Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (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. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25149817   114 EIDEGN-IKLECKAQGFPCPEIKWFTKGSkePVHIGRVY-----------TILRCKCSNEHQYKCVAKNE 171
Cdd:pfam07679  11 EVQEGEsARFTCTVTGTPDPEVSWFKDGQ--PLRSSDRFkvtyeggtytlTISNVQPDDSGKYTCVATNS 78

Caspase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25149817   252 KVALIMSNCSYVHL-PELRTPHCDAQTLADALQKMNYKTVTLADLTLDEMRyfiRVYQKLIGN--------GVYAVFYFV 322
Cdd:pfam00656   2 GLALIIGNNNYPGTkAPLRGCDNDAEALAKTLKSLGFEVRVFEDLTAEEIR---RALRDFAARadhsdgdsFVVVLLYYS 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25149817   323 GHGFEVNGQ------CYLLGVDAPADAhqpqhsMSMDWLLSIFRHKTPdlnLLLLDVCRKFVPYDAisafveyseqfkkf 396
Cdd:pfam00656  79 GHGEQVPGGdiygtdEYLVPVDALTNL------FTGDDCLPSLVGKPK---LFIIDACRGNLEDGG-------------- 135

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25149817   397 hRAHRNMVYGYSTSGGVGAYEVKGEvNGVFMKYLKNHVQ---LEISVIDMLNKVlldigdDQKVCDL----QVPEI-RST 468
Cdd:pfam00656 136 -VVEADFLVAYSTAPGQVSWRNTGS-GSWFIQALCQVLReygHGLDLLSLLTKV------RRRVAEAtgkkQMPCLsSST 207

                  ....
gi 25149817   469 LTHP 472
Cdd:pfam00656 208 LTKK 211

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        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 25149817 104 IPDPEQQVTKEIDEG-NIKLECKAQGFPCPEIKWFTKGSK--------EPVHIGRVYTILRCKCSNEHQYKCVAKNEI 172
Cdd:cd20970   3 ISTPQPSFTVTAREGeNATFMCRAEGSPEPEISWTRNGNLiiefntryIVRENGTTLTIRNIRRSDMGIYLCIASNGV 80

MALT1 Ig-like domain; This is an Immunoglobulin like domain which can be found in the mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) paracaspase. Malt1 is a key component of the Carma1/Bcl10/MALT1 signalosome and is critical for NF-kB signaling in multiple contexts. The MALT1 C-terminal Ig domain is suggested to recruit key factors to promote NF-kB activation. The It is also proposed to undergo Lys63-linked ubiquitylation via TRAF6 in potentially nine different lysines to recruit the IKK complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25149817   499 HELPTPATIRFETQqlvATIWFQFCGNFTNKVYVFASIsdfrpcqedtdmgenEELSENALNHRAFVE-FPEELHCSDVR 577
Cdd:pfam18703   2 HVLPESRCLDFDCG---VQVQLGFAAEFSNVMVIYTTI---------------KEKPPEIQDCTAQLTdFPEDLDMDDKF 63

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 25149817   578 EYNDD-EEGVSMLWI------------LSGLQKIKKEAGLTCEVHLRHVDDPEKTIEMKNVDIGHILITRIK 636
Cdd:pfam18703  64 SNQGTsEEMGSLLLSkedlpdcclytrLCSLQKLKESLVFTVCLHYTYSDMDERVTERQEVDIGKPLVAKLK 135

Caspase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25149817   252 KVALIMSNCSYVHL-PELRTPHCDAQTLADALQKMNYKTVTLADLTLDEMRyfiRVYQKLIGN--------GVYAVFYFV 322
Cdd:pfam00656   2 GLALIIGNNNYPGTkAPLRGCDNDAEALAKTLKSLGFEVRVFEDLTAEEIR---RALRDFAARadhsdgdsFVVVLLYYS 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25149817   323 GHGFEVNGQ------CYLLGVDAPADAhqpqhsMSMDWLLSIFRHKTPdlnLLLLDVCRKFVPYDAisafveyseqfkkf 396
Cdd:pfam00656  79 GHGEQVPGGdiygtdEYLVPVDALTNL------FTGDDCLPSLVGKPK---LFIIDACRGNLEDGG-------------- 135

