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 1782276006 388 GPPIITADATQHAVKHSKGKLECLVGNSPPPDKIVWTFGDVTLSSGSSGRFSVQTVTSDHGVLSSLVLSETLAQDFLLRY 467
Cdd:cd05758     1 GPPIITAEATQPAILGEKARLECLVFSSPPPDRIVWSWDEGFLESGSSGRFSVETFPTEPGVISVLHISGTQRSDFQTSF 80

                          90
                  ....*....|....*...
gi 1782276006 468 NCTAWNRFGTGTALVTLK 485
Cdd:cd05758    81 NCSAWNRFGEGTAIVSLG 98

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1782276006  19 YFSQQPQDQVVVSGQSVTLPCVIVGYRGM-VQWTKDGLALGGERdlpgwtRYSLmgDPLSGEHSLMIDSAELADDAVYEC 97
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVTGTPDPeVSWFKDGQPLRSSD------RFKV--TYEGGTYTLTISNVQPDDSGKYTC 73

                          90
                  ....*....|....*..
gi 1782276006  98 QAT-QAGLRSHRAKLTV 113
Cdd:pfam07679  74 VATnSAGEAEASAELTV 90

Fifth 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 fifth 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 (also known as Neph1), Kirrel2 (also known as Neph3), and Drosophila RST (also known as 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 1782276006 388 GPPIITADATQHAVKHSKGKLECLVGNSPPPDKIVWTFGDVTLSSGSSGRFSVQTVTSDHGVLSSLVLSETLAQDFLLRY 467
Cdd:cd05758     1 GPPIITAEATQPAILGEKARLECLVFSSPPPDRIVWSWDEGFLESGSSGRFSVETFPTEPGVISVLHISGTQRSDFQTSF 80

                          90
                  ....*....|....*...
gi 1782276006 468 NCTAWNRFGTGTALVTLK 485
Cdd:cd05758    81 NCSAWNRFGEGTAIVSLG 98

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1782276006  19 YFSQQPQDQVVVSGQSVTLPCVIVGYRGM-VQWTKDGLALGGERdlpgwtRYSLmgDPLSGEHSLMIDSAELADDAVYEC 97
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVTGTPDPeVSWFKDGQPLRSSD------RFKV--TYEGGTYTLTISNVQPDDSGKYTC 73

                          90
                  ....*....|....*..
gi 1782276006  98 QAT-QAGLRSHRAKLTV 113
Cdd:pfam07679  74 VATnSAGEAEASAELTV 90

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1782276006 136 YNLTCRASGAKPAAEITWYRDGEVMDTAIYSKTRMEDGKRELAVSMLPVVPEDKDSGRTYTCRVLNPA 203
Cdd:pfam08205  17 VVATCSSAGGKPAPRITWYLDGKPLEAAETSSEQDPESGLVTVTSELKLVPSRSDHGQSLTCQVSYGA 84

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1782276006 311 PKPMNVDIGMDAAFTCTWTGNPPLTLAWTKQG------SSVVLSNGNTLQLKAVTQEDAGTYTC 368
Cdd:cd20957     8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGkplghsSRVQILSEDVLVIPSVKREDKGMYQC 71

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 1782276006  19 YFSQQPQDQVVVSGQSVTLPCVIVGYRGMV-QWTKDGLALGGERDlpgwTRYSLMGDplsgeHSLMIDSAELA-----DD 92
Cdd:cd05722     3 YFLSEPSDIVAMRGGPVVLNCSAESDPPPKiEWKKDGVLLNLVSD----ERRQQLPN-----GSLLITSVVHSkhnkpDE 73

                          90       100
                  ....*....|....*....|....
gi 1782276006  93 AVYECQATQAGLR---SHRAKLTV 113
Cdd:cd05722    74 GFYQCVAQNESLGsivSRTARVTV 97

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1782276006  227 QPQTVMEGAKVLFICSASANPEITGYRWSKGGVPISEANGDSLEVTVDHSYFT-DPVS--------CEVSNSVGSTNVST 297
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTiSNVTpedsgtytCAATNSSGSASSGT 81

