Second 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 second 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 (Neph1), Kirrel2 (Neph3), and Drosophila RST (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 2038251889 146 DPVITGGPVISIRAGDPLNLTCHADNAKPAATITWMKNGEVLNGATYYKTLLRDGKRESIISTLFVSSSEIENGQTITCR 225
Cdd:cd05759     1 DPVIEGGPVISLQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFTCR 80

                          90
                  ....*....|....*...
gi 2038251889 226 ATNKAVPGGKETTVTINI 243
Cdd:cd05759    81 ARNEAIPNGKETSITLDV 98

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2038251889   51 PQDQVVVAGQPVSLLCAIPGY-HGLLLWIKDGlaigvGRDLSGYPRYSVggDHLSGEHHLMIQRAELQDDAMYECQAIQA 129
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSpPPEVTWYKQG-----GKLLAESGRFSV--SRSGSTSTLTISNVTPEDSGTYTCAATNS 73

                           90
                   ....*....|..
gi 2038251889  130 AI-RSRPARLTV 140
Cdd:smart00410  74 SGsASSGTTLTV 85

Second 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 second 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 (Neph1), Kirrel2 (Neph3), and Drosophila RST (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 2038251889 146 DPVITGGPVISIRAGDPLNLTCHADNAKPAATITWMKNGEVLNGATYYKTLLRDGKRESIISTLFVSSSEIENGQTITCR 225
Cdd:cd05759     1 DPVIEGGPVISLQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFTCR 80

                          90
                  ....*....|....*...
gi 2038251889 226 ATNKAVPGGKETTVTINI 243
Cdd:cd05759    81 ARNEAIPNGKETSITLDV 98

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2038251889  338 PESITVDLGSDATFHCAWIGNPSLTIVWMK----------RGSGVVLSNENTLTLRNVRQEDAGKYVCRAvVPRVGAGER 407
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKqggkllaesgRFSVSRSGSTSTLTISNVTPEDSGTYTCAA-TNSSGSASS 79

                   ....*.
gi 2038251889  408 DITLTV 413
Cdd:smart00410  80 GTTLTV 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2038251889 147 PVITGGPV-ISIRAGDPLNLTCHADnAKPAATITWMKNGEVLNGATYYKTLLRDGkresiISTLFVSSSEIENGQTITCR 225
Cdd:pfam07679   1 PKFTQKPKdVEVQEGESARFTCTVT-GTPDPEVSWFKDGQPLRSSDRFKVTYEGG-----TYTLTISNVQPDDSGKYTCV 74

                          90
                  ....*....|....*...
gi 2038251889 226 ATNKAvpGGKETTVTINI 243
Cdd:pfam07679  75 ATNSA--GEAEASAELTV 90

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 2038251889  49 QQPQDQVVVAGQPVSLLCAIPGYHG--LLLWIKDGLAIgvgrDLSGYPRYSVGGDHLsgehhlMIQRAELQDDAMYECQA 126
Cdd:cd05724     2 VEPSDTQVAVGEMAVLECSPPRGHPepTVSWRKDGQPL----NLDNERVRIVDDGNL------LIAEARKSDEGTYKCVA 71

                          90
                  ....*....|....*.
gi 2038251889 127 --IQAAIRSRPARLTV 140
Cdd:cd05724    72 tnMVGERESRAARLSV 87

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2038251889 430 GEKGQIKCFIRSTPPPDrIAWSWKENVLESgtSGRYTVetvsTDEGVISTLTISNIVRADfQTIYNCTAWNSFGSDTEII 509
Cdd:pfam07679  15 GESARFTCTVTGTPDPE-VSWFKDGQPLRS--SDRFKV----TYEGGTYTLTISNVQPDD-SGKYTCVATNSAGEAEASA 86

                  ...
gi 2038251889 510 RLK 512
Cdd:pfam07679  87 ELT 89

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2038251889  46 SFTQQPQDQVVVAGQPVSLLCAIPGYHGLLL-WIKDGLAIGVGRdlsgypRYSVggDHLSGEHHLMIQRAELQDDAMYEC 124
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVTGTPDPEVsWFKDGQPLRSSD------RFKV--TYEGGTYTLTISNVQPDDSGKYTC 73

