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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530401363   152 GGNVTLTCQVSGaYPPAKILWLRNLTQPeviIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICRADSPVGVREMEIWL 231
Cdd:smart00410   9 GESVTLSCEASG-SPPPEVTWYKQGGKL---LAESGRFSVSRSGSTSTLTISNVTPE-DSGTYTCAATNSSGSASSGTTL 83

                   ..
gi 530401363   232 SV 233
Cdd:smart00410  84 TV 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530401363   152 GGNVTLTCQVSGaYPPAKILWLRNLTQPeviIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICRADSPVGVREMEIWL 231
Cdd:smart00410   9 GESVTLSCEASG-SPPPEVTWYKQGGKL---LAESGRFSVSRSGSTSTLTISNVTPE-DSGTYTCAATNSSGSASSGTTL 83

                   ..
gi 530401363   232 SV 233
Cdd:smart00410  84 TV 85

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 530401363 155 VTLTCQVSGaYPPAKILWLRNltqpEVIIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICRADSPVGVRE 226
Cdd:cd00096    1 VTLTCSASG-NPPPTITWYKN----GKPLPPSSRDSRRSELGNGTLTISNVTLE-DSGTYTCVASNSAGGSA 66

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530401363   152 GGNVTLTCQVSGaYPPAKILWLRNLTQPeviIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICRADSPVGVREMEIWL 231
Cdd:smart00410   9 GESVTLSCEASG-SPPPEVTWYKQGGKL---LAESGRFSVSRSGSTSTLTISNVTPE-DSGTYTCAATNSSGSASSGTTL 83

                   ..
gi 530401363   232 SV 233
Cdd:smart00410  84 TV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530401363  139 PSLLSEPMKT-CFTGGNVTLTCQVSGaYPPAKILWLRNltqpEVIIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICR 217
Cdd:pfam13927   2 PVITVSPSSVtVREGETVTLTCEATG-SPPPTITWYKN----GEPISSGSTRSRSLSGSNSTLTISNVTRS-DAGTYTCV 75

                  .
gi 530401363  218 A 218
Cdd:pfam13927  76 A 76

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 530401363 152 GGNVTLTCQVSGaYPPAKILWLRNLTQPEVIIQpssRHLITQDGQnsTLTIHNCsQDLDEGYYICRADSPV-GVREMEIW 230
Cdd:cd20970   17 GENATFMCRAEG-SPEPEISWTRNGNLIIEFNT---RYIVRENGT--TLTIRNI-RRSDMGIYLCIASNGVpGSVEKRIT 89

                 ...
gi 530401363 231 LSV 233
Cdd:cd20970   90 LQV 92

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 530401363  152 GGNVTLTCQVSGAYPPAKILWLRNLTQPEviiqPSSRHLITQDGQ-NSTLTIhNCSQDLDEGYYICRADSPVGVREMEI 229
Cdd:pfam00047  11 GDSATLTCSASTGSPGPDVTWSKEGGTLI----ESLKVKHDNGRTtQSSLLI-SNVTKEDAGTYTCVVNNPGGSATLST 84

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) 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, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-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, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-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 the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. 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 530401363 152 GGNVTLTCQVSGAYPPAkILWLR----NLTQPEVIIQPSSRHLITQDGQnstLTIHNCsQDLDEGYYICRADSPVG 223
Cdd:cd05726   14 GRTVTFQCETKGNPQPA-IFWQKegsqNLLFPYQPPQPSSRFSVSPTGD---LTITNV-QRSDVGYYICQALNVAG 84

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 530401363 138 GPSLLSEPMKTCFTGGN----VTLTCQVSGAyPPAKILWLRNLTqpEVIIQPSSRHLITqDGqnsTLTIHNCSQDLDEGY 213
Cdd:cd04967    1 GPVFEEQPDDTIFPEDSdekkVALNCRARAN-PVPSYRWLMNGT--EIDLESDYRYSLV-DG---TLVISNPSKAKDAGH 73

