Fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1). These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development. Neph1 and 2 may mediate axonal guidance and synapse formation in certain areas of the CNS. In the kidney they participate in the formation of the slit diaphragm.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568959971 418 GPPIISSTQTQHALHGEKGQIKCFIRSTPPPDRIAWSWKENVLESGTSGRYTVETVNTEEGVISTLTISNIVRADFQTIY 497
Cdd:cd05898    1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAWAWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFQTHY 80

                         90
                 ....*....|....*...
gi 568959971 498 NCTAWNSFGSDTEIIRLK 515
Cdd:cd05898   81 NCTAWNSFGSGTAIIQLE 98

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 568959971  335 PRMTSEPQSLLVDLGSDAVFSCAWIGNPSLTIVWMKRGS-------GVVLSNEK--TLTLKSVRQEDAGKYVCRAVVPrV 405
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQplrssdrFKVTYEGGtyTLTISNVQPDDSGKYTCVATNS-A 79

                          90
                  ....*....|.
gi 568959971  406 GAGEREVTLTV 416
Cdd:pfam07679  80 GEAEASAELTV 90

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 568959971 267 VTFHCSAKANPAVTqYRWAKRGHIIKEASGELYRTTVDYTYFSEPVS--------CEVTNALGsTNLSRTVDVYFG 334
Cdd:cd05850   23 VTLACRARASPPAT-YRWKMNGTELKMEPDSRYRLVAGNLVISNPVKakdagsyqCLASNRRG-TVVSREASLRFG 96

Fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1). These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development. Neph1 and 2 may mediate axonal guidance and synapse formation in certain areas of the CNS. In the kidney they participate in the formation of the slit diaphragm.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568959971 418 GPPIISSTQTQHALHGEKGQIKCFIRSTPPPDRIAWSWKENVLESGTSGRYTVETVNTEEGVISTLTISNIVRADFQTIY 497
Cdd:cd05898    1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAWAWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFQTHY 80

                         90
                 ....*....|....*...
gi 568959971 498 NCTAWNSFGSDTEIIRLK 515
Cdd:cd05898   81 NCTAWNSFGSGTAIIQLE 98

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568959971  335 PRMTSEPQSLLVDLGSDAVFSCAWIGNPSLTIVWMKRGS-------GVVLSNEK--TLTLKSVRQEDAGKYVCRAVVPrV 405
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQplrssdrFKVTYEGGtyTLTISNVQPDDSGKYTCVATNS-A 79

                          90
                  ....*....|.
gi 568959971  406 GAGEREVTLTV 416
Cdd:pfam07679  80 GEAEASAELTV 90

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568959971 341 PQSLLVDLGSDAVFSCAWIGNPSLTIVWMKRG------SGVVLSNEKTLTLKSVRQEDAGKYVC 398
Cdd:cd20957    8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGkplghsSRVQILSEDVLVIPSVKREDKGMYQC 71

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568959971  433 GEKGQIKCFIRSTPPPDrIAWSWKENVLESgtSGRYTVetvnTEEGVISTLTISNIVRADfQTIYNCTAWNSFGSDTEII 512
Cdd:pfam07679  15 GESARFTCTVTGTPDPE-VSWFKDGQPLRS--SDRFKV----TYEGGTYTLTISNVQPDD-SGKYTCVATNSAGEAEASA 86

                  ...
gi 568959971  513 RLK 515
Cdd:pfam07679  87 ELT 89

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568959971   49 SFSQQPQDQVVVSGQPVTLLCAI---PEYDgfVLWIKDglalgvGRDLSSYPQYLVVGNHlsGEHHLKILRAELQDDAVY 125
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVtgtPDPE--VSWFKD------GQPLRSSDRFKVTYEG--GTYTLTISNVQPDDSGKY 71

                  ....
gi 568959971  126 ECQA 129
Cdd:pfam07679  72 TCVA 75

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568959971  54 PQDQVVVSGQPVTLLCAI-----PEydgfVLWIKDGLALGVGRdlssypqylvvgNHLSGEHHLKILRAELQDDAVYECQ 128
Cdd:cd05725    4 PQNQVVLVDDSAEFQCEVggdpvPT----VRWRKEDGELPKGR------------YEILDDHSLKIRKVTAGDMGSYTCV 67

                         90
                 ....*....|....*..
gi 568959971 129 A--IQAAIRSRpARLTV 143
Cdd:cd05725   68 AenMVGKIEAS-ATLTV 83

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568959971 267 VTFHCSAKANPAVTqYRWAKRGHIIKEASGELYRTTVDYTYFSEPVS--------CEVTNALGsTNLSRTVDVYFG 334
Cdd:cd05850   23 VTLACRARASPPAT-YRWKMNGTELKMEPDSRYRLVAGNLVISNPVKakdagsyqCLASNRRG-TVVSREASLRFG 96

Fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1). These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development. Neph1 and 2 may mediate axonal guidance and synapse formation in certain areas of the CNS. In the kidney they participate in the formation of the slit diaphragm.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568959971 418 GPPIISSTQTQHALHGEKGQIKCFIRSTPPPDRIAWSWKENVLESGTSGRYTVETVNTEEGVISTLTISNIVRADFQTIY 497
Cdd:cd05898    1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAWAWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFQTHY 80

