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 37181272   29 PQILVHPQDQLFQGPGPARMSCQASGQPPPTIRWLLNGQPLSM--VPPDPHHLLPdgtllllqpPARG-------HAHDG 99
Cdd:cd07693    1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETdkDDPRSHRIVL---------PSGSlfflrvvHGRKG 71

                         90       100       110
                 ....*....|....*....|....*....|.
gi 37181272  100 QalsTDLGVYTCEASNRLGTAVSRGARLSVA 130
Cdd:cd07693   72 R---SDEGVYVCVAHNSLGEAVSRNASLEVA 99

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37181272   564 SRSPGVPLLPDTSTFYGSLIAELPSSTPARPSPQVPAVRRLPPQLAQLSSPCSSSDSLCSRRGLSSPRLSLAPAEAWKAK 643
Cdd:PHA03247 2586 ARRPDAPPQSARPRAPVDDRGDPRGPAPPSPLPPDTHAPDPPPPSPSPAANEPDPHPPPTVPPPERPRDDPAPGRVSRPR 2665

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37181272   644 KKQELQHAN--SSPLLRGSHslelRACELGNRGSKNLSQSPGAVPQALVAWRALGPKLlsssnelvtrhlpPAPLFPHET 721
Cdd:PHA03247 2666 RARRLGRAAqaSSPPQRPRR----RAARPTVGSLTSLADPPPPPPTPEPAPHALVSAT-------------PLPPGPAAA 2728

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37181272   722 PPTQSQQTQPPVAPQAPSSILLPAAPIPILSPCSP-----PSPQASSLSGPSPASSRLSSSSLSSLGEDQDSVLTPEEVA 796
Cdd:PHA03247 2729 RQASPALPAAPAPPAVPAGPATPGGPARPARPPTTagppaPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPP 2808

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 37181272   797 LCLELSEGEETPRNSvspmPRAPSPPTTygyISVPTASEFtdmgrtgggvgpkggvllcPPRPCLTPTPSEGSLANG 873
Cdd:PHA03247 2809 AAVLAPAAALPPAAS----PAGPLPPPT---SAQPTAPPP-------------------PPGPPPPSLPLGGSVAPG 2859

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37181272    136 FQIQPRDMVAVVGEQFTLECgPPWGHPEPTVSWWKDGKPLalQPGRH---TVSGG--SLLMARAEKSDEGTYMCVATNSA 210
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTC-TVTGTPDPEVSWFKDGQPL--RSSDRfkvTYEGGtyTLTISNVQPDDSGKYTCVATNSA 79

                   ....*..
gi 37181272    211 GHRESRA 217
Cdd:pfam07679   80 GEAEASA 86

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 37181272   29 PQILVHPQDQLFQGPGPARMSCQASGQPPPTIRWLLNGQPLSM--VPPDPHHLLPdgtllllqpPARG-------HAHDG 99
Cdd:cd07693    1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETdkDDPRSHRIVL---------PSGSlfflrvvHGRKG 71

                         90       100       110
                 ....*....|....*....|....*....|.
gi 37181272  100 QalsTDLGVYTCEASNRLGTAVSRGARLSVA 130
Cdd:cd07693   72 R---SDEGVYVCVAHNSLGEAVSRNASLEVA 99

Fibronectin type III domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37181272    347 PPQEVTLKP-GNGTVFVSWVPPPaeNHNGIIRGYQV-WSLGNTSLPPANWTVVGEQTQLEIATHMPGS-YCVQVAAVTGA 423
Cdd:pfam00041    2 APSNLTVTDvTSTSLTVSWTPPP--DGNGPITGYEVeYRPKNSGEPWNEITVPGTTTSVTLTGLKPGTeYEVRVQAVNGG 79

                   ....*.
gi 37181272    424 GAGEPS 429
Cdd:pfam00041   80 GEGPPS 85

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37181272  347 PPQEVTLKPGNGT-VFVSWVPPPAENhnGIIRGYQV-WSLGNTSLPPANWTVVGEQTQLEIaTHM-PGS-YCVQVAAVTG 422
Cdd:cd00063    3 PPTNLRVTDVTSTsVTLSWTPPEDDG--GPITGYVVeYREKGSGDWKEVEVTPGSETSYTL-TGLkPGTeYEFRVRAVNG 79

