NCBI Conserved Domain Search

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). 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 human APEG-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.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 174.20 E-value: 2.85e-51

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 768 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEY 847
Cdd:cd20975    1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEY 80

                         90
                 ....*....|.
gi 145699119 848 GARQCEARLEV 858
Cdd:cd20975   81 GARQCEARLEV 91

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 115.82 E-value: 9.57e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  621 PVFEIPLQNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNELG 700
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                          90
                  ....*....|
gi 145699119  701 QATCASSLAV 710
Cdd:pfam07679  81 EAEASAELTV 90

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 97.71 E-value: 2.33e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  768 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQrRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEY 847
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSD-RFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSA 79

                          90
                  ....*....|.
gi 145699119  848 GARQCEARLEV 858
Cdd:pfam07679  80 GEAEASAELTV 90

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk 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. 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 titin Z1z2 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.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 76.08 E-value: 1.04e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 620 APVFEIPLQNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNEL 699
Cdd:cd20972    1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSV 80

                         90
                 ....*....|.
gi 145699119 700 GQATCASSLAV 710
Cdd:cd20972   81 GSDTTSAEIFV 91

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.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 74.84 E-value: 2.90e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 621 PVFEIPLQNMVVAPGADVLLKCIITANPPPQVSWKKDGSML--HSEGRLLIRaEGERHTLLLREAQAADAGSYTATATNE 698
Cdd:cd05744    1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVrpDSAHKMLVR-ENGRHSLIIEPVTKRDAGIYTCIARNR 79

                         90
                 ....*....|..
gi 145699119 699 LGQATCASSLAV 710
Cdd:cd05744   80 AGENSFNAELVV 91

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.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 74.45 E-value: 3.02e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 768 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEY 847
Cdd:cd05744    1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                         90
                 ....*....|.
gi 145699119 848 GARQCEARLEV 858
Cdd:cd05744   81 GENSFNAELVV 91

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 73.69 E-value: 5.47e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119   776 DQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEYGARQCEAR 855
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTT 82


                   ...
gi 145699119   856 LEV 858
Cdd:smart00410  83 LTV 85

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 73.69 E-value: 6.09e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119   628 QNMVVAPGADVLLKCIITANPPPQVSWKKDG-SMLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQATCAS 706
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                   ....
gi 145699119   707 SLAV 710
Cdd:smart00410  82 TLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 72.21 E-value: 1.56e-15

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 145699119  621 PVFEIPLQNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATN 697
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 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.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 71.72 E-value: 2.79e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 621 PVFEIPLQNMVVAPGADVLLKCIITANPPPQVSWKKDGSML-HSEGRLLIRAEGE-RHTLLLREAQAADAGSYTATATNE 698
Cdd:cd05892    1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLqYNTDRISLYQDNCgRICLLIQNANKKDAGWYTVSAVNE 80

                         90
                 ....*....|..
gi 145699119 699 LGQATCASSLAV 710
Cdd:cd05892   81 AGVVSCNARLDV 92

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.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 71.68 E-value: 3.44e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 768 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRP--DQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVN 845
Cdd:cd20951    1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPssIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                         90
                 ....*....|....
gi 145699119 846 EYGARQCEARLEVR 859
Cdd:cd20951   81 IHGEASSSASVVVE 94

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.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 70.53 E-value: 9.48e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 621 PVFEIPLQNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSE---GRLLIRAEGERHTLLLREAQAADAGSYTATATN 697
Cdd:cd20951    1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSsipGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                         90
                 ....*....|....
gi 145699119 698 ELGQATCASSLAVR 711
Cdd:cd20951   81 IHGEASSSASVVVE 94

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.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 69.73 E-value: 1.26e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 768 PTFKVSLMDQSVR-EGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEaEGGLcrlRILAAERGDAGFYTCKAVNE 846
Cdd:cd20978    1 PKFIQKPEKNVVVkGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVE-DGTL---TIINVQPEDTGYYGCVATNE 76

                         90
                 ....*....|..
gi 145699119 847 YGARQCEARLEV 858
Cdd:cd20978   77 IGDIYTETLLHV 88

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. 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 telokin Ig domain 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.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 67.60 E-value: 7.12e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 773 SLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEYGARQC 852
Cdd:cd20973    3 TLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATC 82


                 ....*.
gi 145699119 853 EARLEV 858
Cdd:cd20973   83 SAELTV 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 67.21 E-value: 8.18e-14

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 145699119  767 PPTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLcRLRILAAERGDAGFYTCKAVN 845
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNS-TLTISNVTRSDAGTYTCVASN 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.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 64.27 E-value: 6.94e-13

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 145699119 638 VLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQATCAS 706
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASAS 69

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.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 64.72 E-value: 7.58e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 628 QNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLhSEGRLLIRAEgerHTLLLREAQAADAGSYTATATNELGQATCASS 707
Cdd:cd05725    5 QNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGEL-PKGRYEILDD---HSLKIRKVTAGDMGSYTCVAENMVGKIEASAT 80


                 ...
gi 145699119 708 LAV 710
Cdd:cd05725   81 LTV 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.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 63.76 E-value: 1.31e-12

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 145699119 630 MVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQAT 703
Cdd:cd05748    2 IVVRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKS 75

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.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 64.02 E-value: 1.53e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 621 PVFEI-PLQNM-VVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAEGerhTLLLREAQAADAGSYTATATNE 698
Cdd:cd04969    1 PDFELnPVKKKiLAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDG---SLKIKNVTKSDEGKYTCFAVNF 77

                         90
                 ....*....|..
gi 145699119 699 LGQATCASSLAV 710
Cdd:cd04969   78 FGKANSTGSLSV 89

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.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 63.81 E-value: 1.73e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 767 PPTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFaeEAEGGLCRLRILAAERGDAGFYTCKAVNE 846
Cdd:cd20976    1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRS--TCEAGVGELHIQDVLPEDHGTYTCLAKNA 78

                         90
                 ....*....|..
gi 145699119 847 YGARQCEARLEV 858
Cdd:cd20976   79 AGQVSCSAWVTV 90

Unstructured region on SPEG complex protein; SPEG_u2 is a region of natively unstructured but conserved sequence on Striated muscle-specific serine/threonine-protein kinase proteins in higher eukaryotes. It lies between two I-set immunoglobulin, pfam07679, domains. The function is not known.

Pssm-ID: 293256 Cd Length: 57 Bit Score: 60.60 E-value: 1.18e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 145699119  711 RPGGSTSPFSSPITSDEEYLSPPEEFPEPGETWPRTPTMKLSPSQDHDSSDSSSKAP 767
Cdd:pfam16650   1 EPGGAKSPFSSPITSDEEYLSPPEEFPEPEEAWHKTPAMKLSPSQAHQAPDTGSKAP 57

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.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 60.55 E-value: 2.73e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 768 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVR--PDQRRFAEEAEGGLCrLRILAAERGDAGFYTCKAVN 845
Cdd:cd05892    1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQynTDRISLYQDNCGRIC-LLIQNANKKDAGWYTVSAVN 79

                         90
                 ....*....|...
gi 145699119 846 EYGARQCEARLEV 858
Cdd:cd05892   80 EAGVVSCNARLDV 92

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. 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 telokin Ig domain 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.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 59.13 E-value: 8.86e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 626 PLQNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAEGERH-TLLLREAQAADAGSYTATATNELGQATC 704
Cdd:cd20973    3 TLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLcSLIISDVCGDDSGKYTCKAVNSLGEATC 82


                 ....*.
gi 145699119 705 ASSLAV 710
Cdd:cd20973   83 SAELTV 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

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 58.28 E-value: 1.33e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 628 QNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEG-RLLIRAEGerhTLLLREAQAADAGSYTATATNELGQATCAS 706
Cdd:cd20952    7 QNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDeRITTLENG---SLQIKGAEKSDTGEYTCVALNLSGEATWSA 83


