Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435  140 QIQPRDMVAVVGEQFTLECGPPWGHPEPTVSWWKDGKPLAL-QPGRHTVSGGSLLMARAEKSDEGTYMCVATNSAGHRES 218
Cdd:cd05724    1 RVEPSDTQVAVGEMAVLECSPPRGHPEPTVSWRKDGQPLNLdNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERES 80

                 ....*..
gi 17511435  219 RAARVSI 225
Cdd:cd05724   81 RAARLSV 87

Fibronectin type III domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435    350 PPQEVTLKP-GNGTVFVSWVPPPaeNHNGIIRGYQV-WSLGNTSLPPANWTVVGEQTQLEIATHMPGS-YCVQVAAVTGA 426
Cdd:pfam00041    2 APSNLTVTDvTSTSLTVSWTPPP--DGNGPITGYEVeYRPKNSGEPWNEITVPGTTTSVTLTGLKPGTeYEVRVQAVNGG 79

                   ....*.
gi 17511435    427 GAGEPS 432
Cdd:pfam00041   80 GEGPPS 85

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435  140 QIQPRDMVAVVGEQFTLECGPPWGHPEPTVSWWKDGKPLAL-QPGRHTVSGGSLLMARAEKSDEGTYMCVATNSAGHRES 218
Cdd:cd05724    1 RVEPSDTQVAVGEMAVLECSPPRGHPEPTVSWRKDGQPLNLdNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERES 80

                 ....*..
gi 17511435  219 RAARVSI 225
Cdd:cd05724   81 RAARLSV 87

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435     143 PRDMVAVVGEQFTLECgPPWGHPEPTVSWWKDGKPLALQPGRHTVSG----GSLLMARAEKSDEGTYMCVATNSAGHRES 218
Cdd:smart00410    1 PPSVTVKEGESVTLSC-EASGSPPPEVTWYKQGGKLLAESGRFSVSRsgstSTLTISNVTPEDSGTYTCAATNSSGSASS 79

                    ..
gi 17511435     219 RA 220
Cdd:smart00410   80 GT 81

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435     32 PQILVHPQDQLFQGPGPARMSCQASGQPPPTIRWLLNGQPLSmvpPDPHHllpdgtllllqppaRGHAHDG-------QA 104
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLR---SSDRF--------------KVTYEGGtytltisNV 63

                           90       100
                   ....*....|....*....|....*...
gi 17511435    105 LSTDLGVYTCEASNRLGTAVSRgARLSV 132
Cdd:pfam07679   64 QPDDSGKYTCVATNSAGEAEAS-AELTV 90

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435     347 PSAPPQEVTLKPGNGTVFVSWVPPPAENHNGIIRGYQVwSLGNTSLPPANWTVVGEQTQLEIATHMPGS-YCVQVAAVTG 425
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRV-EYREEGSEWKEVNVTPSSTSYTLTGLKPGTeYEFRVRAVNG 79

                    ....
gi 17511435     426 AGAG 429
Cdd:smart00060   80 AGEG 83

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435      47 GPARMSCQASGQPPPTIRWLLNGqpLSMVPPDPHHLlpdgtllllqppARGHAHDG-----QALSTDLGVYTCEASNRLG 121
Cdd:smart00410   10 ESVTLSCEASGSPPPEVTWYKQG--GKLLAESGRFS------------VSRSGSTStltisNVTPEDSGTYTCAATNSSG 75

                            90
                    ....*....|.
gi 17511435     122 TaVSRGARLSV 132
Cdd:smart00410   76 S-ASSGTTLTV 85

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435   567 SRSPGVPLLPDTSTFYGSLIAELPSSTPARPSPQVPAVRRLPPQLAQLSSPCSSSDSLCSRRGLSSPRLSLAPAEAWKAK 646
Cdd:PHA03247 2586 ARRPDAPPQSARPRAPVDDRGDPRGPAPPSPLPPDTHAPDPPPPSPSPAANEPDPHPPPTVPPPERPRDDPAPGRVSRPR 2665

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435   647 KKQELQHAN--SSPLLRGSHslelRACELGNRGSKNLSQSPGAVPQALVAWRALGPKLlsssnelvtrhlpPAPLFPHET 724
Cdd:PHA03247 2666 RARRLGRAAqaSSPPQRPRR----RAARPTVGSLTSLADPPPPPPTPEPAPHALVSAT-------------PLPPGPAAA 2728

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435   725 PPTQSQQTQPPVAPQAPSSILLPAAPIPILSPCSP-----PSPQASSLSGPSPASSRLSSSSLSSLGEDQDSVLTPEEVA 799
Cdd:PHA03247 2729 RQASPALPAAPAPPAVPAGPATPGGPARPARPPTTagppaPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPP 2808

