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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823906    91 GGNVTLTCQVSGaYPPAKILWLRNLTQPeviIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICRADSPVGVREMEIWL 170
Cdd:smart00410   9 GESVTLSCEASG-SPPPEVTWYKQGGKL---LAESGRFSVSRSGSTSTLTISNVTPE-DSGTYTCAATNSSGSASSGTTL 83

                   ..
gi 578823906   171 SV 172
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 578823906    91 GGNVTLTCQVSGaYPPAKILWLRNLTQPeviIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICRADSPVGVREMEIWL 170
Cdd:smart00410   9 GESVTLSCEASG-SPPPEVTWYKQGGKL---LAESGRFSVSRSGSTSTLTISNVTPE-DSGTYTCAATNSSGSASSGTTL 83

                   ..
gi 578823906   171 SV 172
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 578823906  94 VTLTCQVSGaYPPAKILWLRNltqpEVIIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICRADSPVGVRE 165
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 578823906    91 GGNVTLTCQVSGaYPPAKILWLRNLTQPeviIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICRADSPVGVREMEIWL 170
Cdd:smart00410   9 GESVTLSCEASG-SPPPEVTWYKQGGKL---LAESGRFSVSRSGSTSTLTISNVTPE-DSGTYTCAATNSSGSASSGTTL 83

                   ..
gi 578823906   171 SV 172
Cdd:smart00410  84 TV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823906   78 PSLLSEPMKT-CFTGGNVTLTCQVSGaYPPAKILWLRNltqpEVIIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICR 156
Cdd:pfam13927   2 PVITVSPSSVtVREGETVTLTCEATG-SPPPTITWYKN----GEPISSGSTRSRSLSGSNSTLTISNVTRS-DAGTYTCV 75

                  .
gi 578823906  157 A 157
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 578823906  91 GGNVTLTCQVSGaYPPAKILWLRNLTQPEVIIQpssRHLITQDGQnsTLTIHNCsQDLDEGYYICRADSPV-GVREMEIW 169
Cdd:cd20970   17 GENATFMCRAEG-SPEPEISWTRNGNLIIEFNT---RYIVRENGT--TLTIRNI-RRSDMGIYLCIASNGVpGSVEKRIT 89

                 ...
gi 578823906 170 LSV 172
Cdd:cd20970   90 LQV 92

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 578823906  91 GGNVTLTCQVSGAYPPAkILWLR----NLTQPEVIIQPSSRHLITQDGQnstLTIHNCsQDLDEGYYICRADSPVG 162
Cdd:cd05726   14 GRTVTFQCETKGNPQPA-IFWQKegsqNLLFPYQPPQPSSRFSVSPTGD---LTITNV-QRSDVGYYICQALNVAG 84

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 578823906   91 GGNVTLTCQVSGAYPPAKILWLRNLTQPEviiqPSSRHLITQDGQ-NSTLTIhNCSQDLDEGYYICRADSPVGVREMEI 168
Cdd:pfam00047  11 GDSATLTCSASTGSPGPDVTWSKEGGTLI----ESLKVKHDNGRTtQSSLLI-SNVTKEDAGTYTCVVNNPGGSATLST 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 578823906  77 GPSLLSEPMKTCFTGGN----VTLTCQVSGAyPPAKILWLRNLTqpEVIIQPSSRHLITqDGqnsTLTIHNCSQDLDEGY 152
Cdd:cd04967    1 GPVFEEQPDDTIFPEDSdekkVALNCRARAN-PVPSYRWLMNGT--EIDLESDYRYSLV-DG---TLVISNPSKAKDAGH 73

                         90       100
                 ....*....|....*....|
gi 578823906 153 YICRADSPVG-VREMEIWLS 171
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 578823906  84 PMKTCFT-----GGNVTLTCQVSGAYPPAKILWLRN---LTQPEVIIQPSSRHLITqdgQNSTLTIHnCSQDLDEGYYIC 155
Cdd:cd05761    7 PVITGFTspvveGDEITLTCTTSGSKPAADIRWFKNdkeLKGVKEVQESGAGKTFT---VTSTLRFR-VDRDDDGVAVIC 82

                 ....*
gi 578823906 156 RADSP 160
Cdd:cd05761   83 RVDHE 87

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. 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 578823906  89 FTGGNVTLTCQVSGAyPPAKILWLRNLTQpeviIQPSSRHLITQDGQNSTLTIHNCSQDL-DEGYYICRADSPVG 162
Cdd:cd05893   13 FEGMPVTFTCRVAGN-PKPKIYWFKDGKQ----ISPKSDHYTIQRDLDGTCSLHTTASTLdDDGNYTIMAANPQG 82

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as 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. 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823906  78 PSLLSEPM-KTCFTGGNVTLTCQVSGaYPPAKILWLRNLTQPE-VIIQPSSRH---LITQDGQnstLTIHNcSQDLDEGY 152
Cdd:cd05765    1 PALVNSPThQTVKVGETASFHCDVTG-RPQPEITWEKQVPGKEnLIMRPNHVRgnvVVTNIGQ---LVIYN-AQPQDAGL 75

                         90       100
                 ....*....|....*....|
gi 578823906 153 YICRADSPVGVREMEIWLSV 172
Cdd:cd05765   76 YTCTARNSGGLLRANFPLSV 95

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 578823906  77 GPSLLSEPMKTCF----TGGNVTLTCQVSgAYPPAKILWLRNLTqpEVIIQPSSRHliTQDGQNstLTIHNCSQDLDEGY 152
Cdd:cd05850    2 GPVFEEQPSSTLFpegsAEEKVTLACRAR-ASPPATYRWKMNGT--ELKMEPDSRY--RLVAGN--LVISNPVKAKDAGS 74

