Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. 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 second Ig-like domain of JAM1 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, the A strand of the I-set is discontinuous but lacks 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 1843657940 135 PTVNIPSSATIGNRAVLTCSEQDGSPPSEYTWFKDGIVMPTNPKSTRAFSNSSYVLNPTTGELVFDPLSASDTGEYSCEA 214
Cdd:cd20950     1 PTVNIPSSATIGNRAVLTCSEPDGSPPSEYTWFKDGVVMPTNPKSTRAFSNSSYSLDPTTGELVFDPLSASDTGEYSCEA 80

                          90
                  ....*....|....*..
gi 1843657940 215 RNGYGTPMTSNAVRMEA 231
Cdd:cd20950    81 RNGYGTPMRSNAVRMEA 97

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. 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 second Ig-like domain of JAM1 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, the A strand of the I-set is discontinuous but lacks 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 1843657940 135 PTVNIPSSATIGNRAVLTCSEQDGSPPSEYTWFKDGIVMPTNPKSTRAFSNSSYVLNPTTGELVFDPLSASDTGEYSCEA 214
Cdd:cd20950     1 PTVNIPSSATIGNRAVLTCSEPDGSPPSEYTWFKDGVVMPTNPKSTRAFSNSSYSLDPTTGELVFDPLSASDTGEYSCEA 80

                          90
                  ....*....|....*..
gi 1843657940 215 RNGYGTPMTSNAVRMEA 231
Cdd:cd20950    81 RNGYGTPMRSNAVRMEA 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 1843657940   36 PEVRIPENNPVKLSCAYSGFSSPRVEWKFDQGdttRLVCYNNKITASYEDRVTFLptgiTFKSVTREDTGTYTCMVSEEG 115
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGG---KLLAESGRFSVSRSGSTSTL----TISNVTPEDSGTYTCAATNSS 74

                           90
                   ....*....|
gi 1843657940  116 GNSYGEVKVK 125
Cdd:smart00410  75 GSASSGTTLT 84

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1843657940  142 SATIGNRAVLTCsEQDGSPPSEYTWFKDGIVMPTNPKSTRAFSNSsyvlnpTTGELVFDPLSASDTGEYSCEARNGYGT 220
Cdd:smart00410   5 TVKEGESVTLSC-EASGSPPPEVTWYKQGGKLLAESGRFSVSRSG------STSTLTISNVTPEDSGTYTCAATNSSGS 76

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. 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 second Ig-like domain of JAM1 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, the A strand of the I-set is discontinuous but lacks 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 1843657940 135 PTVNIPSSATIGNRAVLTCSEQDGSPPSEYTWFKDGIVMPTNPKSTRAFSNSSYVLNPTTGELVFDPLSASDTGEYSCEA 214
Cdd:cd20950     1 PTVNIPSSATIGNRAVLTCSEPDGSPPSEYTWFKDGVVMPTNPKSTRAFSNSSYSLDPTTGELVFDPLSASDTGEYSCEA 80

                          90
                  ....*....|....*..
gi 1843657940 215 RNGYGTPMTSNAVRMEA 231
Cdd:cd20950    81 RNGYGTPMRSNAVRMEA 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 1843657940   36 PEVRIPENNPVKLSCAYSGFSSPRVEWKFDQGdttRLVCYNNKITASYEDRVTFLptgiTFKSVTREDTGTYTCMVSEEG 115
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGG---KLLAESGRFSVSRSGSTSTL----TISNVTPEDSGTYTCAATNSS 74

                           90
                   ....*....|
gi 1843657940  116 GNSYGEVKVK 125
Cdd:smart00410  75 GSASSGTTLT 84

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 1843657940 149 AVLTCSEQdGSPPSEYTWFKDGIVMPTNPKSTRAFSNSSyvlnpttGELVFDPLSASDTGEYSCEARNGYGTPMTSNA 226
Cdd:cd00096     1 VTLTCSAS-GNPPPTITWYKNGKPLPPSSRDSRRSELGN-------GTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1843657940 143 ATIGNRAVLTCSEQDGSPPSEYTWFKDGIVMPTNpkstRAFSNSSyvLNPTTGELVFDPLSASDTGEYSCEARNGYG 219
Cdd:cd20959    14 AQVGMRAQLHCGVPGGDLPLNIRWTLDGQPISDD----LGITVSR--LGRRSSILSIDSLEASHAGNYTCHARNSAG 84

