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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639524 152 SSDVIVPEGSSVRLTCRARGYPEPIVTWRREDGNEIVLKDNVGTKTlapsfRGEVLKLSKISRNEMGSYLCIASNGVPPS 231
Cdd:cd20970   9 SFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRE-----NGTTLTIRNIRRSDMGIYLCIASNGVPGS 83

                ....*....
gi 24639524 232 VSKRISLSI 240
Cdd:cd20970  84 VEKRITLQV 92

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639524     49 SNVSVAVGRDATFTCHVRHLGGYRVGWLKADTKaiqaihenVITHNPRVTVSHlDQNTWNLHIKAVSEEDRGGYMCQLNT 128
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGK--------LLAESGRFSVSR-SGSTSTLTISNVTPEDSGTYTCAATN 72

                   .
gi 24639524    129 D 129
Cdd:smart00410  73 S 73

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639524 152 SSDVIVPEGSSVRLTCRARGYPEPIVTWRREDGNEIVLKDNVGTKTlapsfRGEVLKLSKISRNEMGSYLCIASNGVPPS 231
Cdd:cd20970   9 SFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRE-----NGTTLTIRNIRRSDMGIYLCIASNGVPGS 83

                ....*....
gi 24639524 232 VSKRISLSI 240
Cdd:cd20970  84 VEKRITLQV 92

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24639524    152 SSDVIVPEGSSVRLTCRARGYPEPIVTWRREDGNEIVLKDNVgtkTLAPSFRGEVLKLSKISRNEMGSYLCIASNG 227
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRF---SVSRSGSTSTLTISNVTPEDSGTYTCAATNS 73

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639524    255 APLGTDVQIECHVEASPKSINYWIKDTGEMIVTSGKYHVQESSqsmyeTKMSMIVRKFQKDDVGSYRCIAKNSLGEVDSS 334
Cdd:smart00410   6 VKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSG-----STSTLTISNVTPEDSGTYTCAATNSSGSASSG 80

                   ....
gi 24639524    335 IRLY 338
Cdd:smart00410  81 TTLT 84

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. 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 fourth Ig-like domain of hemolin 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 domains, members of the I-set have a discontinuous A strand but lack 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, 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 24639524 245 VIQVPNQLVGAPLGTDVQIECHVEASPKSINYWIKDTGEMIVTSGKYHVqessqsmyeTKMSMIVRKFQKDDVGSYRCIA 324
Cdd:cd20978   3 FIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATV---------EDGTLTIINVQPEDTGYYGCVA 73

                        90
                ....*....|....
gi 24639524 325 KNSLGEVDSSIRLY 338
Cdd:cd20978  74 TNEIGDIYTETLLH 87

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639524    42 PEFVESISNVSVAVGRDATFTCHVRHLGGYRVGWLKadtkaiqaihENVITHNPRVTVSHLDQNTWNLHIKAVSEEDRGG 121
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYK----------NGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGT 71

                  ....
gi 24639524   122 YMCQ 125
Cdd:pfam13927  72 YTCV 75

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639524 152 SSDVIVPEGSSVRLTCRARGYPEPIVTWRREDGNEIVLKDNVGTKTlapsfRGEVLKLSKISRNEMGSYLCIASNGVPPS 231
Cdd:cd20970   9 SFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRE-----NGTTLTIRNIRRSDMGIYLCIASNGVPGS 83

                ....*....
gi 24639524 232 VSKRISLSI 240
Cdd:cd20970  84 VEKRITLQV 92

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24639524   151 TSSDVIVPEGSSVRLTCRARGYPEPIVTWRREDGNEIvlkdNVGTKTLAPSFRGEVLKLSKISRNEMGSYLCIASN 226
Cdd:pfam13927   7 SPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPIS----SGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639524   144 PDFISedTSSDVIVPEGSSVRLTCRARGYPEPIVTWRREDgneivlkdnvgtKTLAPSFRGEV--------LKLSKISRN 215
Cdd:pfam07679   1 PKFTQ--KPKDVEVQEGESARFTCTVTGTPDPEVSWFKDG------------QPLRSSDRFKVtyeggtytLTISNVQPD 66

                          90       100
                  ....*....|....*....|....*
gi 24639524   216 EMGSYLCIASNGVpPSVSKRISLSI 240
Cdd:pfam07679  67 DSGKYTCVATNSA-GEAEASAELTV 90

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639524    255 APLGTDVQIECHVEASPKSINYWIKDTGEMIVTSGKYHVQESSqsmyeTKMSMIVRKFQKDDVGSYRCIAKNSLGEVDSS 334
Cdd:smart00410   6 VKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSG-----STSTLTISNVTPEDSGTYTCAATNSSGSASSG 80

                   ....
gi 24639524    335 IRLY 338
Cdd:smart00410  81 TTLT 84

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639524   244 PVIQVPNQLVGAPLGTDVQIECHVEASPKSINYWIKDTGEMIvtsgkyHVQESSQSMYETKMSMIVRKFQKDDVGSYRCI 323
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPIS------SGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75

