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Conserved domains on  [gi|922665150|pdb|5CFO|B]
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Chain B, Stimulator of Interferon Genes

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
STING_C super family cl17092
C-terminal domain of STING; STING (stimulator of interferon genes, also known as MITA, ERIS, ...
 3-197 1.51e-89

C-terminal domain of STING; STING (stimulator of interferon genes, also known as MITA, ERIS, MPYS and TMEM173) is a master regulator that mediates cytokine production in response to microbial invasion by directly sensing bacterial secondary messengers such as the cyclic dinucleotide bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) and leading to the activation of IFN regulatory factor 3 (IRF3) through TANK-binding kinase 1 (TBK1) stimulation. STING is also a signaling adaptor in the IFN response to cytosolic DNA. This detection of foreign materials is the first step to a successful immune responses. STING is localized in the ER and comprised of an predicted N-terminal transmembrane region and a C-terminal c-di-GMP binding domain.


The actual alignment was detected with superfamily member pfam15009:

Pssm-ID: 473064  Cd Length: 293  Bit Score: 264.48  E-value: 1.51e-89
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5CFO_B          3 LSKVEESQLNEKENKNVADGLAWSYYFGYLKFVLPELEKQIEKTSKFRSKEKFVKKMFILIPSNCFWDDKIPGSDydpqN 82
Cdd:pfam15009  97 PSLVEVSEICEKKGLNVAHGLAWSYYIGYLKLVLPGLEERIEEYEDSHNVTFGSRRLHILIPLDCFVPDDLEKAD----P 172

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5CFO_B         83 RITFEGNTEPLEKTRGGVFLRHYKHSVYEIKDGENEPWFCIMEYATPLLTLYDMSVAQPGELSREERDAQVVVFLRKLQD 162
Cdd:pfam15009 173 NIEFLHELPEQKIDRAGVKGRVYKHSVYRILDEGGKPYYCVLEYATPLLTLFAMSQDALAGFSREDRLEQALLFYRTLED 252

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
5CFO_B        163 ILEGDRACQGKYELVTFSPDR------DLADVMLRKLKDSE 197
Cdd:pfam15009 253 ILEDSPECRNLYRLIVYNDEDedgshfDLSKEILRHLRQEE 293
 
Name Accession Description Interval E-value
TMEM173 pfam15009
Transmembrane protein 173; Transmembrane protein 173, also known as stimulator of interferon ...
 3-197 1.51e-89

Transmembrane protein 173; Transmembrane protein 173, also known as stimulator of interferon genes protein (STING), is a transmembrane adaptor protein which is involved in innate immune signalling processes. It induces expression of type I interferons (IFN-alpha and IFN-beta) via the NF-kappa-B and IRF3, pathways in response to non-self cytosolic RNA and dsDNA.


Pssm-ID: 464441  Cd Length: 293  Bit Score: 264.48  E-value: 1.51e-89
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5CFO_B          3 LSKVEESQLNEKENKNVADGLAWSYYFGYLKFVLPELEKQIEKTSKFRSKEKFVKKMFILIPSNCFWDDKIPGSDydpqN 82
Cdd:pfam15009  97 PSLVEVSEICEKKGLNVAHGLAWSYYIGYLKLVLPGLEERIEEYEDSHNVTFGSRRLHILIPLDCFVPDDLEKAD----P 172

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5CFO_B         83 RITFEGNTEPLEKTRGGVFLRHYKHSVYEIKDGENEPWFCIMEYATPLLTLYDMSVAQPGELSREERDAQVVVFLRKLQD 162
Cdd:pfam15009 173 NIEFLHELPEQKIDRAGVKGRVYKHSVYRILDEGGKPYYCVLEYATPLLTLFAMSQDALAGFSREDRLEQALLFYRTLED 252

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
5CFO_B        163 ILEGDRACQGKYELVTFSPDR------DLADVMLRKLKDSE 197
Cdd:pfam15009 253 ILEDSPECRNLYRLIVYNDEDedgshfDLSKEILRHLRQEE 293
STING_C_metazoan-like cd22658
C-terminal domain of Stimulator Of Interferon Genes (STING) protein in metazoans; This model ...
 18-197 4.23e-89