                         90
                 ....*....|
gi 37181272  423 AGAGEPSRPV 432
Cdd:cd00063   80 GGESPPSESV 89

Fibronectin type 3 domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37181272  164 PTVSWWKDGKPLALQPGRHTVSGGSLLMARAEKSDEGTYMCVATNSAGHRESRAARVSIQ----EPQDYTEPVELLAVRI 239
Cdd:COG3401   47 TTKESPGTLLVAAGLSSGGGLGTGGRAGTTSGVAAVAVAAAPPTATGLTTLTGSGSVGGAtntgLTSSDEVPSPAVGTAT 126

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37181272  240 QLENVTLLNP-DPAEGPKPRPAVWLSWKVSGPAAPAQSYTALFRTQTAPGGQGAPWAEELLAG-WQSAELGGLHWGQDYE 317
Cdd:COG3401  127 TATAVAGGAAtAGTYALGAGLYGVDGANASGTTASSVAGAGVVVSPDTSATAAVATTSLTVTStTLVDGGGDIEPGTTYY 206

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37181272  318 FKVRPSSGRARGPDSNVLLLRLPEKVPSApPQEVTLKP-GNGTVFVSWVPPPAENhngiIRGYQVWsLGNTSLPPanWTV 396
Cdd:COG3401  207 YRVAATDTGGESAPSNEVSVTTPTTPPSA-PTGLTATAdTPGSVTLSWDPVTESD----ATGYRVY-RSNSGDGP--FTK 278

                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 37181272  397 VGEQTQLEI--ATHMPG-SYCVQVAAVTgaGAGEPSRP 431
Cdd:COG3401  279 VATVTTTSYtdTGLTNGtTYYYRVTAVD--AAGNESAP 314

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37181272    136 FQIQPRDMVAVVGEQFTLECgPPWGHPEPTVSWWKDGKPLalQPGRH---TVSGG--SLLMARAEKSDEGTYMCVATNSA 210
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTC-TVTGTPDPEVSWFKDGQPL--RSSDRfkvTYEGGtyTLTISNVQPDDSGKYTCVATNSA 79

                   ....*..
gi 37181272    211 GHRESRA 217
Cdd:pfam07679   80 GEAEASA 86

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 37181272   29 PQILVHPQDQLFQGPGPARMSCQASGQPPPTIRWLLNGQPLSM--VPPDPHHLLPdgtllllqpPARG-------HAHDG 99
Cdd:cd07693    1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETdkDDPRSHRIVL---------PSGSlfflrvvHGRKG 71

                         90       100       110
                 ....*....|....*....|....*....|.
gi 37181272  100 QalsTDLGVYTCEASNRLGTAVSRGARLSVA 130
Cdd:cd07693   72 R---SDEGVYVCVAHNSLGEAVSRNASLEVA 99

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 37181272  140 PRDMVAVVGEQFTLECgPPWGHPEPTVSWWKDGKPLALQPGRHTVSGGSLLMARAEKSDEGTYMCVATNSAG 211
Cdd:cd20978    8 EKNVVVKGGQDVTLPC-QVTGVPQPKITWLHNGKPLQGPMERATVEDGTLTIINVQPEDTGYYGCVATNEIG 78

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 37181272  139 QPRDMVAVVGEQFTLECGPPwGHPEPTVSWWKDGKPL---ALQPGRHTV---SGG----SLLMARAEKSDEGTYMCVATN 208
Cdd:cd07693    6 HPSDLIVSKGDPATLNCKAE-GRPTPTIQWLKNGQPLetdKDDPRSHRIvlpSGSlfflRVVHGRKGRSDEGVYVCVAHN 84

                         90
                 ....*....|....
gi 37181272  209 SAGHRESRAARVSI 222
Cdd:cd07693   85 SLGEAVSRNASLEV 98

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 37181272  140 PRDMVAVVGEQFTLECgPPWGHPEPTVSWWKDGKPLALQPGR-HTVSGGSLLMARAEKSDEGTYMCVATNSAG 211
Cdd:cd20952    6 PQNQTVAVGGTVVLNC-QATGEPVPTISWLKDGVPLLGKDERiTTLENGSLQIKGAEKSDTGEYTCVALNLSG 77

