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 1812283891 120 DPVIDGGPEVLLNAGESYNLTCVSRGAKPPSMVEWMKDGLPIEGAVSTTEVLSDRKRVTTRSYLPVHPIDTDTGRNYSCV 199
Cdd:cd05759     1 DPVIEGGPVISLQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFTCR 80

                          90
                  ....*....|....*...
gi 1812283891 200 STNQAAPSGKSTTVTLNV 217
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 1812283891  20 RFSQEPADQSVVRGQTVILSCVVFNYSGIV-QWTKDGLALGIGEDlrawPRYRVLRDQELGQYNLEILLADLSDDALYEC 98
Cdd:cd05722     3 YFLSEPSDIVAMRGGPVVLNCSAESDPPPKiEWKKDGVLLNLVSD----ERRQQLPNGSLLITSVVHSKHNKPDEGFYQC 78

                          90
                  ....*....|....*....
gi 1812283891  99 QAPDAALR---SRRAKLTV 114
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 1812283891 120 DPVIDGGPEVLLNAGESYNLTCVSRGAKPPSMVEWMKDGLPIEGAVSTTEVLSDRKRVTTRSYLPVHPIDTDTGRNYSCV 199
Cdd:cd05759     1 DPVIEGGPVISLQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFTCR 80

                          90
                  ....*....|....*...
gi 1812283891 200 STNQAAPSGKSTTVTLNV 217
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 1812283891  312 PQPKTVDVDSDVTLNCKWAGNPPLTLTWFKKGSNMVLSNSN----------QLYLKSVTQADAGQYVCKAiVPRIGVGET 381
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRfsvsrsgstsTLTISNVTPEDSGTYTCAA-TNSSGSASS 79

                   ....*.
gi 1812283891  382 EVTLTV 387
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 1812283891 307 ILLVEPQPKTVDVDSDVTLNCKWAGNPPLTLTWFK-------KGSNMVLSNSNQLYLKSVTQADAGQYVCKAIVPrigVG 379
Cdd:cd20952     1 IILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKdgvpllgKDERITTLENGSLQIKGAEKSDTGEYTCVALNL---SG 77

                  ....*...
gi 1812283891 380 ETEVTLTV 387
Cdd:cd20952    78 EATWSAVL 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283891  20 RFSQEPADQSVVRGQTVILSCVVfnySG----IVQWTKDglalgiGEDLRAWPRYRVLRDQelGQYNLEILLADLSDDAL 95
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTV---TGtpdpEVSWFKD------GQPLRSSDRFKVTYEG--GTYTLTISNVQPDDSGK 70

                  ....*
gi 1812283891  96 YECQA 100
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 1812283891  397 PVQYAVRGERGGVKCYIASTPPPdKIVWAWKENVWEKEKGtlleRYTVEQSkpaaeggGVLSTLTINNVMESDFlSTYNC 476
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPP-EVTWYKQGGKLLAESG----RFSVSRS-------GSTSTLTISNVTPEDS-GTYTC 68

                           90
                   ....*....|....*.
gi 1812283891  477 TAWNAFGPGTMIITLE 492
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 1812283891 228 EPRSVL--EG---DRVTFTCQAHANPPIMgYRWAKGGVVLQGARESVFTTKADHSFFTEPVS--------CLVFNAVGkT 294
Cdd:cd05850     8 QPSSTLfpEGsaeEKVTLACRARASPPAT-YRWKMNGTELKMEPDSRYRLVAGNLVISNPVKakdagsyqCLASNRRG-T 85

                          90
                  ....*....|.
gi 1812283891 295 NVSILVDVHFG 305
Cdd:cd05850    86 VVSREASLRFG 96

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283891 390 PPIISSEP-VQYAVRGERGGVKCYIASTPPPdKIVWawkenvwekekgTLLERYTVEQSKPAAEGGGVLSTLTINNVMES 468
Cdd:pfam13927   1 KPVITVSPsSVTVREGETVTLTCEATGSPPP-TITW------------YKNGEPISSGSTRSRSLSGSNSTLTISNVTRS 67

                          90
                  ....*....|..
gi 1812283891 469 DFlSTYNCTAWN 480
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 1812283891 120 DPVIDGGPEVLLNAGESYNLTCVSRGAKPPSMVEWMKDGLPIEGAVSTTEVLSDRKRVTTRSYLPVHPIDTDTGRNYSCV 199
Cdd:cd05759     1 DPVIEGGPVISLQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFTCR 80

