Domain present in ZO-1 and Unc5-like netrin receptors; Domain of unknown function.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578811262   439 TSNMTYGTFNFLGGRLMIPNTGISLLIPPDAIPRGKIYEIYLTLHKPEDVRLPLAGCQTLLSPIVSCGPPGVLLTRPVIL 518
Cdd:smart00218   1 PSFLVSGTFDARGGRLRGPRTGVRLIIPPGAIPQGTRYTCYLVVHKTLSTPPPLEEGETLLSPVVECGPHGALFLRPVIL 80

                           90       100
                   ....*....|....*....|....
gi 578811262   519 AMDHCGEPSPDSWSLRLKKQSCEG 542
Cdd:smart00218  81 EVPHCASLRPRDWEIVLLRSENGG 104

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 578811262   245 WSPWSKWSACGLDC---THWRSRECSDPAPRNGGEECQGTDLDTRNCTSDLC 293
Cdd:smart00209   1 WSEWSEWSPCSVTCgggVQTRTRSCCSPPPQNGGGPCTGEDVETRACNEQPC 52

Domain present in ZO-1 and Unc5-like netrin receptors; Domain of unknown function.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578811262   439 TSNMTYGTFNFLGGRLMIPNTGISLLIPPDAIPRGKIYEIYLTLHKPEDVRLPLAGCQTLLSPIVSCGPPGVLLTRPVIL 518
Cdd:smart00218   1 PSFLVSGTFDARGGRLRGPRTGVRLIIPPGAIPQGTRYTCYLVVHKTLSTPPPLEEGETLLSPVVECGPHGALFLRPVIL 80

                           90       100
                   ....*....|....*....|....
gi 578811262   519 AMDHCGEPSPDSWSLRLKKQSCEG 542
Cdd:smart00218  81 EVPHCASLRPRDWEIVLLRSENGG 104

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 578811262 153 QEPLAKEVSLEQGIVLPCRPPEGIPPAEVEWLRNEDLVDpSLDPNVYITREHSLVVRQARLADTANYTCVAKNIVARRRS 232
Cdd:cd05724    2 VEPSDTQVAVGEMAVLECSPPRGHPEPTVSWRKDGQPLN-LDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERES 80

                 ....*..
gi 578811262 233 ASAAVIV 239
Cdd:cd05724   81 RAARLSV 87

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578811262  151 FEQEPLAKEVSLEQGIVLPCRPpEGIPPAEVEWLRNEDLVDPSldPNVYITRE---HSLVVRQARLADTANYTCVAKNIV 227
Cdd:pfam07679   3 FTQKPKDVEVQEGESARFTCTV-TGTPDPEVSWFKDGQPLRSS--DRFKVTYEggtYTLTISNVQPDDSGKYTCVATNSA 79

                          90
                  ....*....|..
gi 578811262  228 ArRRSASAAVIV 239
Cdd:pfam07679  80 G-EAEASAELTV 90

Thrombospondin type 1 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 578811262  246 SPWSKWSACGLDC---THWRSRECSDPAPrnGGEECQGTDLDTRNCTSDLC 293
Cdd:pfam00090   1 SPWSPWSPCSVTCgkgIQVRQRTCKSPFP--GGEPCTGDDIETQACKMDKC 49

Domain present in ZO-1 and Unc5-like netrin receptors; Domain of unknown function.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578811262   439 TSNMTYGTFNFLGGRLMIPNTGISLLIPPDAIPRGKIYEIYLTLHKPEDVRLPLAGCQTLLSPIVSCGPPGVLLTRPVIL 518
Cdd:smart00218   1 PSFLVSGTFDARGGRLRGPRTGVRLIIPPGAIPQGTRYTCYLVVHKTLSTPPPLEEGETLLSPVVECGPHGALFLRPVIL 80

                           90       100
                   ....*....|....*....|....
gi 578811262   519 AMDHCGEPSPDSWSLRLKKQSCEG 542
Cdd:smart00218  81 EVPHCASLRPRDWEIVLLRSENGG 104

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 578811262 153 QEPLAKEVSLEQGIVLPCRPPEGIPPAEVEWLRNEDLVDpSLDPNVYITREHSLVVRQARLADTANYTCVAKNIVARRRS 232
Cdd:cd05724    2 VEPSDTQVAVGEMAVLECSPPRGHPEPTVSWRKDGQPLN-LDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERES 80

                 ....*..
gi 578811262 233 ASAAVIV 239
Cdd:cd05724   81 RAARLSV 87

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (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 Ig I1 domain of the titin I-band 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, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578811262 174 EGIPPAEVEWLRNEDLVDPSLDPNVYITRE----HSLVVRQARLADTANYTCVAKNIvARRRSASAAVIV 239
Cdd:cd20951   25 QGKPDPEVKWYKNGVPIDPSSIPGKYKIESeygvHVLHIRRVTVEDSAVYSAVAKNI-HGEASSSASVVV 93

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578811262  151 FEQEPLAKEVSLEQGIVLPCRPpEGIPPAEVEWLRNEDLVDPSldPNVYITRE---HSLVVRQARLADTANYTCVAKNIV 227
Cdd:pfam07679   3 FTQKPKDVEVQEGESARFTCTV-TGTPDPEVSWFKDGQPLRSS--DRFKVTYEggtYTLTISNVQPDDSGKYTCVATNSA 79

                          90
                  ....*....|..
gi 578811262  228 ArRRSASAAVIV 239
Cdd:pfam07679  80 G-EAEASAELTV 90

