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Conserved domains on  [gi|38372863|sp|Q80H93|]
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RecName: Full=ORF8b protein; AltName: Full=Accessory protein 8b; AltName: Full=Non-structural protein 8b; Short=ns8b

Protein Classification

ORF8 protein( domain architecture ID 1792315)

ORF8 protein, a viral accessory protein that has been proposed to interfere with immune responses, consists of an N-terminal signal sequence followed by an immunoglobulin (Ig)-like fold, similar to the ORF8 Ig-like domain protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
ORF8-Ig_SARS-CoV-2-like super family cl40466
SARS-CoV-2 ORF8 immunoglobulin (Ig) domain protein and related proteins; This family includes ...
 7-82 8.80e-51

SARS-CoV-2 ORF8 immunoglobulin (Ig) domain protein and related proteins; This family includes the ORF8 immunoglobulin (Ig) domain protein of Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2, also known as a 2019 novel coronavirus, 2019-nCoV) and related Sarbecovirus ORF8 proteins including those classified as type II, such as bat coronavirus Rf1 ORF8, and those classified as type III, such as Bat SARS coronavirus HKU3-1 ORF8. SARS-CoV-2 causes the disease called "coronavirus disease 2019" (COVID-19). SARS-CoV-2 ORF8 is a fast-evolving protein in SARS-related CoVs, and a potential pathogenicity factor which evolves rapidly to counter the immune response and facilitate the transmission between hosts. A 382 nucleotide deletion in SARS-CoV-2 ORF8 was found to correlate with milder disease and a lower incidence of hypoxia. SARS-CoV-2 ORF8 interacts with a variety of host proteins, including many factors involved in ERAD. It disrupts IFN-I signaling when exogenously overexpressed in cells, and downregulates MHC-I.


The actual alignment was detected with superfamily member cd21642:

Pssm-ID: 454761  Cd Length: 119  Bit Score: 155.21  E-value: 8.80e-51
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 38372863   7 VRYNTRGNTYSTAWLCALGKVLPFHRWHTMVQTCTPNVTINCQDPAGGALIARCWYLHEGHQTAAFRDVLVVLNKR 82
Cdd:cd21642  44 IRYNTRGNTYSTAWLCALGKVLPFHRWHTMVQACTPNVTINCQDPVGGALIARCWYLHEGHQTAAFRDILVVLFKR 119
 
Name Accession Description Interval E-value
ORF8-Ig_Bat_SARS_CoV_Rf1_type-II-like cd21642
ORF8 immunoglobulin (Ig) domain protein of bat coronavirus Rf1, a type II ORF8, and related ...
 7-82 8.80e-51

ORF8 immunoglobulin (Ig) domain protein of bat coronavirus Rf1, a type II ORF8, and related proteins; This subfamily includes the ORF8 immunoglobulin (Ig) domain proteins of bat coronavirus Rf1 (Bat SARS CoV Rf1) and Bat CoV 273/2005, which have been classified previously as type II ORF8 proteins. They belong to a family which includes the ORF8 immunoglobulin (Ig) domain protein of Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2, also known as a 2019 novel coronavirus, 2019-nCoV) and other related Sarbecovirus ORF8's, such as Bat SARS coronavirus HKU3-1 ORF8 which has been classified previously as a type III ORF8. SARS-CoV-2 causes the disease called "coronavirus disease 2019" (COVID-19). SARS-CoV-2 ORF8 protein (also known as ns8 and accessory protein 8) is a fast-evolving protein in SARS-related CoVs, and a potential pathogenicity factor which evolves rapidly to counter the immune response and facilitate the transmission between hosts. A 382 nucleotide deletion in SARS-CoV-2 ORF8 was found to correlate with milder disease and a lower incidence of hypoxia. SARS-CoV-2 ORF8 interacts with a variety of host proteins, including many factors involved in ERAD. It disrupts IFN-I signaling when exogenously overexpressed in cells, and downregulates MHC-I. In most SARS-CoVs, ORF8 is split into overlapping ORF8a and ORF8b proteins; the N- and C-terminus of SARS-CoV-2 ORF8 is similar to SARS-CoV ORF8a and ORF8b, respectively.


Pssm-ID: 394946  Cd Length: 119  Bit Score: 155.21  E-value: 8.80e-51
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 38372863   7 VRYNTRGNTYSTAWLCALGKVLPFHRWHTMVQTCTPNVTINCQDPAGGALIARCWYLHEGHQTAAFRDVLVVLNKR 82
Cdd:cd21642  44 IRYNTRGNTYSTAWLCALGKVLPFHRWHTMVQACTPNVTINCQDPVGGALIARCWYLHEGHQTAAFRDILVVLFKR 119
bCoV_NS8 pfam12093
Betacoronavirus NS8 protein; This family of proteins includes the accessory proteins encoded ...
 7-79 8.83e-40