                 ....
gi 145699119 707 SLAV 710
Cdd:cd20952   84 VLDV 87

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.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 57.96 E-value: 2.20e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 620 APVFEIPLQNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLI----RAEGERHTLL-LREAQAADAGSYTAT 694
Cdd:cd20956    1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVgdyvTSDGDVVSYVnISSVRVEDGGEYTCT 80


                 ....*....
gi 145699119 695 ATNELGQAT 703
Cdd:cd20956   81 ATNDVGSVS 89

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

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 57.51 E-value: 2.66e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 770 FKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGlcrLRILAAERGDAGFYTCKAVNEYGA 849
Cdd:cd20952    2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGS---LQIKGAEKSDTGEYTCVALNLSGE 78


                 ....*....
gi 145699119 850 RQCEARLEV 858
Cdd:cd20952   79 ATWSAVLDV 87

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.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 56.57 E-value: 3.60e-10

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 145699119 785 VIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGlCRLRILAAERGDAGFYTCKAVNEYG 848
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGN-GTLTISNVTLEDSGTYTCVASNSAG 63

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk 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. 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 titin Z1z2 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.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 56.59 E-value: 6.74e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 621 PVFEIPLQNMVVAPGADVLLKCIITANPPPQVSWKKDGSM--LHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNE 698
Cdd:cd20974    1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVisTSTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                         90
                 ....*....|..
gi 145699119 699 LGQATCASSLAV 710
Cdd:cd20974   81 SGQATSTAELLV 92

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.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 55.67 E-value: 9.03e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 779 VREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCrLRILAAERGDAGFYTCKAVNEYGARqcEARLEV 858
Cdd:cd05748    4 VRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETTASSTS-LVIKNAKRSDSGKYTLTLKNSAGEK--SATINV 80


                 .
gi 145699119 859 R 859
Cdd:cd05748   81 K 81

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.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 54.32 E-value: 4.02e-09

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 145699119 626 PLQNMVVAPGADVLLKCIITANPPPQVSWkkdgsmLHSeGRLLIRAEG----ERHTLLLREAQAADAGSYTATATNELG 700
Cdd:cd20978    7 PEKNVVVKGGQDVTLPCQVTGVPQPKITW------LHN-GKPLQGPMEratvEDGTLTIINVQPEDTGYYGCVATNEIG 78

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. 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.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 53.95 E-value: 5.86e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 768 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAE-GGLCRLRILAAERGDAGFYTCKAVNE 846
Cdd:cd05893    1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYTIQRDlDGTCSLHTTASTLDDDGNYTIMAANP 80

                         90
                 ....*....|..
gi 145699119 847 YGARQCEARLEV 858
Cdd:cd05893   81 QGRISCTGRLMV 92

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.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 53.49 E-value: 8.02e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 769 TFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVR---PDQRRFAEEAEGglcrLRILAAERGDAGFYTCKAVN 845
Cdd:cd20949    1 TFTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISasvADMSKYRILADG----LLINKVTQDDTGEYTCRAYQ 76


                 ...
gi 145699119 846 EYG 848
Cdd:cd20949   77 VNS 79

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk 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. 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 titin Z1z2 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.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 52.59 E-value: 1.70e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 767 PPTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVR--PDqrrFAEEAEGGLCRLRILAAERGDAGFYTCKAV 844
Cdd:cd20972    1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQnsPD---IQIHQEGDLHSLIIAEAFEEDTGRYSCLAT 77

                         90
                 ....*....|....
gi 145699119 845 NEYGARQCEARLEV 858
Cdd:cd20972   78 NSVGSDTTSAEIFV 91

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.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 52.20 E-value: 1.88e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 145699119 781 EGQDVIMSIRVQGEPKPVVSWLRNRQPVRP-DQRRFAEEAEgglcrLRILAAERGDAGFYTCKAVNEYGARQCEARL 856
Cdd:cd05723   11 ESMDIVFECEVTGKPTPTVKWVKNGDVVIPsDYFKIVKEHN-----LQVLGLVKSDEGFYQCIAENDVGNAQASAQL 82

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. 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. 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 structures of the titin-A168169 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.

Pssm-ID: 409563 Cd Length: 93 Bit Score: 52.09 E-value: 2.53e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 768 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAE-RGDAGFYTCKAVNE 846
Cdd:cd20971    2 PHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEIIADGLKYRIQEFKGGYHQLIIASVtDDDATVYQVRATNQ 81


                 ..
gi 145699119 847 YG 848
Cdd:cd20971   82 GG 83

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.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 52.13 E-value: 2.66e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 621 PVFEIPLQ--NMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEG-RLLIRAEGErhTLLLREAQAADAGSYTATATN 697
Cdd:cd20970    1 PVISTPQPsfTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNtRYIVRENGT--TLTIRNIRRSDMGIYLCIASN 78


                 ...
gi 145699119 698 ELG 700
Cdd:cd20970   79 GVP 81

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth 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.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 51.88 E-value: 3.77e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 623 FEIPLQNMVVAPGADVLLKCIITANPPPQVSWKKDGSM--------LHSEGRLLIRAEGErhtLLLREAQAADAGSYTAT 694
Cdd:cd05726    2 FVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQnllfpyqpPQPSSRFSVSPTGD---LTITNVQRSDVGYYICQ 78

                         90
                 ....*....|....*.
gi 145699119 695 ATNELGQATCASSLAV 710
Cdd:cd05726   79 ALNVAGSILAKAQLEV 94

large tegument protein UL36; Provisional

Pssm-ID: 223021 [Multi-domain] Cd Length: 3151 Bit Score: 56.87 E-value: 5.68e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  204 ALLPPPSPrvgKRALPGPSTQP-PATP--TSPHRRAQEPSLPEDITTTEEKRGKKPKSSGPSLAGTVESRPQTPLSEASG 280
Cdd:PHA03247 2557 PAAPPAAP---DRSVPPPRPAPrPSEPavTSRARRPDAPPQSARPRAPVDDRGDPRGPAPPSPLPPDTHAPDPPPPSPSP 2633

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  281 RLSALG----------RSPRLVRAGSRILdklqfFEERRRSLERSDSPPAPLRPWVPlRKAR-------SLEQPKSEGGA 343
Cdd:PHA03247 2634 AANEPDphppptvpppERPRDDPAPGRVS-----RPRRARRLGRAAQASSPPQRPRR-RAARptvgsltSLADPPPPPPT 2707

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  344 AWGTPEASQEELRSPRGSVAERRRLFQQKAASL------------DERTRQRSATSDLELRFAQELGRIRrSTSREELVR 411
Cdd:PHA03247 2708 PEPAPHALVSATPLPPGPAAARQASPALPAAPAppavpagpatpgGPARPARPPTTAGPPAPAPPAAPAA-GPPRRLTRP 2786

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  412 SHESLRATLQRAPSPREPGEPPLFSRPSTPKTSRAVSPAATQPPPPSGAGKSGDEPGRPRSR-----------GPVGRTE 480
Cdd:PHA03247 2787 AVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPPslplggsvapgGDVRRRP 2866

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  481 PGEGPQQEIKRRDQFPLTRSRAIQECRSPV-----PPYTADPPESRTKAPSGRKREPPAQAVRFLPWATPGVEDSVLPQT 555
Cdd:PHA03247 2867 PSRSPAAKPAAPARPPVRRLARPAVSRSTEsfalpPDQPERPPQPQAPPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPT 2946


                  ....*..
gi 145699119  556 LEKNRAG 562
Cdd:PHA03247 2947 TDPAGAG 2953

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.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 51.10 E-value: 6.01e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 620 APVFEIPLQNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGRLlIRAEGERHTLLLREAQAADAGSYTATATNEL 699
Cdd:cd20976    1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADR-STCEAGVGELHIQDVLPEDHGTYTCLAKNAA 79

