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 1812283889 121 DPVIDGGPEVLLNAGESYNLTCVSRGAKPPSMVEWMKDGLPIEGAVSTTEVLSDRKRVTTRSYLPVHPIDTDTGRNYSCV 200
Cdd:cd05759     1 DPVIEGGPVISLQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFTCR 80

                          90
                  ....*....|....*...
gi 1812283889 201 STNQAAPSGKSTTVTLNV 218
Cdd:cd05759    81 ARNEAIPNGKETSITLDV 98

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283889  21 RFSQEPADQSVVRGQTVILSCVVFNYSGIV-QWTKDGLALGIGEDlrawPRYRVLRDQELGQYNLEILLADLSDDALYEC 99
Cdd:cd05722     3 YFLSEPSDIVAMRGGPVVLNCSAESDPPPKiEWKKDGVLLNLVSD----ERRQQLPNGSLLITSVVHSKHNKPDEGFYQC 78

                          90
                  ....*....|....*....
gi 1812283889 100 QAPDAALR---SRRAKLTV 115
Cdd:cd05722    79 VAQNESLGsivSRTARVTV 97

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 1812283889 121 DPVIDGGPEVLLNAGESYNLTCVSRGAKPPSMVEWMKDGLPIEGAVSTTEVLSDRKRVTTRSYLPVHPIDTDTGRNYSCV 200
Cdd:cd05759     1 DPVIEGGPVISLQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFTCR 80

                          90
                  ....*....|....*...
gi 1812283889 201 STNQAAPSGKSTTVTLNV 218
Cdd:cd05759    81 ARNEAIPNGKETSITLDV 98

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283889  313 PQPKTVDVDSDVTLNCKWAGNPPLTLTWFKKGSNMVLSNSN----------QLYLKSVTQADAGQYVCKAiVPRIGVGET 382
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRfsvsrsgstsTLTISNVTPEDSGTYTCAA-TNSSGSASS 79

                   ....*.
gi 1812283889  383 EVTLTV 388
Cdd:smart00410  80 GTTLTV 85

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283889 308 ILLVEPQPKTVDVDSDVTLNCKWAGNPPLTLTWFK-------KGSNMVLSNSNQLYLKSVTQADAGQYVCKAIVPrigVG 380
Cdd:cd20952     1 IILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKdgvpllgKDERITTLENGSLQIKGAEKSDTGEYTCVALNL---SG 77

                  ....*...
gi 1812283889 381 ETEVTLTV 388
Cdd:cd20952    78 EATWSAVL 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283889  21 RFSQEPADQSVVRGQTVILSCVVfnySG----IVQWTKDglalgiGEDLRAWPRYRVLRDQelGQYNLEILLADLSDDAL 96
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTV---TGtpdpEVSWFKD------GQPLRSSDRFKVTYEG--GTYTLTISNVQPDDSGK 70

                  ....*
gi 1812283889  97 YECQA 101
Cdd:pfam07679  71 YTCVA 75

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283889  398 PVQYAVRGERGGVKCYIASTPPPdKIVWAWKENVWEKEKGtlleRYTVEQSkpaaeggGVLSTLTINNVMESDFlSTYNC 477
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPP-EVTWYKQGGKLLAESG----RFSVSRS-------GSTSTLTISNVTPEDS-GTYTC 68

                           90
                   ....*....|....*.
gi 1812283889  478 TAWNAFGPGTMIITLE 493
Cdd:smart00410  69 AATNSSGSASSGTTLT 84

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283889 229 EPRSVL--EG---DRVTFTCQAHANPPIMgYRWAKGGVVLQGARESVFTTKADHSFFTEPVS--------CLVFNAVGkT 295
Cdd:cd05850     8 QPSSTLfpEGsaeEKVTLACRARASPPAT-YRWKMNGTELKMEPDSRYRLVAGNLVISNPVKakdagsyqCLASNRRG-T 85

                          90
                  ....*....|.
gi 1812283889 296 NVSILVDVHFG 306
Cdd:cd05850    86 VVSREASLRFG 96

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283889 391 PPIISSEP-VQYAVRGERGGVKCYIASTPPPdKIVWawkenvwekekgTLLERYTVEQSKPAAEGGGVLSTLTINNVMES 469
Cdd:pfam13927   1 KPVITVSPsSVTVREGETVTLTCEATGSPPP-TITW------------YKNGEPISSGSTRSRSLSGSNSTLTISNVTRS 67

                          90
                  ....*....|..
gi 1812283889 470 DFlSTYNCTAWN 481
Cdd:pfam13927  68 DA-GTYTCVASN 78

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 1812283889 121 DPVIDGGPEVLLNAGESYNLTCVSRGAKPPSMVEWMKDGLPIEGAVSTTEVLSDRKRVTTRSYLPVHPIDTDTGRNYSCV 200
Cdd:cd05759     1 DPVIEGGPVISLQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFTCR 80

