Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1344537316   43 EMVIGNNIQLTCHsAEGSPSPQYSWKsynaQNQQRPLTQP----VSGEP----LLLKNISTETAGYYICTSSNDVGIESC 114
Cdd:smart00410   5 TVKEGESVTLSCE-ASGSPPPEVTWY----KQGGKLLAESgrfsVSRSGststLTISNVTPEDSGTYTCAATNSSGSASS 79

                   ....
gi 1344537316  115 NITV 118
Cdd:smart00410  80 GTTL 83

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1344537316   43 EMVIGNNIQLTCHsAEGSPSPQYSWKsynaQNQQRPLTQP----VSGEP----LLLKNISTETAGYYICTSSNDVGIESC 114
Cdd:smart00410   5 TVKEGESVTLSCE-ASGSPPPEVTWY----KQGGKLLAESgrfsVSRSGststLTISNVTPEDSGTYTCAATNSSGSASS 79

                   ....
gi 1344537316  115 NITV 118
Cdd:smart00410  80 GTTL 83

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1344537316  31 VPPSKPDcSIQGEMVIgnniqLTChSAEGSPSPQYSWK-SYNAQNQQRPLTQPVSGE-------PLLLKNISTETAGYYI 102
Cdd:cd05734     6 VQPNDQD-GIYGKAVV-----LNC-SADGYPPPTIVWKhSKGSGVPQFQHIVPLNGRiqllsngSLLIKHVLEEDSGYYL 78

                  ....*...
gi 1344537316 103 CTSSNDVG 110
Cdd:cd05734    79 CKVSNDVG 86

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. 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 1344537316  43 EMVIGNNIQLTCHsAEGSPSPQYSWKSYNAQ---NQQRPLTQPVSGE-PLLLKNISTETAGYYICTSSNDVGIESCN 115
Cdd:cd05744    11 EVQEGRLCRFDCK-VSGLPTPDLFWQLNGKPvrpDSAHKMLVRENGRhSLIIEPVTKRDAGIYTCIARNRAGENSFN 86

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. 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. The second Ig-like domain of JAM1 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, the A strand of the I-set is discontinuous but lacks a C" strand. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1344537316  36 PDCSIQGEMVIGNNIQLTCHSAEGSPSPQYSW-----------KSYNAQNQQRPLTQPVSGEpLLLKNISTETAGYYICT 104
Cdd:cd20950     1 PTVNIPSSATIGNRAVLTCSEPDGSPPSEYTWfkdgvvmptnpKSTRAFSNSSYSLDPTTGE-LVFDPLSASDTGEYSCE 79

                  ....*.
gi 1344537316 105 SSNDVG 110
Cdd:cd20950    80 ARNGYG 85

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1344537316  47 GNNIQLTCHsAEGSPSPQYSW-KSYNAQNQQRP--LTQPVSGEPLLLKNISTETAGYYICTSSNDVGIE 112
Cdd:cd05736    15 GVEASLRCH-AEGIPLPRVQWlKNGMDINPKLSkqLTLIANGSELHISNVRYEDTGAYTCIAKNEGGVD 82

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. 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 this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus 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 1344537316  36 PDCsiqgEMVIGNNIQLTChSAEGSPSPQYSWkSYNAQNQQ----RPLTQPVSGEpLLLKNISTETAGYYICTSSNDVGI 111
Cdd:cd20976     9 KDL----EAVEGQDFVAQC-SARGKPVPRITW-IRNAQPLQyaadRSTCEAGVGE-LHIQDVLPEDHGTYTCLAKNAAGQ 81

                  ....*..
gi 1344537316 112 ESCNITV 118
Cdd:cd20976    82 VSCSAWV 88

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 1344537316  50 IQLTChSAEGSPSPQYSWKSYNAQNQQRPLTQPVSGEP---LLLKNISTETAGYYICTSSNDVG 110
Cdd:cd00096     1 VTLTC-SASGNPPPTITWYKNGKPLPPSSRDSRRSELGngtLTISNVTLEDSGTYTCVASNSAG 63

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1344537316  47 GNNIQLTChSAEGSPSPQYSWKsyNAQNQQRPLTQPVS----GEPLLLKNISTETAGYYICTSSNDVG 110
Cdd:cd20970    17 GENATFMC-RAEGSPEPEISWT--RNGNLIIEFNTRYIvrenGTTLTIRNIRRSDMGIYLCIASNGVP 81

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1344537316  47 GNNIQLTCHSAEGSPSPQYSW-KSYNAQNQQRPLTQPVSGEP----LLLKNISTETAGYYICTSSNDVGIESCNITV 118
Cdd:cd05750    14 GSKLVLKCEATSENPSPRYRWfKDGKELNRKRPKNIKIRNKKknseLQINKAKLEDSGEYTCVVENILGKDTVTGNV 90