Inhibition of host PKR by virus

The protein kinase regulated by RNA, PKR, plays an important function in innate immune response. The N-terminal includes a repeated domain that confers dsRNA-binding activity while the C-terminal confers the kinase activity. The best characterized substrate of PKR is the alpha-subunit of protein synthesis initiator 2 (eIF-2alpha(J02645:9606) ). When phosphorylated by PKR, eIF-2alpha leads to an inhibition of translation. Therefore, PKR is a key factor in the host antiviral response, through inhibition of protein synthesis during viral infection.


Viruses have evolved specific mechanisms to prevent the establishment of an antiviral state by inhibiting key components of the signaling pathway . For instance, several viral proteins antagonists of PKR have been identified, many of which are RNA-binding proteins. Among them, E3L(P21605) and K3L(P18378) from vaccinia and sigma3(P07939) protein from reoviruses. E3L(P21605) was found to inhibit host PKR activity through direct interaction. Hepatitis C virus NS5A(P27958), Herpes simplex 1 US11(P04487), and Kaposi’s sarcoma vIRF-2 protein also interact with and inhibit PKR. Some viruses including HCMV or MCMV alter PKR subcellular localization while others direct PKR to degradation like Rift valley fever virus NSs(P21698:9606) protein.

Matching UniProtKB/Swiss-Prot entries

165 entries grouped by protein (browse by keywords)

All proteins are shown (view only 89 complete proteome entries)

1 entry

G-protein coupled receptor BILF1

BILF1_EBVB9
Epstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4) reference strain

1 entry

E1B 55 kDa protein (E1B-55K) (E1B protein, large T-antigen) (E1B-495R)

E1B55_ADE02
Human adenovirus C serotype 2 (HAdV-2) (Human adenovirus 2) reference strain

3 entries

Protein E3 (p25)

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E3_VACCC
Vaccinia virus (strain Copenhagen) (VACV) reference strain
E3_VACCW
Vaccinia virus (strain Western Reserve) (VACV) (Vaccinia virus (strain WR)) reference strain
E3_VAR67
Variola virus (isolate Human/India/Ind3/1967) (VARV) (Smallpox virus) reference strain

Protein E3

3 entries

mRNA export factor ICP27 homolog (Mta) (ORF57 protein homolog) (Protein SM)

Select_allDeselect_all
ICP27_EBVA8
Epstein-Barr virus (strain AG876) (HHV-4) (Human herpesvirus 4) reference strain
ICP27_EBVB9
Epstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4) reference strain
ICP27_EBVG
Epstein-Barr virus (strain GD1) (HHV-4) (Human herpesvirus 4)

2 entries

Protein IRS1

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IRS1_HCMVA
Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5) reference strain

Protein IRS1 (HQRF1)

IRS1_HCMVM
Human cytomegalovirus (strain Merlin) (HHV-5) (Human herpesvirus 5) reference strain

3 entries

Protein K3

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K3_VACCC
Vaccinia virus (strain Copenhagen) (VACV) reference strain
K3_VACCW
Vaccinia virus (strain Western Reserve) (VACV) (Vaccinia virus (strain WR)) reference strain

Protein K3 (Protein K2)

K3_SWPVK
Swinepox virus (strain Kasza) (SWPV)

Protein K3 homolog

8 entries

Nucleoprotein (Protein N) (Nucleocapsid protein)

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NCAP_HRSVA
Human respiratory syncytial virus A (strain A2) reference strain
NCAP_HRSVB
Human respiratory syncytial virus B (strain B1) reference strain
NCAP_MPV15
Murine pneumonia virus (strain 15) (MPV) reference strain

Nucleoprotein (Nucleocapsid protein) (NP) (Protein N)

