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 1008446971 119 PNDLLSIHKPQNVKCETSGSYPPAKLTWLLDGKPIRNAVVTEEV-TDSFTGSIIS---LNVVADNDGKDLVCRANNPRFP 194
Cdd:cd05759     8 PVISLQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKELlKDGKRETTVStllITPSDLDTGRTFTCRARNEAIP 87

                  ..
gi 1008446971 195 GG 196
Cdd:cd05759    88 NG 89

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1008446971  323 EPLVVQCHVDSIPeDVRFSWTYNTSKGVFPVLGAKMHNNGGVSTLHFNP-STEDIDSLSCWATNDVGKQEQP 393
Cdd:smart00410  10 ESVTLSCEASGSP-PPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNvTPEDSGTYTCAATNSSGSASSG 80

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 1008446971 119 PNDLLSIHKPQNVKCETSGSYPPAKLTWLLDGKPIRNAVVTEEV-TDSFTGSIIS---LNVVADNDGKDLVCRANNPRFP 194
Cdd:cd05759     8 PVISLQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKELlKDGKRETTVStllITPSDLDTGRTFTCRARNEAIP 87

                  ..
gi 1008446971 195 GG 196
Cdd:cd05759    88 NG 89

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1008446971 117 VTPNDLLSIHKPQNV--KCETSGSYPPAKLTWLLDGKPIRNAVVT-EEVTDSFTGSIIS---LNVVADNDGKDLVCRANN 190
Cdd:pfam08205   3 IEPPASLLEGEGPEVvaTCSSAGGKPAPRITWYLDGKPLEAAETSsEQDPESGLVTVTSelkLVPSRSDHGQSLTCQVSY 82

                  ...
gi 1008446971 191 PRF 193
Cdd:pfam08205  83 GAL 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
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1008446971  23 GPFLEGDELFLSCQVTGGRPRPSLTWWHNNTLIDGVVD----SSETSFTIVNQLT 73
Cdd:cd05761    14 SPVVEGDEITLTCTTSGSKPAADIRWFKNDKELKGVKEvqesGAGKTFTVTSTLR 68

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1008446971  323 EPLVVQCHVDSIPeDVRFSWTYNTSKGVFPVLGAKMHNNGGVSTLHFNP-STEDIDSLSCWATNDVGKQEQP 393
Cdd:smart00410  10 ESVTLSCEASGSP-PPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNvTPEDSGTYTCAATNSSGSASSG 80

Fibronectin type III domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1008446971 462 DQGEAKLLYRALGDKPMFRLHSLHPGREYQIMVYAENAKGRSEP 505
Cdd:pfam00041  41 NSGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGGEGPP 84

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 1008446971 119 PNDLLSIHKPQNVKCETSGSYPPAKLTWLLDGKPIRNAVVTEEV-TDSFTGSIIS---LNVVADNDGKDLVCRANNPRFP 194
Cdd:cd05759     8 PVISLQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKELlKDGKRETTVStllITPSDLDTGRTFTCRARNEAIP 87

                  ..
gi 1008446971 195 GG 196
Cdd:cd05759    88 NG 89

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1008446971 117 VTPNDLLSIHKPQNV--KCETSGSYPPAKLTWLLDGKPIRNAVVT-EEVTDSFTGSIIS---LNVVADNDGKDLVCRANN 190
Cdd:pfam08205   3 IEPPASLLEGEGPEVvaTCSSAGGKPAPRITWYLDGKPLEAAETSsEQDPESGLVTVTSelkLVPSRSDHGQSLTCQVSY 82

                  ...
gi 1008446971 191 PRF 193
Cdd:pfam08205  83 GAL 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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1008446971 230 VTLRCDSSARPSPYgYRWYHDGHLVALNESGGVLPI--DHILTLKSIQKKSQGQYACFATNTEGGSYSSPF 298
Cdd:cd00096     1 VTLTCSASGNPPPT-ITWYKNGKPLPPSSRDSRRSElgNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1008446971 220 VNSPVKEGTDVTLRCDSSARPSPYgYRWYHDGHLVALNESGGVLPIDHILTLKSIQKKSQGQYACFATNTEG 291
Cdd:cd20952     7 QNQTVAVGGTVVLNCQATGEPVPT-ISWLKDGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSG 77

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 1008446971 210 PKVSVKLDSGvNSPVKEGTDVTLRCDSSARPSPyGYRWYHDGHLV-ALNESGGVLPIDHILTLKSIQKKSQGQYACFATN 288
Cdd:cd20970     1 PVISTPQPSF-TVTAREGENATFMCRAEGSPEP-EISWTRNGNLIiEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASN 78

                  ....*...
gi 1008446971 289 TEGGSYSS 296
Cdd:cd20970    79 GVPGSVEK 86

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
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1008446971  23 GPFLEGDELFLSCQVTGGRPRPSLTWWHNNTLIDGVVD----SSETSFTIVNQLT 73
Cdd:cd05761    14 SPVVEGDEITLTCTTSGSKPAADIRWFKNDKELKGVKEvqesGAGKTFTVTSTLR 68

