Coronavirus Envelope (E) small membrane protein; This family contains the Envelope (E) small membrane protein of betacoronaviruses, including the E proteins from three highly pathogenic human coronaviruses (CoVs) such as Middle East respiratory syndrome (MERS) CoV, Severe acute respiratory syndrome (SARS) CoV, and SARS-CoV-2, also known as 2019 novel CoV (2019-nCoV) or COVID-19 virus. There are five essential genes in CoVs that result in the following gene products: Spike (S) protein, Membrane (M) glycoprotein, Nucleocapsid (N), Envelope (E) protein, and the Orf1ab (a large polyprotein known as replicase/protease); all are required to produce a structurally complete viral particle. The E protein is a small polypeptide (76-109 amino acids) that contains a single alpha-helical transmembrane domain. It plays a central role in virus morphogenesis and assembly. It acts as a viroporin and self-assembles in host membranes forming homopentameric protein-lipid pores that allow ion transport with poor selectivity. For some CoVs, such as mouse hepatitis virus (MHV) and SARS-CoV, deletion of the E gene did not completely abolish replication, but the virions were severely disabled from infecting new host cells with significantly reduced viral titers. In animal models, SARS-CoV lacking the E gene also showed significantly attenuated viral titers, likely due to its deficiency in suppressing host stress response and apoptosis induction. Moreover, the PDZ-binding motif (PBM) at the C-terminus of SARS-CoV E protein was shown to interact with a host PDZ protein called syntenin and lead to its relocation from nucleus to cytoplasm during SARS-CoV infection, thereby activating p38 kinase to induce the overexpression of inflammatory cytokines. Thus, the E protein is involved in both, viral replication and pathogenesis during CoV infection.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 568982533 106 HETFG-FKVAVIASIVSCAIILLMSMAFLTCCLLkCVQ 142
Cdd:cd21533    5 QEQIGsFIVNFFIFTVVCAITLLVCMAFLTATRL-CVQ 41

Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR); The complement control protein (CCP) modules (also known as short consensus repeats SCRs or SUSHI repeats) contain approximately 60 amino acid residues and have been identified in several proteins of the complement system. A missense mutation in seventh CCP domain causes deficiency of the b subunit of factor XIII.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568982533    41 CAQLHPPPQGTLQVVRGDgTSLGTVLIFHCPSGHQMVGSGLLTCAWNGStvdWSSGSPVC 100
Cdd:smart00032   1 CPPPPDIENGTVTSSSGT-YSYGDTVTYSCDPGYTLIGSSTITCLENGT---WSPPPPTC 56

Middle East respiratory syndrome-related coronavirus Envelope small membrane protein and similar proteins; This group contains the Envelope (E) small membrane protein of Middle East respiratory syndrome (MERS) coronavirus (CoV), as well as E proteins from related coronaviruses. There are five essential genes in CoVs that result in the following gene products: Spike (S) protein, Membrane (M) glycoprotein, Nucleocapsid (N), Envelope (E) protein, and the Orf1ab (a large polyprotein known as replicase/protease); all are required to produce a structurally complete viral particle. The E protein is a small polypeptide (76-109 amino acids) that contains a single alpha-helical transmembrane domain. It plays a central role in virus morphogenesis and assembly. It acts as a viroporin and self-assembles in host membranes forming homopentameric protein-lipid pores that allow ion transport with poor selectivity. For some CoVs, such as mouse hepatitis virus (MHV) and SARS-CoV, deletion of the E gene did not completely abolish replication, but the virions were severely disabled from infecting new host cells with significantly reduced viral titers. In animal models, SARS-CoV lacking the E gene also showed significantly attenuated viral titers, likely due to its deficiency in suppressing host stress response and apoptosis induction. Moreover, the PDZ-binding motif (PBM) at the C-terminus of SARS-CoV E protein was shown to interact with a host PDZ protein called syntenin and lead to its relocation from nucleus to cytoplasm during SARS-CoV infection, thereby activating p38 kinase to induce the overexpression of inflammatory cytokines. Thus, the E protein is involved in both, viral replication and pathogenesis during CoV infection.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 568982533 106 HETFG-FKVAVIASIVSCAIILLMSMAFLTCCLLkCVQ 142
Cdd:cd21533    5 QEQIGsFIVNFFIFTVVCAITLLVCMAFLTATRL-CVQ 41

Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR); The complement control protein (CCP) modules (also known as short consensus repeats SCRs or SUSHI repeats) contain approximately 60 amino acid residues and have been identified in several proteins of the complement system. A missense mutation in seventh CCP domain causes deficiency of the b subunit of factor XIII.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568982533    41 CAQLHPPPQGTLQVVRGDgTSLGTVLIFHCPSGHQMVGSGLLTCAWNGStvdWSSGSPVC 100
Cdd:smart00032   1 CPPPPDIENGTVTSSSGT-YSYGDTVTYSCDPGYTLIGSSTITCLENGT---WSPPPPTC 56

Middle East respiratory syndrome-related coronavirus Envelope small membrane protein and similar proteins; This group contains the Envelope (E) small membrane protein of Middle East respiratory syndrome (MERS) coronavirus (CoV), as well as E proteins from related coronaviruses. There are five essential genes in CoVs that result in the following gene products: Spike (S) protein, Membrane (M) glycoprotein, Nucleocapsid (N), Envelope (E) protein, and the Orf1ab (a large polyprotein known as replicase/protease); all are required to produce a structurally complete viral particle. The E protein is a small polypeptide (76-109 amino acids) that contains a single alpha-helical transmembrane domain. It plays a central role in virus morphogenesis and assembly. It acts as a viroporin and self-assembles in host membranes forming homopentameric protein-lipid pores that allow ion transport with poor selectivity. For some CoVs, such as mouse hepatitis virus (MHV) and SARS-CoV, deletion of the E gene did not completely abolish replication, but the virions were severely disabled from infecting new host cells with significantly reduced viral titers. In animal models, SARS-CoV lacking the E gene also showed significantly attenuated viral titers, likely due to its deficiency in suppressing host stress response and apoptosis induction. Moreover, the PDZ-binding motif (PBM) at the C-terminus of SARS-CoV E protein was shown to interact with a host PDZ protein called syntenin and lead to its relocation from nucleus to cytoplasm during SARS-CoV infection, thereby activating p38 kinase to induce the overexpression of inflammatory cytokines. Thus, the E protein is involved in both, viral replication and pathogenesis during CoV infection.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 568982533 106 HETFG-FKVAVIASIVSCAIILLMSMAFLTCCLLkCVQ 142
Cdd:cd21533    5 QEQIGsFIVNFFIFTVVCAITLLVCMAFLTATRL-CVQ 41