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37181272  139 QPRDMVAVVGEQFTLECGPPwGHPEPTVSWWKDGKPLALQPGRHTV--SGGSLLMARAEKSDEGTYMCVATNSAGHRESR 216
Cdd:cd20970    8 PSFTVTAREGENATFMCRAE-GSPEPEISWTRNGNLIIEFNTRYIVreNGTTLTIRNIRRSDMGIYLCIASNGVPGSVEK 86

                 ....*.
gi 37181272  217 AARVSI 222
Cdd:cd20970   87 RITLQV 92

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37181272   35 PQDQLFQGPGPARMSCQASGQPPPTIRWLLNGQPLsmvppdphhllpdgtllLLQPPARGHAHDGQAL------STDLGV 108
Cdd:cd04978    6 PPSLVLSPGETGELICEAEGNPQPTITWRLNGVPI-----------------EPAPEDMRRTVDGRTLifsnlqPNDTAV 68

                         90
                 ....*....|...
gi 37181272  109 YTCEASNRLGTAV 121
Cdd:cd04978   69 YQCNASNVHGYLL 81

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37181272  135 DFQIQP--RDMVAVVGEQFTLECGPPwGHPEPTVSWWKDGKPLALQPGRHTVSGGSLLMARAEKSDEGTYMCVATNSAGH 212
Cdd:cd04969    2 DFELNPvkKKILAAKGGDVIIECKPK-ASPKPTISWSKGTELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGK 80

                 ....*
gi 37181272  213 RESRA 217
Cdd:cd04969   81 ANSTG 85

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. 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. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 37181272  140 PRDMVAVVGEQFTLECGPPwGHPEPTVSWWKDGKPLALQpGRHTVSGGSLLMARAEKSDEGTYMCVATNSAG 211
Cdd:cd05728    6 ISDTEADIGSSLRWECKAS-GNPRPAYRWLKNGQPLASE-NRIEVEAGDLRITKLSLSDSGMYQCVAENKHG 75

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37181272     29 PQILVHPQDQLFQGPGPARMSCQASGQPPPTIRWLLNGQPLSmvpPDPHHllpdgtllllqppaRGHAHDG-------QA 101
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLR---SSDRF--------------KVTYEGGtytltisNV 63

                           90       100
                   ....*....|....*....|....*...
gi 37181272    102 LSTDLGVYTCEASNRLGTAVSRgARLSV 129
Cdd:pfam07679   64 QPDDSGKYTCVATNSAGEAEAS-AELTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37181272     28 PPQILVHPQDQLFQGPGPARMSCQASGQPPPTIRWLLNGQPLSMVPPDPHHLLPDGTLLLLQPPARGHAhdgqalstdlG 107
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDA----------G 70

                   ....*...
gi 37181272    108 VYTCEASN 115
Cdd:pfam13927   71 TYTCVASN 78

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 37181272   32 LVHPQDQLFQGPGPARMSCQASGQPPPTIRWLLNGQPLSMVPPDPHHLLPDGTLLLLQPPARGHAhdgqalSTDLGVYTC 111
Cdd:cd05722    5 LSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVSDERRQQLPNGSLLITSVVHSKHN------KPDEGFYQC 78

                         90
                 ....*....|....*....
gi 37181272  112 EASN-RLGTAVSRGARLSV 129
Cdd:cd05722   79 VAQNeSLGSIVSRTARVTV 97

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37181272  136 FQIQPRDMVAVVGEQFTLECGPPwGHPEPTVSWWKDGKPLALQPGRHTVSGG---SLLMARAEKSDEGTYMCVATNSAGh 212
Cdd:cd20972    4 FIQKLRSQEVAEGSKVRLECRVT-GNPTPVVRWFCEGKELQNSPDIQIHQEGdlhSLIIAEAFEEDTGRYSCLATNSVG- 81

                         90
                 ....*....|
gi 37181272  213 RESRAARVSI 222
Cdd:cd20972   82 SDTTSAEIFV 91