                         90
                 ....*....|.
gi 145699119 700 GQATCASSLAV 710
Cdd:cd20976   80 GQVSCSAWVTV 90

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.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 50.97 E-value: 6.91e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 773 SLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLcrLRILAAERGDAGFYTCKAVNE-YGARQ 851
Cdd:cd20970    8 PSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENGTT--LTIRNIRRSDMGIYLCIASNGvPGSVE 85


                 ....*..
gi 145699119 852 CEARLEV 858
Cdd:cd20970   86 KRITLQV 92

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 50.61 E-value: 8.44e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 145699119 630 MVVAPGADVLLKCIITANPPPQVSWKK-DGSMLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQA 702
Cdd:cd05894    5 IVVVAGNKLRLDVPISGEPAPTVTWSRgDKAFTATEGRVRVESYKDLSSFVIEGAEREDEGVYTITVTNPVGED 78

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. 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.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 50.48 E-value: 9.37e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 768 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEY 847
Cdd:cd20990    1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRA 80


                 .
gi 145699119 848 G 848
Cdd:cd20990   81 G 81

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.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 49.52 E-value: 1.51e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 145699119 782 GQDVIMSIRVQGEPKPVVSWLRNRQPVrPDQRRFaeEAEGGLCRLRILAAErgDAGFYTCKAVNEYGARQCEARLEV 858
Cdd:cd05728   14 GSSLRWECKASGNPRPAYRWLKNGQPL-ASENRI--EVEAGDLRITKLSLS--DSGMYQCVAENKHGTIYASAELAV 85

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.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 49.77 E-value: 1.53e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 768 PTFKVSLMDQS--VREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEaEGGLcrlRILAAERGDAGFYTCKAVN 845
Cdd:cd04969    1 PDFELNPVKKKilAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILP-DGSL---KIKNVTKSDEGKYTCFAVN 76

                         90
                 ....*....|...
gi 145699119 846 EYGARQCEARLEV 858
Cdd:cd04969   77 FFGKANSTGSLSV 89

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.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 49.09 E-value: 3.63e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 775 MDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVR-----PDQRRFAEEAeGGLCRLRILAAERG--DAGFYTCKAVNEY 847
Cdd:cd07693    8 SDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLEtdkddPRSHRIVLPS-GSLFFLRVVHGRKGrsDEGVYVCVAHNSL 86

                         90
                 ....*....|..
gi 145699119 848 G-ARQCEARLEV 858
Cdd:cd07693   87 GeAVSRNASLEV 98

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 47.39 E-value: 7.85e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 145699119  776 DQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFaeeaegglcrlrILAAERGDAGFYTCKAVNEYG 848
Cdd:pfam13895   8 PTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPNFF------------TLSVSAEDSGTYTCVARNGRG 68

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.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 47.78 E-value: 8.14e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 145699119 793 GEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCrlrILAAERGDAGFYTCKAVNEYGARQCE-ARLEV 858
Cdd:cd05724   24 GHPEPTVSWRKDGQPLNLDNERVRIVDDGNLL---IAEARKSDEGTYKCVATNMVGERESRaARLSV 87

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth 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.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 48.03 E-value: 9.21e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 770 FKVSLMDQSVREGQDVIMSIRVQGEPKPVVSW--------LRNRQPVRPDQRrFAEEAEGglcRLRILAAERGDAGFYTC 841
Cdd:cd05726    2 FVVKPRDQVVALGRTVTFQCETKGNPQPAIFWqkegsqnlLFPYQPPQPSSR-FSVSPTG---DLTITNVQRSDVGYYIC 77

                         90
                 ....*....|....*....
gi 145699119 842 KAVNEYGARQCEARLEVRG 860
Cdd:cd05726   78 QALNVAGSILAKAQLEVTD 96

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

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 46.86 E-value: 1.14e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 145699119 781 EGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGglcrLRILAAERGDAGFYTCKAVNEYGARQCEARLEV 858
Cdd:cd05745    1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSGT----LRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 46.71 E-value: 1.28e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 145699119 782 GQDVIMSIRVQGEPKPVVSWLRNRQPVrPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEYG 848
Cdd:cd05743    1 GETVEFTCVATGVPTPIINWRLNWGHV-PDSARVSITSEGGYGTLTIRDVKESDQGAYTCEAINTRG 66

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.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 47.18 E-value: 1.36e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 145699119 626 PLQNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAEGerhTLLLREAQ-AADAGSYTATATNELGQ 701
Cdd:cd20958    6 PMGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFPNG---TLVIENVQrSSDEGEYTCTARNQQGQ 79

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(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. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 47.28 E-value: 1.45e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 145699119 638 VLLKCIITANPPPQVSWKKDGSMLHSE-----GRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQATCASSLAV 710
Cdd:cd05869   20 ITLTCEASGDPIPSITWRTSTRNISSEektldGHIVVRSHARVSSLTLKYIQYTDAGEYLCTASNTIGQDSQSMYLEV 97

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.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 47.23 E-value: 1.69e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 767 PPTFKV--SLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGlcRLRILAAERGDAGFYTCKAV 844
Cdd:cd05730    1 PPTIRArqSEVNATANLGQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFNEDGS--EMTILDVDKLDEAEYTCIAE 78

                         90
                 ....*....|....
gi 145699119 845 NEYGARQCEARLEV 858
Cdd:cd05730   79 NKAGEQEAEIHLKV 92

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.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 46.47 E-value: 2.11e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 145699119 626 PLQNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAEGerhTLLLREAQAADAGSYTATATNELGQA 702
Cdd:cd20968    5 PPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLESG---SLRIHNVQKEDAGQYRCVAKNSLGIA 78

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. 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.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 46.63 E-value: 2.25e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 621 PVFEIPLQNMVVAPGADVLLKCIITANPPPQVSWKKDGSML--HSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNE 698
Cdd:cd05893    1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQIspKSDHYTIQRDLDGTCSLHTTASTLDDDGNYTIMAANP 80

                         90
                 ....*....|..
gi 145699119 699 LGQATCASSLAV 710
Cdd:cd05893   81 QGRISCTGRLMV 92

Immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409398 Cd Length: 101 Bit Score: 46.71 E-value: 2.30e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 145699119 781 EGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQ--RRFAEEAEGG---LCRLRILAAERGDAGFYTCKAVNEYG 848
Cdd:cd05735   17 KGQKKEMSCTAHGEKPIIVRWEKEDTIINPSEmsRYLVTTKEVGdevISTLQILPTVREDSGFFSCHAINSYG 89

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.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 46.44 E-value: 2.45e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 627 LQNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAEGERHTLLLREaqaaDAGSYTATATNELGQATCAS 706
Cdd:cd05728    6 ISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAGDLRITKLSLS----DSGMYQCVAENKHGTIYASA 81


                 ....
gi 145699119 707 SLAV 710
Cdd:cd05728   82 ELAV 85

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 46.58 E-value: 2.50e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 618 LEAPVFEIPlQNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATN 697
Cdd:cd05747    2 LPATILTKP-RSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYKSTFEISKVQMSDEGNYTVVVEN 80

                         90
                 ....*....|.
gi 145699119 698 ELGQATCASSL 708
Cdd:cd05747   81 SEGKQEAQFTL 91

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.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 46.29 E-value: 2.50e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 145699119 624 EIPLQNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAeGERHTLLLREAQAADAGSYTATATNELG 700
Cdd:cd04978    3 IIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRT-VDGRTLIFSNLQPNDTAVYQCNASNVHG 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.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 46.29 E-value: 2.50e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 145699119 781 EGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILaaERGDAGFYTCKAVNEYGARQCEARLEVR 859
Cdd:cd04978   13 PGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVDGRTLIFSNL--QPNDTAVYQCNASNVHGYLLANAFLHVL 89