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 17511435   800 LCLELSEGEETPRNSvspmPRAPSPPTTygyISVPTASEFtdmgrtgggvgpkggvllcPPRPCLTPTPSEGSLANG 876
Cdd:PHA03247 2809 AAVLAPAAALPPAAS----PAGPLPPPT---SAQPTAPPP-------------------PPGPPPPSLPLGGSVAPG 2859

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435  140 QIQPRDMVAVVGEQFTLECGPPWGHPEPTVSWWKDGKPLAL-QPGRHTVSGGSLLMARAEKSDEGTYMCVATNSAGHRES 218
Cdd:cd05724    1 RVEPSDTQVAVGEMAVLECSPPRGHPEPTVSWRKDGQPLNLdNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERES 80

                 ....*..
gi 17511435  219 RAARVSI 225
Cdd:cd05724   81 RAARLSV 87

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435     143 PRDMVAVVGEQFTLECgPPWGHPEPTVSWWKDGKPLALQPGRHTVSG----GSLLMARAEKSDEGTYMCVATNSAGHRES 218
Cdd:smart00410    1 PPSVTVKEGESVTLSC-EASGSPPPEVTWYKQGGKLLAESGRFSVSRsgstSTLTISNVTPEDSGTYTCAATNSSGSASS 79

                    ..
gi 17511435     219 RA 220
Cdd:smart00410   80 GT 81

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 17511435  154 FTLECgPPWGHPEPTVSWWKDGKPL---ALQPGRHTVSGGSLLMARAEKSDEGTYMCVATNSAGHRESRAA 221
Cdd:cd00096    1 VTLTC-SASGNPPPTITWYKNGKPLppsSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 17511435    139 FQIQPRDMVAVVGEQFTLECGPPwGHPEPTVSWWKDGKPLA---LQPGRHTVSGGSLLMARAEKSDEGTYMCVATN 211
Cdd:pfam13927    4 ITVSPSSVTVREGETVTLTCEAT-GSPPPTITWYKNGEPISsgsTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 17511435  148 AVVGEQFTLECGPPwGHPEPTVSWWKDGKPLALQPGRHTVS--GGSLLMARAEKSDEGTYMCVATNSAGHRES 218
Cdd:cd05730   15 ANLGQSVTLACDAD-GFPEPTMTWTKDGEPIESGEEKYSFNedGSEMTILDVDKLDEAEYTCIAENKAGEQEA 86

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth 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. This group 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435  144 RDMVAVVGEQFTLECgPPWGHPEPTVSWWKDGKPLALqPGRHTV-SGGSLLMARAEK-SDEGTYMCVATNSAGHRESRAA 221
Cdd:cd20958    8 GNLTAVAGQTLRLHC-PVAGYPISSITWEKDGRRLPL-NHRQRVfPNGTLVIENVQRsSDEGEYTCTARNQQGQSASRSV 85

                 ....
gi 17511435  222 RVSI 225
Cdd:cd20958   86 FVKV 89

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. 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 17511435  139 FQIQPRDMVAVVGEQFTLECGPpWGHPEPTVSWWKDGKPLALQPG--RHTVSGGSLLM-----ARAEKSDEGTYMCVATN 211
Cdd:cd05722    4 FLSEPSDIVAMRGGPVVLNCSA-ESDPPPKIEWKKDGVLLNLVSDerRQQLPNGSLLItsvvhSKHNKPDEGFYQCVAQN 82

                         90
                 ....*....|....*
gi 17511435  212 -SAGHRESRAARVSI 225
Cdd:cd05722   83 eSLGSIVSRTARVTV 97

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435  143 PRDMVAVVGEQFTLECGPPwGHPEPTVSWWKDGKPLALQPGRHTVS---GGSLLMARAEKSDEGTYMCVATNSAGHRESR 219
Cdd:cd05738    6 PQLKVVEKARTATMLCAAS-GNPDPEISWFKDFLPVDTATSNGRIKqlrSGALQIENSEESDQGKYECVATNSAGTRYSA 84

                 ....*..
gi 17511435  220 AARVSIQ 226
Cdd:cd05738   85 PANLYVR 91

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 17511435   32 PQILVHPQDQL-FQGPGPARMSCQASGQPPPTIRWLLNGQPLSmvppdphhllpdgtllllQPPARGHAHDG-----QAL 105
Cdd:cd20978    1 PKFIQKPEKNVvVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQ------------------GPMERATVEDGtltiiNVQ 62

                         90       100
                 ....*....|....*....|
gi 17511435  106 STDLGVYTCEASNRLGTAVS 125
Cdd:cd20978   63 PEDTGYYGCVATNEIGDIYT 82

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 17511435    150 VGEQFTLECGPPWGHPEPTVSWWKDGK----PLALQPGRHTVSGGSLLMARAEKSDEGTYMCVATNSAGHRESRAA 221
Cdd:pfam00047   10 EGDSATLTCSASTGSPGPDVTWSKEGGtlieSLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSATLSTS 85