                          90
                  ....*....|....*...
gi 1812283889 201 STNQAAPSGKSTTVTLNV 218
Cdd:cd05759    81 ARNEAIPNGKETSITLDV 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1812283889 307 PILLVEPQPKTVDVDSDVTLNCKWAGNPPLTLTWFKKG---------SNMVLSNSNQLYLKSVTQADAGQYVCKA 372
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGepissgstrSRSLSGSNSTLTISNVTRSDAGTYTCVA 76

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283889 122 PVIDGGPEVLLNAGESYNLTCVSRGAKPPSMVEWMKDGLPIEGAVSTTEVLSDRKRVTTRSYLPVHPIDTDTGRNYSCVS 201
Cdd:pfam08205   1 PTIEPPASLLEGEGPEVVATCSSAGGKPAPRITWYLDGKPLEAAETSSEQDPESGLVTVTSELKLVPSRSDHGQSLTCQV 80

                  ....
gi 1812283889 202 TNQA 205
Cdd:pfam08205  81 SYGA 84

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283889 308 ILLVEPQPKTVDVDSDVTLNCKWAGNPPLTLTWFK-------KGSNMVLSNSNQLYLKSVTQADAGQYVCKAIVPrigVG 380
Cdd:cd20952     1 IILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKdgvpllgKDERITTLENGSLQIKGAEKSDTGEYTCVALNL---SG 77

                  ....*...
gi 1812283889 381 ETEVTLTV 388
Cdd:cd20952    78 EATWSAVL 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 1812283889 324 VTLNCKWAGNPPLTLTWFKKGS---------NMVLSNSNQLYLKSVTQADAGQYVCKAIVPRIGVGETEV 384
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKplppssrdsRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283889  21 RFSQEPADQSVVRGQTVILSCVVfnySG----IVQWTKDglalgiGEDLRAWPRYRVLRDQelGQYNLEILLADLSDDAL 96
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTV---TGtpdpEVSWFKD------GQPLRSSDRFKVTYEG--GTYTLTISNVQPDDSGK 70

                  ....*
gi 1812283889  97 YECQA 101
Cdd:pfam07679  71 YTCVA 75

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 1812283889 312 EPQPKTVDVDSDVTLNCKWAGNPPLTLTWFKKGSNMVLS-----NSNQLYLKSVTQADAGQYVCKAivpRIGVGETEV-- 384
Cdd:cd05725     3 RPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGryeilDDHSLKIRKVTAGDMGSYTCVA---ENMVGKIEAsa 79

                  ....
gi 1812283889 385 TLTV 388
Cdd:cd05725    80 TLTV 83

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1812283889 311 VEPQPKTVDVDSDVTLNCKWAGNPPLTLTWFKKG------SNMVLSNSNQLYLKSVTQADAGQYVC 370
Cdd:cd20957     6 IDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGkplghsSRVQILSEDVLVIPSVKREDKGMYQC 71

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 1812283889 116 LIPPDDPVIDGGPEVLlnAGESYNLTCVSRGAKPPSMVEWMKDGLPIEGAVSTTEvlsDRKRVTTRSYLPVHPIDTDTGR 195
Cdd:cd05885     1 LVAPENPVVEVREQAV--EGGEVELSCLVPRSRPAATLRWYRDRKELKGVSSGQE---NGKVWSVASTVRFRVDRKDDGG 75

                          90       100
                  ....*....|....*....|....*
gi 1812283889 196 NYSCVSTNQAAPSG--KSTTVTLNV 218
Cdd:cd05885    76 IVICEAQNQALPSGhsKQTQYVLDV 100

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283889 128 PEVLLNAGESYNLTCVSRGAKPPSM-VEWMKDGLPIEGAVSTTEVLSDR-KRVTTRSYLPVHPIDTDTGRNYSCVSTNQA 205
Cdd:cd00098     7 PSPEEKGGGKVTLVCLVSGFYPKDItVTWLKNGVPLTSGVSTSSPVEPNdGTYSVTSSLTVPPSDWDEGATYTCVVTHES 86

                  ....*....
gi 1812283889 206 APSGKSTTV 214
Cdd:cd00098    87 LKSPLSKTW 95

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as 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. 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 1812283889 307 PILLVEPQPKTVDVDSDVTLNCKWAGNPPLTLTWFKKG--------------SNMVLSNSNQLYLKSVTQADAGQYVCKA 372
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKQVpgkenlimrpnhvrGNVVVTNIGQLVIYNAQPQDAGLYTCTA 80

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1812283889 221 PPTVTLSIEPRSVLEGDRVTFTCQAHANPPIMgYRWAKGGVVLQGARESVFTTKADHSFFT 281
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPT-ITWYKNGEPISSGSTRSRSLSGSNSTLT 60

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283889 122 PVIDGGPE-VLLNAGESYNLTCVSRGAKPPSmVEWMKDGLPIEGavsttevlSDRKRVTT---RSYLPVHPIDTDTGRNY 197
Cdd:pfam07679   1 PKFTQKPKdVEVQEGESARFTCTVTGTPDPE-VSWFKDGQPLRS--------SDRFKVTYeggTYTLTISNVQPDDSGKY 71

