beta-trefoil domain found in the interleukin-1 (IL-1) family of cytokines; The IL-1 family of cytokines comprises 11 members, including 7 pro-inflammatory agonists (IL-1alpha, IL-1beta, IL-18, IL-33, IL-36alpha, IL-36beta, IL-36gamma) and 4 defined or putative antagonists (IL-1R antagonist (IL-1Ra), IL-36Ra, IL-37, and IL-38) exerting anti-inflammatory activities. These members can have complimentary or distinct biological functions. All family members share a common structure at the C-terminus, which is comprised by of a typical beta-trefoil fold consisting of 12-beta-strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2465537200  46 LTLPSYFRIKDAHQKALYTRNGQLLLGDPDSDNYSPEKVCILPNRGLDRSKVPIFLGMQGGSCCLACVKTREGPLLQLED 125
Cdd:cd23302     2 LPMARYYIIKYADQKALYTRDGQLLVGDPVADNCCAEKICILPNRGLDRTKVPIFLGIQGGSRCLACVETEEGPSLQLED 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2465537200 126 VNIEDLYKGGEQTTRFTFFQRSLGSAFRLEAAACPGWFLCGPAEPQQPVQLTKESEPSTHTEFYFEMS 193
Cdd:cd23302    82 VNIEELYKGGEEATRFTFFQSSSGSAFRLEAAAWPGWFLCGPAEPQQPVQLTKESEPSARTKFYFEQS 149

beta-trefoil domain found in interleukin-38 (IL-38) and similar proteins; IL-38, also called interleukin-1 family member 10, or IL-1F10, or family of interleukin 1-theta, or FIL1 theta, or interleukin-1 HY2, or IL-1HY2, or interleukin-1 theta, or IL-1 theta, acts as cytokine with immunomodulatory activity. Alone, it does not induce cytokine production, but reduces IL22 and IL17A production by T-cells in response to heat-killed Candida albicans. It also reduces IL36G-induced production of IL8 by peripheral blood mononuclear cells. It increases IL6 production by dendritic cells stimulated by bacterial lipopolysaccharides (LPS). IL-38 contains a beta-trefoil domain, which is characterized by 12 beta strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2465537200  46 LTLPSYFRIKDAHQKALYTRNGQLLLGDPDSDNYSPEKVCILPNRGLDRSKVPIFLGMQGGSCCLACVKTREGPLLQLED 125
Cdd:cd23302     2 LPMARYYIIKYADQKALYTRDGQLLVGDPVADNCCAEKICILPNRGLDRTKVPIFLGIQGGSRCLACVETEEGPSLQLED 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2465537200 126 VNIEDLYKGGEQTTRFTFFQRSLGSAFRLEAAACPGWFLCGPAEPQQPVQLTKESEPSTHTEFYFEMS 193
Cdd:cd23302    82 VNIEELYKGGEEATRFTFFQSSSGSAFRLEAAAWPGWFLCGPAEPQQPVQLTKESEPSARTKFYFEQS 149

Interleukin-1 / 18; This family includes interleukin-1 and interleukin-18.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2465537200  76 SDNYSPEKVCILPNRGLDR-SKVPIFLGMQGGSCCLACVKTREgPLLQLEDVNIEDLYKGGEQTTRFTFFQRSLGSAFRL 154
Cdd:pfam00340   4 QNLNLEVKFDMSFYKGDSDdSKIPVTLGIKGKKLYLSCVNKDE-PVLQLEEVNIPKLIKNKESDKRFFFIRSESKNYVEF 82

