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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584041    294 ENVTLICRVHGSPNTVIAWdytnqvyeSRSKPVKSLQKQRIYIEllredeskirkfgHDVFVSRLTIVNARKSDEGVYTC 373
Cdd:smart00410  10 ESVTLSCEASGSPPPEVTW--------YKQGGKLLAESGRFSVS-------------RSGSTSTLTISNVTPEDSGTYTC 68

                           90
                   ....*....|....*..
gi 24584041    374 LAENPGGKDSVHISVVV 390
Cdd:smart00410  69 AATNSSGSASSGTTLTV 85

Leucine-rich repeat (LRR) protein [Transcription];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584041  59 RNLSLSGVPEYLSPEVQVLDLSHNHIFYLEENAFLTTHLQNLQKLlirnGTLKYLNQRSFTQLQILIELDLSNNLLVDlL 138
Cdd:COG4886  54 SLLLRDLLLSSLLLLLSLLLLLLLSLLLLSLLLLGLTDLGDLTNL----TELDLSGNEELSNLTNLESLDLSGNQLTD-L 128

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584041 139 PNVFDCLSKVRAIFLNGNLLQALrHGVFRNLKYLHKIELKRNRLVSIDAkAFVGVPLLSQIYLDNNELTKLRvESFQDLT 218
Cdd:COG4886 129 PEELANLTNLKELDLSNNQLTDL-PEPLGNLTNLKSLDLSNNQLTDLPE-ELGNLTNLKELDLSNNQITDLP-EPLGNLT 205

                       170
                ....*....|
gi 24584041 219 KLTALSLVEN 228
Cdd:COG4886 206 NLEELDLSGN 215

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584041    294 ENVTLICRVHGSPNTVIAWdytnqvyeSRSKPVKSLQKQRIYIEllredeskirkfgHDVFVSRLTIVNARKSDEGVYTC 373
Cdd:smart00410  10 ESVTLSCEASGSPPPEVTW--------YKQGGKLLAESGRFSVS-------------RSGSTSTLTISNVTPEDSGTYTC 68

                           90
                   ....*....|....*..
gi 24584041    374 LAENPGGKDSVHISVVV 390
Cdd:smart00410  69 AATNSSGSASSGTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584041   277 KPKIVYPTLSTSINTSkENVTLICRVHGSPNTVIAWDYTNQVYESRSkpvkslqkqriyiellredeskIRKFGHDVFVS 356
Cdd:pfam13927   1 KPVITVSPSSVTVREG-ETVTLTCEATGSPPPTITWYKNGEPISSGS----------------------TRSRSLSGSNS 57

                          90       100
                  ....*....|....*....|.
gi 24584041   357 RLTIVNARKSDEGVYTCLAEN 377
Cdd:pfam13927  58 TLTISNVTRSDAGTYTCVASN 78

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24584041   146 SKVRAIFLNGNLLQALRHGVFRNLKYLHKIELKRNRLVSIDAKAFVGVPLLSQIYLDNNEL 206
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

Leucine rich repeat C-terminal domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 24584041    228 NPWNCTCDLQMFRDFVIGMNLYTPPTS--CHYPLQLRGRLWiEDQPEAFACK 277
Cdd:smart00082   1 NPFICDCELRWLLRWLQANEHLQDPVDlrCASPSSLRGPLL-ELLHSEFKCP 51

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584041    294 ENVTLICRVHGSPNTVIAWdytnqvyeSRSKPVKSLQKQRIYIEllredeskirkfgHDVFVSRLTIVNARKSDEGVYTC 373
Cdd:smart00410  10 ESVTLSCEASGSPPPEVTW--------YKQGGKLLAESGRFSVS-------------RSGSTSTLTISNVTPEDSGTYTC 68

                           90
                   ....*....|....*..
gi 24584041    374 LAENPGGKDSVHISVVV 390
Cdd:smart00410  69 AATNSSGSASSGTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584041   277 KPKIVYPTLSTSINTSkENVTLICRVHGSPNTVIAWDYTNQVYESRSkpvkslqkqriyiellredeskIRKFGHDVFVS 356
Cdd:pfam13927   1 KPVITVSPSSVTVREG-ETVTLTCEATGSPPPTITWYKNGEPISSGS----------------------TRSRSLSGSNS 57