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.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 46.03 E-value: 3.19e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  625 IPLQNMVVAPGADVLLKC-IITANPPPQVSWKKDGSMLHsEGRLLIRAEGER--HTLLLREAQAADAGSYTATATNELGQ 701
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCsASTGSPGPDVTWSKEGGTLI-ESLKVKHDNGRTtqSSLLISNVTKEDAGTYTCVVNNPGGS 79


                  ..
gi 145699119  702 AT 703
Cdd:pfam00047  80 AT 81

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.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 45.97 E-value: 3.20e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 626 PLQNMVVAPGADVLLKCIITA-NPPPQVSWKKDGSMLHSEG--RLLIRAEGERHTLLLREAQAADAGSYTATATNELGQA 702
Cdd:cd05750    5 EMKSQTVQEGSKLVLKCEATSeNPSPRYRWFKDGKELNRKRpkNIKIRNKKKNSELQINKAKLEDSGEYTCVVENILGKD 84


                 ....*...
gi 145699119 703 TCASSLAV 710
Cdd:cd05750   85 TVTGNVTV 92

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 46.15 E-value: 3.37e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 621 PVFEI-PLQNMVVAP-GADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAEGerhTLLLREAQAADAGSYTATATNE 698
Cdd:cd05852    1 PTFEFnPMKKKILAAkGGRVIIECKPKAAPKPKFSWSKGTELLVNNSRISIWDDG---SLEILNITKLDEGSYTCFAENN 77

                         90
                 ....*....|..
gi 145699119 699 LGQATCASSLAV 710
Cdd:cd05852   78 RGKANSTGVLSV 89

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and 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 and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 45.86 E-value: 3.53e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 629 NMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGrllIRAEGERHTLLLREAQAADAGSYTATATNELGQATCASSL 708
Cdd:cd05731    4 STMVLRGGVLLLECIAEGLPTPDIRWIKLGGELPKGR---TKFENFNKTLKIENVSEADSGEYQCTASNTMGSARHTISV 80


                 ...
gi 145699119 709 AVR 711
Cdd:cd05731   81 TVE 83

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. 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.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 45.48 E-value: 5.13e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 629 NMVVAPGADVLLKCIITANPPPQVSWKKDGSMLH--SEGRLLIRAEGErHTLLLREAQAADAGSYTATATNELGQATCAS 706
Cdd:cd20990    9 DLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRpdSAHKMLVRENGV-HSLIIEPVTSRDAGIYTCIATNRAGQNSFNL 87


                 ....
gi 145699119 707 SLAV 710
Cdd:cd20990   88 ELVV 91

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. 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 structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. 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.

Pssm-ID: 409559 Cd Length: 82 Bit Score: 45.31 E-value: 5.32e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 145699119 632 VAPGADVLLKCIItANPPPQVSWKKDGSMLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATAtnelGQATCASSLAV 710
Cdd:cd20967    9 VSKGHKIRLTVEL-ADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVA----GGEKCSFELFV 82

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 44.69 E-value: 6.90e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  631 VVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAegerhtlllreAQAADAGSYTATATNELG 700
Cdd:pfam13895  10 VVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPNFFTLS-----------VSAEDSGTYTCVARNGRG 68

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 44.94 E-value: 8.81e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 768 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQ-RRFAEEAEGGlcRLRILAAERGDAGFYTCKAVNE 846
Cdd:cd05736    1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPKLsKQLTLIANGS--ELHISNVRYEDTGAYTCIAKNE 78


                 ..
gi 145699119 847 YG 848
Cdd:cd05736   79 GG 80

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.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 44.31 E-value: 1.15e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 145699119 629 NMVVAPGADVLLKCiitaNPP-----PQVSWKKDGSMLHSEG-RLLIRAEGerhTLLLREAQAADAGSYTATATNELG 700
Cdd:cd05724    6 DTQVAVGEMAVLEC----SPPrghpePTVSWRKDGQPLNLDNeRVRIVDDG---NLLIAEARKSDEGTYKCVATNMVG 76

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 44.45 E-value: 1.17e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 779 VREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEYGARQCEARLEV 858
Cdd:cd05894    7 VVAGNKLRLDVPISGEPAPTVTWSRGDKAFTATEGRVRVESYKDLSSFVIEGAEREDEGVYTITVTNPVGEDHASLFVKV 86

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; 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. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). 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.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 44.52 E-value: 1.29e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 145699119 635 GADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLI-RAEGERHTLLLREAQAADAGSYTATATNELGQ 701
Cdd:cd05729   19 ANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGtKVEEKGWSLIIERAIPRDKGKYTCIVENEYGS 86

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.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 44.61 E-value: 1.40e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 767 PPTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCR---LRILAAERGDAGFYTCKA 843
Cdd:cd20954    1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKATGSTPGEYKDLLYDPNVRILPngtLVFGHVQKENEGHYLCEA 80


                 ....*.
gi 145699119 844 VNEYGA 849
Cdd:cd20954   81 KNGIGS 86

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 43.63 E-value: 1.69e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 145699119 635 GADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNELG 700
Cdd:cd05743    1 GETVEFTCVATGVPTPIINWRLNWGHVPDSARVSITSEGGYGTLTIRDVKESDQGAYTCEAINTRG 66

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.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 43.54 E-value: 1.86e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 776 DQSVREGQDVIMSIRVQGEPKPVVSWLRN-------RQPVRPDQrrfaeeaegglcRLRILAAERGDAGFYTCKAVNEYG 848
Cdd:cd05725    6 NQVVLVDDSAEFQCEVGGDPVPTVRWRKEdgelpkgRYEILDDH------------SLKIRKVTAGDMGSYTCVAENMVG 73

                         90
                 ....*....|
gi 145699119 849 ARQCEARLEV 858
Cdd:cd05725   74 KIEASATLTV 83

Eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar protein; member of the I-set of IgSF domains; The members here are composed of the eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar proteins. Myosin light-chain kinase (MLCK) is a key regulator of different forms of cell motility involving actin and myosin II. Agonist stimulation of smooth muscle cells increases cytosolic Ca2+ which binds calmodulin. This Ca2+-calmodulin complex in turn binds to and activates MLCK. Activated MLCK leads to the phosphorylation of the 20 kDa myosin regulatory light chain (RLC) of myosin II and the stimulation of actin-activated myosin MgATPase activity. MLCK is widely present in vertebrate tissues; it phosphorylates the 20 kDa RLC of both smooth and nonmuscle myosin II. Phosphorylation leads to the activation of the myosin motor domain and altered structural properties of myosin II. In smooth muscle MLCK it is involved in initiating contraction. In nonmuscle cells, MLCK may participate in cell division and cell motility; it has been suggested MLCK plays a role in cardiomyocyte differentiation and contraction through regulation of nonmuscle myosin II.

Pssm-ID: 409419 Cd Length: 99 Bit Score: 44.17 E-value: 1.96e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 776 DQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGlCRLRILAAERGDAGFYTCKAVNEYGARQCEAR 855
Cdd:cd05762   10 DMKVRAGESVELFCKVTGTQPITCTWMKFRKQIQEGEGIKIENTENS-SKLTITEGQQEHCGCYTLEVENKLGSRQAQVN 88


                 ...
gi 145699119 856 LEV 858
Cdd:cd05762   89 LTV 91

Fourth immunoglobulin (Ig)-like domain of platelet-derived growth factor receptor (PDGFR); The members here are composed of the fourth immunoglobulin (Ig)-like domain of platelet-derived growth factor receptor (PDGFR; also known as cluster of differentiation (CD) 140a) alpha and beta. PDGF is a potent mitogen for connective tissue cells. PDGF-stimulated processes are mediated by three different PDGFs (PDGF-A,PDGF-B, and PDGF-C). PDGFR alpha binds to all three PDGFs, whereas the PDGFR beta binds only to PDGF-B. PDGF alpha is organized as an extracellular component having five Ig-like domains, a transmembrane segment, and a cytoplasmic portion having protein tyrosine kinase activity. In mice, PDGFR alpha and PDGFR beta are essential for normal development.