                   ....
gi 1782276006  298 LVDV 301
Cdd:smart00410  82 TLTV 85

Third immunoglobulin domain in Cluster of Differentiation (CD) 22; member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain in Cluster of Differentiation (CD) 22 (also known as Siglec-2). CD22, a sialic-acid binding immunoglobulin type-lectin (Siglec) family member, is an inhibitory co-receptor of the B-cell receptor (BCR). The inhibitory function of CD22 and its restricted expression on B cells makes CD22 an attractive target against dysregulated B cells that cause autoimmune diseases and B-cell-derived cancers. CD22 plays a vital role in establishing a baseline level of B-cell inhibition, and thus is an important determinant of homeostasis in humoral immunity. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. 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' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1782276006 220 PSVTLSVQPQ--TVMEGAKVLFICS-ASANPEITGYRWSKGGVPISEANGDSL---EVTVDHSyftDPVSCEVSNSVG 291
Cdd:cd20937     1 PKLEIKVTPSdaIVREGDSVTMTCEvSSSNPEYTTVSWLKDGTSLKKQNTFTLnlrEVTKDQS---GKYCCQVSNDVG 75

Fifth 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 fifth 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 (also known as Neph1), Kirrel2 (also known as Neph3), and Drosophila RST (also known as 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 1782276006 388 GPPIITADATQHAVKHSKGKLECLVGNSPPPDKIVWTFGDVTLSSGSSGRFSVQTVTSDHGVLSSLVLSETLAQDFLLRY 467
Cdd:cd05758     1 GPPIITAEATQPAILGEKARLECLVFSSPPPDRIVWSWDEGFLESGSSGRFSVETFPTEPGVISVLHISGTQRSDFQTSF 80

                          90
                  ....*....|....*...
gi 1782276006 468 NCTAWNRFGTGTALVTLK 485
Cdd:cd05758    81 NCSAWNRFGEGTAIVSLG 98

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1782276006 305 PRLLSEPKPMNVDIGMDAAFTCTWTGNPPLTLAWTKQGSSV-------VLSNGN--TLQLKAVTQEDAGTYTCKAIVPrI 375
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLrssdrfkVTYEGGtyTLTISNVQPDDSGKYTCVATNS-A 79

                          90
                  ....*....|.
gi 1782276006 376 GVAERDVTLTV 386
Cdd:pfam07679  80 GEAEASAELTV 90

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1782276006  19 YFSQQPQDQVVVSGQSVTLPCVIVGYRGM-VQWTKDGLALGGERdlpgwtRYSLmgDPLSGEHSLMIDSAELADDAVYEC 97
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVTGTPDPeVSWFKDGQPLRSSD------RFKV--TYEGGTYTLTISNVQPDDSGKYTC 73

                          90
                  ....*....|....*..
gi 1782276006  98 QAT-QAGLRSHRAKLTV 113
Cdd:pfam07679  74 VATnSAGEAEASAELTV 90

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1782276006 310 EPKPMNVDIGMDAAFTCTWTGNPPLTLAWTKQGSsvVLSNGNTLQLKAVTQEDAGTYTCKAIVPRIGVAERDVTLTV 386
Cdd:pfam13895   5 TPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGS--AISSSPNFFTLSVSAEDSGTYTCVARNGRGGKVSNPVELTV 79

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1782276006   24 PQDQVVVSGQSVTLPCVIVGYRG-MVQWTKDGLALGGERDlpgwtRYSLmgDPLSGEHSLMIDSAELADDAVYECQAT-Q 101
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPpEVTWYKQGGKLLAESG-----RFSV--SRSGSTSTLTISNVTPEDSGTYTCAATnS 73

                           90
                   ....*....|..
gi 1782276006  102 AGLRSHRAKLTV 113
Cdd:smart00410  74 SGSASSGTTLTV 85

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1782276006 311 PKPMNVDIGMDAAFTCTWTGNPPLTLAWTKQG------SSVVLSNGNTLQLKAVTQEDAGTYTC 368
Cdd:cd20957     8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGkplghsSRVQILSEDVLVIPSVKREDKGMYQC 71