NCAP_BRSV3
Bovine respiratory syncytial virus (strain 391-2) (BRS)
NCAP_BRSVA
Bovine respiratory syncytial virus (strain A51908) (BRS)
NCAP_BRSVR
Bovine respiratory syncytial virus (strain Rb94) (BRS)
NCAP_HRSV1
Human respiratory syncytial virus B (strain 18537)
NCAP_ORSVW
Ovine respiratory syncytial virus (strain WSU 83-1578) (ORSV)

134 entries

Non-structural protein 1 (NS1) (NS1A)

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NS1_I34A1
Influenza A virus (strain A/Puerto Rico/8/1934 H1N1) reference strain
NS1_I57A5
Influenza A virus (strain A/Singapore/1/1957 H2N2) reference strain
NS1_I68A4
Influenza A virus (strain A/Hong Kong/1/1968 H3N2) reference strain
NS1_I77AF
Influenza A virus (strain A/Gull/Maryland/704/1977 H13N6) reference strain
NS1_I96A0
Influenza A virus (strain A/Goose/Guangdong/1/1996 H5N1 genotype Gs/Gd) reference strain
NS1_INBLE
Influenza B virus (strain B/Lee/1940) reference strain
NS1_I000W
Influenza A virus (strain A/Wa-182)
NS1_I000X
Influenza A virus (strain A/X-31 H3N2)
NS1_I00A0
Influenza A virus (strain A/Duck/Hong Kong/2986.1/2000 H5N1 genotype C)
NS1_I00A1
Influenza A virus (strain A/New Zealand:South Canterbury/35/2000 H1N1)
NS1_I01A0
Influenza A virus (strain A/Silky Chicken/Hong Kong/SF189/2001 H5N1 genotype A)
NS1_I01A1
Influenza A virus (strain A/Chicken/Hong Kong/YU562/2001 H5N1 genotype B)
NS1_I01A2
Influenza A virus (strain A/Chicken/Hong Kong/FY150/2001 H5N1 genotype D)
NS1_I01A3
Influenza A virus (strain A/Chicken/Hong Kong/715.5/2001 H5N1 genotype E)
NS1_I02A0
Influenza A virus (strain A/Chicken/Brescia/1902 H7N7)
NS1_I02A1
Influenza A virus (strain A/Guinea fowl/Hong Kong/38/2002 H5N1 genotype X0)
NS1_I02A2
Influenza A virus (strain A/Chicken/Hong Kong/31.2/2002 H5N1 genotype X1)
NS1_I02A3
Influenza A virus (strain A/Chicken/Hong Kong/37.4/2002 H5N1 genotype X2)
NS1_I02A4
Influenza A virus (strain A/Silky Chicken/Hong Kong/YU100/2002 H5N1 genotype X3)
NS1_I02A5
Influenza A virus (strain A/Chicken/Hong Kong/96.1/2002 H5N1 genotype Y)
NS1_I02A6
Influenza A virus (strain A/Chicken/Hong Kong/YU22/2002 H5N1 genotype Z)
NS1_I03A0
Influenza A virus (strain A/Hong Kong/212/2003 H5N1 genotype Z+)
NS1_I03A1
Influenza A virus (strain A/Chicken/Shantou/4231/2003 H5N1 genotype V)
NS1_I06A0
Influenza A virus (strain A/Russia:St.Petersburg/8/2006 H1N1)
NS1_I07A0
Influenza A virus (strain A/USA:Texas/UR06-0195/2007 H1N1)
NS1_I18A0
Influenza A virus (strain A/Brevig Mission/1/1918 H1N1) (Influenza A virus (strain A/South Carolina/1/1918 H1N1))
NS1_I30A0
Influenza A virus (strain A/Swine/Iowa/15/1930 H1N1)
NS1_I33A0
Influenza A virus (strain A/Wilson-Smith/1933 H1N1) (Influenza A virus (strain A/WS/1933 H1N1))
NS1_I34A0
Influenza A virus (strain A/Fowl plague virus/Rostock/8/1934 H7N1)
NS1_I35A3
Influenza A virus (strain A/USA:Phila/1935 H1N1)
NS1_I36A0
Influenza A virus (strain A/Henry/1936 H1N1)
NS1_I40A0
Influenza A virus (strain A/Hickox/1940 H1N1)
NS1_I43A0
Influenza A virus (strain A/USA:Iowa/1943 H1N1)
NS1_I45A0
Influenza A virus (strain A/USA:Huston/AA/1945 H1N1)
NS1_I47A0
Influenza A virus (strain A/Fort Monmouth/1/1947 H1N1)
NS1_I49A0