                          90
                  ....*....|....*...
gi 1812283891 200 STNQAAPSGKSTTVTLNV 217
Cdd:cd05759    81 ARNEAIPNGKETSITLDV 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1812283891 306 PILLVEPQPKTVDVDSDVTLNCKWAGNPPLTLTWFKKG---------SNMVLSNSNQLYLKSVTQADAGQYVCKA 371
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 1812283891 121 PVIDGGPEVLLNAGESYNLTCVSRGAKPPSMVEWMKDGLPIEGAVSTTEVLSDRKRVTTRSYLPVHPIDTDTGRNYSCVS 200
Cdd:pfam08205   1 PTIEPPASLLEGEGPEVVATCSSAGGKPAPRITWYLDGKPLEAAETSSEQDPESGLVTVTSELKLVPSRSDHGQSLTCQV 80

                  ....
gi 1812283891 201 TNQA 204
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 1812283891 307 ILLVEPQPKTVDVDSDVTLNCKWAGNPPLTLTWFK-------KGSNMVLSNSNQLYLKSVTQADAGQYVCKAIVPrigVG 379
Cdd:cd20952     1 IILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKdgvpllgKDERITTLENGSLQIKGAEKSDTGEYTCVALNL---SG 77

                  ....*...
gi 1812283891 380 ETEVTLTV 387
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 1812283891 323 VTLNCKWAGNPPLTLTWFKKGS---------NMVLSNSNQLYLKSVTQADAGQYVCKAIVPRIGVGETEV 383
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKplppssrdsRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283891  20 RFSQEPADQSVVRGQTVILSCVVfnySG----IVQWTKDglalgiGEDLRAWPRYRVLRDQelGQYNLEILLADLSDDAL 95
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTV---TGtpdpEVSWFKD------GQPLRSSDRFKVTYEG--GTYTLTISNVQPDDSGK 70

                  ....*
gi 1812283891  96 YECQA 100
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 1812283891 311 EPQPKTVDVDSDVTLNCKWAGNPPLTLTWFKKGSNMVLS-----NSNQLYLKSVTQADAGQYVCKAivpRIGVGETEV-- 383
Cdd:cd05725     3 RPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGryeilDDHSLKIRKVTAGDMGSYTCVA---ENMVGKIEAsa 79

                  ....
gi 1812283891 384 TLTV 387
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 1812283891 310 VEPQPKTVDVDSDVTLNCKWAGNPPLTLTWFKKG------SNMVLSNSNQLYLKSVTQADAGQYVC 369
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 1812283891 115 LIPPDDPVIDGGPEVLlnAGESYNLTCVSRGAKPPSMVEWMKDGLPIEGAVSTTEvlsDRKRVTTRSYLPVHPIDTDTGR 194
Cdd:cd05885     1 LVAPENPVVEVREQAV--EGGEVELSCLVPRSRPAATLRWYRDRKELKGVSSGQE---NGKVWSVASTVRFRVDRKDDGG 75

                          90       100
                  ....*....|....*....|....*
gi 1812283891 195 NYSCVSTNQAAPSG--KSTTVTLNV 217
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 1812283891 127 PEVLLNAGESYNLTCVSRGAKPPSM-VEWMKDGLPIEGAVSTTEVLSDR-KRVTTRSYLPVHPIDTDTGRNYSCVSTNQA 204
Cdd:cd00098     7 PSPEEKGGGKVTLVCLVSGFYPKDItVTWLKNGVPLTSGVSTSSPVEPNdGTYSVTSSLTVPPSDWDEGATYTCVVTHES 86

                  ....*....
gi 1812283891 205 APSGKSTTV 213
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 1812283891 306 PILLVEPQPKTVDVDSDVTLNCKWAGNPPLTLTWFKKG--------------SNMVLSNSNQLYLKSVTQADAGQYVCKA 371
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKQVpgkenlimrpnhvrGNVVVTNIGQLVIYNAQPQDAGLYTCTA 80

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 1812283891  21 FSQEPADQSVVRGQTVILSCVVFNYS-GIVQWTKDGLALgIGEDLRawpryrvLRDQELGqyNLEILLADLSDDALYECQ 99
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPvPTISWLKDGVPL-LGKDER-------ITTLENG--SLQIKGAEKSDTGEYTCV 71