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578811262 150 NFEQEPLAKEVSLEQG--IVLPCRPpEGIPPAEVEWLRNEDLVDPSldPNVYITREHSLVVRQARLADTANYTCVAKNIV 227
Cdd:cd04969    2 DFELNPVKKKILAAKGgdVIIECKP-KASPKPTISWSKGTELLTNS--SRICILPDGSLKIKNVTKSDEGKYTCFAVNFF 78

                         90
                 ....*....|..
gi 578811262 228 ARRRSaSAAVIV 239
Cdd:cd04969   79 GKANS-TGSLSV 89

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 578811262 151 FEQEPL-AKEVSLEQGIVLPCRPpEGIPPAEVEWLRNEDLVdpSLDPNVYITREHSLVVRQARLADTANYTCVAKNIVAR 229
Cdd:cd20978    3 FIQKPEkNVVVKGGQDVTLPCQV-TGVPQPKITWLHNGKPL--QGPMERATVEDGTLTIINVQPEDTGYYGCVATNEIGD 79

                         90
                 ....*....|
gi 578811262 230 RRSaSAAVIV 239
Cdd:cd20978   80 IYT-ETLLHV 88

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 578811262 151 FEQEPLAKEVSLEQGIVLPCRPpEGIPPAEVEWLRNEDLVdPSLDPNVYITREHSLVVRQARLADTANYTCVAKNIvarr 230
Cdd:cd20952    2 ILQGPQNQTVAVGGTVVLNCQA-TGEPVPTISWLKDGVPL-LGKDERITTLENGSLQIKGAEKSDTGEYTCVALNL---- 75

                         90
                 ....*....|..
gi 578811262 231 rSASAAVIVYVD 242
Cdd:cd20952   76 -SGEATWSAVLD 86

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 578811262 154 EPLAKEVSLEQGIVLPCRPpEGIPPAEVEWlRNEDLVDPslDPNVYITREHSLVVRQARLADTANYTCVAKNIVArRRSA 233
Cdd:cd05725    3 RPQNQVVLVDDSAEFQCEV-GGDPVPTVRW-RKEDGELP--KGRYEILDDHSLKIRKVTAGDMGSYTCVAENMVG-KIEA 77

                 ....*.
gi 578811262 234 SAAVIV 239
Cdd:cd05725   78 SATLTV 83

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 578811262 175 GIPPAEVEWLRNEDLVDPSLDPNVYITREHS-LVVRQARLADTANYTCVAKNIVArrrSASAAVIVYV 241
Cdd:cd05748   18 GRPTPTVTWSKDGQPLKETGRVQIETTASSTsLVIKNAKRSDSGKYTLTLKNSAG---EKSATINVKV 82

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 578811262 153 QEPLAKEVSLEQGIVLPCRPPEGIPPAEVEWLRNEDLVDPSLDPNVYI--TREHS-LVVRQARLADTANYTCVAKNIVAr 229
Cdd:cd05750    4 KEMKSQTVQEGSKLVLKCEATSENPSPRYRWFKDGKELNRKRPKNIKIrnKKKNSeLQINKAKLEDSGEYTCVVENILG- 82

                         90
                 ....*....|
gi 578811262 230 RRSASAAVIV 239
Cdd:cd05750   83 KDTVTGNVTV 92

Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an alternative disulphide binding pattern compared to the canonical TSP1 domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 578811262  246 SPWSKWSACGLDC---THWRSRECSDPaPRNGGEECqGTDLDTRNCTSDLC 293
Cdd:pfam19028   4 SEWSEWSECSVTCgggVQTRTRTVIVE-PQNGGRPC-PELLERRPCNLPPC 52

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 578811262 151 FEQEPLAKEVSLEQGIVLPCRPpEGIPPAEVEWLRNEDLVDPSlDPNVYITRE---HSLVVRQARLADTANYTCVAKN 225
Cdd:cd05744    3 FLQAPGDLEVQEGRLCRFDCKV-SGLPTPDLFWQLNGKPVRPD-SAHKMLVREngrHSLIIEPVTKRDAGIYTCIARN 78

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members, VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4). VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. 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 578811262 153 QEPLAKEVSLEQGIVLPCRPpEGIPPAEVEWLRNedlvDPSLDPNVYITREHSLVVRQARLADTANYTCVAKNIVAR-RR 231
Cdd:cd04976    8 KQQVLEATAGKRSVRLPMKV-KAYPPPEVVWYKD----GLPLTEKARYLTRHSLIIKEVTEEDTGNYTILLSNKQSNvFK 82

                 ....*...
gi 578811262 232 SASAAVIV 239
Cdd:cd04976   83 NLTATLVV 90

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 578811262 155 PLAKEVSLEQGIVLPCRPpEGIPPAEVEWLRNEDLVDPslDPNVYITREHSLVVRQARLADTANYTCVAKNIVARRRSAS 234
Cdd:cd20968    6 PTNVTIIEGLKAVLPCTT-MGNPKPSVSWIKGDDLIKE--NNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIAYSKP 82

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gi 578811262 235 AAVIV 239
Cdd:cd20968   83 VTIEV 87

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 578811262 166 IVLPCRPpEGIPPAEVEWLRNEDLVDPSldPNVYITREHSLVVRQARLADTANYTCVAKNIVARRRSASAAVI 238
Cdd:cd05723   15 IVFECEV-TGKPTPTVKWVKNGDVVIPS--DYFKIVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQASAQLII 84