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 16758636  29 SVYSPQTAVQVPENDSVKLPCIYSGF-SSPRVEWKFVQGSTTALVCYNNQITVPYADRVTFSSSGITFSSVTRKDNGEYT 107
Cdd:cd20946   1 TVPSSQQVVTVVENQEVILSCKTPKKtSSPRVEWKKLQRDVTFVVFQNNKIQGDYKGRAEILGTNITIKNVTRSDSGKYR 80

                        90       100
                ....*....|....*....|..
gi 16758636 108 CMVS-EDGGQNYGEVSIHLTVL 128
Cdd:cd20946  81 CEVSaRSDGQNLGEVTVTLEVL 102

First Ig-like domain of Junctional adhesion molecule-1 (JAM1)and similar domains; a member of the V-set of IgSF domains; The members here are composed of the first Ig-like domain of Junctional Adhesion Molecule-1 (JAM1)and similar domains. 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 first Ig-like domain of JAM1 is a member of the V-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C'-C" in the other.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758636  29 SVYSPQTAVQVPENDSVKLPCIYSGF-SSPRVEWKFVQGSTTALVCYNNQITVPYADRVTFSSSGITFSSVTRKDNGEYT 107
Cdd:cd20946   1 TVPSSQQVVTVVENQEVILSCKTPKKtSSPRVEWKKLQRDVTFVVFQNNKIQGDYKGRAEILGTNITIKNVTRSDSGKYR 80

                        90       100
                ....*....|....*....|..
gi 16758636 108 CMVS-EDGGQNYGEVSIHLTVL 128
Cdd:cd20946  81 CEVSaRSDGQNLGEVTVTLEVL 102

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758636   133 KPTVSIPSS---VTIGNRAVLTCsEHDGSPPSEYSWFKDGVPMLTADAkktrafinSSYTIDPKSGDLVFDPVSAFDSGE 209
Cdd:pfam13927   1 KPVITVSPSsvtVREGETVTLTC-EATGSPPPTITWYKNGEPISSGST--------RSRSLSGSNSTLTISNVTRSDAGT 71

                  ....*..
gi 16758636   210 YYCEAQN 216
Cdd:pfam13927  72 YTCVASN 78

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758636    141 SVTIGNRAVLTCsEHDGSPPSEYSWFKDGVPMLTADAKKTRAFINSSYTidpksgdLVFDPVSAFDSGEYYCEAQNGYGT 220
Cdd:smart00410   5 TVKEGESVTLSC-EASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTST-------LTISNVTPEDSGTYTCAATNSSGS 76

                   .
gi 16758636    221 A 221
Cdd:smart00410  77 A 77

First Ig-like domain of Junctional adhesion molecule-1 (JAM1)and similar domains; a member of the V-set of IgSF domains; The members here are composed of the first Ig-like domain of Junctional Adhesion Molecule-1 (JAM1)and similar domains. 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 first Ig-like domain of JAM1 is a member of the V-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C'-C" in the other.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758636  29 SVYSPQTAVQVPENDSVKLPCIYSGF-SSPRVEWKFVQGSTTALVCYNNQITVPYADRVTFSSSGITFSSVTRKDNGEYT 107
Cdd:cd20946   1 TVPSSQQVVTVVENQEVILSCKTPKKtSSPRVEWKKLQRDVTFVVFQNNKIQGDYKGRAEILGTNITIKNVTRSDSGKYR 80

                        90       100
                ....*....|....*....|..
gi 16758636 108 CMVS-EDGGQNYGEVSIHLTVL 128
Cdd:cd20946  81 CEVSaRSDGQNLGEVTVTLEVL 102

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758636   133 KPTVSIPSS---VTIGNRAVLTCsEHDGSPPSEYSWFKDGVPMLTADAkktrafinSSYTIDPKSGDLVFDPVSAFDSGE 209
Cdd:pfam13927   1 KPVITVSPSsvtVREGETVTLTC-EATGSPPPTITWYKNGEPISSGST--------RSRSLSGSNSTLTISNVTRSDAGT 71