                         90       100
                 ....*....|....*....|
gi 530401363 214 YICRADSPVG-VREMEIWLS 232
Cdd:cd04967   74 YQCLATNTVGsVLSREATLQ 93

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues, and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system, where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530401363 145 PMKTCFT-----GGNVTLTCQVSGAYPPAKILWLRN---LTQPEVIIQPSSRHLITqdgQNSTLTIHnCSQDLDEGYYIC 216
Cdd:cd05761    7 PVITGFTspvveGDEITLTCTTSGSKPAADIRWFKNdkeLKGVKEVQESGAGKTFT---VTSTLRFR-VDRDDDGVAVIC 82

                 ....*
gi 530401363 217 RADSP 221
Cdd:cd05761   83 RVDHE 87

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530401363 134 VQIRGpsllSEPMKTCFTGGNVTLTCQVSGaYPPAKILWLRNltqPEVIIQPSSRHLITQDGqnSTLTIHNCSQdLDEGY 213
Cdd:cd05730    4 IRARQ----SEVNATANLGQSVTLACDADG-FPEPTMTWTKD---GEPIESGEEKYSFNEDG--SEMTILDVDK-LDEAE 72

                         90       100
                 ....*....|....*....|
gi 530401363 214 YICRADSPVGVREMEIWLSV 233
Cdd:cd05730   73 YTCIAENKAGEQEAEIHLKV 92

First immunoglobulin (Ig) domain of contactin-5; 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-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530401363 138 GPSLLSEPMKTCFTGGN----VTLTCQVSGAyPPAKILWLRNLTqpEVIIQPSSRH-LItqDGqnsTLTIHNCSQDLDEG 212
Cdd:cd05848    1 GPVFVQEPDDAIFPTDSdekkVILNCEARGN-PVPTYRWLRNGT--EIDTESDYRYsLI--DG---NLIISNPSEVKDSG 72

                         90
                 ....*....|..
gi 530401363 213 YYICRADSPVGV 224
Cdd:cd05848   73 RYQCLATNSIGS 84

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 530401363 138 GPSLLSEPMKTCF----TGGNVTLTCQVSgAYPPAKILWLRNLTqpEVIIQPSSRHliTQDGQNstLTIHNCSQDLDEGY 213
Cdd:cd05850    2 GPVFEEQPSSTLFpegsAEEKVTLACRAR-ASPPATYRWKMNGT--ELKMEPDSRY--RLVAGN--LVISNPVKAKDAGS 74

                         90
                 ....*....|
gi 530401363 214 YICRADSPVG 223
Cdd:cd05850   75 YQCLASNRRG 84

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 530401363 155 VTLTCQVSGayPPAKILWLRNlTQPeviIQPSSRhlITQDGQNSTLTIHNCSQDlDEGYYICRADSPVGVR 225
Cdd:cd05740   18 VTLTCEPET--QNTSYLWWFN-GQS---LPVTPR--LTLSNGNRTLTLLNVTRE-DAGAYQCEISNPVSAN 79

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530401363 152 GGNVTLTCQVSGAyPPAKILWLRN---LTQpeviiqpSSRHLITQDGqnsTLTIHNCSQdLDEGYYICRADSPVGVREME 228
Cdd:cd04969   17 GGDVIIECKPKAS-PKPTISWSKGtelLTN-------SSRICILPDG---SLKIKNVTK-SDEGKYTCFAVNFFGKANST 84

                 ....*
gi 530401363 229 IWLSV 233
Cdd:cd04969   85 GSLSV 89

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530401363 155 VTLTCQVSGAyPPAKILW---LRNLTQPEVIIqpSSRHLITQDGQNSTLTIHNCsQDLDEGYYICRADSPVGVREMEIWL 231
Cdd:cd05869   20 ITLTCEASGD-PIPSITWrtsTRNISSEEKTL--DGHIVVRSHARVSSLTLKYI-QYTDAGEYLCTASNTIGQDSQSMYL 95