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25149817   397 hRAHRNMVYGYSTSGGVGAYEVKGEvNGVFMKYLKNHVQ---LEISVIDMLNKVlldigdDQKVCDL----QVPEI-RST 468
Cdd:pfam00656 136 -VVEADFLVAYSTAPGQVSWRNTGS-GSWFIQALCQVLReygHGLDLLSLLTKV------RRRVAEAtgkkQMPCLsSST 207

                  ....
gi 25149817   469 LTHP 472
Cdd:pfam00656 208 LTKK 211

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        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 25149817 104 IPDPEQQVTKEIDEG-NIKLECKAQGFPCPEIKWFTKGSK--------EPVHIGRVYTILRCKCSNEHQYKCVAKNEI 172
Cdd:cd20970   3 ISTPQPSFTVTAREGeNATFMCRAEGSPEPEISWTRNGNLiiefntryIVRENGTTLTIRNIRRSDMGIYLCIASNGV 80

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 25149817   114 EIDEG-NIKLECKAQGFPCPEIKWFTKGSKEP---------VHIGRVYTILRCKCSNEHQYKCVAKN 170
Cdd:pfam13927  12 TVREGeTVTLTCEATGSPPPTITWYKNGEPISsgstrsrslSGSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (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. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 25149817 120 IKLECKAQGFPCPEIKWFTKGSKEPVHIGRVY---------TILRCKCSNEHQYKCVAKNEIRE 174
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRrselgngtlTISNVTLEDSGTYTCVASNSAGG 64

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. 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 titin Z1z2 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        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25149817 100 PLRWIPDPEQQvtkEIDEGN-IKLECKAQGFPCPEIKWFTKG----SKEPVHI---GRVYTILRCKCSNEH--QYKCVAK 169
Cdd:cd20972   1 PPQFIQKLRSQ---EVAEGSkVRLECRVTGNPTPVVRWFCEGkelqNSPDIQIhqeGDLHSLIIAEAFEEDtgRYSCLAT 77

                        90
                ....*....|...
gi 25149817 170 NEIREGSPYSEIY 182
Cdd:cd20972  78 NSVGSDTTSAEIF 90

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25149817 102 RWIPDPEQQVtkEIDEGNIKLECKAQGFPCPEIKWFTKGSkePVHI----------GRVyTILRCKCSNEHQ-YKCVAKN 170
Cdd:cd04978   1 YWIIEPPSLV--LSPGETGELICEAEGNPQPTITWRLNGV--PIEPapedmrrtvdGRT-LIFSNLQPNDTAvYQCNASN 75

                .
gi 25149817 171 E 171
Cdd:cd04978  76 V 76

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 25149817 118 GNIKLECKAQGFPCPEIKWFTKGSKEPVHIG------RVYTILRCKCSNEHQYKCVAKN 170
Cdd:cd05876  11 QSLVLECIAEGLPTPTVKWLRPSGPLPPDRVkyqnhnKTLQLLNVGESDDGEYVCLAEN 69

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 25149817 118 GNIKLECKAQGFPCPEIKWfTKGSKEPVHIGRVYT-------ILRCKCSNEHQYKCVAKN 170
Cdd:cd04969  18 GDVIIECKPKASPKPTISW-SKGTELLTNSSRICIlpdgslkIKNVTKSDEGKYTCFAVN 76

MALT1 Ig-like domain; This is an Immunoglobulin like domain which can be found in the mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) paracaspase. Malt1 is a key component of the Carma1/Bcl10/MALT1 signalosome and is critical for NF-kB signaling in multiple contexts. The MALT1 C-terminal Ig domain is suggested to recruit key factors to promote NF-kB activation. The It is also proposed to undergo Lys63-linked ubiquitylation via TRAF6 in potentially nine different lysines to recruit the IKK complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25149817   499 HELPTPATIRFETQqlvATIWFQFCGNFTNKVYVFASIsdfrpcqedtdmgenEELSENALNHRAFVE-FPEELHCSDVR 577
Cdd:pfam18703   2 HVLPESRCLDFDCG---VQVQLGFAAEFSNVMVIYTTI---------------KEKPPEIQDCTAQLTdFPEDLDMDDKF 63

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 25149817   578 EYNDD-EEGVSMLWI------------LSGLQKIKKEAGLTCEVHLRHVDDPEKTIEMKNVDIGHILITRIK 636
Cdd:pfam18703  64 SNQGTsEEMGSLLLSkedlpdcclytrLCSLQKLKESLVFTVCLHYTYSDMDERVTERQEVDIGKPLVAKLK 135