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 116007996  262 ADRKYEIECQAIGSRPPAKITWWMGNLELHG--HSQKVSEDGNVSTSV--LSITPTREDHGKALSCRATNELVRNGiRET 337
Cdd:cd05759    14 AGVPYNLTCRARGAKPAAEIIWFRDGEQLEGavYSKELLKDGKRETTVstLLITPSDLDTGRTFTCRARNEAIPNG-KET 92

                  ....*.
gi 116007996  338 AMKLNV 343
Cdd:cd05759    93 SITLDV 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 116007996   165 EEGGSLEVTCVVYGGsPPPTVIWLMNGQLQNSVVDYT-YDGAINSKLVVRNLSRIHQhAVYTCQASN 230
Cdd:pfam13927   14 REGETVTLTCEATGS-PPPTITWYKNGEPISSGSTRSrSLSGSNSTLTISNVTRSDA-GTYTCVASN 78

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116007996     35 LRVLVNSSAQIKCDVgssqADDKVLLVVWYKNNLPIYSYDtrgahagtpshwrdeevleDRAVFRTHKEPAELIINPVKE 114
Cdd:smart00410    4 VTVKEGESVTLSCEA----SGSPPPEVTWYKQGGKLLAES-------------------GRFSVSRSGSTSTLTISNVTP 60

                            90       100
                    ....*....|....*....|....*.
gi 116007996    115 KDAGNFRCRVDFKLSQTRnSNVNLEV 140
Cdd:smart00410   61 EDSGTYTCAATNSSGSAS-SGTTLTV 85

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 116007996  262 ADRKYEIECQAIGSRPPAKITWWMGNLELHG--HSQKVSEDGNVSTSV--LSITPTREDHGKALSCRATNELVRNGiRET 337
Cdd:cd05759    14 AGVPYNLTCRARGAKPAAEIIWFRDGEQLEGavYSKELLKDGKRETTVstLLITPSDLDTGRTFTCRARNEAIPNG-KET 92

                  ....*.
gi 116007996  338 AMKLNV 343
Cdd:cd05759    93 SITLDV 98

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116007996  362 IEEGDDVYFECKVHANPAAyKVVWKHNHQIIQHNQRAGVIVSSG---DLALQGVTRHQAGNYTCTASNVEGDGDSNvVEL 438
Cdd:cd05744    12 VQEGRLCRFDCKVSGLPTP-DLFWQLNGKPVRPDSAHKMLVRENgrhSLIIEPVTKRDAGIYTCIARNRAGENSFN-AEL 89

                  ..
gi 116007996  439 KV 440
Cdd:cd05744    90 VV 91

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116007996    363 EEGDDVYFECKVHANPAAYKVVWKHNHQIIQHNQRAGVIVSSGDLALQ--GVTRHQAGNYTCTASNVEGDGDSNvVELKV 440
Cdd:smart00410    7 KEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTisNVTPEDSGTYTCAATNSSGSASSG-TTLTV 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 116007996  170 LEVTCVVYGgSPPPTVIWLMNGQ-LQNSVVDYTYDGAINSKLVVRNLSRIHQhAVYTCQASNFHKKYVATNI 240
Cdd:cd00096     1 VTLTCSASG-NPPPTITWYKNGKpLPPSSRDSRRSELGNGTLTISNVTLEDS-GTYTCVASNSAGGSASASV 70

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 116007996  462 AEIVCEVDAFPPPEnFKWSFNNTAETFDMPQSGFRPHSaqGSTLTYTPVKEMDFGTIMCWADNNVGQQKE 531
Cdd:cd00096     1 VTLTCSASGNPPPT-ITWYKNGKPLPPSSRDSRRSELG--NGTLTISNVTLEDSGTYTCVASNSAGGSAS 67

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

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 116007996    267 EIECQAIGSrPPAKITWWMGNLELHGHSQKVSEDGNVSTSVLSITP-TREDHGKaLSCRATNElvrNGIRETAMKLNV 343
Cdd:smart00410   13 TLSCEASGS-PPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNvTPEDSGT-YTCAATNS---SGSASSGTTLTV 85