                  ..
gi 2038251889 125 QA 126
Cdd:pfam07679  74 VA 75

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 2038251889 415 GPPIISSTQTQHALHGEKGQIKCFIRSTPPPDRIAWSWKENVLESGTSGRYTVETVSTDEGVISTLTISNIVRADFQTIY 494
Cdd:cd05758     1 GPPIITAEATQPAILGEKARLECLVFSSPPPDRIVWSWDEGFLESGSSGRFSVETFPTEPGVISVLHISGTQRSDFQTSF 80

                          90
                  ....*....|....*...
gi 2038251889 495 NCTAWNSFGSDTEIIRLK 512
Cdd:cd05758    81 NCSAWNRFGEGTAIVSLG 98

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2038251889 332 PRMSSEPESITVDLGSDATFHCAWIGNPSLTIVWMKRGS-------GVVLSNEN--TLTLRNVRQEDAGKYVCRAVVPrV 402
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQplrssdrFKVTYEGGtyTLTISNVQPDDSGKYTCVATNS-A 79

                          90
                  ....*....|.
gi 2038251889 403 GAGERDITLTV 413
Cdd:pfam07679  80 GEAEASAELTV 90

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2038251889 141 LVPPDDPVITG--GPVisiRAGDPLNLTCHADNAKPAATITWMKNGEVLNGATYYKTlLRDGKRESIISTLFVSSSEIEN 218
Cdd:cd05761     1 LGVPEKPVITGftSPV---VEGDEITLTCTTSGSKPAADIRWFKNDKELKGVKEVQE-SGAGKTFTVTSTLRFRVDRDDD 76

                          90       100
                  ....*....|....*....|....*.
gi 2038251889 219 GQTITCRATNKAVPGG-KETTVTINI 243
Cdd:cd05761    77 GVAVICRVDHESLTSTpKQTQQVLEV 102

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 2038251889 334 MSSEPESITVDLGSDATFHCAWIGNPSLTIVWMKRGSGVVLSNEN--------TLTLRNVRQEDAGKYVCRAVVPRVGAG 405
Cdd:cd20970     5 TPQPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRyivrengtTLTIRNIRRSDMGIYLCIASNGVPGSV 84

                  ....*...
gi 2038251889 406 ERDITLTV 413
Cdd:cd20970    85 EKRITLQV 92

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 2038251889 332 PRMSSEPES-ITVDLGSDATFHCAWIGNPSLTIVWMKRG------SGVVLSNENTLTLRNVRQEDAGKYVCRAvVPRVGA 404
Cdd:cd20978     1 PKFIQKPEKnVVVKGGQDVTLPCQVTGVPQPKITWLHNGkplqgpMERATVEDGTLTIINVQPEDTGYYGCVA-TNEIGD 79

                  ....*....
gi 2038251889 405 GERDITLTV 413
Cdd:cd20978    80 IYTETLLHV 88

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 2038251889 349 ATFHCAWIGNPSLTIVWMKRGSGV---------VLSNENTLTLRNVRQEDAGKYVCRAVVPRVGAGERDI 409
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLppssrdsrrSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3; also known as cell adhesion molecule 2 (CADM2)). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Ig domains are likely to participate in ligand binding and recognition.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2038251889 140 VLVPPDDPVITG--GPVISiraGDPLNLTCHADNAKPAATITWMKNGEVLNGATYYKTLLRDGKRESIISTLFVSSSEIE 217
Cdd:cd05884     1 VLGVPEKPQISGftSPVME---GDHIQLTCKTSGSKPAADIRWFKNDKEVKDVKYLKAEDANRKTFTVSSSLDFHVDRDD 77

                          90       100
                  ....*....|....*....|....
gi 2038251889 218 NGQTITCRATNKAVPGGKETTVTI 241
Cdd:cd05884    78 DGVAITCRVDHESLTATPQIAMQV 101