                          90       100
                  ....*....|....*....|..
gi 1812283889 198 SCVSTNqaaPSGK-STTVTLNV 218
Cdd:pfam07679  72 TCVATN---SAGEaEASAELTV 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 1812283889 307 PILLVEPQP-KTVDVDSDVTLNCKWAGNPPLTLTWFKKG----SNMVLSN--SNQLYLKSVTQADAGQYVCKAiVPRIGV 379
Cdd:cd20978     1 PKFIQKPEKnVVVKGGQDVTLPCQVTGVPQPKITWLHNGkplqGPMERATveDGTLTIINVQPEDTGYYGCVA-TNEIGD 79

                  ....*....
gi 1812283889 380 GETEVTLTV 388
Cdd:cd20978    80 IYTETLLHV 88

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283889 307 PILLVEPQPKTVDVDSDVTLNCKWAGNPPLTLTWFKKGS------------NMVLSNSNQLYLKSV----TQADAGQYVC 370
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQpletdkddprshRIVLPSGSLFFLRVVhgrkGRSDEGVYVC 80

                  ..
gi 1812283889 371 KA 372
Cdd:cd07693    81 VA 82

Second immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and Necl-5), and similar domains; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and nectin-like protein 5 (Necl-5)) and similar proteins. Poliovirus (PV) binds to its cellular receptor (PVR/CD155) to initiate infection. CD155 is a membrane-anchored, single-span glycoprotein; its extracellular region has three Ig-like domains. There are four different isotypes of CD155 (referred to as alpha, beta, gamma, and delta), these result from alternate splicing of the CD155 mRNA, and have identical extracellular domains. CD155-beta and CD155-gamma are secreted, while CD155-alpha and CD155-delta are membrane-bound and function as PV receptors. The virus recognition site is contained in the amino-terminal domain, D1. Having the virus attachment site on the receptor distal from the plasma membrane may be important for successful initiation of infection of cells by the virus. CD155 binds in the poliovirus "canyon" and has a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. This group also includes the second Ig-like domain of nectin-1, also known as poliovirus receptor related protein(PVRL)1 or CD111.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283889 122 PVIDGGPEVLLNAGESYNLTCVSRGAKPPSMVEWMKDglpIEGAVSTTEVLSDRKRVTTRSYLPVHPIDTDTGRNYSCVS 201
Cdd:cd05719     3 NSLEGGPALLIGGEPTLVATCISANGKPPASVTWETD---LKGEASTTQVRGSNGTVTVTSRYRLVPSREADGQPLTCVV 79

                          90
                  ....*....|....*..
gi 1812283889 202 TNQAAPSGKSTTVTLNV 218
Cdd:cd05719    80 EHPSLEKDQRISVTLNV 96

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283889 306 GPILLVEPQPKTVDVDSD---VTLNCKWAGNPPLTLTWFKKGSNMVLSNSNQLYL--------KSVTQADAGQYVCKAIV 374
Cdd:cd04967     1 GPVFEEQPDDTIFPEDSDekkVALNCRARANPVPSYRWLMNGTEIDLESDYRYSLvdgtlvisNPSKAKDAGHYQCLATN 80

                          90
                  ....*....|..
gi 1812283889 375 PRIGVGETEVTL 386
Cdd:cd04967    81 TVGSVLSREATL 92

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283889  21 RFSQEPADQSVVRGQTVILSCVVFNY-SGIVQWTKDGLALGIGEDLRawpryrvlRDQELGQYNLEILLADLSDDALYEC 99
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCEATGSpPPTITWYKNGEPISSGSTRS--------RSLSGSNSTLTISNVTRSDAGTYTC 74

                  ..
gi 1812283889 100 QA 101
Cdd:pfam13927  75 VA 76

Immunoglobulin C1-set domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1812283889 140 LTCVSRGAKPPSM-VEWMKDGLPI-EGAVSTTEVLSDRKRVTTRSYLPVHPIDTDTGRNYSC 199
Cdd:pfam07654  17 LTCLVTGFYPPDItVTWLKNGQEVtEGVKTTPPSPNSDWTYQLSSYLTVTPSDWESGDEYTC 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283889 391 PPIISSEPVQY-AVRGERGGVKCYIASTPPPdKIVWAWKENVWEKEKgtllERYTVEQSkpaaegggvlsTLTINNVMES 469
Cdd:cd20978     1 PKFIQKPEKNVvVKGGQDVTLPCQVTGVPQP-KITWLHNGKPLQGPM----ERATVEDG-----------TLTIINVQPE 64

                          90
                  ....*....|....*
gi 1812283889 470 DfLSTYNCTAWNAFG 484
Cdd:cd20978    65 D-TGYYGCVATNEIG 78

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1812283889 324 VTLNCKWAGNPPLTLTWFKKGS-------NMVLSnSNQLYLKSVTQADAGQYVCKAIVPrIGVGETEVTLTV 388
Cdd:cd05745     5 VDFLCEAQGYPQPVIAWTKGGSqlsvdrrHLVLS-SGTLRISRVALHDQGQYECQAVNI-VGSQRTVAQLTV 74