Influenza A virus (strain A/Chicken/Germany/n/1949 H10N7)
NS1_I49A1
Influenza A virus (strain A/Duck/Germany/1949 H10N7)
NS1_I50A0
Influenza A virus (strain A/Fort Warren/1/1950 H1N1)
NS1_I51A0
Influenza A virus (strain A/USA:Albany/12/1951 H1N1)
NS1_I54A0
Influenza A virus (strain A/Leningrad/1/1954 H1N1)
NS1_I54A2
Influenza A virus (strain A/Malaysia:Malaya/302/1954 H1N1)
NS1_I56A1
Influenza A virus (strain A/Duck/Czechoslovakia/1956 H4N6)
NS1_I56A2
Influenza A virus (strain A/Duck/England/1/1956 H11N6)
NS1_I56A3
Influenza A virus (strain A/Equine/Prague/1/1956 H7N7)
NS1_I57A0
Influenza A virus (strain A/Japan/305/1957 H2N2)
NS1_I57A1
Influenza A virus (strain A/Leningrad/134/1957 H2N2)
NS1_I57A2
Influenza A virus (strain A/Leningrad/134/17/1957 H2N2)
NS1_I57A3
Influenza A virus (strain A/Leningrad/134/47/1957 H2N2)
NS1_I59A0
Influenza A virus (strain A/Chicken/Scotland/1959 H5N1)
NS1_I60A0
Influenza A virus (strain A/Ann Arbor/6/1960 H2N2)
NS1_I61A1
Influenza A virus (strain A/Swine/Wisconsin/1/1961 H1N1)
NS1_I63A1
Influenza A virus (strain A/Turkey/Canada/1963 H6N8)
NS1_I66A0
Influenza A virus (strain A/Turkey/Ontario/7732/1966 H5N9)
NS1_I66A1
Influenza A virus (strain A/Turkey/Wisconsin/1/1966 H9N2)
NS1_I67A0
Influenza A virus (strain A/Tokyo/3/1967 H2N2)
NS1_I68A0
Influenza A virus (strain A/Aichi/2/1968 H3N2)
NS1_I68A3
Influenza A virus (strain A/Turkey/Ontario/6118/1968 H8N4)
NS1_I68A5
Influenza A virus (strain A/Korea/426/1968 H2N2)
NS1_I69A0
Influenza A virus (strain A/England/878/1969 H3N2)
NS1_I70A0
Influenza A virus (strain A/Qu/7/1970 H3N2)
NS1_I71A1
Influenza A virus (strain A/Memphis/1/1971 H3N2)
NS1_I71A2
Influenza A virus (strain A/Turkey/Oregon/1971 H7N3)
NS1_I72A2
Influenza A virus (strain A/Udorn/307/1972 H3N2)
NS1_I72A3
Influenza A virus (strain A/Memphis/102/1972 H3N2)
NS1_I72A4
Influenza A virus (strain A/Memphis/101/1972 H3N2)
NS1_I72A5
Influenza A virus (strain A/Shearwater/Australia/1972 H6N5)
NS1_I72A6
Influenza A virus (strain A/Tern/Turkmenia/18/1972 H3N3)
NS1_I73A4
Influenza A virus (strain A/Equine/London/1416/1973 H7N7)
NS1_I73A5
Influenza A virus (strain A/Port Chalmers/1/1973 H3N2)
NS1_I75A0
Influenza A virus (strain A/Beijing/39/1975 H3N2)
NS1_I76A0
Influenza A virus (strain A/Anas acuta/Primorje/695/1976 H2N3)
NS1_I76A2
Influenza A virus (strain A/Duck/Alberta/60/1976 H12N5)
NS1_I76A5
Influenza A virus (strain A/Mallard/Alberta/88/1976 H3N8)
NS1_I76A6
Influenza A virus (strain A/Memphis/110/1976 H3N2)
NS1_I77A0
Influenza A virus (strain A/Alaska/6/1977 H3N2)
NS1_I77A4
Influenza A virus (strain A/Swine/Colorado/1/1977 H3N2)
NS1_I77A9
Influenza A virus (strain A/Equine/New Market/1/1977 H7N7)
NS1_I77AA
Influenza A virus (strain A/Brazil/11/1978 H1N1)
NS1_I77AB
Influenza A virus (strain A/USSR/90/1977 H1N1)
NS1_I77AG
Influenza A virus (strain A/Budgerigar/Hokkaido/1/1977 H4N6)
NS1_I78A1
Influenza A virus (strain A/Mallard/Alberta/827/1978 H8N4)
NS1_I78A3
Influenza A virus (strain A/Mallard/New York/6750/1978 H2N2)
NS1_I78A4
Influenza A virus (strain A/Mallard/New York/6874/1978 H3N2)
NS1_I78A7
Influenza A virus (strain A/Memphis/2/1978 H3N2)
NS1_I78A8
Influenza A virus (strain A/Memphis/18/1978 H3N2)
