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 1768008261 122 APQVLGGPSVSLVAGVPGNLTCRSRGdARPAPELLWFRDGIRLDGTSFHQTILKDKATGTVENILFLTPSSHDDGTTLIC 201
Cdd:cd05759     1 DPVIEGGPVISLQAGVPYNLTCRARG-AKPAAEIIWFRDGEQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFTC 79

                          90
                  ....*....|....*....
gi 1768008261 202 RARSQALPTGRDTAVTLSL 220
Cdd:cd05759    80 RARNEAIPNGKETSITLDV 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 1768008261   27 PEDMVVLLGQEARLPCSL-GAYRGLVQWTKDGLALGGERDlpgwsRYwiSGNSASGQHDLHIKPVELEDEASYECQAS-Q 104
Cdd:smart00410   1 PPSVTVKEGESVTLSCEAsGSPPPEVTWYKQGGKLLAESG-----RF--SVSRSGSTSTLTISNVTPEDSGTYTCAATnS 73

                           90
                   ....*....|..
gi 1768008261  105 AGLRSRPAQLHV 116
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 1768008261 122 APQVLGGPSVSLVAGVPGNLTCRSRGdARPAPELLWFRDGIRLDGTSFHQTILKDKATGTVENILFLTPSSHDDGTTLIC 201
Cdd:cd05759     1 DPVIEGGPVISLQAGVPYNLTCRARG-AKPAAEIIWFRDGEQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFTC 79

                          90
                  ....*....|....*....
gi 1768008261 202 RARSQALPTGRDTAVTLSL 220
Cdd:cd05759    80 RARNEAIPNGKETSITLDV 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1768008261 309 PILQAKPKPVSVDVGKDASFSCAWRGNPLPRITWTRLGG---------SQVLSSGPTLRLPSVALEDAGDYVCRAE 375
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEpissgstrsRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768008261   27 PEDMVVLLGQEARLPCSL-GAYRGLVQWTKDGLALGGERDlpgwsRYwiSGNSASGQHDLHIKPVELEDEASYECQAS-Q 104
Cdd:smart00410   1 PPSVTVKEGESVTLSCEAsGSPPPEVTWYKQGGKLLAESG-----RF--SVSRSGSTSTLTISNVTPEDSGTYTCAATnS 73

                           90
                   ....*....|..
gi 1768008261  105 AGLRSRPAQLHV 116
Cdd:smart00410  74 SGSASSGTTLTV 85

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768008261 129 PSVSLVAGVPGN--LTCRSRGdARPAPELLWFRDGIRLDGTSFHQTILKDKATGTVENILFLTPSSHDDGTTLICRARSQ 206
Cdd:pfam08205   5 PPASLLEGEGPEvvATCSSAG-GKPAPRITWYLDGKPLEAAETSSEQDPESGLVTVTSELKLVPSRSDHGQSLTCQVSYG 83

                  ..
gi 1768008261 207 AL 208
Cdd:pfam08205  84 AL 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 1768008261  25 QQPEDMVVLLGQEARLPCslGAYRGL----VQWTKDG--LALGGERdlpgwsRYWISGNSasgqhdLHIKPVELEDEASY 98
Cdd:cd05724     2 VEPSDTQVAVGEMAVLEC--SPPRGHpeptVSWRKDGqpLNLDNER------VRIVDDGN------LLIAEARKSDEGTY 67

                          90       100
                  ....*....|....*....|
gi 1768008261  99 ECQASQ-AGLR-SRPAQLHV 116
Cdd:cd05724    68 KCVATNmVGEReSRAARLSV 87

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768008261 233 QTVQEGEKVTFLCQASAQPPVTGYRWAKGGSPvLGARGP------------RLEV----VADATFLTepvsCEVSNAVGS 296
Cdd:cd05750     9 QTVQEGSKLVLKCEATSENPSPRYRWFKDGKE-LNRKRPknikirnkkknsELQInkakLEDSGEYT----CVVENILGK 83

                  ....*....
gi 1768008261 297 ANRSTALEV 305
Cdd:cd05750    84 DTVTGNVTV 92

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 1768008261 122 APQVLGGPSVSLVAGVPGNLTCRSRGdARPAPELLWFRDGIRLDGTSFHQTILKDKATGTVENILFLTPSSHDDGTTLIC 201
Cdd:cd05759     1 DPVIEGGPVISLQAGVPYNLTCRARG-AKPAAEIIWFRDGEQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFTC 79

                          90
                  ....*....|....*....
gi 1768008261 202 RARSQALPTGRDTAVTLSL 220
Cdd:cd05759    80 RARNEAIPNGKETSITLDV 98