                  ....*..
gi 16758636   210 YYCEAQN 216
Cdd:pfam13927  72 YTCVASN 78

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 16758636 148 AVLTCsEHDGSPPSEYSWFKDGVPMLTADakktrafiNSSYTIDPKSGDLVFDPVSAFDSGEYYCEAQNGYGTAMRSEA 226
Cdd:cd00096   1 VTLTC-SASGNPPPTITWYKNGKPLPPSS--------RDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 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 16758636 143 TIGNRAVLTCSEHDGSPPSEYSWFKDGVPMLTADAKKTRafinssyTIDPKSGDLVFDPVSAFDSGEYYCEAQNGYGTA 221
Cdd:cd20959  15 QVGMRAQLHCGVPGGDLPLNIRWTLDGQPISDDLGITVS-------RLGRRSSILSIDSLEASHAGNYTCHARNSAGSA 86

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 16758636 141 SVTIGNRAVLTCSEHDGSPPSEYSWFKDGvpmltADAKKTRAfINSSYTIDPKSGDLVFDPVSAFDSGEYYCEAQNGYG 219
Cdd:cd05750  10 TVQEGSKLVLKCEATSENPSPRYRWFKDG-----KELNRKRP-KNIKIRNKKKNSELQINKAKLEDSGEYTCVVENILG 82

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758636 147 RAVLTCseH-DGSPPSEYSWFKDGVPMltADAKktrafinSSYTIDPKSGDLVFDPVSAFDSGEYYCEAQNGYGTAMRSE 225
Cdd:cd05760  18 RVTLRC--HiDGHPRPTYQWFRDGTPL--SDGQ-------GNYSVSSKERTLTLRSAGPDDSGLYYCCAHNAFGSVCSSQ 86

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 16758636    32 SPQTAVQVPENDSVKLPCIYSGFSS-PRVEWKFvQGSTtalvcYNNQITVPYADRVTFSSSgITFSSVTRKDNGEYTCMV 110
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGSPgPDVTWSK-EGGT-----LIESLKVKHDNGRTTQSS-LLISNVTKEDAGTYTCVV 73

                          90
                  ....*....|...
gi 16758636   111 SEDGGQNYGEVSI 123
Cdd:pfam00047  74 NNPGGSATLSTSL 86

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 16758636  45 VKLPCIYSGFSSPRVEWKFVQGSttalvcynNQITVPYADRVTFSSSGITFSSVTRKDNGEYTCMVSEDGG 115
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKNGKP--------LPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758636     44 SVKLPCIYSGFSSPRVEWKFVQ---GSTTALVCYNNQITVPYA-----DRVTFSSSG------ITFSSVTRKDNGEYTCM 109
Cdd:smart00406   1 SVTLSCKFSGSTFSSYYVSWVRqppGKGLEWLGYIGSNGSSYYqesykGRFTISKDTskndvsLTISNLRVEDTGTYYCA 80

                   .
gi 16758636    110 V 110
Cdd:smart00406  81 V 81

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 16758636 139 PSSVTI--GNRAVLTCsEHDGSPPSEYSWFKDGVPMltadakKTRAFINSSYTIDPKSGDLVFDPV-----SAFDSGEYY 211
Cdd:cd07693   7 PSDLIVskGDPATLNC-KAEGRPTPTIQWLKNGQPL------ETDKDDPRSHRIVLPSGSLFFLRVvhgrkGRSDEGVYV 79

                        90
                ....*....|....*
gi 16758636 212 CEAQNGYGTAMRSEA 226
Cdd:cd07693  80 CVAHNSLGEAVSRNA 94

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 16758636 157 GSPPSEYSWFKDGVPMltadakktrafiNSSYTIDPKSGDLVFDPVSAFDSGEYYCEAQNGYGTAMRSEAVRM 229
Cdd:cd05728  25 GNPRPAYRWLKNGQPL------------ASENRIEVEAGDLRITKLSLSDSGMYQCVAENKHGTIYASAELAV 85

