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 2776451018 141 KTLTVNTGALLTMSVSANGgTPPYKYAWKKDGQPV----------DGQTTdTFSKPGAQSADAGKYTCVVTDSAEKAqsv 210
Cdd:pfam07679   8 KDVEVQEGESARFTCTVTG-TPDPEVSWFKDGQPLrssdrfkvtyEGGTY-TLTISNVQPDDSGKYTCVATNSAGEA--- 82

                  ....*....
gi 2776451018 211 tSVECTVTV 219
Cdd:pfam07679  83 -EASAELTV 90

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2776451018 141 KTLTVNTGALLTMSVSANGgTPPYKYAWKKDGQPV----------DGQTTdTFSKPGAQSADAGKYTCVVTDSAEKAqsv 210
Cdd:pfam07679   8 KDVEVQEGESARFTCTVTG-TPDPEVSWFKDGQPLrssdrfkvtyEGGTY-TLTISNVQPDDSGKYTCVATNSAGEA--- 82

                  ....*....
gi 2776451018 211 tSVECTVTV 219
Cdd:pfam07679  83 -EASAELTV 90

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2776451018  141 KTLTVNTGALLTMSVSANGGTPPYKYAWKKDGQPVDGQTTDTFSKPG---------AQSADAGKYTCVVTDSAEKAQSVT 211
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGststltisnVTPEDSGTYTCAATNSSGSASSGT 81

                   ...
gi 2776451018  212 SVE 214
Cdd:smart00410  82 TLT 84

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2776451018 141 KTLTVNTGALLTMSVSANGgTPPYKYAWKKDGQPV----------DGQTTdTFSKPGAQSADAGKYTCVVTDSAEKAqsv 210
Cdd:pfam07679   8 KDVEVQEGESARFTCTVTG-TPDPEVSWFKDGQPLrssdrfkvtyEGGTY-TLTISNVQPDDSGKYTCVATNSAGEA--- 82

                  ....*....
gi 2776451018 211 tSVECTVTV 219
Cdd:pfam07679  83 -EASAELTV 90

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2776451018 130 VVPLAFVKNLdktltVNTGALLTMSVSANGGTPPYKYAWKKDGQPVDGQTTDTFSKPGAQS----------ADAGKYTCV 199
Cdd:cd20959     4 IIPFAFGEGA-----AQVGMRAQLHCGVPGGDLPLNIRWTLDGQPISDDLGITVSRLGRRSsilsidsleaSHAGNYTCH 78

                  ....*....
gi 2776451018 200 VTDSAEKAQ 208
Cdd:cd20959    79 ARNSAGSAS 87

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2776451018 160 GTPPYKYAWKKDGQPVDG------QTTDTFSK---PGAQSADAGKYTCVVTDSAEKAqsvtSVECTVTV 219
Cdd:cd05748    18 GRPTPTVTWSKDGQPLKEtgrvqiETTASSTSlviKNAKRSDSGKYTLTLKNSAGEK----SATINVKV 82

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2776451018 160 GTPPYKYAWKKDGQPVDGQTTDTFSK---------PGAQSADAGKYTCVVTDSAEKAQSVT 211
Cdd:cd00096     9 GNPPPTITWYKNGKPLPPSSRDSRRSelgngtltiSNVTLEDSGTYTCVASNSAGGSASAS 69

Phage tail protein, TP901-1 family [Mobilome: prophages, transposons];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2776451018  36 IDVTTLCSTEQ--ENINGLGA-SSEISMSGNFYLNQAQNALRDAYDNDALYAFKVLFPSGKGFKFLAEVRQHTWSSGTNG 112
Cdd:COG5437    40 VDVTSKDSAGGwrELLAGAGVkSASVSGEGIFKDDASDAALRAAFFDGEVRDFQVVIPDFGTIEGPFQVTALEYAGPHDG 119

                          90
                  ....*....|....*
gi 2776451018 113 VVAATFSLRMKGKPV 127
Cdd:COG5437   120 EATYSLTLESAGALT 134

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2776451018 141 KTLTVNTGALLTMSVSANGGTPPYKYAWKKDGQPVDGQTTDTFSKPG-----------AQSADAGKYTCVVTDSAEKAqs 209
Cdd:cd05750     7 KSQTVQEGSKLVLKCEATSENPSPRYRWFKDGKELNRKRPKNIKIRNkkknselqinkAKLEDSGEYTCVVENILGKD-- 84

                          90
                  ....*....|
gi 2776451018 210 vtSVECTVTV 219
Cdd:cd05750    85 --TVTGNVTV 92

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2776451018 148 GALLTMSVSANGGTPPYKYAWKKDGQPVDGQTTD-TFSKPG------AQSADAGKYTCVVTDSA 204
Cdd:cd05724    12 GEMAVLECSPPRGHPEPTVSWRKDGQPLNLDNERvRIVDDGnlliaeARKSDEGTYKCVATNMV 75

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 2776451018 144 TVNTGALLTMSVSANGGTPPyKYAWKKDGQPVDGQTTDTFSKP-------GAQSADAGKYTCVVTDSAEKAqsvtSVECT 216
Cdd:cd20952    10 TVAVGGTVVLNCQATGEPVP-TISWLKDGVPLLGKDERITTLEngslqikGAEKSDTGEYTCVALNLSGEA----TWSAV 84

                  ...
gi 2776451018 217 VTV 219
Cdd:cd20952    85 LDV 87