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 2465537200 155 EAAACPGWFLCGPAEPQQPVQLTK-ESEPSTHTEFYF 190
Cdd:pfam00340  83 ESAAYPGWFIATKQEEDLPVFLVNtAGGQDSITDFQI 119

beta-trefoil domain found in interleukin-38 (IL-38) and similar proteins; IL-38, also called interleukin-1 family member 10, or IL-1F10, or family of interleukin 1-theta, or FIL1 theta, or interleukin-1 HY2, or IL-1HY2, or interleukin-1 theta, or IL-1 theta, acts as cytokine with immunomodulatory activity. Alone, it does not induce cytokine production, but reduces IL22 and IL17A production by T-cells in response to heat-killed Candida albicans. It also reduces IL36G-induced production of IL8 by peripheral blood mononuclear cells. It increases IL6 production by dendritic cells stimulated by bacterial lipopolysaccharides (LPS). IL-38 contains a beta-trefoil domain, which is characterized by 12 beta strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2465537200  46 LTLPSYFRIKDAHQKALYTRNGQLLLGDPDSDNYSPEKVCILPNRGLDRSKVPIFLGMQGGSCCLACVKTREGPLLQLED 125
Cdd:cd23302     2 LPMARYYIIKYADQKALYTRDGQLLVGDPVADNCCAEKICILPNRGLDRTKVPIFLGIQGGSRCLACVETEEGPSLQLED 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2465537200 126 VNIEDLYKGGEQTTRFTFFQRSLGSAFRLEAAACPGWFLCGPAEPQQPVQLTKESEPSTHTEFYFEMS 193
Cdd:cd23302    82 VNIEELYKGGEEATRFTFFQSSSGSAFRLEAAAWPGWFLCGPAEPQQPVQLTKESEPSARTKFYFEQS 149

beta-trefoil domain found in interleukin-1 receptor antagonist protein (IL-1RA) and similar proteins; IL-1RA, also called IL-1RN, or IRAP, or ICIL-1RA, or IL1 inhibitor, inhibits the activity of interleukin-1 (IL-1) by binding to receptor IL1R1 and preventing its association with the co-receptor IL1RAP for signaling. It has no IL-1 like activity. IL-1RN binds functional interleukin-1 receptor IL1R1 with greater affinity than decoy receptor IL1R2; however, the physiological relevance of the latter association is unknown. IL-1RN contains a beta-trefoil domain, which is characterized by 12 beta strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2465537200  52 FRIKDAHQKALYTRNGQLLLGDPDSDNYS-PEKVCILPNRGLDRSKVPIFLGMQGGSCCLACVKTREGPLLQLEDVNIED 130
Cdd:cd23297     6 YRIWDVNQKSLYLRNNQLVAGYLQGPNAAlEEKIFWVPNRAFEPEPLPVILGIHDGSRCLSCVKSGDEPRLQLEDVDITD 85

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2465537200 131 LYKGGEQTTRFTFFQRSLGSAFRLEAAACPGWFLCGPAEPQQPVQLT-KESEPSTHTEFYFE 191
Cdd:cd23297    86 LPRNGKQSARFTFFRSYRDGLWRFESAAHPGWFLCTSMRADQPVSLTnMPDEGVMVTDFYFQ 147

beta-trefoil domain found in the family of interleukin-36 (IL-36) and similar proteins; The IL-36 family includes three members, IL-36 alpha (also called FIL1 epsilon, or interleukin-1 epsilon, or IL-1 epsilon, or interleukin-1 family member 6, or IL-1F6), IL-36 beta (also called FIL1 eta, or interleukin-1 eta, or IL-1 eta, or interleukin-1 family member 8, or IL-1F8, or interleukin-1 homolog 2, or IL-1H2), and IL-36 gamma (also called IL-1-related protein 2, or IL-1RP2, or interleukin-1 epsilon, or IL-1 epsilon, or interleukin-1 family member 9, or IL-1F9, or interleukin-1 homolog 1, or IL-1H1). They act as cytokines that bind to and signals through the IL1RL2/IL-36R receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells linked to a pro-inflammatory response. They are parts of the IL-36 signaling system that is thought to be present in epithelial barriers and to take part in local inflammatory response; like the IL-1 system with which they share the co-receptor IL1RAP. They may be involved in skin inflammatory response by acting on keratinocytes, dendritic cells, and indirectly on T-cells to drive tissue infiltration, cell maturation and cell proliferation. Members in this family contain a beta-trefoil domain, which is characterized by 12 beta strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2465537200  49 PSYFRIKDAHQKALyTRNGQLLLGDPDSDNYSPEKVCILPNR---GLDRSK-VPIFLGMQGGSCCLACVKTREGPLLQLE 124
Cdd:cd23300     2 PSSRHIRDLNQQVW-VLQGNTLIAVPRSDNVTPVTLALIPCRdteFLEKDKgNPIYLGIKGPELCLFCEEIGGQPTLQLK 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2465537200 125 DVNIEDLYKGGEQTTRFTFFQRSLGSAFRLEAAACPGWFLCGPAEPQQPVQLTKESEPSTHTEFYFEM 192
Cdd:cd23300    81 EKNIMDLYNEPEAVKPFLFYHNQTGSTSTFESAAYPGWFIASSSEGGQPIILTKERGKTYNTNFYLDS 148