Pssm-ID: 409445 Cd Length: 101 Bit Score: 43.70 E-value: 2.55e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 145699119 644 ITANPPPQVSWKKDGSMLHSEGRLLIRAEGERH------TLLLREAQAADAGSYTATATNE 698
Cdd:cd05859   27 VEAYPPPQIRWLKDNRTLIENLTEITTSTRNVQetryvsKLKLIRAKEEDSGLYTALAQNE 87

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

Pssm-ID: 143223 Cd Length: 69 Bit Score: 42.55 E-value: 2.94e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 145699119 638 VLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAEGerhTLLLREAQAADAGSYTATATNELGQATCASSLA 709
Cdd:cd05746    1 VQIPCSAQGDPEPTITWNKDGVQVTESGKFHISPEG---YLAIRDVGVADQGRYECVARNTIGYASVSMVLS 69

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and 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, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. 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 lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 43.16 E-value: 3.65e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 624 EIPLQNMVVAPGADVLLKCIITANPPPQVSWKKDG-----------SMLHSEGRLLIRAegerHTLLLREAQaadaGSYT 692
Cdd:cd05733    5 EQSPKDYIVDPRDNITIKCEAKGNPQPTFRWTKDGkffdpakdprvSMRRRSGTLVIDN----HNGGPEDYQ----GEYQ 76

                         90
                 ....*....|
gi 145699119 693 ATATNELGQA 702
Cdd:cd05733   77 CYASNELGTA 86

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains. Included in this group is Drosophila LAR (DLAR).

Pssm-ID: 409401 Cd Length: 82 Bit Score: 42.58 E-value: 4.29e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 625 IPLQNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIraegERHTLLLREAQaaDAGSYTATATNELGQATC 704
Cdd:cd05739    2 IPPSNHEVMPGGSVNLTCVAVGAPMPYVKWMKGGEELTKEDEMPV----GRNVLELTNIY--ESANYTCVAISSLGMIEA 75


                 ....*..
gi 145699119 705 ASSLAVR 711
Cdd:cd05739   76 TAQVTVK 82

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.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 42.92 E-value: 4.42e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 145699119 635 GADVLLKCIITANPPPQVSWKKDGSmlhsegRLLIRAEGE----RHTLLLREAQAADAGSYTATATNELGQ 701
Cdd:cd05856   19 GSSVRLKCVASGNPRPDITWLKDNK------PLTPPEIGEnkkkKWTLSLKNLKPEDSGKYTCHVSNRAGE 83

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 42.20 E-value: 7.31e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 778 SVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEYGARQCEARLE 857
Cdd:cd05891   12 TIMEGKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVKLEQGKYASLTIKGVTSEDSGKYSINVKNKYGGETVDVTVS 91


                 .
gi 145699119 858 V 858
Cdd:cd05891   92 V 92

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth 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. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 42.13 E-value: 8.08e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 627 LQNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSE-----GRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQ 701
Cdd:cd05732    8 LENQTAVELEQITLTCEAEGDPIPEITWRRATRGISFEegdldGRIVVRGHARVSSLTLKDVQLTDAGRYDCEASNRIGG 87

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.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 41.93 E-value: 8.26e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 145699119 630 MVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQAT 703
Cdd:cd20949    9 TTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRAYQVNSIAS 82

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 42.09 E-value: 9.69e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 767 PPTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNR-------QPVRPDQRRFAEEAEGGLCRLRILAAergDAGFY 839
Cdd:cd05734    1 PPRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKgsgvpqfQHIVPLNGRIQLLSNGSLLIKHVLEE---DSGYY 77

                         90
                 ....*....|
gi 145699119 840 TCKAVNEYGA 849
Cdd:cd05734   78 LCKVSNDVGA 87

transcriptional regulator ICP4; Provisional

Pssm-ID: 223039 [Multi-domain] Cd Length: 1352 Bit Score: 46.32 E-value: 1.03e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  171 PPSGLHREEPDLQPQPASDALRPRPALPPPSKSALLPPPSPRVGKRALPGPSTQPPAT-----PTSPHRRAQEPSLPEDI 245
Cdd:PHA03307   99 SPAREGSPTPPGPSSPDPPPPTPPPASPPPSPAPDLSEMLRPVGSPGPPPAASPPAAGaspaaVASDAASSRQAALPLSS 178

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  246 TTTEEKRGKKPKSSGPSLAGTVESRPQTPLSEASGRLSALGRSPRLVRAGSRildklqffeERRRSLERSDSPPAPLRPW 325
Cdd:PHA03307  179 PEETARAPSSPPAEPPPSTPPAAASPRPPRRSSPISASASSPAPAPGRSAAD---------DAGASSSDSSSSESSGCGW 249

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  326 -----VPLRKARSLEQPKSEGGAAWGTPEASQEELRSPRGSVAERRRLFQQKAASLDERTRQRSATSDLELRFAQELGRI 400
Cdd:PHA03307  250 gpeneCPLPRPAPITLPTRIWEASGWNGPSSRPGPASSSSSPRERSPSPSPSSPGSGPAPSSPRASSSSSSSRESSSSST 329

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 145699119  401 RRSTSREELVRSHESlrATLQRAPSPREPGEPPLFSRPSTPKTSRAVSPAATQPPP---PSGAGKSGDEPGRPRSRGPV 476
Cdd:PHA03307  330 SSSSESSRGAAVSPG--PSPSRSPSPSRPPPPADPSSPRKRPRPSRAPSSPAASAGrptRRRARAAVAGRARRRDATGR 406

large tegument protein UL36; Provisional

Pssm-ID: 223021 [Multi-domain] Cd Length: 3151 Bit Score: 46.47 E-value: 1.04e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  160 RGRALSIHVSIPPSGLHREEPDLQPQPASDALRPRPALPPPSKSALLPPPSPRvgKRALPGP------STQPPATPTSPH 233
Cdd:PHA03247 2632 SPAANEPDPHPPPTVPPPERPRDDPAPGRVSRPRRARRLGRAAQASSPPQRPR--RRAARPTvgsltsLADPPPPPPTPE 2709

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  234 RR--AQEPSLPEDITTTEEKRGK---------KPKSSGPSLAGTVESR-----PQTPLSEASGRLSALGRSPRLVRAGSR 297
Cdd:PHA03247 2710 PAphALVSATPLPPGPAAARQASpalpaapapPAVPAGPATPGGPARParpptTAGPPAPAPPAAPAAGPPRRLTRPAVA 2789

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  298 ILDKlqffeerrrSLERSDSPPAPLRPWVPL-----------RKARSLEQPKSEGGAAWGTPEASQEELRSPRGSVA--- 363
Cdd:PHA03247 2790 SLSE---------SRESLPSPWDPADPPAAVlapaaalppaaSPAGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVApgg 2860

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  364 --ERRRLFQQKAASLDERTRQRSatsdlelrfaqelgrirRSTSREELVRSHESLRatlQRAPSPREPGEPPLFSRPSTP 441
Cdd:PHA03247 2861 dvRRRPPSRSPAAKPAAPARPPV-----------------RRLARPAVSRSTESFA---LPPDQPERPPQPQAPPPPQPQ 2920

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  442 KTSRAvsPAATQPPPPSgagksgdePGRPRSRGPvgrtePGEGPQQEIKRRDQFPLTRSRAIQECRSPVPPYTADPPESR 521
Cdd:PHA03247 2921 PQPPP--PPQPQPPPPP--------PPRPQPPLA-----PTTDPAGAGEPSGAVPQPWLGALVPGRVAVPRFRVPQPAPS 2985


                  ....*
gi 145699119  522 TKAPS 526
Cdd:PHA03247 2986 REAPA 2990

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.

