annotation project)