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

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 116007996    456 VARNEAAEIVCEVDAFPPPEnFKWSFNNTaeTFDMPQSGFRP-HSAQGSTLTYTPVKEMDFGTIMCWADNNVGQQKEP 532
Cdd:smart00410    6 VKEGESVTLSCEASGSPPPE-VTWYKQGG--KLLAESGRFSVsRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80

Fibronectin type III domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116007996   545 APTNCTVVNQTSDSLEVYCIEGFDGGMR-QWFLMEIFDQHSGQLQANISAKFAALSVT--GLDAGRLFRIYVYAVNGRGR 621
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPPDGNGPiTGYEVEYRPKNSGEPWNEITVPGTTTSVTltGLKPGTEYEVRVQAVNGGGE 81

                   .
gi 116007996   622 S 622
Cdd:pfam00041   82 G 82

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 116007996  262 ADRKYEIECQAIGSRPPAKITWWMGNLELHG--HSQKVSEDGNVSTSV--LSITPTREDHGKALSCRATNELVRNGiRET 337
Cdd:cd05759    14 AGVPYNLTCRARGAKPAAEIIWFRDGEQLEGavYSKELLKDGKRETTVstLLITPSDLDTGRTFTCRARNEAIPNG-KET 92

                  ....*.
gi 116007996  338 AMKLNV 343
Cdd:cd05759    93 SITLDV 98

Second immunoglobulin (Ig)-like domain of nectin-like molcule-1 (Necl-1); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molcule-1 (Necl-1; also known as cell adhesion molecule3 (CADM3)). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains is essential to cell-cell adhesion and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116007996  265 KYEIECQAIGSRPPAKITWWMGNLELHGHSQKVSEDGNVST----SVLSITPTREDHGKALSCRATNELVRNGIRETAMK 340
Cdd:cd07705    21 KAKLRCTSSGSKPAANIKWRKGDQELEGAPTSVQEDGNGKTftvsSSVEFQVTREDDGAEITCSVGHESLHDSDRSTSQR 100

                  ...
gi 116007996  341 LNV 343
Cdd:cd07705   101 IEV 103

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116007996  362 IEEGDDVYFECKVHANPAAyKVVWKHNHQIIQHNQRAGVIVSSG---DLALQGVTRHQAGNYTCTASNVEGDGDSNvVEL 438
Cdd:cd05744    12 VQEGRLCRFDCKVSGLPTP-DLFWQLNGKPVRPDSAHKMLVRENgrhSLIIEPVTKRDAGIYTCIARNRAGENSFN-AEL 89

                  ..
gi 116007996  439 KV 440
Cdd:cd05744    90 VV 91

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 116007996  365 GDDVYFECKVHANPAAyKVVWKHNHQIIQHNQRAgVIVSSGDLALQGVTRHQAGNYTCTASNVEGDGDS 433
Cdd:cd04969    17 GGDVIIECKPKASPKP-TISWSKGTELLTNSSRI-CILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANS 83

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116007996   359 PEDIE--EGDDVYFECKVHANPAAyKVVWKHNHQIIQHNQRaGVIVSSGD---LALQGVTRHQAGNYTCTASNVEGDgDS 433
Cdd:pfam07679    7 PKDVEvqEGESARFTCTVTGTPDP-EVSWFKDGQPLRSSDR-FKVTYEGGtytLTISNVQPDDSGKYTCVATNSAGE-AE 83

                   ....*..
gi 116007996   434 NVVELKV 440
Cdd:pfam07679   84 ASAELTV 90

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116007996   356 NLNPEDIEEGDDVYFECKVHANPAAyKVVWKHNHQIIqhNQRAGVIVSSgdlalqgVTRHQAGNYTCTASNVEGDGDSNV 435
Cdd:pfam13895    5 TPSPTVVTEGEPVTLTCSAPGNPPP-SYTWYKDGSAI--SSSPNFFTLS-------VSAEDSGTYTCVARNGRGGKVSNP 74

                   ....*
gi 116007996   436 VELKV 440
Cdd:pfam13895   75 VELTV 79

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 116007996  170 LEVTCVVYGgSPPPTVIWLMNGQ-LQNSVVDYTYDGAINSKLVVRNLSRIHQhAVYTCQASNFHKKYVATNI 240
Cdd:cd00096     1 VTLTCSASG-NPPPTITWYKNGKpLPPSSRDSRRSELGNGTLTISNVTLEDS-GTYTCVASNSAGGSASASV 70