                  .
gi 1812283891 100 A 100
Cdd:cd20952    72 A 72

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283891 121 PVIDGGPE-VLLNAGESYNLTCVSRGAKPPSmVEWMKDGLPIEGavsttevlSDRKRVTT---RSYLPVHPIDTDTGRNY 196
Cdd:pfam07679   1 PKFTQKPKdVEVQEGESARFTCTVTGTPDPE-VSWFKDGQPLRS--------SDRFKVTYeggTYTLTISNVQPDDSGKY 71

                          90       100
                  ....*....|....*....|..
gi 1812283891 197 SCVSTNqaaPSGK-STTVTLNV 217
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 1812283891 306 PILLVEPQP-KTVDVDSDVTLNCKWAGNPPLTLTWFKKG----SNMVLSN--SNQLYLKSVTQADAGQYVCKAiVPRIGV 378
Cdd:cd20978     1 PKFIQKPEKnVVVKGGQDVTLPCQVTGVPQPKITWLHNGkplqGPMERATveDGTLTIINVQPEDTGYYGCVA-TNEIGD 79

                  ....*....
gi 1812283891 379 GETEVTLTV 387
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 1812283891 306 PILLVEPQPKTVDVDSDVTLNCKWAGNPPLTLTWFKKGS------------NMVLSNSNQLYLKSV----TQADAGQYVC 369
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQpletdkddprshRIVLPSGSLFFLRVVhgrkGRSDEGVYVC 80

                  ..
gi 1812283891 370 KA 371
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 1812283891 121 PVIDGGPEVLLNAGESYNLTCVSRGAKPPSMVEWMKDglpIEGAVSTTEVLSDRKRVTTRSYLPVHPIDTDTGRNYSCVS 200
Cdd:cd05719     3 NSLEGGPALLIGGEPTLVATCISANGKPPASVTWETD---LKGEASTTQVRGSNGTVTVTSRYRLVPSREADGQPLTCVV 79

                          90
                  ....*....|....*..
gi 1812283891 201 TNQAAPSGKSTTVTLNV 217
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 1812283891 305 GPILLVEPQPKTVDVDSD---VTLNCKWAGNPPLTLTWFKKGSNMVLSNSNQLYL--------KSVTQADAGQYVCKAIV 373
Cdd:cd04967     1 GPVFEEQPDDTIFPEDSDekkVALNCRARANPVPSYRWLMNGTEIDLESDYRYSLvdgtlvisNPSKAKDAGHYQCLATN 80

                          90
                  ....*....|..
gi 1812283891 374 PRIGVGETEVTL 385
Cdd:cd04967    81 TVGSVLSREATL 92

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1812283891  20 RFSQEPADQSVVRGQTVILSCVVFNY-SGIVQWTKDGLALGIGEDLRawpryrvlRDQELGQYNLEILLADLSDDALYEC 98
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCEATGSpPPTITWYKNGEPISSGSTRS--------RSLSGSNSTLTISNVTRSDAGTYTC 74

                  ..
gi 1812283891  99 QA 100
Cdd:pfam13927  75 VA 76

Immunoglobulin C1-set domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1812283891 139 LTCVSRGAKPPSM-VEWMKDGLPI-EGAVSTTEVLSDRKRVTTRSYLPVHPIDTDTGRNYSC 198
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 1812283891 390 PPIISSEPVQY-AVRGERGGVKCYIASTPPPdKIVWAWKENVWEKEKgtllERYTVEQSkpaaegggvlsTLTINNVMES 468
Cdd:cd20978     1 PKFIQKPEKNVvVKGGQDVTLPCQVTGVPQP-KITWLHNGKPLQGPM----ERATVEDG-----------TLTIINVQPE 64

                          90
                  ....*....|....*
gi 1812283891 469 DfLSTYNCTAWNAFG 483
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 1812283891 323 VTLNCKWAGNPPLTLTWFKKGS-------NMVLSnSNQLYLKSVTQADAGQYVCKAIVPrIGVGETEVTLTV 387
Cdd:cd05745     5 VDFLCEAQGYPQPVIAWTKGGSqlsvdrrHLVLS-SGTLRISRVALHDQGQYECQAVNI-VGSQRTVAQLTV 74