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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 29791550    254 REGDDVTLKCQADGNPPPTSFNFNIKGKKVT-------VTDKDVYTLT--GVTRADSGVYKCSLLDNDVMESTQI-VTV 322
Cdd:smart00410   7 KEGESVTLSCEASGSPPPEVTWYKQGGKLLAesgrfsvSRSGSTSTLTisNVTPEDSGTYTCAATNSSGSASSGTtLTV 85

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 29791550 427 EAEGSPKPEVQWSVNGT------DDETSYVNGKATYKLTVVPSKNLTVSCLVTNKLG 477
Cdd:cd05867  22 QVEGIPTPNITWSINGApiegtdPDPRRHVSSGALILTDVQPSDTAVYQCEARNRHG 78

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 29791550    254 REGDDVTLKCQADGNPPPTSFNFNIKGKKVT-------VTDKDVYTLT--GVTRADSGVYKCSLLDNDVMESTQI-VTV 322
Cdd:smart00410   7 KEGESVTLSCEASGSPPPEVTWYKQGGKLLAesgrfsvSRSGSTSTLTisNVTPEDSGTYTCAATNSSGSASSGTtLTV 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29791550    333 GKVLKKLGENLVVSLEKNASSEVKVTWTKDNRKLDKLPD--------------FSQLRYSDAGLYVCDVSIEGIKHSFSF 398
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGrfsvsrsgststltISNVTPEDSGTYTCAATNSSGSASSGT 81

                   ....
gi 29791550    399 ELTV 402
Cdd:smart00410  82 TLTV 85

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 29791550 427 EAEGSPKPEVQWSVNGT------DDETSYVNGKATYKLTVVPSKNLTVSCLVTNKLG 477
Cdd:cd05867  22 QVEGIPTPNITWSINGApiegtdPDPRRHVSSGALILTDVQPSDTAVYQCEARNRHG 78

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 29791550   340 GENLVVSLEKNASSEVKVTWTKDNRKLDKLPDF--SQLRYSDAGLYVCDVSIEGIKH-SFSFELTV 402
Cdd:pfam13895  14 GEPVTLTCSAPGNPPPSYTWYKDGSAISSSPNFftLSVSAEDSGTYTCVARNGRGGKvSNPVELTV 79

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 29791550    254 REGDDVTLKCQADGNPPPTSFNFNIKGKKVT-------VTDKDVYTLT--GVTRADSGVYKCSLLDNDVMESTQI-VTV 322
Cdd:smart00410   7 KEGESVTLSCEASGSPPPEVTWYKQGGKLLAesgrfsvSRSGSTSTLTisNVTPEDSGTYTCAATNSSGSASSGTtLTV 85

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 29791550   248 VSQSPIREGDDVTLKCQADGNPPPtSFNFNIKGKKVTvTDKDVYTLTgVTRADSGVYKCSLLDNDVMESTQIVTVS 323
Cdd:pfam13895   6 PSPTVVTEGEPVTLTCSAPGNPPP-SYTWYKDGSAIS-SSPNFFTLS-VSAEDSGTYTCVARNGRGGKVSNPVELT 78

Immunoglobulin I-set domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 29791550   253 IREGDDVTLKCQADGNPPPT-SFNFNikGKKVTVTDK-------DVYTLT--GVTRADSGVYKC 306
Cdd:pfam07679  12 VQEGESARFTCTVTGTPDPEvSWFKD--GQPLRSSDRfkvtyegGTYTLTisNVQPDDSGKYTC 73

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 29791550 259 VTLKCQADGNPPPT--------SFNFNIKGKKVTVTDKDVYTLTGVTRADSGVYKC 306
Cdd:cd00096   1 VTLTCSASGNPPPTitwykngkPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTC 56

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 29791550 253 IREGDDVTLKCQADGNPPPTSFnFNIKGKKVTVTDKD--------VYTL--TGVTRADSGVYKCS 307
Cdd:cd05744  12 VQEGRLCRFDCKVSGLPTPDLF-WQLNGKPVRPDSAHkmlvrengRHSLiiEPVTKRDAGIYTCI 75

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
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 29791550 252 PIREGDDVTLKCQADGNPPPT------SFNFNIKGKKVTVTDKDVYTLTGVTRADSGVYKC 306
Cdd:cd20952  10 TVAVGGTVVLNCQATGEPVPTiswlkdGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTC 70

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 29791550 127 VHKKPSAPVIKNKVKELENGKLTqlgeCVVESANPAADLIWMKNNQALvdDGKTIIITSDVTKDPVTglssTSSRLQYTA 206
Cdd:cd07705   3 IPQKPQITGYESAFKEKDKAKLR----CTSSGSKPAANIKWRKGDQEL--EGAPTSVQEDGNGKTFT----VSSSVEFQV 72

                        90
                ....*....|....*
gi 29791550 207 RKEDVASQFPCVAKH 221
Cdd:cd07705  73 TREDDGAEITCSVGH 87

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 29791550 259 VTLKCQADGNPPPTsFNFNIKGKKVTVTDKDVYTLTG--------VTRADSGVYKCSLLDNDVMESTQIVTVSF 324
Cdd:cd04967  22 VALNCRARANPVPS-YRWLMNGTEIDLESDYRYSLVDgtlvisnpSKAKDAGHYQCLATNTVGSVLSREATLQF 94

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
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 29791550 253 IREGDDVTLKCQADGNPPPT-SFNFN------IKGKKVTVTDKDVYTLTGVTRADSGVYKCS 307
Cdd:cd20970  14 AREGENATFMCRAEGSPEPEiSWTRNgnliieFNTRYIVRENGTTLTIRNIRRSDMGIYLCI 75

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 29791550 131 PSAPVIKNKVKELENGKLTQLgECVVESANPAADLIWMKNNQALVDdgktiiiTSDVTKDPVTGLSSTSSRLQYTARKED 210
Cdd:cd05761   4 PEKPVITGFTSPVVEGDEITL-TCTTSGSKPAADIRWFKNDKELKG-------VKEVQESGAGKTFTVTSTLRFRVDRDD 75

                        90       100
                ....*....|....*....|..
gi 29791550 211 VASQFPCVAKH--VTGPNQVST 230
Cdd:cd05761  76 DGVAVICRVDHesLTSTPKQTQ 97

Immunoglobulin Constant-1 (C1)-set domain; The members here are composed of C1-set domains, classical Ig-like domains resembling the antibody constant domain. Members of the IgC1 family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, while the IgC domain is involved in oligomerization and molecular interactions. 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 strands by G, F, C, and C'.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 29791550 167 WMKNNQALVDDgktiiITSDVTKDPVTGLSSTSSRLQYTARKEDVASQFPCVAKHVTGPNQVS 229
Cdd:cd00098  35 WLKNGVPLTSG-----VSTSSPVEPNDGTYSVTSSLTVPPSDWDEGATYTCVVTHESLKSPLS 92