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1782276006 137 NLTCRASGaKPAAEITWYRDGEVMDTAIYSKTRMEDGKRELavSMLPVVPEdkDSGrTYTCRVLNPA 203
Cdd:cd00096     2 TLTCSASG-NPPPTITWYKNGKPLPPSSRDSRRSELGNGTL--TISNVTLE--DSG-TYTCVASNSA 62

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1782276006 307 LLSEPKPMNVDIGMDAAFTCTWTGNPPLTLAWTKQGSSV--------VLSNGnTLQLKAVTQEDAGTYTCKAIVPrIGVA 378
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLlgkderitTLENG-SLQIKGAEKSDTGEYTCVALNL-SGEA 79

                  ....*...
gi 1782276006 379 ERDVTLTV 386
Cdd:cd20952    80 TWSAVLDV 87

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1782276006 308 LSEPKPMNVDIGMDAAFTCTWTGNPPLTLAWTKQGSSVVLS-----NGNTLQLKAVTQEDAGTYTCKA--IVpriGVAER 380
Cdd:cd05725     1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGryeilDDHSLKIRKVTAGDMGSYTCVAenMV---GKIEA 77

                  ....*.
gi 1782276006 381 DVTLTV 386
Cdd:cd05725    78 SATLTV 83

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1782276006 128 IRVKAHTPYNLTCRASGAKPAAEITWYRDGEVMDTAIYSKtrmeDGKRELAVSMLPVVPEDKDSGRTYTCRVLNPAAPAG 207
Cdd:pfam00047   6 VTVLEGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVK----HDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSAT 81

                  ....*
gi 1782276006 208 LQTSV 212
Cdd:pfam00047  82 LSTSL 86

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 1782276006 309 SEPKPMNVDIGMDAAFTCTWTGNPPLTLAWTKQGSSVVLSNG------NTLQLKAVTQEDAGTYTCKAiVPRIGVAERDV 382
Cdd:cd20978     6 KPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMEratvedGTLTIINVQPEDTGYYGCVA-TNEIGDIYTET 84

                  ....
gi 1782276006 383 TLTV 386
Cdd:cd20978    85 LLHV 88

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1782276006 319 GMDAAFTCTWTGNPPLTLAWTKQGSS-------VVLSNGnTLQLKAVTQEDAGTYTCKAIVPrIGVAERDVTLTV 386
Cdd:cd05745     2 GQTVDFLCEAQGYPQPVIAWTKGGSQlsvdrrhLVLSSG-TLRISRVALHDQGQYECQAVNI-VGSQRTVAQLTV 74

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1782276006 223 TLSVQPQTVMEGAKVLFICSASANPEITgYRWSKGGVPISEA-NGDSLEVTVDHS--YFtdpvsCEVSNSVGS 292
Cdd:pfam13895   3 VLTPSPTVVTEGEPVTLTCSAPGNPPPS-YTWYKDGSAISSSpNFFTLSVSAEDSgtYT-----CVARNGRGG 69

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1782276006  22 QQPQDQVVVSGQSVTLPCVIVGYR----GMVQWTKDGLALGGERDLPGWT----------RYSLMGDPLSGEHSLMIDSA 87
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMseasTSVYWYRQPPGKGPTFLIAYYSngseegvkkgRFSGRGDPSNGDGSLTIQNL 80

                          90       100
                  ....*....|....*....|....*....
gi 1782276006  88 ELADDAVYECQATQAGLR--SHRAKLTVL 114
Cdd:pfam07686  81 TLSDSGTYTCAVIPSGEGvfGKGTRLTVL 109

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 1782276006  19 YFSQQPQDQVVVSGQSVTLPCVIVGYRGMV-QWTKDGLALGGERDlpgwTRYSLMGDplsgeHSLMIDSAELA-----DD 92
Cdd:cd05722     3 YFLSEPSDIVAMRGGPVVLNCSAESDPPPKiEWKKDGVLLNLVSD----ERRQQLPN-----GSLLITSVVHSkhnkpDE 73