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 16758636 141 SVTIGNRAVLTCsEHDGSPPSEYSWFKDGVPMltadaKKTRAFInssytIDPKSgdLVFDPVSAFDSGEYYCEAQNGYGT 220
Cdd:cd05725   8 VVLVDDSAEFQC-EVGGDPVPTVRWRKEDGEL-----PKGRYEI-----LDDHS--LKIRKVTAGDMGSYTCVAENMVGK 74

                .
gi 16758636 221 A 221
Cdd:cd05725  75 I 75

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758636   139 PSSVTIGNRAVLTCSEhDGSPPSEYSWFKDGVPMltadAKKTRAFINSsytidpksgdlvfdpVSAFDSGEYYCEAQNGY 218
Cdd:pfam13895   8 PTVVTEGEPVTLTCSA-PGNPPPSYTWYKDGSAI----SSSPNFFTLS---------------VSAEDSGTYTCVARNGR 67

                  .
gi 16758636   219 G 219
Cdd:pfam13895  68 G 68

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 16758636 145 GNRAVLTCSEHDGSPPSEYSWFKDGVPMltadakktrAFINSSYTIDPKSGDLVFDPVSAFDSGEYYCEAQNGYGTA 221
Cdd:cd20979  15 GQPTVLECVTEGGDQGVKYSWLKDGKSF---------NWQEHNVAQRKDEGSLVFLKPQASDEGQYQCFAETPAGVA 82

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. 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. The Ig-like domain of the Twitchin is a member of the I-set 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. 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758636 133 KPTVSipsSVTIGNRAVLTCsEHDGSPPSEYSWFKDGVPmLTADAKKTRAFINSSYtidpksgDLVFDPVSAFDSGEYYC 212
Cdd:cd20949   5 NAYVT---TVKEGQSATILC-EVKGEPQPNVTWHFNGQP-ISASVADMSKYRILAD-------GLLINKVTQDDTGEYTC 72

                        90       100
                ....*....|....*....|....
gi 16758636 213 EAQNGYGTAmrseavrMEAVELNV 236
Cdd:cd20949  73 RAYQVNSIA-------SDMQERTV 89

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758636 134 PTVSIPSSVT-----IGNRAVLTCsEHDGSPPSEYSWFKDGVPMLTADAKktrafinssYTIDPKSGDLVFDPVSAFDSG 208
Cdd:cd05730   2 PTIRARQSEVnatanLGQSVTLAC-DADGFPEPTMTWTKDGEPIESGEEK---------YSFNEDGSEMTILDVDKLDEA 71

                        90
                ....*....|...
gi 16758636 209 EYYCEAQNGYGTA 221
Cdd:cd05730  72 EYTCIAENKAGEQ 84

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 16758636  37 VQVPENDSVKLPCIYSGFSSPRVEWKfvqgSTTALVCYNNQITVPYADR--VTFsssgITFSSVTRKDNGEYTCMVsEDG 114
Cdd:cd20961   3 LTVSQGQPVKLNCSVEGMEEPDIQWV----KDGAVVQNLDQLYIPVSEQhwIGF----LSLKSVERSDAGRYWCQV-EDG 73

                        90
                ....*....|...
gi 16758636 115 GQNYGEVSIHLTV 127
Cdd:cd20961  74 GETEISQPVWLTV 86

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758636 147 RAVLTCSEHdGSPPSEYSWFKDGvpmltadakkTRAFINSSYTIDPKSGDLVF-DPVSAFDSGEYYCEAQNGYGTAMRSE 225
Cdd:cd05848  21 KVILNCEAR-GNPVPTYRWLRNG----------TEIDTESDYRYSLIDGNLIIsNPSEVKDSGRYQCLATNSIGSILSRE 89