NS1_I78AA
Influenza A virus (strain A/Pintail/Alberta/268/1978 H6N2)
NS1_I78AC
Influenza A virus (strain A/Turkey/Minnesota/501/1978 H6N8)
NS1_I78AF
Influenza A virus (strain A/Gull/Maryland/1824/1978 H13N6)
NS1_I79A1
Influenza A virus (strain A/Pintail/Alberta/119/1979 H4N6)
NS1_I79A2
Influenza A virus (strain A/Pintail/Alberta/121/1979 H7N8)
NS1_I79A3
Influenza A virus (strain A/Pintail/Alberta/358/1979 H3N6)
NS1_I79A7
Influenza A virus (strain A/Grey teal/Australia/2/1979 H4N4)
NS1_I80A2
Influenza A virus (strain A/Seal/Massachusetts/1/1980 H7N7)
NS1_I80A4
Influenza A virus (strain A/Memphis/4/1980 H3N2)
NS1_I80A6
Influenza A virus (strain A/Duck/Hokkaido/8/1980 H3N8)
NS1_I80A8
Influenza A virus (strain A/Turkey/Minnesota/833/1980 H4N2)
NS1_I80AA
Influenza A virus (strain A/India/6263/1980 H1N1)
NS1_I80AC
Influenza A virus (strain A/Gull/Massachusetts/26/1980 H13N6)
NS1_I80AD
Influenza A virus (strain A/Gull/Minnesota/945/1980 H13N6)
NS1_I82A3
Influenza A virus (strain A/Seal/Massachusetts/133/1982 H4N5)
NS1_I82A8
Influenza A virus (strain A/Turkey/Bethlehem-Glilit/1492-B/1982 H1N1)
NS1_I83A1
Influenza A virus (strain A/Chile/1/1983 H1N1)
NS1_I83A4
Influenza A virus (strain A/Turkey/Ireland/1378/1983 H5N8)
NS1_I83A5
Influenza A virus (strain A/Chicken/Pennsylvania/1/1983 H5N2)
NS1_I83A6
Influenza A virus (strain A/Chicken/Pennsylvania/1370/1983 H5N2)
NS1_I83A8
Influenza A virus (strain A/Hong Kong/5/1983 H3N2)
NS1_I84A2
Influenza A virus (strain A/Whale/Maine/328/1984 H13N2)
NS1_I85A3
Influenza A virus (strain A/Chicken/Victoria/1/1985 H7N7)
NS1_I85A7
Influenza A virus (strain A/Ruddy Turnstone/New Jersey/47/1985 H4N6)
NS1_I86A3
Influenza A virus (strain A/Equine/Tennessee/5/1986 H3N8)
NS1_I87A1
Influenza A virus (strain A/Mallard/Ohio/556/1987 H5N9)
NS1_I88A4
Influenza A virus (strain A/Herring gull/DE/677/1988 H2N8)
NS1_I89A1
Influenza A virus (strain A/Beijing/352/1989 H3N2)
NS1_I89A7
Influenza A virus (strain A/Equine/Jillin/1/1989 H3N8)
NS1_I91A0
Influenza A virus (strain A/Equine/Alaska/1/1991 H3N8)
NS1_I96A2
Influenza A virus (strain A/USA:Memphis/10/1996 H1N1)
NS1_I96A3
Influenza A virus (strain A/China:Nanchang/11/1996 H1N1)
NS1_I97A0
Influenza A virus (strain A/Chicken/Hong Kong/220/1997 H5N1 genotype Gs/Gd)
NS1_I97A1
Influenza A virus (strain A/Hong Kong/156/1997 H5N1 genotype Gs/Gd)
NS1_INBAC
Influenza B virus (strain B/Ann Arbor/1/1966 [cold-adapted])
NS1_INBAD
Influenza B virus (strain B/Ann Arbor/1/1966 [wild-type])
NS1_INBBA
Influenza B virus (strain B/BA/1978)
NS1_INBGA
Influenza B virus (strain B/GA/1986)
NS1_INBGL
Influenza B virus (strain B/GL/1954)
NS1_INBHK
Influenza B virus (strain B/Hong Kong/8/1973)
NS1_INBHT
Influenza B virus (strain B/HT/1984)
NS1_INBID
Influenza B virus (strain B/ID/1986)
NS1_INBMD
Influenza B virus (strain B/Maryland/1959)
NS1_INBPA
Influenza B virus (strain B/PA/1979)
NS1_INBRU
Influenza B virus (strain B/RU/1969)
NS1_INBSI
Influenza B virus (strain B/Singapore/222/1979)
NS1_INBSJ
Influenza B virus (strain B/Singapore/1964)
NS1_INBVJ
Influenza B virus (strain B/Victoria/1987)
NS1_INBYA
Influenza B virus (strain B/Yamagata/1/1973)