First 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 first 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 first 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 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, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37181272  131 VLREdfqiQPRDMVAVVGEQFTLECGPPWGHPEPTVSWWKDGKPLALQpgRHTVS----GGSLLMARAEKSDEGTYMCVA 206
Cdd:cd20979    2 VLKE----QPAEVLFREGQPTVLECVTEGGDQGVKYSWLKDGKSFNWQ--EHNVAqrkdEGSLVFLKPQASDEGQYQCFA 75

                         90
                 ....*....|.
gi 37181272  207 TNSAGHRESRA 217
Cdd:cd20979   76 ETPAGVASSRV 86

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 37181272  147 VGEQFTLECgPPWGHPEPTVSWWKDGKPL----ALQPGRHTVSGGSLLMARAEKSDEGTYMCVATNSAG 211
Cdd:cd05729   18 AANKVRLEC-GAGGNPMPNITWLKDGKEFkkehRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYG 85

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. 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 37181272  135 DFQIQPRDMVAVVGEQFTLECGPpWGHPEPTVSWWKDGKPLAlQPGRHTVSGGSLLMARAEKSDEGTYMCVATNSAGhRE 214
Cdd:cd05851    3 DINVKFKDTYALKGQNVTLECFA-LGNPVPVIRWRKILEPMP-ATAEISMSGAVLKIFNIQPEDEGTYECEAENIKG-KD 79

                 ....*....
gi 37181272  215 SRAARVSIQ 223
Cdd:cd05851   80 KHQARVYVQ 88

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 37181272  140 PRDMVAVVGEQFTLECGPPwGHPEPTVSWWKDGKPLALQPGRHTVSG--GSLLMARAEKSDEGTYMCVATNSAG 211
Cdd:cd20976    8 PKDLEAVEGQDFVAQCSAR-GKPVPRITWIRNAQPLQYAADRSTCEAgvGELHIQDVLPEDHGTYTCLAKNAAG 80

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 37181272   48 MSCQASGQPPPTIRWLLNGQPLSMvPPDPHHLLPDGTLLLLQPPArghahdgqalSTDLGVYTCEASNRLGTAVSRGARL 127
Cdd:cd05850   25 LACRARASPPATYRWKMNGTELKM-EPDSRYRLVAGNLVISNPVK----------AKDAGSYQCLASNRRGTVVSREASL 93

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37181272  143 MVAVVGEQFTLECgPPWGHPEPTVSWWKDGKPLAlQPGRHTV----SGGSLLMARAEKSDEGTYMCVATNSAGhreSRAA 218
Cdd:cd05748    2 IVVRAGESLRLDI-PIKGRPTPTVTWSKDGQPLK-ETGRVQIettaSSTSLVIKNAKRSDSGKYTLTLKNSAG---EKSA 76

                 ....*
gi 37181272  219 RVSIQ 223
Cdd:cd05748   77 TINVK 81

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. 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 37181272  139 QPRDMVAVVGEQFTLECGPPwGHPEPTVSWWKDGKPLAlQPGRHTVSG----GSLLMARAEKSDEGTYMCVATNSAGHRE 214
Cdd:cd05747    9 KPRSLTVSEGESARFSCDVD-GEPAPTVTWMREGQIIV-SSQRHQITSteykSTFEISKVQMSDEGNYTVVVENSEGKQE 86

                 .
gi 37181272  215 S 215
Cdd:cd05747   87 A 87

Fourth 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 fourth 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 37181272   28 PPQILVHPQDQLFQgPGPA-RMSCQASGQPPPTIRWLLNGQPlsmVPPDPHHLLpdgtllllqpparGH--AHDGQALS- 103
Cdd:cd20956    1 APVLLETFSEQTLQ-PGPSvSLKCVASGNPLPQITWTLDGFP---IPESPRFRV-------------GDyvTSDGDVVSy 63

                         90       100       110
                 ....*....|....*....|....*....|....
gi 37181272  104 --------TDLGVYTCEASNRLGTaVSRGARLSV 129
Cdd:cd20956   64 vnissvrvEDGGEYTCTATNDVGS-VSHSARINV 96