C-terminal domain of Stimulator Of Interferon Genes (STING) protein in metazoans; This model represents the metazoan cytoplasmic ligand-binding domain (LBD, or cyclic-dinucleotide-binding domain) of Stimulator Of Interferon Genes (STING) protein, also called transmembrane protein 173 (TMEM173), mediator of IRF3 activation (MITA), endoplasmic reticulum IFN stimulator (ERIS), or N-terminal methionine-proline-tyrosine-serine plasma membrane tetraspanner (MYSA). STING is a receptor that senses foreign cyclic dinucleotides that are released during bacterial infections as well as in endogenous cyclic GMP-AMP (cGAMP) signaling during viral infection and anti-tumor immunity. STING activates downstream transcription factor IRF3 (interferon regulatory factor 3) and STAT (signal transducer and activator of transcription) via TBK1 ((Tank binding kinase 1), which are responsible for antiviral and innate immune response against intracellular pathogens. STING's activation of IRF3 and STAT induces the production of type 1 interferon and target genes involved in immune cell homing such as chemokines, respectively. STING may also function as a direct cytosolic DNA sensor. STING also has a role in B cell adaptive immunity through modulating B cell receptor signaling via PI3K (phosphatidylinositol 3-kinase). STING is encoded by the STING1 gene in mammals. It is an endoplasmic reticulum (ER) membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signaling domain. The cytoplasmic domain forms a homodimer, which undergoes conformational changes upon binding to cGAMP. Metazoan STING is larger and less compact than the bacterial homologs, so that the metazoan insertions into the core bacterial fold are necessary for induction of autophagy, and the C-terminal tail contains motifs for the recruitment of kinases and transcription factors in vertebrates. Bacterial STING proteins have also been shown to be functional cyclic dinucleotide receptors.


Pssm-ID: 439310  Cd Length: 184  Bit Score: 259.50  E-value: 4.23e-89
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5CFO_B       18 NVADGLAWSYYFGYLKFVLPELEKQIEKTSKFRSKE---KFVKKMFILIPSNCFWDDKIPGSDydpqNRITFEGNTEPLE 94
Cdd:cd22658   1 NVAHGLAWSYYIGYLKLILPELEKSIREYNRANNNElrgRDSWKLHILIPLSCRVPDKLEDAD----SNIRFLDNLPEIT 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5CFO_B       95 KTRGGVFLRHYKHSVYEIKDGENEPWFCIMEYATPLLTLYDMSVAQPGELSREERDAQVVVFLRKLQDILEGDRACQGKY 174
Cdd:cd22658  77 IDRAGIKGRVYKNSIYEILDEGQRPHYCVLEYATPLQTLFEMSQDAQAGFSREERLEQAKLFYRTLKDILENSPECRNRY 156

                       170       180
                ....*....|....*....|....*...
5CFO_B      175 ELVTFSPD-----RDLADVMLRKLKDSE 197
Cdd:cd22658 157 RLIVYDDPaegssHFLSKEILRHLRQQE 184
 
Name Accession Description Interval E-value
TMEM173 pfam15009
Transmembrane protein 173; Transmembrane protein 173, also known as stimulator of interferon ...
 3-197 1.51e-89

Transmembrane protein 173; Transmembrane protein 173, also known as stimulator of interferon genes protein (STING), is a transmembrane adaptor protein which is involved in innate immune signalling processes. It induces expression of type I interferons (IFN-alpha and IFN-beta) via the NF-kappa-B and IRF3, pathways in response to non-self cytosolic RNA and dsDNA.


Pssm-ID: 464441  Cd Length: 293  Bit Score: 264.48  E-value: 1.51e-89
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5CFO_B          3 LSKVEESQLNEKENKNVADGLAWSYYFGYLKFVLPELEKQIEKTSKFRSKEKFVKKMFILIPSNCFWDDKIPGSDydpqN 82
Cdd:pfam15009  97 PSLVEVSEICEKKGLNVAHGLAWSYYIGYLKLVLPGLEERIEEYEDSHNVTFGSRRLHILIPLDCFVPDDLEKAD----P 172

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5CFO_B         83 RITFEGNTEPLEKTRGGVFLRHYKHSVYEIKDGENEPWFCIMEYATPLLTLYDMSVAQPGELSREERDAQVVVFLRKLQD 162
Cdd:pfam15009 173 NIEFLHELPEQKIDRAGVKGRVYKHSVYRILDEGGKPYYCVLEYATPLLTLFAMSQDALAGFSREDRLEQALLFYRTLED 252

