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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 14149694    267 LGGTALLRCGATGVPGPEMSWRRANGRPLNGTVHQEVSSDGTSWTLLgLPAVSHLDSGDYICQAKNFLGASETVISLIV 345
Cdd:smart00410   8 EGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLT-ISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 14149694    431 VRSVKVVGDTYHSVSLVWKAPQAKNTTAFSVLYAVFGQ---HSMRRVIVQPGKTRVTITGLLPKTKYVACV 498
Cdd:smart00060   4 PSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYReegSEWKEVNVTPSSTSYTLTGLKPGTEYEFRV 74

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 14149694    267 LGGTALLRCGATGVPGPEMSWRRANGRPLNGTVHQEVSSDGTSWTLLgLPAVSHLDSGDYICQAKNFLGASETVISLIV 345
Cdd:smart00410   8 EGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLT-ISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 14149694   262 SIRSLLGGTALLRCGATGVPGPEMSWRRaNGRPLNGTVHQEVSSDGTSWTLLgLPAVSHLDSGDYICQAKN 332
Cdd:pfam13927  10 SVTVREGETVTLTCEATGSPPPTITWYK-NGEPISSGSTRSRSLSGSNSTLT-ISNVTRSDAGTYTCVASN 78

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 14149694    431 VRSVKVVGDTYHSVSLVWKAPQAKNTTAFSVLYAVFGQ---HSMRRVIVQPGKTRVTITGLLPKTKYVACV 498
Cdd:smart00060   4 PSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYReegSEWKEVNVTPSSTSYTLTGLKPGTEYEFRV 74

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 14149694 431 VRSVKVVGDTYHSVSLVWKAPQAKNT--TAFSVLYAVFGQHSMRRVIVQPGK-TRVTITGLLPKTKYVACV 498
Cdd:cd00063   4 PTNLRVTDVTSTSVTLSWTPPEDDGGpiTGYVVEYREKGSGDWKEVEVTPGSeTSYTLTGLKPGTEYEFRV 74

Leucine rich repeat C-terminal domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 14149694    201 NPWACDCRLYDLVHLLDgwAPNLAFIETELRCASPRSLAG 240
Cdd:smart00082   1 NPFICDCELRWLLRWLQ--ANEHLQDPVDLRCASPSSLRG 38

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 14149694    267 LGGTALLRCGATGVPGPEMSWRRANGRPLNGTVHQEVSSDGTSWTLLgLPAVSHLDSGDYICQAKNFLGASETVISLIV 345
Cdd:smart00410   8 EGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLT-ISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14149694 262 SIRSLLGGTALLRCGATGVPGPEMSWRRANGRPLNGTVHQEvSSDGTswtlLGLPAVSHLDSGDYICQAKNFLGASETVI 341
Cdd:cd05731   4 STMVLRGGVLLLECIAEGLPTPDIRWIKLGGELPKGRTKFE-NFNKT----LKIENVSEADSGEYQCTASNTMGSARHTI 78

                ....
gi 14149694 342 SLIV 345
Cdd:cd05731  79 SVTV 82

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 14149694   268 GGTALLRCGATGVPGPEMSWRRaNGRPLNGTVHQEVSSDGTSWTLLGLPAVSHlDSGDYICQAKNFLGASETVISLIV 345
Cdd:pfam07679  15 GESARFTCTVTGTPDPEVSWFK-DGQPLRSSDRFKVTYEGGTYTLTISNVQPD-DSGKYTCVATNSAGEAEASAELTV 90

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14149694  63 RLRLERTAIRRVPgEAFRPLGRLEQLWLPYNALS-------------ELNALmlrglrrlrelrlpGNRLAAFPwAALRD 129
Cdd:COG4886 163 SLDLSNNQLTDLP-EELGNLTNLKELDLSNNQITdlpeplgnltnleELDLS--------------GNQLTDLP-EPLAN 226

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 14149694 130 APKLRLLDLQANRLSAVPAEAArfLENLTFLDLSSNQLMRLPQEL 174
Cdd:COG4886 227 LTNLETLDLSNNQLTDLPELGN--LTNLEELDLSNNQLTDLPPLA 269

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 14149694 268 GGTALLRCGATGVPGPEMSWRRANGRPLNGTVHQEVSSDGtswTLLGLPAVSHLDSGDYICQAKN-FLGASETVISLIV 345
Cdd:cd20970  17 GENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENG---TTLTIRNIRRSDMGIYLCIASNgVPGSVEKRITLQV 92