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843657940 131 PPS-KPTVNIpsSATIGNRAVLTCSEQdGSPPSEYTWFKDGIVMPTNPKStRAFSNssyvlnpttGELVFDPL-SASDTG 208
Cdd:cd20958     1 PPFiRPMGNL--TAVAGQTLRLHCPVA-GYPISSITWEKDGRRLPLNHRQ-RVFPN---------GTLVIENVqRSSDEG 67

                          90
                  ....*....|....*..
gi 1843657940 209 EYSCEARNGYGTPMTSN 225
Cdd:cd20958    68 EYTCTARNQQGQSASRS 84

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 1843657940 140 PSS--ATIGNRAVLTCSEQDGSPPSEYTWFKDGIvmPTNPKSTRAfsnssYVLnpTTGELVFDPLSASDTGEYSCEARNG 217
Cdd:cd05724     4 PSDtqVAVGEMAVLECSPPRGHPEPTVSWRKDGQ--PLNLDNERV-----RIV--DDGNLLIAEARKSDEGTYKCVATNM 74

                  ...
gi 1843657940 218 YGT 220
Cdd:cd05724    75 VGE 77

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 1843657940  46 VKLSCAYSGFSSPRVEWKFDQGDTTrlvcynnkiTASYEDRVTFLPTG-ITFKSVTREDTGTYTCMVSEEGG 116
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLP---------PSSRDSRRSELGNGtLTISNVTLEDSGTYTCVASNSAG 63

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843657940  38 VRIPENNPVKLSCAYSGFSSPRVEWKFDQGDTTRlvcyNNKITASYEDRVTFLptgiTFKSVTREDTGTYTCMVSeeggN 117
Cdd:pfam07679  10 VEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRS----SDRFKVTYEGGTYTL----TISNVQPDDSGKYTCVAT----N 77

                          90
                  ....*....|...
gi 1843657940 118 SYGEVKVKLIVLV 130
Cdd:pfam07679  78 SAGEAEASAELTV 90

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1843657940 158 GSPPSEYTWFKDGIVMPTnpkstrafSNSSYVLNpttGELVFDPLSASDTGEYSCEARNGYGT 220
Cdd:cd05728    25 GNPRPAYRWLKNGQPLAS--------ENRIEVEA---GDLRITKLSLSDSGMYQCVAENKHGT 76

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 1843657940  33 SSEPEVRIPENNPVKLSCAYSGFSS-PRVEWKFD--QGDTTRLVCYNNKITASyedrvtflpTGITFKSVTREDTGTYTC 109
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGSPgPDVTWSKEggTLIESLKVKHDNGRTTQ---------SSLLISNVTKEDAGTYTC 71

                          90
                  ....*....|....*
gi 1843657940 110 MVSEEGGNSYGEVKV 124
Cdd:pfam00047  72 VVNNPGGSATLSTSL 86

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843657940 134 KPTVNIPSSATIGNR--AVLTCSEQDgsPPSEYTWFKDGIVMPTNPKSTrafsnssyvLNPTTGELVFDPLSASDTGEYS 211
Cdd:cd05740     1 KPFISSNNSNPVEDKdaVTLTCEPET--QNTSYLWWFNGQSLPVTPRLT---------LSNGNRTLTLLNVTREDAGAYQ 69

                  ....*
gi 1843657940 212 CEARN 216
Cdd:cd05740    70 CEISN 74

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. 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 Lingo-1 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 1843657940  42 ENNPVKLSCAYSGFSSPRVEWkfdqgdttrLVCYNNKITASYEDRVTFLPTG-ITFKSVTREDTGTYTCMVSEEGGNSYG 120
Cdd:cd20969    16 EGHTVQFVCRADGDPPPAILW---------LSPRKHLVSAKSNGRLTVFPDGtLEVRYAQVQDNGTYLCIAANAGGNDSM 86

                  ....*.
gi 1843657940 121 EVKVKL 126
Cdd:cd20969    87 PAHLHV 92

First immunoglobulin (Ig)-like domain of Tyro3 receptor tyrosine kinase (RTK), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Tyro3 receptor tyrosine kinase (RTK). Tyro3 together with Axl and Mer form the Axl/Tyro3 family of receptor tyrosine kinases (RTKs). This family includes Axl (also known as Ark, Ufo, and Tyro7), Tyro3 (also known as Sky, Rse, Brt, Dtk, and Tif), and Mer (also known as Nyk, c-Eyk, and Tyro12). Axl/Tyro3 family receptors have an extracellular portion with two Ig-like domains followed by two fibronectin-types III (FNIII) domains, a membrane-spanning single helix, and a cytoplasmic tyrosine kinase domain. Axl, Tyro3 and Mer are widely expressed in adult tissues, though they show higher expression in the brain, in the lymphatic and vascular systems, and in the testis. Axl, Tyro3, and Mer bind the vitamin K dependent protein Gas6 with high affinity, and in doing so activate their tyrosine kinase activity. Axl/Gas6 signaling may play a part in cell adhesion processes, prevention of apoptosis, and cell proliferation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843657940  37 EVRIPENNPVKLSCAYSGFSSPRVEWKFDQGDTTRLvcYNNKITASYEDRVTFLptgiTFKSVTREDTGTYTCMVsEEGG 116
Cdd:cd20961     2 KLTVSQGQPVKLNCSVEGMEEPDIQWVKDGAVVQNL--DQLYIPVSEQHWIGFL----SLKSVERSDAGRYWCQV-EDGG 74