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
5CFO_B        163 ILEGDRACQGKYELVTFSPDR------DLADVMLRKLKDSE 197
Cdd:pfam15009 253 ILEDSPECRNLYRLIVYNDEDedgshfDLSKEILRHLRQEE 293
STING_C_metazoan-like cd22658
C-terminal domain of Stimulator Of Interferon Genes (STING) protein in metazoans; This model ...
 18-197 4.23e-89

C-terminal domain of Stimulator Of Interferon Genes (STING) protein in metazoans; This model represents the metazoan cytoplasmic ligand-binding domain (LBD, or cyclic-dinucleotide-binding domain) of Stimulator Of Interferon Genes (STING) protein, also called transmembrane protein 173 (TMEM173), mediator of IRF3 activation (MITA), endoplasmic reticulum IFN stimulator (ERIS), or N-terminal methionine-proline-tyrosine-serine plasma membrane tetraspanner (MYSA). STING is a receptor that senses foreign cyclic dinucleotides that are released during bacterial infections as well as in endogenous cyclic GMP-AMP (cGAMP) signaling during viral infection and anti-tumor immunity. STING activates downstream transcription factor IRF3 (interferon regulatory factor 3) and STAT (signal transducer and activator of transcription) via TBK1 ((Tank binding kinase 1), which are responsible for antiviral and innate immune response against intracellular pathogens. STING's activation of IRF3 and STAT induces the production of type 1 interferon and target genes involved in immune cell homing such as chemokines, respectively. STING may also function as a direct cytosolic DNA sensor. STING also has a role in B cell adaptive immunity through modulating B cell receptor signaling via PI3K (phosphatidylinositol 3-kinase). STING is encoded by the STING1 gene in mammals. It is an endoplasmic reticulum (ER) membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signaling domain. The cytoplasmic domain forms a homodimer, which undergoes conformational changes upon binding to cGAMP. Metazoan STING is larger and less compact than the bacterial homologs, so that the metazoan insertions into the core bacterial fold are necessary for induction of autophagy, and the C-terminal tail contains motifs for the recruitment of kinases and transcription factors in vertebrates. Bacterial STING proteins have also been shown to be functional cyclic dinucleotide receptors.


Pssm-ID: 439310  Cd Length: 184  Bit Score: 259.50  E-value: 4.23e-89
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5CFO_B       18 NVADGLAWSYYFGYLKFVLPELEKQIEKTSKFRSKE---KFVKKMFILIPSNCFWDDKIPGSDydpqNRITFEGNTEPLE 94
Cdd:cd22658   1 NVAHGLAWSYYIGYLKLILPELEKSIREYNRANNNElrgRDSWKLHILIPLSCRVPDKLEDAD----SNIRFLDNLPEIT 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5CFO_B       95 KTRGGVFLRHYKHSVYEIKDGENEPWFCIMEYATPLLTLYDMSVAQPGELSREERDAQVVVFLRKLQDILEGDRACQGKY 174
Cdd:cd22658  77 IDRAGIKGRVYKNSIYEILDEGQRPHYCVLEYATPLQTLFEMSQDAQAGFSREERLEQAKLFYRTLKDILENSPECRNRY 156

                       170       180
                ....*....|....*....|....*...
5CFO_B      175 ELVTFSPD-----RDLADVMLRKLKDSE 197
Cdd:cd22658 157 RLIVYDDPaegssHFLSKEILRHLRQQE 184
STING_C cd12146
C-terminal domain of STING; STING (stimulator of interferon genes, also known as MITA, ERIS, ...
 19-197 2.24e-79

C-terminal domain of STING; STING (stimulator of interferon genes, also known as MITA, ERIS, MPYS and TMEM173) is a master regulator that mediates cytokine production in response to microbial invasion by directly sensing bacterial secondary messengers such as the cyclic dinucleotide bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) and leading to the activation of IFN regulatory factor 3 (IRF3) through TANK-binding kinase 1 (TBK1) stimulation. STING is also a signaling adaptor in the IFN response to cytosolic DNA. This detection of foreign materials is the first step to a successful immune responses. STING is localized in the ER and comprised of an predicted N-terminal transmembrane region and a C-terminal c-di-GMP binding domain.