                          90       100
                  ....*....|....*....|.
gi 24584041   357 RLTIVNARKSDEGVYTCLAEN 377
Cdd:pfam13927  58 TLTISNVTRSDAGTYTCVASN 78

Leucine-rich repeat (LRR) protein [Transcription];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584041  59 RNLSLSGVPEYLSPEVQVLDLSHNHIFYLEENAFLTTHLQNLQKLlirnGTLKYLNQRSFTQLQILIELDLSNNLLVDlL 138
Cdd:COG4886  54 SLLLRDLLLSSLLLLLSLLLLLLLSLLLLSLLLLGLTDLGDLTNL----TELDLSGNEELSNLTNLESLDLSGNQLTD-L 128

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584041 139 PNVFDCLSKVRAIFLNGNLLQALrHGVFRNLKYLHKIELKRNRLVSIDAkAFVGVPLLSQIYLDNNELTKLRvESFQDLT 218
Cdd:COG4886 129 PEELANLTNLKELDLSNNQLTDL-PEPLGNLTNLKSLDLSNNQLTDLPE-ELGNLTNLKELDLSNNQITDLP-EPLGNLT 205

                       170
                ....*....|
gi 24584041 219 KLTALSLVEN 228
Cdd:COG4886 206 NLEELDLSGN 215

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 24584041 296 VTLICRVHGSPNTVIAWdytnqvyesrSKPVKSLQkqriyiellredESKIRKFGHDVFVSRLTIVNARKSDEGVYTCLA 375
Cdd:cd00096   1 VTLTCSASGNPPPTITW----------YKNGKPLP------------PSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58

                        90
                ....*....|..
gi 24584041 376 ENP-GGKDSVHI 386
Cdd:cd00096  59 SNSaGGSASASV 70

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 24584041 294 ENVTLICRVHGSPNTVIAWdytnqvyesrskpvkslQKQRIYIELLREDESkIRKFGHDvfvsrLTIVNARKSDEGVYTC 373
Cdd:cd20970  18 ENATFMCRAEGSPEPEISW-----------------TRNGNLIIEFNTRYI-VRENGTT-----LTIRNIRRSDMGIYLC 74

                        90
                ....*....|....*...
gi 24584041 374 LAEN-PGGKDSVHISVVV 390
Cdd:cd20970  75 IASNgVPGSVEKRITLQV 92

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

                        10        20        30
                ....*....|....*....|....*....|....*
gi 24584041 356 SRLTIVNARKSDEGVYTCLAENPGGKDSVHISVVV 390
Cdd:cd05748  48 TSLVIKNAKRSDSGKYTLTLKNSAGEKSATINVKV 82

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24584041    72 PEVQVLDLSHNHIFYLEENAFltTHLQNLQKLLIRNGTLKYLNQRSFTQLQILIELDLSNNLL 134
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLDDGAF--KGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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 24584041 278 PKIVYPTLSTSINTSKENVTLICRVHGSPNTVIAWDYTnqvyesrSKPVkslqkqriyiellrEDESKIRKFGHdvfvSR 357
Cdd:cd20978   1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHN-------GKPL--------------QGPMERATVED----GT 55

                        90       100       110
                ....*....|....*....|....*....|...
gi 24584041 358 LTIVNARKSDEGVYTCLAENPGGKDSVHISVVV 390
Cdd:cd20978  56 LTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins; member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and related proteins. The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members: VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1) and VEGFR-3 (Flt-4). VEGF-A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF; VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group also contains alpha-type platelet-derived growth factor receptor precursor (PDGFR)-alpha (CD140a), and PDGFR-beta (CD140b). PDGFRs alpha and beta have an extracellular component with five Ig-like domains, a transmembrane segment, and a cytoplasmic portion that has protein tyrosine kinase activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584041 294 ENVTLICRVHGSPNTVI--AWDYtnqvyesrskPVKSLQKQRIYIELLREDESKIRKFghdvfVSRLTIVNARKSDEGVY 371
Cdd:cd05742  18 ETLVLNCTANVNLNEVVdfQWTY----------PSEKEGKLALLKPDIKVDWSEPGEF-----VSTLTIPEATLKDSGTY 82