                  ...
gi 24639524   324 AKN 326
Cdd:pfam13927  76 ASN 78

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639524     49 SNVSVAVGRDATFTCHVRHLGGYRVGWLKADTKaiqaihenVITHNPRVTVSHlDQNTWNLHIKAVSEEDRGGYMCQLNT 128
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGK--------LLAESGRFSVSR-SGSTSTLTISNVTPEDSGTYTCAATN 72

                   .
gi 24639524    129 D 129
Cdd:smart00410  73 S 73

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639524 153 SDVIVPEGSSVRLTCRARGYPEPIVTWRReDGNEIVL-KDNVGT-KTLAPSfrGEVLKLSKI----SRNEMGSYLCIASN 226
Cdd:cd07693   8 SDLIVSKGDPATLNCKAEGRPTPTIQWLK-NGQPLETdKDDPRShRIVLPS--GSLFFLRVVhgrkGRSDEGVYVCVAHN 84

                        90
                ....*....|....
gi 24639524 227 GVPPSVSKRISLSI 240
Cdd:cd07693  85 SLGEAVSRNASLEV 98

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first 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. This group belongs to the I-set of IgSF domains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639524 147 ISEDTSSDVIVPEGSS---VRLTCRARGYPEPIVTWRReDGNEIvlkdnvgtkTLAPSFR-----GEVLKLSKISRNEMG 218
Cdd:cd04967   3 VFEEQPDDTIFPEDSDekkVALNCRARANPVPSYRWLM-NGTEI---------DLESDYRyslvdGTLVISNPSKAKDAG 72

                        90       100
                ....*....|....*....|....
gi 24639524 219 SYLCIASNGVPPSVSKRISLSIHF 242
Cdd:cd04967  73 HYQCLATNTVGSVLSREATLQFGY 96

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; 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 and 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, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24639524 151 TSSDVIVPEGSSVRLTCRARGYPEPIVTWRREDGNeiVLKDNVGTKtlapSFrGEVLKLSKISRNEMGSYLCIASNGV 228
Cdd:cd05731   1 SESSTMVLRGGVLLLECIAEGLPTPDIRWIKLGGE--LPKGRTKFE----NF-NKTLKIENVSEADSGEYQCTASNTM 71

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24639524 261 VQIECHVEASPKSINYWIKDtGEMIVTSGKYHVqesSQSMYETkmsmiVRKFQKDDVGSYRCIAKNSLGEVDSSIRL 337
Cdd:cd05746   1 VQIPCSAQGDPEPTITWNKD-GVQVTESGKFHI---SPEGYLA-----IRDVGVADQGRYECVARNTIGYASVSMVL 68

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24639524 158 PEGSSVRLTCRARGYPEPIVTWrredgneivLKDNvgtKTLAPSFRGE------VLKLSKISRNEMGSYLCIASNGV 228
Cdd:cd05856  17 PVGSSVRLKCVASGNPRPDITW---------LKDN---KPLTPPEIGEnkkkkwTLSLKNLKPEDSGKYTCHVSNRA 81

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24639524 160 GSSVRLTCRARGYPEPIVTWRReDGNEIvlkdNVGTKTLAPSFRGEVLKLSKISRNEMGSYLCIASN 226
Cdd:cd05730  18 GQSVTLACDADGFPEPTMTWTK-DGEPI----ESGEEKYSFNEDGSEMTILDVDKLDEAEYTCIAEN 79

First immunoglobulin (Ig) domain of contactin-2; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. 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-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639524 149 EDTSSDVIVPEGSS---VRLTCRARGYPEPIVTWRReDGNEIVLKDNVGTKTLApsfrGEVLKLSKISRNEMGSYLCIAS 225
Cdd:cd05850   6 EEQPSSTLFPEGSAeekVTLACRARASPPATYRWKM-NGTELKMEPDSRYRLVA----GNLVISNPVKAKDAGSYQCLAS 80

                        90
                ....*....|....*..
gi 24639524 226 NGVPPSVSKRISLSIHF 242
Cdd:cd05850  81 NRRGTVVSREASLRFGF 97

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. 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 Lingo-1 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 24639524 155 VIVPEGSSVRLTCRARGYPEPIVTWRREDGNEIVLKDNvGTKTLAPsfrGEVLKLSKISRNEMGSYLCIASNGV 228
Cdd:cd20969  12 VFVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSN-GRLTVFP---DGTLEVRYAQVQDNGTYLCIAANAG 81

First immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639524 147 ISEDTSSDVIVPEGSS---VRLTCRARGYPEPIVTWRREDGNEIVLKDNVgtktlapSFRGEVLKLSKISR-NEMGSYLC 222
Cdd:cd05849   3 VFEEQPIDTIYPEESTegkVSVNCRARANPFPIYKWRKNNLDIDLTNDRY-------SMVGGNLVINNPDKyKDAGRYVC 75

                ....
gi 24639524 223 IASN 226
Cdd:cd05849  76 IVSN 79

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (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.

