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 2220064140 392 GPPTISSTQTQQALHGEKGQIKCFIRSTPPPDRIAWSWKETVLESGTSGRYTVETVNTEEGVISTLTMSNIVPADFQTIY 471
Cdd:cd05898     1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAWAWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFQTHY 80

                          90
                  ....*....|....*...
gi 2220064140 472 NCTAWNSFGSDTEIIRLK 489
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 2220064140 309 PRMAAEPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGS-------GVVLSNENL--LTLKSVRQEDAGKYVCRAVVPrV 379
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQplrssdrFKVTYEGGTytLTISNVQPDDSGKYTCVATNS-A 79

                          90
                  ....*....|.
gi 2220064140 380 GAGEKEVSLTV 390
Cdd:pfam07679  80 GEAEASAELTV 90

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2220064140 228 LSVEPQPVLEGNLVKFHCSAKANPPVTfYRWAKGGSIIKEVTGD-TYEVIVDHS-FFTepvsCEVTNPLGSTnISRNVDV 305
Cdd:pfam13895   4 LTPSPTVVTEGEPVTLTCSAPGNPPPS-YTWYKDGSAISSSPNFfTLSVSAEDSgTYT----CVARNGRGGK-VSNPVEL 77

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 2220064140 392 GPPTISSTQTQQALHGEKGQIKCFIRSTPPPDRIAWSWKETVLESGTSGRYTVETVNTEEGVISTLTMSNIVPADFQTIY 471
Cdd:cd05898     1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAWAWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFQTHY 80

                          90
                  ....*....|....*...
gi 2220064140 472 NCTAWNSFGSDTEIIRLK 489
Cdd:cd05898    81 NCTAWNSFGSGTAIIQLE 98

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2220064140 309 PRMAAEPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGS-------GVVLSNENL--LTLKSVRQEDAGKYVCRAVVPrV 379
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQplrssdrFKVTYEGGTytLTISNVQPDDSGKYTCVATNS-A 79

                          90
                  ....*....|.
gi 2220064140 380 GAGEKEVSLTV 390
Cdd:pfam07679  80 GEAEASAELTV 90

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2220064140  315 PQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGSGVVLSNENL----------LTLKSVRQEDAGKYVCRAvVPRVGAGEK 384
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFsvsrsgststLTISNVTPEDSGTYTCAA-TNSSGSASS 79

                   ....*.
gi 2220064140  385 EVSLTV 390
Cdd:smart00410  80 GTTLTV 85

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 2220064140  22 QQPQDLVVVAGQPVTLPCTIPGYH--GVVLWIKDGLALgvgrDLSGYPRYTVigDHGSgehhLRIQRVELMDDAVFECQA 99
Cdd:cd05724     2 VEPSDTQVAVGEMAVLECSPPRGHpePTVSWRKDGQPL----NLDNERVRIV--DDGN----LLIAEARKSDEGTYKCVA 71

                          90
                  ....*....|....*.
gi 2220064140 100 --VQAAMRSRPARLTV 113
Cdd:cd05724    72 tnMVGERESRAARLSV 87

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2220064140 125 GPVVSLRAGDP-LNLTCHADNAKPAASIIWIRNGEVLNGAMyskVSIETFLrDGRRESTVSTLYLSPSNIETGQQIICKA 203
Cdd:pfam08205   5 PPASLLEGEGPeVVATCSSAGGKPAPRITWYLDGKPLEAAE---TSSEQDP-ESGLVTVTSELKLVPSRSDHGQSLTCQV 80

                  ..
gi 2220064140 204 SN 205
Cdd:pfam08205  81 SY 82

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2220064140  407 GEKGQIKCFIRSTPPPdRIAWSWKETVLeSGTSGRYTVetvnTEEGVISTLTMSNIVPADfQTIYNCTAWNSFGSDTEII 486
Cdd:smart00410   9 GESVTLSCEASGSPPP-EVTWYKQGGKL-LAESGRFSV----SRSGSTSTLTISNVTPED-SGTYTCAATNSSGSASSGT 81

                   ...
gi 2220064140  487 RLK 489
Cdd:smart00410  82 TLT 84

First immunoglobulin (Ig) domain of contactin-2; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2220064140 232 PQPVLEGNlVKFHCSAKANPPVTfYRWAKGGSIIKEVTGDTYEVIVDHSFFTEPVS--------CEVTNPLGsTNISRNV 303
Cdd:cd05850    15 PEGSAEEK-VTLACRARASPPAT-YRWKMNGTELKMEPDSRYRLVAGNLVISNPVKakdagsyqCLASNRRG-TVVSREA 91

                  ....*
gi 2220064140 304 DVYFG 308
Cdd:cd05850    92 SLRFG 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 2220064140 392 GPPTISSTQTQQALHGEKGQIKCFIRSTPPPDRIAWSWKETVLESGTSGRYTVETVNTEEGVISTLTMSNIVPADFQTIY 471
Cdd:cd05898     1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAWAWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFQTHY 80