beta-trefoil domain found in interleukin-37 (IL-37) and similar proteins; IL-37, also called FIL1 zeta, or IL-1X, or interleukin-1 family member 7, or IL-1F7, or interleukin-1 homolog 4, or IL-1H, or IL-1H4, or interleukin-1 zeta, or IL-1 zeta, or interleukin-1-related protein, or IL-1RP1, or interleukin-23, or IL-23, acts as a suppressor of innate inflammatory and immune responses involved in curbing excessive inflammation. This function requires SMAD3. It suppresses, or reduces, proinflammatory cytokine production, including IL1A and IL6, as well as CCL12, CSF1, CSF2, CXCL13, IL1B, IL23A, and IL1RN, but spares anti-inflammatory cytokines and inhibits dendritic cell activation. IL-37 contains a beta-trefoil domain, which is characterized by 12 beta strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2465537200  49 PSYFRIKDAHQKALyTRNGQLLLGDPDSDNYSPEKVCILPNRGLDRSKV---PIFLGMQGGSCCLAC--VKTREGPLLQL 123
Cdd:cd23301     3 PKKFIIRDTNQQVL-VLDSGNLVAVPDKSYIKPETFYVLASHLRSASEEkgnPIFLAVSKGELCLCCekVKGQKHPSLQL 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2465537200 124 EDVNIEDLYKGGEQTTR-FTFFQRSLGSAFRLEAAACPGWFLCGPAEPQQPVQLTKESEPSTHTEFYFE 191
Cdd:cd23301    82 KKKKINELNSQKEKELLpFTFYKEKVGSYFTLESAANPGYFICTSNTPGQPVGVTDKLGKEKNIEFSFV 150

beta-trefoil domain found in interleukin-1 beta (IL-1 beta) and similar proteins; IL-1 beta, also called catabolin, is a potent inflammatory cytokine that activates the inflammatory process. It was initially discovered as the major endogenous pyrogen. It induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-cell activation and antibody production, and fibroblast proliferation and collagen production. IL-1 beta promotes Th17 differentiation of T-cells and synergizes with IL12/interleukin-12 to induce IFN-gamma synthesis from T-helper 1 (Th1) cells. It plays a role in angiogenesis by inducing vascular endothelial growth factor (VEGF) production synergistically with tumor necrosis factor (TNF) and IL-6. IL-1 beta contains a C-terminal beta-trefoil domain, which is characterized by 12 beta strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2465537200  95 SKVPIFLGMQGGSCCLACVKTREGPLLQLEDVNIEDLYKGGEQTtRFTFFQR-SLGSAFRLEAAACPGWFLCGPAEPQQP 173
Cdd:cd23296    54 GKIPVALGIKGKNLYLSCVKKGDKPTLQLEEVDPKNDSKSKDLK-RFLFYKIeSIGSTTTFESAAFPGWYISTSQAENQP 132

                          90
                  ....*....|....*.
gi 2465537200 174 VQLTKESEPSTHTEFY 189
Cdd:cd23296   133 VFLGNQKGQQRITDFT 148