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768008261 315 PKPVSVDVGKDASFSCAWRGNPLPRITWTRLGGSQ-----VLSSGPTLRLPSVALEDAGDYVCRAEPRRtglGGGTAQAR 389
Cdd:cd04968     8 PADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPssqweITTSEPVLEIPNVQFEDEGTYECEAENSR---GKDTVQGR 84

                  ...
gi 1768008261 390 LTV 392
Cdd:cd04968    85 IIV 87

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768008261 314 KPKPVSVDVGKDASFSCAWRGNPLPRITWTRlGGSQVLSSG----------PTLRLPSVALEDAGDYVCRAEprrTGLGG 383
Cdd:pfam07679   6 KPKDVEVQEGESARFTCTVTGTPDPEVSWFK-DGQPLRSSDrfkvtyeggtYTLTISNVQPDDSGKYTCVAT---NSAGE 81

                  ....*....
gi 1768008261 384 GTAQARLTV 392
Cdd:pfam07679  82 AEASAELTV 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 1768008261 314 KPKPVSVDVGKDASFSCAWRGNPLPRITWTRLGG------SQVLSSGpTLRLPSVALEDAGDYVCRAEprrTGLGGGTAQ 387
Cdd:cd05725     3 RPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGelpkgrYEILDDH-SLKIRKVTAGDMGSYTCVAE---NMVGKIEAS 78

                  ....*
gi 1768008261 388 ARLTV 392
Cdd:cd05725    79 ATLTV 83

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 1768008261 309 PILQAKPKP--VSVDVGKDASFSCAWRGNPLPRITWTRLGGS--------QVLSSGPTLRLPSVALEDAGDYVCRAeprr 378
Cdd:cd20970     1 PVISTPQPSftVTAREGENATFMCRAEGSPEPEISWTRNGNLiiefntryIVRENGTTLTIRNIRRSDMGIYLCIA---- 76

                          90
                  ....*....|....
gi 1768008261 379 TGLGGGTAQARLTV 392
Cdd:cd20970    77 SNGVPGSVEKRITL 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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1768008261 326 ASFSCAWRGNPLPRITWTRLGGSQVLSSGP---------TLRLPSVALEDAGDYVCRAE 375
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDsrrselgngTLTISNVTLEDSGTYTCVAS 59

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768008261 323 GKDASFSCAWRGNPLPRITWTRlGGSQ--------VLSSGpTLRLPSVALEDAGDYVCRA 374
Cdd:cd05745     2 GQTVDFLCEAQGYPQPVIAWTK-GGSQlsvdrrhlVLSSG-TLRISRVALHDQGQYECQA 59

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 1768008261 309 PILQAKPKPVSVDVGKDASFSCAWRGNPLPRITWTRLGG--------SQVLSSGPTLRLPSVALEDAGDYVCRAEPRrtg 380
Cdd:cd20976     2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQplqyaadrSTCEAGVGELHIQDVLPEDHGTYTCLAKNA--- 78

                          90
                  ....*....|..
gi 1768008261 381 LGGGTAQARLTV 392
Cdd:cd20976    79 AGQVSCSAWVTV 90

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of human fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. FGFR2 is required for male sex determination. 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 1768008261 309 PILQAK-PKPVSVDVGKDASFSCAWRGNPLPRITWTR---LGGSQVLSSG-------------------PTLRLPSVALE 365
Cdd:cd05858     1 PILQAGlPANTSVVVGTDAEFVCKVYSDAQPHIQWLKhveKNGSKYGPDGlpyvevlktagvnttdkeiEVLYLRNVTFE 80

                  ....*....
gi 1768008261 366 DAGDYVCRA 374
Cdd:cd05858    81 DAGEYTCLA 89

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 1768008261 117 MVPPEAPQVLGGPSvSLVAGVPGNLTCRSRGdARPAPELLWFRDGIRLDGTSFHQTILKDKaTGTVENILFLTPSSHDDG 196
Cdd:cd05761     1 LGVPEKPVITGFTS-PVVEGDEITLTCTTSG-SKPAADIRWFKNDKELKGVKEVQESGAGK-TFTVTSTLRFRVDRDDDG 77

                          90
                  ....*....|....*
gi 1768008261 197 TTLICRARSQALPTG 211
Cdd:cd05761    78 VAVICRVDHESLTST 92

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768008261 129 PSVSLVAGVPGN--LTCRSRGdARPAPELLWFRDGIRLDGTSFHQTILKDKATGTVENILFLTPSSHDDGTTLICRARSQ 206
Cdd:pfam08205   5 PPASLLEGEGPEvvATCSSAG-GKPAPRITWYLDGKPLEAAETSSEQDPESGLVTVTSELKLVPSRSDHGQSLTCQVSYG 83