                          90
                  ....*....|....*...
gi 2220064140 472 NCTAWNSFGSDTEIIRLK 489
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 2220064140 392 GPPTISSTQTQQALHGEKGQIKCFIRSTPPPDRIAWSWKETVLESGTSGRYTVETVNTEEGVISTLTMSNIVPADFQTIY 471
Cdd:cd05758     1 GPPIITAEATQPAILGEKARLECLVFSSPPPDRIVWSWDEGFLESGSSGRFSVETFPTEPGVISVLHISGTQRSDFQTSF 80

                          90
                  ....*....|....*...
gi 2220064140 472 NCTAWNSFGSDTEIIRLK 489
Cdd:cd05758    81 NCSAWNRFGEGTAIVSLG 98

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 2220064140 315 PQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRG------SGVVLSNENLLTLKSVRQEDAGKYVC 372
Cdd:cd20957     8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGkplghsSRVQILSEDVLVIPSVKREDKGMYQC 71

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2220064140   24 PQDLVVVAGQPVTLPCTIPGY-HGVVLWIKDGLALgvgrdLSGYPRYTVIGDHGSgeHHLRIQRVELMDDAVFECQAV-Q 101
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSpPPEVTWYKQGGKL-----LAESGRFSVSRSGST--STLTISNVTPEDSGTYTCAATnS 73

                           90
                   ....*....|..
gi 2220064140  102 AAMRSRPARLTV 113
Cdd:smart00410  74 SGSASSGTTLTV 85

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 2220064140 114 LVPPEDPVIGG--GPVVSlraGDPLNLTCHADNAKPAASIIWIRNGEVLNGAMYSKVSietflrDGRRESTV-STLYLSP 190
Cdd:cd05761     1 LGVPEKPVITGftSPVVE---GDEITLTCTTSGSKPAADIRWFKNDKELKGVKEVQES------GAGKTFTVtSTLRFRV 71

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2220064140 191 SNIETGQQIICKASNKAVPNG-KETSVTIDI 220
Cdd:cd05761    72 DRDDDGVAVICRVDHESLTSTpKQTQQVLEV 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 2220064140 311 MAAEPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGSGVVLSNEN--------LLTLKSVRQEDAGKYVCRAVVPRVGAG 382
Cdd:cd20970     5 TPQPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRyivrengtTLTIRNIRRSDMGIYLCIASNGVPGSV 84

                  ....*...
gi 2220064140 383 EKEVSLTV 390
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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2220064140 314 EPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGSGVVLSNENLLTL-------KSVRQEDAGKYVCravVPRVGAGEKEV 386
Cdd:cd20952     5 GPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLengslqiKGAEKSDTGEYTC---VALNLSGEATW 81

                  ....
gi 2220064140 387 SLTV 390
Cdd:cd20952    82 SAVL 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2220064140 407 GEKGQIKCFIRSTPPPDrIAWSWKETVLESgtSGRYTVetvnTEEGVISTLTMSNIVPADfQTIYNCTAWNSFGSDTEII 486
Cdd:pfam07679  15 GESARFTCTVTGTPDPE-VSWFKDGQPLRS--SDRFKV----TYEGGTYTLTISNVQPDD-SGKYTCVATNSAGEAEASA 86

                  ...
gi 2220064140 487 RLK 489
Cdd:pfam07679  87 ELT 89

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 2220064140 314 EPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGSGVVL--------------SNENLLTLKSVRQEDAGKYVCRAV 375
Cdd:cd05726     5 KPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQNLLfpyqppqpssrfsvSPTGDLTITNVQRSDVGYYICQAL 80

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2220064140 309 PRMAAEPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGSGV------------VLSNENLLTLKSV----RQEDAGKYVC 372
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLetdkddprshriVLPSGSLFFLRVVhgrkGRSDEGVYVC 80

                  ..
gi 2220064140 373 RA 374
Cdd:cd07693    81 VA 82

Second immunoglobulin (Ig)-like domain of nectin-like molecule-4 (Necl-4); 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-4 (Necl-4; also known as cell adhesion molecule 4 (CADM4)). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1-Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Ig domains are likely to participate in ligand binding and recognition. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. In injured peripheral nerve cells, the mRNA signal for both Necl-4 and Necl-5 was observed to be elevated. 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 2220064140 114 LVPPEDPVIGggpvVSLRA--GDPLNLTCHADNAKPAASIIWIRNGEVLNGAMYSKvsietflRDGRRESTVSTLYLSPS 191
Cdd:cd05885     1 LVAPENPVVE----VREQAveGGEVELSCLVPRSRPAATLRWYRDRKELKGVSSGQ-------ENGKVWSVASTVRFRVD 69

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2220064140 192 NIETGQQIICKASNKAVPNG--KETSVTIDI 220
Cdd:cd05885    70 RKDDGGIVICEAQNQALPSGhsKQTQYVLDV 100

Immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2220064140 393 PPTISS-TQTQQALHGEKGQIKCFIRSTPPPdRIAWSWKETVLESGTSGRYTVETVNTEEGVISTLTMSNIVPADfQTIY 471
Cdd:cd05735     3 PAMITSyPNTTLATKGQKKEMSCTAHGEKPI-IVRWEKEDTIINPSEMSRYLVTTKEVGDEVISTLQILPTVRED-SGFF 80

                          90       100
                  ....*....|....*....|
gi 2220064140 472 NCTAWNSFGSDTEIIRLKEQ 491
Cdd:cd05735    81 SCHAINSYGEDRGIIQLTVQ 100

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 2220064140 310 RMAAEPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGSGVVLSNENLLT---------LKSVRQEDAGKYvcrAVVPRVG 380
Cdd:cd05747     5 TILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITsteykstfeISKVQMSDEGNY---TVVVENS 81

                          90
                  ....*....|
gi 2220064140 381 AGEKEVSLTV 390
Cdd:cd05747    82 EGKQEAQFTL 91

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 2220064140 314 EPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGSGVVLS-----NENLLTLKSVRQEDAGKYVCRAvVPRVGAGEKEVSL 388
Cdd:cd05725     3 RPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGryeilDDHSLKIRKVTAGDMGSYTCVA-ENMVGKIEASATL 81

                  ..
gi 2220064140 389 TV 390
Cdd:cd05725    82 TV 83

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 2220064140 309 PRMAAEPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGSGVVLSNEN--------LLTLKSVRQEDAGKYVCRAvVPRVG 380
Cdd:cd20976     2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRstceagvgELHIQDVLPEDHGTYTCLA-KNAAG 80

                          90
                  ....*....|
gi 2220064140 381 AGEKEVSLTV 390
Cdd:cd20976    81 QVSCSAWVTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2220064140 393 PPTISST-QTQQALHGEKGQIKCFIRSTPPPdRIAWSWKETVLESGTSGRYTVETVNteegviSTLTMSNIVPADFQTiY 471
Cdd:pfam13927   1 KPVITVSpSSVTVREGETVTLTCEATGSPPP-TITWYKNGEPISSGSTRSRSLSGSN------STLTISNVTRSDAGT-Y 72

                  ....*.
gi 2220064140 472 NCTAWN 477
Cdd:pfam13927  73 TCVASN 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2220064140  20 FSQQPQDLVVVAGQPVTLPCTIPGY-HGVVLWIKDGLALGVGRDLSGYprytvigdHGSGEHHLRIQRVELMDDAVFECQ 98
Cdd:pfam13927   4 ITVSPSSVTVREGETVTLTCEATGSpPPTITWYKNGEPISSGSTRSRS--------LSGSNSTLTISNVTRSDAGTYTCV 75

                  .
gi 2220064140  99 A 99
Cdd:pfam13927  76 A 76

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2220064140 128 VSLRAGDPLNLTCHADnAKPAASIIWIRNGEVLngamyskvsIETFLRDGRRESTVSTLYLSPSNIETGQQIICKASN 205
Cdd:pfam13927  11 VTVREGETVTLTCEAT-GSPPPTITWYKNGEPI---------SSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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 2220064140 113 VLVPPEDPVIGG--GPVVSlraGDPLNLTCHADNAKPAASIIWIRNGEVLNGAMYSKVSietflRDGRRESTV-STLYLS 189
Cdd:cd05884     1 VLGVPEKPQISGftSPVME---GDHIQLTCKTSGSKPAADIRWFKNDKEVKDVKYLKAE-----DANRKTFTVsSSLDFH 72

                          90
                  ....*....|....*....
gi 2220064140 190 PSNIETGQQIICKASNKAV 208
Cdd:cd05884    73 VDRDDDGVAITCRVDHESL 91

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2220064140 309 PRMAAEPQSLQVDLGSDAVFNCAWTGNPSLTIVWMKRGSGV-------VLSNEN---LLTLKSVRQEDAGKYVCRAvvpR 378
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVrpdsahkMLVRENgrhSLIIEPVTKRDAGIYTCIA---R 77

                          90
                  ....*....|...
gi 2220064140 379 VGAGEKEVSLTVN 391
Cdd:cd05744    78 NRAGENSFNAELV 90

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 2220064140  24 PQDLVVVAGQPVTLPCTI-----PGyhgvVLWIKDGLALGVGRdlsgyprYTVIGDHGsgehhLRIQRVELMDDAVFECQ 98
Cdd:cd05725     4 PQNQVVLVDDSAEFQCEVggdpvPT----VRWRKEDGELPKGR-------YEILDDHS-----LKIRKVTAGDMGSYTCV 67

                          90
                  ....*....|....*...
gi 2220064140  99 A---VQAAMRSrpARLTV 113
Cdd:cd05725    68 AenmVGKIEAS--ATLTV 83