Second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2); 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 2 (Necl-2; also known as cell adhesion molecule 1 (CADM1)). Nectin-like molecules (Necls) have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-2 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 116007996  267 EIECQAIGSRPPAKITWWMGNLELHGHS--QKVSEDGNVSTSVLSITPTREDHGKALSC 323
Cdd:cd05883    23 ELNCTAMASKPAATIRWFKGNKELTGKSevEEWYSRMFTVTSQLMLKVTKEDDGVPVIC 81

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 116007996  357 LNPEDIE--EGDDVYFEC---KVHANPaayKVVWKHNHQIIQHNQRAGVIVSSGDLALQGVTRHQAGNYTCTASNVEGDG 431
Cdd:cd05724     2 VEPSDTQvaVGEMAVLECsppRGHPEP---TVSWRKDGQPLNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGER 78

                  ....*....
gi 116007996  432 DSNVVELKV 440
Cdd:cd05724    79 ESRAARLSV 87

Sixth 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 sixth 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 116007996  142 VPPTQPIIFNErrlridsraGPYEEGGSLEVTCVVYGGSPPPTVIWLMNGQ--LQNSVVDYTYDGAINSKLVVRNLSRIH 219
Cdd:cd20959     1 PPRIIPFAFGE---------GAAQVGMRAQLHCGVPGGDLPLNIRWTLDGQpiSDDLGITVSRLGRRSSILSIDSLEASH 71

                          90       100
                  ....*....|....*....|
gi 116007996  220 QhAVYTCQASNF--HKKYVA 237
Cdd:cd20959    72 A-GNYTCHARNSagSASYTA 90

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 116007996  165 EEGGSLEVTCVVYGgSPPPTVIWLMNG-QLQNSVVDYTYDGaINSKLVVRNLSRIHQHAvYTCQASN 230
Cdd:cd20970    15 REGENATFMCRAEG-SPEPEISWTRNGnLIIEFNTRYIVRE-NGTTLTIRNIRRSDMGI-YLCIASN 78

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 116007996  157 IDSRAGPYEEGGSLEVTCVVyGGSPPPTVIWLMNG---QLQNSVVDYTYDGAInskLVVRNLSRIHQhAVYTCQASNFHK 233
Cdd:cd04978     4 IEPPSLVLSPGETGELICEA-EGNPQPTITWRLNGvpiEPAPEDMRRTVDGRT---LIFSNLQPNDT-AVYQCNASNVHG 78

                  ....
gi 116007996  234 KYVA 237
Cdd:cd04978    79 YLLA 82

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116007996    165 EEGGSLEVTCVVYGgSPPPTVIWLMNGQ---LQNSVVDYTYDGAiNSKLVVRNLSRIHQhAVYTCQASNFHKKYVA-TNI 240
Cdd:smart00410    7 KEGESVTLSCEASG-SPPPEVTWYKQGGkllAESGRFSVSRSGS-TSTLTISNVTPEDS-GTYTCAATNSSGSASSgTTL 83

                    ..
gi 116007996    241 TI 242
Cdd:smart00410   84 TV 85

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. 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 116007996  364 EGDDVYFECKVHANPAAyKVVWKHNHQIIQHN--------QRAGVIVssgdLALQGVTRHQAGNYTCTASNVEG 429
Cdd:cd05892    14 EGDPVRLECQISAIPPP-QIFWKKNNEMLQYNtdrislyqDNCGRIC----LLIQNANKKDAGWYTVSAVNEAG 82

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 116007996  365 GDDVYFECKVHANPAaYKVVWKHNHQIIQHNQRAGViVSSGDLALQGVTRHQ-AGNYTCTASNVEGDGDSNVVELKV 440
Cdd:cd20958    15 GQTLRLHCPVAGYPI-SSITWEKDGRRLPLNHRQRV-FPNGTLVIENVQRSSdEGEYTCTARNQQGQSASRSVFVKV 89