Betacoronavirus NS8 protein; This family of proteins includes the accessory proteins encoded by the ORF8 in coronaviruses, also known as accessory protein 8, or non-structural protein 8 (NS8). This is distinct from NSP8, which is encoded on the replicase polyprotein. Proteins in this family are typically between 39 to 121 amino acids in length. This protein has two conserved sequence motifs: EDPCP and INCQ. It may modulate viral pathogenicity or replication in favour of human adaptation. ORF8 was suggested as one of the relevant genes in the study of human adaptation of the virus. This entry includes the NS8a and NS8b proteins from human SARS coronavirus (SARS-CoV). Recently, the the structure of SARS-CoV-2 ORF has been determined and revealed a core of approximately 60 residues similar to SARS-CoV ORF7a, the Ig-like fold, with the addition of two dimerization interfaces unique to SARS-CoV-2 ORF8. It forms a covalent disulfide-linker dimer through an N-terminal sequence specific to SARS-CoV-2 and a separate non-covalent interface is formed by another SARS-CoV-2 specific sequence. The presence of these interfaces shows that SARS-CoV-2 ORF8 can form unique large-scale assemblies not possible for SARS-CoV, potentially mediating unique immune suppression and evasion activities.


Pssm-ID: 152528  Cd Length: 126  Bit Score: 127.49  E-value: 8.83e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38372863     7 VRYNTRGNTYSTAWLCAL-----GKVLPFH--RWHTMVQTCTPNVTINCQDPAGGALIARCWYLHEGHQTAAFRDVLVVL 79
Cdd:pfam12093  47 IKIGSRGNTYKSARLCALcegdyGKRIPFHyeMFGNMTISCEPNLEINCQAPAGGALIARCSYDHDGHQFAAFHDVLVVL 126
 
Name Accession Description Interval E-value
ORF8-Ig_Bat_SARS_CoV_Rf1_type-II-like cd21642
ORF8 immunoglobulin (Ig) domain protein of bat coronavirus Rf1, a type II ORF8, and related ...
 7-82 8.80e-51

ORF8 immunoglobulin (Ig) domain protein of bat coronavirus Rf1, a type II ORF8, and related proteins; This subfamily includes the ORF8 immunoglobulin (Ig) domain proteins of bat coronavirus Rf1 (Bat SARS CoV Rf1) and Bat CoV 273/2005, which have been classified previously as type II ORF8 proteins. They belong to a family which includes the ORF8 immunoglobulin (Ig) domain protein of Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2, also known as a 2019 novel coronavirus, 2019-nCoV) and other related Sarbecovirus ORF8's, such as Bat SARS coronavirus HKU3-1 ORF8 which has been classified previously as a type III ORF8. SARS-CoV-2 causes the disease called "coronavirus disease 2019" (COVID-19). SARS-CoV-2 ORF8 protein (also known as ns8 and accessory protein 8) is a fast-evolving protein in SARS-related CoVs, and a potential pathogenicity factor which evolves rapidly to counter the immune response and facilitate the transmission between hosts. A 382 nucleotide deletion in SARS-CoV-2 ORF8 was found to correlate with milder disease and a lower incidence of hypoxia. SARS-CoV-2 ORF8 interacts with a variety of host proteins, including many factors involved in ERAD. It disrupts IFN-I signaling when exogenously overexpressed in cells, and downregulates MHC-I. In most SARS-CoVs, ORF8 is split into overlapping ORF8a and ORF8b proteins; the N- and C-terminus of SARS-CoV-2 ORF8 is similar to SARS-CoV ORF8a and ORF8b, respectively.


Pssm-ID: 394946  Cd Length: 119  Bit Score: 155.21  E-value: 8.80e-51
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 38372863   7 VRYNTRGNTYSTAWLCALGKVLPFHRWHTMVQTCTPNVTINCQDPAGGALIARCWYLHEGHQTAAFRDVLVVLNKR 82
Cdd:cd21642  44 IRYNTRGNTYSTAWLCALGKVLPFHRWHTMVQACTPNVTINCQDPVGGALIARCWYLHEGHQTAAFRDILVVLFKR 119
bCoV_NS8 pfam12093
Betacoronavirus NS8 protein; This family of proteins includes the accessory proteins encoded ...
 7-79 8.83e-40

Betacoronavirus NS8 protein; This family of proteins includes the accessory proteins encoded by the ORF8 in coronaviruses, also known as accessory protein 8, or non-structural protein 8 (NS8). This is distinct from NSP8, which is encoded on the replicase polyprotein. Proteins in this family are typically between 39 to 121 amino acids in length. This protein has two conserved sequence motifs: EDPCP and INCQ. It may modulate viral pathogenicity or replication in favour of human adaptation. ORF8 was suggested as one of the relevant genes in the study of human adaptation of the virus. This entry includes the NS8a and NS8b proteins from human SARS coronavirus (SARS-CoV). Recently, the the structure of SARS-CoV-2 ORF has been determined and revealed a core of approximately 60 residues similar to SARS-CoV ORF7a, the Ig-like fold, with the addition of two dimerization interfaces unique to SARS-CoV-2 ORF8. It forms a covalent disulfide-linker dimer through an N-terminal sequence specific to SARS-CoV-2 and a separate non-covalent interface is formed by another SARS-CoV-2 specific sequence. The presence of these interfaces shows that SARS-CoV-2 ORF8 can form unique large-scale assemblies not possible for SARS-CoV, potentially mediating unique immune suppression and evasion activities.