                  ..
gi 1843657940 117 NS 118
Cdd:cd20961    75 ET 76

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843657940 126 LIVLVPPSKPTVNIpssatiGNRAVLTCSEQdGSPPSEYTWFKDGivmptnpkstRAFSNSSYVLNPTTGELVFDPLSAS 205
Cdd:cd20957     2 LSATIDPPVQTVDF------GRTAVFNCSVT-GNPIHTVLWMKDG----------KPLGHSSRVQILSEDVLVIPSVKRE 64

                          90
                  ....*....|.
gi 1843657940 206 DTGEYSCEARN 216
Cdd:cd20957    65 DKGMYQCFVRN 75

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 1843657940 140 PSSAT--IGNRAVLTCsEQDGSPPSEYTWFKDGIVMPTNPkstrafSNSSYVLNPTTgeLVFDPLSASDTGEYSCEARNG 217
Cdd:cd04978     6 PPSLVlsPGETGELIC-EAEGNPQPTITWRLNGVPIEPAP------EDMRRTVDGRT--LIFSNLQPNDTAVYQCNASNV 76

                  ....*....
gi 1843657940 218 YGtPMTSNA 226
Cdd:cd04978    77 HG-YLLANA 84

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 1843657940  38 VRIPENNPVKLSCAYSGFSSPRVEWKFDQGDTTRLVCYNNKITASYedrvtflpTGITFKSVTREDTGTYTCMVSeeggN 117
Cdd:cd05748     2 IVVRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETTASS--------TSLVIKNAKRSDSGKYTLTLK----N 69

                          90
                  ....*....|...
gi 1843657940 118 SYGEVKVKLIVLV 130
Cdd:cd05748    70 SAGEKSATINVKV 82

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843657940  35 EPE-VRIPENNPVKLSCAYSGFSSPRVEWKFDQGDTTrlvcyNNKITASYEDRVTFLPTG-ITFKSVTREDTGTYTCmvs 112
Cdd:cd20954     7 EPVdANVAAGQDVMLHCQADGFPTPTVTWKKATGSTP-----GEYKDLLYDPNVRILPNGtLVFGHVQKENEGHYLC--- 78

                          90
                  ....*....|....*..
gi 1843657940 113 eEGGNSYGEVKVKLIVL 129
Cdd:cd20954    79 -EAKNGIGSGLSKVIFL 94

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1843657940 146 GNRAVLTCSEQDGSPPSEYTWFKDGivMPTNpkstraFSNSSYVLNPTTGELVFDPLSASDTGEYSCEARNGYG 219
Cdd:cd20979    15 GQPTVLECVTEGGDQGVKYSWLKDG--KSFN------WQEHNVAQRKDEGSLVFLKPQASDEGQYQCFAETPAG 80

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 1843657940 140 PSSATI--GNRAVLTCsEQDGSPPSEYTWFKDGivmptNPKSTRAFSNSSYVLNPTTGELVFDPL-----SASDTGEYSC 212
Cdd:cd07693     7 PSDLIVskGDPATLNC-KAEGRPTPTIQWLKNG-----QPLETDKDDPRSHRIVLPSGSLFFLRVvhgrkGRSDEGVYVC 80

                          90
                  ....*....|....
gi 1843657940 213 EARNGYGTPMTSNA 226
Cdd:cd07693    81 VAHNSLGEAVSRNA 94

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843657940 131 PPSKPTVNIPSSATIGNRAVLTCSEQdGSPPSEYTWFKDGivMPTNPKSTRafsnssYVLNPTTGELVFDPLSASDTGEY 210
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSAR-GKPVPRITWIRNA--QPLQYAADR------STCEAGVGELHIQDVLPEDHGTY 71

                          90
                  ....*....|
gi 1843657940 211 SCEARNGYGT 220
Cdd:cd20976    72 TCLAKNAAGQ 81