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116007996  361 DIEEGDDVYFECKVHANPAAYKV-VWKHNHQIIQ------HNQRAGVIVSSGDLALQGVTRHQAGNYTCTASNVeGDGDS 433
Cdd:cd04970    13 DITVGENATLQCHASHDPTLDLTfTWSFNGVPIDlekiegHYRRRYGKDSNGDLEIVNAQLKHAGRYTCTAQTV-VDSDS 91

                          90
                  ....*....|.
gi 116007996  434 NVVELKVMYKP 444
Cdd:cd04970    92 ASATLVVRGPP 102

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 116007996  267 EIECQAIGSRPPAKITWWMGNLELHGHSQKvSEDGNV--STSVLSITPTREDHGKALSCRATNE-LVRNGIRETAMKLNV 343
Cdd:cd05885    22 ELSCLVPRSRPAATLRWYRDRKELKGVSSG-QENGKVwsVASTVRFRVDRKDDGGIVICEAQNQaLPSGHSKQTQYVLDV 100

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 116007996  456 VARNEAAEIVCEVDAFPPPeNFKWSfnntAETFDMPQSgfRPHSAQGSTLTYTPVKEMDFGTIMCWADNNVGQ 528
Cdd:cd05725     9 VLVDDSAEFQCEVGGDPVP-TVRWR----KEDGELPKG--RYEILDDHSLKIRKVTAGDMGSYTCVAENMVGK 74

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 116007996   166 EGGSLEV--TCVVYGGSPPPTVIWLMNGQLQNSVVDYTYDGAIN------SKLVVRNLSRIHQHAVyTCQASN 230
Cdd:pfam08205   11 EGEGPEVvaTCSSAGGKPAPRITWYLDGKPLEAAETSSEQDPESglvtvtSELKLVPSRSDHGQSL-TCQVSY 82

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 116007996  165 EEGGSLEVTCVVyGGSPPPTVIWLMNGQ-LQNSVVDYTYDgaiNSKLVVRNLsRIHQHAVYTCQASNFH-KKYVATNITI 242
Cdd:cd20978    14 KGGQDVTLPCQV-TGVPQPKITWLHNGKpLQGPMERATVE---DGTLTIINV-QPEDTGYYGCVATNEIgDIYTETLLHV 88

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116007996  361 DIEEGDDVYFECKVHANP-AAYKvvWKHNHQIIQHNQRagVIVSSGDLALQGVTRHQAGNYTCTASNVEGDGDSNvVELK 439
Cdd:cd05728    10 EADIGSSLRWECKASGNPrPAYR--WLKNGQPLASENR--IEVEAGDLRITKLSLSDSGMYQCVAENKHGTIYAS-AELA 84

                  .
gi 116007996  440 V 440
Cdd:cd05728    85 V 85

Second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3); 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-3 (Necl-3; also known as cell adhesion molecule 2 (CADM2)). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Ig domains are likely to participate in ligand binding and recognition.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116007996  252 EISFNNQPMSADRKYEIECQAIGSRPPAKITWWMGNLELHGHSQKVSEDGNVST----SVLSITPTREDHGKALSCRATN 327
Cdd:cd05884     9 QISGFTSPVMEGDHIQLTCKTSGSKPAADIRWFKNDKEVKDVKYLKAEDANRKTftvsSSLDFHVDRDDDGVAITCRVDH 88

                  .
gi 116007996  328 E 328
Cdd:cd05884    89 E 89

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 116007996  362 IEEGDDVYFECKVHANPAAyKVVWKHNHQIIQHNQRAGVIvSSGDLALQGVTRHQAGNYTCTASNVEGDGDSNVVELKV 440
Cdd:cd20968    11 IIEGLKAVLPCTTMGNPKP-SVSWIKGDDLIKENNRIAVL-ESGSLRIHNVQKEDAGQYRCVAKNSLGIAYSKPVTIEV 87

First immunoglobulin (Ig) domain of contactin-5; 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-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 116007996  179 GSPPPTVIWLMNGQLQNSVVDYTYDgAINSKLVVRNLSRIHQHAVYTCQASN 230
Cdd:cd05848    30 GNPVPTYRWLRNGTEIDTESDYRYS-LIDGNLIISNPSEVKDSGRYQCLATN 80