1 entry

Non-structural protein S (NSs)

NSS_RVFVZ
Rift valley fever virus (strain ZH-548 M12) (RVFV) reference strain

3 entries

RNA-binding protein (Vmw21)

Select_allDeselect_all
RNB_HHV11
Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1) reference strain
RNB_HHV2H
Human herpesvirus 2 (strain HG52) (HHV-2) (Human herpes simplex virus 2) reference strain

Probable RNA-binding protein

RNB_HHV1M
Human herpesvirus 1 (strain MP) (HHV-1) (Human herpes simplex virus 1)

3 entries

Outer capsid protein sigma-3 (Sigma3)

Select_allDeselect_all
SIGM3_REOVL
Reovirus type 1 (strain Lang) (T1L) (Mammalian orthoreovirus 1) reference strain
SIGM3_REOVD
Reovirus type 3 (strain Dearing) (T3D) (Mammalian orthoreovirus 3)
SIGM3_REOVJ
Reovirus type 2 (strain D5/Jones) (T2J) (Mammalian orthoreovirus 2)

2 entries

Protein HHLF1

Select_allDeselect_all
TRS1_HCMVA
Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5) reference strain
TRS1_HCMVM
Human cytomegalovirus (strain Merlin) (HHV-5) (Human herpesvirus 5) reference strain

Protein TRS1

1 entry

Viral IRF2-like protein (vIRF-2)

VIRF2_HHV8P
Human herpesvirus 8 type P (isolate GK18) (HHV-8) (Kaposi's sarcoma-associated herpesvirus) reference strain