                        90
                ....*....|....*....
gi 24584041 372 TCLAENPGGKDSVHISVVV 390
Cdd:cd05742  83 TCAARSGVMKKEKQTSVSV 101

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584041 296 VTLICRVHGSPNTVIAWdytnqVYESRSKPVKSlqkQRIYIEllrEDESkirkfghdvfvsrLTIVNARKSDEGVYTCLA 375
Cdd:cd20952  17 VVLNCQATGEPVPTISW-----LKDGVPLLGKD---ERITTL---ENGS-------------LQIKGAEKSDTGEYTCVA 72

                        90
                ....*....|....*
gi 24584041 376 ENPGGKDSVHISVVV 390
Cdd:cd20952  73 LNLSGEATWSAVLDV 87

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 24584041 282 YPTLSTSINTSKENVTLICRVHGSPNTVIAWdytnqvyesrSKPVKSL-QKQRIYIellREDESkirkfghdvfvsrLTI 360
Cdd:cd04969   6 NPVKKKILAAKGGDVIIECKPKASPKPTISW----------SKGTELLtNSSRICI---LPDGS-------------LKI 59

                        90       100       110
                ....*....|....*....|....*....|
gi 24584041 361 VNARKSDEGVYTCLAENPGGKDSVHISVVV 390
Cdd:cd04969  60 KNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

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 24584041 294 ENVTLICRVHGSPNTVIAWDytNQVYesrskpvkslQKQRIyieLLREDESKirkfGHDVF--VSRLTIVNARKSDEGVY 371
Cdd:cd05765  16 ETASFHCDVTGRPQPEITWE--KQVP----------GKENL---IMRPNHVR----GNVVVtnIGQLVIYNAQPQDAGLY 76

                ....*....
gi 24584041 372 TCLAENPGG 380
Cdd:cd05765  77 TCTARNSGG 85

Fifth 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 fifth 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
                ....*....|....*....|....*....|....*
gi 24584041 358 LTIVNA-RKSDEGVYTCLAENPGG---KDSVHISV 388
Cdd:cd20958  55 LVIENVqRSSDEGEYTCTARNQQGqsaSRSVFVKV 89

Third 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 third 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 third 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 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, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

                        10        20
                ....*....|....*....|....*....
gi 24584041 357 RLTIVNARKSDEGVYTCLAENPGGKDSVH 385
Cdd:cd20977  59 RLLFKTTLPEDEGVYTCEVDNGVGKPQKH 87

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

                        10        20        30
                ....*....|....*....|....*....|....*
gi 24584041 356 SRLTIVNARKSDEGVYTCLAENPGGKDSVHISVVV 390
Cdd:cd05894  52 SSFVIEGAEREDEGVYTITVTNPVGEDHASLFVKV 86

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

                        10        20        30
                ....*....|....*....|....*....|....*
gi 24584041 356 SRLTIVNARKSDEGVYTCLAENPGGKDSVHISVVV 390
Cdd:cd05750  58 SELQINKAKLEDSGEYTCVVENILGKDTVTGNVTV 92

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. 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 24584041 278 PKIVYPTLSTSInTSKENVTLICRVHGSPNTVIAWDYTNqvyesrskpvkslqkqriyiELLREDESKIRKFGHDVFVSR 357
Cdd:cd05892   1 PMFIQKPQNKKV-LEGDPVRLECQISAIPPPQIFWKKNN--------------------EMLQYNTDRISLYQDNCGRIC 59

                        90       100
                ....*....|....*....|....*...
gi 24584041 358 LTIVNARKSDEGVYTCLAENPGGKDSVH 385
Cdd:cd05892  60 LLIQNANKKDAGWYTVSAVNEAGVVSCN 87

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584041    295 NVTLICRVHGS--PNTVIAWdytnqvyeSRSKPVKSLqkqriyiELLREDESKIRKFGHDVFVSR-------------LT 359
Cdd:smart00406   1 SVTLSCKFSGStfSSYYVSW--------VRQPPGKGL-------EWLGYIGSNGSSYYQESYKGRftiskdtskndvsLT 65

                           90
                   ....*....|....
gi 24584041    360 IVNARKSDEGVYTC 373
Cdd:smart00406  66 ISNLRVEDTGTYYC 79