                ..
gi 16758636 226 AV 227
Cdd:cd05848  90 AL 91

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 16758636  48 PCIYSGFSSPRVEWKFVQ-------GSTTALVCYNNQiTVPYADRVTFSSSG--ITFSSVTRKDNGEYTCMVS 111
Cdd:cd05740   2 PFISSNNSNPVEDKDAVTltcepetQNTSYLWWFNGQ-SLPVTPRLTLSNGNrtLTLLNVTREDAGAYQCEIS 73

First immunoglobulin (Ig) domain of contactin-2; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758636 134 PTVSIPSSVTIGNRAvltcsehDGSPPSEYSWFKDGVPMLTADakktrafiNSSYTIdpKSGDLVF-DPVSAFDSGEYYC 212
Cdd:cd05850  15 PEGSAEEKVTLACRA-------RASPPATYRWKMNGTELKMEP--------DSRYRL--VAGNLVIsNPVKAKDAGSYQC 77

                        90
                ....*....|....
gi 16758636 213 EAQNGYGTAMRSEA 226
Cdd:cd05850  78 LASNRRGTVVSREA 91

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758636  44 SVKLPCIYSGFSSPRVEWKfvqgsttalvcYNNQITVPYADRVTFS--SSGITFSSVTRKDNGEYTCMVSEDGGQNygEV 121
Cdd:cd05730  20 SVTLACDADGFPEPTMTWT-----------KDGEPIESGEEKYSFNedGSEMTILDVDKLDEAEYTCIAENKAGEQ--EA 86

                ....*...
gi 16758636 122 SIHLTVLV 129
Cdd:cd05730  87 EIHLKVFA 94

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758636 134 PTVSIPSS-----VTIGNRAVLTCSEhDGSPPSEYSWFKDGVPMLTadakktrafINSSYTIDPKSGDLVFDPVSAFDSG 208
Cdd:cd20970   1 PVISTPQPsftvtAREGENATFMCRA-EGSPEPEISWTRNGNLIIE---------FNTRYIVRENGTTLTIRNIRRSDMG 70

                        90
                ....*....|....*...
gi 16758636 209 EYYCEAQNGYGTAMRSEA 226
Cdd:cd20970  71 IYLCIASNGVPGSVEKRI 88

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758636 139 PSSVTI--GNRAVLTCSEHdGSPPSEYSWFKDgvpmltADAKKTRAFINSSytidpKSGDLVFDPVSAFDSGEYYCEAQN 216
Cdd:cd20968   6 PTNVTIieGLKAVLPCTTM-GNPKPSVSWIKG------DDLIKENNRIAVL-----ESGSLRIHNVQKEDAGQYRCVAKN 73

                        90
                ....*....|....
gi 16758636 217 GYGTAMrSEAVRME 230
Cdd:cd20968  74 SLGIAY-SKPVTIE 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 16758636 145 GNRAVLTCSEhDGSPPSEYSWFKDGVPmltadakktraFINSSYTIDPKSGDLVFDPVSAFDSGEYYCEAQNGYGT 220
Cdd:cd20978  16 GQDVTLPCQV-TGVPQPKITWLHNGKP-----------LQGPMERATVEDGTLTIINVQPEDTGYYGCVATNEIGD 79

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 16758636 145 GNRAVLTCsEHDGSPPSEYSWFKDGVPMLTADAKKTRAFinssytidpKSGDLVFDPVSAFDSGEYYCEAQNGYG 219
Cdd:cd05867  14 GETARLDC-QVEGIPTPNITWSINGAPIEGTDPDPRRHV---------SSGALILTDVQPSDTAVYQCEARNRHG 78

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16758636 139 PSSVT--IGNRAVLTCsEHDGSPPSEYSWFKDGVPMLTADAKKTRafinssyTIDPKSgdLVFDPVSAFDSGEYYCEAQN 216
Cdd:cd04978   6 PPSLVlsPGETGELIC-EAEGNPQPTITWRLNGVPIEPAPEDMRR-------TVDGRT--LIFSNLQPNDTAVYQCNASN 75

                ....*.
gi 16758636 217 GYGTAM 222
Cdd:cd04978  76 VHGYLL 81