Pssm-ID: 152528  Cd Length: 126  Bit Score: 127.49  E-value: 8.83e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38372863     7 VRYNTRGNTYSTAWLCAL-----GKVLPFH--RWHTMVQTCTPNVTINCQDPAGGALIARCWYLHEGHQTAAFRDVLVVL 79
Cdd:pfam12093  47 IKIGSRGNTYKSARLCALcegdyGKRIPFHyeMFGNMTISCEPNLEINCQAPAGGALIARCSYDHDGHQFAAFHDVLVVL 126
ORF8-Ig_SARS-CoV-2-like cd21640
SARS-CoV-2 ORF8 immunoglobulin (Ig) domain protein and related proteins; This family includes ...
 7-79 1.16e-25

SARS-CoV-2 ORF8 immunoglobulin (Ig) domain protein and related proteins; This family includes the ORF8 immunoglobulin (Ig) domain protein of Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2, also known as a 2019 novel coronavirus, 2019-nCoV) and related Sarbecovirus ORF8 proteins including those classified as type II, such as bat coronavirus Rf1 ORF8, and those classified as type III, such as Bat SARS coronavirus HKU3-1 ORF8. SARS-CoV-2 causes the disease called "coronavirus disease 2019" (COVID-19). SARS-CoV-2 ORF8 is a fast-evolving protein in SARS-related CoVs, and a potential pathogenicity factor which evolves rapidly to counter the immune response and facilitate the transmission between hosts. A 382 nucleotide deletion in SARS-CoV-2 ORF8 was found to correlate with milder disease and a lower incidence of hypoxia. SARS-CoV-2 ORF8 interacts with a variety of host proteins, including many factors involved in ERAD. It disrupts IFN-I signaling when exogenously overexpressed in cells, and downregulates MHC-I.


Pssm-ID: 439221  Cd Length: 104  Bit Score: 91.15  E-value: 1.16e-25
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 38372863   7 VRYnTRGNTYSTAWLCA--LGKVLPFHRWHTMV--QTCTPnVTINCQDPAGGALIARCWYLHEGHQTAAFRDVLVVL 79
Cdd:cd21640  30 IRV-GARKSAPLIELCVdeAGKKSPIHYIDIGNytVSCLP-FTINCQEPKLGSLVVRCSYYYDFLEYHDVRVVLDFI 104
ORF8-Ig_bat_SARS-CoV_HKU3-1_type-III-like cd21643
ORF8 immunoglobulin (Ig) domain protein of bat SARS coronavirus HKU3-1 ORF8, a type III ORF8, ...
 21-80 1.15e-04

ORF8 immunoglobulin (Ig) domain protein of bat SARS coronavirus HKU3-1 ORF8, a type III ORF8, and related proteins; This subfamily includes the ORF8 immunoglobulin (Ig) domain proteins of Bat SARS coronavirus HKU3-1 and Bat SARS-like coronavirus Rs3367, which have been classified previously as type III ORF8's. They belong to a family which includes the ORF8 immunoglobulin (Ig) domain protein of Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2, also known as a 2019 novel coronavirus, 2019-nCoV) and other related Sarbecovirus ORF8's, such as bat coronavirus Rf1 (Bat SARS CoV Rf1) ORF8 which has been classified previously as a type II ORF8. SARS-CoV-2 causes the disease called "coronavirus disease 2019" (COVID-19). SARS-CoV-2 ORF8 protein (also known as ns8 and accessory protein 8) is a fast-evolving protein in SARS-related CoVs, and a potential pathogenicity factor which evolves rapidly to counter the immune response and facilitate the transmission between hosts. A 382 nucleotide deletion in SARS-CoV-2 ORF8 was found to correlate with milder disease and a lower incidence of hypoxia. SARS-CoV-2 ORF8 interacts with a variety of host proteins, including many factors involved in ERAD. It disrupts IFN-I signaling when exogenously overexpressed in cells, and downregulates MHC-I.


Pssm-ID: 394947  Cd Length: 120  Bit Score: 37.59  E-value: 1.15e-04
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 38372863  21 LCA--LGKVLPFH--RWHTMVQTCTPnVTINCQDPAGGALIARCWYLHEghqTAAFRDVLVVLN 80
Cdd:cd21643  59 LCEgdYGKRIPIHyeMFGNYTISCEP-LEINCQAPPVGSLIVRCSYDYD---FVEHHDVRVVLD 118
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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