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gi 24639524 157 VPEGSSVRLTCRARGYPEPIVTWRREDGNEIvlkdnvGTKTLAPSFRGEVLKLSKISRNEMGSYLCIASN 226
Cdd:cd05764  12 VLEGQRATLRCKARGDPEPAIHWISPEGKLI------SNSSRTLVYDNGTLDILITTVKDTGAFTCIASN 75

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24639524 261 VQIECHVEASPKSINYWIKDTGEMIVTSGKYHVQESSQSmyetkmSMIVRKFQKDDVGSYRCIAKNSLGEVDSSI 335
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNG------TLTISNVTLEDSGTYTCVASNSAGGSASAS 69

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639524 144 PDFISEDTSSDVIvpEGSSVRLTCRARGYPEPIVTWR------REDGNEIVLKDNVGTKTLApsfrgevlkLSKISRNEM 217
Cdd:cd05744   1 PHFLQAPGDLEVQ--EGRLCRFDCKVSGLPTPDLFWQlngkpvRPDSAHKMLVRENGRHSLI---------IEPVTKRDA 69

                ....*....
gi 24639524 218 GSYLCIASN 226
Cdd:cd05744  70 GIYTCIARN 78

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639524 144 PDFISEDTSSDVIVPEGSSVRLTCRARGYPEPIVTWRRedgneivlkdnvGTKTLAPSFRGEV-----LKLSKISRNEMG 218
Cdd:cd04969   1 PDFELNPVKKKILAAKGGDVIIECKPKASPKPTISWSK------------GTELLTNSSRICIlpdgsLKIKNVTKSDEG 68

                ....*...
gi 24639524 219 SYLCIASN 226
Cdd:cd04969  69 KYTCFAVN 76

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third 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. This group belongs to the I-set of IgSF domains.

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gi 24639524 154 DVIVPEGSSVRLTCRARGYPEPIVTWRREDGNEIvlkdnvGTKTLAPSfrGEVLKLSKISRNEMGSYLCIASN 226
Cdd:cd04968  10 DTYALKGQTVTLECFALGNPVPQIKWRKVDGSPS------SQWEITTS--EPVLEIPNVQFEDEGTYECEAEN 74

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 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, members of the I-set have a discontinuous A strand but lack 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

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24639524 152 SSDVIVPEGSSVRLTCRARGYPEPIVTWRReDGNEIVLKDnvgtktlaPSFRGE---VLKLSKISRNEMGSYLCIASN 226
Cdd:cd20952   6 PQNQTVAVGGTVVLNCQATGEPVPTISWLK-DGVPLLGKD--------ERITTLengSLQIKGAEKSDTGEYTCVALN 74

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.

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gi 24639524 152 SSDVIVPEGSSVRLTCRARGYPEPIVTWRREDGneiVLKDNVGTKtlapSFRGEVLKLSKISRNEMGSYLCIASNG 227
Cdd:cd05876   2 SSSLVALRGQSLVLECIAEGLPTPTVKWLRPSG---PLPPDRVKY----QNHNKTLQLLNVGESDDGEYVCLAENS 70

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. 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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24639524 259 TDVQIECHVEASPKSINYWIKDtGEMIVTSGKYHVQESSqsmyetkmSMIVRKFQKDDVGSYRCIAKNSLGEVDSSIRL 337
Cdd:cd05723  13 MDIVFECEVTGKPTPTVKWVKN-GDVVIPSDYFKIVKEH--------NLQVLGLVKSDEGFYQCIAENDVGNAQASAQL 82

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group 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, members of the I-set have a discontinuous A strand but lack a C" strand.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24639524 258 GTDVQIECHVEASPKSINYWIKDTGEmivTSGKYH-VQESSQSMYETKMSMIVRKFQKDDVGSYRCIAKNSLG 329
Cdd:cd20954  16 GQDVMLHCQADGFPTPTVTWKKATGS---TPGEYKdLLYDPNVRILPNGTLVFGHVQKENEGHYLCEAKNGIG 85

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. 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 fourth Ig-like domain of hemolin 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 domains, members of the I-set have a discontinuous A strand but lack 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, 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.

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gi 24639524 144 PDFISEdTSSDVIVPEGSSVRLTCRARGYPEPIVTWRRedgNEIVLKDNVGTKTLAPSfrGEVLKLSKISRNemGSYLCI 223
Cdd:cd20978   1 PKFIQK-PEKNVVVKGGQDVTLPCQVTGVPQPKITWLH---NGKPLQGPMERATVEDG--TLTIINVQPEDT--GYYGCV 72

                ...
gi 24639524 224 ASN 226
Cdd:cd20978  73 ATN 75

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

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gi 24639524 163 VRLTCRARGYPEPIVTWRRE----DGNEIVLKDNVGTKTLApsfRGEVLKLSKISRNEMGSYLCIASNGV 228
Cdd:cd05869  20 ITLTCEASGDPIPSITWRTStrniSSEEKTLDGHIVVRSHA---RVSSLTLKYIQYTDAGEYLCTASNTI 86