C-terminal domain of Retinoic acid-inducible gene (RIG)-I-like Receptors, Cereblon (CRBN), and similar protein domains; Retinoic acid-inducible gene (RIG)-I-like Receptors (RLRs) are cytoplasmic RNA receptors that recognize non-self RNA and act as molecular sensors to detect viral pathogens. They play crucial roles in innate antiviral responses, including the production of proinflammatory cytokines and type I interferon. There are three RLRs in vertebrates, RIG-I, LGP2, and MDA5. They are characterized by a central DExD/H-box helicase domain and a C-terminal domain, both of which are responsible for binding viral RNA. Cereblon is part of an E3 ubiquitin ligase complex, together with damaged DNA binding protein 1 (DDB1), CUL4A and ROC1. Cereblon interacts directly with DDB1, although the C-terminal domain characterized here does not contribute to that interaction. The C-terminal domain of Cereblon was shown to contain the binding site for thalidomide and its analogs, a class of teratogenic drugs that exhibit an antiproliferative effect on myelomas. Mutations in CRBN, some of which map onto the C-terminal domain, were associated with autosomal recessive mental retardation, which may have to do with interactions between CRBN and ion channels in the brain. RLRs and Cereblon contain a common conserved zinc binding site in their C-terminal domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225455302   10 TFSCRNCRNPVAfwqDliSKDFWGKsgraflfHHAMNIVVGEKEEKQLITG-----------LFTIANISCSNCGEVMGW 78
Cdd:pfam03226   2 VFQCKRCNTILG---D--SLALVSS-------GRELNTIVLKKVTRNVVVGkelvtsesgfdDCTYSPLFCAGCGAVLGR 69

                          90       100
                  ....*....|....*....|....
gi 225455302   79 KYVQAYePRERYKEGKFIIERAKI 102
Cdd:pfam03226  70 KYRSTP-EELDYKRGLFCLETDAI 92

Yippee zinc-binding/DNA-binding /Mis18, centromere assembly; This family includes both Yippee-type proteins and Mis18 kinetochore proteins. Yippee are putative zinc-binding/DNA-binding proteins. Mis18 are proteins involved in the priming of centromeres for recruiting CENP-A. Mis18-alpha and beta form part of a small complex with Mis18-binding protein. Mis18-alpha is found to interact with DNA de-methylases through a Leu-rich region located at its carboxyl terminus. This entry also includes the CULT domain proteins such as Cereblon.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225455302   10 TFSCRNCRNPVAfwqDliSKDFWGKsgraflfHHAMNIVVGEKEEKQLITG-----------LFTIANISCSNCGEVMGW 78
Cdd:pfam03226   2 VFQCKRCNTILG---D--SLALVSS-------GRELNTIVLKKVTRNVVVGkelvtsesgfdDCTYSPLFCAGCGAVLGR 69

                          90       100
                  ....*....|....*....|....
gi 225455302   79 KYVQAYePRERYKEGKFIIERAKI 102
Cdd:pfam03226  70 KYRSTP-EELDYKRGLFCLETDAI 92

Yippee zinc-binding/DNA-binding /Mis18, centromere assembly; This family includes both Yippee-type proteins and Mis18 kinetochore proteins. Yippee are putative zinc-binding/DNA-binding proteins. Mis18 are proteins involved in the priming of centromeres for recruiting CENP-A. Mis18-alpha and beta form part of a small complex with Mis18-binding protein. Mis18-alpha is found to interact with DNA de-methylases through a Leu-rich region located at its carboxyl terminus. This entry also includes the CULT domain proteins such as Cereblon.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225455302   10 TFSCRNCRNPVAfwqDliSKDFWGKsgraflfHHAMNIVVGEKEEKQLITG-----------LFTIANISCSNCGEVMGW 78
Cdd:pfam03226   2 VFQCKRCNTILG---D--SLALVSS-------GRELNTIVLKKVTRNVVVGkelvtsesgfdDCTYSPLFCAGCGAVLGR 69

                          90       100
                  ....*....|....*....|....
gi 225455302   79 KYVQAYePRERYKEGKFIIERAKI 102
Cdd:pfam03226  70 KYRSTP-EELDYKRGLFCLETDAI 92