Pssm-ID: 213389  Cd Length: 181  Bit Score: 234.49  E-value: 2.24e-79
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5CFO_B       19 VADGLAWSYYFGYLKFVLPELEKQIEKTSKFRSKEKFVKKMFILIPSNCFWDDKIPGSDydpqNRITFEGNTEPLEKTRG 98
Cdd:cd12146   1 VAHGLAWSYYIGYLKLILPELEERIRQYEDKNNVTLEVKKLFILIPLSCYVPPSLKDAD----ENIEFAENLEELIIDRA 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5CFO_B       99 GVFLRHYKHSVYEIKD-GENEPWFCIMEYATPLLTLYDMSVAQPGELSREERDAQVVVFLRKLQDILEGDRACQGKYELV 177
Cdd:cd12146  77 GVKDRVYKNSVYKIRPnGDKRPYYCAMEYATPLNTLFDMSQDSEAAFSREERLEQAKLFYRTLRDILEDSPECQGLYELI 156

                       170       180
                ....*....|....*....|....*
5CFO_B      178 TFSPD-----RDLADVMLRKLKDSE 197
Cdd:cd12146 157 YYEDFdeddsVDLSQVILQHLRQQE 181
STING-like cd22587
C-terminal domain of metazoan Stimulator Of Interferon Genes (STING) protein, bacterial STING, ...
 18-177 3.91e-33

C-terminal domain of metazoan Stimulator Of Interferon Genes (STING) protein, bacterial STING, and similar proteins; This model represents the cytoplasmic ligand-binding domain (LBD, or cyclic-dinucleotide-binding domain) of Stimulator Of Interferon Genes (STING) protein, also called transmembrane protein 173 (TMEM173), mediator of IRF3 activation (MITA), endoplasmic reticulum IFN stimulator (ERIS), or N-terminal methionine-proline-tyrosine-serine plasma membrane tetraspanner (MYSA) of metazoa, as well as STING proteins in bacteria. STING is a receptor that senses foreign cyclic dinucleotides that are released during bacterial infections as well as in endogenous cyclic GMP-AMP (cGAMP) signaling during viral infection and anti-tumor immunity. STING activates downstream transcription factor IRF3 (interferon regulatory factor 3) and STAT (signal transducer and activator of transcription) via TBK1 ((Tank binding kinase 1), which are responsible for antiviral and innate immune response against intracellular pathogens. STING's activation of IRF3 and STAT induces the production of type 1 interferon and target genes involved in immune cell homing such as chemokines, respectively. STING may also function as a direct cytosolic DNA sensor. STING also has a role in B cell adaptive immunity through modulating B cell receptor signaling via PI3K (phosphatidylinositol 3-kinase). STING is encoded by the STING1 gene in mammals. It is an endoplasmic reticulum (ER) membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signaling domain. The cytoplasmic domain forms a homodimer, which undergoes conformational changes upon binding to cGAMP. Bacterial STING proteins are functional cyclic dinucleotide receptors and define a minimal homodimeric scaffold that selectively responds to cyclic di-GMP. They couple the recognition of cyclic dinucleotides with the formation of protein filaments to drive oligomerization of TIR effector domains and rapid NAD+ cleavage. Bacterial STING occurs primarily as a fusion to a Toll/interleukin-1 receptor (TIR, or Toll and IL-1 receptor) adaptor domain; TIR domains can function as beta-nicotinamide adenine dinucleotide (NAD+) hydrolases in plant and animal immunity. Bacterial STING homologs are 20% smaller and markedly compact, such that the metazoan insertions into the core bacterial fold are necessary for induction of autophagy, and the C-terminal tail contains motifs for the recruitment of kinases and transcription factors in vertebrates.


Pssm-ID: 439309  Cd Length: 157  Bit Score: 116.18  E-value: 3.91e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5CFO_B       18 NVADGLAWSYYFGYLKFVLPELEKQIEKTSKFRSKEKFVKKMFILIPSNCFWDDKIpgsDYDPQNRITFEGNTEPLEKTR 97
Cdd:cd22587   1 LPSTALAIGYYENFLKPVCPELLENKGIENNNEGKKYKDFKLKILIPLDLDDDDKL---QFEAYKNIHGLKELSIKTKDG 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5CFO_B       98 ggvflRHYKHSVYEIKDgeNEPWFCIMEYATPLLTLYDMSVAQPG-------ELSREERDAQVVVFLRKLQDILEGDRAC 170
Cdd:cd22587  78 -----RPYPFSIYVDID--NEGKLCILDFPTTLNGLNEAIQLYLPkdfigksEDKELLEERELRNFYRTLKYLIERNPEC 150


                ....*..
5CFO_B      171 QGKYELV 177
Cdd:cd22587 151 RGIVEII 157
 
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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