Pssm-ID: 409365 Cd Length: 90 Bit Score: 41.43 E-value: 1.27e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 145699119 646 ANPPPQVSWKKDGSMLHSEGRLLiraegERHTLLLREAQAADAGSYTATATN 697
Cdd:cd04976   29 AYPPPEVVWYKDGLPLTEKARYL-----TRHSLIIKEVTEEDTGNYTILLSN 75

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 41.55 E-value: 1.30e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 767 PPTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVrPDQrrfAEEAEGGLCrLRILAAERGDAGFYTCKAVNE 846
Cdd:cd05851    1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKILEPM-PAT---AEISMSGAV-LKIFNIQPEDEGTYECEAENI 75

                         90
                 ....*....|...
gi 145699119 847 YGARQCEARLEVR 859
Cdd:cd05851   76 KGKDKHQARVYVQ 88

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.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 41.36 E-value: 1.38e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 767 PPTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEgglcRLRILAAERGDAGFYTCKAVNE 846
Cdd:cd20957    1 PLSATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSED----VLVIPSVKREDKGMYQCFVRND 76

                         90
                 ....*....|..
gi 145699119 847 YGARQCEARLEV 858
Cdd:cd20957   77 GDSAQATAELKL 88

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.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 41.45 E-value: 1.63e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 629 NMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGR-LLIRAEGERHTLLLREAQAADAGSYTATATNELGQATCASS 707
Cdd:cd05763    8 DITIRAGSTARLECAATGHPTPQIAWQKDGGTDFPAAReRRMHVMPEDDVFFIVDVKIEDTGVYSCTAQNSAGSISANAT 87


                 ...
gi 145699119 708 LAV 710
Cdd:cd05763   88 LTV 90

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as 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. 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.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 41.38 E-value: 1.92e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 768 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWL-----RNRQPVRPDQRRfAEEAEGGLCRLRILAAERGDAGFYTCK 842
Cdd:cd05765    1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEkqvpgKENLIMRPNHVR-GNVVVTNIGQLVIYNAQPQDAGLYTCT 79

                         90
                 ....*....|....*.
gi 145699119 843 AVNEYGARQCEARLEV 858
Cdd:cd05765   80 ARNSGGLLRANFPLSV 95

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as 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. 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.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 41.00 E-value: 1.96e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 626 PLQNMVVApGADVLLKCIITANPPPQVSWKKDgsmLHSEGRLLIRAEGERHT--------LLLREAQAADAGSYTATATN 697
Cdd:cd05765    7 PTHQTVKV-GETASFHCDVTGRPQPEITWEKQ---VPGKENLIMRPNHVRGNvvvtnigqLVIYNAQPQDAGLYTCTARN 82


                 ...
gi 145699119 698 ELG 700
Cdd:cd05765   83 SGG 85

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 40.80 E-value: 2.36e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 145699119 778 SVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGlCRLRILAAERGDAGFYTCKAVNEYGARQCEARL 856
Cdd:cd05747   14 TVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYK-STFEISKVQMSDEGNYTVVVENSEGKQEAQFTL 91

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; 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. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 40.99 E-value: 2.46e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 632 VAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGRL-LIRAEGERHTLLLREAQAADAGSYTATATNELG 700
Cdd:cd05857   16 VPAANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHRIgGYKVRNQHWSLIMESVVPSDKGNYTCVVENEYG 85

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (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.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 40.54 E-value: 2.56e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 628 QNMVVAPGADVLLKCIITANPPPQVSW-KKDGSMLHSEGRLLIRAEGerhTLLLREAQAADAGSYTATATNELGQATCAS 706
Cdd:cd05764    8 HELRVLEGQRATLRCKARGDPEPAIHWiSPEGKLISNSSRTLVYDNG---TLDILITTVKDTGAFTCIASNPAGEATARV 84


                 ....
gi 145699119 707 SLAV 710
Cdd:cd05764   85 ELHI 88

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six IG-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 40.73 E-value: 2.57e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 145699119 626 PLQNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLH----SEGRlliRAEGErhTLLLREAQAADAGSYTATATNELG 700
Cdd:cd05868    5 APTNLVLSPGEDGTLICRANGNPKPSISWLTNGVPIEiaptDPSR---KVDGD--TIIFSKVQERSSAVYQCNASNEYG 78

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk 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. 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 titin Z1z2 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.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 40.41 E-value: 3.25e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 768 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQR-RFAEEAEGGLCRLRILAAERGDAGFYTCKAVNE 846
Cdd:cd20974    1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTLpGVQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                         90
                 ....*....|..
gi 145699119 847 YGARQCEARLEV 858
Cdd:cd20974   81 SGQATSTAELLV 92

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 40.27 E-value: 3.51e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 778 SVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEYGARQCEARLE 857
Cdd:cd05737   12 TIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLKVEAGRTVYFTINGVSSEDSGKYGLVVKNKYGSETSDVTVS 91


                 .
gi 145699119 858 V 858
Cdd:cd05737   92 V 92

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.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 40.26 E-value: 3.59e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 145699119 637 DVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAEgerHTLLLREAQAADAGSYTATATNELGQATCASSLAV 710
Cdd:cd05723   14 DIVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKE---HNLQVLGLVKSDEGFYQCIAENDVGNAQASAQLII 84

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 40.32 E-value: 4.01e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 621 PVFEIPLQNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSE--GRLLIRAEGERhtLLLREAQAADAGSYTATATNE 698
Cdd:cd05736    1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPKlsKQLTLIANGSE--LHISNVRYEDTGAYTCIAKNE 78

                         90
                 ....*....|..
gi 145699119 699 LGQATCASSLAV 710
Cdd:cd05736   79 GGVDEDISSLFV 90

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.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 40.21 E-value: 4.21e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 617 PLEApvfEIPLQNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRaegERHTLLLREAQAADAGSYTATAT 696
Cdd:cd20957    1 PLSA---TIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQIL---SEDVLVIPSVKREDKGMYQCFVR 74


                 ....*....
gi 145699119 697 N--ELGQAT 703
Cdd:cd20957   75 NdgDSAQAT 83

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.

Pssm-ID: 409417 Cd Length: 95 Bit Score: 39.91 E-value: 5.45e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 145699119 632 VAPGADVLLKCIITANPPPQVSWKKDGSMLhSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQAtCAS 706
Cdd:cd05760   13 IQPSSRVTLRCHIDGHPRPTYQWFRDGTPL-SDGQGNYSVSSKERTLTLRSAGPDDSGLYYCCAHNAFGSV-CSS 85

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 39.51 E-value: 6.58e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 145699119 640 LKCIITANPPPQVSWKKDGSMLHSEGRLLIRAE-GERHTLLLREAQAADAGSYTATATNELGQATCASSLAV 710
Cdd:cd05891   21 LTCTVFGNPDPEVIWFKNDQDIELSEHYSVKLEqGKYASLTIKGVTSEDSGKYSINVKNKYGGETVDVTVSV 92

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six IG-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 39.58 E-value: 7.16e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 145699119 782 GQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGlcRLRILAAERGDAGFYTCKAVNEYG 848
Cdd:cd05868   14 GEDGTLICRANGNPKPSISWLTNGVPIEIAPTDPSRKVDGD--TIIFSKVQERSSAVYQCNASNEYG 78

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

Pssm-ID: 409387 Cd Length: 97 Bit Score: 39.00 E-value: 1.07e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 145699119 635 GADVLLKCIITANPPPQVSWKKDGSMLH----------SEGRLLIRaegerhTLLLREAQAADAGSYTATATNE 698
Cdd:cd05722   16 GGPVVLNCSAESDPPPKIEWKKDGVLLNlvsderrqqlPNGSLLIT------SVVHSKHNKPDEGFYQCVAQNE 83