                         90
                 ....*....|....*...
gi 568959971 498 NCTAWNSFGSDTEIIRLK 515
Cdd:cd05898   81 NCTAWNSFGSGTAIIQLE 98

Fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (also known as Neph1), Kirrel2 (also known as Neph3), and Drosophila RST (also known as irregular chiasm C-roughest) protein. These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568959971 418 GPPIISSTQTQHALHGEKGQIKCFIRSTPPPDRIAWSWKENVLESGTSGRYTVETVNTEEGVISTLTISNIVRADFQTIY 497
Cdd:cd05758    1 GPPIITAEATQPAILGEKARLECLVFSSPPPDRIVWSWDEGFLESGSSGRFSVETFPTEPGVISVLHISGTQRSDFQTSF 80

                         90
                 ....*....|....*...
gi 568959971 498 NCTAWNSFGSDTEIIRLK 515
Cdd:cd05758   81 NCSAWNRFGEGTAIVSLG 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568959971  335 PRMTSEPQSLLVDLGSDAVFSCAWIGNPSLTIVWMKRG---------SGVVLSNEKTLTLKSVRQEDAGKYVCRA 400
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGepissgstrSRSLSGSNSTLTISNVTRSDAGTYTCVA 76

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568959971 341 PQSLLVDLGSDAVFSCAWIGNPSLTIVWMKRG------SGVVLSNEKTLTLKSVRQEDAGKYVC 398
Cdd:cd20957    8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGkplghsSRVQILSEDVLVIPSVKREDKGMYQC 71

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 568959971 335 PRMTSEPQSLLV-DLGSDAVFSCAWIGNPSLTIVWMKRGSGVVLSNEK------TLTLKSVRQEDAGKYVCRAvVPRVGA 407
Cdd:cd20978    1 PKFIQKPEKNVVvKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERatvedgTLTIINVQPEDTGYYGCVA-TNEIGD 79

                 ....*....
gi 568959971 408 GEREVTLTV 416
Cdd:cd20978   80 IYTETLLHV 88

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 568959971 337 MTSEPQSLLVDLGSDAVFSCAWIGNPSLTIVWMKRGSGVVLSNEK--------TLTLKSVRQEDAGKYVCRAVVPRVGAG 408
Cdd:cd20970    5 TPQPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRyivrengtTLTIRNIRRSDMGIYLCIASNGVPGSV 84

                 ....*...
gi 568959971 409 EREVTLTV 416
Cdd:cd20970   85 EKRITLQV 92

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568959971 337 MTSEPQSLLVDLGSDAVFSCAWIGNPSLTIVWMKRGSGVVLSNEK-------TLTLKSVRQEDAGKYVCRA 400
Cdd:cd20952    2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERittlengSLQIKGAEKSDTGEYTCVA 72

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568959971   426 QTQHALHGEKGQIKCFIRSTPPPdRIAWSWKENVLeSGTSGRYTVetvnTEEGVISTLTISNiVRADFQTIYNCTAWNSF 505
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPP-EVTWYKQGGKL-LAESGRFSV----SRSGSTSTLTISN-VTPEDSGTYTCAATNSS 74

                           90
                   ....*....|
gi 568959971   506 GSDTEIIRLK 515
Cdd:smart00410  75 GSASSGTTLT 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568959971  156 PVISLRAGDPLNLTCHADNAKPAASIIWLRKGEVINGATYSKtllrDGKRESIVSTLFISPGDVENGQSIVCRATNkaiP 235
Cdd:pfam00047   4 PTVTVLEGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVK----HDNGRTTQSSLLISNVTKEDAGTYTCVVNN---P 76

                  ....*....
gi 568959971  236 GGKETSVTI 244
Cdd:pfam00047  77 GGSATLSTS 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568959971   49 SFSQQPQDQVVVSGQPVTLLCAI---PEYDgfVLWIKDglalgvGRDLSSYPQYLVVGNHlsGEHHLKILRAELQDDAVY 125
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVtgtPDPE--VSWFKD------GQPLRSSDRFKVTYEG--GTYTLTISNVQPDDSGKY 71

                  ....
gi 568959971  126 ECQA 129
Cdd:pfam07679  72 TCVA 75

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568959971 348 LGSDAVFSCAWIGNPSLTIVWMKRGSGVVLSNEK-------TLTLKSVRQEDAGKYVCRaVVPRVGA 407
Cdd:cd05856   18 VGSSVRLKCVASGNPRPDITWLKDNKPLTPPEIGenkkkkwTLSLKNLKPEDSGKYTCH-VSNRAGE 83

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; 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 and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. 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 568959971 336 RMTSEPQSLLVDLGSDAVFSCAWIGNPSLTIVWMKRGSGVVLSN---------EKTLTLKSVRQEDAGKYVCrAVVPRVG 406
Cdd:cd05747    5 TILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQrhqitsteyKSTFEISKVQMSDEGNYTV-VVENSEG 83