                         90
                 ....*....|
gi 578823906 153 YICRADSPVG 162
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 578823906  94 VTLTCQVSGayPPAKILWLRNlTQPeviIQPSSRhlITQDGQNSTLTIHNCSQDlDEGYYICRADSPVGVR 164
Cdd:cd05740   18 VTLTCEPET--QNTSYLWWFN-GQS---LPVTPR--LTLSNGNRTLTLLNVTRE-DAGAYQCEISNPVSAN 79

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. 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 structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 578823906  91 GGNVTLTCQVSGAYPPAKilWLRNLTQpeviIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICRA 157
Cdd:cd20967   12 GHKIRLTVELADPDAEVK--WYKDGQE----LQSSSKVIFESIGAKRTLTVQQASLA-DAGEYQCVA 71

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 578823906  91 GGNVTLTCQVSGAyPPAKILWLRN---LTQpeviiqpSSRHLITQDGqnsTLTIHNCSQdLDEGYYICRADSPVGVREME 167
Cdd:cd04969   17 GGDVIIECKPKAS-PKPTISWSKGtelLTN-------SSRICILPDG---SLKIKNVTK-SDEGKYTCFAVNFFGKANST 84

                 ....*
gi 578823906 168 IWLSV 172
Cdd:cd04969   85 GSLSV 89

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823906  78 PSLLSEPMKTCFTGGN-VTLTCQVSGaYPPAKILWLRNL-TQPEVIIQPSSRHLITQDGqNSTLTIHNCSQDlDEGYYIC 155
Cdd:cd20954    2 PRWIVEPVDANVAAGQdVMLHCQADG-FPTPTVTWKKATgSTPGEYKDLLYDPNVRILP-NGTLVFGHVQKE-NEGHYLC 78

                 ....*..
gi 578823906 156 RADSPVG 162
Cdd:cd20954   79 EAKNGIG 85

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 578823906  81 LSEPMKTCFTGGNVTLTCQVSGAYPP-AKILWLRNLT-QPEVIIQPSSRHliTQDG---QNSTLTIhnCSQDLDEGY-YI 154
Cdd:cd00098    4 LLPPSPEEKGGGKVTLVCLVSGFYPKdITVTWLKNGVpLTSGVSTSSPVE--PNDGtysVTSSLTV--PPSDWDEGAtYT 79

                 ....
gi 578823906 155 CRAD 158
Cdd:cd00098   80 CVVT 83

First 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 first 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823906  79 SLLSEPMKT-CFTGGNVTLTCQVSGAyPPAKILWLR-----NLTQPEVIIQPSSRHLITQDGQNSTltiHNCSqdlDEGY 152
Cdd:cd05722    3 YFLSEPSDIvAMRGGPVVLNCSAESD-PPPKIEWKKdgvllNLVSDERRQQLPNGSLLITSVVHSK---HNKP---DEGF 75

                 ....*
gi 578823906 153 YICRA 157
Cdd:cd05722   76 YQCVA 80

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823906    93 NVTLTCQVSG-AYPPAKILWLR--NLTQPEVI----------IQPSSRHLITQDGQNS----TLTIHNCSQDlDEGYYIC 155
Cdd:smart00406   1 SVTLSCKFSGsTFSSYYVSWVRqpPGKGLEWLgyigsngssyYQESYKGRFTISKDTSkndvSLTISNLRVE-DTGTYYC 79

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 578823906  91 GGNVTLTCQVSGAyPPAKILWLRNLTQpeviiQPSSRHLITQDgqnSTLTIHNCsQDLDEGYYICRADSPVG 162
Cdd:cd05725   12 DDSAEFQCEVGGD-PVPTVRWRKEDGE-----LPKGRYEILDD---HSLKIRKV-TAGDMGSYTCVAENMVG 73

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823906  91 GGNVTLTCQVSGaYPPAKILWLRNLTQPEViiqpSSRHLITQDGqnsTLTIHNCSQDlDEGYYICRADSPVGVREMEIWL 170
Cdd:cd05745    2 GQTVDFLCEAQG-YPQPVIAWTKGGSQLSV----DRRHLVLSSG---TLRISRVALH-DQGQYECQAVNIVGSQRTVAQL 72

                 ..
gi 578823906 171 SV 172
Cdd:cd05745   73 TV 74

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 578823906  91 GGNVTLTCQVSGaYPPAKILWL----RNLTQPEVIIQPSSRHLITQdgqNSTLTIHNCSQDlDEGYYICRADSPVG 162
Cdd:cd05734   16 GKAVVLNCSADG-YPPPTIVWKhskgSGVPQFQHIVPLNGRIQLLS---NGSLLIKHVLEE-DSGYYLCKVSNDVG 86

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class II beta chain. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes and they are also expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain has two globular domains (N- and C-terminal) and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 578823906  76 RGPSLLSEPMKTCFTGGNVTLTCQVSGAYPPA-KILWLRN 114
Cdd:cd05766    2 VQPSVKVSPTKTGPLEHPNLLVCSVTGFYPAEiEVKWFRN 41

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578823906   89 FTGGNVTLTCQVSGaYPPAKILWLRNltqpeviiqpssrHLITQDGQNS-TLTIHNCsqdlDEGYYICRA 157
Cdd:pfam13895  12 TEGEPVTLTCSAPG-NPPPSYTWYKD-------------GSAISSSPNFfTLSVSAE----DSGTYTCVA 63