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 2038251889 336 SEPESITVDLGSDATFHCAWIGNPSLTIVWMKRGSGVVLS-----NENTLTLRNVRQEDAGKYVCRAvVPRVGAGERDIT 410
Cdd:cd05725     2 KRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGryeilDDHSLKIRKVTAGDMGSYTCVA-ENMVGKIEASAT 80

                  ...
gi 2038251889 411 LTV 413
Cdd:cd05725    81 LTV 83

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2038251889 147 PVITGGPVISIRAGDPLNLTCHADNAKPAATITWMKNGEVLNGATYYKTLLRDGKRESIISTLFVSSSEIENGQTITCRA 226
Cdd:pfam08205   1 PTIEPPASLLEGEGPEVVATCSSAGGKPAPRITWYLDGKPLEAAETSSEQDPESGLVTVTSELKLVPSRSDHGQSLTCQV 80

                  ..
gi 2038251889 227 TN 228
Cdd:pfam08205  81 SY 82

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2038251889 337 EPESITVDLGSDATFHCAWIGNPSLTIVWMKRGSGVVL--------------SNENTLTLRNVRQEDAGKYVCRAV 398
Cdd:cd05726     5 KPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQNLLfpyqppqpssrfsvSPTGDLTITNVQRSDVGYYICQAL 80

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 2038251889  49 QQPQDQVVVAGQPVSLLCAIPGYHG--LLLWIKDGLAIgvgrDLSGYPRYSVGGDHLsgehhlMIQRAELQDDAMYECQA 126
Cdd:cd05724     2 VEPSDTQVAVGEMAVLECSPPRGHPepTVSWRKDGQPL----NLDNERVRIVDDGNL------LIAEARKSDEGTYKCVA 71

                          90
                  ....*....|....*.
gi 2038251889 127 --IQAAIRSRPARLTV 140
Cdd:cd05724    72 tnMVGERESRAARLSV 87

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2038251889 147 PVITGgPVISIRAGDPLNLTCHADNaKPAATITWMKNGEVLNGATyyktllrdgkresiisTLFVSSSEIENGQTITCRA 226
Cdd:pfam13895   2 PVLTP-SPTVVTEGEPVTLTCSAPG-NPPPSYTWYKDGSAISSSP----------------NFFTLSVSAEDSGTYTCVA 63

                          90
                  ....*....|....*..
gi 2038251889 227 TNKAVpGGKETTVTINI 243
Cdd:pfam13895  64 RNGRG-GKVSNPVELTV 79

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2038251889 337 EPESITVDLGSDATFHC-AWIGNPSLTIVWmKRGSGVVLSNE----NTLTLRNVRQEDAGKYVC 395
Cdd:cd05754     7 EPRSQEVRPGADVSFICrAKSKSPAYTLVW-TRVNGTLPSRAmdfnGILTIRNVQLSDAGTYVC 69

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2038251889 430 GEKGQIKCFIRSTPPPDrIAWSWKENVLESgtSGRYTVetvsTDEGVISTLTISNIVRADfQTIYNCTAWNSFGSDTEII 509
Cdd:pfam07679  15 GESARFTCTVTGTPDPE-VSWFKDGQPLRS--SDRFKV----TYEGGTYTLTISNVQPDD-SGKYTCVATNSAGEAEASA 86

                  ...
gi 2038251889 510 RLK 512
Cdd:pfam07679  87 ELT 89

Second immunoglobulin (Ig)-like domain of nectin-like molcule-1 (Necl-1); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molcule-1 (Necl-1; also known as cell adhesion molecule3 (CADM3)). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains is essential to cell-cell adhesion and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2038251889 144 PDDPVITGGpVISIRAGDPLNLTCHADNAKPAATITWMKNGEVLNGATyyKTLLRDGKRESiistlFVSSSEIE------ 217
Cdd:cd07705     4 PQKPQITGY-ESAFKEKDKAKLRCTSSGSKPAANIKWRKGDQELEGAP--TSVQEDGNGKT-----FTVSSSVEfqvtre 75