                          90       100
                  ....*....|....*....|....
gi 1782276006  93 AVYECQATQAGLR---SHRAKLTV 113
Cdd:cd05722    74 GFYQCVAQNESLGsivSRTARVTV 97

Second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R; also known as cluster of differentiation (CD) 121). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three IG-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta. This group also contains ILIR-like 1 (IL1R1L) which maps to the same chromosomal location as IL1R1 and IL1R2.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1782276006 335 TLAWTK-----QGSSVVLSNGNTLQLKAVTQEDAGTYTCKAIVPRIGVAeRDVTLTVN 387
Cdd:cd05757    31 PIQWYKdckplQGDKRFIPKGSKLLIQNVTEEDAGNYTCKFTYTHNGKQ-YNVTRTIS 87

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 1782276006 305 PRLLSEPKPMNVDIGMDAAFTCTWTGNPPLTLAWTKQGSSV------------VLSNGNTLQLKAV----TQEDAGTYTC 368
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLetdkddprshriVLPSGSLFFLRVVhgrkGRSDEGVYVC 80

                          90
                  ....*....|....*....
gi 1782276006 369 KAiVPRIGVA-ERDVTLTV 386
Cdd:cd07693    81 VA-HNSLGEAvSRNASLEV 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 1782276006 305 PRLLSEPKPMNVDIGMDAAFTCTWTGNPPLTLAWTKQGSSV---------VLSNG-NTLQLKAVTQEDAGTYTCKAiVPR 374
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVrpdsahkmlVRENGrHSLIIEPVTKRDAGIYTCIA-RNR 79

                          90
                  ....*....|..
gi 1782276006 375 IGVAERDVTLTV 386
Cdd:cd05744    80 AGENSFNAELVV 91

Immunoglobulin Constant-1 (C1)-set domain; The members here are composed of C1-set domains, classical Ig-like domains resembling the antibody constant domain. Members of the IgC1 family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, while the IgC domain is involved in oligomerization and molecular interactions. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other strands by G, F, C, and C'.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1782276006 137 NLTCRASGAKPA-AEITWYRDGEVMDTAI--YSKTRMEDGKRELAvSMLPVVPEDKDSGRTYTCRVLNPAAPAGLQTSV 212
Cdd:cd00098    18 TLVCLVSGFYPKdITVTWLKNGVPLTSGVstSSPVEPNDGTYSVT-SSLTVPPSDWDEGATYTCVVTHESLKSPLSKTW 95

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1782276006  24 PQDQVVVSGQSVTLPCVIvgyRG----MVQWTKDglalGGErdLPGwTRYSLMGDplsgeHSLMIDSAELADDAVYECQA 99
Cdd:cd05725     4 PQNQVVLVDDSAEFQCEV---GGdpvpTVRWRKE----DGE--LPK-GRYEILDD-----HSLKIRKVTAGDMGSYTCVA 68

                          90
                  ....*....|....*
gi 1782276006 100 TQA-GLRSHRAKLTV 113
Cdd:cd05725    69 ENMvGKIEASATLTV 83

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1782276006 306 RLLSEPKPMNVDIGMDAAFTCTWTGNPPLTLAWTKQGSSVVLSN---------GNTLQLKAVTQEDAGTYT 367
Cdd:cd05747     5 TILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQrhqitsteyKSTFEISKVQMSDEGNYT 75

CH2 domain (second constant Ig domain of the heavy chain) in immunoglobulin E (IgE); member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second constant domain of the heavy chain of immunoglobulin E (IgE). The basic structure of immunoglobulin (Ig) molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda; each is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta, and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). The different classes of antibodies vary in their heavy chains; the IgE class has the epsilon type. This domain (Cepsilon2) of IgE is in place of the flexible hinge region found in IgG.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1782276006 138 LTCRASGAKPA-AEITWYRDGEVM-DTAIYSKTRMEDGKRELAVSMLPVVPEDKDSGRTYTCRVLNPA 203
Cdd:cd05847    21 LLCLISGYTPStIEVEWLVDGQVAtLSAASTAPQKEEGGTFSTTSKLNVTQEDWKSGKTYTCKVTHQG 88