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

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 38.38 E-value: 1.11e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 145699119 635 GADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAEGerhTLLLREAQAADAGSYTATATNELGQATCASSLAV 710
Cdd:cd05745    2 GQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSG---TLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

transcriptional regulator ICP4; Provisional

Pssm-ID: 223039 [Multi-domain] Cd Length: 1352 Bit Score: 42.47 E-value: 1.27e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  171 PPSGLHREEPDLQPQPASDALRPRPALPPPSKSALLPPPSPrvGKRALPGPSTQPPATPTSPHRRAQEPSLPEDITTTEE 250
Cdd:PHA03307   71 PPPGPGTEAPANESRSTPTWSLSTLAPASPAREGSPTPPGP--SSPDPPPPTPPPASPPPSPAPDLSEMLRPVGSPGPPP 148

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  251 KRGKK--PKSSGPSLAGTVESRPQTPLSEASGRLSALGRSPRLVRAGSRILDKLQFFEERRRSlerSDSPPAPLRPWVPL 328
Cdd:PHA03307  149 AASPPaaGASPAAVASDAASSRQAALPLSSPEETARAPSSPPAEPPPSTPPAAASPRPPRRSS---PISASASSPAPAPG 225

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  329 RKARSLEQPKSEGGAAWGTPE-ASQEELRSPRGSVAERRRLFQQKAASLDERTR-----QRSATSDLELRFAQELGRIR- 401
Cdd:PHA03307  226 RSAADDAGASSSDSSSSESSGcGWGPENECPLPRPAPITLPTRIWEASGWNGPSsrpgpASSSSSPRERSPSPSPSSPGs 305

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  402 -----RSTSREELVRSHES-LRATLQRAPSPREPGEPPLFS-----RPSTPKTSRAVSPAATQPPPPSGAGKSGDEPGRP 470
Cdd:PHA03307  306 gpapsSPRASSSSSSSRESsSSSTSSSSESSRGAAVSPGPSpsrspSPSRPPPPADPSSPRKRPRPSRAPSSPAASAGRP 385

                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 145699119  471 RSRGpVGRTEPGEGPQQEikRRDQFPLTRSRAIQECRSPVP--PYTADPPESRTKAPSGRKREPPAQAVRF 539
Cdd:PHA03307  386 TRRR-ARAAVAGRARRRD--ATGRFPAGRPRPSPLDAGAASgaFYARYPLLTPSGEPWPGSPPPPPGRVRY 453

Fifth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB, and TrkC; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth domain of Trk receptors TrkA, TrkB, and TrkC, an immunoglobulin (Ig)-like domain which binds to neurotrophin. The Trk family of receptors are tyrosine kinase receptors. They are activated by dimerization, leading to autophosphorylation of intracellular tyrosine residues, and triggering the signal transduction pathway. TrkA, TrkB, and TrkC share significant sequence homology and domain organization. The first three domains are leucine-rich domains while the fourth and fifth domains are Ig-like domains playing a part in ligand binding. TrkA, TrkB, and TrkC mediate the trophic effects of the neurotrophin Nerve Growth Factor (NGF) family. TrkA is recognized by NGF. TrkB is recognized by brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-4. TrkC is recognized by NT-3. NT-3 is promiscuous as in some cell systems it activates TrkA and TrkB receptors. TrkA is a receptor found in all major NGF targets, including the sympathetic, trigeminal, and dorsal root ganglia, cholinergic neurons of the basal forebrain, and the striatum. TrKB transcripts are found throughout multiple structures of the central and peripheral nervous systems. The TrkC gene is expressed throughout the mammalian nervous system. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409360 Cd Length: 96 Bit Score: 38.92 E-value: 1.33e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 145699119 641 KCI---ITANPPPQVSWKKDGSML------HSEGRLLIRAEGERH-TLLLREAQAADAGSYTATATNELGQAT 703
Cdd:cd04971   16 WCIpftVRGNPKPTLTWYHNGAVLnesdyiRTEIHYEAATPTEYHgCLKFDNPTHVNNGNYTLVASNEYGQDS 88

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; 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. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 38.68 E-value: 1.47e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 145699119 791 VQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEYGA 849
Cdd:cd05857   28 AAGNPTPTMRWLKNGKEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGS 86

DNA polymerase III subunits gamma and tau; Validated

Pssm-ID: 236090 [Multi-domain] Cd Length: 824 Bit Score: 42.28 E-value: 1.62e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 417 RATLQRAPSP--REPGEPPLFSRPSTPKTSRAVSPAAtQPPPPSGAGKSGDEPGRPRSRGPVGRTEPGEGPQQeikrrdq 494
Cdd:PRK07764 372 RGLLARLERLerRLGVAGGAGAPAAAAPSAAAAAPAA-APAPAAAAPAAAAAPAPAAAPQPAPAPAPAPAPPS------- 443

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 145699119 495 fpltRSRAIQECRSPVPPYTADPPESRTKAPSGRKREPPAQAVRFLPWATPGVE 548
Cdd:PRK07764 444 ----PAGNAPAGGAPSPPPAAAPSAQPAPAPAAAPEPTAAPAPAPPAAPAPAAA 493

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 38.34 E-value: 1.85e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 145699119 640 LKCIITANPPPQVSWKKDGSMLHSEGRLLIRAEGERH-TLLLREAQAADAGSYTATATNELGQATCASSLAV 710
Cdd:cd05737   21 LTCNVWGDPPPEVSWLKNDQALAFLDHCNLKVEAGRTvYFTINGVSSEDSGKYGLVVKNKYGSETSDVTVSV 92

transcriptional regulator ICP4; Provisional

Pssm-ID: 223039 [Multi-domain] Cd Length: 1352 Bit Score: 42.08 E-value: 2.08e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  220 GPSTQPPATPTSPHRRAQEPSLPediTTTEEKRGKKPKSSGPSLAGTVESRPQTPLSEASGRLSALGRSP--RLVRAGSR 297
Cdd:PHA03307   70 GPPPGPGTEAPANESRSTPTWSL---STLAPASPAREGSPTPPGPSSPDPPPPTPPPASPPPSPAPDLSEmlRPVGSPGP 146

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  298 ILDKLQFFEERRRSLERSDSPPAPLrPWVPLRKARSLEQPKSEGGAAwgTPEASQEELRSPRGSVaeRRRLFQQKAASLD 377
Cdd:PHA03307  147 PPAASPPAAGASPAAVASDAASSRQ-AALPLSSPEETARAPSSPPAE--PPPSTPPAAASPRPPR--RSSPISASASSPA 221

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  378 ERtrqRSATSDLELRFAQELGRIRRSTSREELVRSHESL-RATLQRAPSPREPGEPPLFSRPSTPKTSRAVSPAATQPPP 456
Cdd:PHA03307  222 PA---PGRSAADDAGASSSDSSSSESSGCGWGPENECPLpRPAPITLPTRIWEASGWNGPSSRPGPASSSSSPRERSPSP 298

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119  457 PSGAGKSGDEPGRPRSRGPVGRTEPGEGPqqeiKRRDQFPLTRSRAIQECRSPVPPYTADPPESRTKAPSGRKREPPAQA 536
Cdd:PHA03307  299 SPSSPGSGPAPSSPRASSSSSSSRESSSS----STSSSSESSRGAAVSPGPSPSRSPSPSRPPPPADPSSPRKRPRPSRA 374


                  ...
gi 145699119  537 VRF 539
Cdd:PHA03307  375 PSS 377

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.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 37.99 E-value: 2.20e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 145699119 781 EGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGglcrLRILAAERGDAGFYTCKAVNEYG 848
Cdd:cd20968   13 EGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLESGS----LRIHNVQKEDAGQYRCVAKNSLG 76

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.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 38.14 E-value: 2.43e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 628 QNMVVAPGADVLLKCIITANPPPQVSWKKDGSML---HSEGRLLIRAEGerhTLLLREAQAADAGSYTATATNELGQATC 704
Cdd:cd20969   10 QQVFVDEGHTVQFVCRADGDPPPAILWLSPRKHLvsaKSNGRLTVFPDG---TLEVRYAQVQDNGTYLCIAANAGGNDSM 86


                 ....*.
gi 145699119 705 ASSLAV 710
Cdd:cd20969   87 PAHLHV 92

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of human fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. FGFR2 is required for male sex determination. 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.