                 ....*....
gi 568959971 407 AGEREVTLT 415
Cdd:cd05747   84 KQEAQFTLT 92

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. 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 568959971 336 RMTSEPQSLLVDLGSDAVFSCAWIGNPSLTIVWMKrGSGVVLSNEKTLTLKS-------VRQEDAGKYVCRAVVPRVGAG 408
Cdd:cd20968    1 KITRPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIK-GDDLIKENNRIAVLESgslrihnVQKEDAGQYRCVAKNSLGIAY 79

                 ....*...
gi 568959971 409 EREVTLTV 416
Cdd:cd20968   80 SKPVTIEV 87

CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568959971  150 PIILGGPVIsLRAGDP-LNLTCHADNAKPAASIIWLRKGEVINGATYSKTLLRDGKRESIVSTLFISPGDVENGQSIVCR 228
Cdd:pfam08205   1 PTIEPPASL-LEGEGPeVVATCSSAGGKPAPRITWYLDGKPLEAAETSSEQDPESGLVTVTSELKLVPSRSDHGQSLTCQ 79

                  ...
gi 568959971  229 ATN 231
Cdd:pfam08205  80 VSY 82

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 568959971 340 EPQSLLVDLGSDAVFSC-AWIGNPSLTIVWMKRGSGVVLSNEK-------TLTLKSVRQEDAGKYVCravVPRVGAGERE 411
Cdd:cd05724    3 EPSDTQVAVGEMAVLECsPPRGHPEPTVSWRKDGQPLNLDNERvrivddgNLLIAEARKSDEGTYKC---VATNMVGERE 79

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568959971  335 PRMTSEPQSllVDLGSDAVFSCAWIGNPSLTIVWMKRGSgvVLSNEKTLTLKSVRQEDAGKYVCRAVVPRVGAGEREVTL 414
Cdd:pfam13895   2 PVLTPSPTV--VTEGEPVTLTCSAPGNPPPSYTWYKDGS--AISSSPNFFTLSVSAEDSGTYTCVARNGRGGKVSNPVEL 77

                  ..
gi 568959971  415 TV 416
Cdd:pfam13895  78 TV 79

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 568959971 437 QIKCFIRSTPPPdRIAWSWKENVLESGTSGRYTVETVNteegviSTLTISNIVRADfQTIYNCTAWNSFGSDTE 510
Cdd:cd00096    2 TLTCSASGNPPP-TITWYKNGKPLPPSSRDSRRSELGN------GTLTISNVTLED-SGTYTCVASNSAGGSAS 67

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. 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 this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus 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 568959971 335 PRMTSEPQSLLVDLGSDAVFSCAWIGNPSLTIVWMKRGSGVVLSNEKT--------LTLKSVRQEDAGKYVCRAvVPRVG 406
Cdd:cd20976    2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRStceagvgeLHIQDVLPEDHGTYTCLA-KNAAG 80

                         90
                 ....*....|
gi 568959971 407 AGEREVTLTV 416
Cdd:cd20976   81 QVSCSAWVTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568959971   49 SFSQQPQDQVVVSGQPVTLLCAIPEYDG-FVLWIKDGLALGVGRDLSSYpqylvvgnHLSGEHHLKILRAELQDDAVYEC 127
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCEATGSPPpTITWYKNGEPISSGSTRSRS--------LSGSNSTLTISNVTRSDAGTYTC 74

                  ..
gi 568959971  128 QA 129
Cdd:pfam13927  75 VA 76

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 568959971 336 RMTSEPQSLLVDLGSDAVFSCAWIGNPSLTIVWMKRGSGVVLS---------NEKTLTLKSVRQEDAGKYVCRA 400
Cdd:cd20949    1 TFTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASvadmskyriLADGLLINKVTQDDTGEYTCRA 74

Immunoglobulin C1-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568959971  142 TVLVPPDDPiiLGGPVIslragdplnLTCHADNAKPAA-SIIWLRKG-EVINGATYSKTLLRDGKRESIVSTLFISPGDV 219
Cdd:pfam07654   2 YVFPPSPEE--LGKPNT---------LTCLVTGFYPPDiTVTWLKNGqEVTEGVKTTPPSPNSDWTYQLSSYLTVTPSDW 70

                          90
                  ....*....|....
gi 568959971  220 ENGQSIVCRATNKA 233
Cdd:pfam07654  71 ESGDEYTCRVEHEG 84

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 568959971 166 LNLTCHAdNAKPAASIIWLRKGEVINGATYSKTLLRDGKresivSTLFISPGDVENGQSIVCRATNKAipGGKETSVT 243
Cdd:cd00096    1 VTLTCSA-SGNPPPTITWYKNGKPLPPSSRDSRRSELGN-----GTLTISNVTLEDSGTYTCVASNSA--GGSASASV 70

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 568959971  48 YSFSQQPQDQVVVSGQPVTLLC-AIPEYDGFVLWIKDGLALGVGRDlSSYPQY----LVVGNHLSGEHHLKilraelqDD 122
Cdd:cd05722    2 LYFLSEPSDIVAMRGGPVVLNCsAESDPPPKIEWKKDGVLLNLVSD-ERRQQLpngsLLITSVVHSKHNKP-------DE 73