                  ..
gi 1768008261 207 AL 208
Cdd:pfam08205  84 AL 85

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. 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. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768008261 314 KPKPVSVDVGKDASFSCAWRGNPLPRITWTRLGgsQVLSS-------GPTLRLPSVALEDAGDYVCRAEPRRtglGGGTA 386
Cdd:cd05728     5 VISDTEADIGSSLRWECKASGNPRPAYRWLKNG--QPLASenrieveAGDLRITKLSLSDSGMYQCVAENKH---GTIYA 79

                  ....*.
gi 1768008261 387 QARLTV 392
Cdd:cd05728    80 SAELAV 85

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1768008261 314 KPKPVSVDVGKDASFSCAWRGNPLPRITWTRLGgsQVLSSG-----------PTLRLPSVALEDAGDYVCRAE 375
Cdd:cd05747     9 KPRSLTVSEGESARFSCDVDGEPAPTVTWMREG--QIIVSSqrhqitsteykSTFEISKVQMSDEGNYTVVVE 79

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 1768008261 117 MVPPEAPQVlgGPSVSLVAGVPGNLTCRSRgDARPAPELLWFRDGIRLDGTSFHQtilKDKATGTVENILFLTPSSHDDG 196
Cdd:cd05885     1 LVAPENPVV--EVREQAVEGGEVELSCLVP-RSRPAATLRWYRDRKELKGVSSGQ---ENGKVWSVASTVRFRVDRKDDG 74

                          90
                  ....*....|....*.
gi 1768008261 197 TTLICRARSQALPTGR 212
Cdd:cd05885    75 GIVICEAQNQALPSGH 90

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 1768008261  21 PHFLQQPED-MVVLLGQEARLPCSL-GAYRGLVQWTKDGLALGGErdlpgwsrywiSGNSASGQHDLHIKPVELEDEASY 98
Cdd:cd20978     1 PKFIQKPEKnVVVKGGQDVTLPCQVtGVPQPKITWLHNGKPLQGP-----------MERATVEDGTLTIINVQPEDTGYY 69

                          90
                  ....*....|....*....
gi 1768008261  99 ECQA-SQAGLRSRPAQLHV 116
Cdd:cd20978    70 GCVAtNEIGDIYTETLLHV 88

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 1768008261 116 VMVPPEAPQVLGGPSvSLVAGVPGNLTCRSRGdARPAPELLWFRDGIRLDGTSFHQTILKDKATGTVENILFLTPSSHDD 195
Cdd:cd05884     1 VLGVPEKPQISGFTS-PVMEGDHIQLTCKTSG-SKPAADIRWFKNDKEVKDVKYLKAEDANRKTFTVSSSLDFHVDRDDD 78

                          90
                  ....*....|...
gi 1768008261 196 GTTLICRARSQAL 208
Cdd:cd05884    79 GVAITCRVDHESL 91

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup 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. 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. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin 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. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768008261 314 KPKPVSVDVGKDASFSCAWRGNPLPRITWTRLGGS----------QVLSSGPTLRLPSVALEDAGDYVCRAeprRTGLGG 383
Cdd:cd05763     5 TPHDITIRAGSTARLECAATGHPTPQIAWQKDGGTdfpaarerrmHVMPEDDVFFIVDVKIEDTGVYSCTA---QNSAGS 81

                  ....*....
gi 1768008261 384 GTAQARLTV 392
Cdd:cd05763    82 ISANATLTV 90

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1768008261 323 GKDASFSCAWRGNPLPRITWTRLGGS------QVLSSGPTLRLPSVALEDAGDYVCRAEPRRtglggGTAQARLTV 392
Cdd:cd05731    10 GGVLLLECIAEGLPTPDIRWIKLGGElpkgrtKFENFNKTLKIENVSEADSGEYQCTASNTM-----GSARHTISV 80

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. 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 I1 domain of the titin I-band 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, 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 1768008261  21 PHFLQQPEDMVVLLGQEARLPCSL-GAYRGLVQWTKDGLALGGERDLPgwsRYWIsgNSASGQHDLHIKPVELEDEASYE 99
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVqGKPDPEVKWYKNGVPIDPSSIPG---KYKI--ESEYGVHVLHIRRVTVEDSAVYS 75

                  ...
gi 1768008261 100 CQA 102
Cdd:cd20951    76 AVA 78

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1768008261 310 ILQAKPKPVSVDVGKDASFSCAWRGNPLPRITWTRLGgsQVLSSGP--------TLRLPSVALEDAGDYVCRAE 375
Cdd:cd20978     3 FIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNG--KPLQGPMeratvedgTLTIINVQPEDTGYYGCVAT 74

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1768008261 309 PILQAKPKPVSVDVGKDASFSCAWRGNPLPRITWTRLGGS---------QVLSSGPTLRLPSVALEDAGDYVCRA 374
Cdd:cd05736     1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDinpklskqlTLIANGSELHISNVRYEDTGAYTCIA 75