Pssm-ID: 409444 Cd Length: 105 Bit Score: 38.40 E-value: 2.55e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 629 NMVVAPGADVLLKCIITANPPPQVSW----KKDGSMLHSEG----RLLIRA-----EGERHTLLLREAQAADAGSYTATA 695
Cdd:cd05858   10 NTSVVVGTDAEFVCKVYSDAQPHIQWlkhvEKNGSKYGPDGlpyvEVLKTAgvnttDKEIEVLYLRNVTFEDAGEYTCLA 89


                 ....*
gi 145699119 696 TNELG 700
Cdd:cd05858   90 GNSIG 94

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. 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. 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 structures of the titin-A168169 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.

Pssm-ID: 409563 Cd Length: 93 Bit Score: 37.83 E-value: 2.97e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 620 APVFEIPLQNMVVAPGADVLLKCIITANPPPQVSWKK-------DGSMLHSEGRLliraeGERHTLLLREAQAADAGSYT 692
Cdd:cd20971    1 APHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRqgkeiiaDGLKYRIQEFK-----GGYHQLIIASVTDDDATVYQ 75

                         90
                 ....*....|.
gi 145699119 693 ATATNELGQAT 703
Cdd:cd20971   76 VRATNQGGSVS 86

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third 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. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 37.53 E-value: 3.31e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 145699119 633 APGADVLLKCIITANPPPQVSWKK-DGSMLHSEGRLliRAEGerhTLLLREAQAADAGSYTATATNELGQAT 703
Cdd:cd04968   14 LKGQTVTLECFALGNPVPQIKWRKvDGSPSSQWEIT--TSEP---VLEIPNVQFEDEGTYECEAENSRGKDT 80

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409458 Cd Length: 95 Bit Score: 37.66 E-value: 3.62e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 628 QNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAEGERHTLLLREAQAADA----GSYTATATNELGQAT 703
Cdd:cd05874    9 KDYIVDPRENIVIQCEAKGKPPPSFSWTRNGTHFDIDKDPKVTMKPNTGTLVINIMNGEKAeayeGVYQCTARNERGAAV 88


                 ....*...
gi 145699119 704 cASSLAVR 711
Cdd:cd05874   89 -SNNIVIR 95

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2); 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 2 (VEGFR-2). 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. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-2 (KDR/Flk-1) is a major mediator of the mitogenic, angiogenic and microvascular permeability-enhancing effects of VEGF-A; 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. VEGF-A also interacts with VEGFR-1, which it binds more strongly than VEGFR-2. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. 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.

Pssm-ID: 409450 Cd Length: 89 Bit Score: 37.21 E-value: 3.66e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 145699119 623 FEIPLQNMVVAP-GADVLLKCIITANPPPQVSWKKDGSMLhsEGRLLIRAEgerHTLLLREAQAADAGSYTATATN 697
Cdd:cd05864    4 LGSGMESLVEAKvGERVRIPVKYLGYPPPEIKWYKNGIPI--ESNHTIKAG---HVLTIMEVTEKDAGNYTVVLTN 74

Immunoglobulin (Ig)-like domain at the C-terminus of semaphorins; The members here are composed of the immunoglobulin (Ig)-like domain in semaphorins. Semaphorins are transmembrane protein that have important roles in a variety of tissues. Functionally, semaphorins were initially characterized for their importance in the development of the nervous system and in axonal guidance. Later they have been found to be important for the formation and functioning of the cardiovascular, endocrine, gastrointestinal, hepatic, immune, musculoskeletal, renal, reproductive, and respiratory systems. Semaphorins function through binding to their receptors and transmembrane semaphorins also serves as receptors themselves. Although molecular mechanism of semaphorins is poorly understood, the Ig-like domains may be involved in ligand binding or dimerization.

Pssm-ID: 409368 Cd Length: 88 Bit Score: 37.44 E-value: 3.66e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 145699119 626 PLQNMVVAPGADVLLKCIITANPPPqVSWKKDGSMLHSEG--RLLIRAEGerhTLLLREAQAADAGSYT 692
Cdd:cd04979    2 SFKQISVKEGDTVILSCSVKSNNAP-VTWIHNGKKVPRYRspRLVLKTER---GLLIRSAQEADAGVYE 66

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.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 37.22 E-value: 4.22e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 145699119 635 GADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLIRAEgERHTLLLREAQAADAGSYTATATNELGQATCASSLAV 710
Cdd:cd05730   18 GQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFNE-DGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92

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.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 37.37 E-value: 4.32e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 779 VREGQDVIMSIRVQGEPKPVVSWL-RNRQPVRPDQRRFAEEAEGGLCRLRILAAErgDAGFYTCKAVNEYGARQCEARLE 857
Cdd:cd20969   14 VDEGHTVQFVCRADGDPPPAILWLsPRKHLVSAKSNGRLTVFPDGTLEVRYAQVQ--DNGTYLCIAANAGGNDSMPAHLH 91


                 .
gi 145699119 858 V 858
Cdd:cd20969   92 V 92

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.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 37.29 E-value: 4.91e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 145699119 632 VAPGADVLLKCIITANPPPQVSWKKD-GSM------LHSEGRLLIRAEGerhTLLLREAQAADAGSYTATATNELG 700
Cdd:cd20954   13 VAAGQDVMLHCQADGFPTPTVTWKKAtGSTpgeykdLLYDPNVRILPNG---TLVFGHVQKENEGHYLCEAKNGIG 85

Third 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 third 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 third 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).

Pssm-ID: 409569 Cd Length: 93 Bit Score: 36.99 E-value: 6.15e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 621 PVFEIPLQNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGRLLI----RAEGERhtLLLREAQAADAGSYTATAT 696
Cdd:cd20977    1 PVPQYVSKDMMAKAGDVTMIYCMYGSNPTAHPNYFKNGKDVNGNPEDRItrhnRTSGKR--LLFKTTLPEDEGVYTCEVD 78

                         90
                 ....*....|....*
gi 145699119 697 NELGQ-ATCASSLAV 710
Cdd:cd20977   79 NGVGKpQKHSLKLTV 93

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 36.53 E-value: 6.89e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145699119 622 VFEIPLQNMVVAPGADVLLKCIITANPPPQVSWKKDG---SMLHSEGRLLIRAEGerhTLLLREAQAADAGSYTATATNE 698
Cdd:cd05738    1 IIDMGPQLKVVEKARTATMLCAASGNPDPEISWFKDFlpvDTATSNGRIKQLRSG---ALQIENSEESDQGKYECVATNS 77


                 ..
gi 145699119 699 LG 700
Cdd:cd05738   78 AG 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.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 36.41 E-value: 8.18e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 145699119 628 QNMVVAPGADVLLKCIITANPPPQVSWKKDGSMLHSEGrllirAEGERH----TLLLREAQAADAGSYTATATNELG 700
Cdd:cd05867    7 QSHLYGPGETARLDCQVEGIPTPNITWSINGAPIEGTD-----PDPRRHvssgALILTDVQPSDTAVYQCEARNRHG 78

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; 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. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). 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.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 36.43 E-value: 9.33e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 145699119 793 GEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEYGARQCEARLEV 858
Cdd:cd05729   30 GNPMPNITWLKDGKEFKKEHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYGSINHTYDVDV 95