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 1843657940 127 IVLVPPSKPTVnipssaTIGNRAVLTCSEQdGSPPSEYTWFKDGIVMPTNPKSTRAFSNssyvlnpttGELVFDPLSASD 206
Cdd:cd20952     1 IILQGPQNQTV------AVGGTVVLNCQAT-GEPVPTISWLKDGVPLLGKDERITTLEN---------GSLQIKGAEKSD 64

                          90
                  ....*....|....
gi 1843657940 207 TGEYSCEARNGYGT 220
Cdd:cd20952    65 TGEYTCVALNLSGE 78

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843657940  41 PENNPVKLSCAYSGFSSPRVEWKFDQgdtTRLVcyNNKITASYEDRVTflptgITFKSVTREDTGTYTCMVSEEGG--NS 118
Cdd:cd05856    17 PVGSSVRLKCVASGNPRPDITWLKDN---KPLT--PPEIGENKKKKWT-----LSLKNLKPEDSGKYTCHVSNRAGeiNA 86

                  ....*.
gi 1843657940 119 YGEVKV 124
Cdd:cd05856    87 TYKVDV 92

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 1843657940 146 GNRAVLTCSEQdGSPPSEYTWFKDGivmptnpkstRAFSNSSYVLNPTTGELVFDPLSASDTGEYSCEARNGYGTPMTSN 225
Cdd:cd20978    16 GQDVTLPCQVT-GVPQPKITWLHNG----------KPLQGPMERATVEDGTLTIINVQPEDTGYYGCVATNEIGDIYTET 84

                  ..
gi 1843657940 226 AV 227
Cdd:cd20978    85 LL 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 1843657940  45 PVKLSCAYSGFSSPRVEWkfdqgdttrlvCYNNKITASYEDRVTFLPTGITFKSVTREDTGTYTCMVSEEGGNSYGEVKV 124
Cdd:cd20978    18 DVTLPCQVTGVPQPKITW-----------LHNGKPLQGPMERATVEDGTLTIINVQPEDTGYYGCVATNEIGDIYTETLL 86

                  .
gi 1843657940 125 K 125
Cdd:cd20978    87 H 87

Immunoglobulin C1-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1843657940 140 PSSATIGNRAVLTCSEQDGSPPS-EYTWFKDGIVMPTNPKST--RAFSNSSYVLnptTGELVFDPLSASDTGEYSC 212
Cdd:pfam07654   6 PSPEELGKPNTLTCLVTGFYPPDiTVTWLKNGQEVTEGVKTTppSPNSDWTYQL---SSYLTVTPSDWESGDEYTC 78

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843657940  37 EVRIPENNPVKLSCAYSGFSSPRVEWKFDQgdttRLVCYNNKITASYED---RVTFLptgitFKSVTREDTGTYTCMVSE 113
Cdd:cd05892     9 NKKVLEGDPVRLECQISAIPPPQIFWKKNN----EMLQYNTDRISLYQDncgRICLL-----IQNANKKDAGWYTVSAVN 79

                  ...
gi 1843657940 114 EGG 116
Cdd:cd05892    80 EAG 82

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1843657940 146 GNRAVLTCSEQdGSPPSEYTWFKDGIVMPTNPKstraFSNSSYVLNptTGELV----FDPLSASDTGEYSCEARNGYGT 220
Cdd:cd20956    16 GPSVSLKCVAS-GNPLPQITWTLDGFPIPESPR----FRVGDYVTS--DGDVVsyvnISSVRVEDGGEYTCTATNDVGS 87

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843657940 139 IPSSATI--GNRAVLTCSEQdGSPPSEYTWFKDGivmPTNPKSTRafSNSSYVLnPTTGELVFDPLSASDTGEYSCEARN 216
Cdd:cd05763     5 TPHDITIraGSTARLECAAT-GHPTPQIAWQKDG---GTDFPAAR--ERRMHVM-PEDDVFFIVDVKIEDTGVYSCTAQN 77

                          90
                  ....*....|
gi 1843657940 217 GYGTpMTSNA 226
Cdd:cd05763    78 SAGS-ISANA 86

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843657940  45 PVKLSCAYSGFSSPRVEWKFDQgdttRLVCYNNKITASYEDRvtflptgITFKSVTREDTGTYTCMVSEEGGNSYGEVKV 124
Cdd:cd20957    18 TAVFNCSVTGNPIHTVLWMKDG----KPLGHSSRVQILSEDV-------LVIPSVKREDKGMYQCFVRNDGDSAQATAEL 86

                  ..
gi 1843657940 125 KL 126
Cdd:cd20957    87 KL 88