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14149694 267 LGGTALLRCGATGVPGPEMSWRRaNGRPLNGTVHQEVSSDGTSwTLLGLPAVSHLDSGDYICQAKNFLGASETVISLIVT 346
Cdd:cd05736  14 PGVEASLRCHAEGIPLPRVQWLK-NGMDINPKLSKQLTLIANG-SELHISNVRYEDTGAYTCIAKNEGGVDEDISSLFVE 91

                .
gi 14149694 347 E 347
Cdd:cd05736  92 D 92

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 14149694    431 VRSVKVVGDTYHSVSLVWKAPQAKNTTAFSVLYAVFGQ---HSMRRVIVQPGKTRVTITGLLPKTKYVACV 498
Cdd:smart00060   4 PSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYReegSEWKEVNVTPSSTSYTLTGLKPGTEYEFRV 74

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 14149694 266 LLGGTALLRCGATGVPGPEMSWRRaNGRPLNGTVHQEVSSDGTSWTLlglpAVSHLDSGDYICQAKNFLGASETVISLIV 345
Cdd:cd20978  14 KGGQDVTLPCQVTGVPQPKITWLH-NGKPLQGPMERATVEDGTLTII----NVQPEDTGYYGCVATNEIGDIYTETLLHV 88

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 14149694 268 GGTALLRCGATGVPGPEMSWRrangrpLNGTVHQEVSSDGTSW---TLLGLPAVSHLDSGDYICQAKNFLG 335
Cdd:cd04978  14 GETGELICEAEGNPQPTITWR------LNGVPIEPAPEDMRRTvdgRTLIFSNLQPNDTAVYQCNASNVHG 78

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 14149694 261 ASIRSLLGGTALLRCGATGVPGPEMSWRRANGRPLNGTVHQevssdgTSWTLLGLPAVSHLDSGDYICQAKNFLG 335
Cdd:cd04968   9 ADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWEIT------TSEPVLEIPNVQFEDEGTYECEAENSRG 77

Second 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 second 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 the 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 (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, 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 Slit-2 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14149694 261 ASIRSLLGGTALLRCGA-TGVPGPEMSWRRaNGRPLN-GTVHQEVSSDGTswtlLGLPAVSHLDSGDYICQAKNFLGASE 338
Cdd:cd05724   5 SDTQVAVGEMAVLECSPpRGHPEPTVSWRK-DGQPLNlDNERVRIVDDGN----LLIAEARKSDEGTYKCVATNMVGERE 79

                .
gi 14149694 339 T 339
Cdd:cd05724  80 S 80

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 14149694 268 GGTALLRCGATGVPGPEMSWRRA------NGRPLNGtvHQEVSSDGTSwTLLGLPAVSHLDSGDYICQAKNFLG 335
Cdd:cd05732  16 LEQITLTCEAEGDPIPEITWRRAtrgisfEEGDLDG--RIVVRGHARV-SSLTLKDVQLTDAGRYDCEASNRIG 86

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 14149694 263 IRSLLGGTALLRCGATGVPGPEMSWRRANgRPLNGTVhqEVSSDGtswTLLGLPAVSHLDSGDYICQAKNFLG 335
Cdd:cd05851  11 TYALKGQNVTLECFALGNPVPVIRWRKIL-EPMPATA--EISMSG---AVLKIFNIQPEDEGTYECEAENIKG 77

Leucine rich repeat;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 14149694   131 PKLRLLDLQANRLSAVPAEAARFLENLTFLDLSSNQLMRLPQELIVSWAHLE 182
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLR 52

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third 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. 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. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 14149694 255 ELHPGVASIRslLGGTALLRCGATGVPGPEMSWRRaNGRPLNGTVHQEVSSDGTswtlLGLPAVSHLDSGDYICQAKN 332
Cdd:cd20957   5 TIDPPVQTVD--FGRTAVFNCSVTGNPIHTVLWMK-DGKPLGHSSRVQILSEDV----LVIPSVKREDKGMYQCFVRN 75

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14149694 265 SLLGGTALLRCGATGVPGPEMSWRRANG-RPLNGTVHQevssDGTSWtlLGLPAVSHLDSGDYICQAKNFLGASETVISL 343
Cdd:cd05876   7 ALRGQSLVLECIAEGLPTPTVKWLRPSGpLPPDRVKYQ----NHNKT--LQLLNVGESDDGEYVCLAENSLGSARHAYYV 80

