Cytokine interleukin-12p40 C-terminus; IL12p40_C is the largely beta stranded C-terminal, D3, domain of interleukin-12p40 or interleukin-12B. This interleukin is produced on stimulation by macrophage-engulfed micro-organizms and other stimuli, when it dimerizes with interleukin-12p35 to form a heterodimer which then binds to receptors on natural killer cells to activate them to destroy the micro-organizms. This domain contains two disulfide bridges, one of which serves to bind p40 to p35 and the other to hold the beta strands within the domain together. The cupped shape of the p35 binding interface matches the elbow-like bend between D2 and D3 in p40. The domain is often associated with family fn3, pfam00041.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 735997434  123 KTFLKCEAPNYSGRFTCSWLVQRN---MDLKFnIKSSSSsPDSRAVTCGMaslsaekvtldqrDYEKYSVSCQEDVTCPT 199
Cdd:pfam10420   1 KTFLKCEAKNYSGNFTCSWRWDSRrngADVKF-IKASRG-SGQQGVTCSL-------------DGGGYGLTCQDHSFCPY 65

                          90
                  ....*....|....*
gi 735997434  200 AEETLPIELALEARQ 214
Cdd:pfam10420  66 AEESHPIEVTLEAIS 80

Cytokine interleukin-12p40 C-terminus; IL12p40_C is the largely beta stranded C-terminal, D3, domain of interleukin-12p40 or interleukin-12B. This interleukin is produced on stimulation by macrophage-engulfed micro-organizms and other stimuli, when it dimerizes with interleukin-12p35 to form a heterodimer which then binds to receptors on natural killer cells to activate them to destroy the micro-organizms. This domain contains two disulfide bridges, one of which serves to bind p40 to p35 and the other to hold the beta strands within the domain together. The cupped shape of the p35 binding interface matches the elbow-like bend between D2 and D3 in p40. The domain is often associated with family fn3, pfam00041.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 735997434  123 KTFLKCEAPNYSGRFTCSWLVQRN---MDLKFnIKSSSSsPDSRAVTCGMaslsaekvtldqrDYEKYSVSCQEDVTCPT 199
Cdd:pfam10420   1 KTFLKCEAKNYSGNFTCSWRWDSRrngADVKF-IKASRG-SGQQGVTCSL-------------DGGGYGLTCQDHSFCPY 65

                          90
                  ....*....|....*
gi 735997434  200 AEETLPIELALEARQ 214
Cdd:pfam10420  66 AEESHPIEVTLEAIS 80

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 735997434  43 GETVNLTC---DTPEEDdITW--------TSDQRHGVIGSGKTLTITVKEFLDAGQYTC 90
Cdd:cd20970   17 GENATFMCraeGSPEPE-ISWtrngnliiEFNTRYIVRENGTTLTIRNIRRSDMGIYLC 74

Cytokine interleukin-12p40 C-terminus; IL12p40_C is the largely beta stranded C-terminal, D3, domain of interleukin-12p40 or interleukin-12B. This interleukin is produced on stimulation by macrophage-engulfed micro-organizms and other stimuli, when it dimerizes with interleukin-12p35 to form a heterodimer which then binds to receptors on natural killer cells to activate them to destroy the micro-organizms. This domain contains two disulfide bridges, one of which serves to bind p40 to p35 and the other to hold the beta strands within the domain together. The cupped shape of the p35 binding interface matches the elbow-like bend between D2 and D3 in p40. The domain is often associated with family fn3, pfam00041.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 735997434  123 KTFLKCEAPNYSGRFTCSWLVQRN---MDLKFnIKSSSSsPDSRAVTCGMaslsaekvtldqrDYEKYSVSCQEDVTCPT 199
Cdd:pfam10420   1 KTFLKCEAKNYSGNFTCSWRWDSRrngADVKF-IKASRG-SGQQGVTCSL-------------DGGGYGLTCQDHSFCPY 65

                          90
                  ....*....|....*
gi 735997434  200 AEETLPIELALEARQ 214
Cdd:pfam10420  66 AEESHPIEVTLEAIS 80

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 735997434  43 GETVNLTC---DTPEEDdITW--------TSDQRHGVIGSGKTLTITVKEFLDAGQYTC 90
Cdd:cd20970   17 GENATFMCraeGSPEPE-ISWtrngnliiEFNTRYIVRENGTTLTIRNIRRSDMGIYLC 74

First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs). Interactions between IgG and FcgammaR are important to the initiation of cellular and humoral response. IgG binding to FcgammaR leads to a cascade of signals and ultimately to functions such as antibody-dependent-cellular-cytotoxicity (ADCC), endocytosis, phagocytosis, release of inflammatory mediators, etc. FcgammaR has two Ig-like domains. This group also contains FcepsilonRI which binds IgE with high affinity.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 735997434  32 VVEVD--WTPDAPGETVNLTCD---TPEEDDITWtsdqRH-GVIGSGKTLTITVKE--FLDAGQYTCHKGGETLS 98
Cdd:cd05752    2 VVSLDppWTTVFQGEKVTLTCQgfySPEQNSTQW----YHnGTLISSTSSSYRIVAatVNDSGEYRCQTQGSSLS 72