                 ..
gi 530401363 232 SV 233
Cdd:cd05869   96 EV 97

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth 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. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530401363 147 KTCFTGGNVTLTCQVSGAyPPAKILW---LRNLTQPEViiQPSSRHLITQDGQNSTLTIHNCsQDLDEGYYICRADSPVG 223
Cdd:cd05732   11 QTAVELEQITLTCEAEGD-PIPEITWrraTRGISFEEG--DLDGRIVVRGHARVSSLTLKDV-QLTDAGRYDCEASNRIG 86

                         90
                 ....*....|
gi 530401363 224 VREMEIWLSV 233
Cdd:cd05732   87 GDQQSMYLEV 96

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530401363  151 TGGNVTLTCQVSGAYPPA--KILWLRNLT--QPEVII----------QPSSRHLITQDGQNS--TLTIHNCSQDlDEGYY 214
Cdd:pfam07686  10 LGGSVTLPCTYSSSMSEAstSVYWYRQPPgkGPTFLIayysngseegVKKGRFSGRGDPSNGdgSLTIQNLTLS-DSGTY 88

                          90       100
                  ....*....|....*....|
gi 530401363  215 ICRADSPVGVREM-EIWLSV 233
Cdd:pfam07686  89 TCAVIPSGEGVFGkGTRLTV 108

Immunoglobulin Constant-1 (C1)-set domain; The members here are composed of C1-set domains, classical Ig-like domains resembling the antibody constant domain. Members of the IgC1 family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, while the IgC domain is involved in oligomerization and molecular interactions. 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 strands by G, F, C, and C'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530401363 142 LSEPMKTCFTGGNVTLTCQVSGAYPP-AKILWLRNLT-QPEVIIQPSSRHliTQDG---QNSTLTIhnCSQDLDEGY-YI 215
Cdd:cd00098    4 LLPPSPEEKGGGKVTLVCLVSGFYPKdITVTWLKNGVpLTSGVSTSSPVE--PNDGtysVTSSLTV--PPSDWDEGAtYT 79

                 ....
gi 530401363 216 CRAD 219
Cdd:cd00098   80 CVVT 83

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.

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gi 530401363 139 PSLLSEPMKTCFTGGN-VTLTCQVSGAyPPAKILWLRNlTQPEVI--IQPSSRHLITQDGQNSTLTI-HNCSQDLDEGYY 214
Cdd:cd07693    1 PRIVEHPSDLIVSKGDpATLNCKAEGR-PTPTIQWLKN-GQPLETdkDDPRSHRIVLPSGSLFFLRVvHGRKGRSDEGVY 78

                         90
                 ....*....|
gi 530401363 215 ICRADSPVGV 224
Cdd:cd07693   79 VCVAHNSLGE 88

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) 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, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-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, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-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 the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. 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 530401363 152 GGNVTLTCQVSGAyPPAKILWLRNLTQpeviiQPSSRHLITQDgqnSTLTIHNCsQDLDEGYYICRADSPVG 223
Cdd:cd05725   12 DDSAEFQCEVGGD-PVPTVRWRKEDGE-----LPKGRYEILDD---HSLKIRKV-TAGDMGSYTCVAENMVG 73

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. 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 530401363 147 KTCFTGGNVTLTCQV-SGAYPpaKILWLR----NLTQ------PEVIIQPSSrhLITQDGQNSTLTIHNCSQDlDEGYYI 215
Cdd:cd04974   11 QTVVLGSDVEFHCKVySDAQP--HIQWLKhvevNGSKygpdglPYVTVLKVA--GVNTTGEENTLTISNVTFD-DAGEYI 85

                         90
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gi 530401363 216 CRADSPVGVREMEIWLS 232
Cdd:cd04974   86 CLAGNSIGLSFHSAWLT 102

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 530401363 152 GGNVTLTCQVSGaYPPAKILWL----RNLTQPEVIIQPSSRHLITQdgqNSTLTIHNCSQDlDEGYYICRADSPVG 223
Cdd:cd05734   16 GKAVVLNCSADG-YPPPTIVWKhskgSGVPQFQHIVPLNGRIQLLS---NGSLLIKHVLEE-DSGYYLCKVSNDVG 86