                ..
gi 14149694 344 IV 345
Cdd:cd05876  81 TV 82

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 14149694 268 GGTALLRCGATGVPGPEMSWRRaNGRPLN-GTVHQEVSSDGTSWTLLgLPAVSHLDSGDYICQAKNFLGASETVISLIV 345
Cdd:cd05744  15 GRLCRFDCKVSGLPTPDLFWQL-NGKPVRpDSAHKMLVRENGRHSLI-IEPVTKRDAGIYTCIARNRAGENSFNAELVV 91

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 14149694 268 GGTALLRCGATGVPGPEMSWRRANG------RPLNGTVHQEVSSDGTswtlLGLPAVSHLDSGDYICQAKNFLGA 336
Cdd:cd20954  16 GQDVMLHCQADGFPTPTVTWKKATGstpgeyKDLLYDPNVRILPNGT----LVFGHVQKENEGHYLCEAKNGIGS 86

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. 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 titin Z1z2 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 14149694 254 PELHPGVASIRSLLGGTALLRCGATGVPGPEMSWRRaNGRPLNGTVHQEV---SSDGTSwtLLGLPAVSHLDSGDYICQA 330
Cdd:cd20974   1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFR-DGQVISTSTLPGVqisFSDGRA--KLSIPAVTKANSGRYSLTA 77

                        90
                ....*....|....*.
gi 14149694 331 KNFLGASETVISLIVT 346
Cdd:cd20974  78 TNGSGQATSTAELLVL 93

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. 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 titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 14149694 268 GGTALLRCGATGVPGPEMSWRRaNGRPLNGTVHQEVSSDGTSWTLLGLPAVSHlDSGDYICQAKNFLGASETVISLIV 345
Cdd:cd20972  16 GSKVRLECRVTGNPTPVVRWFC-EGKELQNSPDIQIHQEGDLHSLIIAEAFEE-DTGRYSCLATNSVGSDTTSAEIFV 91

Fourth 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 fourth 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 14149694 268 GGTALLRCGATGVPGPEMSWRRaNGRPLNGT----VHQEVSSDGTswtllglpAVSHL--------DSGDYICQAKNFLG 335
Cdd:cd20956  16 GPSVSLKCVASGNPLPQITWTL-DGFPIPESprfrVGDYVTSDGD--------VVSYVnissvrveDGGEYTCTATNDVG 86

                .
gi 14149694 336 A 336
Cdd:cd20956  87 S 87

Leucine rich repeat C-terminal domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 14149694    201 NPWACDCRLYDLVHLLDgwAPNLAFIETELRCASPRSLAG 240
Cdd:smart00082   1 NPFICDCELRWLLRWLQ--ANEHLQDPVDLRCASPSSLRG 38

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14149694 258 PGVASIRSllGGTALLRCGATGVPGPEMSWRRaNGRPLNGTVHQEVSSDGTSWTLLGLPAVSHLDSGDYICQAKNFLGaS 337
Cdd:cd05737   8 PDVVTIME--GKTLNLTCNVWGDPPPEVSWLK-NDQALAFLDHCNLKVEAGRTVYFTINGVSSEDSGKYGLVVKNKYG-S 83

                ..
gi 14149694 338 ET 339
Cdd:cd05737  84 ET 85

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. 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. The Ig-like domain of the Twitchin is a member of the I-set 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. 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 14149694 268 GGTALLRCGATGVPGPEMSWRRaNGRPLNGTVHQEVSSDGTSWTLLgLPAVSHLDSGDYICQAKNFLGASETVISLIV 345
Cdd:cd20949  14 GQSATILCEVKGEPQPNVTWHF-NGQPISASVADMSKYRILADGLL-INKVTQDDTGEYTCRAYQVNSIASDMQERTV 89

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. 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 14149694 268 GGTALLRCGATGVPGPEMSWRRAN--------GRPLNGTVhqEVSSDGTSwTLLGLPAVSHLDSGDYICQAKNFLGASET 339
Cdd:cd05870  16 NGAATLSCKAEGEPIPEITWKRASdghtfsegDKSPDGRI--EVKGQHGE-SSLHIKDVKLSDSGRYDCEAASRIGGHQK 92

                ....
gi 14149694 340 VISL 343
Cdd:cd05870  93 SMYL 96