                          90       100
                  ....*....|....*....|..
gi 2038251889 218 -NGQTITCRATNKAVPGGKETT 238
Cdd:cd07705    76 dDGAEITCSVGHESLHDSDRST 97

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 2038251889 163 LNLTCHAdNAKPAATITWMKNGEVLNGATYYKTLLRDGKresiiSTLFVSSSEIENGQTITCRATNKAvpGGKETTVT 240
Cdd:cd00096     1 VTLTCSA-SGNPPPTITWYKNGKPLPPSSRDSRRSELGN-----GTLTISNVTLEDSGTYTCVASNSA--GGSASASV 70

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2038251889  46 SFTQQPQDQVVVAGQPVSLLCAIPGYHGLLL-WIKDGLAIGVGRdlsgypRYSVggDHLSGEHHLMIQRAELQDDAMYEC 124
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVTGTPDPEVsWFKDGQPLRSSD------RFKV--TYEGGTYTLTISNVQPDDSGKYTC 73

                  ..
gi 2038251889 125 QA 126
Cdd:pfam07679  74 VA 75

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2038251889 332 PRMSSEPESITVDLGSDATFHCAWIGNPSLTIVWMKRGSGVVLSNENTLTLRNV----------------RQEDAGKYVC 395
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKDDPRSHRIVlpsgslfflrvvhgrkGRSDEGVYVC 80

                          90
                  ....*....|....*...
gi 2038251889 396 RAVVPRVGAGERDITLTV 413
Cdd:cd07693    81 VAHNSLGEAVSRNASLEV 98

Second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2; also known as cell adhesion molecule 1 (CADM1)). Nectin-like molecules (Necls) have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-2 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2038251889 141 LVPPDDPVITGGPVISIRaGDPLNLTCHADNAKPAATITWMKNGEVLNGATYYKTLLRDGKResIISTLFVSSSEIENGQ 220
Cdd:cd05883     1 LVPPRNLVIDIQKDTAVE-GEEIELNCTAMASKPAATIRWFKGNKELTGKSEVEEWYSRMFT--VTSQLMLKVTKEDDGV 77

                          90
                  ....*....|...
gi 2038251889 221 TITCRATNKAVPG 233
Cdd:cd05883    78 PVICLVDHPAVKD 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2038251889 416 PPIISST-QTQHALHGEKGQIKCFIRSTPPPdRIAWSWKENVLESGTSGRYTVETVStdegviSTLTISNIVRADFQTiY 494
Cdd:pfam13927   1 KPVITVSpSSVTVREGETVTLTCEATGSPPP-TITWYKNGEPISSGSTRSRSLSGSN------STLTISNVTRSDAGT-Y 72

                  ....*.
gi 2038251889 495 NCTAWN 500
Cdd:pfam13927  73 TCVASN 78

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2038251889 333 RMSSEPESITVDLGSDATFHCAWIGNPSLTIVWMKrGSGVVLSN-------ENTLTLRNVRQEDAGKYVCRA 397
Cdd:cd20968     1 KITRPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIK-GDDLIKENnriavleSGSLRIHNVQKEDAGQYRCVA 71

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2038251889 332 PRMSSEPESITVDLGSDATFHCAWIGNPSLTIVWMKRGSGVVLSNENT--------LTLRNVRQEDAGKYVCRA 397
Cdd:cd20976     2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRStceagvgeLHIQDVLPEDHGTYTCLA 75

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 2038251889 333 RMSSEPESITVDLGSDATFHCAWIGNPSLTIVWMKRGSGVVLSN---------ENTLTLRNVRQEDAGKYVCrAVVPRVG 403
Cdd:cd05747     5 TILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQrhqitsteyKSTFEISKVQMSDEGNYTV-VVENSEG 83

                  ....*....
gi 2038251889 404 AGERDITLT 412
Cdd:cd05747    84 KQEAQFTLT 92