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435  142 QPRDMVAVVGEQFTLECGPpWGHPEPTVSWWK-DGKPLAlQPGRHTvSGGSLLMARAEKSDEGTYMCVATNSAGhRESRA 220
Cdd:cd04968    7 FPADTYALKGQTVTLECFA-LGNPVPQIKWRKvDGSPSS-QWEITT-SEPVLEIPNVQFEDEGTYECEAENSRG-KDTVQ 82

                 ....*.
gi 17511435  221 ARVSIQ 226
Cdd:cd04968   83 GRIIVQ 88

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh 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. This group 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435  141 IQPRDMVAVVGEQFTLECGPPwGHPEPTVSWWK-------DGKPLALQPGRHTVSGGSLLMARAEKSDEGTYMCVATNSA 213
Cdd:cd20954    6 VEPVDANVAAGQDVMLHCQAD-GFPTPTVTWKKatgstpgEYKDLLYDPNVRILPNGTLVFGHVQKENEGHYLCEAKNGI 84

                 .
gi 17511435  214 G 214
Cdd:cd20954   85 G 85

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. 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 lacks a C" strand.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435   28 QDSPPQILVHPQDQLFqgpgparMSCQASGQPPPTIRWLLNGQPLSmVPPDPHHLLPDGTLLLLQPPARGHAHDGQalst 107
Cdd:cd05733    5 EQSPKDYIVDPRDNIT-------IKCEAKGNPQPTFRWTKDGKFFD-PAKDPRVSMRRRSGTLVIDNHNGGPEDYQ---- 72

                         90       100
                 ....*....|....*....|...
gi 17511435  108 dlGVYTCEASNRLGTAVSRGARL 130
Cdd:cd05733   73 --GEYQCYASNELGTAISNEIRL 93

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435   49 ARMSCQASGQPPPTIRWLLNGQPLSMVPPDPHHLLPDGTLLLLQPPARGHAhdgqalstdlGVYTCEASNRLGTAVSRGA 128
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDS----------GTYTCVASNSAGGSASASV 70

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 17511435  143 PRDMVAVVGEQFTLECGPPwGHPEPTVSWWKDGKPLALqpGR-HTVSGGSLLMARAEKSDEGTYMCVATNSAGHRESRA 220
Cdd:cd05725    4 PQNQVVLVDDSAEFQCEVG-GDPVPTVRWRKEDGELPK--GRyEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASA 79

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 17511435  150 VGEQFTLECgPPWGHPEPTVSWWKDGKPL----ALQPGRHTVSGGSLLMARAEKSDEGTYMCVATNSAG 214
Cdd:cd05729   18 AANKVRLEC-GAGGNPMPNITWLKDGKEFkkehRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYG 85

Fibronectin type III domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435    350 PPQEVTLKP-GNGTVFVSWVPPPaeNHNGIIRGYQV-WSLGNTSLPPANWTVVGEQTQLEIATHMPGS-YCVQVAAVTGA 426
Cdd:pfam00041    2 APSNLTVTDvTSTSLTVSWTPPP--DGNGPITGYEVeYRPKNSGEPWNEITVPGTTTSVTLTGLKPGTeYEVRVQAVNGG 79

                   ....*.
gi 17511435    427 GAGEPS 432
Cdd:pfam00041   80 GEGPPS 85

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 17511435  140 QIQPRDMVavvgeqfTLECGPPwGHPEPTVSWWKDGKPLALQPGRHTVSGG--SLLMARAEKSDEGTYMCVATNSAGH 215
Cdd:cd05760   12 EIQPSSRV-------TLRCHID-GHPRPTYQWFRDGTPLSDGQGNYSVSSKerTLTLRSAGPDDSGLYYCCAHNAFGS 81

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435  141 IQPRDMVAVVGEQFTLECGPPwGHPEPTVSWWKDGKPLALQPGRHTVSGGSLLMARAEKSDEGTYMCVATNSAGHRESRA 220
Cdd:cd20957    6 IDPPVQTVDFGRTAVFNCSVT-GNPIHTVLWMKDGKPLGHSSRVQILSEDVLVIPSVKREDKGMYQCFVRNDGDSAQATA 84

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 17511435  150 VGEQFTLECGPPwGHPEPTVSWWKDGKPLALQ-PGRHTVSGGSLLMARAEKSDEGTYMCVATNSAGH 215
Cdd:cd05856   18 VGSSVRLKCVAS-GNPRPDITWLKDNKPLTPPeIGENKKKKWTLSLKNLKPEDSGKYTCHVSNRAGE 83

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17511435  139 FQIQPRDMVAVVGEQFTLECGPPwGHPEPTVSWWKDGK---PLALQPGRHTVSGGSLL-MARAEKSDEGTYMCVATNSAG 214
Cdd:cd05763    2 FTKTPHDITIRAGSTARLECAAT-GHPTPQIAWQKDGGtdfPAARERRMHVMPEDDVFfIVDVKIEDTGVYSCTAQNSAG 80