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 1008446971 131 VKCETSGSYPPAKLTWL-----LDGKPIRnavVTEEVT-DSFT-GSIISLNVVADNDGKDLVCRANNPRFPGGSLEDRRQ 203
Cdd:cd07705    24 LRCTSSGSKPAANIKWRkgdqeLEGAPTS---VQEDGNgKTFTvSSSVEFQVTREDDGAEITCSVGHESLHDSDRSTSQR 100

                  ...
gi 1008446971 204 IHV 206
Cdd:cd07705   101 IEV 103

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1008446971 224 VKEGTDVTLRCDSSARPSPYGYrWYHDGHLVA--------LNESGgvlpiDHILTLKSIQKKSQGQYACFATNTEG 291
Cdd:cd05744    12 VQEGRLCRFDCKVSGLPTPDLF-WQLNGKPVRpdsahkmlVRENG-----RHSLIIEPVTKRDAGIYTCIARNRAG 81

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1008446971 220 VNSPVKEGTDVTLRCDSSARPSPyGYRWYHDGHLVALNESGGVLPIDHiLTLKSIQKKSQGQYACFATNTEGGSYSSPFD 299
Cdd:cd20968     7 TNVTIIEGLKAVLPCTTMGNPKP-SVSWIKGDDLIKENNRIAVLESGS-LRIHNVQKEDAGQYRCVAKNSLGIAYSKPVT 84

                  ....
gi 1008446971 300 LIIQ 303
Cdd:cd20968    85 IEVE 88

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1008446971 221 NSPVKEGTDVTLRCDSSARPS-PYGYRWYHDGHLVALNESGG------VLPIDHILTLKSIQKKSQGQYACFAtNTEGGS 293
Cdd:cd04970    11 NADITVGENATLQCHASHDPTlDLTFTWSFNGVPIDLEKIEGhyrrryGKDSNGDLEIVNAQLKHAGRYTCTA-QTVVDS 89

                          90
                  ....*....|...
gi 1008446971 294 YSSPFDLIIQYAP 306
Cdd:cd04970    90 DSASATLVVRGPP 102

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1008446971  323 EPLVVQCHVDSIPeDVRFSWTYNTSKGVFPVLGAKMHNNGGVSTLHFNP-STEDIDSLSCWATNDVGKQEQP 393
Cdd:smart00410  10 ESVTLSCEASGSP-PPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNvTPEDSGTYTCAATNSSGSASSG 80

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1008446971 230 VTLRCDSSARPSPyGYRWYHDGHLVALNES---GGVLPIDHI----LTLKSIQKKSQGQYACFATNTEG 291
Cdd:cd05869    20 ITLTCEASGDPIP-SITWRTSTRNISSEEKtldGHIVVRSHArvssLTLKYIQYTDAGEYLCTASNTIG 87

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1008446971  27 EGDELFLSCQVTGGRPRPSLTWWHNNTLIDGVVDSSETS-----FTIVNQLtrRHTPRSFWKSH-LECRASSSAIAGD 98
Cdd:pfam08205  13 EGPEVVATCSSAGGKPAPRITWYLDGKPLEAAETSSEQDpesglVTVTSEL--KLVPSRSDHGQsLTCQVSYGALRGS 88

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1008446971 222 SPVKEGTDVTLRCDSSARPSPyGYRWYHDGHLVALNESGGVLPiDHILTLKSIQKKSQGQYACFATNTEGGSYSS 296
Cdd:cd04969    12 ILAAKGGDVIIECKPKASPKP-TISWSKGTELLTNSSRICILP-DGSLKIKNVTKSDEGKYTCFAVNFFGKANST 84

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1008446971 133 CETSGSYPPAKLTWLLDGKPIRNAVVTEEVTDSFT-GSIISLNVVADNDGKDLVCRANNPRFPGGSledRRQIH 205
Cdd:cd05885    25 CLVPRSRPAATLRWYRDRKELKGVSSGQENGKVWSvASTVRFRVDRKDDGGIVICEAQNQALPSGH---SKQTQ 95

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk 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. 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 titin Z1z2 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1008446971 209 PPKVSVKLDSgvnSPVKEGTDVTLRCDSSARPSPYgYRWYHDGHL------VALNESGGVlpidHILTLKSIQKKSQGQY 282
Cdd:cd20972     1 PPQFIQKLRS---QEVAEGSKVRLECRVTGNPTPV-VRWFCEGKElqnspdIQIHQEGDL----HSLIIAEAFEEDTGRY 72

                          90
                  ....*....|....
gi 1008446971 283 ACFATNTEGGSYSS 296
Cdd:cd20972    73 SCLATNSVGSDTTS 86

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1008446971 222 SPVKEGTDVTLRCDSSARPSPYgYRWYHDGhlVALNESGGVLPI---DHILTLKSIQKKSQGQYACFATNTEGGSYSS 296
Cdd:cd05760    11 AEIQPSSRVTLRCHIDGHPRPT-YQWFRDG--TPLSDGQGNYSVsskERTLTLRSAGPDDSGLYYCCAHNAFGSVCSS 85